The Official Publication of

Perinatal Medicine Foundation

Turkish Perinatology Society

Turkish Society of Ultrasound in Obstetrics and Gynecology

ISSN 1305–3124

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Volume 21 | Issue 3 | December 2013

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To promote the development of global open access to scientificinformation and research, the journal provides copyrights of allonline published papers (except where otherwise noted) for free useof readers, scientists, and institutions (such as link to the content orpermission for its download, distribution, printing, copying, andreproduction in any medium, without any changing and except thecommercial purpose), under the terms of CC BY-NC-ND 3.0 License(www.creativecommons.org/licenses/by-nc-nd/3.0), provided theoriginal work is cited. To get permission for commercial purposeplease contact the publisher.

Conflicts of Interest

The authors should disclose all issues concerning financial relationship,conflict of interest, and competing interest that may potentially influ-ence the results of the research or scientific judgment. All financial con-tributions or sponsorship, financial relations, and areas of conflict ofinterest should be clearly explained in the cover letter to the Editor-in-Chief at the time of submission, with full assurance that any relateddocument will be submitted to the journal when requested. For thedetails of journal's "Conflicts of Interest Policy" please visit www.peri-nataljournal.com.

Publication InfoOwnership: On behalf of the Perinatal Medicine FoundationCihat fienManaging Editor: Murat YaylaAdministrative Office: Cumhuriyet Cad. 30/5 Elmada¤, Taksim34367 ‹stanbul

Due the Press Law of Turkish Republic dated as June 26, 2004 andnumbered as 5187, this publication is classified as a local periodi-cal. Perinatal Journal is published by Deomed Publishing (Copyright© 2013, Perinatal Medicine Foundation).

Publication Coordinator: ‹lknur DemirelEnglish Editor: Fikret YeflilyurtGraphic Design: Tolga Erbay Page Layout: Nurgül ÖzcanPress: Birmat Matbaac›l›k, Yüzy›l Mahallesi MASS‹T 1. Cad. No:131 Ba¤c›lar, ‹stanbul, Tel: (0212) 629 05 59-60

Printed on acid-free paper (December 2013).

The Official publication of Perinatal Medicine Foundation, Turkish Perinatology Society and Turkish Society of Ultrasound in Obstetrics and Gynecology

DescriptionPerinatal Journal, the official publication of Perinatal Medicine Foundation, Turkish Perinatology Society and Turkish Society of Ultrasound in Obstetrics and Gynecology, is an international online open access peer-reviewed scientific journal (e-ISSN 1305-3124) published triannually in English. The manuscripts which are accept-ed for publication in the Perinatal Journal are published as a parallel publication of Turkish version in “Perinatoloji Dergisi” (p-ISSN:1300-5251, e-ISSN:1305-3132). Translation in to Turkish language is pro-vided by the publisher as free of charge for authors. This is automat-ically accepted by the authors of manuscripts at the time of submis-sion.

The journal mainly includes original clinical and experimental research articles, case reports, reviews, editorial and opinion articles, and a letters column. Perinatal Journal can be read by perinatolo-gists, obstetricians, gynecologists, radiologists, pediatricians, sonog-raphers, midwives, radiographers, and scientific members of other related areas.

Aim and Scope Perinatal Journal aims to create an interdisciplinary scientific plat-form for sharing and discussing topics on perinatal medicine and to share its experience with international scientific community.

CopyrightPeriantal Journal does not officially agree with the ideas of manu-scripts published in the journal and does not guarantee for any prod-uct or service advertisements in its content. Scientific and legal responsibilities of published articles belong to their authors. Materials such as pictures, figures, tables etc. sent with manuscripts should be original or if they were published before written approval of copyright holder should be sent with manuscript for publishing together.

All published materials will become the sole property of, and will be copyrighted by Perinatal Journal. Therefore, "Acknowledgement of Authorship and Transfer of Copyright Agreement" are requested in addition to manuscripts that are to be assessed. Acknowledgement of Authorship and Transfer of Copyright Agreement form is available online at www.perinataljournal.com. No payment is done for manuscripts under the name of copyright or others approved for publishing in the journal and no publication cost is charged; however, reprints are at authors’ cost.

Deomed PublishingSarayard› Cad. Cemhan-Do¤an ‹fl Merkezi No: 100/16 HasanpaflaKad›köy 34722 IstanbulTelefon: +90 216 414 83 43 (Pbx) Fax: +90 216 414 83 42e-mail: medya@deomed.com • www.deomed.com

www.perinataljournal.com

Editor-in-ChiefCihat fien, Istanbul, Turkey

Associate EditorsMurat Yayla, Istanbul, Turkey

Olufl Api, Istanbul, Turkey

Advisory BoardAbdallah Adra, Beyrut, LübnanArif Akflit, Eskiflehir, TürkiyeAris Antsaklis, Atina, YunanistanSaadet Arsan, Ankara, TürkiyeAbdel-Latif Ashmaig, Hartum, SudanAlev At›fl-Ayd›n, ‹stanbul, TürkiyeAhmet Baschat, Baltimore, MD, ABDAhmet Baflaran, Konya, TürkiyeYeflim Baytur, Manisa, TürkiyeLous Cabero-Roura, Barselona, ‹spanyaManuel Carrapato, Porto, PortekizJose M. Carrera, Barselona, ‹spanyaJulene Carvalho, Londra, ‹ngiltereRabih Chaoui, Berlin, AlmayaFrank Chervenak, New York, NY, ABDBülent Çakmak, Tokat, TürkiyeFiliz Çayan, Mersin, TürkiyeEbru Çelik, Malatya, TürkiyeVincenzo D’Addario, Bari, ‹talyaNur Daniflmend, ‹stanbul, TürkiyeCansun Demir, Adana, TürkiyeJan Deprest, Leuven, BelçikaEbru Dikensoy, Gaziantep, TürkiyeGian Carlo DiRenzo, Perugia, ‹talyaTony Duan, Shanghai, ÇinJoachim Dudenhausen, Berlin, AlmanyaAlaa Ebrashy, Kahire, M›s›rElif Gül Yapar Eyi, Ankara, TürkiyeAli Gedikbafl›, ‹stanbul, TürkiyeUlrich Gembruch, Bonn, AlmanyaAnne Greenough, Londra, ‹ngiltereGökhan Göynümer, ‹stanbul, TürkiyeArif Güngören, Hatay, TürkiyeMelih A.Güven, ‹stanbul, TürkiyeJoseph Haddad, Paris, FransaDavor Jurkovic, Londra, ‹ngiltereOliver Kagan, Tübingen, AlmanyaÖmer Kandemir, Ankara, TürkiyeBurçin Kavak, Elaz›¤, Türkiye‹schiro Kawabata, Osaka, Japonya Selahattin Kumru, Düzce, Türkiye

As›m Kurjak, Zagrep, H›rvatistanNilgün Kültürsay, ‹zmir, TürkiyeMalcome Levene, Leeds, ‹ngiltereNarendra Malhotra, Agra, UP, HindistanGiampaolo Mandruzzato, Trieste, ‹talyaAlexandra Matias, Porto, PortekizRatko Matijevic, Zagrep, H›rvatistanIsrael Meizner, Tel Aviv, ‹srailMohammed Momtaz, Kahire, M›s›rGiovanni Monni, Cagliari, ‹talyaErcüment Müngen, ‹stanbul, TürkiyeKypros Nicolaides, Londra, ‹ngiltereLütfü Öndero¤lu, Ankara, TürkiyeSoner Recai Öner, ‹zmir, TürkiyeOkan Özkaya, Isparta, TürkiyeAlexander Papitashvilli, Tiflis, Gürcistan‹brahim Polat, ‹stanbul, TürkiyeRitsuko Pooh, Osaka, JaponyaRuben Quintero, Tampa, FL, ABDNebojsa Radunovic, Belgrad, S›rbistanGuiseppe Rizzo, Roma, ‹talyaRoberto Romero, Detroit, MI, ABDLevent Salt›k, ‹stanbul, TürkiyeHaluk Sayman, ‹stanbul, TürkiyeMekin Sezik, Isparta, TürkiyeYunus Söylet, ‹stanbul, TürkiyeMilan Stanojevic, Zagrep, H›rvatistanFlorin Stomatian, Cluj, RomanyaJiri Sonek, Dayton, OH, ABDTurgay fiener, Eskiflehir, TürkiyeStephen Robson, Newcastle, ‹ngiltereAlper Tanr›verdi, Ayd›n, TürkiyeEbru Tar›m, Adana, TürkiyeNeslihan Tekin, Eskiflehir, TürkiyeIlan Timor-Tritsch, New York, NY, ABDSeyfettin Uluda¤, ‹stanbul, TürkiyeLiliana Voto, Buenos Aires, ArjantinMiroslaw Wielgos, Varflova, PolonyaSimcha Yagel, Tel Aviv, ‹srailAhmet Yal›nkaya, Diyarbak›r, TürkiyeIvica Zalud, Honolulu, HI, ABD

The Official Publication of Perinatal Medicine Foundation, Turkish Perinatology Society and Turkish Society of Ultrasound in Obstetrics and Gynecology

Correspondence: Perinatal Journal, Perinatal Medicine Foundation,Cumhuriyet Cad. 30/5 Elmada¤, Taksim 34367 ‹stanbul, TurkeyPhone: (0212) 225 52 15 • Fax: (0212) 225 23 22 e-mail: editor@perinataljournal.comwww.perinataljournal.com

Names are in alphabetical order.

Volume 21 | Issue 3 | December 2013

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Perinatal Journalii

Coverage

The manuscripts should be prepared for one of the following article categorieswhich are peer-reviewed:

• Clinical Research Article• Experimental Study• Case Report• Technical Note• Letter to the Editor

In addition, the journal includes article categories which do not require a peerreview process but are prepared by the Editorial Board or consist of invited arti-cles, titled as:

• Editorial• Viewpoint Article • Review Article • Abstracts• Announcements• Erratum

Manuscript Evaluation

All submissions to Perinatal Journal must be original, unpublished, and notunder the review of any other publication. This is recorded by the system auto-matically with the IP number, the date and time of submission. On behalf of allauthors the corresponding author should state that all authors are responsiblefor the manuscripts. The name, date, and place of the relevant meeting shouldbe stated if the submission is a work that was previously presented in a scientif-ic meeting.

Following the initial review, manuscripts which have been accepted forconsideration are reviewed by at least two reviewers. The Editors of the journaldecide to accept or reject the manuscript considering the comments of thereviewers. They are authorized to reject or revise the manuscript, to suggestrequired corrections and changes upon the comments and suggestions ofreviewers, and/or to correct or condense the text by permission of the corre-sponding author. They have also the right to reject a manuscript after authors’revision. Author(s) should provide additional relevant data, documents, or infor-mation upon the editorial request if necessary.

Ethical Issues

All manuscripts presenting data obtained from studies involving human subjectsmust include a statement that the written informed consent of the participantswas obtained and that the study was approved by an institutional ethics boardor an equivalent body. This institutional approval should be submitted with themanuscript. Authors of case reports must submit the written informed consentof the subject(s) of the report or of the patient’s legal representatives for thepublication of the manuscript. All studies should be carried out in accordancewith the World Medical Association Declaration of Helsinki, covering the latestrevision date. Patient confidentiality must be protected according to the univer-sally accepted guidelines and rules. Manuscripts reporting the results of experi-mental studies on animals must include a statement that the study protocol wasapproved by the animal ethics committee of the institution and that the studywas conducted in accordance with the internationally accepted guidelines,including the Universal Declaration of Animal Rights, European Convention forthe Protection of Vertebrate Animals Used for Experimental and Other ScientificPurposes, Principles of Laboratory Animal Science, and the Handbook for theCare and Utilization of Laboratory Animals. The authors are strongly requestedto send the approval of the ethics committee together with the manuscript. Inaddition, manuscripts on human and animal studies should describe proceduresindicating the steps taken to eliminate pain and suffering.

The authors should also disclose all issues concerning financial relationship,conflict of interest, and competing interest that may potentially influence theresults of the research or scientific judgment. All financial contributions or spon-sorship, financial relations, and areas of conflict of interest should be clearlyexplained in the cover letter to the Editor-in-Chief at the time of submission,

with full assurance that any related document will be submitted to the journalwhen requested. For the details of journal's "Conflict of Interest Policy" pleaseread the PDF document which includes "Conflicts of Interest DisclosureStatement".

Perinatal Journal follows the ethics flowcharts developed by the Committeeon Publication Ethics (COPE) for dealing with cases of possible scientific miscon-duct and breach of publication ethics. For detailed information please visitwww.publicationethics.org.

Manuscript Preparation

In addition to the rules listed below, manuscripts to be published in PerinatalJournal should be in compliance with the Uniform Requirements forManuscripts Submitted to Biomedical Journals published by InternationalCommittee of Medical Journal Editors (ICMJE) of which latest version is availableat www.icmje.org.

Authors are requested to ensure that their manuscript follows the appro-priate guidelines such as CONSORT for randomized controlled trials, STROBE forobservational studies, STARD for diagnostic accuracy studies, and PRISMA forsystematic reviews and meta-analyses, for the study design and reporting ifapplicable.

Authorship and Length of Texts

The author(s) must declare that they were involved in at least 3 of the 5 stagesof the study stated in the “Acknowledgement of Authorship and Transfer ofCopyright Agreement” as “designing the study”, “collecting the data”, “ana-lyzing the data”, “writing the manuscript” and “confirming the accuracy of thedata and the analyses”. Those who do not fulfill this prerequisite should not bestated as an author.

Original research articles base on clinical or experimental studies. Themain text should not exceed 2500 words (max. 16 pages) and there should bea maximum 6 authors

Case reports should illustrate interesting cases including their treatmentoptions. The main text should not exceed 2000 words (max. 8 pages) and thereshould be a maximum 5 authors.

Viewpoint articles: Only by invitation and should be no more than 2000words long (max. 8 pages).

Review articles: Only by invitation and should be no more than 4000-5000 words long (max. 20 pages).

Technical notes aims to present a newly diagnostic or therapeuticmethod. They should not exceed 2000 words (max. 8 pages) and include a max-imum of 10 references.

Letters to the Editor should be no more than 500 words long (max. 2pages) and include a maximum of 10 references.

Sections in the Manuscripts

Manuscripts should be designed in the following order: title page, abstract,main text, references, and tables, with each typeset on a separate page:

Page 1 - Title pagePage 2 - Abstract and key wordsPage 3 and next - Main textNext Page - ReferencesNext Page - Table heading and tables (each table should be placed in sep-

arate pages)Next Page - Figure legends and figures (each figure should be placed in

separate pages)Last Page - Appendices (patient forms, surveys etc.)

Title pageThis page should only include the title of the manuscript, which should be care-fully chosen to better reflect the contents of the study. No anusual abbreviationsshould be used in the title of the manuscript. A short title as running headingnot exceeding 40 characters should be given which is desired to appear on toppart of continuing pages when journal is published.

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Volume 21 | Issue 3 | December 2013 iii

Instructions for the Authorswww.perinataljournal.com

Abstract pageAbstracts should not contain any abbreviation and references. They should beprepared under following designs.

— Abstracts of research articles should be max. 250 words and struc-tured in four paragraphs using the following subtitles: Objective, Methods,Results, and Conclusion. Following the abstract, each abstract page shouldinclude max. 5 key words separated with comma and written in lower cases.

— Abstracts of case reports should be max. 125 words and structured inthree paragraphs using the following subtitles: Objective, Case, Conclusion.Following the abstract, each abstract page should include max. 3 key words sep-arated with comma and written in lower cases.

— Abstracts of review articles should be max. 300 words and presentednot structured in one paragraph. Following the abstract, each abstract pageshould include max. 5 key words separated with comma and written in lowercases.

— Abstracts of technical notes should be max. 125 words and structuredin three paragraphs using the following subtitles: Objective, Technique,Conclusion. Following the abstract, each abstract page should include max. 3key words separated with comma and written in lower cases.

Main text:The sections in main text are defined according to the manuscript type.

— In research articles, main text should consist of sections titled as"Introduction, Methods, Results, Discussion and Conclusion". Each title mayhave subtitles. The categories of subtitles should be clearly defined.

The Introduction section should include a brief summary of the base of thework and clearly states the purpose of the study.

The Methods section should contain a detailed description of the material,the study design and clinical and laboratory tests, and statistical methods used.A statement regarding the ethical issues should also be given in this section.

The Results section should provide the main findings of the study. Datashould be concisely presented, preferably in tables or graphs.

The Discussion section should mainly rely on the results derived from thestudy, with relevant citations from the most recent literature.

The Conclusion section should briefly and claearly present the conclusionsderived from the results of the study. It should be in compliance with the aim ofthe work and and point out its application in clinical practice.

— In Case Reports, main text should be divided with the titles"Introduction, Case(s), Discussion". Reported case(s) should be introducedclearly including the case story, and the results of laboratory tests should begiven in table format as far as possible.

— The text of the reviews articles should follow the "Introduction" andbe organized under subtitles which should clearly define the text's context cat-egorization. The Reviews are expected to include wide surveying of literatureand reflect the author's personal experiences as far as possible.

— The text of the technical note type of articles should be divided into"Introduction, Technic, Discussion". The presented technic should be definedbriefly under the related title, and include illustrations or figures as soon as pos-sible.

— Letters to the Editor should not have titled sections. If there is a cita-tion about a formerly published article within the text, reference(s) should beprovided.

References

References used in the text should be directly related to the topic, as recent aspossible and in enough numbers. They should be numbered in square bracketsin the order in which they are mentioned in the text including Tables andFigures. Citation order should be checked carefully.

Only published articles or articles in press can be used in references.Unpublished data including conference papers or personal communicationsshould not be used. Papers published in only electronic journals or in thepreprint or online first issues of the electronic versions of conventional periodi-cals should be absolutely presented with DOI (digital object identifier) numbers.

Journal titles should be abbreviated according to the Index Medicus. Allauthors if six or fewer should be listed; otherwise, the first six and “et al.”should be written.

Direct use of references is strongly recommended and the authors may beasked to provide the first and last pages of certain references. Publication of themanuscript will be suspended until this request is fulfilled by the author(s).

The style and punctuation should follow the formats outlined below:

— Standard journal article: Hammerman C, Bin-Nun A, Kaplan M.Managing the patent ductus arteriosus in the premature neonate: a new lookat what we thought we knew. Semin Perinatol 2012;36:130-8.

— Article published in an only electronic journal: Lee J, Romero R, XuY, Kim JS, Topping V, Yoo W, et al. A signature of maternal anti-fetal rejectionin spontaneous preterm birth: chronic chorioamnionitis, anti-human leukocyteantigen antibodies, and C4d. PLoS ONE 2011;6:e16806. doi:10.1371/journal.pone.0011846.

— Book: Jones KL. Practical perinatology. New York: Springer; 1990. p.112-9.

— Chapter in a book: Sibai BM, Frangieh AY. Eclampsia. In: Gleicher N,editors. Principles and practice of medical therapy in pregnancy. 3rd ed. NewYork: Appleton&Lange; 1998. p. 1022-7.

Figures and tables

All illustrations (photographs, graphics, and drawings) accompanying the man-uscript should be referred to as “figure”. All figures should be numbered con-secutively and mentioned in the text. Figure legends should be added at the endof the text as a separate section. Each figure should be prepared as a separatedigital file in “jpeg” format, with a minimum 300 dpi or better resolution. Allillustrations should be original. Illustrations published elsewhere should be sub-mitted with the written permission of the original copyright holder. For recog-nizable photographs of human subjects, written permission signed by thepatient or his/her legal representative should be submitted; otherwise, patientnames or eyes must be blocked out to prevent identification. Microscopic pho-tographs should include information on staining and magnification.

Each table should be prepared on a separate page with table heading ontop of the table. Table heading should be added to the main text file on a sep-arate page when a table is submitted as a supplementary file.

Submission

For a swift peer review, Perinatal Journal operates a web-based submission, peerreview and manuscript tracking system. Authors are required to submit theirarticles online. Details of how to submit online can be found at www.perina-taljournal.com.

Submission Checklist

The following list will be useful during the final check of a manuscript beforesubmission:

1. Manuscript length (max. 4000 words for research articles)

2. Number of authors (max. 6 authors for research articles)

3. Title page (no anusual abbreviations)

4. Abstracts (max. 250 words for research articles)

5. Key words (max. 5 keys for research articles)

6. Main text (subtitles)

7. References (listed according to the rules of ICMJE)

8. Figures and tables (numbering; legends and headings; copyrightinfo/permission)

9. Cover letter

10. Acknowledgement of Authorship and Transfer of CopyrightAgreement (undersigned by all authors)

11. Conflicts of Interest Disclosure Statement (if necessary)

Volume 21 | Issue 3 | December 2013 v

Research Articles

The analysis of amniocentesis results of pregnants who are at 16-22 weeks of gestation and | 101undergone genetic amniocentesis

Genetik amniyosentez yap›lan 16-22 haftal›k gebelerin amniyosentez sonuçlar›n›n de¤erlendirilmesi

Alev Timur, ‹brahim Uyar, ‹brahim Gülhan, Nagehan Tan Saz, Alper ‹leri, Mehmet Özeren

Comparison of the use of dinoprostone and oxytocin for induction in cases | 107with Bishop score of ≤4

Bishop skoru 4 ve alt›nda olan gebelerde do¤um indüksiyonunda dinoproston ve oksitosin kullan›lmas›n›n karfl›laflt›r›lmas›

Özlem Yörük, Ayflegül Öksüzo¤lu, Yaprak Engin Üstün, Ayla Aktulay, Elif Gül Yapar Eyi, Salim Erkaya

Emergency peripartum hysterectomy: our experiences with 189 cases | 113

Acil peripartum histerektomiler: 189 olgu deneyimimiz

Abdulkadir Turgut, Muhammed Erdal Sak, Ali Özler, Hatice Ender Soydinç, Neval Yaman Görük, Talip Karaçor, Ahmet Yal›nkaya

The effect of maternal smoking during pregnancy on Doppler parameters | 119

Maternal sigara kullam›n›n Doppler ölçümleri üzerine etkisinin araflt›r›lmas›

Turab Janbakhisov, Özlen Emekçi, Erkan Ça¤l›yan, Ali Cenk Özay, Ferruh Acet, Sabahattin Altunyurt

Evaluation of prenatal ultrasonographic markers in aneuploidy cases | 124

Anöploidi olgular›n›n prenatal ultrasonografik belirteçlerinin de¤erlendirilmesi

Orkun Çetin, Fatma Ferda Verit Atmaca, Ayflegül Deregözü, Ali Galip Zebitay, O¤uz Yücel

Obesity at conceivement interferes with placental weight but not birth weight | 129

Pre-konsepsiyonel obezite plasental a¤›rl›¤› etkilemekle birlikte do¤um a¤›rl›¤›n› etkilememektedir

Gülengül Köken, Seda Köse, Da¤›stan Ar›öz, Mehmet Y›lmazer, Ayflenur Çak›r Güngör

The effects of gestational diabetes mellitus screening and diagnostic tests on fetal macrosomia | 133

Gebelik diyabeti tarama ve tan› testlerinin fetal makrozomi üzerine etkileri

U¤ur Keskin, Cihangir Mutlu Ercan, Saadettin Güngör, Kaz›m Emre Karaflahin, Ali Ergün, Mustafa Öztürk, Özlem Öztürk

The factors affecting the procedure duration during second trimester genetic | 138amniocentesis: retrospective analysis

‹kinci trimester genetik amniyosentezde ifllem süresine etki eden faktörler

Servet Hac›velio¤lu, Ahmet Uysal, Ayflenur Çak›r Güngör, Meryem Gencer, Emine Coflar

Placental and newborn birth weight in term pregnancy | 144

Term gebelikte plasenta ve yenido¤an do¤um a¤›rl›¤›

Cem Ard›ç, Resul Ar›soy, Emin Erhan Dönmez, Sevcan Arzu Ar›kan, Emre Erdo¤du, Semih Tu¤rul

ContentsVolume 21, Issue 3, December 2013

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Erratum

Erratum: Placental and newborn birth weight in term pregnancy | 151Yenido¤an otopsileri: Tek merkez deneyimiHatice Tatar Aksoy, S. Suna O¤uz, Nurdan Urafl, Ömer Erdeve, Hatice Bayramo¤lu, Sema Zergero¤lu, U¤ur Dilmen

Index

Subject and author indexes | 152

Reviewer indexini | 154

Contents

The analysis of amniocentesis results of pregnantswho are at 16-22 weeks of gestation and undergone

genetic amniocentesisAlev Timur1, ‹brahim Uyar2, ‹brahim Gülhan2, Nagehan Tan Saz2, Alper ‹leri2, Mehmet Özeren2

1Gynecology & Obstetrics Clinic, Private Sada Hospital, ‹zmir, Turkey 2Ege Maternity Ward, Tepecik Training and Research Hospital, ‹zmir, Turkey

IntroductionAmniocentesis based on the examination of amnioticcells has been a significant invasive technique in prena-tal diagnosis. It was first performed in 1950s for gender

determination.[1] Steele and Breg started karyotypedetermination in a classic way by culturing the cellsblended into amniotic fluid from fetal skin and urinarysystem.[2] Today, their major practice indications are

Abstract

Objective: It is aimed to evaluate the chromosome analysis results ofcases who undergone genetic amniocentesis for prenatal diagnosis.

Methods: Amniocentesis indications, culture successes, karyotyperesults, screening ultrasounds and gestational prognoses of 311amniocentesis cases referred to our perinatology clinic betweenNovember 2010 and April 2011 were evaluated retrospectively.Statistical analysis of the data was carried out by PredictiveAnalytics Software (PASW) package program.

Results: The mean age and gestational week of the cases who hadamniocentesis procedure were found to be 32.72±7.49 and17.98±6.56, respectively. The mean pregnancy number was2.46±1.45, the mean delivery number was 1.32±1.21, the meandelivery week was 38.24±1.32, and the mean newborn weight was3131±113 g. Chromosomal anomaly rate was found as 5.8%, whilefetal loss rate was 0.9%. It was found that the most frequent amnio-centesis indication was the risk increase at triple test (29.9%). Cellculture was successful in all 311 cases, except two cases (99.3%).

Conclusion: In this study, chromosomal anomaly rate was foundas 5.8%. In our study, the increased risk at triple test was found asthe most frequent amniocentesis indication.

Key words: Amniocentesis, prenatal diagnosis, karyotype.

Correspondence: ‹brahim Gülhan, MD. Tepecik E¤itim ve Araflt›rma Hastanesi, Ege Do¤umevi, ‹zmir, Turkey.e-mail: drigulhan@yahoo.com

Received: September 6, 2013; Accepted: November 25, 2013

©2013 Perinatal Medicine Foundation

Available online at:www.perinataljournal.com/20130213001

doi:10.2399/prn.13.0213001QR (Quick Response) Code:

Research Article

Perinatal Journal 2013;21(3):101-106

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Genetik amniyosentez yap›lan 16-22 haftal›kgebelerin amniyosentez sonuçlar›n›nde¤erlendirilmesiAmaç: Prenatal tan› amaçl› genetik amniyosentez yap›lan olgula-r›n kromozom analizi sonuçlar›n› de¤erlendirmek.

Yöntem: Kas›m 2010 - Nisan 2011 tarihleri aras›nda perinatolojiservisimizde yap›lan 311 amniyosentez olgusunun amniyosentezendikasyonlar›, kültür baflar›lar›, karyotip sonuçlar› ile tarama ul-trasonlar› ve gebelik prognozlar› retrospektif olarak de¤erlendiril-di. Verilerin istatistiksel analizi Predictive Analytics Software(PASW) paket program› ile yap›ld›.

Bulgular: Amniyosentez iflleminin yap›ld›¤› olgularda ortalamayafl ve gebelik haftas› s›ras›yla 32.72±7.49 ve 17.98±6.56 olarak bu-lundu. Ortalama gebelik say›s› 2.46±1.45, ortalama do¤um say›s›1.32±1.21, ortalama do¤um haftas› 38.24±1.32 ve ortalama bebeka¤›rl›¤› ise 3131±113 gram olarak tespit edildi. Kromozom anoma-lisi oran› %5.8 bulundu. Fetal kay›p oran› %0.9 olarak saptand›.En s›k amniyosentez endikasyonu üçlü testte risk art›fl› olarak tes-pit edildi (%29.9). Üç yüz onbir olgudan ikisi d›fl›nda hücre kültü-rü baflar›l› oldu (%99.3).

Sonuç: Bu çal›flmada kromozom anomalisi oran› %5.8 olarak bu-lunmufltur. Çal›flmam›zda üçlü testte artm›fl risk, en s›k amniyo-sentez endikasyonu olarak tespit edilmifltir.

Anahtar sözcükler: Amniyosentez, prenatal tan›, karyotip.

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abnormality in the screening tests applied for tri-somies, advanced maternal age, structural anomalies atultrasonography, delivery with chromosomal anomalyand chromosomal translocations known in one ofspouses.

Amniocentesis is conventionally applied between16 and 20 weeks of gestational for karyotype determi-nation. At this period, the rate of living cells to thenon-living cells in the amniotic fluid is higher com-pared to late (>20) weeks of gestation.[3] While thereare studies reporting high fetal loss rates when appliedat early weeks of gestation, there are also studiesreporting that fetal loss for the procedure is increasedwhen applied after 18 weeks of gestation.[4,5]

Markers detected in ultrasonographic examinationssuch as nuchal translucency, echogenic intestine, shortfemur, pyelectasis, lack of nasal bone, choroid plexuscsyt, and echogenic intracardiac focus are associatedwith Down syndrome and other aneuploidies.[6]

Prenatal screening tests conducted for Down syn-drome diagnosis are more significant than the secondtrimester ultrasonographic screening tests.Amniocentesis requirement increases when ultrasono-graphic markers are detected when screening morechromosomal anomalies in structural abnormalities,and therefore this procedure increases abortus rateeven a little.

Our aim in this study is to evaluate genetic amnio-centesis results, screening ultrasound and gestationalprognoses of 16-22 weeks pregnant cases who were fol-lowed up at our clinic, and undergone genetic amnio-centesis.

MethodsPatients who referred to our perinatology clinicbetween November 2010 and April 2011 and under-gone amniocentesis were included to the study. Asinclusion criteria, patients who were between 16 and22 weeks of gestation, found to have risk increase in thefirst or second trimester Down syndrome screeningtests, or undergone amniocentesis for diagnosis pur-pose since they were 35 years old or above were chosenfor the study (cut off value was determined as 1/270 fordouble and triple tests).[7] The amniocentesis results ofthe cases chosen for the study were retrospectivelyscanned for prenatal diagnosis.

At our hospital, genetic consultancy is provided tocases who are suggested amniocentesis. Before the pro-

cedure, informed consent forms were received fromthe couples who accept the intervention.

Before amniocentesis, each fetus is examined byUSG in detail and the location of placenta, amount ofamniotic fluid and procedure location are determined.Completed 35th age was accepted as advanced maternalage. It was expressed to cases who received or did notreceive genetic consultancy that risk calculation mightbe performed by non-invasive methods (triple test,detailed USG). Cut off value as increased risk at triplewas determined as 1/270; however, risk calculation wasdone amniocentesis option was offered to cases inwhich chromosomal anomaly markers were detected byultrasonography among risky cases below 1/270.

All cases were called for control according to theirkaryotype result, and fetal losses after intervention, anddelivery time and type, newborn findings and neonatalprognosis in cases followed up from post-procedure upto delivery were recorded.

Amniocentesis procedures of the cases included toour study were carried out between 16 and 22 weeks ofgestation. Skin cleaning was done by povidone-iodine,and disposable 2, 5 or 10 ml injectors and 9 cm 20 or22 G spinal needles were used for puncture and aspira-tion. Interventions are done by free hand techniquewith the help of USG. Incoming fluid is aspirated byapplying slight negative pressure and amniotic fluid iscollected as 1 ml per gestational week. For cases withRh incompatibility risk, 300 μg anti-D IgG and post-procedure oral antibiotic and paracetamol are pre-scribed.

Collected fluids were sent to a private laboratoryfor analysis. Giemsa banding technique was used forevaluation after amniotic fluid culture. 20-50metaphase plates which were accepted sufficient foreach case were analyzed for numerical and structuralabnormalities in chromosomes. Mean cell culture peri-od was 14-20 days and the results were obtained aver-agely in 21 days.

Statistical analysis of the data was carried out byPredictive Analytics Software (PASW) package pro-gram. Definitive statistics were expressed asmean±standard deviation for continuous data, and asobservation number and percentage (%) for categoricaldata. Significance levels and 95% confidence intervalsfor risk factors were calculated by chi-square test. Pvalues less than 0.05 were accepted as statistically sig-nificant.

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ResultsMean age and gestational week in cases who hadamniocentesis procedure were 32.72±7.49 and17.98±6.56, respectively. The mean pregnancy numberwas 2.46±1.45, the mean delivery number was1.32±1.21, the mean delivery week was 38.24±1.32, andthe mean newborn weight was 3131±113 g (Table 1).

Chromosomal anomaly rate was found as 5.8%(18/309) according to amniotic culture results, anddetailed distribution was given in Tables 2 and 3.Except cases found to have anomalies, stable transloca-tion was found in 2 cases [t (7,22)(p11,2; q11,2), t(2,10)(q31; q22)], and variant of normal was found in 6cases [46 inv (9)(p11q12)]. In 291 of the pregnants(94.2%) fetal karyotype was found to be normal/vari-ant of normal/stable translocation. The distribution ofcytogenetic results obtained in the karyotyping accord-ing to amniocentesis indications are given in Table 3.

In our amniocentesis series, the success rate ofachieving cell culture was 99.7% (309/311), and cul-ture failure rate was 0.3% (2/311). The amniocentesisindication in two cases without any culture reproduc-tion was risk increase in double test for one case, andanencephaly detection in anomaly USG screening forthe other case. Pregnancy of the case found to haveanencephaly was terminated at 20 weeks. Other casedelivered a healthy baby (3250 g) at 38 weeks.

In the distribution of cases according to theiramniocentesis indications, advanced maternal age wasthe biggest group with 152 cases (48.8%). However, 50of these cases had triple test and 26 of them had dou-ble test, and their test results became compatible withincreased biochemical risk except age risk.Amniocentesis was carried out in 76 cases (25.1%) onlyfor advanced maternal age. Also, increased risk at tripletest was found in 93 cases (29.9%) who were not at anadvanced maternal age, fetal anomaly at USG wasfound in 37 cases (11.8%), and increased risk at doubletest was found in 24 cases (8.3%). Anomalies detectedby ultrasonography were central nervous system anom-alies in particular, cardiac anomalies, pelviectasis, cys-tic hygroma, hydrops fetalis, hyperechogenic intestine,choroid plexus cyst, and omphalocele. Beside theseanomalies, two cases had baby with trisomy 21 historyand one case had baby with trisomy 18 history. In theseconditions, risk increase at triple test was the most fre-quent amniocentesis indication with 143 cases (93+50).

Pregnancy was terminated in 30 cases (9.6%) out of311 amniocentesis cases. While the termination reasonwas chromosomal anomaly in 15 cases out of 30 cases,it was fetal anomalies found at US against normal kary-otype in other 15 cases. The termination indications in15 cases with normal karyotype and 2 cases with stabletranslocation and addition were central nervous systemanomaly in 10 cases, cardiac anomaly in 2 cases,hydrops fetalis in 2 cases and multiple anomaly in onecase. Anomalies found in 15 cases of whom pregnan-cies were terminated due to chromosomal anomalywere trisomy 21 in 8 cases, trisomy 18 in 3 cases,Turner syndrome in 2 cases, del(9)(p24) unstabletranslocation in 1 case and 69XXX karyotype in onecase. One case who had triploid did not accept termi-nation. Three out of four cases with stable transloca-tion and addition received genetic consultancy anddelivered healthy babies at term by cesarean section.

Abortus was seen in five cases and in utero mortfetalis in two cases among patients who had amniocen-tesis. While the reason for performing amniocentesison one case that had normal fetal karyotype result was‘advanced maternal age’ and abnormal USG, it wasabnormal USG findings for four cases. In other twocases, chromosomal anomaly was found according toamniocentesis results. Abortus occurred within 30 daysin four cases that had normal fetal karyotype result andundergone amniocentesis due to abnormal USG indi-

Table 1. Demographic data of the cases who undergone amniocen-tesis.

Ortalama (±SD)

Age 32.72±7.49

Pregnancy number 2.46±1.45

Delivery number 1.32±1.21

Gestational weeks at delivery 38.24±1.32

Birth weight (gram) 3131±113

Table 2. Karyotype results.

Karyotype Case number Percentage (%)

Normal 291 94.2%

Trisomy 21 8 2.5%

Trisomy 18 3 0.9%

Turner syndrome 2 0.6%

69XXX 2 0.6%

Unstable karyotype 3 0.9%

Total 309 100

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cation. The amniocentesis indication was abnormalUSG findings in another case who had abortion with-in one week after the procedure and found to have69XXX.

Early fetal loss rate associated with amniocentesisdue to the loss of 3 fetuses with normal fetal karyotypeand no anomaly in the first 30 days after the procedurewas found as 0.9%.

In utero mort fetalis developed 6 weeks later (24weeks) in one case who had normal fetal karyotyperesult and undergone amniocentesis due to advancedmaternal age indication. It was seen 5 weeks after theprocedure (22 weeks) in another case who found tohave trisomy 18 and undergone amniocentesis due toadvanced maternal age.

Early membrane rupture was observed in two cases(0.6%) and preterm labor in one case (0.3%) within theamniocentesis group.

Abnormal karyotype was detected in 9 (19.5%)patients out of 46 patients who were found to haveanomaly in ultrasonography. Only one (1.1%) case outof 89 cases, who found to have normal results in fetalanomaly USG, had abnormal karyotype. Accordingly,there was statistically significant relationship betweenhaving fetal anomaly in USG and having abnormalkaryotype in amniocentesis (p=0.015).

DiscussionAmniocentesis which is the oldest prenatal diagnosismethod is mostly performed at 16-18 weeks of gestationfor genetic diagnosis purposes. The procedure indica-tions are advanced maternal age in particular, increasedrisk at triple test, child history with chromosomal anom-aly, or fetal anomaly detection at USG.

In our study, it was found that the most frequentintervention reason alone is increased risk at triple testwith 93 (29.9%) cases, and advanced maternal age wasthe second one with 76 (25.1%) risk. Sjögren et al. foundthat the most frequent reason among amniocentesiscases was advanced maternal age with 57% of the cases.[8]

This rate is 87% in the study of Milewczyk et al.[9] In thestudy of Bal et al., they found the rate of maternal age as51%.[10] In various amniocentesis studies published inTurkey, advanced maternal age is reported as the mostfrequent intervention reason.[11-13]

In our amniocentesis series, chromosomal anomalywas found in 18 (5.8%) cases. This rate was foundbetween 3.3% and 4.5% in other series published inTurkey.[11-14] Baflaran et al. found chromosomal anomalyrate in 11 cases (3.5%) out of 301 cases.[14] While Sjögrenet al. reported this rate as 2.5% in their study performedon 211 cases,[8] Milewczyk et al. found the rate as 5.4%.[9]

We found chromosomal anomaly in 3 (3.84%) cases out

Table 3. The distribution of cytogenetic results obtained in the karyotyping according to amniocentesis indications.

Delivery with Advanced Fetal Increased Increased risk NT chromosom al anomaly maternal age anomaly at USG risk at triple test at double test increase

(n=3) (n=76) (n=37) (n=143) (n=50) (n=1)

No reproduction (n=2 – – 1 - 1 –

Normal karyotype (n=283) 3 72 29 133 45 1

Trisomy 21 (n=8) – – 2 4 2 –

Trisomy 18 (n=3) – 1 1 – 1 –

45X (Turner syndrome) (n=2) – – 2 – – –

69XXX (n=2) – – 1 1 – –add (15)(p13), add (21)(p13),del (9)(p24)[unstable karyotype] (n=3)

t(7,22) (p11,2;q11,2), – 1 – 1 – –t(2,10) (q31;q22)[stable translocation] (n=2)

46inv (9) (p11q12) – 3 – 2 1 –[normal variant] (n=6)

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of 76 cases who undergone amniocentesis due toadvanced maternal age. They were trisomy 18,t(7,22)(p11,2;q11,2), and add(15)(p13). Sjögren et al.reported this rate 2.2% for cases above 35 years old andas 5.3% for cases above 40 years old.[8] Nagel et al. foundthis rate as 4.7% for cases at 36 years old and above, andterminated 70.8% of pregnancies.[15] In the studies per-formed in Turkey, chromosomal anomaly rates werefound between 1.2% and 13.3% in cases who undergoneamniocentesis due to advanced maternal age indica-tion.[10,13,16]

In our study, chromosomal anomaly was found in 6(4.2%) out of 143 cases who undergone amniocentesisdue to increased risk at triple test (≥1/270) Qi et al.,[7]

reported in their multi-centered study that they foundchromosomal anomaly in 22 (3%) cases out of 727 whohad amniocentesis by considering cut-off value as≥1/270. Four of detected chromosomal anomaly caseswere trisomy 21, 1 case was 69XXX, 1 case wasd(21)(p13), and 1 case was t(2,10)(q31;q22).

Yüce et al. found chromosomal anomaly rate as 3.7%in cases who undergone amniocentesis due to increasedrisk at triple test.[13] Wenstrom et al. detected 15 (2.9%)fetal karyotype anomalies in 516 cases who had tripletest risk.[17] Bal et al. reported chromosomal anomaly rateas 3.9% in cases who had high risk for chromosomalanomaly at triple test.[10]

We found chromosomal anomaly in 3 (6%) cases outof 50 cases who undergone amniocenteses due to highrisk at double test. Of detected chromosomal anomalies,2 cases had trisomy 21 and 1 case had trisomy 18. Therelationship between double test and amniocentesis isstronger than the relationship between triple test andamniocentesis. Today, double test is preferred more fre-quently as anomaly screening. Triple test is used mostlikely to screen the risk increase of spina bifida.

There are prominent differences among chromoso-mal anomaly detection rates in the amniocentesis seriesperformed due to the detection of fetal anomaly at USG.This rate is reported between 4% and 27.1% in variousseries.[13,18-20] Stoll et al. found chromosomal anomaly at8.9% after amniocentesis performed on 119 cases whohad fetal USG anomaly.[20] Rizzo et al. reported chromo-somal anomaly in 16.8% of 173 fetuses who found tohave fetal anomaly at ultrasonography.[18] Hsieh et al.reported this rate as 20.27% in 148 cases with fetal USGanomaly.[21] In our case, we found chromosomal anomalyin 4 (10.8) cases among 37 cases who undergone amnio-centesis due to fetal anomaly detection at USG. By these

data, the possibility to detect chromosomal anomaly atamniocentesis increases in the presence of fetal anomaly(rather than maternal age and triple test). At experiencedhands, fetal loss rates due to amniocentesis is not higherthan 0.5-1%. While Eddlemann et al. found fetal lossrate as 0.15% in their series consisting of 1605 cases,[22]

Armstrong et al. reported fetal loss rate as 0.2% in theirseries consisting of 28.163 cases.[23] Fetal loss rate inLockwood’s amniocentesis series consisting of 1375cases is 0.40%.[21] Anderson et al. found this rate as0.80% in their series consisting of 1200 cases.[24] Eydouxet al. found fetal loss rate 1.3%.[25] In Turkey, fetal lossrates were found to be between 0.6% and 3.3%.[10,11,14]

In our amniocentesis series, fetal loss occurred in 3out of 311 cases within 30 days. Our loss rate is 0.9%,and it is consistent with the results reported in the liter-ature. The patient should be informed in detail aboutthe risks before the amniocentesis procedure. Informingpatient about this matter is significant in terms of judi-cial and medical problems.

Cytogenetic analysis of amniotic cells indicates fetalgenotype with accuracy level reaching 99%. Accordingto our amniocentesis results, fetal cell reproduction wasnot occurred only 2 cases and culture success was foundas 99.3%. Lack of culture reproduction of these cases wasaffiliated with the contamination by related laboratory.Similarly, culture success was found 98% by Güven et al.who sent amniotic fluids to an external center.[26] In theseries published in 2006 by Müngen et al. and consistedof 2068 cases, culture success was reported 98.2%.[27]

Tabor et al. found mosaicism 0.1% which is a significantproblem in chromosomal analyses.[28] In such a case, cor-docentesis is suggested instead of re-performance ofamniocentesis. No mosaicism was found in our study.

In amniocentesis group, early membrane rupturewas found in 2 cases (0.6%) and preterm labor was foundin one case (0.3%). Early membrane rupture was report-ed 1-1.2% after amniocentesis in the study performedby Phubong et al.[29] In the study performed by Borrelliet al., preterm labor was reported in 6% of 1416 cases.[30]

ConclusionConsequently, we found chromosomal anomaly rate5.8% and fetal loss rate 0.9% in our study. Increasedrisk at triple test and advanced maternal age are themost frequent indications of amniocentesis.

Conflicts of Interest: No conflicts declared.

References1. Drugan A, Johnson MP, Evans MJ. Amniocentesis In: Evans

MI (Ed). Reproductive Risks and Prenatal Diagnosis. NewYork: Appleton&Lange; 1992. p. 191-200.

2. Steele WW, Breg WR. Chromosome analysis of humanamniotic fluid celss. Lancet 1966;1(7434):383-5.

3. Gerbie AB, Elias S. Technigue for midtrimester amniocen-tesis for prenatal diagnosis. Semin Perinatol 1980;4:159-63.

4. Lynch L, Berkovvitz RL. Amniocentesis, skin biopsy, umbil-ical cord blood sampling in the prenatal diagnosis of geneticdisorders. In: Reece EA, Hobbins JC,Mahoney MJ (Eds).Medicine of the Fetus and Mother. Philadelphia: JB.Lippincott; 1992. p. 641-52.

5. Kong CW, Leung TN, Leung TY, Chan LW, Sahota DS,Fung TY, et al. Risk factors for procedure-related fetal loss-es after mid-trimester genetic amniocentesis. Prenat Diagn2006;26:925-30.

6. Twining P. Chromosome abnormalities. In: Twining P, McHugo JM, Pilling DW (Eds). Textbook of FetalAbnormalities. New York: Churchill Livingstone; 2000. p.315-44

7. Qi QW, Jiang YL, Liu JT, Bian XM, Li Y, Lü SM, et al.Second trimester maternal serum screening for Down's syn-drome in women of advanced maternal age: a multi-centerprospective study. [Article in Chinese] Zhonghua Fu ChanKe Za Zhi 2008;43:737-41.

8. Sjögren B, Uddenberg N. Decision making during the pre-natal diagnostic procedure. A questionnaire and interviewstudy of 211 women participating in prenatal diagnosis.Prenat Diagn 1988;8:263-73.

9. Milewczyk P, Lipiƒski T, Hamela-Olkowska A, Jalinik K,Czajkowski K, Zaremba J. Genetic amniocentesis in the IIDepartment of Obstetrics and Gynecology of the MedicalUniversity of Warsaw. [Article in Polish] Ginekol Pol2004;75:603-8.

10. Bal F, U¤ur G, Y›ld›z A, fiahin ‹, Menekfle A. 2. trimesterriskli gebeliklerinde amniyosentez uygulamalar›. TürkiyeKlinikleri Jinekoloji Obstetrik Dergisi 1995;5:249-56.

11. Yayla M, Bayhan G, Yal›nkaya A, Alp N. Yüksek riskli gebe-liklerde 2. trimester genetikamniyosentez: 165 olgununklinik de¤erlendirilmesi. Perinatoloji Dergisi 1999;7:40-6.

12. Cengizo¤lu B, Karageyim Y, Kars B, Altunda¤ M, Turan C,Ünal O. Üç y›ll›k dönemdeki amniyosentez sonuçlar›.Perinatoloji Dergisi 2002;1:14-7.

13. Yüce H, Çelik H, Güratefl B, Erol D, Hanay F, Elyas H.Karyotip analizi amac› ile genetik amniyosentez uygulanan356 olgunun retrospektif analizi. Perinatoloji Dergisi2006;14:73-6.

14. Baflaran S, Karaman B, Ayd›nl› K, Yüksel A. Amniyotik s›v›,trofoblast dokusu ve fetal kan örne¤inde sitogenetikincelemeler. 527 olguluk seri sonuçlar›. Jinekoloji ObstetrikDergisi 1992;6:81-9.

15. Nagel HT, Knegt AC, Kloosterman MD, Wildschut HI,Leschot NJ, Vandenbussche FP. Invasive prenatal diagnosisin the Netherlands, 1991-2000: number of procedures, indi-

cations and abnormal results detected. Ned TijdschrGeneeskd 2004;31:1538-43.

16. Taner CE, Alt›nbaflo¤lu FH, Özkiriflçi FH, ‹mren A,Büyüktosun C, Özgenç Y, Derin G. ‹leri maternal yafl gebe-liklerinde amniyosentez sonuçlar›. Perinatoloji Dergisi2002;4:336-9.

17. Wenstrom KD, Williamson RA, Grant SS, Hudson JD,Getchell P. Evaluation of multipl-marker screening forDown syndrome in a statewide population. Am J ObstetGynecol 1993;169:793-7.

18. Rizzo N, Pittalis MC, Pilu G, Orsini LF, Perolo A, BovicelliL. Prenatal karyotyping in malformed fetus. Prenat Diagn1990;10:17-23.

19. Dallaire L, Michaud J, Melancon SB, Potier M, Lambert M,Mitchell G, et al. Prenatal diagnosis of fetal anomalies dur-ing the second trimester of pregnancy: their characterizationand delineation of defects in pregnancies at risk. PrenatDiagn 1991;11:629-35.

20. Stoll C, Dott B, Alembik Y, Roth M. Evalution of routineprenatal ultrasound examination in detecting fetal chromo-somal abnormalities in a low risk population. Hum Genet1993;91:37-41.

21. Hsieh FJ, Ko TM, Tseng LH, Chang LS, Pan MF, ChuangSM, et al. Prenatal cytogenetic diagnosis in amniocentesis. JFormos Med Assoc 1992;91:276-82.

22. Eddleman K, Berkowitz R, Kharbutli Y, Malone F, VidaverJ, Porter TF, et al. Pregnancy loss rates after midtrimesteramniocentesis: the FASTER trial. Am J Obstet Gynecol2003;189:S111.

23. Armstrong J, Cohen AW, Bombard AT, Bondi R.Comparison of amniocentesis-related loss rates betweenobstetrician-gynecologists and perinatologists. ObstetGynecol 2002;99:65S.

24. Anderson RL, Goldberg JD, Golbus MS. Prenatal diagnosismultipl gestation. 20 years experience with amniocentesis.Prenat Diagn 1991;11:263-70.

25. Eydoux P, Choiset A, Porrier NL, Thepot F, Tapia SS,Alliet J, et al. Chromosomal prenatal diagnosis: Study of 936cases of intrauterin abnormalities after ultrasound assess-ment. Prenat Diagn 1989;9:255-68.

26. Güven MA, Ceylaner S. Amniyosentez ve kordosentez ileprenaral tan›: 181 olgunun de¤erlendirilmesi. PerinatolojiDergisi 2005;13:25-9.

27. Müngen E, Tütüncü L, Muhcu M, Yergök YZ. Pregnancyoutcome following second-trimester amniocentesis: a case-control Study. Am J Perinatol 2006;23:25-30.

28. Tabor A, Madsen M, Philip J. Randomised controlled trial ofgenetic amniocentesis in 4606 low risk women. Lancet1986;1:1287-93.

29. Phupong V, Ultchaswadi P. Spontaneous reseal of rupturedmembranes after genetic amniocentesis. J Med Assoc Thai2006;89:1033-5.

30. Borrelli AL, Cobellis L, Di Domenico A, Felicetti M,Laboccetta A, Ferrara C, et al. Fetal and maternal amniocen-tesis complications]. [Article in Italian] Minerva Ginecol2006;58:423-7.

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Comparison of the use of dinoprostone and oxytocinfor induction in cases with Bishop score of ≤4

Özlem Yörük, Ayflegül Öksüzo¤lu, Yaprak Engin Üstün, Ayla Aktulay, Elif Gül Yapar Eyi, Salim Erkaya Zekai Tahir Burak Maternal Health Training and Research Hospital, Ankara, Turkey

Abstract

Objective: The aim of this study is to compare the efficiency, reli-ability, and maternal and perinatal complications of dinoprostoneand oxytocin for induction of labor, both separately and together,in women with a Bishop score of ≤4.

Methods: A total of 279 primigravida patients, diagnosed witholigohydramnios and prolonged pregnancy, over 37 weeks of gesta-tion with a Bishop score of ≤4 and had been admitted to our hospi-tal’s delivery unit for labor induction between January and April2013 were divided into three groups. Thirty-four patients who wereadministered intravaginal dinoprostone formed the 1st group. The2nd group consisted of 204 patients who were administered intra-venous oxytocin. The 41 patients in the 3rd group were initiallyadministered dinoprostone and subsequently oxytocin. Age, bodymass index (BMI), the duration of the latent and active phases oflabor, presence of meconium, and changes in the NST were record-ed for each pregnant woman. Delivery method, birth weight andgender of the neonates were also recorded. Indications for caesareansection and maternal and neonatal complications were investigated.

Results: When these three groups were compared, no difference wasfound in terms of age, gravida, parity, BMI and duration of pregnan-cy. However; comparison of the 3 groups for latent and active phasesindicated that the active phase to be significantly shorter in thepatients administered dinoprostone (p=0.001). When compared forthe caesarean section ratios, 1st and 3rd groups were found to havehigher ratios than the 2nd group (p=0.000). No difference was notedamong the 3 groups in terms of maternal and perinatal outcomes.

Conclusion: Although dinoprostone increases caesarean sectionratio, it decreases the active phase of labor and does not affectmaternal and fetal morbidity. The labor induction method to bechosen may change depending on the patient and option of thephysician doing the evaluation.

Key words: Dinoprostone, labor induction, oxytocin.

Correspondence: Özlem Yörük, MD. Zekai Tahir Burak Kad›n Sa¤l›¤› E¤itim ve Araflt›rma Hastanesi, Ankara, Turkey.e-mail: özlemese@gmail.com

Received: June 5, 2013; Accepted: September 10, 2013

©2013 Perinatal Medicine Foundation

Available online at:www.perinataljournal.com/20130213002

doi:10.2399/prn.13.0213002QR (Quick Response) Code:

Research Article

Perinatal Journal 2013;21(3):107-112

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Bishop skoru 4 ve alt›nda olan gebelerde do¤umindüksiyonunda dinoproston ve oksitosinkullan›lmas›n›n karfl›laflt›r›lmas›Amaç: Çal›flmam›z›n amac› term veya günafl›m› gebeliklerde ser-viksi olgunlaflt›rma ve do¤um eylemi indüksiyonunda s›k kullan›-lan ajanlardan dinoproston ve oksitosin kullan›mlar›n›n ayr› ayr› vebirlikte kullan›mlar›n›n etkinli¤ini, güvenirlili¤ini, maternal ve pe-rinatal komplikasyonlar›n› karfl›laflt›rmakt›r.

Yöntem: Hastanemiz do¤um ünitesinde 2013 Ocak-Nisan ayla-r›nda oligohidroamnios ve günafl›m› gebelik tan›lar›yla do¤um in-düksiyonu için yat›r›lm›fl 37 gebelik haftas› üzerinde, Bishop sko-ru ≤4 olan primigravid 279 hasta 3 gruba ayr›ld›. ‹ntravajinal di-noproston uygulanan 34 hasta grup 1’i, intravenöz oksitosin uygu-lanan 204 hasta grup 2’yi oluflturdu. Grup 3’ü oluflturan 41 hasta-ya ise önce dinoproston, takibinde ise oksitosin uyguland›. Gebe-lerin yafl›, vücut kitle indeksleri (VK‹), do¤um eyleminin latent veaktif fazlar›n›n süresi, mekonyum varl›¤›, NST de¤ifliklikleri kay›tedildi. Olgular›n do¤um flekilleri, bebeklerin do¤um kilosu ve cin-siyetleri not edildi. Sezaryen endikasyonlar› ile anneye ve yenido-¤ana ait komplikasyonlar araflt›r›ld›.

Bulgular: Bu üç grup karfl›laflt›r›ld›¤›nda aralar›nda yafl, VK‹ vegebelik süresi aç›s›ndan fark bulunamad›. Ancak 3 grup latent sü-re ve aktif süre aç›s›ndan karfl›laflt›r›ld›¤›nda dinoproston uygula-nan hastalarda aktif sürenin anlaml› olarak daha k›sa oldu¤unubulduk (p=0.001). Bu üç grup sezaryen oran› aç›s›ndan karfl›laflt›-r›ld›¤›nda grup 1 ve 3’de grup 2’ye göre anlaml› olarak daha fazlasezaryen uyguland›¤› görüldü (p=0.000). Maternal ve perinatal so-nuçlar aç›s›ndan 3 grup aras›nda fark bulunmad›.

Sonuç: Sonuç olarak dinoproston sezaryen oranlar›n› art›rmas›nara¤men do¤umun aktif dönemini k›saltmakta, maternal ve fetalmorbiditeyi etkilememektedir. Do¤um indüksiyonu için kullan›la-cak yöntemin seçimi, hastaya ve de¤erlendirmeyi yapacak olan he-kimin tercihine göre de¤iflebilir.

Anahtar sözcükler: Dinoproston, eylem indüksiyonu, oksitosin.

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IntroductionThe induction of labor is to initiate regular uterinecontractions mechanically or by pharmacologicalmethods in order to provide labor following the pro-gressive cervical dilatation before spontaneous laborbegins.[1] The induction of labor is suggested for caseswhere maintaining pregnancy poses risk for mother orfetus. Approximately 20-30% of all pregnant womenare induced.[2,3]

Although oxytocin is a safe and effective inducer ofuterine contractions during the induction of labor, ithas less or no effect on cervical maturity. In caseswhere cervix is not appropriate, it is generally hard ortakes long to induce labor, and the rates of attemptedlabor and caesarean labor increase. Prostaglandinpreparations are used to prepare cervix which is notappropriate for induction. Recently, dinoprostonewhich is applied vaginally and provides regular low-dose and controlled prostaglandin E2 release is fre-quently used for labor induction. This new design alsohas a retraction system, so it can be easily and quicklyretracted at the end of 12 hours of dosing or in thebeginning of active labor.

Since the use of prostaglandin E1 (misoprostol) forlabor induction is not approved in our country by theregulations of Turkish Drug and Medical DeviceInstitution of the Ministry of Health, we planned astudy in order to compare the use of dinoprostone andoxytocin, which we assumed economic, on patientswith Bishop score of ≤4.

MethodsThe patient files of 279 primigravida patients, diag-nosed with oligohydramnios and prolonged pregnancy,over 37 weeks of gestation with a Bishop score of ≤4and had been admitted to our hospital’s delivery unitfor labor induction between January and April 2013were examined retrospectively.

After uterine was separated into 4 quadrants byPhelan technique,[4] pockets with amniotic fluid weremeasured on vertical plane, and their total amount wasrecorded as amniotic fluid index (AFI). It was consid-ered as oligohydramnios when obtained total value wasbelow 5 cm. Since the oligohydramnios is associatedwith bad perinatal outcomes, labor induction is initiat-ed in many pregnancies which are at or near term.

Pregnancies which were 41 weeks and 4 days andabove were considered as prolonged pregnancy accord-ing to our clinical protocols.

The patients were divided into 3 groups. In the firstgroup consisting of 34 pregnants, 10 mg dinoprostone(Propess® ovule, Vitalis, Ankara, Turkey) was placedinto posterior vaginal fornix and their labors were fol-lowed up. Propess ovule was kept in the freezerbetween -10°C and -20°C as stated in the prospectus,and applied by taking out of the freezer just before theapplication. After applied, they were treated as medicalwaste. Low-dose oxytocin protocol was applied to 204pregnants constituting the second group (Synpitan®,Deva, ‹stanbul, Turkey). Synpitan ampule was kept inthe room temperature below 25°C. The third groupincluded 41 patients who were initially applied dino-prostone but could not get into active labor at least 12hours because of displacement of dinoprostone andoxytocin induction was started.

High risky pregnants (diabetes mellitus, hyperten-sion, multiple pregnancy, intrauterine growth retarda-tion etc.) and cases with early membrane rupture andfetal anomaly were excluded from the study.

The weeks of the gestation were recorded.Gestational ages of patients who could not rememberthe date of last menstrual period were determinedaccording to first trimester or early second trimesterultrasonography. Ages and body mass indexes (BMI) ofthe pregnants were recorded.

The duration of the latent and active phases oflabor, presence of meconium, and changes in the NSTwere recorded for each pregnant woman.

Dinoprostone was placed into ovule posteriorfornix horizontally. The presence of contractions withfrequent intervals less than two minutes and lastingmore than 90 seconds was considered as hyperstimula-tion and dinoprostone vaginal ovule was removed andthe pregnant was turned to her left side, oxygen wasapplied with 500 ml crystalloid solution infusion andnasal cannula or mask.[5]

As intravenous infusion, oxytocin (Synpitan®, Deva)was started at 2 mU/min as 5 units of intravenous with-in 500 cc 5% dextrose and it was increased 2 mU/minevery 20 minutes until it reached 36 mU/min. Totalinduction duration was recorded.

The duration until cervix effacement was 70% anddilatation was 4 cm was deemed as the latent phase ofthe delivery while the duration until cervix effacement

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and dilatation were both full was deemed as the activephase of the delivery; and both durations were recorded.

The patients were monitored during labor. In NSTevaluation, fetal heart rate acceleration at least for 15seconds and 15 beat/min in 20 minutes was consideredas reactive, while decreases at least for 15 seconds and15 beats were considered as deceleration, and non-presence of these accelerations and decelerations wereconsidered as non-reactive.[5] NST was carried out byPhilips 50A or Corometrics model 170 monitors byusing external ultrasonographic transducer. AFI wasmeasured by using Mindray M5 3.5 MHz linear probe.

Delivery types, birth weights and genders ofneonates were recorded. Caesarean indications andmaternal and fetal complications were screened.Bleeding after delivery or caesarean more than normalwith uterine relaxation was considered as atonic bleed-ing. Conditions such as the need for resuscitation duringat delivery, fifth minute Apgar score below 7, presenceof encephalopathy (lethargy, stupor, hypotonia, andabnormal or insufficient reflex findings including lack ofsucking reflex), development of multiple organ dysfunc-tion (encephalopathy and involvement of at least oneorgan), need for mechanical ventilation, breathing tostart late, and the pH value of blood gas lower than 7.2were considered as perinatal asphyxia. The diagnosis oftemporal fetal tachypnea was established by tachypneastarted within the first 6 hours after birth and continuedat least for 12 hours as well as respiration increase inchest radiography, vascular congestion, and observingfluid accumulation at fissures and costophrenic angle,and the lack of other diseases having similar findings.

Statistical Analysis

Distribution of numerical data was analyzed byKolmogorov-Smirnov test. The difference of variables

displaying normal distribution among 3 groups wasanalyzed by one-way analysis of variance. Paired com-parisons afterwards were done by Tukey test. The dif-ference of variables not displaying normal distributionamong 2 groups was analyzed by Mann-Whitney Utest while it was analyzed for 3 groups by Kruskal-Wallis test, and then paired comparisons were done byDunn test. The data was expressed as mean±standarddeviation or median (minimum-maximum). The corre-lation among qualitative variables was analyzed byPearson chi-square test and Fisher exact test. Theanalyses were carried out by SPSS for Windows 20.0(SPSS Inc., Chicago, IL, USA). p<0.05 was consideredas the statistical significance limit.

ResultsThe 279 patients included to this study constituted8.9% of 3133 deliveries carried out within 3 months.Mean age of the patients was found as 26.2±5.3. Whenthe three groups were compared, no difference wasfound among them in terms of age, BMI and weeks ofgestation. However, there was significant differenceamong them in terms of latent duration and activeduration. These results are given in Table 1.

While meconium was seen in 26 patients (12.7%) inthe Group 2, it was seen in 6 patients (11.5%) in theGroup 3; but there was no patient with meconium inthe Group 1. There was no significant differenceamong three groups in terms of meconium (p=0.077).

Abnormal NST findings were observed in 6patients (17.6%) in the Group 1, in 35 patients (17.2%)in the Group 2 and in 12 patients (29.3%) in the Group3. When analyzed in terms of abnormal NST findings,there was no difference among 3 groups (p=0.490).

It was seen that caesarean section was applied to 18patients (52.9%) in the Group 1, 70 patients (34.3%) in

Table 1. Demographic and clinical data of the groups*.

Group 1 Group 2 Group 3(N=34) (N=204) (N=41) p

Age (year) 26.2±4.6 26.1±5.1 24.8±5.5 0.480BMI† (kg/m2) 29.8±4.7 29.9±4.9 31.6±7.4 0.259Duration of pregnancy (day) 287.3±3.5 288.0±3.3 287.6±3.2 0.185Latent period (min) 858.97±524.96 639.49±569.89 1665.24±1341.71 0.000Active period (min) 154.11±132.86 229.60±184.81 246.87±269.20 0.001

*Values are given as mean±standard deviation. †BMI: body mass index.

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the Group 2, and 28 patients (68.3%) in the Group 3.When these three groups were compared for caesareanrates, it was seen that the rate was higher in Group 1and Group 3 than Group 2 (p=0.000). In terms of cae-sarean indications, there was no significant differenceamong 3 groups (p=0.275). These indications areshown in Table 2.

While the caesarean rate at our hospital’s deliveryunit was 39.7% in general, our primary caesarean ratewas 18%.

When neonate weights were analyzed, it was seenthat there was no significant difference among groups(it was 3461±428 g in Group 1, 3469±414 g in Group2, and 3451±408 g in Group 3; p=0.110). It was seenthat 2 neonates were followed up at intense care unitdue to perinatal asphyxia and they were dischargedfrom the hospital as were.

The most common problem when using dinopros-tone was miscarriage in 12 (29.2%) out of 41 patientsconstituting Group 3. Hyperstimulation associatedwith dinoprostone was observed in 6 patients (14.6%).

Maternal complications in our study were observedin 8 patients (2.8%). There was atonia which wasrecovered by treatment in 4 patients (1.4%), infectionin 1 patient (0.3%) and the need for blood transfusionin 3 patients (1.0%). During this period, atonia wasseen in 9 (0.28%) out of 3133 patients, 7 patients(0.22%) needed blood transfusion.

DiscussionOne of the major delivery problems for a pregnantnear term is the condition of cervix. When cervix isrigid, induction of labor by inappropriate methodsgenerally will cause bad results. Patient should beinformed about the indication of labor induction, andinformed consent form should be received. The suit-ability of maternal pelvic bone structure for vaginaldelivery should be evaluated; fetal weight and presen-

tation should certainly be known. WHO stated theindications of labor induction in the guide published in2011. Induction of labor is suggested when the weeksof gestation is above 41 and early membrane rupture ispresent. It is suggested to use intravenous oxytocinalone or oral misoprostol (25 μg, with intervals of 2hours) or low-dose vaginal misoprostol (25 μg, withintervals of 6 hours) when low-dose vaginalprostaglandins cannot be provided during the induc-tion of labor. WHO states that balloon can be appliedor the combination of oxytocin and balloon whenprostaglandin or misoprostol cannot be provided.[6]

Mechanical or pharmacological agents are used forthe induction of labor. Mozurkewich et al. reviewed283 studies on the methods used for the induction oflabor between 1980 and 2010, and found that dinopro-stone and misoprostol are more effective than othermethods for carrying out the delivery within 24 hours,and that mechanical methods cause less hyperstimula-tion than these two methods, but lead to more mater-nal and neonatal infection morbidity.[7]

Oxytocin infusion for the induction of labor may faileven when combined with amniotomy if cervix is notsuitable. The caesarean rates increases in unsuccessfulinductions.[8-10] Calder et al. showed that delivery dura-tion, maternal fever, caesarean and fetal asphyxiaincrease when amniotomy was applied together withoxytocin to patients whom cervices are not preparedcompared to patients with ripened cervices.[11]

Dinoproston has been used since 1970, and it stim-ulates myometrial contractions as well as ripeningcervix. When compared with other induction methods,it is reported that less and equal amount of maternaland fetal complications are observed.[12-14]

It was reported by Perry and Leaphart that placingdinoprostone ovule into intra-cervical decreased theperiod up to delivery without any increase in caesareanrate, infection morbidity or any other labor complica-tions.[15]

Table 2. Caesarean indications of the groups.

Group 1 Group 2 Group 3(N=34) (N=204) (N=41)

Fetal distress, n (%) 6 ( 33.3) 31 (44.3) 11 (39.3)

Cephalopelvic disproportion, n (%) 10 (55.8) 21 (30.0) 8 (28.6)

Dystocia, n (%) 2 (11.1) 10 (14.3) 7 (7.1)

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In the literature, the studies comparing intravenousoxytocin and dinoprostone use during the induction oflabor showed that dinoprostone causes less deliveryfailure than oxytocin and it is more effective and reli-able method,[16-18] the study conducted by Koç et al.comparing oxytocin and dinoprostone reported thatlabor occurred in a short time by oxytocin and causedless cesarean delivery even there is no statistical signif-icance.[19]

In our study, we found that active labor phase wassignificantly shorter although latent duration waslonger in dinoprostone group compared to oxytocingroup (p=0.000). Mazouni C et al. indicated in theirstudy that there was no maternal and fetal morbidity inpatients applied dinoprostone while the caesarean ratewas 3.5 times more.[20]

The caesarean rates vary between 7-27% by dino-prostone use in the literature.[21,22] In our study, weobserved that delivery by caesarean was higher inGroups 1 and 3 than the oxytocin group (p=0.000).High caesarean rate (68.3%) in Group 3 shows that thecaesarean rate will increase in pregnants who areapplied dinoprostone but need to undergo other meth-ods for some reasons. For caesarean indications, we didnot detect any difference among the groups in terms offetal distress and non-progressive labor. However,cephalopelvic disproportion was observed only in55.6% (n=10) of the Group 1 applied dinoprostone,which was higher than other two groups but the differ-ence was statistically not significant (p=0.275).

We believe that the high caesarean rate in all 3groups is caused for the low number of patients in thegroups and medicolegal concerns.

In the studies, hyperstimulation rate based on dino-prostone use varies between 8.3% and 16%.[23,24] In ourstudy, hyperstimulation rate was 14.6%.

It was seen that 2 neonates were followed up atintense care unit due to perinatal asphyxia and theywere discharged from the hospital as were. No perina-tal and early neonatal mortality was observed.

We believe that our study has weak points whichshould be emphasized. One of them is the inevitablemethodological issues which are seen in all retrospec-tive studies. Other one is the disproportionality inpatient number affecting statistical analysis.

ConclusionDinoprostone is a method approved by FDA for theinduction of labor at term pregnancies. Even though itincreases caesarean rates, it decreases the active periodof labor, and does not affect maternal and fetal morbid-ity. The method to be used may differ according to thepreference of patient and physician. However, patientand fetus should be kept under close observation.Supporting to study greater patient groups willincrease the reliability of results.

Conflicts of Interest: No conflicts declared.

References1. Ventura SJ, Martin JA, Curtin SC, Mathews TJ. Report of

final natality statistics,1995. Monthly vital statistics report;vol.45, no.11(Suppl). Hyattsville, MD: National Center forHealth Statistics; 1997.

2. Coonrod DV, Bay RC, Kishi GY. The epidemiology oflabor induction: Arizona, 1997. Am J Obstet Gynecol2000;18:1355-62.

3. Bishop EH. Pelvic scoring for elective induction. ObstetGynecol 1964;24:266-8.

4. Phelan JP, Smith CV, Broussard P, SmallM. Amniotic vol-ume assessment using four quadrant technique in pregnancybetween 36 and 42 weeks’ gestation. J Reprod Med1987;32:540-2.

5. F. C. Chr›stensen, M›tra Tehran›far, Ajaose L. Gonzalez ,Clifford R. Qualls, Valerie J. Rappaport, William F.Rayburn. Randomized trial of concurrent oxytocin with asustained-release dinoprostone vaginal insert for laborinduction at term. Am J Obstetric Gnynaecology2002;186:61-5.

6. WHO. Recommendations for induction of labour. Geneva:WHO; 2011.

7. Mozurkewich EL, Chilimigras JL, Berman DR, Perni UC,Romero VC, King VJ, et al. Methods of induction of labour:a systematic review. BMC Pregnancy Childbirth 2011;11:84.

8. Parashi S, Bonabi NB, Rashidi A. Re: Oxytocin induct ion oflabour: a comparison of two protocols. Aust N Z J ObstetGynaecol 2005;45:540.

9. Boulvain M, Kelly A, Lohse C, Stan C, Irion O. Mechanicalmethods for induction of labour. Cochrane Database SystRev 2001;(4):CD001233.

10. Alfirevic Z, Kelly AJ, Dowswell T. Intravenous oxytocinalone for cervical ripening and induction of labour.Cochrane Database Syst Rev 2009;(4):CD003246.

11. Calder AA. Cervical ripening in prostaglandins and theirinhibitors in clinical obstetrics and gynecology. In:Bygdeman M, Gsand B, Keith L (Eds). Lancaster, Boston:MTP Press Ltd.; 1986. p. 154.

12. Austin SC, Sanchez-Ramos L, Adair CD. Labor inductionwith intravaginal misoprostol compared with the dinopros-tone vaginal insert: a systematic review and metaanalysis. AmJ Obstet Gynecol 2010;202:624.e1-9.

13. Tanir HM, Sener T, Yildiz C, Kaya M, Kurt I. A prospectiverandomized trial of labor induction with vaginal controlled-release dinoprostone inserts with or without oxytocin andmisoprostol+oxytocin. Clin Exp Obstet Gynecol 2008;35:65-8.

14. Facchinetti F, Venturini P, Verocchi G, Volpe A.Comparison of two preparations of dinoprostone for pre-induction of labour in nulliparous women with veryunfavourable cervical condition: a randomised clinical trial.Eur J Obstet Gynecol Reprod Biol 2005;119:189-93.

15. Perry MY, WL Leaphart. Randomized trial of intracervicalvs.posterior fornix dinoprostone for induction of labor.Obstet Gynecol 2004;103:13-7.

16. Ekman G, Granstrom L, Ulmsten U. Induction of labourwith intravenous oxytocin or vaginal PGE2 suppositories.Acta Obstet Gynecol Scand 1986;65:857-9.

17. Legarth J, Lyndrup J, Dahl C, Philipsen T, Eriksen PS.Prostaglandin E2 vaginal suppository for induction oflabour: an efficient, safe and popular method. Eur J ObstetGynecol Reprod Biol 1987;26: 233-8.

18. MacLennan AH, Green RC. The effect of intravaginal-prostaglandin F2 alpha on labour after spontaneous and arti-ficial rupture of the membranes. Aust N Z J Obstet Gynaecol1980;20:87-90.

19. Koc O, Duran B, Ozdemirci S, Albayrak M, Koc U.Oxytocin versus sustained-release dinoprostone vaginal pes-sary for labor induction of unfavorable cervix with Bishopscore ≥4 and ≤6: a randomized controlled trial. ObstetGynaecol Res 2013;39:790-8.

20. Mazouni C, Provensal M, Ménard JP, Heckenroth H,Guidicelli B, Bretelle F. Evaluation of controlled-releasedinoprostone Propess for labor induction. Gynecol ObstetFertil 2006;34:489-92.

21. Calder AA, Johnson TA. Cervical ripening in nulliparae.Release of prostaglandin from ‘Propess’ and efficacy andsafety in the induction of labour. Calder AA, Keirse MJNC,MacKenzieI Z, Editors. Propess-RS: a clinical review.Haslemere: Euromed Communications; 1996. p. 1-4.

22. MacKenzie IZ. Cervical ripening in nulliparae. Release ofprostaglandin from ‘Propess’ and efficacy and safety in theinduction of labour. Calder AA, Keirse MJNC, MacKenzieIZ (Eds). Propess-RS: a clinical review. Haslemere: EuromedCommunications; 1996. p. 37-9.

23. Mc Namara H, Koufogianis A, Benjamin A. Safety and effec-tiveness of cervidil for cervical ripening. Canadian phase IVopen label study. 55th Annual Meeting of Society ofObstetrics and Gynecologists of Canada (SGOC), June 25-29, 1999, Ottowa, Ontaroi, Canada.

24. Crane JM, Young DC, Butt KD, Bennett KA, Hutchens D.Excessive uterine activity accompanying induced labor.Obstet Gynecol 2001;97:926-31.

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Emergency peripartum hysterectomy: our experiences with 189 cases

Abdulkadir Turgut, Muhammed Erdal Sak, Ali Özler, Hatice Ender Soydinç, Neval Yaman Görük, Talip Karaçor, Ahmet Yal›nkaya

Department of Obstetrics&Gynecology, Faculty of Medicine, Dicle University, Diyarbak›r, Turkey

Abstract

Objective: To estimate the incidence, indications, risk factors,complications, and maternal morbidity and mortality associatedwith emergency peripartum hysterectomy.

Methods: A retrospective study was performed on 189 cases thathad required emergency peripartum hysterectomy betweenJanuary 1993 and February 2012. Demographic and clinical datawere collected and interpreted on these patients operated at theobstetrics & gynecology department of a tertiary care center.

Results: The mean age and number of parities were 34.3 and 5.4,respectively. Caesarean section has been performed on 70.4% ofbirths prior to emergency peripartum hysterectomy. Induction oflabour had been performed on 32.8% of cases. The most commonplacentation anomaly was placenta praevia percreata (20.1%). Theleading indications for hysterectomy were uterine atony (31.7%),uterine rupture (25.4%) and abnormal placentation (22.2%).Subtotal (63.5%) or total (36.5%) hysterectomies were performed.Relaparotomy due to hemorrhage or ureter ligation was requiredin 22.8% of cases. Intensive care unit follow-up was necessary in66.1% of patients. Mortality rate was 6.9%.

Conclusion: Emergency peripartum hysterectomy is a high riskbut a life saving operation which is associated with significantmaternal and fetal morbidity and mortality. Obstetricians shouldidentify patients at risk and anticipate the procedure and compli-cations, as early intervention and proper management facilitateoptimal outcome.

Key words: Emergency, haemorrhage, hysterectomy, peripar-tum, uterine atony.

Correspondence: Abdulkadir Turgut, MD. Dicle Üniversitesi T›p Fakültesi Kad›n Hastal›klar› ve Do¤um Anabilim Dal›, Diyarbak›r, Turkey.e-mail: abdulkadirturgut@gmail.com

Received: July 4, 2013; Accepted: August 17, 2013

©2013 Perinatal Medicine Foundation

Available online at:www.perinataljournal.com/20130213003

doi:10.2399/prn.13.0213003QR (Quick Response) Code:

Research Article

Perinatal Journal 2013;21(3):113-118

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Acil peripartum histerektomiler: 189 olgu deneyimimiz

Amaç: Acil peripartum histerektominin insidans›n›, endikasyonla-r›n›, risk faktörlerini, komplikasyonlar›n›, maternal morbidite vemortalitesini de¤erlendirmek.

Yöntem: Bu retrospektif çal›flma Ocak-1993 ile fiubat-2012 tarih-leri aras›nda, acil peripartum histerektomi uygulanm›fl 189 olgu ileyap›lm›flt›r. Demografik ve klinik veriler, üçüncü basamak bir sa¤-l›k merkezinin kad›n hastal›klar› ve do¤um klini¤inde opere edil-mifl hastalardan elde edilmifl ve de¤erlendirilmifltir.

Bulgular: Ortalama yafl ve do¤um say›lar› s›ras›yla 34.3 ve 5.4 idi.Acil peripartum histerektomi öncesi do¤umlar›n %70.4’ü sezaryenile gerçeklefltirildi. Olgular›n %32.8’inde do¤um indüksiyonu uy-gulanm›flt›. Plasenta previa perkreta, en s›k rastlanan plasentasyonanomalisi idi (%20.1). En s›k histerektomi endikasyonlar›, uterusatonisi (%31.7), uterus rüptürü (%25.4) ve anormal plasentasyon(%22.2) idi. Histerektomiler, subtotal (%63.5) veya total (%36.5)olarak gerçeklefltirildi. Olgular›n %22.8’inde, kanama veya üreterligasyonu nedeniyle, relaparatomi gerçeklefltirildi. Hastalar›n%66.1’i yo¤un bak›m ünitesinde takip edildi. Mortalite oran› %6.9idi.

Sonuç: Acil peripartum histerektomi, maternal ve fetal morbiditeve mortalite ile oldukça iliflkili, yüksek riskli ancak hayat kurtaranbir operasyondur. Erken müdahale ve uygun yönetim, optimal so-nuç almam›z› kolaylaflt›raca¤› için kad›n do¤um hekimleri, risk al-t›ndaki hastalar› belirlemeli, komplikasyonlar› ve yap›lacak ifllemiönceden tahmin etmelidir.

Anahtar sözcükler: Acil, hemoraji, histerektomi, peripartum,uterus atonisi.

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IntroductionEmergency peripartum hysterectomy (EPH) is consid-ered one of the riskiest and dramatic operations inmodern obstetrics, where the uterus is removed in anemergency arising during caesarean section or imme-diately following a vaginal delivery. It is performed incase of life threatening haemorrhage during or imme-diately after abdominal or vaginal deliveries. Recently,the number of pregnant women with scarred uterusfrom prior uterine incision increses in parallel to thenumber of caesarean deliveries.[1,2] Patients with scarreduterus are vulnerable to serious complications likeuterine rupture, placenta praevia and morbidly adher-ent placenta. Recent reports suggest that the vastmajority of emergency peripartum hysterectomiesoccur in the setting of an abnormally adherent placen-ta or uterine atony.[3]

Massive hemorrhage after childbirth is the leadingcause of maternal mortality and morbidity in the devel-oping countries. It occurs with a frequency of 1-2 in1000 deliveries in developed countries, and it is evenmore prevalent in the developing world.[1,2]

Haemorrhage after vaginal or abdominal deliveries isamenable to medical and surgical treatments.Peripartum hysterectomy is reserved for situations inwhich severe obstetric haemorrhage fails to respond toconservative treatment.[1,4]

Studies on risk factors for EPH are inconsistent.[1-9]

There is a need to identify risk factors for EPH, ademanding surgical procedure associated with a highrate of complications, morbidity and mortality. In thismanner, both patients may be referred and counseledproperly and more effective preventive strategies maybe developed.

This study aims to study the incidence, indications,risk factors and complications of EPH in the obstetricsand gynecology department of a tertiary care centerand attempts to identify the risk factors that might pre-dict the patients likely to undergo this procedure.

MethodsThis is a retrospective review of medical records thatwas undertaken on cases of EPH performed at a terti-ary care center in the period between January 1993 andFebruary 2012. Approval of local Institutional ReviewBoard had been obtained. Patients’ charts, pathology

reports and departmental statistical reports wereextracted and reviewed in order to gather relevantdemographic and clinical data (such as age, parity, typeof labour, indication of caesarean section, and maternaland fetal complications). The surgeons attended theoperations were senior staff of the department. Clinicalresults including a period of 19 years have been com-pared in this review. Indication for surgery was con-firmed from operative and histological records.Emergency peripartum hysterectomy was defined as ahysterectomy carried out for haemorrhage unrespon-sive to conservative treatment within 24 hours of deliv-ery. Conservative treatment adopted included intra-venous oxytocin, uterine packing and curettage. Therelevant information on each case regarding the histo-ry, delivery and operative details and the duration ofhospital were derived from patient files.

Statistical Analysis

Statistical analysis was carried out using the SPSS 11.0computer program (SPSS Inc., Chicago, IL, USA). Inthe analysis, the percentages, the minimum and maxi-mum values were used. Mann-Whitney test, chi-squareor Fisher’s exact test, Spearman's correlation analysis,the mean±standard deviation, minimum and maximumvalues, odds ratio analysis methods were used. P <0.05was considered significant.

ResultsA total of 56,174 women were delivered. The inci-dence of EPH was 3.36 per 1000 deliveries. Ninety ofthe cases (47.6%) delivered in our clinic, 97 patients(51.3%) in an external centre and 2 patients deliveredat home and were referred to our clinic. Of the 189cases, the mean age was 34.3±5.5 (range: 18-49), themean gestational week was 35.4±4.3 (range: 20-40), theaverage gravidity was 6.7±3.2 (range: 1-18) and theaverage parity was 5.4±2.8 (range: 0-15). The opera-tions included were performed after caesarean sectionin 133 cases (70.4%) or after vaginal delivery in 56cases (29.6%).

The leading indications for hysterectomy wereuterine atony in 60 cases (31.7%), uterine rupture in 48cases (25.4%) and placentation abnormalities in 42cases (22.2%) (Table 1). Caesarean hysterectomy wasperformed in 89 cases (47.1%) and postpartum hys-terectomy was performed in 100 cases (52.9%).

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Subtotal hysterectomy was performed in 120 cases(63.5%) and total hysterectomy in 69 cases (36.5%).

The risk of placentation abnormalities in those witha previous caesarean section was very high (OR 19.8,95% CI 2.7-148.9, p=0.000). When the risk of placen-tation abnormalities were evaluated in terms of thenumber of the previous caesarean section, theincreased risk in those with one caesarean section was9 times more (OR 9.0, 95% CI 1.1-71.6, p=0.038), inthose with two caesarean section was 41 times more(OR 41.1, 95% CI 4.9-344.5, p=0.001) and in thosewith three or more caesarean section was 38 timesmore (OR 38.9, 95% CI 4.9-311.3, p=0.001).

The most common form of the placentation abnor-malities was placenta praevia percreata observed in 38(20.1%) patients. The average duration of hysterecto-my was 137.8±37.1 minutes. Induction of labour wasperformed in 62 (32.8%) patients. Mortality occurredin 13 (6.9%) cases and the main cause of mortality wasmassive hemorrhage in 12 (%92.3) patients. Morbidityoccurred in 97 (51.3%) cases (Table 2). Positive corre-lations were found between morbidity and duration of

hospital stay (r=0.406, p=0.000), duration of intensivecare unit stay (r=0.293, p=0.000), the amount of bloodtransfused (r=0.328, p=0.000), and negative correla-tions were found between morbidity and 1st min.Apgar score (r=-0.289, p=0.004) and 5th min. Apgarscore (r=-0.297, p=0.003) of the newborns.

The most common form of the morbidity was rela-parotomy that performed in 43 (22.8%) cases. Of the43 cases, relaparotomy performed in 41 cases due tointraabdominal hemorrhage, in one case due tointraabdominal hemorrhage and ligation of ureters andin the rest one due to intraabdominal compress reten-tion. The second most common was postoperativefebrile reaction observed in 23 (12.2%) cases, and thethird most common was wound dehiscence and infec-tion observed in 17 (9%) cases (Table 3). The averageamount of blood products transfused to our patientswas 6.1±4.1 (range: 0-24) units. Follow-up in intensivecare unit was necessary for 125 (66.1%) cases. Themean duration of intensive care unit stay was 1.7±2.8(range: 0-18) and the mean duration of hospital staywas 9.2±6.6 (range: 1-45) days. When compared withtotal hysterectomy group, hypogastric artery ligation(p=0.044) and relaparotomy (p=0.046) observed lessfrequent in the subtotal hysterectomy group.

The mean fetal birth weight was 2804.4±1126.7(range: 520-6700) grams. Of fetuses, the mean 1st min.Apgar score was 3.2±3.3 (range: 0-10) and 5th min.Apgar score was 4.2±4.1 (range: 0-10).

Table 1. Indications for hysterectomy.

Indications for hysterectomy. n %

Uterine atony 60 31.7

Uterine rupture 48 25.4

Placentation anomaly 42 22.2

Ablatio placenta 16 8.5

Uterine bleeding due to pelvic peritonitis 13 6.9

Vesicouterine rupture 5 2.6

Others* 5 2.6

*Uterine bleeding due to fibroid, cervix cancer or choriocarcinoma.

Table 2. Clinical and procedural details.

n %

Previous caesarean section 140 74.1

Relaparatomy 43 22.8

Mortality 13 6.9

Morbidity 97 51.3

Induction of labour 62 32.8

Intensive care unit stay 125 66.1

Total vs. subtotal hysterectomy 69 vs. 120 36.5 vs. 63.5

Table 3. Postoperative morbidities.

Morbidity n %

Relaparotomy (hemorrhage and others) 43 22.8

Postoperative febrile reaction 23 12.2

Dehiscence and wound infection 17 9

Bladder injury 11 5.8

DIC 10 5.3

Acute renal failure 8 4.2

Ureter injury 6 3.2

ARDS 5 2.6

Cardiac arrest 5 2.6

Ileus 3 1.6

Others* 11 5.8

*ARDS= acute respiratory distress syndrome; DIC= disseminated intravascularcoagulation; others= foreign body, intracranial hemorrhage, diabetes incipitus,pleural effusion, ischemic hepatitis, sheehan’s syndrome, pulmoner tromboem-boli, bowel injury, cervical cuff haemorrhage, iliac vein injury and sepsis.

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DiscussionPeripartum hysterectomy is performed in the treat-ment of life-threatening obstetric hemorrhage duringor immediately after abdominal or vaginal deliveriesthat cannot be controlled by conventional methods.The incidence reported in the literature varies from0.2-1.3 per 1000 deliveries.[1-5] In our series, the inci-dence of EPH was 3.36 per 1000 deliveries. The rea-son for the high incidence may be due to the fact thatour hospital is the sole tertiary care center serving tothe patients of seven provinces.

The indications for EPH are mainly morbidlyadherent placenta, ruptured uterus and uterine atony.[1-

5] In the recent literature, an increasing proportion ofhysterectomies are being done for morbidly adherentplacenta and a decreasing proportion for uterine atonycompared; this may be attributed to the better treat-ment of uterine atony, especially withprostaglandin.[3,4,6] Another reason for this may be theincrease in the number of caesarean deliveries over thepast decade, since caesarean delivery is a well-estab-lished risk for the development of placenta praevia andaccreta.[5,7,8] Uterine rupture and secondly uterine atonywere the most common indications for hysterectomy inour series and this is consistent with relevant data fromdeveloping countries in the literature.[6,7,10] The highercaesarean section rate and more successful conservativetreatment of uterine atony with uterotonic agents(especially prostaglandin analogues) and operativeinterventions explain the differences between differentseries. In contrast, by increasing caesarean section ratesand significant reduction in the incidence of uterinerupture and atony due to modern antenatal and intra-partum care, placenta accreta has replaced uterine rup-ture and atony exist as the most common indication foremergency peripartum hysterectomy in the developedworld.[9,11-13] We found that placental abruption canconstitute a risk of hysterectomy as well. We cameacross with only one publication regarding this issue inthe literature.[9] This issue is noteworthy and must bestudied in further studies.

Previous caesarean section and placenta praevia,especially when both coexist, are the main risk factorsfor the development of placenta accreta. The percent-age of placentation abnormalities was 22.2% and themost common form was placenta praevia percreata.Placentation abnormalities appear to be the third mostcommon cause of EPH in our series. In the literature,

it was suggested to be the second most common indi-cation for obstetric hysterectomy in patients with aprevious caesarean section.[2-4] In accordance with theliterature, in our study, the increased risk of placenta-tion abnormalities in those with previous caesareansection was about 19 times more, and this ratio wasobserved to increase 41 times more as the number ofprevious caesarean section increases.

It is well-known that increased numbers of previouscaesarean section is a strong risk factor for emergencyperipartum hysterectomy.[2,8,9,11,12] Caesarean delivery isstrongly linked to emergency caesarean hysterectomythrough diverse mechanisms. Firstly, caesarean sectionper se appears to increase the risk of hysterectomy.Secondly, caesarean section predisposes to abnormalplacentation (placenta praevia, placenta accreta/percre-ta) in future pregnancies. The third mechanism is thatthe risk of caesarean section in a subsequent pregnan-cy is increased following a primary caesarean section.Improvements in radiological imaging modalities suchas ultrasonography, coupled with Doppler and mag-netic resonance imaging have made the antenatal iden-tification of placenta accreta/percreta less problemat-ic.[2,5,7-9] Hence, women with placenta praevia and previ-ous caesarean delivery or any uterine surgical proce-dure should undergo careful and detailed sonographicand Doppler evaluation. In the meantime, adequatecounselling and preparations can be made for the pos-sibility of EPH.

Emergency peripartum hysterectomy is usuallyassociated with significant rate of maternal morbidityand mortality. The overall morbidity was reported inthe range of 30-40%.[2,3,5,7] In our series, rate of mortal-ity was 6.9%. Morbidities such as relaparotomy due tomassive haemorrhage, febrile reaction, wound infec-tion or urinary system problems occurred in 51.3% ofour cases. In our study, positive correlations werefound between morbidity and duration of hospital stay,duration of intensive care unit stay, the amount ofblood transfused, and negative correlations were foundbetween morbidity and 1st min. Apgar score and 5thmin. Apgar score of the newborns. Besides these data,due to being observed morbidity in 10 out of 13patients developed mortality, it can be said that mor-bidity reduces maternal comfort and increases the riskof life, and have unfavourable effects on the newborn.

Hemorrhagic shock is the most common reason formaternal mortality. Emboli, streptococcic septic shock

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and cardiopulmonary arrest are the other main causesof death.[1,2,6,11] Our high rate of mortality may be par-tially explained by the instantaneous lack of adequatecross-matched blood products that limit the time avail-able for any other conservative procedures. The highmortality rates may be related to a low rate of antena-tal follow-up, low socioeconomic status of patients, andthe fact that critical patients were referred from otherhospitals. Some conservative surgical procedureswould have been undertaken before resorting to emer-gency peripartum hysterectomy. The increasing use ofeffective conservative surgical techniques may bereducing the need for hysterectomy among womensuffering major hemorrhage. High rate of mortalitymay be lowered with improvement of intensive careconditions and blood transfusion facilities. Extensiveblood loss occurs almost invariably in candidates forperipartum hysterectomy therefore precautions mustbe made. The average amount of blood products trans-fused to our patients was 6.1±4.1 units.

The high rates of complications after peripartumhysterectomy ensource not only from the need formassive blood transfusions, coagulopathy, and injury ofthe urinary tract, but also with the need for re-explo-ration due to febrile morbidity and persistent bleed-ing.[1,4,12] In our study, relaparotomy performed in22.8% of the patients due to massive hemorrhage, andit was followed by febrile reaction that was the secondmost common with 12.2%.

Since EPH is associated with intra- and postopera-tive complications and high rate of maternal morbidi-ty, some measures of conservative management wouldhave been undertaken before performing the proce-dure. In terms of medical conservative measures, oxy-tocin and prostaglandin preparations can be initiallytried. Conservative surgical options include over-sewing the placental bed, placement of uterine balloonand the use of brace sutures. The newer ‘purposedesigned’ uterine tamponade balloon can be particular-ly effective in the management of haemorrhage due toplacenta praevia.[1,4,5,8] The proportion of women whoescaped hysterectomy since haemorrhage was success-fully arrested with conservative management isobscure.

It has been suggested that a total hysterectomyshould be preferred to a subtotal hysterectomy becausethe cervical branch of the uterine artery will remainintact especially when placenta accreta is located in thelower segment of the uterus.[3,5,7-9] Subtotal hysterecto-

my is a faster and technically safer procedure for des-perately ill patients and those with massive adhesionsover the lower uterine segment. In addition, there wassignificantly less blood loss with subtotal hysterectomycompared with total hysterectomy.[1,4,7] Total abdomi-nal hysterectomy seems to be more appropriate, butsubtotal hysterectomy may be considered in circum-stances where operation should be completed in short-est time possible.[3,6,8] The reason for the higher propor-tion of subtotal hysterectomies in our series may beexplained by the fact that we mostly dealed withpatients in worse clinical condition. In addition in ourstudy, when compared with total hysterectomy group,hypogastric artery ligation and relaparotomy observedless frequent in the subtotal hysterectomy group.These advantages of subtotal hysterectomy may con-tribute to the reduction of morbidity.

In keeping with the recommendations ofRANZCOG, a multidisciplinary approach must beused for all women. In cases with a high risk of post-partum haemorrhage, pre-discussions with gynaeco-logical oncologists must be made. This issue gainsimportance especially when the control of blood lossbecomes difficult.[5]

Some limitations of the study should be considered.The sample size may be relatively small and since theissue is prone to be influenced by many factors, clinicalrelevance of less clear associations may constitutedoubt.

ConclusionAny patient with a history of caesarean section, currentplacenta praevia, or, in particular, both conditionsshould be prepared for possible emergency peripartumhysterectomy at the time of delivery. Even though it isa risky procedure, emergency peripartum hysterecto-my has no alternative as a potentially life-saving proce-dure. Not only timely identification of patients isimportant, but also operation must be performed time-ly and by experienced surgeon to minimize mortalityand morbidity.

Conflicts of Interest: No conflicts declared.

References1. Umezurike CC, Feyi-Waboso PA, Adisa CA. Peripartum

hysterectomy in Aba southeastern Nigeria. Aust N Z JObstet Gynaecol 2008;48:580-2.

2. El-Jallad MF, Zayed F, Al-Rimawi HS. Emergency peripar-tum hysterectomy in Northern Jordan: indications andobstetric outcome (an 8-year review). Arch Gynecol Obstet2004;270:271-3.

3. Demirci O, Tu¤rul AS, Yilmaz E, Tosun Ö, Demirci E,Eren YS. Emergency peripartum hysterectomy in a tertiaryobstetric center: nine years evaluation. J Obstet GynaecolRes 2011;37:1054-60.

4. Awan N, Bennett MJ, Walters WA. Emergency peripartumhysterectomy: a 10-year review at the Royal Hospital forWomen, Sydney. Aust N Z J Obstet Gynaecol 2011;51:210-5.

5. Engelsen IB, Albrechtsen S, Iversen OE. Peripartum hys-terectomy-incidence and maternal morbidity. Acta ObstetGynecol Scand 2001;80:409-12.

6. Yamani Zamzami TY. Indication of emergency peripartumhysterectomy: review of 17 cases. Arch Gynecol Obstet2003;268:131-5.

7. Yucel O, Ozdemir I, Yucel N, Somunkiran A. Emergencyperipartum hysterectomy: a 9-year review. Arch GynecolObstet 2006;274:84-7.

8. Ozden S, Yildirim G, Basaran T, Gurbuz B, Dayicioglu V.Analysis of 59 cases of emergent peripartum hysterectomiesduring a 13-year period. Arch Gynecol Obstet 2005;271:363-7.

9. Kayabasoglu F, Guzin K, Aydogdu S, Sezginsoy S,Turkgeldi L, Gunduz G. Emergency peripartum hysterecto-my in a tertiary Istanbul hospital. Arch Gynecol Obstet2008;278:251-6.

10. Ossola MW, Somigliana E, Mauro M, Acaia B, Benaglia L,Fedele L. Risk factors for emergency postpartum hysterecto-my: the neglected role of previous surgically induced abor-tions. Acta Obstet Gynecol Scand 2011;90:1450-3.

11. Selo-Ojeme DO, Bhattacharjee P, Izuwa-Njoku NF, KadirRA.Emergency peripartum hysterectomy in a tertiaryLondon hospital. Arch Gynecol Obstet 2005;271:154-9.

12. Zorlu CG, Turan C, Iflik AZ, Daniflman N, Mungan T,Gökmen O. Emergency hysterectomy in modern obstetricpractice. Changing clinical perspective in time. Acta ObstetGynecol Scand 1998;77:186-90.

13. Katchy KC, Ziad F, Al Nashmi N, Diejomaoh MF.Emergency obstetric hysterectomy in Kuwait: a clinicopathological analysis. Arch Gynecol Obstet 2006;273:360-5.

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The effect of maternal smoking during pregnancy onDoppler parameters

Turab Janbakhisov1, Özlen Emekçi2, Erkan Ça¤l›yan2, Ali Cenk Özay2, Ferruh Acet2,Sabahattin Altunyurt2

Department of Obstetrics & Gynecology, Faculty of Medicine, Dokuz Eylül University, ‹zmir, Turkey

Abstract

Objective: It is suggested that smoking has adverse effects on pla-centa development by decreasing placental vascularization.Cigarette exposure is associated with intrauterine and perinataldeath, preterm labor, ablatio placenta, placenta previa andintrauterine growth retardation. The aim of this study is to inves-tigate the effect of smoking on fetal Doppler ultrasound wave-forms and its pathophysiological relationship with fetal birthweight.

Methods: The study was conducted in Gynecology andObstetrics Department of Dokuz Eylül University betweenJanuary 13th and 24th April 2011. One hundred nineteen single-ton pregnancies were included to the study. Group 1 consisted of22 patients who were smoking 4-10 cigarettes daily. Group 2 con-sisted of 97 non-smoker patients before and during their pregnan-cies. Patients’ maternal uterine, fetal umbilical and fetal middlecerebral arteries Doppler measurements were done on 37th weekof gestation.

Results: Weight gain in the Group 1 was statistically higher thannon-smoking patients. There were statistically significant changesin fetal Doppler measurements, but no difference was found inmaternal Doppler waveforms between the two groups. Maternaluterine artery Doppler waveforms were similar in both groups; infact fetal umbilical artery and middle cerebral artery waveformswere statistically higher for Group 1.

Conclusion: Cigarette contains nicotine, carbon monoxide andthousands of other toxic chemicals. Carbon monoxide reduces theoxygen transfer to the fetus. Chronic tobacco use decreases pla-cental blood flow, hypoxic pathologic environment occurs, andchanges appear on fetal Doppler ultrasound waveforms.

Key words: Doppler ultrasound, intrauterine growth retardation,smoking.

Correspondence: Özlen Emekçi, MD. Dokuz Eylül Üniversitesi T›p Fakültesi Kad›n Hastal›klar› ve Do¤um Anabilim Dal›, ‹zmir, Turkey.e-mail: özlenemekci@yahoo.com

Received: June 13, 2013; Accepted: August 17, 2013

©2013 Perinatal Medicine Foundation

Available online at:www.perinataljournal.com/20130213004

doi:10.2399/prn.13.0213004QR (Quick Response) Code:

Research Article

Perinatal Journal 2013;21(3):119-123

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Maternal sigara kullam›n›n Doppler ölçümleri üzerine etkisinin araflt›r›lmas›Amaç: Sigaran›n, plasental vaskülarizasyonu azaltarak, plasentalgeliflim üzerine olumsuz etki oluflturdu¤u öne sürülmektedir. Siga-ra kullan›m›, intrauterin ve perinatal ölüm, preterm eylem, ablas-yo plasenta, plasenta previa ve intrauterin geliflme gerili¤i ile ilifl-kili bulunmufltur. Bu çal›flmadaki amac›m›z sigara kullan›m›n›n fe-tal do¤um a¤›rl›¤› ile olan patofizyolojik iliflkisi ve fetal Dopplerak›mlar› üzerine etkisini incelemektir.

Yöntem: Çal›flmaya Dokuz Eylül Üniversitesi T›p Fakültesi Ka-d›n Hastal›klar› ve Do¤um Anabilim Dal› Obstetrik poliklini¤ine13 Ocak 2011 - 24 Nisan 2011 tarihleri aras›nda baflvuran toplam119 tekil gebeli¤i olan hasta al›nd›. Sigara kullan›m miktar› 4-10/gün olan toplam 22 hasta Grup 1 olarak çal›flmaya dahil edildi.Gebeli¤i s›ras›nda ve gebelikten önce hiç sigara kullanmam›fl olan97 hasta ise Grup 2 olarak çal›flmaya dahil edildi. Bütün gebelerin37. gestasyonel haftada maternal uterin arter, umbilikal arter veorta serebral arter Doppler de¤erlendirilmesi yap›ld›.

Bulgular: Günde 4-10 aras›nda sigara kullan›m› olan gebelerde,hiç kullanmayanlara göre gebelikte kilo al›m› anlaml› flekilde dahafazla bulunmufltur. Sigara kullan›m›n›n maternal Doppler ak›mla-r› üzerine etkisi görülmezken, fetal Doppler ak›mlar›ndaki etkilen-me iki grup aras›nda anlaml› olarak farkl› bulunmufltur. Her ikigrup için uterin arter Doppler ak›mlar› benzer iken, umbilikal ar-ter ve orta serebral arter Doppler ak›mlar›nda Grup 1’de anlaml›olarak daha yüksek de¤erler kaydedilmifltir.

Sonuç: Sigara; nikotin, karbon monoksit ve binlerce toksik kimya-sal bileflik içermektedir. Sigaradaki karbon monoksit, fetuse oksi-jen transportunu azaltmaktad›r. Kronik tütün kullan›m› ile plasen-tal kan ak›m› azalmakta; patolojik hipoksik ortam meydana gel-mekte ve fetal Doppler ak›mlar›nda de¤ifliklikler oluflmaktad›r.

Anahtar sözcükler: Doppler ultrason, intrauterin geliflme gerili-¤i, sigara.

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IntroductionSmoking is a modifiable risk which has an influence ongestational complications and neonatal growth.Smoking rate among women in the reproductive agerange is reported as 11.6% for Turkey according to2008 data.[1] Although this rate seems to be decreasingin recent years, it is reported as 22% in the USA.[2]

Only 18-25% of smoker women quit smoking whentheir pregnancies are confirmed.[1,2]

Many chemical materials in cigarette affect humanhealth negatively.[3] Maternal smoking habit causes ges-tational complications and affects baby growth nega-tively.[2,3] Although the relationship of maternal smok-ing with low birth weight and preterm labor has beenshown, the mechanism causing this relationship is stillcontroversial.[4,5] It is suggested that cigarette and thechemical materials in cigarette decrease placental vas-cularization and have a negative effect on placentalgrowth.[6] The etiology of preterm labor and intrauter-ine growth retardation is multifactorial; however, it hasbeen shown in the prospective study of Larsen et al.that smoking is the major factor causing the highestdecrease in fetal growth percentile curves.[7,8]

Smoking has been found to be associated withincreased miscarriage risk, intrauterine and perinataldeath, preterm labor, ablation placenta, placenta previaand intrauterine growth retardation. Besides, it hasbeen shown that smoking decreases preeclampsia riskby decreasing thromboxane A2 synthesis. It has beenalso found that sudden infant mortality rate in smokerpregnants increased 3 times more than non-smokerpregnants.[9]

Cigarette includes nicotine, carbon monoxide andthousands of toxic chemical compounds. These toxicsubstances in cigarette are associated with gestationalcomplications. Carbon monoxide in cigarette decreas-es oxygen transfer to fetus, and nicotine causes decreas-es in uterine blood flow.[9]

Our aim in this study is to investigate the effect ofsmoking on fetal Doppler ultrasound waveforms andits pathophysiological relationship with fetal birthweight.

MethodsThe study included 119 women with singleton preg-nancy who applied to Gynecology and ObstetricsDepartment of Dokuz Eylül University betweenJanuary 13th and 24th April 2011. The patients with

pregnancy-induced hypertensive diseases (preeclamp-sia, eclampsia), chronic hypertension, gestational dia-betes, morbid obesity, drug use, comorbid disease orwith multiple pregnancies were excluded from thestudy. Group 1 included 22 patients who were smoking4-10 cigarettes daily, and Group 2 included 97 patientswho were non-smokers before and during their preg-nancies.

Gestational ages of the patients were determinedaccording to the first day of their last menstrual peri-ods. In doubtful cases, gestational week was deter-mined by ultrasonographic examination. Weights,heights and body mass index (BMI; kg/m2) of allpatients were calculated. Maternal and fetal Dopplermeasurements of all patients were done and recordedon 37 weeks of gestation. Pulsatility index (PI), resist-ance index (RI) and systole diastole (S/D) flow rateswere recorded in maternal uterine artery (UtA) meas-urements. After bilateral maternal uterine artery meas-urements were done, half of the total of right and leftuterine artery Doppler measurements was calculatedand a single value was recorded. Pulsatility index (PI),resistance index (RI) and systole diastole (S/D) flowrates were recorded in fetal umbilical artery (UmbA)measurements. Similarly, middle cerebral artery(MCA) Doppler examination was conducted.Resistance index (RI), pulsatility index (PI), peak sys-tolic velocity (PSV) and systole diastole (S/D) flowrates of middle cerebral artery were examined.

C-reactive protein (CRP; 0.1-8.2 mg/L), total cho-lesterol (T. chol; 0-200 mg/dl), triglyceride (Trig; 0-200 mg/dl), high density lipoprotein (HDL; 40-60mg/dl), low density lipoprotein (LDL; 0-130 mg/dl)levels were checked through blood samples collectedfrom the patients at the same period.

The statistical analysis of data was performed bySPSS (Statistical Package for Social Sciences) version15 (SPSS Inc., Chicago, IL, USA). Continuous vari-ables were given as mean±standard deviation (SD) withthe lowest and the highest values in parenthesis. It wasfound out that all data are non-parametric and Mann-Whitney U and χ2 tests were used for comparison ofboth groups. p<0.05 was considered statistically signif-icant for all tests.

ResultsComparison of overall characteristics of both groups isgiven in Table 1. Mean age of Group 1 was found tobe 29.8±4.2 (range: 23-38) years while it was 29.2±4.8

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(range: 19-40) years and it was considered similar forboth groups (p=0.546). Statistically no difference wasobserved between groups in terms of parity (2.1±1.7and 2.3±1.5; p=0.623). For the comparison of BMI, itwas found to be 27.1±2.0 (range: 23.0-30.7) kg/m2 forGroup 1 and 27.2±2.6 (range: 21.1- 30.8) kg/m2 forGroup 2 (p=0.524). Weight gain was found as 17.3±2.8(range: 13.5-24.0) kg for Group 1 and 13.6±4.5 (range:4.0-24.0) kg for Group 2. Weight gain was significant-ly high in pregnants who were smoking 4-10 cigarettesdaily compared to non-smokers (p=0.000).

Additionally, statistically no significant differencewas found at total cholesterol and LDL levels ofgroups in terms of lipid parameters (p=0.803 andp=0.240, respectively). On the other hand, HDL levelwas significantly low for Group 1 (p=0.001). HDLlevel was recorded as 52.8±7.4 (range: 42.0-68.0) mg/dlfor Group 1 and as 62.4±12.9 (range: 41.0-94.0) mg/dlfor Group 2. Triglyceride level was found statisticallyhigher in Group 1 compared to Group 2 (p=0.028).Triglyceride level was found as 278.4±97.9 (range:128.0-428.0) mg/dl for Group 1 one and 236.5±82.9(range: 117.0-567.0) mg/dl for Group 2. When groupswere compared for CRP level, it was found as 6.7±4.2(range: 2.7-17.1) mg/L for Group 1 while it was6.11±6.07 (range: 0.5-37.6) mg/L in Group 2. Thisresult was not considered as statistically significant(p=0.258). Compared data of both groups in terms of

fetal gender are given in Table 1. Fetal gender ofGroup 1 consisted of 44.5% female and 54.5% malewhile it was 54.6% female and 45.4% male for Group2 (p=0.436).

In addition to these results, comparison of maternaland fetal Doppler waveforms for Group 1 and Group 2is shown in Table 2. Statistically no significant differ-ence was found when UtA PI, RI and S/D flows werecompared between groups (p=0.432, p=0.317 andp=0.472, respectively). For Group 1, UmbA S/D ratewas found as 2.6±0.5 (range: 1.8-3.3), UmbA RI as0.6±0.1 (range: 0.4-0.7) and UmbA PI as 0.9±0.2(range: 0.6-1.5). For Group 2, UmbA S/D rate wasfound as 2.3±0.4 (range: 1.1-3.4), UmbA RI as 0.6±0.1(range: 0.4-0.7) and UmbA PI as 0.8±0.1 (range: 0.5-1.1). Umbilical artery Doppler flows was found to bestatistically significant between two groups (p= 0.010for UmbA S/D; p=0.008 for UmbA RI; p=0.016 forUmbA PI). UmbA Doppler flows found to be statisti-cally significant are not different clinically. WhenDoppler MCA values were compared between groups,it was found that MCA S/D was 2.6±0.5 (range: 1.8-3.3), MCA RI was 0.8±0.1 (range: 0.7-0.9), MCA PIwas 1.7±0.3 (range: 1.2-2.2) and MCA PSV was61.8±12.2 (range: 42.3-82.5) for Group 1 while MCAS/D was 4.2±1.2 (range: 2.0-7.4), MCA RI was 0.7±0.1(range: 0.5-0.9), MCA PI was 1.5±0.3 (range: 0.7-2.1)and MCA PSV was 57.4±12.4 (range: 37.5-99.9) for

Table 1. Data of the pregnants included to the study.

Group 1 Group 2N=22 N=97 P*

Age 29.82±4.22 29.16±4.75 0.546

Parity 2.1±1.7 2.3±1.5 0.623

BMI (kg/m2) 27.10±2.00 27.24±2.64 0.524

Weight gain (kg) 17.29±2.81 13.56±4.53 0.000

T. cholesterol (mg/dl) 246.00±48.78 242.10±38.02 0.803

Triglyceride (mg/dl) 278.36±97.96 236.49±82.91 0.028

HDL (mg/dl) 52.82±7.36 62.41±12.93 0.001

LDL (mg/dl) 148.18±42.68 145.09±61.98 0.240

CRP (mg/L) 6.62±4.22 6.11±6.07 0.258

Newborn weight (g) 3328.18±231.05 3379.12±356.45 0.334

Baby’s gender:

Female (n, %) 10 (%44.5) 53 (%54.6)0.436

Male (n, %) 12 (%54.5) 44 (%45.4)

*p<0.05 was considered as significant.

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Group 2. Comparison of MCA values showed thatS/D, RI and PI values in Group 1 patients were statis-tically higher than the values of Group 2 patients; how-ever, this difference is not clinically significant (p=0.004, p=0.002 and p=0.008, respectively). AlthoughMCA PSV rates were found to be higher in Group 1patients, they were not considered as statistically sig-nificant (p=0.076).

DiscussionIn this paper, the impact of smoking on maternal andfetal Doppler flows and on fetal birth weight was stud-ied. The relationship of smoking with low fetal birthweight is well-known. It was shown in the study con-ducted by Rizzo et al. in 2009 that chronic tobacco usedoes not affect placental volume and placental vascu-larization at first trimester although it causes decreasesin fetal birth weight.[4] No intrauterine growth retarda-tion was detected in any 22 patients included in ourstudy. Unlike contemporary studies, it was proven inour study that smoking 4-10 cigarettes daily has noeffect on fetal birth weight. It was shown in the studycarried out by Vielwert et al. in 2006 that smoking 15or more cigarettes daily is associated with decrease ingrowth rate (p=0.007) and low birth weight (p=0.002)at third trimester, and that fetal birth weight is notaffected in pregnancies whose smoking is limited (lessthan 15).[6]

There are studies in the literature analyzing therelationship of smoking with weight gain and loss.Some studies evaluate weight changes and eating habits

of individuals, who are severely smoking-addicted,during smoking cessation periods. In the study per-formed by Grebenstein in 2013, it was shown thatnicotine is not associated with weight gain.[10] In ourstudy, weight gain of smoker pregnants was found tobe higher than non-smoker pregnants. Although cur-rently there is no study analyzing the impact of smok-ing on weight gain during pregnancy, it can be assert-ed that they increase weight gain by considering psy-chologically that baby may be affected negatively.Therefore, additional studies are required to analyzethese pregnants psychologically. Unlike our study, thestudy of Newnham et al. performed in 1990 suggestedthat both maternal and fetal weight gains are lower insmoker pregnants.[11]

Chronic tobacco exposure deteriorates vasculariza-tion in placental bed due to toxic chemical compounds.Reduction in intervillous area and decrease in capillaryvolume were observed in the histological examination ofplacentas of smoker pregnants. Decreased angiogenesisand increased resistance in placenta affect maternal andfetal Doppler flows.[6,11-13] In the results of our study, itwas seen that UmbA and MCA Doppler flows are affect-ed by smoking. Acute effect of nicotine on fetal UmbAflows was analyzed in the study conducted by Brunerand Forouzan in 1991 and diastolic flow loss was shownin UmbA.[12] In 1990, Newnham et al. examined theeffects of smoking on pregnants at 24 weeks of gestation.In the result of Newnham et al.’s study, no differencewas found between UmbA S/D rates of smoker andnon-smoker pregnants. Newnham et al. assert that toxicchemicals in cigarette cause periodical changes onDoppler flows but they do not have chronic effects.[11] Itwas shown by the study of Rizzo et al. performed in2009 that smoking during first trimester does not affectfetal Doppler flows.[4] There is no study examining therelationship of smoking with fetal and maternal Dopplerflows particularly at third trimester. Therefore, affectedUmbA and MCA Doppler flows recorded in our studiesprovide a new perspective to the literature.

Smoking activates immune system and creates a lowsystemic inflammatory response, and particularly caus-es increase in CRP values.[14] Humoral immune systemis suppressed in pregnancy; on the other hand, CRPand sedimentation increases are known by acute phasereactants.[15] In our study, no high value was detectedfor CRP although they were close to upper limit, andit was found that there was no statistically significantdifference in CRP levels of smoker pregnants com-pared to non-smoker pregnants.

Table 2. Comparison of Doppler findings between groups.

Group 1 Group 2N=22 N=97 P*

MCA-PSV 61.80±12.18 57.36±12.43 0.076

MCA-RI 0.79±0.06 0.74±0.07 0.002

MCA PI 1.66±0.29 1.45±0.29 0.008

MCA S/D 5.26±1.64 4.20±1.23 0.004

UmbA RI 0.60±0.07 0.55±0.06 0.008

UmbA PI 0.94±0.23 0.82±0.13 0.016

UmbA S/D 2.57±0.48 2.27±0.38 0.010

UtA RI 0.47±0.08 0.45±0.06 0.432

UtA PI 0.73±0.02 0.75±0,22 0.317

UtA S/D 2.06±0.71 2.11±0.79 0.472

*p<0.05 was considered as significant.

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Physiological metabolic adaptations occur duringpregnancy. In the studies examining effects of preg-nancy on lipid and lipid metabolism, it was found outthat total cholesterol, triglyceride, LDL and HDL val-ues are increased during pregnancy.[16] In our study, weexamined the effect of smoking on lipid profile duringpregnancy. It was shown by our study that smoking issignificantly associated with decreased HDL levels andincreased triglyceride levels. Carbon monoxide andnitrosamines in cigarette creates oxidative stress and itwas proven that it is associated with the decrease inHDL levels and vascular endothelial damage.[17]

ConclusionConsequently, our data show that smoking 4-10 ciga-rettes daily does not change maternal uterine arteryflows while affecting fetal Doppler flows. It was provenby our study that there is no effect on fetal birth weighteven though there are changes in fetal Doppler flowswhen smoking is limited to 4-10 times daily.

Conflicts of Interest: No conflicts declared.

References1. Bilir N. Dünya’da ve Türkiye’de Tütün Kullan›m›

Etiyolojisi. Ankara: Hacettepe Üniversitesi Halk Sa¤l›¤›Anabilim Dal›; 2008.

2. Batech M, Tonstad S, Job JS, Chinnock R, Oshiro B, MerrittTA, et al. Estimating the impact of smoking cessation duringpregnancy: the San Bernardino County experience. JCommunity Health 2013;4:1-10.

3. Huruba D, Sikolova V, Kunzova S, Kasikova K. The role ofsmoking in the epigenetic modification of phenotype: thelatest knowledge about smoking-induced pathways. [Articlein Czech] Cas Lek Cesk 2013;152:31-5.

4. Rizzo G, Capponi A, Pietrolucci ME, Arduini D. Effects ofmaternal cigarette smoking on placental volume and vascu-larization measured by 3-dimensional power Doppler ultra-sonography at 11+0 to 13+6 weeks of gestation. Am J ObstetGynecol 2009;200:415.e1-5.

5. Castles A, Adams EK, Melvin CL, Kelsch C, Boulton ML.Effects of smoking during pregnancy: five meta-analyses.Am J Prev Med 1999;16:208-15.

6. Vielwerth SE, Jensen RB, Larsen T, Greisen G. The impactof maternal smoking on fetal and infant growth. Early HumDev 2007;83:491-5.

7. Larsen T, Greisen G, Petersen S. Intrauterin growth corre-lation to postnatal growth-influence of risk factors and com-plications in pregnancy. Early Hum Dev 1997;47:157-65.

8. Guiot C, Gaglioti P, Oberto M, Piccoli E, Rosato R, TodrosT. Is three dimensional power Doppler ultrasound useful inthe assessment of placental perfusion in normal and growthrestricted pregnancies? Ultrasound Obstet Gynecol2008;31:171-6.

9. American College of Obstetricians and Gynecologists.ACOG committee opinion: smoking cessation during preg-nancy. Obstet Gynecol 2010;116:1241-45.

10. Grebenstein PE, Thompson IE, Rowland NE. The effects ofextended intravenous nicotine administration on body weightand meal patterns in male Sprague-Dawley rats.Psychopharmacology 2013;3:43-7.

11. Newnham JP, Patterson L, James I, Reid SE. Effects ofmaternal cigaratte smoking on ultrasonic measurements offetal growth and on Doppler flow velocity waveforms. EarlyHum Dev 1990;24:23-26.

12. Bruner JP, Forouzan I. Smoking and buccally administerednicotine. Acute effect on uterine and umbilical arteryDoppler flow velocity waveforms. J Reprod Med1991;36:436-40.

13. Campbell S. Placental vasculature as visualized by 3D powerDoppler angiography and 3D color Doppler imaging.Ultrasound Obstet Gynecol 2007;309:17-20.

14. Yano Y, Hoshide S, Shimada K, Kario K. The impact of cig-arette smoking on 24-hour blood pressure, inflammatoryand hemostatic activity, and cardiovascular risk in Japanesehypertensive patients. J Clin Hypertens (Greenwich)2013;15:234-40.

15. Rico-Rosillo MG, Vega-Robledo GB. Immunological mech-anism involved in pregnancy. [Article in Spanish] GinecolObstet Mex 2012;80:332-40.

16. Lippi G, Albiero A, Montagnana M. Lipid and lipoproteinprofile in physiological pregnancy. Clin Lab 2007;53:173-7.

17. Rao ChS, Subash YE. The effect of chronic tobacco smok-ing and chewing on the lipid profile. J Clin Diagn Res2013;7:31-4.

Evaluation of prenatal ultrasonographic markers in aneuploidy cases

Orkun Çetin, Fatma Ferda Verit Atmaca, Ayflegül Deregözü, Ali Galip Zebitay, O¤uz Yücel Clinics of Gynecology&Obstetrics, Süleymaniye Maternity Training and Research Hospital, Istanbul, Turkey

Introduction

Chromosomal anomalies are one of the most signifi-cant reasons of fetal morbidity and mortality. Invasiveprenatal diagnostic procedures are used for the diagno-sis of fetal aneuploidy. These diagnosis methods are

recommended only to pregnants who have high risk ofchromosomal anomaly since they may progress withpregnancies resulting with 1-2% high miscarriagerates.[1] Another method to determine pregnants inhigh risk group is the second trimester ultrasonograph-ic evaluation. This evaluation should be able to

Abstract

Objective: The aim of our study is to evaluate the major structur-al anomalies and minor ultrasonographic markers in aneuploidycases of our clinic.

Methods: Between the January 2008 and July 2012, 1517 casesthat had genetic amniocentesis were analyzed. Fifty-three caseswith proven aneuploidy were evaluated from cytogenetic recordsof fetuses. The ultrasonographic findings of aneuploidic fetusesfound during fetal anomaly screening at 18-22 weeks of gestationwere analyzed.

Results: Thirty-five of 53 aneuploidic fetuses which were includ-ed in the study were trisomy 21, 7 of them were trisomy 18, 2 ofthem were trisomy 13, 6 of them were 47,XXY (Klinefelter syn-drome), and 3 of them were 45,X (Turner syndrome). The mostfrequently observed minor ultrasonographic marker in trisomy 21cases was increased nuchal thickness. Most commonly seen majorstructural anomaly in trisomy 18 cases was hydrops fetalis while itwas hyperechogenic intracardiac focus in trisomy 13 cases.

Conclusion: Ultrasonography usage in the diagnosis of fetuses withchromosomal anomaly gradually increases. Invasive prenatal testshould be suggested to the family in the presence of serious structur-al anomalies or in the existence of several ultrasonographic findings.

Key words: Aneuploidy, fetal ultrasonography, major structuralanomaly.

Correspondence: Orkun Çetin, MD. Süleymaniye Do¤umevi E¤itim ve Araflt›rma Hastanesi Kad›n Hastal›klar› ve Do¤um Klini¤i, ‹stanbul, Turkeye-mail: drorkuncetin34@hotmail.com

Received: June 15, 2013; Accepted: August 17, 2013

©2013 Perinatal Medicine Foundation

Available online at:www.perinataljournal.com/20130213005

doi:10.2399/prn.13.0213005QR (Quick Response) Code:

Research Article

Perinatal Journal 2013;21(3):124-128

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Anöploidi olgular›n›n prenatal ultrasonografikbelirteçlerinin de¤erlendirilmesiAmaç: Çal›flmam›z›n amac›; klini¤imizde anöploidi saptanan olgu-larda majör yap›sal anomalilerin ve minör ultrasonografik belirteç-lerin de¤erlendirilmesidir.

Yöntem: Ocak 2008 - Temmuz 2012 tarihleri aras›nda genetikamniyosentez incelemesi yap›lan 1517 olgu incelendi. Fetüslere aitsitogenetik kay›tlardan anöploidi saptanan 53 olgu de¤erlendirme-ye al›nd›. Anöploidisi olan fetüslerin 18-22 gebelik haftalar›nda ya-p›lan fetal anomali taramas›nda saptanan ultrasonografik bulgular›gözden geçirildi.

Bulgular: Çal›flmaya dahil edilen 53 anöploidik fetüsün 35’i trizo-mi 21, 7’si trizomi 18, 2’si trizomi 13, 6’s› 47,XXY Klinefelter sen-dromu, 3’ü 45,X Turner sendromu olarak rapor edilen olgulard›.Trizomi 21 olgular›nda en s›k izlenen minör ultrasonografik belir-teç artm›fl ense kal›nl›¤›yd›. Trizomi 18 olgular›nda en s›k majöryap›sal anomali hidrops fetalis olarak karfl›m›za ç›kt›. Trizomi 13olgular›nda en s›k kalpte hiperekojen odak izlendi.

Sonuç: Kromozom anomalili fetuslar›n tan›s›nda ultrasonografi-nin kullan›m› giderek artmaktad›r. Fetusta ciddi yap›sal anomalivarl›¤›nda veya birden fazla ultrasonografik bulgu varl›¤›nda aile-ye invaziv prenatal test önerilmelidir.

Anahtar sözcükler: Anöploidi, fetal ultrasonografi, majör yap›salanomali.

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research abnormal ultrasonographic findings includingboth major structural anomalies and minor (moderate)markers that will distinguish euploid fetuses from ane-uploidic fetuses.[2] Ultrasonographic findings of chro-mosomal anomalies can be listed as ventriculomegaly,holoprosencephaly, choroid plexus cyst, Dandy-Walker complex, cleft palate and lip, micrognathia,nasal hypoplasia, nuchal edema, cystic hygroma,diaphragmatic hernia, cardiac defects, duodenal atre-sia, short extremities, clinodactyly, polydactyly, andsyndactyly.[3]

The purpose of our study is to evaluate in our clin-ic the major structural anomalies and minor ultrasono-graphic markers in cases found to be aneuploidic.

MethodsTotally 1517 cases that undergone genetic amniocen-tesis between January 2008 and July 2012 were evalu-ated. Fifty-three cases who found to be aneuploidic bycytogenetic records of fetuses were included to thestudy. Amniocentesis indications were chromosomalabnormality history in the family, advanced maternalage, high risk at screening tests, some markers found inultrasonographic examinations, and structural anom-alies. Ultrasonographic findings of aneuploidic fetuseswhich were detected during fetal anomaly screening at18-22 weeks of gestation were reviewed. Babies lost atearly periods, and those without karyotype analysiswere excluded from the study. Ultrasonographic exam-inations were done by the specialists in our clinic viaVoluson 730 Expert ultrasound device and 3.5 MHzprobe. Amniocentesis procedure was carried out incompany with ultrasonography after abdominal regionwas cleaned twice by octenidine hydrochloridethrough 22-gauge spinal needle. Twenty metaphaseswere expected at least in 5 cultures. Detecting samechromosomal defect in two different cell cultures onmore than two cells was considered as mosaicism.During ultrasonographic examination, head, face,neck, thorax (image of atriums and ventricles, andmajor vessel outlets), abdominal cavity, extremities(hands and feet), spinal cord, long bones, and genitalarea of fetuses were evaluated. Abnormalities of eachorgan were recorded. As ultrasonographic marker def-initions, nuchal skin thickness being 6 mm or thicker,existence of choroid plexus cysts at any number andsize on cerebral ventricles, echogenicity increase incardiac ventricle, and renal pelvis diameter exceeding 4

mm were considered as renal pelvicaliectasis whilefemur and humerus lengths being 0.85 shorter thanexpected length was considered as short femur andhumerus. Major structural anomalies were determinedas central nervous system anomalies, cardiac defects,abdominal anomalies, renal anomalies, extremityanomalies, cystic hygroma, fetal hydrops and facialanomalies.

ResultsThe mean age of 53 patients who undergone ultra-sonographic examination was 32.5 (range: 17-44)years, mean weeks of gestation was 19.9 (range: 18-23)weeks. Thirty-five (66.03%) of 53 aneuploidic fetusesincluded to the study were reported to have trisomy 21,7 (13.2%) of them were trisomy 18, 2 (3.77%) of themwere trisomy 13, 6 (11.32%) of them were 47,XXYKlinefelter syndrome, and 3 (5.66%) of them were45,X Turner syndrome (Table 1).

Totally 35 trisomy 21 cases were detected. Noanomaly was detected ultrasonographically in 15(42.85%) of these cases. One or more major and/orminor ultrasonographic anomalies were detected in 20cases (57.14%). Nine of them were major structuralanomaly while 28 of them were ultrasonographicmarkers. In three cases, major structural anomalies andminor ultrasonographic markers were observedtogether. Cardiovascular system anomaly seen in 5cases (14.28%) was the most common major structuralanomaly. Ventricular septal defect was detected in 4out of 5 cases (11.42%). As the second most frequent-ly observed anomaly, central nervous system anomalywas found in 4 cases (11.42%). The most frequentlyseen minor ultrasonographic marker in trisomy 21cases was the increased nuchal thickness which wasseen in 20% of them (7/35). Short femur and shorthumerus was seen in 6 cases (17.14%) while nasalhypoplasia was seen in 5 cases (14.28%), and pelvi-caliectasis was seen in 4 cases (11.42%) (Table 2).

Table 1. The distribution of aneuploidy cases.

Anomaly Case number

Trisomy 21 35 (66.03%)Trisomy 18 7 (13.2%)Trisomy 13 2 (3.77%)45,X 3 (5.66%)47,XXY 6 (11.32%)

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In our study, there were seven trisomy 18 cases. Allcases had ultrasonographic marker. The most commonmajor structural anomaly detected was hydrops fetalis(42.85%). Following hydrops fetalis, cardiovascularsystem anomalies and central nervous system anom-alies were the next common anomalies which wereseen in 28.27% of the cases. Among cardiovascular sys-tem anomalies, there was ventricular septal defect inone case (14.28), and coarctation of aorta in 2 cases(14.28%). As central nervous system anomaly, therewas ventriculomegaly in 2 cases (28.57%). Choroidplexus cysts in 2 cases (28.57%) and pelvicaliectasis in2 cases (28.57%) were the most common minor mark-ers (Table 2).

In our study, trisomy 13 was detected in 2 cases. Allthese cases had ultrasonographic markers. Also, allcases had hyperechogenic intracardiac focus. In onecase, face anomaly (cleft lip) accompanied to thisanomaly, and hyperechogenic intestine accompaniedin another case (Table 2).

We found Turner syndrome in 3 cases in our study.Ultrasonographic anomaly was detected in all of thecases. Also cystic hygroma was seen in all cases. Inaddition to cystic hygroma, hyperechogenic intestinewas found in one case (Table 2).

We detected Klinefelter syndrome in 6 cases in ourstudy. In one of these cases (16.66%) had major struc-tural anomaly and 5 of them (83.33%) had minor ultra-sonographic marker. Only one case had no ultrasono-graphic finding. We found ventricular septal defect inone case (16.66%) as major structural anomaly. Pesequinovarus was seen in 3 cases (66.66%) as the most

common minor ultrasonographic marker. It was fol-lowed by the hyperechogenic intracardiac focus,hyperechogenic intestine and pelvicaliectasis, eachseen in two cases (33.33%) (Table 2).

DiscussionChromosomal anomalies are seen in every 0.1% to0.2% live birth.[4,5] In our study, we analyzed 53 aneu-ploidy cases (3.49%) among 1517 amniocenteses con-ducted for different indications. Abnormal ultrasoundfindings were found in 37 (69.81%) out of 53 aneu-ploidic cases.

The most common structural anomalies in fetuseswith trisomy 13 are the mid-facial line defects.[6] In ourstudy, although case number was insufficient (totallytwo trisomy 13 cases), cleft lip was found in 50% ofcases. Nyberg and Souter indicated in their study per-formed on trisomy 13 cases that the central nervoussystem anomalies were the most common major struc-tural anomaly, and hyperechogenic intracardiac focuswas the most common minor ultrasonographic mark-er.[7] In our study, hyperechogenic intracardiac focuswas detected in all trisomy 13 cases. Taslimi et al.reported in their study that the possibility to detect anultrasonographic finding after 18 weeks of gestation atsecond trimester increased 22.2% (from 43.7% to64.5%).[8] In our study, mean weeks of gestation forultrasonographic examination was 19.9. Althoughthese weeks of gestation have high chance for detectingultrasonographic marker, they are late weeks of gesta-tion in case of a medical evacuation.

Table 2. Prevalence of ultrasonographic markers in aneuploidic cases.

Anomaly Trisomy 21 Trisomy 18 Trisomy 13 47,XXY 45,X

Choroid plexus cyst 3 (8.57%) 2 (28.57%) - - -Ventriculomegaly 2 (5.71%) 2 (28.57%) - - -Ventricular septal defect 4 (11.42%) 2 (28.57%) - 1 (16.66%) -Hyperechogenic intracardiac focus 3 (8.57%) - 2 (100%) 2 (33.33%) -Increased nuchal thickness 7 (20%) - - - -Hyperechogenic intestine - 1 (14.28%) 1 (50%) 2 (33.33%) 1 (33.33%)Short femur-humerus 6 (17.14%) 2 (28.57%) - - -Pelvicaliectasis 4 (11.42%) 1 (14.28%) - 2 (33.33%) -Nasal hypoplasia 5 (14.28%) - - - -Hydrops fetalis - 3 (42.85%) - - -Pes equinovarus - - - 3 (50%) -Single umbilical artery - - - 1 (16.66%) -Cystic hygroma - - - - 3 (100%)

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Major or minor ultrasonographic anomaly wasdetected in all trisomy 18 cases in our study. In thestudy of DeVore where second trimester ultrasono-graphic findings of trisomy 18 cases were analyzed,non-cardiac anomalies (77%) were found to be morecommon than cardiac anomalies.[9] In our study,hydrops fetalis was the most common major structuralanomaly in trisomy 18 cases. It is followed by cardio-vascular system and central nervous system anomalies.Given the minor ultrasonographic markers, choroidplexus cysts were the most common ultrasound findingin trisomy 18 cases. In all trisomy 18 cases, choroidplexus cysts were accompanied by pelvicaliectasis. Inthe meta-analysis of Yoder et al., it was found that tri-somy 18 risk increased 13.8 times in fetuses whichfound to have isolated choroid plexus cyst in secondtrimester ultrasonography.[10] Also, amniocentesis wassuggested to patients with isolated choroid plexus cystonly when maternal age was above 36, and trisomy 18risk was found to be high in fetal screening tests (high-er than 1/3000).[8]

In our study, abnormalities were found in ultra-sonographic examination in all cases with Turner syn-drome. The reason for this high rate is that the pheno-typic findings of cases with Turner syndrome were assevere as much to detect during first and early secondtrimesters ultrasonographically.[11] The most commonmajor structural anomaly seen in the cases with Turnersyndrome is cystic hygroma as seen in our study.

Down syndrome (trisomy 21) is in the primarychromosome anomaly that perinatologists researchcarefully due to its possibility (1.41 per 1000 livebirths).[12] Even though various rates were reported indifferent studies, it was reported that structural anom-alies were detected in second trimester ultrasono-graphic examination almost 30% of fetuses with Downsyndrome.[13-15]

According to meta-analysis results of Smith-Bindman et al., increased nuchal thickness is the mostsignificant ultrasonographic marker for distinguishingfetuses with Down syndrome from those withoutDown syndrome.[16] It was reported that increasednuchal thickness increases trisomy 21 risk 17 timesmore. In our study, increased nuchal thickness was themost common minor ultrasonographic marker (20%)in trisomy 21 cases. There were major structuralanomalies in 9 fetuses (25.71%) with trisomy 21. In thestudy of DeVore and Romero, this rate was found to be

between 20% and 87%, and relatively higher rate wasreported compared to our study.[17] The reason is thatthe cardiovascular system anomalies were at a higherrate in DeVore and Romero’s study than our study. Inthe study of Papp et al., major structural anomaly ratewas reported as 28.5% and cardiovascular systemanomalies were reported as the most common majorstructural anomalies.[18] This study was the most similarstudy for both major structural anomaly prevalenceand the most common anomaly that we shouldresearch. Kallen et al. performed a postnatal series ofstudy on fetuses with Down syndrome and reportedventricular septal defect rate as high as 28%.[19] In ourstudy, ventricular septal defect rate was found to be11.42% (4 cases).

Hypoplasia or lack of nasal bone in fetuses withDown syndrome is also a common marker. Bromley etal. reported this rate as 43%.[20] In a study performed byTaner et al. in Turkey, this rate was found as10.52%.[21] We found the rate of hypoplasia or lack ofnasal bone as 14.28% in our study. This rate was con-sistent with the study of Taner et al.

Klinefelter syndrome (47,XXY) is seen in prenataldiagnostic series with a rate of 0.15%.[22] Klinefeltersyndrome is caused by the lack of specific prenatal mal-formations, and establishing prenatal diagnosis bychance.[23] In the study of Grunchy et al., it was report-ed that oligohydramnios, bilateral renal agenesia andcongenital cardiac anomalies were the most commonanomalies seen in non-mosaic 47,XXY cases.[24]

Although the case number in our study was not suffi-cient (6 cases with Klinefelter syndrome), the mostcommon malformation in our study was the pesequinovarus anomaly. When other malformations areanalyzed, ventricular septal defect was seen as majorstructural anomaly while hyperechogenic intracardiacfocus, pelvicaliectasis and hyperechogenic intestinewere seen as minor anomalies. The variety of anom-alies detected prenatally was consistent with the litera-ture.

Retrospective planning of our study, low number ofcases with aneuploidy, not performing ultrasonograph-ic examination by same physician each time can be alllisted as the disadvantages of our study.Ultrasonographic examination at 11 and 13 weeks ofgestation and maternal serum markers help diagnosisat a rate of 95% in terms of chromosomal anomalies.[25]

Determining the frequency of particular markers for

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each karyotype anomaly would be helpful in aneu-ploidy screening.

Trisomy 13 and trisomy 18 are the aneuploidiesproviding sonographic findings at a high rate.Therefore, second trimester obstetric ultrasonographyseems to be helpful for detecting trisomy 13 and tri-somy 18. Sonographic markers cannot be detected in aconsiderable part of trisomy 21 cases. Therefore, usingfirst and second trimester biochemical screening teststogether with sonographic findings will increase thepossibility to detect structural chromosomal anomalies.

ConclusionUltrasonography usage in the diagnosis of fetuses withchromosomal anomaly gradually increases. Invasiveprenatal test should be suggested to the family in thepresence of serious structural anomalies or in the exis-tence of several ultrasonographic findings.

Conflicts of Interest: No conflicts declared.

References1. Scott F, Peters H, Boogert T, Robertson R, Anderson J,

McLennan A, et al. The loss rates for invasive prenatal test-ing in a specialised obstetric ultrasound practice. Aust N Z JObstet Gynaecol 2002;42:55-8.

2. Nyberg DA, Souter VL. Sonographic markers of fetal aneu-ploidy. Clin Perinatol 2000;27:761-89.

3. Nikolaides KH, Sebire NJ, Snijders RJM. 11-14 Week ScanDiagnosis of Fetal Abnormalities. New York: Parthenon;1999.

4. Adams MM, Erickson JD, Layde PM, Oakley GP. Down'ssyndrome. Recent trends in the United States. JAMA1981;246:758-60.

5. The California Expanded AFP Screening Program: PrenatalCare Provider Handbook. Berkeley, CA: The CaliforniaExpanded AFP Screening Program; 1997.

6. McGahan JP, Nyberg DA, Mack LA. Sonography of facialfeatures of alobar and semilobar holoprosencephaly. AJR AmJ Roentgenol 1990;154:143-8.

7. Nyberg DA, Souter VL. Sonographic markers of fetal tri-somies: second trimester. J Ultrasound Med 2001;20:655-74.

8. Taslimi MM, Acosta R, Chueh J, Hudgins L, Hunter K,Druzin ML, et al. Detection of sonographic markers of fetalaneuploidy depends on maternal and fetal characteristics. JUltrasound Med 2005;24:811-5.

9. DeVore GR. Second trimester ultrasonography may identi-fy 77 to 97% of fetuses with trisomy 18. J Ultrasound Med2000;19:565-76.

10. Yoder PR, Sabbagha RE, Gross SJ, Zelop CM. The second-trimester fetus with isolated choroid plexus cysts: a meta-analysis of risk of trisomies 18 and 21. Obstet Gynecol1999;93(5 Pt 2):869-72.

11. Shields LE, Carpenter LA, Smith KM, Nghiem HV.Ultrasonographic diagnosis of trisomy 18: is it practical in theearly second trimester? J Ultrasound Med 1998;17:327-31.

12. Wright DE, Bray I. Estimating birth prevalence of Down’ssyndrome. J Epidemiol Biostat 2000;5:89-97.

13. Rotmensch S, Liberati M, Bronshtein M, Schoenfeld-Dimaio M, Shalev J, Ben-Rafael Z, et al. Prenatal sono-graphic findings in 187 fetuses with Down syndrome. PrenatDiagn 1997;17:1001-9.

14. Vintzileos AM, Egan JF. Adjusting the risk for trisomy 21 onthe basis of second-trimester ultrasonography. Am J ObstetGynecol 1995;172:837-44.

15. Nyberg DA, Resta RG, Luthy DA, Hickok DE, Mahony BS,Hirsch JH. Prenatal sonographic findings of Down syn-drome: review of 94 cases. Obstet Gynecol 1990;76(3 Pt1):370-7.

16. Smith-Bindman R, Hosmer W, Feldstein VA, Deeks JJ,Goldberg JD. Second-trimester ultrasound to detect fetuseswith Down syndrome: a meta-analysis. JAMA 2001;285:1044-55.

17. DeVore GR, Romero R. Combined use of genetic sonogra-phy and maternal serum triple-marker screening: an effectivemethod for increasing the detection of trisomy 21 in womenyounger than 35 years. J Ultrasound Med 2001;20:645-54.

18. Papp C, Szigeti Z, Tóth-Pál E, Hajdú J, Joó JG, Papp Z.Ultrasonographic findings of fetal aneuploidies in the secondtrimester--our experiences. Fetal Diagn Ther 2008;23:105-13.

19. Källén B, Mastroiacovo P, Robert E. Major congenital mal-formations in Down syndrome. Am J Med Genet1996;65:160-6.

20. Bromley B, Lieberman E, Shipp TD, Benacerraf BR. Fetalnose bone length: a marker for Down syndrome in the sec-ond trimester. J Ultrasound Med 2002;21:1387-94.

21. Taner CE, Aygören MO, Kayar ‹, Derin G. Down sendrom-lu olgularda ultrasonografik bulgular. Perinatoloji Dergisi2009;17:65-9

22. Lanfranco F, Kamischke A, Zitzmann M, Nieschlag E.Klinefelter's syndrome. Lancet 2004;364(9430):273-83.

23. Marteau TM, Nippert I, Hall S, Limbert C, Reid M, BobrowM, et al.; DADA Study Group. Outcomes of pregnanciesdiagnosed with Klinefelter syndrome: the possible influence ofhealth professionals. Prenat Diagn 2002;22:562-6.

24. Gruchy N, Vialard F, Decamp M, Choiset A, Rossi A, LeMeur N, et al. Pregnancy outcomes in 188 French cases ofprenatally diagnosed Klinefelter syndrome. Hum Reprod2011;26:2570-5.

25. Biggio JR Jr. First trimester ultrasound screening for fetal ane-uploidy and middle cerebral artery Doppler assessment forfetal alloimmunization. Curr Opin Pediatr 2005;17:713-9.

Obesity at conceivement interferes with placentalweight but not birth weight

Gülengül Köken1, Seda Köse1, Da¤›stan Ar›öz1, Mehmet Y›lmazer1, Ayflenur Çak›r Güngör2

1Department of Obstetrics&Gynecology, Faculty of Medicine, Afyon Kocatepe University, Afyonkarahisar, Turkey2Department of Obstetrics&Gynecology, Faculty of Medicine, Çanakkale Onsekiz Mart Universtiy, Çanakkale, Turkey

IntroductionMultidirectional relationships among mother, placentaand fetus are very complex and more appropriate inter-actions among them result in a healthier mother and ababy.

It is known that there is a correlation between pla-cental weight, birth weight and gestational age.Placental localization, maternal weight gain, age, lyingposition of the mother, sex of the fetus might affect theneonatal birth weight.[1,2] Many studies have considered

Abstract

Objective: Obesity is a well-known risk factor for the pregnancyoutcome. We aimed to assess the relationship among pre-concep-tional obesity, birth weight and placental weight.

Methods: Regularly followed-up 259 women were divided intotwo groups according to their pre-conceptional body mass index(BMI). There were 177 patients in the non-obese group who hadBMI below 25 and 82 patients in the obese group who had BMIequal to or above 25. Babies and placentas were weighted, placen-tal weight to birth weight ratio (PW/BW) were calculated.

Results: While birth weight did not differ between the groupssignificantly (3294±420 vs. 3389±425), mean placental weight wassignificantly higher in the obese group (610±114 vs. 659±128)(p=0.004). There was a strong relationship between PW/BW ratioand maternal pre-pregnancy body mass index (BMI). This ratiowas higher in the obese group when compared to the non-obesepatients (18.63±3.11 vs. 19.44±2.95) (p=0.054).

Conclusion: Our findings may be interpreted as the obesity caus-es ineffective nutrition of the baby so that relatively bigger placen-tas are needed by the fetus to reach its potential size. Further stud-ies must be done to clarify the relationship between placental suf-ficiencies of obese patients.

Key words: Birth weight, obesity, placenta, pregnancy.

Correspondence: Ayflenur Çak›r Güngör, MD. Çanakkale Onsekiz Mart Üniversitesi Kad›n Hastal›klar› ve Do¤um Anabilim Dal›, Çanakkale, Turkey.e-mail: dr_aysecakir@hotmail.com

Received: August 16, 2013; Accepted: September 27, 2013

©2013 Perinatal Medicine Foundation

Available online at:www.perinataljournal.com/20130213006

doi:10.2399/prn.13.0213006QR (Quick Response) Code:

Research Article

Perinatal Journal 2013;21(3):129-132

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Pre-konsepsiyonel obezite plasental a¤›rl›¤› etkilemekle birlikte do¤um a¤›rl›¤›n› etkilememektedirAmaç: Obezite gebelik sonuçlar›n› etkileyen risk faktörlerindendir.Bu çal›flmada konsepsiyon öncesi obezite ile do¤um a¤›rl›¤› ve pla-sental a¤›rl›k aras›nda iliflki olup olmad›¤›n› araflt›rmay› amaçlad›k.

Yöntem: Düzenli takip edilen 259 gebe pre-konsepsiyonel vücutkitle indeksine (VK‹) göre iki gruba ayr›lm›flt›r. Hastalar›n177’sinin VK‹ 25’in alt›nda, 82’sinin ise 25 veya üzerindedir.Do¤um sonras› bebekler ve plasentalar tart›lm›flt›r ve plasentala¤›rl›¤›n bebek a¤›rl›¤›na oran› (PA/DA) hesaplanm›flt›r.

Bulgular: Gruplar aras›nda do¤um a¤›rl›klar› aç›s›ndan anlaml›fark izlenmezken (3294±420 vs 3389±425), ortalama plasentala¤›rl›k obez grupta anlaml› olarak daha yüksektir (610±114 vs659±128) (p=0.004). PA/DA ile pre-konsepsiyon dönemindekiVK‹ aras›nda güçlü bir iliflki mevcuttur. Bu oran obez grupta kon-trol grubuyla karfl›laflt›r›ld›¤›nda daha yüksektir (18.63±3.11 vs19.44±2.95) (p=0.054).

Sonuç: Bulgular›m›z maternal obezitenin etkin olmayan birbeslenmeye neden oldu¤u ve fetüsün potansiyel boyutuna ulaflmas›için rölatif olarak daha büyük plasentaya gereksinim duydu¤ufleklinde yorumlanabilir. Obez insanlardaki plasental yetmezli¤inaç›kl›¤a kavuflmas› için baflka çal›flmalara da ihtiyaç duyulmaktad›r.

Anahtar sözcükler: Do¤um a¤›rl›¤›, gebelik, obezite, plasenta.

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that the anthropometric characteristics of the parentshave an influence on birth weight.[3,4]

Placental weight is also affected by many factorssuch as maternal anemia, gestational week of birth,maternal systemic diseases, fetal anomalies, abnormalplacental forms and placentation.[5] Dietary changesalso result in changes in placental weight as well asbirth weight.

It is well-known that maternal obesity is stronglyrelated to the poor obstetric outcomes.[6] Pre-pregnan-cy obesity is shown to be related to increased birthweight previously.[7] Although pre-pregnancy obesity isshown to be related to increased inflammation in pla-centa,[8] the relationship between pre-conceptionalobesity and placental weight has not been clarified yet.

The objective of our study is to assess the relation-ship among maternal pre-conceptional obesity, birthweight and placental weight.

MethodsWe conducted our study in the department of gynecol-ogy and obstetrics of a university hospital between2009 and 2011. Local ethical committee approval wastaken for the study.

All patients that were followed-up regularly in ourhospital and delivered after 37th week of gestationwere included into the study. The patients who hadsystemic diseases such as hypertension, diabetes, ane-mia, cardiac disease and respiratory system disease andcomplicated pregnancies such as hyperemesis gravi-darum, gestational diabetes, pregnancy induced hyper-tension, multiple pregnancies, fetal anomalies wereexcluded from the study. Informed consent forms werereceived from the patients. The patients with missingdata were also excluded. Totally 259 women wereincluded in the study.

Soon after the delivery, babies were weighted bythe same digital scale without any clothes after short-ening the umbilical cord by the nurses.

After the spontaneous removal of the placenta itwas evaluated if it was complete. Then they wereweighted on a digital scale by the nurses as soon as pos-sible with its membranes and cord. PW/BW ratio wascalculated by dividing placental weight to birth weightand multiplying the result by 100.[9]

To calculate body mass index (BMI) from the fol-low-up charts of the patients, we determined the

height and pre-pregnancy weight and calculate theBMI by dividing the weight (kg) of the patient to thesquare of her height (m). We calculated the weightgain throughout the pregnancy by subtracting the pre-pregnancy weight of the patient from her weight whenshe was hospitalized for the delivery.

For the statistical evaluation SPSS 11.5 packageprogram (SPSS Inc., Chicago, IL, USA) was used.Descriptive statistics for continuous variables weredefined as mean ± standard deviation and categoricalvariables were expressed as case number and per cent.p<0.05 was accepted as statistical significance.Backward regression analysis was done for adjustingthe significance of the data.

ResultsStudy population (n=259) were divided into two groupsaccording to their BMI. The normal group who hadBMI below 25 consisted of 177 women and the obesegroup who had BMI equal to or above 25 consisted of82 women.

While 94 (53.1%) of the patients in the non-obesegroup undergone more than 5 years of formal educa-tion, 29 of the patients of the obese group (35.4%)undergone more than 5 years of formal education(p=0.001). Thirty-five patients (19.8%) of controlgroup and 8 (9.8%) of study population were employed(p=0.013).

Age, gestational week at birth, parity, sex of thebaby, and hemoglobin levels of the groups weredefined in Table 1.

While birth weight did not differ between thegroups significantly, mean placental weight was signif-icantly higher in the obese group when compared tothe non-obese ones (Table 2).

Although it did not reach a significant level, therewas a strong relationship between the PW/BW ratioand the maternal pre-pregnancy BMI. This ratio washigher in the obese group when compared to the non-obese patients (Table 2).

BMI ≥25 is significantly related to the placentalweight. After adjusting for age, parity, education andemployment, this relationship preserved its signifi-cance.

Placental localization and weight gain during thegestation did not change the birth weight, placentalweight and PW/BW ratio significantly.

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DiscussionIt was recently demonstrated that pregnancies with agreater weight gain of mother ends with a greater birthweight of newborn.[4] Albouy-Llaty et al.[1] showed thatwhile birth weight and abdominal circumference ofbaby is related to the maternal BMI, femur length isrelated to both parents’ height. Pre-pregnancy obesityis shown to be related to increased birth weight previ-ously.[6] In our study, the obese patients had nearly 100g heavier babies when compared to the non-obesepatients. But this difference did not reach statisticallysignificant levels. This might be because of the higherratio of female babies in the obese group when com-pared to the non-obese group. Between the groupsthere was a non-significant but strong difference aboutbaby’s gender (p=0.07). It is well-known that thefemale newborns are relatively smaller than the malenewborns.

Because of the difference of the methods of meas-uring placental weight, comparing the studies aboutthis subject might be very difficult. So this is one of thelimitations of our study as the other studies about thissubject.

Like maternal diet, adipose tissue composition andphysical activity are also related to the placental size.[10]

Hasegawa et al.[5] showed that patients with low mater-nal BMI, preeclampsia, abnormal placental forms andshort umbilical cords had smaller placenta in their ret-rospective study.

In the current study we found that the placentas ofthe patients with pre-pregnancy obesity were heavierthan the placentas of the control group significantly. Itwas concordant with the literature.

In an uncomplicated pregnancy it is known that thelower the PW/BW ratio the higher the nutritional effi-ciency.[11] Maternal anemia and smoking increases thisratio by deteriorating placental circulation. We foundthat PW/BW ratio of the obese group was higher thanthat of the control group. This may be interpreted asthe obesity causes ineffective nutrition of the baby sothat relatively bigger placentas are needed by the fetusto reach its potential size.

In a study, it was shown that there were no correla-tions between placental position and birth weight orlength.[12] In another retrospective study, no correlationsbetween placental position and birth weight and perina-tal outcomes were found.[13] We also could not find arelationship between placental location with either birthweight or placental weight. Although previous studieshave shown a relationship between weight gain duringthe pregnancy and birth weight, we failed to show sucha result perhaps because of the small size of our study.

ConclusionFurther well designed studies must be done for clarify-ing the effect of obesity on placental weight.

Conflicts of Interest: No conflicts declared.

Table 2. Placental weight and birth weight according to BMI.

Variables BMI<25 BMI≥25 P

Birth weight (g) 3294.02±420.00 3389.15±425.56 0.101

Placental weight (g) 610.99±114.72 659.10±128.71 0.004

PW/BW 18.63±3.11 19.44±2.95 0.054

Table 1. The comparison of some parameters among groups.

Variables BMI<25 BMI≥25 P

Age (year) 26.18±4.65 27.83±4.88 0.012

Gestational week at delivery 38.99±1.14 39.13±1.11 0.404

Parity 0.88±0.95 1.45±1.23 0.000

Gender of the baby Female 65 (42.5%) 45 (54.9%)0.07

Male 88 (57.5%) 37 (45.1%)

Hemoglobin level (mg/dl) 11.93±1.38 11.92±1.21 0.098

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References1. Albouy-Llaty M, Thiebaugeorges O, Goua V, Magnin G,

Schweitzer M, Forhan A, et al.; EDEN Mother-ChildCohort Study Group. Influence of fetal and parental factorson intrauterine growth measurements: results of the EDENmother-child cohort. Ultrasound Obstet Gynecol2011;38:673-80.

2. Mamelle N, Cochet V, Claris O. Definition of fetal growthrestriction according to constitutional growth potential. BiolNeonate 2001;80:277-85.

3. Lunde A, Melve KK, Gjessing HK, Skjaerven R, Irgens LM.Genetic and environmental influences on birth weight, birthlength, head circumference, and gestational age by use ofpopulation-based parent-offspring data. Am J Epidemiol2007;165:734-41.

4. Ludwig DS, Currie J. The association between pregnancyweight gain and birthweight: a within-family comparison.Lancet 2010;376:984-90.

5. Hasegawa J, Arakawa K, Nakamura M, Matsuoka R,Ichizuka K, Katsufumi O, et al.Analysis of placental weightcentiles is useful to estimate cause of fetal growth restriction.J Obstet Gynaecol Res 2011;37:1658-65.

6. Addo VN. Body mass index, weight gain during pregnancyand obstetric outcomes. Ghana Med J 2010;44:64-9.

7. Retnakaran R, Ye C, Hanley AJ, Connelly PW, Sermer M,Zinman B, et al. Effect of maternal weight, adipokines, glu-cose intolerance and lipids on infant birth weight amongwomen without gestational diabetes mellitus. CMAJ2012;184:1353-60.

8. Roberts KA, Riley SC, Reynolds RM, Barr S, Evans M,Statham A, et al. Placental structure and inflammation inpregnancies associated with obesity. Placenta 2011;32:247-54.

9. Heinonen S, Taipale P, Saarikoski S. Weights of placentaefrom small-for-gestational age infants revisited. Placenta2001;22:399-404.

10. Jansson T, Powell TL. Role of the placenta in fetal program-ming: underlying mechanisms and potential interventionalapproaches. Clin Sci (London) 2007;113:1-13.

11. Misra DP, Salafia CM, Miller RK, Charles AK. Non-linearand gender-specific relationships among placental growthmeasures and the fetoplacental weight ratio. Placenta2009;30:1052-7.

12. Woods DL, Malan AF, Heese Hde V, Leader LR, vanSchalkwyk DJ. The site of placental insertion and fetalgrowth. S Afr Med J 1980;57:1087-8.

13. Devarajan K, Kives S, Ray JG. Placental location and new-born weight. J Obstet Gynaecol Can 2012;34:325-9.

The effects of gestational diabetes mellitus screeningand diagnostic tests on fetal macrosomia

U¤ur Keskin1, Cihangir Mutlu Ercan1, Saadettin Güngör1, Kaz›m Emre Karaflahin1,Ali Ergün1, Mustafa Öztürk2, Özlem Öztürk3

1Department of Gynecology&Obstetrics, Gülhane Military Academy (GATA), Ankara, Turkey2Clinics of Gynecology&Obstetrics, Etimesgut Military Hospital, Ankara, Turkey

3Department of Medical Biochemistry, Gülhane Military Academy (GATA), Ankara, Turkey

Abstract

Objective: To assign the detection rate of the clinical gestationaldiabetes mellitus by using American Diabetes Association criteria,and to compare the results of the 50 g glucose challenge test(GCT) and 100 g oral glucose tolerance test (OGTT) with fetalmacrosomia. Methods: The results of 50 g GCT and 100 g OGTT of 690 preg-nant were examined for fetal macrosomia. The pregnant dividedinto three groups. Group 1 included pregnant women with normalglucose challenge test (n=580), Group 2 included pregnant womenwith abnormal 50 g GCT but normal 100 g OGTT results (n=66),and Group 3 included pregnant women with a diagnosis of gesta-tional diabetes (n=44). The fetal macrosomia rates within groups(?4000 g) and the efficacy of the 50 g GCT and 100 g OGTT topredict fetal macrosomia were evaluated.Results: The prevalence of the gestational diabetes mellitus was6.3% (CI 4.7-8.4%). The prevalence of the fetal macrosomia was4.4% (26/580; CI 3.0-6,4%) in Group 1, 18.1% (12/66; CI 10.7-29,1%) in Group 2, and 34% (15/44; CI 21-48%) in Group 3. Forthe detection rate of fetal macrosomia, sensitivity and specificity of50 g GCT and 100 g OGTT were 50%, 55%, and 86% and 65%respectively. Positive predictive values were 24% and 34%. Therewas significantly positive correlation between 50 g GCT and 100g OGTT fasting value and birth weight (p). There was no positivecorrelation between 100 g OGTT (1- hour, 2-hour and 3-hour)and birth weight.Conclusion: 50 g GCT and oral glucose tolerance test are notsensitive tests for prediction of the fetal macrosomia. Even ifpatients over 140 mg/dL as a result of 50 g GCT screening test arenot 100 g OGTT positive, they should be followed up closely interms of fetal macrosomia as gestational diabetes mellitus patients.Key words: Fetal macrosomia, gestational diabetes mellitus, glu-cose tolerance test.

Correspondence: U¤ur Keskin, MD. GATA Kad›n Hastal›klar› ve Do¤um Anabilim Dal›, Ankara, Turkey.e-mail: ukeskin22@yahoo.com

Received: July 18, 2013; Accepted: August 18, 2013

©2013 Perinatal Medicine Foundation

Available online at:www.perinataljournal.com/20130213007

doi:10.2399/prn.13.0213007QR (Quick Response) Code:

Research Article

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Gebelik diyabeti tarama ve tan› testlerinin fetalmakrozomi üzerine etkileriAmaç: American Diabetes Association kriterleri kullan›larak ges-tasyonel diabetes mellitus prevalans›n›n belirlenmesi ve gestasyo-nel diyabetes mellitusun komplikasyonlar›ndan birisi olan fetalmakrozominin, 50 g glukoz challenge test (GCT) ve 100 g oralglukoz tolerans testi (OGTT) sonuçlar› ile aras›ndaki ilifllkinin in-celenmesidir. Yöntem: 690 gebenin 50 g GCT ve 100 g OGTT sonuçlar› fetalmakrozomi aç›s›ndan de¤erlendirildi. Gebeler 3 gruba ayr›ld›.Grup 1 (n=580): 50 g GCT sonuçlar› normal gebeler; Grup 2(n=66): 50 g GCT sonuçlar› yüksek ancak 100 g OGTT sonuçlar›normal olan gebeler; Grup 3 (n=44): Gestasyonel diabetes mellitustan›s› alan olgular. Gruplar içerisinde, fetal makrozomi oranlar›(≥4000 g) ve fetal makrozomiyi saptamada 50 g GCT ve 100 gOGTT’nin etkinli¤i araflt›r›ld›. Bulgular: Popülasyonumuzda, gestasyonel diabetes mellitus pre-valans› %6.3 (CI %4.7-8.4) bulundu. Fetal makrozomi prevalans›;Grup 1’de %4.4 (26/580; CI %3.0-6.4), Grup 2’de %18.1 (12/66;CI %10.7-29.1), Grup 3’te ise %34 (15/44; CI %21-48) idi. Fetalmakrozomiyi saptamada, s›ras› ile 50 g GCT ve 100 g OGTT’ninsensitivitesi %50, %55, spesifitesi %86, %65; pozitif prediktifde?erleri ise, %24, %34 bulundu. 50 g GCT ve 100 g OGTT aç-l›k de¤eri ile do¤um kilolar› aras›nda anlaml› pozitif korelasyonsaptand›. 100 g OGTT 1. saat, 2. saat, 3. saat de¤erleri ile fetala¤›rl›klar aras›nda korelasyon saptanmad›.Sonuç: 50 g GCT ve 100 g OGTT makrozomik fetus s›kl›¤›n›nsaptamas›nda duyarl› testler de¤ildir. 50 g GCT tarama sonucu140 mg/dl’nin üzerindeki hastalar 100 g OGTT pozitif olmasa bi-le gestasyonel diyabetes mellitus hastalar› gibi fetal makrozomiaç›s›ndan yak›ndan izlenmelidir.

Anahtar sözcükler: Fetal makrozomi, glukoz tolerans testi, ges-tasyonel diabetes mellitus.

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IntroductionGestational diabetes mellitus (GDM) is defined as thecarbohydrate intolerance detected during pregnancyfirst.[1] Although its prevalence varies by countries, it isgenerally between 3.1% and 6.8%.[2] Screening anddiagnostic tests of gestational diabetes mellitus are per-formed between 24 and 28 weeks of gestation.[3] Today,there has been still no consensus for the screening anddiagnosis tests yet. As in the world, single-phase 75 gOGTT test in addition to 2-phase test approach con-sisting of 50 g glucose challenge test (GCT) and 100 goral glucose tolerance test (OGTT) is adopted inTurkey.

The purpose of these screening and diagnostic testsis to establish early diagnosis and to prevent complica-tions that may develop in mother or baby throughincreases in blood glucose. One of the complications ofgestational diabetes is macrosomia.[4] Widely accepteddefinition of macrosomia is the fetal birth weight over4000 g.[5] According to the bulletin of AmericanCollege of Obstetric and Gynecology (ACOG),although considering 4500 g and above as macrosomicis practical, considering as 4000 g and above is morewidely accepted in terms of reducing mortality andmorbidity.[6,7] There are many risk factors for macro-somic fetus. Gaining too much weight during pregnan-cy, being obese, postterm pregnancy, and macrosomicfetus history are among these factors. The highest riskfactor is to be a diabetic mother. In the studies analyz-ing fetal macrosomia frequency, fetal macrosomia inci-dence at GDM is 16-29% while it is 10% in pregnan-cy not complicated by diabetes.[8] Many risk factorshave been presented. Gaining too much weight duringpregnancy, being obese, postterm pregnancy, andmacrosomic fetus delivery history are among these fac-tors. The highest risk factor is to be a diabetic mother

When the literature is reviewed, it is seen that thepregnant women who have 100 g OGTT results with-in normal limits despite the high 50 g GCT results areunder more risk compared to normal pregnant womenin terms of obstetric outcomes.[9,10]

The purpose of our study is to determine GDMprevalence in our own population, to analyze the rela-tionship of fetal macrosomia which one of the GDMcomplication with the results of 50 g GCT and 100 gOGTT, and to detect cases who have high 50 g GCTresults but within normal limits of 100 g OGTT and toevaluate them in terms of fetal macrosomia.

MethodsThe study performed between September 2009 andAugust 2010 in Gynecology&Obstetrics Departmentand Medical Biochemistry Department of GATAHospital. Results of 999 pregnant women who admit-ted for 50 g GCT at 24-28 weeks of gestation for rou-tine pregnancy follow-up were evaluated retrospective-ly. The results of 690 pregnant women who gave birthin our clinic have been reached. Pregnants who werepositive for 50 g GCT but no OGTT result, pregnantswho had only OGTT results, cases followed up withpre-gestational diabetes diagnosis and multiple preg-nancies were excluded from the study. For OGTT,≥130 mg/dL at 50 g GCT was considered as the limit[11]

and 100 g OGTT diagnostic test was applied topatients who were above this limit. Gestational dia-betes mellitus diagnosis was established when 2 ormore higher values were detected according to ADAcriteria (fasting 105 mg/dL, 1-hour 190 mg/dL, 2-hour165 mg/dL, 3-hour 145 mg/dL).[12] The patients weredivided into 3 groups; Group 1 included normal preg-nants (n=580; 50 g GCT <130 mg/dL), Group 2included pregnants who were established GDM diag-nosis at the limit (n=66; 50 g GCT ≥130 mg/dL, nor-mal 100 g OGTT results), and Group 1 included preg-nants who were established GDM diagnosis (n=44).Those who had birth weight as 4000 g and above wereconsidered as macrosomia. While 13 of the patients ingestational diabetes mellitus group were receivinginsulin therapy and following diet, 31 patients only fol-lowed diet.

Blood samples collected for glucose challenge testand OGTT were taken into gray-capped (BDVacutainer Plastic fluoride/oxalate) tubes. Glucosemeasurement was performed by Olympus AU2700(Hamburg, Germany) auto-analyzer. Hexokinasemethod was used as measurement method.

For statistical analyses, Student’s t-test, Pearsoncorrelation analysis and ROC analysis were used onSPSS 15.0 (SPSS Inc., Chicago, IL, USA) program.Results were considered as statistically significant whenp value was found to be <0.05.

ResultsIn 110 (15.9%, CI 13.4-18.8%) of the 690 patientsincluded to the study, 50 g GCT was positive (≥130),100 g OGTT was used. According to AmericanDiabetes Association (ADA) criteria, 6.3% (44/690; CI

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4.7-8.4%) of the patients were established GDM diag-nosis.

Mean ages of pregnants were 28.8±4.8 in Group 1,30.2±4.6 in Group 2, and 32.0±5.2 in Group 3. Therewas statistically significant difference between Group 1and Group 3 in terms of age (p<0.001). Mean fetalbirth weight was 3422±344 g in Group 1, 3524±455 gin Group 2, and 3380±684 g in Group 3. There wasstatistically no significant difference between groups interms of age or fetal birth weights; however, there wasstatistically significant difference between groups interms of glycemia values at 50 g GCT (1-hour) and 100g OGTT (0, 1, 2, and 3-hours) (Table 1).

When all groups were analyzed together, fetalmacrosomia rate was found to be 7.6% (53/690; CI5.9-9.9%). Mean fetal weight of 53 cases who found tohave fetal macrosomia was 4189±167 g.

When subgroups were evaluated, fetal macrosomiarate was 4.4% (26/580; CI 3.0-6.4%) in Group 1,18.1% (12/66; CI 10.7-29.1%) in Group 2 and 34%(15/44; CI 21-48%) in Group 3. Also, when Groups 2and 3 which have positive 50 g GCT are evaluatedtogether, fetal macrosomia rate was found as 24.5%(27/110; CI 17-33%).

In terms of the relationship of fetal weights of 50 gGCT (+) group (Groups 2 and 3) with GCT andOGTT results, positive correlation was found onlybetween 50 g GCT (1 hour), 100 g OGTT (fasting)and fetal weights (p<0.05); however, there was no cor-relation between fetal weights and 1-hour, 2-hour and3-hour of 100 g OGTT (p>0.05).

When groups with and without fetal macrosomiawere evaluated separately, significant correlation wasfound only between birth weights in the group withoutmacrosomia and 2-hour value of 100 g OGTT(p<0.001) while there was no correlation in macrosom-ic group between 50 g GCT (1-hour) and 100 gOGTT values (Fig. 1).

In Group 2, 50 g GCT result of all macrosomicbabies was found to be above 140 mg/dL (Fig. 1). Inthe ROC analysis of Group 2 with 50 g GCT value atand above 140 mg/dL, macrosomic fetus labor sensitiv-ity was found to be 100% and the specificity was foundto be 45.3% (Fig. 2).

For macrosomia of 50 g GCT, the sensitivity was50%, specificity was 86%, positive predictive value(PPV) was 24%, negative predictive value (NPV) was95%, and likelihood ratio (LR) was 3.9. For macrosomiaof 100 g OGGT according to ADA criteria, sensitivitywas found as 55%, specificity as 65%, positive predictivevalue (PPV) was 34%, negative predictive value (NPV)was 81%, and likelihood ratio (LR) was 1.5.

DiscussionThe prevalence of gestational diabetes mellitus variesbetween 3.1% and 6.8%.[2] In Turkish population, itwas found to be 4.48% according to ADA criteria.[13] Inour study, this rate was found as 6.3% (CI 4.7-8.4%).

In our study, the mean age of pregnant womendiagnosed with GDM was 32±5 while it was 28.8±4.8for normal pregnant women. As known, advancedmaternal age is a risk factor for GDM; therefore, thefindings in our study is consistent with the literature.[14]

Table 1. Demographic, clinical and laboratory data of pregnants who undergone gestational diabetes melli-tus screening at 24-28 weeks of gestation.

Group 1 Group 2 Group 3GCT (-) GCT (+) GDM (-) GDM (+)n= 580 n= 66 n= 44

(Mean±SD) (Mean±SD) (Mean±SD) p

Age 28.8±4.8 30.2±4.6 32.0±5.2 NS

Fetal birth weight 3422±344 3524±455 3380±684 NS

50 g GCT 100±29.3 145.1±9.7 171.6±27.1 <0.001

100 g OGTT Fasting - 84.1±5.7 94±11.4 <0.001

100 g OGTT 1-hour - 158±26.3 198.3±22 <0.001

100 g OGTT 2-hour - 133.8±18.1 165±30.7 <0.001

100 g OGTT 3-hour - 99.4±19.4 129.5±28.5 <0.001

GCT: glucose challenge test, GDM: gestational diabetes mellitus, NS: not significant, OGTT: oral glucose tolerance test,SD: standard deviation.

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Fetal macrosomia is a clinical condition which devel-ops as a result of metabolic events with fetal and mater-nal traumas associated with mechanical factors, andshould be predicted prenatally due to perinatal death;therefore its risk factors and possible complications

should be known and intrapartum and postpartum clin-ical managements should be carried out carefully.

When compared with normoglycemics, macroso-mia is three times higher in diabetics and this is associ-ated with various morbidities in the babies of diabeticmothers.[15] In addition to the gestational diabetes,macrosomia history, pre-gestational weight, weightgained during pregnancy, multiparity, male fetus,pregnancies exceeding 40 weeks, and maternal size arethe other risk factors for macrosomia. Macrosomiaincidence in gestational diabetes is reported as 16-29%in the literature, but this rate is 10% in those withoutgestational diabetes.[8] In our study, macrosomia inci-dence was 5.9% in the group without GDM diagnosis(Groups 1 and 2), and it was 34% in the group withGDM diagnosis. Also, macrosomia rate was found tobe 24.5% in the group (Groups 2 and 3) which waspositive for 50 g GCT. The recent data from Turkeypresents macrosomia rate in the general population as5.15%.[16] In our study, this rate was found as 7.6%.

50 g screening test and 100 g OGTT were com-pared in the literature when other risk factors are gotunder control, and it was found that the possibility ofdelivering macrosomic fetus in cases with high 50 gscreening test result but normal 100 g OGTT resultwas higher than the pregnants with normal 50 gscreening test result.[17] In our study, this rate was 4,4%(CI 3.0-6.4%) in Group 1 (26/580) and 18.1% (CI10.7-29.1%) in Group 2 (12/66).

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It was shown in the literature that the most signifi-cant risk factor for macrosomia was 140 mg/dL positiveGCT.[18] In our study, no macrosomic baby was seen inGroup 2 pregnants who were below 140 mg for 50 gGCT. The sensitivity and specificity for deliveringmacrosomic baby in results at and above 140 mg/dLwere found to be 100% and 45.3%, respectively.

In the studies performed in Turkey, a significantrelationship was detected between macrosomia andblood glucose value found to be high at OGTT. Also,fasting screening test and 2-hour OGTT blood glu-cose level were found to be independent risk factors forfetal weight.[19] In our study, where we evaluated therelationship of fetal birth weight with GCT andOGTT results of the group (Groups 2 and 3) whichwas positive for 50 g GCT, positive correlation wasonly found between 50 g GCT & OGTT fastingresults and birth weights (p<0.05); there was no corre-lation between OGTT 1-hour, 2-hour, and 3-hourvalues and birth weights (p>0.05). Groups with andwithout macrosomia were evaluated separately, birthweights in non-macrosomic group was only correlatedwith OGTT 2-hour (p<0.001) while there was no sig-nificant correlation in 50 g GCT and OGTT values ofmacrosomic group.

In our study, when threshold value of 50 g GCTwas considered as 130 mg/dL, we calculated that sensi-tivity was 50% (37-63%), specificity was 86% (84-89%), PPV was 24% (17-33%), NPV was 95% (93-96%), and LHR was 3.9 (2.8-5.4) for detecting macro-somia while sensitivity was 55% (37-72%), specificitywas 65% (54-74%), PPV was 34% (21-48%), NPVwas 81% (70-89%), and LHR was 1.5 (1.0-2.4) forOGTT.

ConclusionWe have concluded that 50 g GCT and 10 g OGTT(fasting, 1-hour, 2-hour, and 3-hour) are not sensitivetests for detecting macrosomic fetus frequency.

Conflicts of Interest: No conflicts declared.

References1. Metzger BE, Coustan DR. Summary and recommendations

of the Fourth International Workshop-Conference onGestational Diabetes Mellitus. The Organizing Committee.Diabetes Care 1998;21 Suppl 2:B161-7.

2. Dabelea D, Snell-Bergeon JK, Hartsfield CL, Bischoff KJ,Hamman RF, McDuffie RS; Kaiser Permanente of ColoradoGDM Screening Program. Increasing prevalence of gesta-

tional diabetes mellitus (GDM) over time and by birthcohort: Kaiser Permanente of Colorado GDM ScreeningProgram. Diabetes Care 2005;28:579-84.

3. Benjamin F, Wilson SJ, Deutsch S, Seltzer VL, Droesch K,Droesch J. Effect of advancing pregnancy on the glucose tol-erance test and on the 50-g oral glucose load screening testfor gestational diabetes. Obstet Gynecol 1986;68:362-5.

4. Brody SC, Harris R, Lohr K. Screening for gestational dia-betes: a summary of the evidence for the U.S. PreventiveServices Task Force. Obstet Gynecol 2003;101:380-92.

5. Jolly MC, Sebire NJ, Harris JP, Regan L, Robinson S. Riskfactors for macrosomia and its clinical consequences: a studyof 350,311 pregnancies. Eur J Obstet Gynecol Reprod Biol2003;111:9-14.

6. ACOG. Intrauterin Growth Restriction. Washington DC-Practice Bulltein. No 12; 2000.

7. ACOG. Fetal Macrosomia. Washington DC-PracticeBulletin No. 22; 2000.

8. Naylor CD, Sermer M, Chen E, Sykora K. Cesarean deliv-ery in relation to birth weight and gestational glucose toler-ance: pathophysiology or practice style? TorontoTrihospital Gestational Diabetes Investigators. JAMA1996;275:1165-70.

9. Dudhbhai M, Lim L, Bombard A, Juliard K, Meenakshi B,Trachelenberg Y, Weiner Z. Characteristics of patients withabnormal glucose challenge test and normal oral glucose tol-erance test results: comparison with normal and gestationaldiabetic patients. Am J Obstet Gynecol 2006;194:e42-5.

10. Ju H, Rumbold AR, Willson KJ, Crowther CA. Borderlinegestational diabetes mellitus and pregnancy outcomes. BMCPregnancy Childbirth 2008;8:31.

11. Öztürk Ö, Serdar MA, Öztürk M, Kurt ‹. Calculation of uncer-tainty for glucose: may it affect the diagnosis of gestational dia-betes. Turkish Journal of Biochemistry 2012;37:68-72.

12. National Diabetes Data Group. Classification and diagnosisof diabetes mellitus and other categories of glucose intoler-ance. Diabetes 1979;28:1039-57.

13. Karcaaltincaba D, Kandemir O, Yalvac S, Güvendag-GuvenS, Haberal A. Prevalence of gestational diabetes mellitus andgestational impaired glucose tolerance in pregnant womenevaluated by National Diabetes Data Group and Carpenterand Coustan criteria. Int J Gynaecol Obstet 2009;106:246-9.

14. Hyer SL, Shehata HA. Gestational diabetes mellitus.Current Obstet Gynaecol 2005;15:368-74.

15. Coustan D. Making the diagnosis of gestational diabetesmellitus. Clinical Obstet Gynecol 2000;43:99-105.

16. Gül M, Çakar E, Demirci O, Pekin O, Sözen H, VatanseverD, Ertekin AA. Makrozomik gebeliklerin do¤um flekilleri vesonuçlar›. Zeynep Kamil Bülteni 2012;43:46-52.

17. Leikin EL, Jenkins JM, Pomerantz GA, Klein L. Abnormalglucose screening test in pregnancy: a risk factor for fetalmacrosomia. Obstet Gynecol 1987;69:570-3.

18. Mello G, Parretti E, Mecacci F, Lucchetti R, Lagazio C,Pratesi M, Scarselli G. Risk factors for fetal macrosomia: theimportance of a positive oral glucose challenge test. Eur JEndocrinol 1997;137:27-33.

19. Gokcel A, Bagis T, Killicadag EB, Tarim E, Guvener N.Comparison of the criteria forgestational diabetes mellitusby NDDG and Carpenter and Coustan, and the outcomes ofpregnancy. J Endocrinol Invest 2002;25:357-61.

The factors affecting the procedure duration duringsecond trimester genetic amniocentesis:

retrospective analysisServet Hac›velio¤lu, Ahmet Uysal, Ayflenur Çak›r Güngör, Meryem Gencer, Emine Coflar

Department of Obstetrics & Gynecology, Faculty of Medicine, Çanakkale Onsekiz Mart University, Çanakkale, Turkey

Abstract

Objective: Genetic amniocentesis is a method of prenatal diagno-sis which is still the most commonly performed procedure today.The aim of this retrospective observational study was to analyzethe factors affecting the duration of second trimester geneticamniocentesis.Methods: We evaluated the files of 117 patients in the study whoundergone second trimester amniocentesis for genetic diagnosis.The duration that the amniocentesis needle was inside the uterinecavity and the duration of total procedure were both recorded andthe correlation of these parameters with clinical and demographiccharacteristics was evaluated. For each patient, the indications forthe procedure and clinical information were also registered. Results: The mean±SD values of 117 patients for age and the weeksof gestation were 31.7±5.4 years and 18.4±1.7 weeks, respectively.The mean±SD values of the time the amniocentesis needle was insidethe uterine cavity and the total procedure time were 85.3±59.3 and118.7±79.5 seconds, respectively. While there was no differenceamong the operators in terms of the duration that the amniocentesisneedle was inside the uterine cavity (p=0.079), the total proceduredurations were statistically different (p=0.004). The procedure wassignificantly longer in patients with vaginal bleeding prior to amnio-centesis than in patients without vaginal bleeding before the proce-dure (115.0 vs 74.8 s; p=0.030). Both the appearance of the needle tipon ultrasound and the difficulty degree of procedure felt by the oper-ators were found to have a significant impact on the duration of theprocedure (p values were 0.024 and 0.030, respectively).Conclusion: The results of this study objectively show that sec-ond trimester genetic amniocentesis is a relatively short proce-dure. The difficulty degree of the procedure, the appearancedegree of the needle tip on ultrasound and the presence of vaginalbleeding prior to the procedure affect the duration of the proce-dure. A larger scale prospective study is needed on the subject.Key words: Amniocentesis, second trimester, prenatal diagnosis.

Correspondence: Servet Hac›velio¤lu, MD. Çanakkale Onsekiz Mart Üniversitesi T›p Fakültesi Kad›n Hastal›klar› ve Do¤um Anabilim Dal›, Çanakkale, Turkey.e-mail: servetozden@comu.edu.tr

Received: July 11, 2013; Accepted: August 18, 2013

©2013 Perinatal Medicine Foundation

Available online at:www.perinataljournal.com/20130213008

doi:10.2399/prn.13.0213008QR (Quick Response) Code:

Research Article

Perinatal Journal 2013;21(3):138-143

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‹kinci trimester genetik amniyosentezde ifllem süresine etki eden faktörlerAmaç: Genetik amniyosentez günümüzde halen en s›k yap›lan in-vaziv prenatal tan› yöntemidir. Bu retrospektif gözlemsel çal›flma-n›n amac› ikinci trimesterde genetik amaçl› yap›lan amniyosentez-de ifllem süresine etki eden faktörleri ortaya koymakt›r.Yöntem: Çal›flmada ikinci trimesterde genetik tan› amaçl› yap›lan117 amniyosentez vakas›n›n dosyalar› tarand›. Amniyosentez i¤ne-sinin uterus içinde kald›¤› süre ve total süre kaydedildi ve bu para-metrelerin klinik ve demografik özelliklerle olan iliflkisi araflt›r›ld›.Her hasta için ifllem endikasyonu ve klinik bilgiler kaydedildi. Bulgular: Toplam 117 hastan›n yafl ve gebelik haftas› ortala-ma±SD de¤erleri s›ras›yla 31.7±5.4 ve 18.4±1.7’dir. Amniyosentezi¤nesinin uterus içinde kald›¤› süre ve total ifllem sürelerinin orta-lama±SD de¤erleri s›ras›yla 85.3±59.3 ve 118.7±79.5 saniye olaraksaptand›. ‹fllemi yapan doktorlar aras›nda i¤nenin içerde kald›¤›süre yönünden fark bulunmazken (p=0.079); total ifllem süreleridoktorlar aras›nda istatistiksel olarak farkl› bulundu (p=0.004).Amniyosentez öncesi dönemde vajinal kanamas› olan hastalardakanamas› olmayan hastalara göre ifllem anlaml› olarak daha uzunsürdü (115.0 vs 74.8 sn; p=0.030). ‹¤ne ucunun ultrasonda görül-me derecesi ve ifllemi yapan hekim taraf›ndan ifllemin hissedilenzorluk derecesi ifllem süresi üzerinde etkili bulundu (p de¤erleri s›-ras›yla 0.024 ve 0.030).Sonuç: Bu çal›flman›n sonuçlar›, ikinci trimesterde genetik amaçl›yap›lan amniyosentez iflleminin k›sa süreli bir ifllem oldu¤unu ob-jektif olarak göstermifltir. ‹fllemin zorluk derecesi, i¤ne ucunun ul-trasonda görülme derecesi ve ifllem öncesi vajinal kanaman›n var-l›¤› ifllem süresini etkilemektedir. Bu konuda daha genifl kapsaml›prospektif çal›flmalara ihtiyaç vard›r.

Anahtar sözcükler: Amniyosentez, ikinci trimester, prenatal tan›.

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IntroductionAmniocentesis is a procedure applied for more than 40years.[1] Despite the improvements in fetal DNA analy-sis methods in maternal blood recently, secondtrimester genetic amniocentesis is still the most com-monly used invasive prenatal diagnosis methodtoday.[2,3]

Second trimester genetic amniocentesis is the pro-cedure of aspiring amniotic fluid by the needle insert-ed through ultrasound guiding into uterus and amniot-ic cavity through abdominal anterior wall, and it is tra-ditionally performed between 15 and 20 weeks of ges-tation.

Generally, the localizations of fetus and placentaare determined before amniocentesis. If placenta is onanterior wall, the needle is inserted through a locationwithout placenta, or by piercing placenta. During theprocedure, the localization of the needle is continuous-ly monitored by ultrasound as displaying the wholeneedle. Thanks to the increase in the resolutions ofultrasound devices, moving amniocentesis needle for-ward under monitoring is rather faster and reliabletoday.

Amniocentesis is a procedure used frequently dur-ing daily practice, and a significant part of the dailyworkflow of physicians in some busy clinics may beoccupied only for amniocentesis. Thus, presenting fac-tors affecting procedure duration and minimizing theduration for the procedure become significant.Although it is done at a great number, there is still lim-ited data today about the duration length of amniocen-tesis and the factors affecting the duration.[4-7]

Therefore, the aim of this study is to reveal the factorsaffecting the duration length of amniocentesis per-formed for genetic purposes at second trimester.

MethodsThe files of patients who undergone amniocentesis atGynecology and Obstetrics Clinic of ÇanakkaleOnsekiz Mart University between October 2012 andJune 2013 were scanned retrospectively. Before theprocedure, the patients and their husbands wereinformed verbally and in written about the techniqueand possible complications of the procedure. Informedconsents were received from the couples who acceptedto have the procedure. A total of 117 patients whoundergone amniocentesis at second trimester for pre-

natal genetic diagnostic purpose due to various indica-tions and had at least 15 weeks and 0 days of singletongestation were included to the study. The procedureindications were considered as high risk in triple test,high risk in double test, high risk in quadruple test,advanced maternal age (≥35), major anomaly or minormarker presence at ultrasound, history of baby withchromosomal anomaly in family and anxiety presencein family. Ages of patients included to the study werebetween 20 and 42. Patients who had multiple preg-nancies, oligohydramnios presence, vaginal bleeding inthe last two days before the procedure, those who tookaspirin or heparin within the last 12 hours before theprocedure or who had missing data in their files wereexcluded from the study.

Medical histories of all patients included to thestudy including age, last menstrual period, gravida,parity, and abortion numbers were received; theirheights/weights were measured and body mass indexes(BMIs) were calculated. Clinical and demographic datasuch as maternal age, weeks of gestation, procedureindication, laparotomy history, vaginal bleeding pres-ence before procedure, placental localization, and pres-ence of transplacental transmission were recorded.

Amniocentesis Procedure

Amniocentesis procedure was conducted as specifiedbelow as a standard in each patient. First, weeks of ges-tation, placental localization and amniotic fluidamount of all patients were determined by ultrasound(Voluson 730 pro, GE Healthcare, Milwaukee, WI,USA). Before the procedure, routine fetal structuralanomaly screening was carried out and weeks of gesta-tion were confirmed by fetal biometry. Before begin-ning the procedure, polyvidone iodine was applied tolower abdominal quadrants. A sterile area was estab-lished on the procedure zone by sterile cover and theneedle insertion point was determined through theguidance of ultrasound. For the procedure, 15 cm and22-gauge spinal needle was used on each patient as astandard. Upon the contact of ultrasound probe withthe skin, it was considered that “total procedure dura-tion” began. After insertion point was determined withthe guidance of continuous ultrasound image, the nee-dle was inserted as needle was making an angle of 45degree against the probe and it was moved to the cavi-ty from the region where there is no fetal part orumbilical cord segment. Transplacental transmission

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was avoided as much as possible. When the needleentered into the cavity, it was considered that the“duration that needle stayed inside” began. In order todecrease the risk of mentioned maternal cell contami-nation, 1 ml amniotic fluid was taken by a separateinjector, and disposed. Then, 16-20 ml amniotic fluidwas aspired from all patients. After this process, withthe retraction of needle, it is considered that bothdurations are ended and these durations are recorded.These two durations described are recorded as amnio-centesis data for each patient at our clinic. The proce-dure was carried out as standard technique by 5 differ-ent operators through following same rules. Allpatients were monitored as inpatient for two hours interms of acute complications, and then they were dis-charged from the hospital after their fetal heart beatswere checked again. Local anesthesia was applied onno patient during the procedure.

The physician carrying out the procedure subjec-tively evaluated the appearance degree of needle tip onultrasound as poor, average and good, and also the dif-ficulty of the procedure as very easy, easy, average,hard, and very hard.

Statistical Analysis

The data of the study was analyzed by using IBM SPSS20 (SPSS Inc., Chicago, IL, USA). The consistency ofvariables with normal distribution was analyzed byvisual (histogram and probability graphs) and analytic(Kolmogorov-Smirnov test) methods. Mann-WhitneyU test was used for the comparison of two independentgroups in terms of numerical variables while Kruskal-Wallis test was used for the comparison of three ormore independent groups. The paired comparisons

were done by using Mann-Whitney U test, and theywere analyzed by using Bonferroni correction.Arithmetic mean±SD and median (first and third quar-ter values) were given as descriptive statistics. P<0.05was considered as statistically significant.

ResultsMean±SD values for age and weeks of gestation oftotally 117 patients were 31.7±5.4 and 18.4±1.7,respectively. Mean±SD values for the duration thatamniocentesis needle stayed within uterine and totalprocedure duration were found as 85.3±59.3 and118.7±79.5 seconds, respectively. Demographic andclinical data of the patients included to the study weregiven in Table 1, and the indications of amniocentesisprocedure were given in Table 2.

While there was no difference among the physi-cians for the procedure duration that the needle stayedinside (p=0.079), there was statistically significant dif-ference for total procedure durations (p=0.004).

Table 1. Demographic and clinical data of patients included to the study (n=117).

Variable Mean±SD Median (quarters)

Age (year) 31,7±5.4 31.0 (28.3-36.0)

BMI* (kg/m2) 25.6±4.8 25.0 (22.0-28.3)

Weeks of gestation 18.4±1.7 18.1 (17.0-19.3)

Gravida (n) 2.2±1.2 2.0 (1.0-3.0)

Parity (n) 0.3±0.5 0.0 (0.0-0.8)

Abortion (n) 0.4±0.8 0.0 (0.0-1.0)

duration that needle stayed inside (sec) 85.3±59.3 60.0 (50.0-105.0)

Total procedure duration (sec) 118.7±79.5 88.5 (60.0-179.3)

*BMI: body mass index

Table 2. The indications of genetic amniocentesis (n=117).

Indication n %

High risk in triple test 33 28.2

High risk in double test 28 23.9

High risk in quadruple test 25 21.4

Advanced maternal age (≥35) 12 10.3

Anomaly presence at USG* 12 10.3

History of baby with chromosomal anomaly 6 5.1

Anxiety presence in family 1 0.08

*Minor and major anomalies observed during ultrasound were included.

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The procedure took long in patients who had vagi-nal bleeding before amniocentesis compared to thosewithout vaginal bleeding (115.0 vs 74.8 sec; p=0.030).The appearance degree of needle tip on ultrasound andthe difficulty level during the procedure that the physi-cian had was found to have impact on the procedureduration (p values were 0.024 and 0.03, respectively).In paired comparisons conducted by Bonferroni cor-rection, the appearance degree of needle tip on ultra-sound being “poor” or “good” was found to haveimpact on the procedure duration (p=0.004). Similarly,in paired comparisons conducted by Bonferroni cor-rection, there was difference in terms of the procedureduration between the “easy” and “average” groups forthe difficulty level during the procedure that the physi-cian had being “easy” or “average” (p=0.002).

Patient age below or above 35, and BMI below orabove 30 kg/m2, presence of laparotomy history, pla-cental localization and transplacental transmission ofneedle had no impact on the duration that needlestayed within uterine (p>0.05) (Table 3).

On the other hand, no correlation was foundbetween age, height, weight, BMI, weeks of gestation,gravida, parity and abortion number with the durationthat needle stayed within uterine (p>0.05). No compli-cation was observed in any case during procedures,except temporal fetal bradycardia which lasted only for1-2 minutes in one case.

DiscussionThe results of this study objectively showed that theamniocentesis is a short procedure which lasts for 1.5-

Table 3. Comparison of durations that needle stayed within uterine, according to clinical and demographic charac-teristics (n=117).

The duration that needle stayed within uterine (sec)

Mean±SD Median (quarters) P*

Age (year)<35 86.1±108.8 60.0 (50.0-83.0) 0.706≥35 94.0±72.6 64.0 (50.0-120.0)

BMI† (kg/m2)<35 79.7±54.9 65.0 (50.0-90.0) 0.822≥35 80.8±54.9 68.0 (51.0-92.5)

Laparotomy historyYes 96.6±71.0 75.0 (50.0-122.5) 0.317N/A 67.5±33.7 60.0 (50.0-77.5)

Placental localizationAnterior 75.0±35.5 65.0 (51.3-90.0) 0.457Other 84.1±66.7 69.0 (50.0-90.0)

Transplacental transmission of the needleYes 78.1±58.4 60.0 (50.0-88.3) 0.738N/A 80.9±53.0 64.5 (53.5-90.0)

The presence of vaginal bleeding before procedureYes 115.0±99.7 75.5 (52.5-210.0) 0.030N/A 74.8±43.4 61.0 (50.0-90.0)

The appearance degree of needle tipPoor 175.0±106.1 175.0 (100.0-250.0) 0.024**Average 106.1±79.9 90.0 (50.0-130.0)Good 68.9±36.6 60.0 (50.0-80.0)

The difficulty level of the procedure‡

Very easy 37.5±10.6 43.0 (30.0-63.0) 0.003#

Easy 66.8±33.5 60.0 (50.0-80.0)Average 117.5±78.3 90.0 (60.0-157.0)Hard 175.0±106.1 175.0 (100.0-250.0

*Comparisons were performed by using Mann-Whitney U test and Kruskal-Wallis test. †BMI: body mass index **By conducting Bonferroni cor-rection, statistically significant difference in paired comparisons were determined between “poor-good” groups (P=0,004). ‡The difficulty levelof the procedure was assessed by the physician who carried out the procedure, and there was no patient in “very hard” group. #The statisticallysignificant difference in paired comparison performed by Bonferroni correction was found between “easy” and “average” evaluations (p= 0.002).

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2 minutes. This study also detected that the parameterssuch as the appearance degree of needle tip on ultra-sound during amniocentesis procedure, the difficultylevel of the procedure that physician had and the pres-ence of vaginal bleeding before the procedure had animpact on the duration that needle stayed within theuterine during amniocentesis. Maternal age, BMI,laparotomy history, placental localization and transpla-cental transmission of the needle did not affect statisti-cally the procedure duration.

Amniocentesis is known as a short procedure. In theprospective study performed on 316 amniocentesispatients, Tchirikov et al.[7] used 29-gauge atraumaticneedle for the procedure. The authors reported thatmedian value of the procedure duration as 4.0 minutes(quarters: 4.0-5.0). In our study, the median values forthe duration that the needle stayed within the uterineand total procedure durations were 1 and 1.5 minutes,respectively (Table 1). Both durations are quite short-er than those reported in the study of Tchirikov et al.The reason for the duration difference of the studiesmay be caused by the diameter differences of needlesused in the studies. We used 22-gauge (0.7 mm) needlein our study, but 29-gauge (0.34 mm) needle used byTchirikov et al. which is thinner than our needle maycause the procedure duration to extend. Another possi-ble reason is the possibility that procedure duration hasnot been defined similarly, because authors did notstated clearly the beginning and ending criteria for theprocedure duration. Consequently, amniocentesistakes relatively short time and needles with small diam-eter may extend the procedure duration.

In another study[4] including 123 patients whoundergone early amniocentesis (at 10-13 weeks of ges-tation, mean weeks are 12.3), mean amniocentesis peri-od was reported as 4.02 minutes (95% confidenceinterval; range: 3 minutes and 36 seconds - 4 minutesand 18 seconds). On the other hand, total procedureduration in our study was found as 2 minutes (118 sec-onds). The duration found in this research was approx-imately two times higher than the duration found inour study. This difference between the durations mightbe caused by the fulfillment of amniocenteses at earlyweeks of gestation. Because the uterine volume issmaller during early weeks of gestation and the proce-dure might take long when the needle entered into thecavity. Similarly, total procedure duration might bedefined differently in this study, and cause to find dif-ferent procedure durations. In our study, there was no

correlation between the weeks of gestation and proce-dure duration; however, the procedure duration mightbe found longer since the weeks of gestation is smallerat early amniocentesis.

In the study performed in 2005 and included 50amniocentesis cases,[5] the impact of 4D ultrasound onamniocentesis procedure was analyzed. The authorsreported that they used 2D and then 4D ultrasoundduring the procedure, and that the mean value of totalprocedure duration was 1.5±0.7 minutes. In our study,mean total procedure duration was 118.7±79.5. Ourresult seems to be consistent with the result above.Similarly, in another study comparing the impact of4D and 2D ultrasound procedures,[6] mean duration of100 procedures performed by 2D ultrasound wasreported as 25±5.5 seconds. This short duration maybe caused by the different definition of the durationrecorded. Studies discussed above and our resultsshowed that second trimester genetic amniocentesis isa short-duration prenatal diagnostic method eventhough there are seconds of differences.

During the design phase of the study, we aimed toreveal the impacts of possible factors affecting amnio-centesis procedure durations on both “the durationthat the needle stayed inside” and “the total procedureduration”. However, as we found total procedure dura-tion statistically different among physicians who con-ducted the procedure (p=0.004), we did not carry outmore analysis to see the impact of possible factors.Since the durations that the needle stayed inside weresimilar for all physicians (p=0.079), all analyses wereperformed for the durations that the needle stayedinside.

It is difficult to compare our results with otherssince there are very limited data in the literature for thefactors affecting the duration amniocentesis procedure.In our study, the duration of the procedure was foundto be longer when the needle tip was hardly seen onultrasound or the procedure was difficult for the physi-cian (p values were 0.024 and 0.030, respectively). Itmay be an expected condition that both cases extendthe duration. However, the presence of vaginal bleed-ing (except last two days) before the procedure causedthe procedure to last long (p=0.030). In order to com-pare this result, we could not access to the previousstudies. On the other hand, patient age below or above35, and BMI below or above 30 kg/m2 did not affect theprocedure duration (p values were 0.706 and 0.822,

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respectively). The procedure duration might beexpected to last long in patients with higher BMI val-ues; however, it had no impact on the duration. Thisresult showed that amniocentesis was a short-durationprocedure even on overweight patients.

Our study has some limitations. The most impor-tant limitation is the lack of perinatal results. The pos-sible relationship between perinatal morbidity andmortality with amniocentesis duration (i.e. long proce-dure duration may be together with increased pregnan-cy loss) might reinforce our study. In order to put forththe factors affecting the duration of amniocentesis pro-cedure, it is undoubtedly be the best to design a largerscale of prospective study. Being retrospective andincluding rather less patients may be considered as theother limitations. The strength of our study is to be thefirst putting forth the factors affecting amniocentesisdurations according to the literature.

Conclusion

The results of this study objectively show that geneticamniocentesis performed in second trimester is a rela-tively short procedure. The degree of difficulty of theprocedure that physician had, the appearance degree ofthe needle tip on ultrasound, and the presence of vagi-nal bleeding prior to the procedure affect the duration

of the procedure. A larger scale prospective study isneeded to put forth the factors affecting the duration ofamniocentesis procedure.

Conflicts of Interest: No conflicts declared.

References1. Jacobson CB, Barter RH. Intrauterine diagnosis and manage-

ment of genetic defects. Am J Obstet Gynecol 1967;99:796-805.

2. The Canadian Early and Mid-trimester Amniocentesis Trial(CEMAT) Group. Randomized trial to assess safety and fetaloutcome of early and midtrimester amniocentesis. Lancet1998;351:242-7.

3. Dennis Lo YM. Fetal DNA in maternal plasma: progressthrough epigenetics. Ann N Y Acad Sci 2006;1075:74-80.

4. Farrán I, Sánchez MA, Mediano C, Plaja A, Guzmán A, de laRiva AM, et al. Early amniocentesis with the filtration tech-nique: neonatal outcome in 123 singleton pregnancies.Prenat Diagn 2002;22:859-63.

5. Kim SR, Won HS, Lee PR, Kim A. Four-dimensional ultra-sound guidance of prenatal invasive procedures. UltrasoundObstet Gyencol 2005;26:663-5.

6. Tonni G, Centini G, Rosignoli L, Argento C, Centini G. 4Dvs 2D ultrasound-guided amniocentesis. J Clin Ultrasound2009;37:431-5.

7. Tchirikov M, Arnold C, Oshovskyy V, Heinrich UR, ThäleV. Three years’ experience of using a 29-gauge atraumaticneedle for amniocentesis. J Perinat Med 2012;40:413-7.

Placental and newborn birth weight in term pregnancy

Cem Ard›ç, Resul Ar›soy, Emin Erhan Dönmez, Sevcan Arzu Ar›kan, Emre Erdo¤du, Semih Tu¤rul Ministry of Health Zeynep Kamil Maternity & Child Training and Research Hospital, Istanbul, Turkey

Abstract

Objective: To obtain nomograms of placental and birth weight inuncomplicated pregnancies resulting vaginal birth between 37 and42 weeks of gestation.

Methods: This prospective study included 317 normal (withoutany maternal or fetal complication) pregnancies between 37-42weeks of gestation. Detailed history of pregnants has been taken.Their heights and weights have been measured and body massindexes (BMI) have been calculated. Newborn gestational ages atdelivery, birth weights, and placental weights have been recorded.Percentiles of placental weight and newborn birth weight between37-42 weeks have been obtained.

Results: In 317 pregnancies of study, 174 of newborns werefemale (55%) and 146 of newborns were male (45%). There wasno significant difference among male and female newborns forplacental weight, gestational age at delivery, but birth weight ofmales was higher than of female newborns (p=0.004). Fiftieth per-centiles of newborn birth weight between 37-42 weeks were 560,620, 649, 631, 620, and 610 g, respectively. It has been observedthat placental weight has increased until 39 weeks of gestation andthen decreased. 50th percentile of 37-42 weeks newborn birthweight were; 2970, 3220, 3380, 3385, 3400, 3540 g, respectively.Placental weight/newborn birth weight ratio was 0.19±0.03 and ithas been identified that this ratio showed no difference between37 and 42 weeks of gestation.

Conclusion: The nomograms of placental weight and newbornbirth weight obtained between 37 and 42 weeks of gestation couldbe used at evaluation of pregnants and diagnosis of intrauterinegrowth restriction in our country.

Key words: Newborn birth weight, nomogram, placental weight.

Correspondence: Resul Ar›soy, MD. S.B. Zeynep Kamil Kad›n ve Çocuk Hastal›klar› E¤itim ve Araflt›rma Hastanesi, ‹stanbul, Turkey.e-mail: drresular@hotmail.com

Received: June 17, 2013; Accepted: October 14, 2013

©2013 Perinatal Medicine Foundation

Available online at:www.perinataljournal.com/20130213009

doi:10.2399/prn.13.0213009QR (Quick Response) Code:

Research Article

Perinatal Journal 2013;21(3):144-150

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Term gebelikte plasenta ve yenido¤an do¤uma¤›rl›¤›

Amaç: Normal do¤um ile sonuçlanan komplike olmayan gebelik-lerde, plasenta ve yenido¤an a¤›rl›klar›n›n 37-42. gebelik haftalar›aras›ndaki nomogram›n›n elde edilmesi.

Yöntem: Bu prospektif çal›flmada 37-42. gebelik haftalar›nda ya-p›sal olarak normal olan 317 gebe çal›flmaya dahil edildi. Gebele-rin ayr›nt›l› anemnezleri al›nd›, boylar› ölçülerek kilolar› tart›ld›.Vücut kitle indeksleri (VK‹) hesapland›. Yenido¤anlar›n do¤umhaftas› ile birlikte do¤um a¤›rl›klar› ve plasenta a¤›rl›klar› ölçüle-rek kay›t edildi. Plasenta a¤›rl›¤›n›n ve yenido¤an do¤um a¤›rl›¤›-n›n 37-42. gebelik haftalar› aras›nda persentil da¤›l›mlar› elde edil-di.

Bulgular: Çal›flmaya dahil edilen 317 gebelikte, yenido¤anlar›n174’ü (%55) k›z ve 146’s› (%45) erkek bebek idi. K›z ve erkek ye-nido¤anlar aras›nda do¤um haftas› ve plasenta a¤›rl›¤› aç›s›ndananlaml› farkl›l›k saptanmad› ancak do¤um kilolar›n›n erkek bebek-lerde daha fazla oldu¤u tespit edildi (p=0.004). 37-42. gebelik haf-talar› aras›nda plasenta a¤›rl›¤›n›n 50. persentil de¤erleri s›ras›yla560,620, 649, 631, 620 ve 610 g olarak saptand›. Plasenta a¤›rl›¤›-n›n 39. gebelik haftas›na kadar artt›¤› sonras›nda da azald›¤› tespitedildi. 37-42. gebelik haftalar› aras›nda yenido¤an do¤um a¤›rl›¤›-n›n 50. persentil de¤erleri s›ras›yla 2970, 3220, 3380, 3385, 3400ve 3540 g olarak saptand›. Plasenta a¤›rl›¤›/yenido¤an a¤›rl›¤›0.19±0.03 olarak tespit edilmifl olup bu oran›n 37-42. gebelik haf-talar› aras›nda anlaml› de¤iflkenlik göstermedi¤i tespit edilmifltir.

Sonuç: 37-42. gebelik haftalar› aras›nda elde edilen plasenta ve ye-nido¤an nomogramlar›n›n ülkemizdeki gebeliklerin de¤erlendiril-mesinde ve intrauterin geliflim k›s›tl›l›¤› tan›s›nda kullan›labilece¤idüflünülmektedir.

Anahtar sözcükler: Plasenta a¤›rl›¤›, yenido¤an do¤um a¤›rl›¤›,nomogram

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IntroductionPlacenta is the biggest endocrine organ in human bodyresponsible for the intrauterine development of fetus.In the last two decades, findings proving the signifi-cance of placental weight are published increasingly.Placental weight is affected by many factors such asmaternal age, weight, weeks of gestation, geographicalregion, ethnic origin, maternal conditions (smoking,pregestational systemic diseases, preeclampsia, gesta-tional diabetes, endocrinologic pathologies etc.).[1-6]

Conditions affecting placenta also affect fetus indi-rectly. Factors affecting both birth weight and placen-tal weight are similar. Determining birth weight per-centiles of societies according to weeks of gestationhelps clinicians of those societies to diagnose anddetermine therapy process for fetal growth anomaliesand other intrauterine pathologies.

In our study, we aimed to analyze distribution,according to weeks of gestation, of placental and new-born weights between 37 and 42 weeks of gestations.

MethodsOur study included pregnants between 37 and 42weeks of gestation who carried out spontaneous vaginaldelivery at Zeynep Kamil Maternity & Child Trainingand Research Hospital between 01/12/2012 and31/04/2013.

Detailed histories of pregnants were obtained, theirheights and weights were measured, and their bodymass indexes (BMI) were calculated. Birth weights andplacental weights of newborns as well as their birthweeks were measured and recorded. Fetal chromoso-mal and structural anomalies, pregnancies with fetaldeaths, preterm and post-term pregnancies, multiplepregnancies and pregnancies with maternal diseaseswere excluded from the study.

Patient data were analyzed by SPSS 11.5 packageprogram (SPSS Inc., Chicago, IL, USA). Descriptivestatistical analyses and regression analyses were carriedout. One-way ANOVA and Post Hoc-test (TukeyHSD method) were performed. Normal distributionconsistencies of variables were evaluated byKolmogorov-Smirnov test, and independent samplesT test was used. Results were analyzed at 95% confi-dence interval with p<0.05 significance level.

ResultsOur study included 317 pregnancies who were comply-ing with our study criteria. The age range of the caseswas 18-41, mean age was 26.3±5, mean parity was1.7±1.2, and mean BMI was found 28.7±3.9. The rangeof weeks of gestation was 37-42 in the study, and meanweeks of gestation was 39.4±1.4, mean newborn weightwas 3325.4±413 g, and mean placental weight was626±122 g.

While 174 of the newborns were female, 146 of themwere male. There was no significant difference amongmale and female newborns in terms of birth week andplacental weight; however, it was found that birthweights were higher in male babies (p=0.004) (Table 1).

Significance of all models for the correlationsbetween parameters was analyzed. It was found that thecorrelation between placental weight (PW) and mater-nal weight (MW) was linear (PW = MW×1.4+522.2;p=0.037; r2=0.014) (Fig. 1), but it was not consistentwith a significant cubic model (p=0.1). No significantcorrelation was found between PW and maternal BMI(p>0.05). In the comparison of other parameters, it wasfound that cubic regression model was more consistentand significant. The correlation between PW and weeksof gestation (WoG) was weak; the equation of cubicregression analysis was PW= ((WoG×505.3)-(WoG2×6.3)-9508.8) (r2=0.032; p=0.008) (Fig. 2).

The equation of cubic regression analysis for thecorrelation between PW and newborn birth weight(BW) was PW= ((BW×0.9)+(1.1E-005×BW2) + 202.6)(r2=0.31; p<0.001) (Fig. 3). The equation for the corre-lation between newborn BW and WoG was BW=((WoG×1423.5)-(16.7×WoG2)-26783) (r2=0.16;p<0.001) (Fig. 4). Also, the correlation between BW andmaternal BMI was weak but significant, and the equa-tion was BW= ((BMI×30.4)-(0.006×BMI3)+2600)(r2=0.02; p=0.45) (Fig. 5).

The distributions of percentiles of placental weightand newborn birth weight according to weeks of gesta-tion are given in Tables 2 and 3. Placental weight/new-born weight was 0.19±0.03, and it was found that therewas no significant difference between 37 and 42 weeks ofgestation.

DiscussionPlacental weight and newborn birth weight are affect-ed by many maternal, fetal and environmental factors.

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Also, race and genetic structures are shown as the rea-son for this difference. It is also known that placentaland newborn weights are affected by gestational com-plications (preeclampsia, intrauterine growth retarda-

tion, gestational diabetes). The percentiles of placentalweight and newborn birth weight according to weeksof gestation enable clinicians to compare newborn withthe data of population.[1-6]

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Fig. 1. The correlation between maternal weight and placental weight.

Table 1. Weeks of gestation, placental weight and birth weight of newborns according to their genders.

Gender N Mean Standard deviation P

Weeks of gestation Female 174 39.4 1.5 0.933Male 146 39.4 1.4

Placental weight Female 174 624.9 117.9 0.925Male 146 626.2 127.3

Birth weight Female 174 3264.3 407.8 0.004Male 146 3396.7 408.8

Table 2. Percentile of placental weight according to weeks of gestation.

Weeks of Percentilesgestation 5 10 25 50 75 90 95

37 392.50 430.00 503.00 560.00 670.00 745.00 785.00

38 375.90 432.00 520.00 620.00 672.00 789.00 847.90

39 471.85 503.00 560.00 649.00 720.00 829.00 892.70

40 442.40 484.70 544.50 631.00 700.00 770.00 853.00

41 445.00 470.00 560.00 620.00 700.00 780.00 820.00

42 470.00 500.00 575.50 610.00 705.00 800.00

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In this study, placental weight was compared withweeks of gestation, maternal age, newborn birthweight, maternal body mass index variables. The cor-relation between placental weight and weeks of gesta-tion was found to be weak (r2=0.032; p=0.008). In ourstudy, 50th percentile values of placental weightsbetween 37 and 42 weeks of gestation were 560-620-649-631-620, and 610, respectively; and it was seenthat there was an increase until 39 weeks of gestation,but then it decreased. Although it is considered thatplacental weight may display a societal difference,there is no literature presenting current placentalweight percentiles in our country. Almog et al. con-ducted a study on 20.635 singleton and 527 twin preg-nancies between 24 and 44 weeks of gestation, and ana-

lyzed placental weights of female babies, male babiesand twin pregnancies, and the ratio of placental weightto newborn birth weight. They found a significant cor-relation between placental weights and weeks of gesta-tion in all groups evaluated separately (p<0.0001)(r2>99%).[1] Placental weight percentiles of this studywere compared to data of our study and it is seen thatthe placental weights in our study is lower than thosein the study of Almog et al. during the same weeks ofgestation. Almog et al. found that the ratio of placentalweights to newborn birth weights is highly correlatedwith weeks of gestation (r=0.35; p<0.001). In the studyof Haavaldsen et al. performed on 536.954 singletonpregnancies, it was observed that mean placentalweight under age 20 was 647.1 g while it was 691.3 g

Table 3. Percentile of newborn birth weight according to weeks of gestation.

Weeks of Percentilesgestation 5 10 25 50 75 90 95

37 2300.00 2440.00 2720.00 2970.00 3120.00 3430.00 3835.00

38 2449.00 2732.00 2950.00 3220.00 3500.00 3696.00 4087.00

39 2651.00 2753.00 3040.00 3380.00 3630.00 3859.00 3956.00

40 2815.50 2950.00 3090.00 3385.00 3700.00 3933.00 4034.50

41 2950.00 3070.00 3160.00 3400.00 3700.00 3950.00 4125.00

42 3100.00 3380.00 3435.00 3540.00 3750.00 3990.00

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Fig. 2. The correlation between weeks of gestation and placental weight.

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over age 45.[2] Authors, calculating mean placentalweight as 673.1 g, reported that placental weight Zscores of 12.4% of 40-44-year-old women were in thehighest decimal, while 9.6% of them were in the low-

est decimal. Placental weight Z score of pregnants at orabove age 45 was 15.8% as being the highest decimal,the lowest decimal was found to be 10.4%, whichmeans that Haavaldsen et al. found an increasing

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Fig. 3. The correlation between newborn weight and placental weight.

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Fig. 4. The correlation between weeks of gestation and birth weight.

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prevalence between placental weight and maternal ageincrease with placental weight Z score in the highestdecimal (Wald test p<0.001).[2] However, comparingplacentas of patients together in this study who deliverby cesarean and vaginally may pose a problem. Allpatients in our study delivered vaginally, and no corre-lation was detected between placental weight andmaternal age (p=0.397). Also, a similar comparisoncould be not performed since there was limited num-ber pregnancies below age 20 and above age 40 in ourstudy.

Soliman et al. performed a study on 100 non-preeclamptic pregnants to research placental factorsaffecting perinatal and postnatal development, and

they compared placental weight, maternal weight,newborn birth weight, height, head circumference, andchildhood measurements. They found a significantcorrelation between placental weight and maternalweight (r=0.21; p=0.031), and between placentalweight and newborn birth weight (r=0.71; p<0.001).This case supports the idea that mothers with moreweight have bigger placentas, and therefore they havebigger babies. Also, it was observed in this study thatplacental weights were correlating with early child-hood body mass index. In our study, a weak linear cor-relation was found between placental weight andmaternal weight (p=0.037; r2=0.014); however, therewas no correlation between placental weight andmaternal BMI (p>0.05). According to Almog et al., this

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Fig. 5. The correlation between body mass index and birth weight.

Table 4. Comparison of placental weights (gram) at 50th percentile.

Weeks of Current Almong et al.[1] Thompson et al.[7]

gestation study Male Female Male Female

37 560 627 622 620 61038 620 648 640 650 64039 649 664 654 670 66040 631 679 668 690 67041 620 695 680 700 68042 610 707 688 700 690

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rate was found to be correlated with diseases suchcoronary artery disease, diabetes, stroke and hyperten-sion which may develop during adulthood.[1] Salafia etal. used the increase in the ratio of placentalweight/birth weight as an indicator of an insufficientplacenta for normal fetal growth.[8] They reported thatplacental weight increased compared to fetal weightrelatively due to insufficient placental nutrition, andtherefore placental weight/birth weight ratioincreased. These patients are under risk during adult-hood in terms of coronary artery disease, diabetes,hypertension, and respiratory diseases.[3-6]

In our case, there is a significant correlationbetween birth weight and weeks of gestation (r2=0.16;p<0.001); and 50th percentile birth weight of pregnan-cies between 37 and 42 weeks of gestation are 2970,3220, 3380, 3385, 3400, and 3540 g, respectively. Onthe other hand, there was a weak but significant corre-lation between birth weight and maternal BMI(r2=0.02; p=0.45). Thompson et al. carried out a studyfor placental weight percentiles on 198.971 pregnantsof whom 85.7% were Norwegian and were between 24and 44 weeks of gestation, and they excluded patientswho had clinical problems regarding to placenta (pla-centa praevia, abruptio placentae, incomplete placenta,manual extraction, placental curettage etc.) since theywere considered as the factors that might affect placen-tal weight. The authors reported the percentiles of pla-cental weight and of newborn birth weight as gender-specific in their studies. It was found that the placentalweights in both male and female babies were higherthan the placental weights found in our study (Table4). Another disadvantage of the study of Thompson etal. is the method used for measuring placental weight.The authors also reported similarly that placentalweight increased until 39 weeks of gestation, and tend-ed to remain stable after that week. It was found that

birth weights according to weeks of gestation of femaleand male newborns in their study were higher than thenewborn weights in our study (Table 5). Also,Thompson et al. pointed out that placental weight per-centiles and newborn birth weights may vary accordingto weeks of gestation; however, the ratio of placentalweight/newborn birth weight will not indicate a signif-icant difference.[5] In our study, we found placentalweight/newborn weight as 0.19±0.03; however, thisrate did not demonstrate any significant changebetween 37 and 42 weeks of gestation.

ConclusionIt is considered that the current nomograms used andpercentile distributions of our own population arehigher than it is supposed to be, and it is determinedthat it may lead to make mistakes in analyzing cases.Placenta and newborn nomograms obtained in ourstudy between 37 and 42 weeks of gestation may bemore suitable to use in evaluating pregnancies in ourcountry.

Conflicts of Interest: No conflicts declared.

References1. Almog B, Shehata F, Aljabri S,Levin I, Shalom-Paz E, Shrim

A. Placenta weight percentile curves for singleton and twinsdeliveries. Placenta 2011;32:58-62.

2. Havaaldsen C, Samuelsen SO, Eskild A. The association ofmaternal age with placental weight:a population-based studyof 536,954 pregnancies. BJOG 2011;118:1470-6.

3. Soliman AT, Eldabbagh M, Saleem W, Zahredin K, ShatlaE, Adel A. Placental weight: Relation to maternal weight andgrowth parameters of full-term babies at birth and duringchildhood. J Trop Pediatr 2013;59:358-64.

4. Barker DJ, Hales CN, Fall CH, Osmond C, Phipps K, ClarkPM. Type 2 (noninsulin-dependent) diabetes mellitus,hypertension and hyperlipidaemia (syndrome X): relation toreduced fetal growth. Diabetologia 1993;36:62-7.

5. Barker DJ, Osmond C, Golding J, Kuh D, Wadsworth ME.Growth in utero, blood pressure in childhood and adult life,and mortality from cardiovascular disease. BMJ 1989;298:564-7.

6. Frankel S, Elwood P, Sweetnam P, Yarnell J, Smith GD.Birthweight, body-mass index in middle age, and incidentcoronary heart disease. Lancet 1996;348:1478-80.

7. Thompson J, Irgens L, Skjaerven R, Rasmussen S.Placentaweight percentile curves for singleton deliveries. BJOG2007;114:715-20.

8. Salafia CM, Charles AK, Maas EM. Placental and Fetalgrowth restriction. Clin Obstet Gynecol 2006;49:236-56.

Table 5. Comparison of newborn birth weights (gram) at 50th per-centile.

Weeks of Current Thompson et al.[7]

gestation study Male Female

37 2970 3245 318838 3220 3467 336939 3380 3639 353840 3385 3802 368341 3400 3943 380742 3540 4031 3883

We are re-publishing the first page of the article "Newborn autopsies: experience of referral level III neonatalintensive care unit in Turkey" (2013;21:53-59) published in the 2nd issue of our journal in 2013 since the

English abstract was misprinted. We are truly sorry for this mistake.

Erratum: Newborn autopsies: experience of referral level IIIneonatal intensive care unit in Turkey

Hatice Tatar Aksoy1, S. Suna O¤uz1, Nurdan Urafl1, Ömer Erdeve2, Hatice Bayramo¤lu3, Sema Zergero¤lu3, U¤ur Dilmen1,4

1Department of Neonatology, Zekai Tahir Burak Woman Health Training and Research Hospital, Ankara, Turkey2Department of Pediatrics, Faculty of Medicine Ankara University, Ankara, Turkey

3Department of Pathology, Zekai Tahir Burak Woman Health Training and Research Hospital, Ankara, Turkey4Department of Pediatrics, Faculty of Medicine, Y›ld›r›m Beyaz›t University, Ankara, Turkey

AbstractObjective: Neonatal autopsies are a guide to explore the causes of theperinatal mortalities which is important marker for evaluation of thehealth policies. Multidisciplinary approach which includes obstetri-cian, pediatrician, pathologist and geneticist is required for the neona-tal autopsies. In our study, we have examined the significance ofneonatal autopsy in neonatal deaths occurred in our clinic within 2years, and analyzed whether neonatal autopsy has any impact on con-firming and/or modifying reason of death. Methods: Thirty-eight neonatal autopsies between January 2009 andDecember 2010 were evaluated in respect to demographic characteris-tics, clinical and pathological diagnosis retrospectively. Results: Totally 7055 neonates were hospitalized in our neonatalintensive care unit between January 2009 and December 2010. Amongthem, 404 of the neonates passed away (5.7%). Only 38 (9.4%) of theneonates' parents gave permission for autopsy. Fifteen of theseneonates were female (39%) and 23 of them were male (61%). Sixtypercent of these neonates were premature. Prematurity was higher inmale neonates (p=0.001). Median week of gestation was 32 (22-41).Median overall survival of the neonates were 4 (0-80) days. Whencompared according to gender, there was statistically no significantdifference between survival periods. Prematurity rate was quite highamong male neonates (p=0.001). Eighty-three percent of the clinicaldiagnoses were correlated with the pathological diagnosis. Sixty per-cent of the clinical and pathological diagnoses were cardiovascularanomalies, diaphragmatic hernia, perinatal asphyxia and prematurity.Two neonates had pneumonia diagnosis by the autopsy. Only one ofthese cases had chorioamnionitis in the placenta. Conclusion: Neonatal autopsy rates should be increased to decreasethe neonatal mortality rate in our country. Neonatal autopsies shouldbe done with multidisciplinary approach and become prevalent and getmore progress in our country.Key words: Newborn autopsies, mortality, intensive care.

Correspondence: Hatice Tatar Aksoy, MD. Zekai Tahir Burak Kad›n Sa¤l›¤›,E¤itim ve Araflt›rma Hastanesi Neonatoloji Klini¤i, Ankara, Turkey.e-mail: haticetatar@yahoo.com

Received: May 21, 2013; Accepted: August 8, 2013

©2013 Perinatal Medicine Foundation

Available online at:www.perinataljournal.com/20130213010

doi:10.2399/prn.13.0213010QR (Quick Response) Code:

Erratum

Perinatal Journal 2013;21(3):151

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Yenido¤an otopsileri: Tek merkez deneyimiAmaç: Yenido¤an otopsileri, sa¤l›k politikalar›n›n de¤erlendirilmesin-de önemli olan perinatal mortalitenin sebeplerinin belirlenmesinde yolgöstericidir. Yenido¤an otopsisi, kad›n do¤um ve klinik genetik uzma-n›, pediatrist ve patologdan oluflan bir ekip iflidir. Çal›flmam›zda, üni-temizde 2 y›ll›k süreçte meydana gelen neonatal ölümlerde yenido¤anotopsisinin yeri, otopsinin, ölüm nedenini kesinlefltirme ve/veya de¤ifl-tirmede etkili olup olmad›¤› incelenmifltir.Yöntem: Ünitemizde Ocak 2009 - Aral›k 2010 tarihleri aras›nda otop-si izni al›nan 38 hastan›n demografik özellikleri, klinik ve patolojik ta-n›lar› retrospektif olarak incelendi.Bulgular: Belirtilen tarihler aras›nda 7055 hasta yenido¤an yo¤un ba-k›m ünitesine yat›r›lm›fl, 404 hasta kaybedilmifl (%5.7) ve bunlar›n38’inden (%9.4) otopsi izni al›nm›flt›r. Bu hastalar›n 15’i (%39) k›z,23’ü (%61) erkekti. Otopsi yap›lan yenido¤anlar›n %60’› prematüreidi. Hastalar›n ortanca gebelik haftas› 32 (22-41) hafta bulundu. Has-talar›n ortanca ölüm süresi 4 (0-80) gün idi. Cinsiyete göre grupland›-r›ld›¤›nda ölüm süresi aras›nda istatistiksel anlaml› bir fark saptanma-d›. Erkek bebeklerde prematürite oran› belirgin olarak yüksekti(p=0.001). Klinik tan› patolojik tan› ile %83 oran›nda uyumlu idi. Kli-nik ve patolojik tan›lar›n %60’›n› kardiyovasküler anomali, diyaframhernisi, perinatal asfiksi ve prematürite oluflturmakta idi. Otopsi ile 2olguda pnömoni tan›s› konuldu. Bu olgular›n sadece birinin plasenta-s›nda koryoamniyonit tespit edildi.Sonuç: Ülkemizde neonatal mortalitenin düflürülmesi için neonatalotopsi oranlar› artt›r›lmal›, neonatal otopsinin ülke genelinde yayg›n-laflmas› için ekip çal›flmas› yönündeki e¤ilimlerin yayg›nlaflt›r›lmas› vegelifltirilmesi gereklidir.

Anahtar sözcükler: Yenido¤an otopsileri, mortailite, yo¤un bak›m.

Perinatal Journal152

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Subject Index(Volume 21, 2013)

Subject Index��

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Volume 21 | Issue 3 | December 2013 153

Author Index(Volume 21, 2013)

The bold typed references are the ones in which the person is the first author.

Author Index��

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AAcet F. 119Ak›l E. 12Aktulay A. 107Altunyurt S. 119 Ard›ç C. 144Ar›kan D.C. 47Ar›kan S.A. 144Ar›öz D. 129Ar›soy R. 29, 60, 66, 144Arslan F.T. 77

BBal›k G. 35Balo¤lu A. 17Barut S. 23Baflarano¤lu S. 12Baydar Y. 17Bayo¤lu Tekin Y. 35Bayramo¤lu H. 53Beken S. 42Bezircio¤lu ‹. 17Bostanc› E. 60Boza A. 60Büyükkurt S. 85

C-ÇCoflar E. 138Ça¤lar Aytaç P. 1Ça¤l›yan E. 119Çakar E. 29Çak›r Güngör A. 129, 138Çakmak B. 38Çetin O. 23, 72, 124Çok T. 1

DDelibafl ‹.B. 7Demir S.C. 85Demirci E. 29Demirtürk F. 38 Deregözü A. 124Dilli D. 42

Dilmen U. 53Dönmez E.E. 144

EEmekçi Ö. 119Ender Soydinç H. 12, 113 Engin Üstün Y. 107Ercan C.M. 133Erdeve Ö. 53Erdo¤an fi. 85 Erdo¤du E. 29, 60, 66, 144Ergün A. 133Erkaya S. 107 Evsen M.S. 12

FF›nd›k F. 66

GGencer M. 32,138Gülhan ‹. 101Güngör S. 133Güvenda¤ Güven S. 35

HHac›velio¤lu S. 138

‹‹leri A. 101‹ngeç M. 7 ‹skender C. 1‹skit H.S.85

JJanbakhisov T. 119

KKaraca ‹. 7Karaçor T. 113Karakufl R. 60Karaflahin K.E. 133Kaya B. 93Kayap›nar M. 60

Keskin D.D. 72Keskin S. 72Keskin U. 133Khatib G. 85Koca S.B. 42Köken G. 129Köse S. 129

MMete Ural Ü. 35M›s›rl›o¤lu M. 93Mihmanl› V. 66Mirza T. 66Nacar M.C. 38

OO¤uz S.S. 53 Okumufl N. 42 Öksüzo¤lu A. 107

ÖÖrmeci T. 93Özay A.C. 119Özdemir Ö. 72 Özeren M. 101Özgünen F.T. 85Özler A. 12, 113 Özsoy Z. 38Öztürk M. 133Öztürk Ö. 133 Özyüncü Ö. 96

PPalanc› Y. 12Parlakgümüfl A. 1Pekin O. 29, 60Polat M. 60

SSak M.E. 12 , 89, 113Semih T. 144Serin S. 47

fifiengün Y. 66 fiimflek E. 1

TTan Saz N. 101Tar›m E. 1Tatar Aksoy H. 53Timur A. 101Tu¤rul S. 29, 60, 66 Turgut A. 12, 89, 113Tur¤al M. 96

UUrafl N. 53Uyar ‹. 101 Uysal A. 32, 138Uysal F. 32Uzun Çilingir I. 93Üstüner I. 35

VVerit Atmaca F.F. 72, 124Vural H. 89

YYal›nkaya A. 12, 89, 113 Yaman Görük N. 113Yapan Göral N. 17Yapar Eyi E.G. 107Yapça Ö.E. 7Yaz›c›o¤lu A. 96Yeniterzi E. 77Y›lmazer M. 129Yörük Ö. 107Yücel O. 23, 72, 124Yücel Ö.S. 96

ZZebitay A.G. 23, 124 Zenciro¤lu A. 42Zergero¤lu S. 53

Perinatal Journal154

Olufl Api

Alev At›fl Ayd›n

Filiz Çayan

Ebru Çelik

Ebru Dikensoy

Elif Gül Yapar Eyi

Ali Gedikbafl›

Gökhan Göynümer

Selahattin Kumru

Mertihan Kurdo¤lu

Murat Muhcu

Soner Recai Öner

Lütfü Öndero¤lu

Selçuk Özden

Mehmet Özeren

Mehmet Okan Özkaya

Özlem Pata

‹brahim Polat

Mekin Sezik

Turgay fiener

H. Alper Tanr›verdi

Ebru Tar›m

Ahmet Yal›nkaya

Murat Yayla

Reviewer Index(Volume 21, 2013)

The Editorial Staff of the Perinatal Journal expresses their appreciation to the follouing colleagues who have reviewed manuscripts for Volume 21, 2013.*

Reviewer Index��

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*Names are in alphabetical order.