jurnal naoly

Upload: rudi-lado

Post on 07-Jul-2018

217 views

Category:

Documents


0 download

TRANSCRIPT

  • 8/18/2019 jurnal naoly

    1/58

    Obstetrics and Gynecology InternationalVolume 2014 (2014), Article ID 1920!, "ages#tt"$%%d&'doi'org%10'11%2014%1920!

    e*ie+ Article

    ostcoital -leeding$ A e*ie+ on .tiology, Diagnosis,and /anagement#risto"#er /' arney1 and  asmine 3an2

    1De"artment o Obstetrics and Gynecology, 5omac6 Army /edicalenter, 21! eilly oad, 7ort -ragg, 8 20!, :;A2Di*ision o Gynecology

  • 8/18/2019 jurnal naoly

    2/58

    source or t#eir bleeding and a discussion on t#e natural #istory o "ostcoital bleeding in +omen +#o are ound to #a*e no identi@ableetiology on e*aluation'

    1' Introduction

    Vaginal bleeding not related to menstruation is a commonmultiactorial gynecologic com"laint seen by t#e "rimary care clinicianand is a source o distress bot# to "ro*ider and "atient as t#is can be asign o underlying malignancy' ostcoital bleeding consists o s"ottingor bleeding t#at is not related to menstruation and occurs during orater se&ual intercourse' #e "oint "re*alence ranges rom 0'! to 9'0+it# one re"ort indicating t#at t#e annual cumulati*e incidence is Bamong menstruating +omen C1E' 7or "remeno"ausal +omen +#o arenaturally menstruating, s"ontaneous resolution #as been documented

    in 1 at t+o years +it# no urt#er signs o recurrence C4E' About 0o "atients +it# "ostcoital bleeding also e&"erience abnormal uterinebleeding and 1 #a*e dys"areunia C, BE'

    ostcoital bleeding mainly comes rom surace lesions o t#e genitaltract to include cer*ical "oly"s, cer*icitis, ectro"ion, cer*ical intra<e"it#elial lesion (I8), or carcinoma C!E' #e "re*alence o cer*icalcancer in +omen +it# "ostcoital bleeding is '0 to ' and"re*alence o I8 is B' to 1!' CB, 1E' #e large range in"re*alence is due to *ariations in study design, but more im"ortantly

    on study location' ;tudies "erormed in de*elo"ed countries #a*e alo+er "re*alence o cer*ical cancer and I8 due to access to screening"rograms C101E' #e American ollege o Obstetricians andGynecologists and t#e ;ociety or Gynecologic Oncologists #a*e norecommendations on t#e e*aluation o "ostcoital bleeding inmenstruating +omen' In t#e :nited Fingdom, t#ere are also noestablis#ed guidelines to ensure consistent "ractice' #e :nitedFingdom De"artment o 3ealt# re"orted in #e Guidelines or;us"ected ancer t#at urgent reerral (+it#in 2 +ee6s) s#ould be madeor +omen more t#an years o age +it# "ostcoital bleeding or moret#an 4 +ee6s due to ele*ated ris6 or underlying cer*ical cancer andearly reerral (+it#in 4B +ee6s) may be made in all ot#er cases o une&"lained "ostcoital bleeding C14E' #ese recommendations arereuted by F#attab et al' +#o re"ort t#at t#ere is no signi@cantdierence in t#e "re*alence o cer*ical cancer or I8 in +omen eit#erolder or younger t#an years C1E'

    http://www.hindawi.com/journals/ogi/2014/192087/#B1http://www.hindawi.com/journals/ogi/2014/192087/#B3http://www.hindawi.com/journals/ogi/2014/192087/#B4http://www.hindawi.com/journals/ogi/2014/192087/#B5http://www.hindawi.com/journals/ogi/2014/192087/#B6http://www.hindawi.com/journals/ogi/2014/192087/#B7http://www.hindawi.com/journals/ogi/2014/192087/#B6http://www.hindawi.com/journals/ogi/2014/192087/#B8http://www.hindawi.com/journals/ogi/2014/192087/#B13http://www.hindawi.com/journals/ogi/2014/192087/#B10http://www.hindawi.com/journals/ogi/2014/192087/#B13http://www.hindawi.com/journals/ogi/2014/192087/#B14http://www.hindawi.com/journals/ogi/2014/192087/#B15http://www.hindawi.com/journals/ogi/2014/192087/#B1http://www.hindawi.com/journals/ogi/2014/192087/#B3http://www.hindawi.com/journals/ogi/2014/192087/#B4http://www.hindawi.com/journals/ogi/2014/192087/#B5http://www.hindawi.com/journals/ogi/2014/192087/#B6http://www.hindawi.com/journals/ogi/2014/192087/#B7http://www.hindawi.com/journals/ogi/2014/192087/#B6http://www.hindawi.com/journals/ogi/2014/192087/#B8http://www.hindawi.com/journals/ogi/2014/192087/#B13http://www.hindawi.com/journals/ogi/2014/192087/#B10http://www.hindawi.com/journals/ogi/2014/192087/#B13http://www.hindawi.com/journals/ogi/2014/192087/#B14http://www.hindawi.com/journals/ogi/2014/192087/#B15

  • 8/18/2019 jurnal naoly

    3/58

     #e oyal Australian ollege o Obstetricians and Gynaecologists, #eoyal Australian ollege o General ractitioners, #e Australian;ociety or ol"osco"y and er*ical at#ology, and t#e ommon+ealt#De"artment o 3uman ;er*ices and 3ealt# re"ort t#at col"osco"ys#ould be t#e "rimary diagnostic "rocedure in e*aluating +omen +it#

    "ersistent "ostcoital bleeding and #a*e a sus"icious lesion on t#eircer*i& or +omen +it# a riable cer*i& C!E' 8e*ert#eless, t#esego*erning bodies re"ort t#at "ostcoital bleeding alone is not anabsolute indication or col"osco"y C1BE'

     #e "ur"ose o t#is "a"er is to discuss dierent etiologies o "ostcoitalbleeding, to e&amine t#e current literature regarding diagnostice*aluation, and to re*ie+ treatments o t#is concerning sym"tomaccording to underlying etiology' urrently, t#ere is no e*idence romrandomiHed clinical trials or recommendations rom t#e American

    ollege o Obstetricians and Gynecologists or t#e oyal ollege o Obstetricians and Gynaecologists on standard o care or e*aluation o "ostcoital bleeding C12E'

    2' .tiology

     #e dierential diagnosis or +omen +#o "resent +it# "ostcoitalbleeding is broad' /ost +omen +it# "ostcoital bleeding #a*e benigndisease, +#ic# is reassuring gi*en t#at t#e initial concern or bot#"atient and "ro*ider is t#e "ossibility o underlying malignancy' able 1

    outlines some o t#e most common causes or "ostcoital bleeding'

     able 1$ ommon causes o "ostcoital bleeding'

    2'1' ancer #e greatest ear or "atients e&"eriencing "ostcoital bleeding and"ro*iders ta6ing care o t#ese "atients is t#e concern or underlyingmalignancy' ostcoital bleeding is t#e "resenting com"laint in 11 o +omen +it# cer*ical cancer C1E' er*ical cancer is t#e second mostcommon cancer in +omen t#roug#out t#e +orld' Annual globalestimates or t#e year 2000 +ere 2,400 deat#s and 4!0,B00 ne+

    http://www.hindawi.com/journals/ogi/2014/192087/#B7http://www.hindawi.com/journals/ogi/2014/192087/#B16http://www.hindawi.com/journals/ogi/2014/192087/#B12http://www.hindawi.com/journals/ogi/2014/192087/tab1/http://www.hindawi.com/journals/ogi/2014/192087/#B13http://www.hindawi.com/journals/ogi/2014/192087/#B7http://www.hindawi.com/journals/ogi/2014/192087/#B16http://www.hindawi.com/journals/ogi/2014/192087/#B12http://www.hindawi.com/journals/ogi/2014/192087/tab1/http://www.hindawi.com/journals/ogi/2014/192087/#B13

  • 8/18/2019 jurnal naoly

    4/58

    cases= in t#e :nited ;tates in 2009, t#ere +ere estimates t#at t#ere+ere 11,2!0 ne+ cases o cer*ical cancers and 4,0!0 deat#s C1!, 1E' #e mean age or cer*ical cancer is 1'4 years C1!E' #e mostim"ortant ris6 actor or t#is disease include +omen +#o #a*e beeninected +it# a #ig# ris6 strain o t#e #uman "a"illoma *irus (3V), t#e

    *irus belie*ed to cause cer*ical cancer' Ot#er ris6 actors includeimmunosu""ression and smo6ing' able 2 illustrates t#e ris6 o cer*icalcancer in +omen +it# "ostcoital bleeding based on age C19E' #eincidence o +omen +it# "ostcoital bleeding rom cer*ical cancer #assigni@cantly decreased o*er t#e "ast decades due to en#ancedscreening or cer*ical cancer' er*ical cancer screening, *ia cer*icalcytology eit#er +it# or +it#out testing or 3V, allo+s or t#eidenti@cation o "remalignant and malignant cer*ical disease, +#ic# isim"ortant gi*en t#at I8 is largely asym"tomatic C9, 20E' #e mostcommon #isto"at#ologic ty"es o cer*ical cancer include suamous

    cell carcinoma (B9) and adenocarcinoma (2) C21E' O t#e t+oty"es, adenocarcinoma may be less li6ely to "resent +it# "ostcoitalbleeding as lesions may be #ig#er in t#e cer*ical canal and "rotectedrom t#e trauma o intercourse C1, 9E' 5omen "resenting +it#"ostcoital bleeding +#o are ound to #a*e cer*ical cancer oten arediagnosed +it# a #ig#er stage o cancer t#an asym"tomatic +omenC11, 22E'

     able 2$ is6 o cer*ical cancer in +omen +it# "ostcoital bleeding'Alt#oug# cer*ical cancer may be t#e initial concern o "atients"resenting +it# "ostcoital bleeding, *aginal cancer is anot#ergynecologic malignancy or +#ic# "ostcoital bleeding may be t#e"resenting sym"tom' rimary *aginal cancer is res"onsible or o malignant neo"lasms o t#e emale genital tract' #ere area""ro&imately 000 cases diagnosed eac# year in t#e :nited ;tatesand a""ro&imately 900 deat#s C2E' Vaginal intrae"it#elial neo"lasia(VAI8), t#e "recursor lesion to in*asi*e *aginal carcinoma, is also rare+it# an incidence o a""ro&imately 0'2

  • 8/18/2019 jurnal naoly

    5/58

    ancer o t#e endometrium is t#e most common gynecologic cancer int#e :nited ;tates' In 200, t#ere +ere 40,100 cases o cancer o t#eendometrium and !4!4 deat#s attributed to t#is disease C2E' Vaginalbleeding in "ostmeno"ausal +omen is "rimarily secondary to atro"#icc#anges, but t#is sym"tom can be t#e "resenting com"laint in 90 o 

    +omen +it# endometrial carcinoma C29E'

    7inally, t#ere are "rimary malignancies t#at may maniest in t#e lo+ergenital tract and "resent +it# "ostcoital bleeding' rimary malignantlym"#oma o t#e emale genital tract is rare C0E' 8on

  • 8/18/2019 jurnal naoly

    6/58

    2'4' er*ical oly"s

    er*ical "oly"s are not an inreuent incidental @nding durings"eculum e&ams and can be a source o "ostcoital bleeding secondaryto cer*ical trauma +it# intercourse' -ot# endocer*ical and cer*ical

    "oly"s are t#e most common benign neo"lastic gro+t# t#at occurs ont#e cer*i& +it# an incidence o 4 o gynecologic "atients CBE' oly"sty"ically occur in multi"arous "atients in t#eir 40s to 0s' /ost"atients +it# cer*ical "oly"s only #a*e one, but it is not uncommon to#a*e more t#an one' On gross e&amination, t#ey a""ear as smoot#,reddis# "ur"le lobular structures t#at are riable and bleed easily +#entouc#ed' /ost "oly"s are only a e+ centimeters in siHe' oly"s mayarise rom t#e endocer*ical "ortion o t#e cer*i& or a""ear on t#ecer*ical "ortio' It is belie*ed t#at t#ese "oly"s originate rom recurrentinKammation o t#e cer*i& *ersus ocal res"onse to #ormonal

    stimulation'2'' er*ical .ctro"ion

    er*ical ectro"ion reers to t#e e*ersion o t#e endocer*i& +#ic#e&"oses t#e columnar e"it#elium to t#e *aginal milieu' It is im"ortantto note t#at t#e "resence o ectro"ion does not indicate a "at#ologiccondition' #is area o t#e cer*i& may #a*e a reddis# a""earance andbe co*ered +it# yello+ disc#arge in +#ic# most +omen +it#sym"tomatic cer*ical ectro"ion com"lain o *aginal disc#arge' #iscondition is oten seen during adolescence, +omen ta6ing oral

    contrace"ti*e "ills, and "regnancy due to t#e remodeling "rocess o t#e cer*i&' #e e&"osure o t#e columnar e"it#elium o t#e endocer*i&to t#e *agina t#en increases t#e ris6 o bleeding +it# intercourse dueto t#e riability o t#ese cells C!E'

    2'B' el*ic Organ rola"se

    el*ic organ "rola"se reers to t#e #erniation o "el*ic organs Ccer*i&,bladder, rectum, and uterusE to or beyond t#e *aginal +alls' It is #ardto determine t#e e&act "re*alence o "el*ic organ "rola"se or multi"lereasons$ most +omen only "resent +#en sym"toms become se*ere,

    "ro*iders are "oor at screening +omen during routine *isits, many+omen are embarrassed to re"ort t#ese sym"toms to "ro*iders, and+omen +it# minor "rola"se oten do not re"ort t#ese sym"toms tot#eir "ro*iders' is6 actors or "el*ic organ "rola"se include "arity,obesity, age, #ysterectomy, race, consti"ation, and c#ronic coug#' #ere can be signi@cant irritation and trauma to t#e *agina and cer*i&

    http://www.hindawi.com/journals/ogi/2014/192087/#B36http://www.hindawi.com/journals/ogi/2014/192087/#B37http://www.hindawi.com/journals/ogi/2014/192087/#B36http://www.hindawi.com/journals/ogi/2014/192087/#B37

  • 8/18/2019 jurnal naoly

    7/58

    +#en t#ese organs "rola"se t#roug# t#e introitus +#ic# can lead to"ostcoital bleeding CE'

    2'!' Vaginal%Vul*ar .tiologies

    Vaginal atro"#y, also 6no+n as urogenital atro"#y, atro"#ic *aginitis,or *ul*o*aginal atro"#y, results rom a loss o estrogen +#ic# can leadto *ul*o*aginal com"laints suc# as "ostcoital bleeding' #is conditionty"ically occurs in meno"ausal +omen but may also occur in +omen+#o e&"erience a decrease in estrogen' Ot#er com"laints include*aginal dryness, *aginal burning, dys"areunia, decreased lubrication,*aginal disc#arge, and "el*ic "ressure' ?astly, lic#enoid lesions suc# aslic#en "lanus and lic#en sclerosis may also lead to "ostcoital bleeding'

    2'' -enign Vascular 8eo"lasms

    Vascular tumors o t#e emale genital tract are rare C9E' #ese lesionsinclude #emangiomas, lym"#angiomas, angiomatosis, andarterio*enous malormation' /ost tumors are ound incidentally one&am due to t#eir asym"tomatic nature' 3o+e*er, +#en sym"tomatic,"ostcoital bleeding may be a sym"tom associated +it# t#eseconditions C40E'

    2'9' ;e&ual Abuse

    Domestic and se&ual abuse is a serious "ublic #ealt# "roblem in t#e:nited ;tates by +#ic# 2 million Americans are aected C41E'Gynecologists s#ould screen +omen or abuse at e*ery single *isitregardless o com"laints' 7or e&am"le, one study demonstrated t#at'B o +omen +ere diagnosed +it# se&ual abuse "rior to instituting auni*ersal screening "rogram, +#ereas, ater im"lementation o uni*ersal screening, 0 o t#e "o"ulation +as ound to be aected byabuse C42E' De"ending on t#e e&tent o t#e abuse, *ictims maye&"erience signi@cant genital trauma'

    ' Diagnosis

    At t#is time, t#ere are no establis#ed guidelines rom t#e Americanollege o Obstetricians and Gynecologists or t#e oyal ollege o Obstetricians and Gynaecologists or e*idence rom randomiHed clinicaltrials to base recommendations on diagnosis and treatment o "ostcoital bleeding' #e ollo+ing discussion "ro*ides *arious

    http://www.hindawi.com/journals/ogi/2014/192087/#B38http://www.hindawi.com/journals/ogi/2014/192087/#B39http://www.hindawi.com/journals/ogi/2014/192087/#B40http://www.hindawi.com/journals/ogi/2014/192087/#B41http://www.hindawi.com/journals/ogi/2014/192087/#B42http://www.hindawi.com/journals/ogi/2014/192087/#B38http://www.hindawi.com/journals/ogi/2014/192087/#B39http://www.hindawi.com/journals/ogi/2014/192087/#B40http://www.hindawi.com/journals/ogi/2014/192087/#B41http://www.hindawi.com/journals/ogi/2014/192087/#B42

  • 8/18/2019 jurnal naoly

    8/58

    considerations to ta6e into account +#en a""roac#ing a "atient +it#"ostcoital bleeding' 7igure 1  "resents a diagnostic algorit#m or+omen +it# "ostcoital bleeding'

    7igure 1$ Diagnostic a""roac# to "ostcoital bleeding'

    '1' 3istory

    A t#oroug# em"#asis on "atient #istory oten leads to an accuratediagnosis o "ostcoital bleeding' 5it# all gynecologic "atients, it isim"ortant to obtain an accurate menstrual #istory' 7actors +#ic#s#ould be elicited rom t#e "atient include t#e reuency o t#e"atientJs menstrual cycle, days o menstruation, "resence o #ea*y

    bleeding, "resence o intermenstrual bleeding, and +#et#er cycles areregular or irregular' #e duration o normal menstrual Ko+ is days+it# cycles ty"ically lasting bet+een 21 days C4E' linicians s#ouldalso e*aluate i t#e "atient is "ostmeno"ausal +#ic# is de@ned as 12mont#s o amenorr#ea +it#out any ot#er "#ysiologic or "at#ologiccause' /oreo*er, #istory s#ould ocus on +#et#er t#e "atientJs"ostcoital bleeding is truly bleeding t#at occurs as a direct result o intercourse or i it is secondary to irregular menstrual bleeding' 3istorymay also #el" to dierentiate bet+een +#et#er bleeding is originatingrom t#e uterus or cer*i&' atients +it# abnormal uterine bleeding

    oten re"ort #ea*y "eriods, intermenstrual bleeding not related tointercourse, and irregular menstrual cycles'

     #ere are multi"le considerations to ta6e into account or "atients "astmedical #istory' ;creening s#ould be "erormed as to +#et#er t#e"atient #as been diagnosed or #as any sym"toms concerning ableeding disorder' egarding surgical #istory, determine +#et#er t#ere#a*e been surgeries on t#e genital tract +it# ocus on timing andindication or t#e surgery' A detailed se&ual #istory s#ould be obtained+it# ocus on number o "artners, ne+ "artners, and #istory o any

    se&ually transmitted inections or eit#er t#e "atient or #er "artners' Itis im"erati*e to also screen "atients or domestic abuse and%or se&ualabuse as genital tract trauma can lead to "ostcoital bleeding' atientsmay not be +illing to *olunteer t#is inormation or eit#erembarrassment or ear o retaliation' ro*iders s#ould attem"t toestablis# ra""ort +it# t#e "atient and create an en*ironment in +#ic#"atients may be +illing to s#are t#is inormation' I t#e "atientJs"artner is "resent, t#en strategies may be em"loyed to #a*e t#e

    http://www.hindawi.com/journals/ogi/2014/192087/fig1/http://www.hindawi.com/journals/ogi/2014/192087/#B43http://www.hindawi.com/journals/ogi/2014/192087/fig1/http://www.hindawi.com/journals/ogi/2014/192087/#B43

  • 8/18/2019 jurnal naoly

    9/58

    "artner ste" outside t#e e&am room during t#e time o "el*ic e&am, at+#ic# "oint one may also e*aluate t#e "atient "ri*ately or concerns o abuse' 7inally, "ro*iders s#ould ensure cer*ical cancer screening is u"<to

  • 8/18/2019 jurnal naoly

    10/58

    t#e "atient #as com"lained o dys"areunia or "el*ic "ain, t#en it is alsoim"ortant to delineate t#e location o t#e "ain' /ost +omen +ill not@nd a bimanual e&am comortable, so it is im"ortant to s"eci@cally as6+#at on e&am re"roduces t#e "atientJs "ain' 7inally, i t#ere is concernor underlying malignancy, t#en one s#ould also e*aluate t#e inguinal

    lym"# nodes to determine i t#ere is any lym"#adeno"at#y' Arecto*aginal e&am s#ould be "erormed to determine i t#ere are anymasses or nodularities located on t#e anterior surace o t#e rectum ore&tension o disease into t#e "arametrium'

    '' ?aboratory ests

    On s"eculum e&am, t#ere are multi"le cultures t#at may be obtainedto urt#er e*aluate "ostcoital bleeding' 8ucleic acid am"li@cationtesting (8AA) or 8' gonorr#oeae, ' trac#omatis, and ' *aginaliss#ould routinely be obtained in +omen "resenting +it# "ostcoital

    bleeding' .*en t#oug# +et mount is t#e most cost

  • 8/18/2019 jurnal naoly

    11/58

    smears and no ob*ious lesion on e&am' 3o+e*er, t#e 5or6ing Grou" o t#e oyal Australian ollege o General ractice and o Obstetrics andGynecology C!E recommend t#at general "ractitioners reer +omen orcol"osco"y i t#ey #a*e one o t#e ollo+ing uali@cations=ne*ert#eless, it is im"ortant to realiHe t#at t#ese recommendations are

    not e*idence based C1E$(1)"ersistent "ostcoital bleeding,(2)"ostcoitalbleeding associated +it# a single smear suggesti*e o ?G;I? or +orse,()"ostcoital bleeding associated +it# re"eated smears +it# minoraty"ia or +art *irus c#anges'

    Directed bio"sy +it# col"osco"y remains t#e standard or diseasedetection C4E' ecent studies, #o+e*er, #a*e com"ared directedbio"sy to blind our

  • 8/18/2019 jurnal naoly

    12/58

    ultrasonogra"#y' An endometrial t#ic6ness o greater t#an 4 mm in a"atient +it# "ostmeno"ausal bleeding reuires urt#er e*aluation +it#sono#ysterogra"#y, oLce endometrial bio"sy, or #ysterosco"y'Alternati*ely, "ro*iders may also decide to initiate t#e e*aluation o "ostmeno"ausal bleeding +it# "erorming an endometrial bio"sy C0E'

    4' /anagement

     #e maNority o +omen "resenting to t#eir "rimary care "#ysician +it#t#e com"laints o "ostcoital bleeding +ill be ound to #a*e no ob*iousunderlying cause or t#eir bleeding based on #istory, e&am, orlaboratory in*estigation C11E' 8e*ert#eless, t#e reassuring as"ect ist#at B0 o naturally menstruating +omen +it# "ostcoital bleeding +ill

    #a*e s"ontaneous resolution o sym"toms +it#in si& mont#s C4E' 3al o t#ese +omen +ill maintain resolution or t+o years C4E'

    4'1' Inection

    Any +oman +#o is ound to #a*e e*idence o genital tract inections#ould be immediately treated to "re*ent long term re"ercussions' reatment o"tions s#ould be guided based on laboratory andmicrosco"y @ndings' 5it# res"ect to a clinical diagnosis o "el*icinKammatory disease, treatment s#ould not be +it##eld i testing orc#lamydia and gonorr#ea are negati*e as t#e t#ree maNor criteria

    needed or t#e diagnosis o "el*ic inKammatory disease "er t#eenters or Diseases ontrol and t#e 5orld 3ealt# OrganiHation includecer*ical motion tenderness, bilateral adne&al tenderness, andabdominal tenderness'

    4'2' er*ical .ctro"ion

    er*ical ectro"ion does not reuire treatment unless bleeding is"ersistent and bot#ersome to t#e "atient' rior to "roceeding +it#treatment, one s#ould ensure t#at t#ey #a*e ruled out underlyingmalignancy as certain treatments or cer*ical ectro"ion may mas6 or

    e&acerbate malignant lesions' er*ical ablation +it# eit#er cryot#era"yor electrocautery is eecti*e in mitigating urt#er "ostcoital bleeding'3o+e*er, t#ere are signi@cant side eects to include co"ious *aginaldisc#arge until #ealing is com"lete and cer*ical stenosis +#ic# canaect subseuent "regnancies C1E' An alternati*e t#era"y may be touse acidiying agents suc# as boric acid su""ositories B00 mg *aginallyat bedtime C2E'

    http://www.hindawi.com/journals/ogi/2014/192087/#B50http://www.hindawi.com/journals/ogi/2014/192087/#B11http://www.hindawi.com/journals/ogi/2014/192087/#B4http://www.hindawi.com/journals/ogi/2014/192087/#B4http://www.hindawi.com/journals/ogi/2014/192087/#B51http://www.hindawi.com/journals/ogi/2014/192087/#B52http://www.hindawi.com/journals/ogi/2014/192087/#B50http://www.hindawi.com/journals/ogi/2014/192087/#B11http://www.hindawi.com/journals/ogi/2014/192087/#B4http://www.hindawi.com/journals/ogi/2014/192087/#B4http://www.hindawi.com/journals/ogi/2014/192087/#B51http://www.hindawi.com/journals/ogi/2014/192087/#B52

  • 8/18/2019 jurnal naoly

    13/58

    4'' oly"s

    linicians s#ould consider remo*al o sym"tomatic "oly"s or +#en t#eya""ear aty"ical +it# concerns or malignancy' A cer*ical "oly"ectomycan oten be "erormed in t#e oLce +it#out sedation' emo*al is

    "erormed by @rst "lacing a s"eculum into t#e *agina to *isualiHe t#ecer*ical "oly"' A orce" may t#en be used to gras" t#e "oly" at itsbase and t+ist it o' I t#e base is *isualiHed, t#en cauteriHation s#ouldbe "erormed to "re*ent urt#er bleeding' All "oly"s t#at are remo*eds#ould be sent to "at#ology to be e*aluated or malignancy C24E'7urt#ermore, i t#ere is concern or endometrial "oly"s, t#en t#e"atient s#ould be reerred to o"erati*e #ysterosco"y +it# "ossibledilation and curettage'

    4'4' ancer

    ol"osco"y +it# directed bio"sies is indicated or "atients +it#abnormal cytology' I "atients are ound to #a*e I8 on cer*ical bio"sy,t#en one may ollo+ t#e guidelines establis#ed by t#e Americanollege o Obstetricians and Gynecologists or t#e American ;ociety orol"osco"y and er*ical at#ology to determine +#et#er t#e "atientneeds to be reerred or an e&cisional "rocedure *ersus sur*eillance'atients +#o are ound to #a*e genital tract cancer suc# as *aginal orcer*ical cancer s#ould be reerred to a gynecologic oncologist orurt#er e*aluation and treatment'

    4'' Vaginal Atro"#y

    ostcoital bleeding associated +it# *aginal dryness may @rst betreated +it# *aginal moisturiHers and lubricants +#ic# can be used"rior to and during intercourse' Alt#oug# t#ese met#ods may assist+it# ameliorating discomort during intercourse, t#ey do not #a*e anydirect eect on im"ro*ing atro"#ic c#anges' 5omen +#o continue toe&"erience "ostcoital bleeding des"ite lubricants may reuire *aginalestrogen t#era"y' .strogen t#era"y is one o t#e most eecti*etreatment o"tions or *aginal atro"#y as it t#ic6ens t#e *aginale"it#elium and decreases dryness' ?o+ dose *aginal estrogen t#era"y

    s#ould be t#e @rst line treatment or "ostmeno"ausal +omen +it# only*aginal com"laints as it is more eecti*e and also "re*ents "ossibleside eects o systemic treatment' ;"ecial considerations s#ould bemade +it# use o estrogen t#era"y or +omen +#o #a*e breast cancerand%or cardio*ascular disease'

    ' onclusion

    http://www.hindawi.com/journals/ogi/2014/192087/#B52http://www.hindawi.com/journals/ogi/2014/192087/#B54http://www.hindawi.com/journals/ogi/2014/192087/#B52http://www.hindawi.com/journals/ogi/2014/192087/#B54

  • 8/18/2019 jurnal naoly

    14/58

    ostcoital bleeding can be an annoying com"laint or "atients and a+orrisome sym"tom or "ro*iders due to t#e ris6 o underlyingmalignancy' Des"ite being a common gynecologic "roblem, t#ere islarge di*ersity among gynecologists on t#e management o "ostcoitalbleeding CE' :nli6e abnormal uterine bleeding or t#e management o 

    abnormal cytology, t#ere are no recommendations rom go*erningbodies on t#e management o "ostcoital bleeding' atients "resenting+it# "ostcoital bleeding reuire a ull #istory and "#ysical e&aminationto #el" in de*elo"ing a dierential diagnosis to guide e*aluation andtreatment' Alt#oug# most "atients +it# "ostcoital bleeding do not #a*eunderlying malignancy, "ro*iders must "ay close attetion to ensuret#at a""ro"riate screening tests are u"

  • 8/18/2019 jurnal naoly

    15/58

    ' /' ;#a"ley, F' ordan, and ' ' rot, An e"idemiological sur*eyo sym"toms o menstrual loss in t#e community,P -ritis# ournalo General ractice, *ol' 4, no' 02, ""' 9B, 2004' Vie+ atGoogle ;c#olar Q Vie+ at ;co"us

    4' /' ;#a"ley, /' -lagoNe*ic

  • 8/18/2019 jurnal naoly

    16/58

    , ""' 2020, 199' Vie+ at ublis#er Q Vie+ at Google ;c#olar QVie+ at ;co"us

    11' A' 8' osent#al, ' anos6altsis, ' ;mit#, and 5' ' ;outter,#e reuency o signi@cant "at#ology in +omen attending a

    general gynaecological ser*ice or "ostcoital bleeding,P -ritis# ournal o Obstetrics and Gynaecology, *ol' 10, no' 1, ""' 1010B, 2001' Vie+ at ublis#er  Q Vie+ at Google ;c#olar  Q Vie+ at;co"us

    12' ;' #a and ;' ;ab#ar+al, Outcome o col"osco"y in +omen"resenting +it# "ostcoital bleeding and negati*e or no cytologyUresults o a 1

  • 8/18/2019 jurnal naoly

    17/58

    1' A' emal, ' ;iegel, .' 5ard et al', ancer statistics, 2009,PA$ A ancer ournal or linicians, *ol' 9, no' 4, article 22,2009' Vie+ at ublis#er Q Vie+ at Google ;c#olar

    19' /' ;#a"ley, ' ordan, and ' ' rot, A systematic re*ie+ o 

    "ostcoital bleeding and ris6 o cer*ical cancer,P -ritis# ournal o General ractice, *ol' B, no' 2!, ""' 44B0, 200B' Vie+ atGoogle ;c#olar Q Vie+ at ;co"us

    20' R' F#an, 7' A""leton, and ' urner, Is cer*ical intra<e"it#elial neo"lasia sym"tomaticWP ournal o Obstetrics andGynaecology, *ol' 2, no' , ""' B!, 200' Vie+ at ublis#erQ Vie+ at Google ;c#olar Q Vie+ at ;co"us

    21' ' ' Furman, 3' ' 8orris, and .' ' 5il6inson, Atlas o umor

    at#ology$ umors o t#e er*i&, Vagina, and Vul*a, Armed 7orcesInstitute o at#ology, 5as#ington, D, :;A, rd edition, 1992'

    22' 8' /' de ;ouHa, 5' ' ;outter, G' A' /cIndoe, D' ' Gilderdale,and ' FrausH, ;tage I cer*ical cancer$ tumor *olume bymagnetic resonance imaging o screen

  • 8/18/2019 jurnal naoly

    18/58

    2!' G' 5' Geel#oed, D' .' 3enson, ' ' aylor, and A' ;'Fetc#am, arcinoma in situ o t#e *agina ollo+ing treatment orcarcinoma o t#e cer*i&$ a distincti*e clinical entity,P #eAmerican ournal o Obstetrics and Gynecology, *ol' 124, no' ,""' 101B, 19!B' Vie+ at Google ;c#olar Q Vie+ at ;co"us

    2' American ancer ;ociety, ancer acts and @gures 200,PAtlanta, Ga, :;A, A;, 200,#tt"$%%+++'cander'org%do+nloads%;%200A77@nalsecured'"d '

    29' ' -' Goldstein, ' ?' -ree, ' -' -enson et al', .*aluation o t#e +oman +it# "ostmeno"ausal bleeding$ society o radiologistsin ultrasound

  • 8/18/2019 jurnal naoly

    19/58

    ' F' Vasude*a, ' V' #ras#er, and ' /' ic#art, #ronicendometritis$ a clinical and electron microsco"ic study,P #eAmerican ournal o Obstetrics and Gynecology, *ol' 112, no' B,""' !49!, 19!2' Vie+ at Google ;c#olar Q Vie+ at ;co"us

    B' 3' F' 7arrar r' and -' ' 8edoss, -enign tumors o t#euterine cer*i&,P #e American ournal o Obstetrics andGynecology, *ol' 1, ""' 1241!, 19B1' Vie+ at Google ;c#olar QVie+ at ;co"us

    !' /' ' Goldacre, 8' ?oudon, -' 5att et al', ."idemiology andclinical signi@cance o cer*ical erosion in +omen attending aamily "lanning clinic,P -ritis# /edical ournal, *ol' 1, no' B11,""' !4!0, 19!' Vie+ at Google ;c#olar Q Vie+ at ;co"us

    ' ;' /' /a+aNde#, ' ' Al

  • 8/18/2019 jurnal naoly

    20/58

    re"roducti*e

  • 8/18/2019 jurnal naoly

    21/58

    Obstetrics X Gynecology, *ol' 114, "art 1, no' 2, ""' 409411,2009' Vie+ at ublis#er Q Vie+ at Google ;c#olar

    1' G' 5' ;' Fong, ;' 7' Tim, ' 3' #eung, and ' F' 3' #ung,ryot#era"y as t#e treatment modality o "ostcoital bleeding$ a

    randomised clinical trial o eLcacy and saety,P Australian and8e+ Realand ournal o Obstetrics and Gynaecology, *ol' 49, no', ""' 1!24, 2009' Vie+ at ublis#er Q Vie+ at Google ;c#olar QVie+ at ;co"us

    2' ' -el@ore, .' osta, ;' de antis, ' Vassallo, and A' /arino,.ecti*eness and "ersistence o a to"ical treatment or cer*icalectro"ion +it# deo&yribonucleic acid,P /iner*a Ginecologica, *ol'!, no' 4, ""' 4B14BB, 200' Vie+ at Google ;c#olar  Q Vie+ at;co"us

    ' 3' Ferner and ' ?ic#tig, /ullerian adenosarcoma"resenting as cer*ical "oly"s$ a re"ort o se*en cases and re*ie+o t#e literature,P Obstetrics and Gynecology, *ol' 1, no' I, ""'BB9, 199' Vie+ at Google ;c#olar Q Vie+ at ;co"us

    4' 8' *an enterg#em, ' de ae"e, ' *an den -roec6e, '-ourgain, and ' ;erreyn, rimary lym"#oma o t#e cer*i& uteri$a diagnostic c#allenge$ re"ort o t+o cases and re*ie+ o t#eliterature,P .uro"ean ournal o Gynaecological Oncology, *ol' 2B,

    no' 1, ""' B, 200' Vie+ at Google ;c#olar Q Vie+ at ;co"us

    ' 7' Al#aily and A' .+ies, ostcoital bleeding$ a study o t#ecurrent "ractice amongst consultants in t#e :nited Fingdom,P.uro"ean ournal o Obstetrics Gynecology and e"roducti*e-iology, *ol' 144, no' 1, ""' !2!, 2009' Vie+ at ublis#er Q Vie+at Google ;c#olar Q Vie+ at ;co"us

    http://dx.doi.org/10.1097/AOG.0b013e3181b48febhttp://scholar.google.com/scholar_lookup?title=The+role+of+transvaginal+ultrasonography+in+the+evaluation+of+postmenopausal+bleeding&author=ACOG+Committee+Opinion+No.+440&publication_year=2009http://dx.doi.org/10.1111/j.1479-828X.2009.01049.xhttp://scholar.google.com/scholar_lookup?title=Cryotherapy+as+the+treatment+modality+of+postcoital+bleeding%3A+a+randomised+clinical+trial+of+efficacy+and+safety&author=G.+W.+S.+Kong&author=S.+F.+Yim&author=T.+H.+Cheung&author=T.+K.+H.+Chung&publication_year=2009http://www.scopus.com/scopus/inward/record.url?eid=2-s2.0-70349559705&partnerID=K84CvKBR&rel=3.0.0&md5=6c9ccd17253a30c087dacaebcd012842http://scholar.google.com/scholar_lookup?title=Effectiveness+and+persistence+of+a+topical+treatment+for+cervical+ectropion+with+deoxyribonucleic+acid&author=P.+Belfiore&author=E.+Costa&author=S.+de+Cantis&author=R.+Vassallo&author=A.+Marino&publication_year=2005http://www.scopus.com/scopus/inward/record.url?eid=2-s2.0-27144456520&partnerID=K84CvKBR&rel=3.0.0&md5=cf2be5d584d6e723f972d4194d2fd3f2http://www.scopus.com/scopus/inward/record.url?eid=2-s2.0-27144456520&partnerID=K84CvKBR&rel=3.0.0&md5=cf2be5d584d6e723f972d4194d2fd3f2http://scholar.google.com/scholar_lookup?title=Mullerian+adenosarcoma+presenting+as+cervical+polyps%3A+a+report+of+seven+cases+and+review+of+the+literature&author=H.+Kerner&author=C.+Lichtig&publication_year=1993http://www.scopus.com/scopus/inward/record.url?eid=2-s2.0-0027316085&partnerID=K84CvKBR&rel=3.0.0&md5=aaa81e07d6b8e8ea81773352e80f1137http://scholar.google.com/scholar_lookup?title=Primary+lymphoma+of+the+cervix+uteri%3A+a+diagnostic+challenge%3A+report+of+two+cases+and+review+of+the+literature&author=N.+van+Renterghem&author=P.+de+Paepe&author=R.+van+den+Broecke&author=C.+Bourgain&author=R.+Serreyn&publication_year=2005http://www.scopus.com/scopus/inward/record.url?eid=2-s2.0-14644441667&partnerID=K84CvKBR&rel=3.0.0&md5=4853c1e88d27abd8f53cf12e2d4c2c85http://dx.doi.org/10.1016/j.ejogrb.2009.01.014http://scholar.google.com/scholar_lookup?title=Postcoital+bleeding%3A+a+study+of+the+current+practice+amongst+consultants+in+the+United+Kingdom&author=F.+Alfhaily&author=A.+Ewies&publication_year=2009http://scholar.google.com/scholar_lookup?title=Postcoital+bleeding%3A+a+study+of+the+current+practice+amongst+consultants+in+the+United+Kingdom&author=F.+Alfhaily&author=A.+Ewies&publication_year=2009http://www.scopus.com/scopus/inward/record.url?eid=2-s2.0-64149083493&partnerID=K84CvKBR&rel=3.0.0&md5=c5287ffd8f27b3bd14336e2091a5a734http://dx.doi.org/10.1097/AOG.0b013e3181b48febhttp://scholar.google.com/scholar_lookup?title=The+role+of+transvaginal+ultrasonography+in+the+evaluation+of+postmenopausal+bleeding&author=ACOG+Committee+Opinion+No.+440&publication_year=2009http://dx.doi.org/10.1111/j.1479-828X.2009.01049.xhttp://scholar.google.com/scholar_lookup?title=Cryotherapy+as+the+treatment+modality+of+postcoital+bleeding%3A+a+randomised+clinical+trial+of+efficacy+and+safety&author=G.+W.+S.+Kong&author=S.+F.+Yim&author=T.+H.+Cheung&author=T.+K.+H.+Chung&publication_year=2009http://www.scopus.com/scopus/inward/record.url?eid=2-s2.0-70349559705&partnerID=K84CvKBR&rel=3.0.0&md5=6c9ccd17253a30c087dacaebcd012842http://scholar.google.com/scholar_lookup?title=Effectiveness+and+persistence+of+a+topical+treatment+for+cervical+ectropion+with+deoxyribonucleic+acid&author=P.+Belfiore&author=E.+Costa&author=S.+de+Cantis&author=R.+Vassallo&author=A.+Marino&publication_year=2005http://www.scopus.com/scopus/inward/record.url?eid=2-s2.0-27144456520&partnerID=K84CvKBR&rel=3.0.0&md5=cf2be5d584d6e723f972d4194d2fd3f2http://www.scopus.com/scopus/inward/record.url?eid=2-s2.0-27144456520&partnerID=K84CvKBR&rel=3.0.0&md5=cf2be5d584d6e723f972d4194d2fd3f2http://scholar.google.com/scholar_lookup?title=Mullerian+adenosarcoma+presenting+as+cervical+polyps%3A+a+report+of+seven+cases+and+review+of+the+literature&author=H.+Kerner&author=C.+Lichtig&publication_year=1993http://www.scopus.com/scopus/inward/record.url?eid=2-s2.0-0027316085&partnerID=K84CvKBR&rel=3.0.0&md5=aaa81e07d6b8e8ea81773352e80f1137http://scholar.google.com/scholar_lookup?title=Primary+lymphoma+of+the+cervix+uteri%3A+a+diagnostic+challenge%3A+report+of+two+cases+and+review+of+the+literature&author=N.+van+Renterghem&author=P.+de+Paepe&author=R.+van+den+Broecke&author=C.+Bourgain&author=R.+Serreyn&publication_year=2005http://www.scopus.com/scopus/inward/record.url?eid=2-s2.0-14644441667&partnerID=K84CvKBR&rel=3.0.0&md5=4853c1e88d27abd8f53cf12e2d4c2c85http://dx.doi.org/10.1016/j.ejogrb.2009.01.014http://scholar.google.com/scholar_lookup?title=Postcoital+bleeding%3A+a+study+of+the+current+practice+amongst+consultants+in+the+United+Kingdom&author=F.+Alfhaily&author=A.+Ewies&publication_year=2009http://scholar.google.com/scholar_lookup?title=Postcoital+bleeding%3A+a+study+of+the+current+practice+amongst+consultants+in+the+United+Kingdom&author=F.+Alfhaily&author=A.+Ewies&publication_year=2009http://www.scopus.com/scopus/inward/record.url?eid=2-s2.0-64149083493&partnerID=K84CvKBR&rel=3.0.0&md5=c5287ffd8f27b3bd14336e2091a5a734

  • 8/18/2019 jurnal naoly

    22/58

    Obstetrics and Gynecology InternationalVolume 2014 (2014), Article ID 0201, 2 "ages#tt"$%%d&'doi'org%10'11%2014%0201

    .ditorial

    reeclam"sia rediction and /anagementIrene ebelo1,2 and  oZo -ernardes,4,,B

    1De"artment o -ioc#emistry, 7aculty o #armacy, :ni*ersity o orto,

    ua de orge Viterbo 7erreira 22, 400

  • 8/18/2019 jurnal naoly

    23/58

    sul"#ate and etal deli*ery in t#e most se*ere cases, t#e de*elo"edcountries #a*e managed to control t#e #ig# maternal and etalmortality rates related +it# . t#at still aect t#e de*elo"ing countries+it#out adeuate basic clinical ante< and intra"artum acilities C1E'

    3o+e*er, +e 6no+ today t#at . is a more com"le& condition t#atde*elo"s during t#e @rst +ee6s o "regnancy and t#at may #a*econseuences in t#e uture #ealt# o t#e mot#er and c#ild'

    . remains a leading cause not only o maternal and etal mortality int#e de*elo"ing countries, but also o morbidity in t#e de*elo"edcountries accounting or a #ig# number o maternal admissions tointensi*e care units, etal gro+t# restriction, and "remature iatrogenicdeli*eries, +it#out eecti*e early "rediction and%or "re*ention'/oreo*er, +it# t#e increased lie e&"ectancy o t#e de*elo"edcountries it is also 6no+n today t#at +omen +it# #istory o . and

    t#eir os"ring "resent an increased ris6 o uture #y"ertension andcardio*ascular diseases, among ot#ers C1E'

    In t#is s"ecial issue, se*eral aut#ors address t#e abo*e

  • 8/18/2019 jurnal naoly

    24/58

    "reeclam"sia and eclam"sia are maNor contributors o . relatedmaternal and etal morbidity and mortality t#at need to be seriouslyta6en into account and adeuately addressed'

    7inally, A' /atos et al' and ' V' into et al' tac6le t#e issue o . and

    t#e ris6 o uture cardio*ascular disease' A' /atos et al' concluded t#at"re*iously . +omen, eit#er subseuently #y"ertensi*e ornormotensi*e, "resent signi@cant dierences in myelo"ero&idase,nitrites, li*er enHymes, and ot#er cardio*ascular ris6 biomar6ers,+#ose *ariation may be modulated by #a"toglobin 1%2 unctionalgenetic "olymor"#ism' #ey "ro*ide more e*idence not only on t#eassociation bet+een . and uture cardio*ascular diseases, but also ont#e "utati*e "at#ogenic "at#s underlying t#is situation' 3o+e*er, incontrast +it# all t#ese de*elo"ments on t#e recognition andunderstanding o t#e association bet+een . and t#e de*elo"ment o 

    uture cardio*ascular disease, ' V' into et al' s#o+ed t#at t#e maNorityo 141 cases o "reeclam"sia and c#ronic #y"ertension +it#su"erim"osed "reeclam"sia diagnosed at t#eir institution bet+een anuary 2010 and December 201, as +ell as general "ractitioners, didnot ta6e into consideration a "re*ious "regnancy aected by"reeclam"sia as a ris6 actor or uture cardio*ascular disease, namely,in t#e im"lementation o #ealt#y be#a*iours and%or adeuate medicaltreatment' #is s#o+s t#at educational and "re*ention "rograms urgein t#is area, in bot# "atients and t#e general "ractitioners le*els'

    5e #o"e t#is s"ecial issue "ro*ides not only ne+ data or daily clinical

    "ractice, but also ins"iration to "ursue t#e #ard +ay o . researc#, inall its multi"le and com"le& areas'

    Irene ebelo oZo -ernardes

    eerences

    1' -' D' onnealy, ' A' arreno, -' A' Fase, ?' A' 3art, ;' '-lac6+ell, and -' /' ;ibai, A #istory o "rior "reeclam"sia as a

    ris6 actor or "reterm birt#,P American ournal o erinatology,*ol' 1, no' B, ""' 44, 2014' Vie+ at ublis#er  Q Vie+ atGoogle ;c#olar Q Vie+ at ;co"us

    2' I' ebelo, ' -ernardes, .' eNera, and -' atr[cio, an +e "redict"reeclam"siaWP in ontro*ersies in reeclam"sia, .' ;#einer and T' Toge*, .ds', Obstetrics and Gynecology Ad*ances, ""' 1!210,

    http://dx.doi.org/10.1055/s-0033-1353439http://scholar.google.com/scholar_lookup?title=A+history+of+prior+preeclampsia+as+a+risk+factor+for+preterm+birth&author=B.+D.+Connealy&author=C.+A.+Carreno&author=B.+A.+Kase&author=L.+A.+Hart&author=S.+C.+Blackwell&author=B.+M.+Sibai&publication_year=2014http://scholar.google.com/scholar_lookup?title=A+history+of+prior+preeclampsia+as+a+risk+factor+for+preterm+birth&author=B.+D.+Connealy&author=C.+A.+Carreno&author=B.+A.+Kase&author=L.+A.+Hart&author=S.+C.+Blackwell&author=B.+M.+Sibai&publication_year=2014http://www.scopus.com/scopus/inward/record.url?eid=2-s2.0-84901689922&partnerID=K84CvKBR&rel=3.0.0&md5=960dfcb7244304a92ca9b3f1724152e2http://dx.doi.org/10.1055/s-0033-1353439http://scholar.google.com/scholar_lookup?title=A+history+of+prior+preeclampsia+as+a+risk+factor+for+preterm+birth&author=B.+D.+Connealy&author=C.+A.+Carreno&author=B.+A.+Kase&author=L.+A.+Hart&author=S.+C.+Blackwell&author=B.+M.+Sibai&publication_year=2014http://scholar.google.com/scholar_lookup?title=A+history+of+prior+preeclampsia+as+a+risk+factor+for+preterm+birth&author=B.+D.+Connealy&author=C.+A.+Carreno&author=B.+A.+Kase&author=L.+A.+Hart&author=S.+C.+Blackwell&author=B.+M.+Sibai&publication_year=2014http://www.scopus.com/scopus/inward/record.url?eid=2-s2.0-84901689922&partnerID=K84CvKBR&rel=3.0.0&md5=960dfcb7244304a92ca9b3f1724152e2

  • 8/18/2019 jurnal naoly

    25/58

    8o*a ;cience ublis#ers, 8e+ Tor6, 8T, :;A, 2014' Vie+ atGoogle ;c#olar

    Obstetrics and Gynecology InternationalVolume 201 (201), Article ID 420B, 4 "ages#tt"$%%d&'doi'org%10'11%201%420B

    esearc# Article

    .ect o :mbilical ord .ntanglement and osition onregnancy Outcomes8atsu6o Fobayas#i,1 ;#igeru Ao6i,1 /ari ;' Oba,2  suneo

     a6a#as#i,1

     and 7umi6i 3ira#ara

    1erinatal enter or /aternity and 8eonates, To6o#ama ity :ni*ersity/edical enter, 4

  • 8/18/2019 jurnal naoly

    26/58

    De"artment o Obstetrics and Gynecology, To6o#ama ity :ni*ersity3os"ital, To6o#ama, a"an

    ecei*ed 1B /ay 201= Acce"ted 29 une 201

    Academic .ditor$ .*erett /agann

    o"yrig#t > 201 8atsu6o Fobayas#i et al' #is is an o"en accessarticle distributed under t#e reati*e ommons Attribution ?icense,+#ic# "ermits unrestricted use, distribution, and re"roduction in anymedium, "ro*ided t#e original +or6 is "ro"erly cited'

    Abstract

    Introduction' o in*estigate t#e eect o com"le& umbilical cordentanglement "rimarily around t#e trun6 on "regnancy outcomes'

    /et#ods' 5e studied B0! "regnant +omen +it# singleton "regnancies+#o under+ent *aginal deli*ery o an inant at \! +ee6s o gestation'ases +ere classi@ed into no cord, nuc#al cord, and body cord grou"sand de@ned as cases +it#out umbilical cord entanglement, one ormore loo"s o t#e umbilical cord around t#e nec6 only, and umbilicalcord around t#e trun6 only, res"ecti*ely' regnancy outcomes +erecom"ared among t#ese t#ree grou"s' esults' #e no cord, nuc#alcord, and body cord grou" included 4!, 141, and 12 "regnancies,res"ecti*ely' Alt#oug# deli*ery mode +as not signi@cantly dierentamong t#e t#ree grou"s, 1

  • 8/18/2019 jurnal naoly

    27/58

    re"orts regarding umbilical cord entanglement concern nuc#al cordentanglement, +it# no re"orted case concerning any ot#er ty"e o umbilical cord entanglement' #ereore, t#is study aimed toin*estigate t#e eect o com"le& umbilical cord entanglement"rimarily around t#e trun6 on "regnancy outcome'

    2' /aterials and /et#ods

    Data +ere retros"ecti*ely analyHed using t#e medical records o BB+omen +it# singleton "regnancies +#o #ad undergone attem"ted*aginal deli*ery at ! gestational +ee6s bet+een anuary 2004 andDecember 201 at To6o#ama ity :ni*ersity /edical enter' 5omen+it# a serious com"lication, suc# as #y"ertension or diabetes, +#odeli*ered a ne+born +it# congenital anomalies or +it# etalmal"resentation, +ere e&cluded' onseuently, B0! o t#e BB

    +omen +ere included in t#is study' #is study #as been a""ro*ed byt#e et#ics committee o t#e To6o#ama ity :ni*ersity /edical enter' #e "resence or absence o umbilical cord entanglement +asdetermined at t#e le*el o t#e umbilicus during deli*ery' #e no cordgrou" included cases +it#out umbilical cord entanglement' #e nuc#alcord grou" included cases +it# at least one loo" o t#e umbilical cordaround t#e nec6 only' #e body cord grou" included cases +it# t#eumbilical cord +ra""ed around t#e trun6, e&cluding t#e nec6' ases+it# umbilical cord entanglement around multi"le "arts, suc# asentanglement around bot# t#e nec6 and trun6 or around bot# t#e nec6

    and u""er%lo+er limbs, +ere e&cluded' regnancy outcomes +erecom"ared among t#e grou"s$ no cord, nuc#al cord, and body cordgrou"s'

     #e ollo+ing maternal c#aracteristics +ere collected$ maternal age atdeli*ery, "arity, and gestational age at deli*ery' #e main outcomemeasures +ere deli*ery mode, birt# +eig#t, birt# #eig#t, 1

  • 8/18/2019 jurnal naoly

    28/58

     #e no cord grou" included 4! "regnancies, t#e nuc#al cord grou"included 141 "regnancies, and t#e body cord grou" included 12"regnancies' able 1 s#o+s t#e maternal c#aracteristics' 8o signi@cantdierence +as obser*ed among t#e grou"s in maternal age at deli*ery,"arity, or gestational age'

     able 1$ /aternal c#aracteristics, com"ared bet+een t#e grou"s'

     able 2 s#o+s t#e main outcome measures or "regnancy outcomesamong t#e grou"s' 8o signi@cant dierence in deli*ery mode +asobser*ed among t#e grou"s' /oreo*er, t#e grou"s +it# umbilical cordentanglement, +#ic# +ere t#e nuc#al cord and body cord grou"s, #adsigni@cantly longer umbilical cords, com"ared +it# t#e no cord grou"'In "articular, t#e nuc#al cord grou" #ad t#e longest umbilical cord andincluded signi@cantly more cases o e&cessi*ely long umbilical cord';igni@cant dierences in t#e reuencies o 1

  • 8/18/2019 jurnal naoly

    29/58

    not signi@cantly dierent' /oreo*er, -ernad et al' C!E re"orted t#atumbilical cord entanglement mig#t be a cause o intrauterine etaldeat# e*en t#oug# t#ere +as no dierence in orced deli*ery ratesbased on cord entanglement' #e aut#ors recommended t#at rigorousmanagement +it# etal #eart rate monitoring s#ould be conducted

    during deli*ery +#en ultrasonogra"#y clearly re*eals umbilical cordentanglement and cesarean section s#ould be considered +#ennonreassuring etal status is detected'

    In t#e grou"s +it# umbilical cord entanglement, t#e reuencies o 1<minute A"gar scores ! and :A "3 !'10 +ere #ig#er t#an in t#e no cordgrou"' Assima6o"oulos et al' CBE re"orted t#at cases +it# umbilicalcord entanglement more reuently #ad lo+ A"gar scores and lo+ :A"3 as #a*e many ot#er studies or eit#er lo+ A"gar scores or lo+ :A"3 C1, 4, B, , 10, 12E' #e results o t#e "resent study also su""ort t#e

    @ndings o t#ese studies and con@rm t#at t#e "resence or absence o umbilical cord entanglement aects neonatal conditions at deli*ery'

     #e reuency o

  • 8/18/2019 jurnal naoly

    30/58

    o etuses +it# nuc#al cord entanglement tended to be #ig#er'Alt#oug# t#e results o t#e "resent study su""ort t#ose re"orted byOgue# et al' CE, urt#er studies are needed to establis# @rmconclusions regarding t#e relations#i" bet+een umbilical cordentanglement and etal gro+t#'

     #e "resent study #as se*eral limitations' 7irst, it +as conducted +it# asmall sam"le in a single institution' ;econd, t#e eects o nuc#al cordentanglement +ere not e*aluated based on t#e number o loo"s'/oreo*er, cases +it# multi"le umbilical cord entanglements in*ol*ingmulti"le "arts o t#e body, suc# as entanglement around bot# t#e nec6and u""er%lo+er limbs, +ere e&cluded'

    In conclusion, umbilical cord entanglement is associated +it# anincreased ris6 o lo+ A"gar scores and lo+ :A "3' #e "resent studysuggests t#at etuses +it# com"le& umbilical cord entanglement

    "rimarily around t#e trun6, but not t#e nec6, are strongly aected byumbilical cord com"ression during deli*ery' 3o+e*er, deli*ery modes+ere not aected by any ty"e o umbilical cord entanglement, +#ic#su""orts t#e @ndings o "re*ious studies' :mbilical cord entanglementis a common "at#ological condition encountered in daily clinical"ractice' Alt#oug# it mig#t aect neonatal conditions during deli*ery,*aginal deli*ery can be saely "erormed in many cases, and undueconcern s#ould not be "assed on to t#e mot#ers, e*en +#enultrasonogra"#y re*eals t#e "resence o umbilical cord entanglementbeore deli*ery'

    onKict o Interests

     #e aut#ors declare t#at t#ey #a*e no conKict o interests to declare' #e aut#ors con@rm t#at t#e results o t#is "a"er #a*e not beendistorted by researc# unding or conKict o interests'

    eerences

    1' .' ;#einer, ' ;' Abramo+icH, A' ?e*y, ' ;ilberstein, /' /aHor, and

    ' 3ers#6o*itH, 8uc#al cord is not associated +it# ad*erse"erinatal outcome,P Arc#i*es o Gynecology and Obstetrics, *ol'2!4, no' 2, ""' 1, 200B' Vie+ at ublis#er  Q Vie+ at Google;c#olar Q Vie+ at ;co"us

    2' ?' ;c#^er, ' -ur6#ardt, ' Rimmermann, and ' Furmana*icius,8uc#al cords in term and "ostterm deli*eriesUdo +e need to

    http://www.hindawi.com/journals/ogi/2015/342065/#B5http://dx.doi.org/10.1007/s00404-005-0110-2http://scholar.google.com/scholar_lookup?title=Nuchal+cord+is+not+associated+with+adverse+perinatal+outcome&author=E.+Sheiner&author=J.+S.+Abramowicz&author=A.+Levy&author=T.+Silberstein&author=M.+Mazor&author=R.+Hershkovitz&publication_year=2006http://scholar.google.com/scholar_lookup?title=Nuchal+cord+is+not+associated+with+adverse+perinatal+outcome&author=E.+Sheiner&author=J.+S.+Abramowicz&author=A.+Levy&author=T.+Silberstein&author=M.+Mazor&author=R.+Hershkovitz&publication_year=2006http://www.scopus.com/scopus/inward/record.url?eid=2-s2.0-33646003835&partnerID=K84CvKBR&rel=3.0.0&md5=93634c5458adc0d767ec087c8e476de9http://www.hindawi.com/journals/ogi/2015/342065/#B5http://dx.doi.org/10.1007/s00404-005-0110-2http://scholar.google.com/scholar_lookup?title=Nuchal+cord+is+not+associated+with+adverse+perinatal+outcome&author=E.+Sheiner&author=J.+S.+Abramowicz&author=A.+Levy&author=T.+Silberstein&author=M.+Mazor&author=R.+Hershkovitz&publication_year=2006http://scholar.google.com/scholar_lookup?title=Nuchal+cord+is+not+associated+with+adverse+perinatal+outcome&author=E.+Sheiner&author=J.+S.+Abramowicz&author=A.+Levy&author=T.+Silberstein&author=M.+Mazor&author=R.+Hershkovitz&publication_year=2006http://www.scopus.com/scopus/inward/record.url?eid=2-s2.0-33646003835&partnerID=K84CvKBR&rel=3.0.0&md5=93634c5458adc0d767ec087c8e476de9

  • 8/18/2019 jurnal naoly

    31/58

    6no+WP Obstetrics and Gynecology, *ol' 10B, no' 1, ""' 22,200' Vie+ at ublis#er Q Vie+ at Google ;c#olar Q Vie+ at ;co"us

    ' ' 5' Fong, ?' 5' #an, and 5' 5' F' o, 8eonatal outcome andmode o deli*ery in t#e "resence o nuc#al cord loo"s$

    im"lications on "atient counselling and t#e mode o deli*ery,PArc#i*es o Gynecology and Obstetrics, *ol' 292, no' 2, ""' 229, 201' Vie+ at ublis#er  Q Vie+ at Google ;c#olar  Q Vie+ at;co"us

    4' ' D' ?arson, 5' 7' ayburn, ;' rosby, and G' ' #urnau, /ulti"lenuc#al cord entanglements and intra"artum com"lications,PAmerican ournal o Obstetrics and Gynecology, *ol' 1!, no' 4,""' 122121, 199' Vie+ at ublis#er Q Vie+ at Google ;c#olar QVie+ at ;co"us

    ' O' Ogue#, A' Al

  • 8/18/2019 jurnal naoly

    32/58

    10' .' auniau&, -' amsay, ' eellaerts, and T' ;c#oller,erinatal eatures o "regnancies com"licated by nuc#al cord,PAmerican ournal o erinatology, *ol' 12, no' 4, ""' 22,199' Vie+ at ublis#er Q Vie+ at Google ;c#olar Q Vie+ at ;co"us

    11' G' D' V' 3an6ins, ' ' ;nyder, ' ' 3aut#, ?' ' Gilstra" III,and ' 3ammond, 8uc#al cords and neonatal outcome,PObstetrics and Gynecology, *ol' !0, no' , ""' B!B91, 19!'Vie+ at Google ;c#olar Q Vie+ at ;co"us

    12' D' A' #oades, :' ?atHa, and -' A' /ueller, is6 actors andoutcomes associated +it# nuc#al cord$ a "o"ulation

  • 8/18/2019 jurnal naoly

    33/58

    Obstetrics and Gynecology InternationalVolume 201 (201), Article ID 0129, 9 "ages#tt"$%%d&'doi'org%10'11%201%0129

    e*ie+ Article

    /aternal and ediatric 3ealt# Outcomes in relation toGestational Vitamin D ;uLciency;te"#en ' Genuis

    7aculty o /edicine, :ni*ersity o algary and :ni*ersity o Alberta,29

  • 8/18/2019 jurnal naoly

    34/58

    clinicians' .ducation on gestational nutritional reuirements s#ould bea undamental "art o medical education and residency training,instruction t#at #as been sorely lac6ing to date'

    1' Introduction and -ac6ground

    In t#e early and mid

  • 8/18/2019 jurnal naoly

    35/58

    area o study, #o+e*er, t#e e&tent o seuelae associated +it#modi@able gestational determinants is yet unrecogniHed= it is t#us not"ossible to assign "recise costs associated +it# long

  • 8/18/2019 jurnal naoly

    36/58

    C1E' In addition, it is becoming increasingly a""arent t#at *ariousnutritional de@ciencies are +ides"read and may #a*e an enormousim"act on subseuent maternal and etal #ealt#' Increasing e*idencea""ears to con@rm t#at at no "oint t#roug#out t#e lie cycle is it moreim"ortant to secure adeuate nutrient inta6e t#an in "regnancy C2BE'

     #is act, or e&am"le, accounts or t#e em"#asis on olate suLciencyin early gestation CE as +ell as t#e increased study into t#e outcomesrelated to gestational de@ciency o reuired omega

  • 8/18/2019 jurnal naoly

    37/58

     #e +ides"read clinical im"ortance o determining t#e correlationbet+een *itamin D le*els and re"roducti*e outcomes is e*ident' #emedical literature #as ac#ie*ed general consensus t#at *itamin Dle*els t#roug#out muc# o t#e globe, as reKected by "o"ulationmeasurements o 2(O3)D  le*els, are generally inadeuate CE'

    About 2% o t#e "o"ulation in nort#ern climates are consideredde@cient +it# a*erage 2(O3)D  le*els in one study o B! nmol%? C 9E,+ell belo+ t#e 12010 nmol%? le*el t#at #as recently been associated+it# "reerred #ealt# C24E (able 1)' 5it# suc# +ides"read de@ciency, itis *ital to determine +#et#er or not lo+ gestational le*els o *itamin Dare a signi@cant determinant o re"roducti*e and "ediatric #ealt#outcomes'

     able 1$ O"timal adult le*els o *itamin D (as reKected by 2(O3)Dle*els) rom dierent sources'

     #e need or clarity on t#is issue #as also been recogniHed because o dis"arity about recommended dosing among esteemed medicalgrou"s' 5#ile t#e Institute o /edicine (IO/) agrees t#at 4,000 I: o *itamin daily is allo+able and nonto&ic, t#eir actual recommendeddaily inta6e #as been limited to B00 I: daily in general and 400 I:%dayduring gestation C40, 41E' #ese IO/ recommendations or reuired*itamin D inta6e #a*e been "ut into serious uestion C42E, #o+e*er, asa signi@cant statistical error #as been identi@ed in t#e +ay t#eirrecommendations +ere arri*ed at C4E' Accordingly, e&"loration o consensus @ndings on t#e clinical bene@ts o *itamin D

    su""lementation is in order in all medical disci"lines includingre"roducti*e #ealt#care'

    ' ?imitations o Vitamin D esearc# as elated to GestationalOutcomes

    Alt#oug# maternal

  • 8/18/2019 jurnal naoly

    38/58

    bene@cial maternal and neonatal outcomes suc# as reductions in"reeclam"sia, gestational diabetes, small or gestational age inants,"reterm birt#, or rates o cesarean deli*ery C44E' #e a""arentdis"arity bet+een @ndings in *arious studies #as caused some toreKe&i*ely conclude t#at *itamin D status in "regnancy is irrele*ant to

    maternal

  • 8/18/2019 jurnal naoly

    39/58

    B' Gestational Vitamin D ;tatus and Obstetrical Outcomes

     #e list o ad*erse gestational outcomes in "regnancy associated +it#*itamin D insuLciency continues to mount' .arly in "regnancy, ore&am"le, an increased ris6 o @rst trimester miscarriage #as been

    lin6ed to inadeuate maternal *itamin D le*els C49E' Interestingly, onestudy demonstrated t#at nearly #al t#e +omen assessed +it# #abitualmiscarriage +ere ound to #a*e 2(O3)D le*els belo+ ! nmol%? C0E' #is researc# ound t#at lo+er *itamin D le*els +ere associated +it#immune dysregulation in a number o +ays, including dierences inindices in*ol*ing natural 6iller cells, *arious cyto6ines, and certainregulatory "roteins, +#en com"ared to t#ose +it# suLcient *itamin Dle*els C0E' #e aut#ors o t#is study also noted t#at +omen +it# lo+er*itamin D le*els #ad #ig#er degrees o *arious autoantibodiesincluding anti"#os"#oli"id antibody C0E, a clinical state t#at #as been

    associated +it# etal deat#, recurrent early miscarriage, "reeclam"sia,and "lacental insuLciency C1E'

    A number o "a"ers #a*e con@rmed an increased ris6 o de*elo"inggestational diabetes in t#ose +it# inadeuate *itamin D le*els C2, E'Vitamin D suLciency in "regnancy a""ears to be related to im"ro*edinsulin le*els, as +ell as better glucose regulation as reKected by3bA1c le*els C4E' As "regnancies com"licated by gestational diabetes"resent ris6s or assorted ad*erse seuelae, eorts to a*oiddysregulated sugar control in "regnancy are +ort#+#ile' Obesity"resents a conounding inKuence in t#is discussion, #o+e*er, as agreater -/I is associated +it# lo+er *itamin D le*els as +ell as greaterinsulin resistance and ris6 or gestational diabetes' 8umerous studies#a*e also correlated lo+ le*els o *itamin D +it# t#e de*elo"ment o "reeclam"sia C2, , , BE, "er#a"s t#roug# immune mec#anismsin*ol*ing anti"#os"#oli"id antibody C1E, and%or inKammatorymec#anisms in*ol*ing cyto6ines CBE'

    O "articular signi@cance is t#e reality t#at "reterm birt# beore !+ee6s o gestation remains t#e leading cause o neonatal morbidityand mortality C!E' .scalating e*idence in t#e literature con@rms a

    "rotecti*e association bet+een maternal *itamin D suLciency and t#eincidence o "reterm birt# CB0E' A recent study ound t#at t#e rateo occurrence o "reterm birt# a""eared to be in*ersely "arallel to t#ematernal serum 2

  • 8/18/2019 jurnal naoly

    40/58

    and !4'9, and (iii) ! nmol%? or greater' Anot#er study ound t#atinants born beore 2 +ee6s o gestation +ere 2'4 times more li6ely to#a*e *itamin D le*els belo+ 0 nmol%? +#en com"ared +it# t#ose bornater 2 +ee6s o gestation CB1E'

    Ot#er gestational issues also a""ear to be inKuenced by maternal*itamin D le*els' Vitamin D insuLciency, or e&am"le, #as also beencorrelated +it# maternal "eriodontal disease CB2E, a #ig#er li6eli#oodo small or gestational age inants CB, B4E, and an increased ris6 o bacterial *aginosis CBE'

    As +ell as indi*idual studies, systematic re*ie+s e&"loring associationbet+een *itamin D suLciency and #ealt# outcomes #a*e also beenilluminating' A systematic re*ie+ and meta

  • 8/18/2019 jurnal naoly

    41/58

    maternal #ealt#, a recent study "ublis#ed in t#e -ritis# ournal o Obstetrics and Gynecology re"orted t#at serum 2CO3ED le*els in+omen +it# no "ost"artum de"ression +ere signi@cantly #ig#er t#ant#ose in +omen suering +it# "ost"artum de"ression C!E'

    !' Gestational Vitamin D ;tatus and ?ater ?ie Outcomes

    Alt#oug# researc# into etal origins o disease in later lie remains in itsinancy, t#ere is increasing sus"icion t#at gestational nutritionalsuLciency may be a determinant o #ealt# in later lie' 7or e&am"le,"reliminary e*idence suggests t#at insuLcient le*els o "renatal*itamin D may be a actor in t#e de*elo"ment o autism C!4E and lo+erres"iratory inections C!E' A ;"anis# study to t#is end ound t#atmot#ers +#o #ad gestational *itamin D le*els abo*e ! nmol%? #ados"ring +it# a one

  • 8/18/2019 jurnal naoly

    42/58

    20 years C9E' #e aut#ors state t#at *itamin D may #a*e anim"ortant, multiaceted role in t#e de*elo"ment o etal lungs, brain,and boneP C9E' 7inally, gestational *itamin D le*els may im"act adult#ealt# as t#ere is early e*idence t#at *itamin D suLciency in"regnancy may #a*e a "rotecti*e role in t#e de*elo"ment o adult

    onset multi"le sclerosis C94E'

    ' .conomic -urden o Gestational Vitamin D De@ciency

     #e economic im"act o *itamin D de@ciency as it relates to maternal<etal #ealt# is diLcult to obNecti*ely uantiy as insuLcient e*idence#as accumulated t#us ar on t#e totality o s#ort< and long

  • 8/18/2019 jurnal naoly

    43/58

     #ere is escalating attention in t#e scienti@c literature to t#eassociation bet+een myriad nutrients and #ealt# outcomes C100, 101E' raining in clinical nutritional bioc#emistry, nonet#eless, still remains+oeully inadeuate or none&istent in most medical education"rograms C102, 10E' As a result, t#ere are ongoing calls o late or

    curriculum re*ision to incor"orate "ractical training in clinical nutritionC10, 104E' It is a""arent t#at training is reuired to establis# clinicalcom"etency in (i) understanding o t#e role o *arious nutrients in#uman #ealt#, (ii) #o+ to assess nutritional bioc#emistry in "atients,and (iii) and #o+ to inter*ene to secure nutrient suLciency orindi*iduals and "o"ulation grou"s

    5it# t#e mounting e*idence o se*eral #ealt# seuelae associated +it#gestational *itamin D de@ciency, t#e *alue o "reconce"tion educationand care by #ealt# "ro*iders and "ublic #ealt# bodies to secure

    *itamin D suLciency t#roug#out gestation is e*ident' As "regnant+omen C10E, "articularly t#ose +it# dar6 s6in C10BE, are atconsiderable ris6 or e&"eriencing *itamin D insuLciency C9E, it isim"ortant to #a*e a #ig# inde& o sus"icion and to eecti*ely "reclude,assess or, and manage *itamin D inadeuacy, as +ould be done +it#ot#er bioc#emical irregularities'

    Alt#oug# (to t#e aut#orJs 6no+ledge) t#ere are no s"eci@c target le*elsor 2(O3)D during t#e *arious stages o "regnancy t#at correlate +it#o"timal results in relation to maternal and "ediatric #ealt# outcomes,some aut#ors #a*e made recommendations or su""lemental le*els

    t#at a""ear to be sae and eecti*e' #ese recommendations rangerom B00 I:%day rom t#e Institute o /edicine C41E to 2000 I:%day romt#e anadian ediatric ;ociety C10!E, to 4000 I:%daily rom *ariousresearc#ers +#o #a*e concluded t#at t#e latter dose is bot# eLcaciousand sae C2B0E' One researc#er #as suggested t#at t#e dietaryreuirement during "regnancy and lactation may actually be as #ig# asB000 I:%day C10E, but most researc#ers #a*e concluded, +it# ourcurrent 6no+ledge, t#at a su""lemental *itamin D inta6e o 4000I:%day is o"timal C0E' As discussed, indi*idual *itamin D indices canbe inKuenced by *arious determinants des"ite s"eci@c le*els o 

    su""lementation= it is t#us t#e aut#orJs recommendation t#at a"ersonaliHed medical a""roac# be ta6en *ia indi*idual screening or2(O3)D as a routine "art o "reconce"tion and "renatal care'

    5it# e*idence t#at a maNor "ro"ortion o t#e adult "o"ulation CE,"articularly in nort#ern climates C9E, is "otentially de@cient in *itaminD, it a""ears t#at, at minimum, one out o e*ery e+ e&"ectant

    http://www.hindawi.com/journals/ogi/2015/501829/#B94http://www.hindawi.com/journals/ogi/2015/501829/#B95http://www.hindawi.com/journals/ogi/2015/501829/#B96http://www.hindawi.com/journals/ogi/2015/501829/#B97http://www.hindawi.com/journals/ogi/2015/501829/#B97http://www.hindawi.com/journals/ogi/2015/501829/#B98http://www.hindawi.com/journals/ogi/2015/501829/#B99http://www.hindawi.com/journals/ogi/2015/501829/#B100http://www.hindawi.com/journals/ogi/2015/501829/#B31http://www.hindawi.com/journals/ogi/2015/501829/#B34http://www.hindawi.com/journals/ogi/2015/501829/#B101http://www.hindawi.com/journals/ogi/2015/501829/#B24http://www.hindawi.com/journals/ogi/2015/501829/#B105http://www.hindawi.com/journals/ogi/2015/501829/#B106http://www.hindawi.com/journals/ogi/2015/501829/#B105http://www.hindawi.com/journals/ogi/2015/501829/#B30http://www.hindawi.com/journals/ogi/2015/501829/#B31http://www.hindawi.com/journals/ogi/2015/501829/#B94http://www.hindawi.com/journals/ogi/2015/501829/#B95http://www.hindawi.com/journals/ogi/2015/501829/#B96http://www.hindawi.com/journals/ogi/2015/501829/#B97http://www.hindawi.com/journals/ogi/2015/501829/#B97http://www.hindawi.com/journals/ogi/2015/501829/#B98http://www.hindawi.com/journals/ogi/2015/501829/#B99http://www.hindawi.com/journals/ogi/2015/501829/#B100http://www.hindawi.com/journals/ogi/2015/501829/#B31http://www.hindawi.com/journals/ogi/2015/501829/#B34http://www.hindawi.com/journals/ogi/2015/501829/#B101http://www.hindawi.com/journals/ogi/2015/501829/#B24http://www.hindawi.com/journals/ogi/2015/501829/#B105http://www.hindawi.com/journals/ogi/2015/501829/#B106http://www.hindawi.com/journals/ogi/2015/501829/#B105http://www.hindawi.com/journals/ogi/2015/501829/#B30http://www.hindawi.com/journals/ogi/2015/501829/#B31

  • 8/18/2019 jurnal naoly

    44/58

    mot#ers +ill #a*e inadeuate le*els o t#is essential nutrient' 5it# t#erecognition t#at *itamin D "lays an essential role in myriad genes t#atencode or #ealt# and +ell

  • 8/18/2019 jurnal naoly

    45/58

    duration and are associated +it# subseuent adi"osity,P m-io,*ol' B, no' 1, Article ID e02419

  • 8/18/2019 jurnal naoly

    46/58

    ""' 9199, 2014' Vie+ at ublis#er  Q Vie+ at Google ;c#olar  QVie+ at ;co"us

    14' ' 3' ?ane, 7etal "rogramming, e"igenetics, and adultonset disease,P linics in erinatology, *ol' 41, no' 4, ""' 1

    1, 2014' Vie+ at ublis#er Q Vie+ at Google ;c#olar

    1' /' 5eber, ' /' Ayoubi, and O' icone, 8utrition o "regnant+omen$ conseuences or etal gro+t# and adult diseases,PArc#i*es de diatrie, *ol' 22, no' 1, ""' 11B11, 201' Vie+ atublis#er Q Vie+ at Google ;c#olar

    1B' ;' ' Genuis, #e c#emical erosion o #uman #ealt#$ad*erse en*ironmental e&"osure and in

  • 8/18/2019 jurnal naoly

    47/58

    22' /' 7' 3olic6, Vitamin D and #ealt#$ e*aluation, biologicunctions, and recommended dietary inta6e or *itamin D,P inVitamin D$ #ysiology, /olecular -iology, and linicalA""lications, ""' , ;"ringer, 8e+ Tor6, 8T, :;A, 2010' Vie+at Google ;c#olar

    2' /' 7' 3olic6, 8' ' -in6ley, 3' A' -isc#o

  • 8/18/2019 jurnal naoly

    48/58

    29' ' ?' 5agner, ' /c8eil, ;' A' 3amilton et al', A randomiHedtrial o *itamin D su""lementation in 2 community #ealt# centernet+or6s in ;out# arolina,P American ournal o Obstetrics andGynecology, *ol' 20, no' 2, ""' 1!'e11!'e1, 201' Vie+ atublis#er Q Vie+ at Google ;c#olar

    0' A' /it#al and ;' Falra, Vitamin D su""lementation in"regnancy,P Indian ournal o .ndocrinology and /etabolism, *ol'1, no' , ""' 99B, 2014' Vie+ at ublis#er Q Vie+ at Google;c#olar

    1' 3' F' Atras#, F' o#nson, /' Adams, ' 7' ordero, and '3o+se, reconce"tion care or im"ro*ing "erinatal outcomes$t#e time to act,P /aternal and #ild 3ealt# ournal, *ol' 10,su""lement 1, ""' ;;11, 200B' Vie+ at ublis#er  Q Vie+ at

    Google ;c#olar

    2' /arc# o Dimes -irt# Deects 7oundation, /arc# o dimesu"dates$ is early "renatal care too lateWP ontem"orary O-%GT8,*ol' 12, ""' 4!2, 2002' Vie+ at Google ;c#olar

    ' G' -ar6ai, ;' ArbuHo*a, /' -er6enstadt, ;' 3eietH, and 3'uc6le, 7reuency o Do+nSs syndrome and neural

  • 8/18/2019 jurnal naoly

    49/58

    20, no' 10, ""' 121B0, 2010' Vie+ at ublis#er  Q Vie+ atGoogle ;c#olar

    !' /' ' DiN6ers, #e *alue o traditional re*ie+s in t#e era o systematic re*ie+ing,P American ournal o #ysical /edicine X

    e#abilitation, *ol' , no' , ""' 4240, 19B' Vie+ at Google;c#olar

    ' /' 7' 3olic6 and ' ' #en, Vitamin D de@ciency$ a+orld+ide "roblem +it# #ealt# conseuences,P #e American ournal o linical 8utrition, *ol' !, no' 4, ""' 100;10B;,200' Vie+ at Google ;c#olar

    9' ;' ' Genuis, G' F' ;c#+alenberg, /' 8' 3iltH, and ;' A'Vaselena6, Vitamin D status o clinical "ractice "o"ulations at

    #ig#er latitudes$ analysis and a""lications,P International ournalo .n*ironmental esearc# and ublic 3ealt#, *ol' B, no' 1, ""'111!, 2009' Vie+ at ublis#er Q Vie+ at Google ;c#olar Q Vie+at ;co"us

    40' A' ' oss, ' .' /anson, ;' A' Abrams, et al', #e 2011re"ort on dietary reerence inta6es or calcium and *itamin Drom t#e Institute o /edicine$ +#at clinicians need to 6no+,P #e ournal o linical .ndocrinology X /etabolism, *ol' 9B, no' 1, ""', 2011' Vie+ at ublis#er Q Vie+ at Google ;c#olar

    41' Institute o /edicine, Dietary eerence Inta6es or alciumand Vitamin D, 8ational Academies ress, 5as#ington, D, :;A,2010'

    42' G' F' ;c#+alenberg and ;' ' 5#iting, A anadian res"onseto t#e 2010 Institute o /edicine *itamin D and calciumguidelines,P ublic 3ealt# 8utrition, *ol' 14, no' 4, ""' !4B!4,2011' Vie+ at ublis#er Q Vie+ at Google ;c#olar

    4' ' ' Veugelers and ' ' .6+aru, A statistical error in t#eestimation o t#e recommended dietary allo+ance or *itamin D,P8utrients, *ol' B, no' 10, ""' 44!244!, 2014' Vie+ at ublis#er QVie+ at Google ;c#olar

    44' 7' ' reH

  • 8/18/2019 jurnal naoly

    50/58

    analysis o randomiHed controlled trials,P 7ertility and ;terility,*ol' 10, no' , ""' 12!'e412'e4, 201' Vie+ at ublis#er  QVie+ at Google ;c#olar

    4' ;' 8' Farras, ' Anagnostis, ;' A' asc#ou, .' Fandara6i, and

    D' G' Goulis, Vitamin D status during "regnancy$ time or a moreuni@ed a""roac# beyond bordersWP .uro"ean ournal o linical8utrition, *ol' B9, no' , ""' !4!!, 201' Vie+ at Google;c#olar

    4B' ;' 8' Farras, ' Anagnostis, A' etrocHi, ' Ann+eiler, D' '8aug#ton, and D' ' Goulis, /aternal *itamin D status in"regnancy$ a critical a""raisal o current analytical data onmaternal and neonatal outcomes,P 3ormones, *ol' 14, no' 2, ""'22421, 201' Vie+ at ublis#er Q Vie+ at Google ;c#olar

    4!' D' /ic#aels, Doubt Is #eir roduct$ 3o+ IndustrySs Assaulton ;cience #reatens Tour 3ealt#, O&ord :ni*ersity ress, 8e+ Tor6, 8T, :;A, 200'

    4' ;' ' Genuis and ' ' ?i"", .lectromagnetic#y"ersensiti*ity$ act or @ctionWP #e ;cience o t#e otal.n*ironment, *ol' 414, ""' 10112, 2012' Vie+ at ublis#er  QVie+ at Google ;c#olar

    49' ?' -' Andersen, ' ;' rgensen, ' F' ensen et al', Vitamin DinsuLciency is associated +it# increased ris6 o @rst

  • 8/18/2019 jurnal naoly

    51/58

    2' D' F' Dror, Vitamin D status during "regnancy$ maternal,etal, and "ostnatal outcomes,P urrent O"inion in Obstetrics XGynecology, *ol' 2, no' B, ""' 42242B, 2011' Vie+ at ublis#er QVie+ at Google ;c#olar

    ' ' /' -rannon, Vitamin D and ad*erse "regnancyoutcomes$ beyond bone #ealt# and gro+t#,P roceedings o t#e8utrition ;ociety, *ol' !1, no' 2, ""' 20212, 2012' Vie+ atublis#er Q Vie+ at Google ;c#olar

    4' A' .l ?it#y, ' /' Abdella, T' /' .l

  • 8/18/2019 jurnal naoly

    52/58

    B0' ' ?' 5agner, ' -aggerly, ;' /cDonnell et al', ost

  • 8/18/2019 jurnal naoly

    53/58

    B!' A' /ere+ood, ;' D' /e#ta, ' ' #en, 3' -auc#ner, and /' 7'3olic6, Association bet+een *itamin D de@ciency and "rimarycesarean section,P #e ournal o linical .ndocrinology X/etabolism, *ol' 94, no' , ""' 94094, 2009' Vie+ at ublis#er QVie+ at Google ;c#olar

    B' ;' ?' ?oy, 8' ?e6, 7' Ta" et al', Association o maternal*itamin D status +it# glucose tolerance and caesarean section ina multi

  • 8/18/2019 jurnal naoly

    54/58

    !4' .' 7ernell, ;' -eNerot, ' 5esterlund et al', Autism s"ectrumdisorder and lo+ *itamin D at birt#$ a sibling control study,P/olecular Autism, *ol' B, article , 201' Vie+ at ublis#er Q Vie+at Google ;c#olar

    !' /' ' /agnus, ?' ' ;tene, ;' .' 3aberg et al', ros"ecti*estudy o maternal mid

  • 8/18/2019 jurnal naoly

    55/58

    +it# c#ild#ood lung unction and ast#ma' #e Generation ;tudy,P linical X .&"erimental Allergy, 201' Vie+ at ublis#er QVie+ at Google ;c#olar

    2' G' ' Ros6y, ' 3' 3art, A' ' O' 5#ite#ouse et al', Vitamin D

    de@ciency at 1B to 20 +ee6sS gestation is associated +it#im"aired lung unction and ast#ma at B years o age,P Annals o t#e American #oracic ;ociety, *ol' 11, no' 4, ""' !1!!, 2014'Vie+ at ublis#er Q Vie+ at Google ;c#olar Q Vie+ at ;co"us

    ' ' -enetti, ' omberiati, ' a"risto, A' ?' -oner, and D' G'eroni, #era"eutic eects o *itamin D in ast#ma and allergy,P/ini

  • 8/18/2019 jurnal naoly

    56/58

    9' ;' -' ;tole*i6, :' ' 8ygaard, .' 8amor6 et al', renatale&"osure to "olyc#lorinated bi"#enyls and dio&ins is associated+it# increased ris6 o +#eeHe and inections in inants,P 7ood and#emical o&icology, *ol' 49, no' , ""' 1414, 2011' Vie+ atublis#er Q Vie+ at Google ;c#olar

    90' ' /oon, #e role o *itamin D in to&ic metal absor"tion$ are*ie+,P ournal o t#e American ollege o 8utrition, *ol' 1, no'B, ""' 9B4, 1994' Vie+ at ublis#er Q Vie+ at Google ;c#olar QVie+ at ;co"us

    91' ;' ' Genuis, ;ensiti*ity

  • 8/18/2019 jurnal naoly

    57/58

    morbidity,P -ulletin o t#e 5orld 3ealt# OrganiHation, *ol' , no'1, ""' 1, 2010' Vie+ at ublis#er Q Vie+ at Google ;c#olar

    9' F' /' o#nston, F' Gooc#, .' Forol et al', #e economicburden o "rematurity in anada,P -/ ediatrics, *ol' 14, article

    9, 2014' Vie+ at ublis#er Q Vie+ at Google ;c#olar

    99' 5' -' Grant, G' F' ;c#+alenberg, ;' ' Genuis, and ;' '5#iting, An estimate o t#e economic burden and "rematuredeat#s due to *itamin D de@ciency in anada,P /olecular8utrition X 7ood esearc#, *ol' 4, no' , ""' 11!2111, 2010'Vie+ at ublis#er Q Vie+ at Google ;c#olar

    100' ;' /' ;olon

  • 8/18/2019 jurnal naoly

    58/58

    linical -ioc#emistry, *ol' 4B, no' 1, ""' 1491492, 201' Vie+at ublis#er Q Vie+ at Google ;c#olar Q Vie+ at ;co"us

    10B' /' Aucoin, ' 5ea*er, ' #omas, and ?' ones, Vitamin Dstatus o reugees arri*ing in anada$ @ndings rom t#e calgary

    reugee #ealt# "rogram,P anadian 7amily #ysician, *ol' 9, no'4, ""' e1e194, 201' Vie+ at Google ;c#olar Q Vie+ at ;co"us

    10!' anadian ediatric ;ociety, Vitamin D su""lementation$recommendations or anadian mot#ers and inants,P aediatricsX #ild 3ealt#, *ol' 12, no' !, ""' 9, 200!' Vie+ at Google;c#olar

    10' -' 5' 3ollis, Vitamin D reuirement during "regnancy andlactation,P ournal o -one and /ineral esearc#, *ol' 22,

    su""lement 2, ""' V9V44, 200!' Vie+ at ublis#er  Q Vie+ atGoogle ;c#olar

    http://dx.doi.org/10.1016/j.clinbiochem.2013.05.051http://dx.doi.org/10.1016/j.clinbiochem.2013.05.051http://scholar.google.com/scholar_lookup?title=Vitamin+D+levels+and+relative+insufficiency+in+Saskatchewan&author=D.+C.+Lehotay&author=P.+Smith&author=J.+Krahn&author=M.+Etter&author=J.+Eichhorst&publication_year=2013http://www.scopus.com/scopus/inward/record.url?eid=2-s2.0-84884349909&partnerID=K84CvKBR&rel=3.0.0&md5=16348bc0f3f092007b761368f7759978http://scholar.google.com/scholar_lookup?title=Vitamin+D+status+of+refugees+arriving+in+Canada%3A+findings+from+the+calgary+refugee+health+program&author=M.+Aucoin&author=R.+Weaver&author=R.+Thomas&author=L.+Jones&publication_year=2013http://www.scopus.com/scopus/inward/record.url?eid=2-s2.0-84876271570&partnerID=K84CvKBR&rel=3.0.0&md5=0b29a2e6475d8e27e188c577f7599816http://scholar.google.com/scholar_lookup?title=Vitamin+D+supplementation%3A+recommendations+for+Canadian+mothers+and+infants&author=Canadian+Pediatric+Society&publication_year=2007http://scholar.google.com/scholar_lookup?title=Vitamin+D+supplementation%3A+recommendations+for+Canadian+mothers+and+infants&author=Canadian+Pediatric+Society&publication_year=2007http://dx.doi.org/10.1359/jbmr.07s215http://scholar.google.com/scholar_lookup?title=Vitamin+D+requirement+during+pregnancy+and+lactation&author=B.+W.+Hollis&publication_year=2007http://scholar.google.com/scholar_lookup?title=Vitamin+D+requirement+during+pregnancy+and+lactation&author=B.+W.+Hollis&publication_year=2007http://dx.doi.org/10.1016/j.clinbiochem.2013.05.051http://dx.doi.org/10.1016/j.clinbiochem.2013.05.051http://scholar.google.com/scholar_lookup?title=Vitamin+D+levels+and+relative+insufficiency+in+Saskatchewan&author=D.+C.+Lehotay&author=P.+Smith&author=J.+Krahn&author=M.+Etter&author=J.+Eichhorst&publication_year=2013http://www.scopus.com/scopus/inward/record.url?eid=2-s2.0-84884349909&partnerID=K84CvKBR&rel=3.0.0&md5=16348bc0f3f092007b761368f7759978http://scholar.google.com/scholar_lookup?title=Vitamin+D+status+of+refugees+arriving+in+Canada%3A+findings+from+the+calgary+refugee+health+program&author=M.+Aucoin&author=R.+Weaver&author=R.+Thomas&author=L.+Jones&publication_year=2013http://www.scopus.com/scopus/inward/record.url?eid=2-s2.0-84876271570&partnerID=K84CvKBR&rel=3.0.0&md5=0b29a2e6475d8e27e188c577f7599816http://scholar.google.com/scholar_lookup?title=Vitamin+D+supplementation%3A+recommendations+for+Canadian+mothers+and+infants&author=Canadian+Pediatric+Society&publication_year=2007http://scholar.google.com/scholar_lookup?title=Vitamin+D+supplementation%3A+recommendations+for+Canadian+mothers+and+infants&author=Canadian+Pediatric+Society&publication_year=2007http://dx.doi.org/10.1359/jbmr.07s215http://scholar.google.com/scholar_lookup?title=Vitamin+D+requirement+during+pregnancy+and+lactation&author=B.+W.+Hollis&publication_year=2007http://scholar.google.com/scholar_lookup?title=Vitamin+D+requirement+during+pregnancy+and+lactation&author=B.+W.+Hollis&publication_year=2007