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INTERNAINTERNAINTERNAINTERNAINTERNATIONAL CLEARINGHOUSETIONAL CLEARINGHOUSETIONAL CLEARINGHOUSETIONAL CLEARINGHOUSETIONAL CLEARINGHOUSEFOR BIRTH DEFECTS MONITORING SYSTEMSFOR BIRTH DEFECTS MONITORING SYSTEMSFOR BIRTH DEFECTS MONITORING SYSTEMSFOR BIRTH DEFECTS MONITORING SYSTEMSFOR BIRTH DEFECTS MONITORING SYSTEMS
A non-governmental organisation in official relations withthe World Health Organisation
ANNUAL REPORT 1999ANNUAL REPORT 1999ANNUAL REPORT 1999ANNUAL REPORT 1999ANNUAL REPORT 1999with data for 1997with data for 1997with data for 1997with data for 1997with data for 1997
Officers 1998/1999Officers 1998/1999Officers 1998/1999Officers 1998/1999Officers 1998/1999
ChairpersonChairpersonChairpersonChairpersonChairpersonPaul Merlob (Israel, IBDMS)
Vice-ChairpersonVice-ChairpersonVice-ChairpersonVice-ChairpersonVice-ChairpersonElisabeth Robert (France, Central East)
SecretarySecretarySecretarySecretarySecretary-----TTTTTreasurerreasurerreasurerreasurerreasurerCsaba Siffel (Hungary)
PPPPPublished byublished byublished byublished byublished byTHE INTERNATIONAL CENTRE FOR BIRTH DEFECTSTHE INTERNATIONAL CENTRE FOR BIRTH DEFECTSTHE INTERNATIONAL CENTRE FOR BIRTH DEFECTSTHE INTERNATIONAL CENTRE FOR BIRTH DEFECTSTHE INTERNATIONAL CENTRE FOR BIRTH DEFECTS
00195 Roma, Via Sabotino 2, Italy00195 Roma, Via Sabotino 2, Italy00195 Roma, Via Sabotino 2, Italy00195 Roma, Via Sabotino 2, Italy00195 Roma, Via Sabotino 2, Italy
Tel: 0039-06-3701905 E-mail: [email protected]: 0039-06-3701904 Web site: www.icbd.org
DirectorDirectorDirectorDirectorDirectorPierpaolo Mastroiacovo
ConsultantConsultantConsultantConsultantConsultantLorenzo Botto
CoordinatorCoordinatorCoordinatorCoordinatorCoordinatorAldo Rosano
EpidemiologistEpidemiologistEpidemiologistEpidemiologistEpidemiologistCarla Arpino (until September 1998)
Marisa Raffo (from April 1999)
StatisticiansStatisticiansStatisticiansStatisticiansStatisticiansSonia Brescianini
Gian Luca Di Tanna (from February 1999)Aldo Rosano
Data ManagementData ManagementData ManagementData ManagementData ManagementTatjana Dukic
Simonetta Zezza
Annual Report EditorsAnnual Report EditorsAnnual Report EditorsAnnual Report EditorsAnnual Report EditorsBeverley Botting
Eduardo E. CastillaPierpaolo Mastroiacovo
Csaba Siffel
ISSN 0743-5703
The International Centre for Birth Defects acknowledges the financial support received fromthe Centers for Disease Control and Prevention, Atlanta, USA (CDC Grant no. U50/CCU207141-08)Centers for Disease Control and Prevention, Atlanta, USA (CDC Grant no. U50/CCU207141-08)Centers for Disease Control and Prevention, Atlanta, USA (CDC Grant no. U50/CCU207141-08)Centers for Disease Control and Prevention, Atlanta, USA (CDC Grant no. U50/CCU207141-08)Centers for Disease Control and Prevention, Atlanta, USA (CDC Grant no. U50/CCU207141-08);
the European Community European Community European Community European Community European Community ––––– Biomed n. BMH4-CT98-3969 (DG12-S Biomed n. BMH4-CT98-3969 (DG12-S Biomed n. BMH4-CT98-3969 (DG12-S Biomed n. BMH4-CT98-3969 (DG12-S Biomed n. BMH4-CT98-3969 (DG12-SSMI)SMI)SMI)SMI)SMI);the ASM (Associazione Italiana Studio Malformazioni), Milan, ItalyASM (Associazione Italiana Studio Malformazioni), Milan, ItalyASM (Associazione Italiana Studio Malformazioni), Milan, ItalyASM (Associazione Italiana Studio Malformazioni), Milan, ItalyASM (Associazione Italiana Studio Malformazioni), Milan, Italy;and the Department of PDepartment of PDepartment of PDepartment of PDepartment of Pediatrics, Catholic Universityediatrics, Catholic Universityediatrics, Catholic Universityediatrics, Catholic Universityediatrics, Catholic University, Rome, Italy, Rome, Italy, Rome, Italy, Rome, Italy, Rome, Italy.
Printed in Hungary – August 1999
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INTERNATIONAL CLEARINGHOUSEINTERNATIONAL CLEARINGHOUSEINTERNATIONAL CLEARINGHOUSEINTERNATIONAL CLEARINGHOUSEINTERNATIONAL CLEARINGHOUSEFOR BIRTH DEFECTS MONITORING SYSTEMSFOR BIRTH DEFECTS MONITORING SYSTEMSFOR BIRTH DEFECTS MONITORING SYSTEMSFOR BIRTH DEFECTS MONITORING SYSTEMSFOR BIRTH DEFECTS MONITORING SYSTEMS
ANNUAL REPORT 1999ANNUAL REPORT 1999ANNUAL REPORT 1999ANNUAL REPORT 1999ANNUAL REPORT 1999
1. Preface ......................................................................................................................................5
2. Committee Reports2.1 Committee on Environmental and Occupational Risk Assessment (CEORA) ..............72.2 Classification Committee................................................................................................82.3 Committee on Malformation and Drug Exposure (MADRE)..........................................102.4 Multiple Congenital Anomalies Committee ....................................................................142.5 Prenatal Diagnosis Committee .......................................................................................15
3. Research Projects3.1 Prevention strategies based on periconceptional folic acid supplementation .............173.2 MTHFR Project ...............................................................................................................183.3 Neural Tube Defects and primary prevention strategies – BIOMED 2 Project .............22
4. Relationship with Other Organisations ....................................................................................23
5. Contributing Monitoring Systems ............................................................................................25
6. Synopsis of Monitoring Systems .............................................................................................41
7. ICBDMS Feb 98 Definitions of the Reported Malformations ..................................................437.1 Deviation from the ICBDMS Feb 98 Definitions by Registry .........................................46
8. Tabulations of Birth Defects 1997, with Time Trends over Previous Years8.1 Instructions and Recommendations to the Reader ......................................................498.2 Notes on Statistical Analysis ..........................................................................................498.3 List of Tables ...................................................................................................................518.4 Tables and Time Trends .................................................................................................528.5 Observed to Expected Ratio, 1997 ..............................................................................1078.6 Time Trends Graphs 1974-1997 ...............................................................................108
9. Limb Reduction Defects, 1997 ...............................................................................................139
10. Prenatal Diagnosis and Down Syndrome, 1997 ....................................................................145
11. Multiple Congenital Anomalies, 1997 .....................................................................................151
12. References by Programmes, 1998-1999 ..........................................................................157
Contents
Page
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It gives me great pleasure to welcome all readersto the 1999 Annual Report from the International
Clearinghouse for Birth Defects Monitoring Systems(International Clearinghouse). The Clearinghousewas founded in 1974 to provide a forum for the rapidexchange of information among the various birthdefects monitoring or surveillance programs aroundthe world. Our Clearinghouse is an independent, non-profit-making organization that was originally spon-sored by the March of Dimes Birth Defects Founda-tion and has been affiliated since 1986 to the WorldHealth Organization as a non-governmental organi-zation. A center to coordinate the activities of theClearinghouse was found in 1989. The InternationalCentre for Birth Defects (ICBD) initially establishedat the University of Bergen, Norway, was transferredto Rome in 1992 (ICBD, Via Sabotino 2, 00195 Rome,Italy) being generously supported by theAssociazone Italiana Studio Malformazioni (ASM).
At this time, there are 30 participating programmes inthe Clearinghouse contributing on a voluntary basis,representing 34 countries (of which 13 are from theSouth America Programme) and covering approxi-mately 3 millions births each year. The synopsis ofmonitoring systems on page 41, and of contributingprogrammes (pages 25-40) summarize the charac-teristics of each of the programmes and give also thenames and addresses of the Programme Directors.
Until 1996, the tabulation of data was done by malfor-mation. During the last 3 years we have changed thepresentation of our material tabulating it by programme.Since the Clearinghouse programmes are so diverse,it is not possible to make simple comparisons betweenthe data supplied by them. The tabulation by pro-grammes tries to avoid such unreliable comparisons.
The various scientific activities of Clearinghouseare well reflected in the chapters for CommitteeReports and Research Projects. Clearinghouse has7 Scientific Committees, which coordinate, andpromote special studies on specific topics relatedto congenital malformations. The Clearinghousemembers are deeply involved in many collabora-tive research projects in areas of the great actualinterest. Evaluation of the primary prevention ofneural tube defects by periconceptional folic acidsupplementation (BIOMED project and CDC-Atlanta project), and the study of the frequency ofthe C677T mutation of the MTHFR gene and othergenes related to folate/homocysteine metabolismin a representative, anonymous sample of the new-born population – are two examples (from manyothers) of the scientific contributions of Clearing-house members.
The International Clearinghouse is in a good posi-tion to provide assistance and scientific support forprogrammes or countries interested in the field ofbirth defects. To apply for full membership of theClearinghouse, a programme must have accumu-lated appropriate baseline data for a minimum of100,000 births over a period of at least 2 years andmust continue to monitor at least 20,000 births an-nually. Associate members must have establishedbaseline and must monitor at least 5,000 births an-nually. Both types of membership require partici-pation in joint studies and the reporting of selecteddata annually. For more information about theClearinghouse, or about any aspects of our work,please contact initially the director of our Interna-tional Centre in Rome. We will be very pleased toanswer all your requests and to help you in settingup your own programme.
Paul Merlob (Israel - IBDMS)ChairpersonInternational Clearinghouse for Birth Defects Monitoring Systems (ICBDMS)
1. Preface
7
2.1 Committee on Environmental and Occupational Risk Assessment (CEORA)Lorentz M. Irgens (Norway)
involve more than the national average + 1 SD andthe occupation in industry is below the national av-erage – 1 SD or the ”other occupation” is below thenational average – 1 SD. Urban is defined as occu-pation in agriculture is below national average – 1SD and industry above national average + 1 SD oroccupation ”other” is above national + 1 SD. Thedefinitions are based on demographic data from1961, 1970, 1980 and 1991. The Black Belt is de-fined politically as districts in which a high level ofpollution is suspected.
England and WalesThe categorization rural/urban was ment to bebased on postal addresses, and attempts weremade to prepare data accordingly. However, thebasis of this categorization was a census in 1991and is not routinly updated. Thus E&W data will becategorized by an offical system newly developedfor demographic objectives.
Northern NetherlandsNo change in the categorization; will be based onan official address density system.
NorwayNo change in the categorization; will be based onan official “distance to nearest centre” system.
New ZealandWill participate with data categorized in a rural ur-ban system used in New Zealand.
Categorisation of outcome variablesThe separate entities in terms of ”AR diagnoses”will be maintained. Furthermore, ”neural tube de-fects” and ”congenital heart defects” will be estab-lished in addition to ”total birth defects” and”EUROCAT birth defects” (i.e. those monitored byEUROCAT). Attempts will be made to include ”sexratio in all births” wherever feasible.
2. Committee Reports
MembersMembersMembersMembersMembersLorentz M. Irgens (Norway)Barry Borman (New Zealand)Beverley Botting (England and Wales)Hermien de Walle (Northern Netherlands)Martina C. Cornel (Northern Netherlands)Jíri Hóracek (Czech Republic)Antonin Sipek (Czech Republic)
The work is based on the following concept: thereis a general concern that a polluted environmentmay cause birth defects and other adverse perina-tal outcome. However, monitoring systems exist thatmay provide data to clarify the issue. The analysiswill follow a stratified strategy comparing rural/ur-ban gradients between countries. This is done inpart since a pooled analysis is not just justified(rural England and Wales is not equal to rural Nor-way), in part since the strategy will increase the pos-sibility to detect a gradient, if present, covering awider range of rural/urban variables. To specificallyfocus on pollution can not be recommended sincethe exposure in the participating countries are verydifferent. Still, separate data for the black trianglein Czech Republic will be provided.
At the meeting in Florence the following issues werediscussed:
Czech RepublicDuring the last year, Czech Republic prepared dataenabling us in Bergen to produce graphs of seculartrends in low birthweights, mortality and a series ofbirth defects in different areas viz., rural, urban, BlackBelt and other. Some data errors were identifiedand corrected during the year. A special problemmay relate to different ascertainment in the BlackBelt and the other areas.
The definition of rural (approximately 10% of thepopulation) is that occupation in agriculture should
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2.2 Classification CommitteeClaude Stoll (France - Strasbourg)
This proposal needs connecting with many otherexperts or group of experts of different specialitiessuch as embryologists, ultrasonographers, pediatriccardiologists, urologists, orthopedists, etc... It needslarge support of all of the Clearinghouse memberswho want to be involved.
The Classification Committee proposed to breakup the malformations to 5-10 groups and to startwith the limb defects.
In a first step a meeting was organized with a fewexperts from inside and from outside theClearinghouse and EUROCAT. This small group ofexperts could agree on a proposal of classificationwhich could be improved in a second step, by cor-respondence with more experts. After circulationfinal aprouvment of this Classification will be ob-tained and a pilot study could start. This meetingwhich was funded by the Clearinghouse was organ-ized in Strasbourg March 22-23, 1996. The expertswho met in Strasbourg proposed a new Classifica-tion of limb defects.
The Classification Committee proposed to evalu-ate this new classification in an epidemiologic andgenetic way. The participant Programmes will covera large population. Ascertainment of cases will bebased on the use of multiple sources of information.Livebirths and stillbirths will be included in thisstudy. Cases having had prenatal diagnosis per-formed through CVS will be excluded. The exactlocalisation of the limb malformation will be identi-fied according to the new ICBDMS classification.The cases will be classified by the same group,avoiding inconsistency between centers. Analysiswill be carried out and the results will show the valueof this new classification. However a large evalua-tion was not possible as many programs were notable to send data. Therefore this Classification wasevaluate with the cases of some registries only. Itcould be shown that this Classification is working.This Classification was published in American Jour-nal of Medical Genetics, 1998;77:439-441.
Eduardo Castilla who has in charge the classifica-tion of digestive system, collected coding systemsin use in different ICBDMS programmes in order to
MembersMembersMembersMembersMembersClaude Stoll (France - Strasbourg)Guido Cocchi (Italy - IMER)Zully Gelman-Kohan (Israel - IBDMS)John Harris (USA - California)Brian Lowry (Canada - Alberta)Paul Merlob (Israel - IBDMS)
Many people continue to be confused with classi-fication and coding, some others state that anyclassification should start with ICD-10 or ICD-10/BPA-10. ICD is a useful clinical tool and cannot beanything else. For malformation monitoring wemust separate coding and classification.
CodingCodingCodingCodingCoding
The Classification Committee worked on defectdefinitions and proposed definitions concerning olddefects and new defects for reporting cases.As many syndromes are not on ICD10, it was de-cided to treat them separately and to add the McKusick code.BPA-10 is now available on diskette but there is noconversion tool from BPA-9 to BPA-10 yet available.However the Classification Committee is workingon a conversion tool from ICD-9 to ICD-10. Conver-sion from ICD9 to ICD10 is done for three catagoriesof congenital anomalies : Ear, face and neck ; Eye ;Congenital anomalies of heart. The others will beready soon.It was decided that when this conversion will beavailable:- it will be put on the web site for the members ofICBDMS,- a pilot project will be performed for this doublecoding restricted to a few systems,- to work on an automatic match from ICD9 to ICD10.This conversion will be available soon.
ClassificationClassificationClassificationClassificationClassification
Regarding to classification of congenital anomaliesthe committee enlarged by some members of theClearinghouse and experts from outside of theClearinghouse should provide the opportunity for us-ing a uniform classification system and unifying thedata, allowing one to compare them more easily.
Committee Reports
9
Coming back to coding the proposed classifica-tion cannot be a coding manual to ICD-10 which isan alphanumerical coding system in which the con-genital malformations chapter contains the blocksfrom Q00 to Q99. This proposed classificationshould be the backbone for ICD-11 which is start-ing now to be built.
The Committee propose that all ICBDMS membersuse ICD10 starting January 1st, 2000.
Proposal for researchProposal for researchProposal for researchProposal for researchProposal for research
To undertake a study to evaluate the new classifica-tion proposed by ICBDMS in an epidemiologic andgenetic way.The Committee proposed to compare the classifi-cation of limb anomalies with the ICD10 coding andalso to prepare ICD11. It will be checked with WHOwhere they are for ICD11.
know how the data are collected and how a classi-fication in the field can be proposed. He don't thinkthat a multidisciplinary team is needed, a couple ofembryologists and pediatric surgeons could doproposals to the Committee. But the problem is howto approach the classification: on an etiologicalbasis or on a pathogenic and anatomic basis. TheClassification Committee agreed that the anatomicapproach is the more relevant. E. Castilla will pro-pose a classification by the end of the first quarterof 1999.
J. Spranger was approached for the musculo-skel-etal classification. He agrees to participate to theclassification of musculo-skeletal anomalies.
Two other classifications: central nervous systemanomalies and congenital heart defects will be pro-posed by ICBDMS members.
Committee Reports
10
2.3 Committee on Malformation and Drug Exposure (MADRE)Elisabeth Robert (France - Central East)
MembersMembersMembersMembersMembersElisabeth Robert (France - Central East)Aldo Rosano (ICBD, Rome)Sonia Brescianini (ICBD, Rome)Martina Cornel (Northern Netherlands)Catherine de Vigan (France - Paris)Stein Emil Vollset (Norway)
MADRE is an acronym for MAMAMAMAMAlformation DRDRDRDRDRug EEEEEx-posure surveillance. This project was set up to sur-vey the simultaneous occurrence of malformationsand first trimester drug exposures with the aim toraise hypotheses about possible teratogenic effectof either newly marketed drugs or of drugs for whichprescription to women in childbearing age wasmodified.
MethodologyMethodologyMethodologyMethodologyMethodology
Those birth defects registries that have informationreport individual pairs of malformation(s) - drug(s).The methodology was presented in detail else-where (1). In a few words, for each drug-malforma-tion combination where more than two cases are
observed, a set of 2x2 tables is formed and analyzedin the case-control fashion. A case is defined as aninfant with the malformation in question, alone or incombination with other malformations. An infant isconsidered exposed if the mother used the drug inquestion alone or in combination, and unexposedotherwide. The significance of clusters of cases at aspecific drug-malformation pair was assessed bycomparing use of the specific drug with its use in allother malformations.
Coding and checking reported data was taken careof by Elisabeth Robert, statistical analyses were per-formed by Aldo Rosano and Sonia Brescianini at ICBD.Several levels of specificity for drugs and malforma-tions codes were cross-tabulated (3/3, 3/5, 4/5 grids).
ResultsResultsResultsResultsResults
New cases have come from eight programs in 1997and 1998: Japan, Israel, Italy IMER, Italy ISMAC,France Paris, Northern Netherlands, South America,and France Central East. Out of the 3303 new cases,2608 (79%) came from South America (years 1993
Committee Reports
Table 1. Cases of malformed newborns and/or fetuses exposed to drugs in pregnancy
Year 1990 1991 1992 1993 1994 1995 1996 1997 Total
Japan, JAOG 48 41 52 51 35 43 32 57 359
France, Central East 132 146 113 178 183 135 114 22 1023
Italy, IMER 73 71 114 132 75 76 74 615
Italy, IPIMC 189 261 437 394 359 1640
South America, ECLAMC 61 255 458 714 674 624 596 3382
France, Paris 219 170 183 154 136 57 919
Israel, IBDMS 15 15 27 16 6 12 15 14 120
Australia 28 20 20 68
Northern Netherlands 5 11 67 47 32 23 185
Italy, ISMAC 27 21 21 7 7 11 94
Total 546 836 1466 1687 1589 1098 1010 173 8405
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Committee Reports
to 1996). The total number of cases registered inthe database is now 8445 and they are distributedas shown in Table 1. Specific associations were se-
CommentsCommentsCommentsCommentsComments
At previous analysis we suspected an associationbetween spina bifida and heparinspina bifida and heparinspina bifida and heparinspina bifida and heparinspina bifida and heparin. This was basedon 3 cases. There is no new case for this associa-tion, but it stays significant.
Three articles were published in 1998 on theteratogenicity of isoprostol isoprostol isoprostol isoprostol isoprostol (2-4), a prostaglandinused for prevention and treatment of ulcer, but alsofor abortion in some countries. Among the malfor-mations associated with the drug, Möebius syn-drome (cranial nerve paralysis) is frequently de-scribed, as well as limb reduction and scalp de-
fects. We have 30 such exposures in the database,all coming from South America ECLAMC. Amongthem 10 cases are "other congenital anomalies oflimbs" (755), and the association is significant(OR=2.37, 95% CI 1.15-4.90, p=0.02). Of these, 4were total absence of forearm and hand (OR=13.96,95% CI 6.01-32.43, p<0.0001). There were 9 casesof "congenital anomalies of integument" (757),(OR=6.96, 95% CI 3.50-13.86, p<0.0001). Amongthose, 4 were accessory (or ectopic) nipples(OR=5.43, 95% CI 2.08-14.16, p=0.0005).
Besides surveillance, the MADRE project groupestablished a drug "profile" as an illustration of the
lected and examined: expected associations(Table 2), links suspected at previous analysis andnewly suspected links (Table 3).
Table 2. Expected associations
Programme Spina bifidawith fatty acids
Cardiac defectswith antidiabetics
Cleft palate and cleftlip with barbiturates
Hypospadiaswith fatty acids
(741/N03AG) (745+746+747/A10) (749/N03AA) (752.60/N03AG)
Japan, JAOG 7
France, Central East 10 17 9 6
Italy, IMER 6
Italy, IPIMC 18 4 2
South America, ECLAMC 1 4 4 1
France, Paris 3 33 1 5
Israel, IBDMS 2 1
Australia 1
Northern Netherlands 4
Italy, ISMAC 1
Total 14 86 25 15
OR-Mantel Haenszel95% Confidence Interval
4.63(2.63 - 8.13)
2.80(2.09 - 3.74)
2.84(1.79 - 4.52)
2.24(1.29 - 3.89)
Breslow-Dayheterogeneity test
NS NS NS NS
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Committee Reports
different associations that can be found withantiepileptics. Malformations are shown as 3-digitcodes, and, as seen on Figure 1, significant
Table 3. Associations found previously or newly suspected
associations are found with 741 (spina bifida) and749 (orofacial clefts).
Programme Cleft palate and cleft l ipw ith benzodiazepines
(749/N05BA)
Spina bifidaw ith heparin group
(741/B01AB)
Japan, JAOG 3
France, Central East 7 1
Italy, IMER 1
Italy, IPIMC 2 2
South Am erica, ECLAMC 4
France, Paris 4
Israel, IBDMS
Australia
Northern Netherlands
Italy, ISMAC
Total 21 3
OR-Mantel Haenszel95% Confidence Interval
1.23 (0.77-1.95) 6.23 (2.08 -18.67)
Breslow-Dayheterogeneity test
NS NS
Finally, another analysis of the dataset was per-formed in 1998 (reference 5). The general aim wasto assess whether MADRE can be used for identify-ing and quantifying associations between specificcongenital malformations and intrauterine drugexposures. This was performed focusing the atten-tion on antiepileptic drugs. In this analysis onlymalformations known or suspected to be associ-ated with AED exposure were studied. Specific aimswere to evaluate how the measures of effect vary bymodifying the definition of controls, i.e. excludingfrom the control group children affected by malfor-mations known or suspected to be associated toAED exposures and to evaluate separately the ef-
fects of monotherapy and polytherapy. Resultsshow that useful information on the teratogeniceffect of drugs can be derived for the analysis ofa surveillance system. Associations consistentlyidentified by previous studies were confirmed, show-ing a specific effect for fatty acids derivatives andspina bifida, and for barbiturates and oral clefts.Furthermore, the large amount of data also permit-ted us to explore other associations for specificmalformations.
13
0.00
0.50
1.00
1.50
2.00
2.50
3.00
3.50
4.00
4.50
216 524 740 741 742 743 744 745 746 747 748 749 750 751 752 753 754 755 756 757 759
ICD-9 code
OR
Figure 1. Profile for anticonvulsants (N03)
Committee Reports
ReferencesReferencesReferencesReferencesReferences
1. Robert E, Vollset SE, Botto L, Lancaster PAL,Merlob P, Mastroiacovo P, Cocchi G, Ashisawa M,Sakamoto S, Orioli I. Malformation surveillance andmaternal drug exposure: the MADRE project. Int JRisk Safety in Medicine 1994;6:75-118.2. Gonzalez CH, Marques-Dias MJ, Kim CA,Sugayama SM, Da Paz JA, Huson SM, Holmes LB.Congenital abnormalities in Brazilian children as-sociated with misoprostol misuse in first trimesterof pregnancy. Lancet 1998;351:1624-1627.3. Hofmeyr GJ, Milos D, Nikodem VC, de Jager M.Limb reduction anomaly after failed misoprostolabortion. S Afr Med J 1998;88:566-567.
4. Pastuszak A L, Schüler L, Speck-Martins C, Katia-Edni E, Coelho FA, Cordello SM, Vargas F, SchwarzIVD, Larrandaburu M, Safattle H, Meloni VFA, KorenG, Neto C. Use of Misoprostol during Pregnancyand Mobius' Syndrome in Infants. N Eng J Med1998;338:1881-1885.5. Arpino C, Brescianini S, Robert E, Castilla EE,Cocchi G, Cornel M, de Vigan C, Lancaster PA,Merlob P, Sumiyoshi Y, Renzi C, Rosano A,Mastroiacovo P. Use of an international data-base on drugs and malformations (MADRE) to as-sess the teratogenic effects of antiepileptic drugs(submitted).
216 Benign neoplasm of skin524 Dentofacial anomalies740 Anencephalus and similar anomalies741 Spina bifida742 Other congenital anomalies of nervous system743 Congenital anomalies of eye744 Congenital anomalies of ear, face, and neck745 Bulbus cordis anomalies and anomalies of
cardiac septal closure746 Other congenital anomalies of heart747 Other congenitals anomalies of the
circulatory system
ICDICDICDICDICD-9-9-9-9-9 MalformationsMalformationsMalformationsMalformationsMalformationscodecodecodecodecode
LegendLegendLegendLegendLegend
748 Congenital anomalies of respiratory system749 Cleft palate and cleft lip750 Other congenital anomalies of upper alimentary tract751 Other congenital anomalies of digestive system752 Congenital anomalies of genital organs753 Congenital anomalies of urinary system754 Certain congenital musculoskeletal deformities755 Other congenital anomalies of limbs756 Other musculoskeletal anomalies757 Congenital anomalies of the integument759 Other specified and unspecified
congenital anomalies
ICDICDICDICDICD-9-9-9-9-9 MalformationsMalformationsMalformationsMalformationsMalformationscodecodecodecodecode
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Committee Reports
2.4 Multiple Congenital Anomalies CommitteeAldo Rosano (ICBD, Rome)
MembersMembersMembersMembersMembersAldo Rosano (ICBD, Rome)Paul Lancaster (Australia)Gioacchino Scarano ( Italy - BDRCam)Romano Tenconi (Italy - North East)Claude Stoll (France - Strasbourg)Li Zhu ( China - Beijing)
Purpose of the CommitteePurpose of the CommitteePurpose of the CommitteePurpose of the CommitteePurpose of the Committee
The Multiples Committee coordinates and promotesregular surveillance and special studies on infants withmultiple congenital anomalies (MCAs). Surveillanceof MCAs is a longstanding activity of Clearinghouseand enjoys the participation of most member pro-grammes. It is meant to complement surveillance ofindividual defects as currently performed by theClearinghouse, and in essence acts as an additionalsafety net for early identification of teratogens.
Ongoing Surveillance of MCAsOngoing Surveillance of MCAsOngoing Surveillance of MCAsOngoing Surveillance of MCAsOngoing Surveillance of MCAs
The basis for MCA surveillance is the observationthat many teratogens cause patterns of multiplecongenital anomalies rather than only individualanomalies. Thus, by looking carefully at the smallsubset of infants with MCAs the effects of a new orspreading teratogen could be detected morequickly (require fewer cases) than with conventionalsurveil lance of individual defects. TheClearinghouse has developed over the years amultifaceted approach to MCA surveillance that inessence integrates a clinical appraisal of the caseswith several epidemiologic techniques to evaluatedeviation from baseline expectations.
The Multiples Committee has worked with the par-ticipating programmes to conduct and improvethis surveillance activity and to develop the surveil-lance capacity of the ICBD. The Committee is alsoresponsible for the quarterly and yearly surveillancereport. A separate chapter of this Annual Report willbe devoted to the annual review of MCA surveillance.
Report from the Committee Meeting in Florence, 1998Report from the Committee Meeting in Florence, 1998Report from the Committee Meeting in Florence, 1998Report from the Committee Meeting in Florence, 1998Report from the Committee Meeting in Florence, 1998
The most relevant issues discussed during the Com-mittee Meeting held in September 1998 in Florence were:
1. A constant increase in cardiac defects was foundin 1997 quarterly data. We believe that this maybe due to better ascertainment throughultrasonographic diagnostic tools.
2. Heterogeneity of reporting among registries andwithin registries in different years is still a prob-lem for a correct analysis. The reasons for suchheterogeneity could be due to improvement inascertainment and to central coding. Codingwas performed in Atlanta from 1992 to 1994 andat the ICBD from 1995, possibly with a differentapproach. We decided to investigate the prob-lem of coding with double checking a sampleof the database.
3. Committee membership was extended to fournew members.
Special StudiesSpecial StudiesSpecial StudiesSpecial StudiesSpecial Studies
Limb Deficiencies (LD). This ongoing project focuseson infants with a limb deficiencies and one or morenon-limb anomalies. More than 1,300 cases from 11registries have been reported. This project has pro-duced several studies to be submitted to selectedjournals: 1) the distribution and associations ofcongenital anomalies with different types of limbdeficiencies; 2) oromandibular hypogenesis pattern;3) acrorenal pattern. Preliminary results on maternalexposure and complex limb anomalies. were pre-sented at the scientific session of the annual meet-ing held in Florence in September 1998 and relevantpapers will be submitted by the end of 1999.
Looking ForwardLooking ForwardLooking ForwardLooking ForwardLooking Forward
Many new projects were proposed: a study onsyndromic cases among complex limb deficiencieswas proposed by Martina Cornel; a study on VATERassociated with hydrocephaly was proposed byEduardo Castilla and Lorenzo Botto; laterality of LDin MMI will be investigated by Claude Stoll; BrianLowry is interested in a study on unusual cases,attributable to disorganised genes and finallyMartina Cornel will investigate the cases of multi-ples with patterns attributable to known teratogens.
We are keen to have new participating pro-grammes. The registry of Sicily has already sent
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Committee Reports
data, that will be included in the database afterrevision and coding. Ireland and Canada-Albertaare interested in the participation and will confirmtheir availability.
The committee will be kept deeply busy to carry onsuch new projects and to try to improve the accu-racy and reliability of the monitoring activity.
2.5 Prenatal Diagnosis CommitteeGuido Cocchi (Italy - IMER)
cordocentesis ), 3) karyotype and 4) gestational age(wks) at the diagnosis and at the termination.
After 5 years of survey the results confirm a progres-sive increase in the techniques for routine use, alarge variability among countries in the techniquesused (however with a preponderant use of amnio-centesis), in the access to and advice regardingthese techniques, and differences in law relating toelective termination.
Results for 1997 are included in pages 145-149 of thisAnnual Report, emphasising the variability amongcountries, in the proportion of cases terminated.
An analysis was started also for the temporal trendof some specific items that can demonstrate an in-creased use of these procedures and consequentlya reduction in the birth prevalence. Neverthelessthe observed increased in the number of termina-tions is higher than the observed decreased preva-lence at birth.
The interest of Programme Directors (15 partici-pants) and the informative results suggest that thework of this committee should continue. The planfor next year is to continue the Down Syndrome sur-veillance and to start collecting information on theimpact of prenatal ultrasound detection of congeni-tal heart defects. For this latter study a specificsubcommitee was nominated in Florence duringthe last Annual Meeting.
MembersMembersMembersMembersMembersGuido Cocchi (Italy - IMER)Beverley Botting (England and Wales)Martina Cornel (Northern Netherland)Janine Goujard (France - Paris)Antonin Sipek (Czech Republic)
The progressively more extensive use of prenataldiagnosis screening or procedures followed by elec-tive terminations has affected the birth prevalenceof those types of congenital defects that can bedetected prenatally.The epidemiological impact of prenatal diagnosishas been evident to all monitoring programmesoperating in populations where prenatal diagnosisis available and elective terminations are per-formed.In order to evaluate the magnitude of this problemand to collect information on the policies and prac-tices in each country, a committee on Prenatal Di-agnosis was set up in 1994 in order to test the feasi-bility of a collaborative study.The Prenatal Committee asked ICBDMS Pro-gramme Directors to provide information on se-lective terminations for Down Syndrome startingwith data for 1993. The information has been col-lected on the basis of 3 forms specifically designedto collect the number of cases aborted, among thetotal number of cases registered, by maternal age,and for each terminated case recorded: 1) mater-nal age, 2) technique of prenatal diagnosis per-formed (chorion villus sampling, amniocentesis,
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3.1 Prevention strategies based on periconceptional folic acid supplementation – CDC projectPierpaolo Mastroiacovo and Aldo Rosano (ICBD, Rome)Lorenzo D Botto (USA - Atlanta)
Data will be collected from March 1998 to March2001. Participating registries represent a wide spec-trum of background risk of birth defects and ap-proach to primary prevention policies. This variabil-ity is useful to evaluate a range of prevention efforts(e.g, supplementation, food fortification, or combi-nations there of) as well as try and disentangle thecomplex web of issues that lead to the develop-ment, implementation, and acceptance of the poli-cies. These data may be useful to the public as wellas to policy makers to improve the effectiveness ofplanned measures of primary prevention.
In addition, a feasibility study of an internationalsurvey of blood folate levels will be implemented. Itmay be the basis for a future study with the poten-tial to generate accurate data on one of the majorprocess outcomes of folic acid prevention efforts,i.e., blood folate levels among relevant sections ofthe population.
An invitation to participate to the study has beenbe extended to members of the InternationalClearinghouse and other selected registries of birthdefects. The study will be coordinated by the Inter-national Centre for Birth Defects in Rome, Italy.
3. Research Projects
This 3-year project, funded by the Centers forDisease Control, Atlanta, USA, is designed to:
1. describe and compare public health policies re-garding the use of folic acid or multivitamin supple-ments for the primary prevention of neural tube de-fects and other birth defects, and investigate thereasons why different countries, working from thesame published data, adopted different policies(or none);
2. evaluate to what extent current public healthpolicies are being implemented and explore thefactors involved in the compliance and acceptanceof such policies;
3. compare the prevalence of selected birthdefects possibly preventable by folic acid supple-mentation such as neural tube defects, oral clefts,cardiac defects, and limb deficiencies, before andafter initiation of folate prevention strategies, anddetermine whether different strategies are associ-ated with variations in the prevalence of thesedefects.
18
3.2 MTHFR ProjectLorenzo D Botto (USA - Atlanta)
proximately 6 percent. For the heterozygous geno-type in infants, the pooled odds ratio for NTDs is 1.2(95% CI 1.0-1.3). The corresponding pooled oddsratios for mothers of NTD-affected pregnancies is2.1 (95% CI 1.5-2.9) and 1.2 (95% CI 0.9-1.5), for thehomozygous C677T and the heterozygous geno-type, respectively. From the few available studieswith data on paternal genotypes, it appears thatthe fathers’ genotype is not a significant risk factor.The A1298C variant of MTHFR (16) has been lessstudied. Two studies (2, 17) found that the A1298Cvariant decreased MTHFR enzyme activity, thoughto a lesser degree compared to the C677T variant.Neither study showed a significant association be-tween the A1298C allele and NTD risk. However, inone study (2) the C677T/A1298C genotype wasassociated with a possible increased risk for NTDs(odds ratio, 2.0; 95% CI 0.9-4.7). In the other study,no increased risk was reported (17).
International variability of neural tube defects andInternational variability of neural tube defects andInternational variability of neural tube defects andInternational variability of neural tube defects andInternational variability of neural tube defects andof MTHFR genotypes: is there a connection?of MTHFR genotypes: is there a connection?of MTHFR genotypes: is there a connection?of MTHFR genotypes: is there a connection?of MTHFR genotypes: is there a connection?
The incidence of NTDs is unknown, since many af-fected pregnancies end in spontaneous abortion.The prevalence among births varies considerablyamong countries and ethnic groups, and range fromas high as 1 in 100 births in some regions of China(18) to about 1 in 5,000 or less in some Scandinaviancountries (19). In many countries the prevalence isapproximately 1 in 1,000 births (20).
Although many reports on MTHFR genotypes areavailable in several countries worldwide, genotypeprevalences have not been established with preci-sion. It appears however that the prevalence of theC677T allele differs among populations. Allele fre-quencies ranges from less than 10 percent in somegroups of Africans from Sub-Saharan Africa andsome blacks of African origin living in the Americas(21, 22), to higher than 40 percent in Italians (23-31) and among California Hispanics (3). As ex-pected, the frequency of C677T homozygotes fol-lows a ranking similar to that of the allele frequency,and was highest in Italy (18 percent). The preva-lence by sex (32) or by age (33, 34) may vary, al-though these issues have been studied little.
Research Projects
Methylene-tetrahydrofolate reductase (MTHFR)Methylene-tetrahydrofolate reductase (MTHFR)Methylene-tetrahydrofolate reductase (MTHFR)Methylene-tetrahydrofolate reductase (MTHFR)Methylene-tetrahydrofolate reductase (MTHFR)worldwide: a collaborative study of the Interna-worldwide: a collaborative study of the Interna-worldwide: a collaborative study of the Interna-worldwide: a collaborative study of the Interna-worldwide: a collaborative study of the Interna-tional Clearinghousetional Clearinghousetional Clearinghousetional Clearinghousetional Clearinghouse
MTHFR and neural tube defects: the rationaleMTHFR and neural tube defects: the rationaleMTHFR and neural tube defects: the rationaleMTHFR and neural tube defects: the rationaleMTHFR and neural tube defects: the rationale
Because folic acid reduces by half the risk for neu-ral tube defects (NTDs), researchers are investigat-ing mutations of folate-related genes as potentialrisk modifiers. Most studies so far have focused onMTHFR (5,10 methylenetetrahydrofolate reductase),though other genes are also being investigated.MTHFR catalyzes the conversion of 5,10methylenetetrahydrofolate into 5-methyl-tetrahydrofolate (5-MTHF) which is the major circu-lating form of folate. Folate in turn is used in manybiochemical pathways, including the remethylationof homocysteine into methionine and the synthesisof nucleotides. The gene for MTHFR is located onchromosome 1, at 1p36.3 and appears to consist of11 exons (1). Although at least 16 mutations of theMTHFR gene are known, most variants are rare, in-duce severe MTHFR deficiency, and causehomocystinuria, a rare metabolic disorder. Twomutations, however, the thermolabile or C677T al-lele and the A1298C allele, appear common enoughto be of potential interest for their role in commonbirth defects. The C677T allele causes a mildenzymatic dysfunction that results in mildhomocystenemia in persons whose folate status isnot optimal.
The C677T variant has been linked to an increasedrisk of spina bifida and anencephaly, in addition todiseases other than congenital malformations, in-cluding adult cardiovascular disease, stroke, andcoagulation abnormalities.
MTHFR and neural tube defects: the dataMTHFR and neural tube defects: the dataMTHFR and neural tube defects: the dataMTHFR and neural tube defects: the dataMTHFR and neural tube defects: the data
Pooling available data from case-control studies ofMTHFR and neural tube defects (2-14) and exclud-ing one study (15) because of probable overlapwith subsequent study from the same group (2), itcan be estimated that the odds ratios for NTDamong infants with C677T/C677T genotype is 1.7(95% CI 1.4-2.2), with an attributable fraction of ap-
19
The study will provide precise estimates of MTHFRgenotype frequency from well defined populations.In addition because the samples are chosen to rep-resent populations for whom birth defect surveil-lance data are available, the findings will allow tocorrelate genotype frequency with the prevalenceof neural tube defects.
ReferencesReferencesReferencesReferencesReferences
1. Goyette P, Pai A, Milos R, et al. Gene structure ofhuman and mouse methylenetetrahydrofolate re-ductase (MTHFR). Mamm Genome 1998;9:652-6.2. van der Put NM, Gabreels F, Stevens EM, et al. Asecond common mutation in the methylene-tetrahydrofolate reductase gene: an additional riskfactor for neural-tube defects? Am J Hum Genet1998;62:1044-51.3. Shaw GM, Rozen R, Finnell RH, Wasserman CR,Lammer EJ. Maternal vitamin use, genetic varia-tion of infant methylenetetrahydrofolate reductase,and risk for spina bifida. Am J Epidemiol1998;148:30-7.4. Whitehead AS, Gallagher P, Mills JL, et al.A genetic defect in 5,10-methylenetetrahydro-folate reductase in neural tube defects. QJM1995;88:763-6.5. Kirke PN, Mills JL, Whitehead AS, Molloy A, ScottJM. Methylenetetrahydrofolate reductase mutationand neural tube defects [letter]. Lancet1996;348:1037-8.6. Ou CY, Stevenson RE, Brown VK, et al. 5,10Methylenetetrahydrofolate reductase genetic poly-morphism as a risk factor for neural tube defects.Am J Med Genet 1996;63:610-4.7. Ramsbottom D, Scott JM, Molloy A, et al. Are com-mon mutations of cystathionine beta-synthase in-volved in the aetiology of neural tube defects? ClinGenet 1997;51:39-42.8. Koch MC, Stegmann K, Ziegler A, Schroter B,Ermert A. Evaluation of the MTHFR C677T allele andthe MTHFR gene locus in a German spina bifidapopulation. Eur J Pediatr 1998;157:487-92.9. Bjorke-Monsen AL, Ueland PM, Schneede J,Vollset SE, Refsum H. Elevated plasma total homo-cysteine and C677T mutation of the methylene-tetrahydrofolate reductase gene in patients withspina bifida. QJM 1997;90:593-6.
Gaps in knowledge and the Clearinghouse studyGaps in knowledge and the Clearinghouse studyGaps in knowledge and the Clearinghouse studyGaps in knowledge and the Clearinghouse studyGaps in knowledge and the Clearinghouse studyon MTHFR worldwideon MTHFR worldwideon MTHFR worldwideon MTHFR worldwideon MTHFR worldwide
Most studies on population prevalences of MTHFRgenotypes have been based on groups of individu-als that are either convenient samples of relativelyundefined populations, or samples for whom theselection procedure is incompletely documented.Thus, conclusions based on most current datashould be attempted with caution, recognizing thepotential for bias. Large, population-based studieswill be instrumental in assessing the prevalence ofMTHFR genotypes in well-defined, diversepopulations.
To this end, the International Clearinghouse for BirthDefects Monitoring Systems, through itsheadquarter institute, the International Centre forBirth Defects, is conducting a study to assess thefrequency of alleles of genes related to folate andhomocysteine metabolism, including MTHFR andpossibly others, in representative samples ofpopulations worldwide.Typically, in the study samples will be collected fromnewborn screening programmes (although othersources may be used as well) and will be selectedto ensure that the samples are representative of theunderlying population. Each participant pro-gramme ensure that adequate subject protectionis provided. In many cases, this will entail usinganonymous blood spots, i.e., samples devoid ofpersonal identifiers. Information for each samplewill be limited to basic variables. Data from mostcountries will include baby’s sex, birth weight class,and ethnicity, to allow appropriate stratification ofthe results. About 400 samples per program will becollected, to ensure sufficient precision of the esti-mates, though this number may vary depending onthe population structure (e.g., if population sub-groups are included in which the allele frequency isexpected to be low).
To date, participation to the study includes coun-tries from Europe, the Americas (North America andMexico), Asia (China), and the Middle East. Re-sults are expected to become available by the endof 1999.
Research Projects
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10. Molloy AM, Mills JL, Kirke PN, et al. Low bloodfolates in NTD pregnancies are only partly explainedby thermolabile 5,10-methylenetetrahydrofolatereductase: low folate status alone may be the criti-cal factor. Am J Med Genet 1998;78:155-9.11. Boduroglu K, Alikasifoglu M, Anar B, TuncbilekE. 677-->CT mutation on the methylene-tetrahydrofolate reductase gene is not a risk factorfor neural tube defects in Turkey [letter]. Arch DisChild Fetal Neonatal Ed 1998;78:F235.12. Papapetrou C, Lynch SA, Burn J, Edwards YH.Methylenetetrahydrofolate reductase and neuraltube defects [letter]. Lancet 1996;348:58.13. de Franchis R, Buoninconti A, Mandato C, et al.The C677T mutation of the 5,10-methylene-tetrahydrofolate reductase gene is a moderate riskfactor for spina bifida in Italy. J Med Genet1998;35:1009-13.14. Mornet E, Muller F, Lenvoise-Furet A, et al.Screening of the C677T mutation on themethylenetetrahydrofolate reductase gene inFrench patients with neural tube defects. HumGenet 1997;100:512-4.15. van der Put NM, Steegers-Theunissen RP, FrosstP, et al. Mutated methylenetetrahydrofolate reduct-ase as a risk factor for spina bifida. Lancet1995;346:1070-1.16. Viel A, Dall'Agnese L, Simone F, et al. Loss ofheterozygosity at the 5,10-methylenetetra-hydrofolate reductase locus in human ovarian car-cinomas. Br J Cancer 1997;75:1105-10.17. Weisberg I, Tran P, Christensen B, Sibani S, RozenR. A second genetic polymorphism in methylene-tetrahydrofolate reductase (MTHFR) associatedwith decreased enzyme activity. Mol Genet Metab1998;64:169-72.18. Moore CA, Li S, Li Z, et al. Elevated rates ofsevere neural tube defects in a high-prevalencearea in northern China. Am J Med Genet1997;73:113-8.19. International Clearinghouse for Birth DefectsMonitoring Systems. Annual Report 1992. Rome:International Centre for Birth Defects, 1992.20. International Clearinghouse for Birth DefectsMonitoring Systems. Annual Report 1998. Rome:International Centre for Birth Defects, 1998.21. Schneider JA, Rees DC, Liu YT, Clegg JB. World-wide distribution of a common methylene-
tetrahydrofolate reductase mutation [letter]. Am JHum Genet 1998;62:1258-60.22. Pepe G, Camacho Vanegas O, Giusti B, et al.Heterogeneity in world distribution of the thermolabile C677T mutation in 5,10-methylene-tetrahydrofolate reductase [letter]. Am J Hum Genet1998;63:917-20.23. de Franchis R, Mancini FP, D'Angelo A, et al.Elevated total plasma homocysteine and 677C-->T mutation of the 5,10- methylenetetrahydrofolatereductase gene in thrombotic vascular disease [let-ter]. Am J Hum Genet 1996;59:262-4.24. Abbate R, Sardi I, Pepe G, et al. The high preva-lence of thermolabile 5-10-methylenetetrahydro-folate reductase (MTHFR) in Italians is not associ-ated to an increased risk for coronary artery dis-ease (CAD). Thromb Haemost 1998;79:727-30.25. Sacchi E, Tagliabue L, Duca F, Mannucci PM.High frequency of the C677T mutation in themethylenetetrahydrofolate reductase (MTHFR)gene in Northern Italy [letter]. Thromb Haemost1997;78:963-4.26. Cattaneo M, Tsai MY, Bucciarelli P, et al. A com-mon mutation in the methylenetetrahydrofolate re-ductase gene (C677T) increases the risk for deep-vein thrombosis in patients with mutant factor V (fac-tor V:Q506). Arterioscler Thromb Vasc Biol1997;17:1662-6.27. Girelli D, Friso S, Trabetti E, et al. Methylene-tetrahydrofolate reductase C677T mutation, plasmahomocysteine, and folate in subjects from northernItaly with or without angiographically documentedsevere coronary atherosclerotic disease: evidencefor an important genetic-environmental interaction.Blood 1998;91:4158-63.28. Grandone E, Margaglione M, Colaizzo D,Montanaro S, Pavone G, Di Minno G. Presence ofFV Leiden and MTHFR mutation in a patient withcomplicated pregnancies [letter]. Thromb Haemost1997;77:1036-7.29. Margaglione M, D'Andrea G, d'Addedda M, etal. The methylenetetrahydrofolate reductase TT677genotype is associated with venous thrombosis in-dependently of the coexistence of the FV Leidenand the prothrombin A20210 mutation. ThrombHaemost 1998;79:907-11.30. Motti C, Gnasso A, Bernardini S, et al. Commonmutation in methylenetetrahydrofolate reductase.
Research Projects
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Correlation with homocysteine and other risk fac-tors for vascular disease. Atherosclerosis1998;139:377-83.31. Tosetto A, Missiaglia E, Frezzato M, RodeghieroF. The VITA project: C677T mutation in the methyl-ene-tetrahydrofolate reductase gene and risk ofvenous thromboembolism. Br J Haematol1997;97:804-6.32. Rozen R, Fraser FC, Shaw G. Decreased propor-tion of female newborn infants homozygous for the677 C- ->T mutation in methylenetetrahydrofolatereductase [letter]. Am J Med Genet 1999;83:142-3.
33. Matsushita S, Muramatsu T, Arai H, Matsui T,Higuchi S. The frequency of the methylene-tetrahydrofolate reductase-gene mutation varieswith age in the normal population [letter]. Am J HumGenet 1997;61:1459-60.34. Heijmans BT, Gussekloo J, Kluft C, et al. Mortal-ity risk in men is associated with a common muta-tion in the methylene-tetrahydrofolate reductasegene (MTHFR). Eur J Hum Genet 1999;7:197-204.
Research Projects
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3.3 Neural Tube Defects and primary prevention strategies – BIOMED 2 ProjectJanine Goujard (France - Paris)
This project, financially supported by the EuropeanUnion, is being conducted to investigate the rea-sons why different countries within and outside theEU adopt different policies regarding the primaryprevention of neural tube defects (NTDs) by theuse of periconceptional folic acid (objective 1). Weare also interested in determining the extent towhich such policies are being implemented (ob-jective 2). Additionally, we would like to identify timetrends in prevalence in the various countries anddetermine whether different policies have been as-sociated with different time trends in NTD preva-lence (objective 3).
The ICBD and 13 programmes are involved in theproject.
The main action during the first year of the contracthas been to set up and to finalise the material toachieve the three objectives:
- a questionnaire based on interviews, to be com-pleted by each participating country, addressed toa representative of the Public Health Authority inthe country, and to personalities specialised in dif-
ferent specific areas such as the availability anduse of prenatal diagnosis for NTDs, the estimatedcost of disability associated with spina bifida, theresults of surveys regarding multivitamins use in thegeneral population and during the preconceptionalperiod, the degree of social acceptance of preg-nancy termination, the frequency of risks factorssuch as smoking and alcohol use during pregnancyas indicators of acceptance of preventive behav-iours, etc;
- a tabulation on the folate situation in the differentprogrammes: recommendations (official and non-official), availability;
- a questionnaire for the field survey on folate aware-ness, to be completed by each programme on arepresentative sample of pregnant women definedas mothers delivered of non-malformed newborns;
- the protocol for the NTD data collection, from 1.07.87 to 30.06.98 (births) or 1.01.87 to 31.12.98 (in-duced terminations). Records for the 10 first yearshave been centralised by the ICBD.
Research Projects
23
4. Relationship with Other Organisations
World Health Organisation
The International Clearinghouse is a non-governmen-tal organisation in official relations with the WorldHealth Organization. WHO is represented at the An-nual Meetings of the International Clearing-house byDr Victor Boulyzhenkov, Director of Human GeneticsProgram. WHO supports the Annual Meeting of theInternational Clearinghouse. In September 1998 the1st edition of the World Atlas of Birth Defects was pub-lished in cooperation with Human Genetics Pro-gramme, WHO. The project to produce the secondedition of the Atlas is in preparation.
EUROCAT
EUROCAT (EUropean Registration Of CongenitalAnomalies and Twins) is the only international or-ganisation other than the Clearinghouse which col-lects and publishes data on birth defects preva-lence and undertakes collaborative research. Thereis reciprocal representation of the two organisationsat annual meetings.
World Alliance of Organisationsfor the Prevention of Birth Defects
This organisation was established in 1994 on theinitiative of the March of Dimes Birth DefectsFoundation. The Clearinghouse is a member organi-sation, and is represented at the Board of Directors.
Associazione Italiana StudioMalformazioni (ASM)
The International Centre for Birth Defects (ICBD) is lo-cated within the offices of ASM, a non-profitorganisation for the study of birth defects. ICBD is gladto acknowledge the generous support from ASM.
25
Canada, Alberta
Alberta Congenital Anomalies Surveillance SystemAlberta Congenital Anomalies Surveillance SystemAlberta Congenital Anomalies Surveillance SystemAlberta Congenital Anomalies Surveillance SystemAlberta Congenital Anomalies Surveillance System
History: This programme began in 1966 as a gen-eral Registry for Handicapped Children. This wasdisbanded in 1980 and continued as a surveillanceprogramme for live and stillborn infants with con-genital anomalies who were born in the Province ofAlberta. The programme became an associatemember of the International Clearinghouse in 1996.
Size and coverage: All live and stillbirths in theprovince are covered which at present comprisesabout 40,000 births per year. The definition of still-birth is 20 weeks or more or 500 grams or more. Thevast majority of births occur in hospital (approxi-mately 97%). In 1997 a special fetal congenitalanomalies surveillance system was started to in-clude those fetuses with congenital anomalies whowere either spontaneously lost prior to 20 weeks orwhere there was termination as a result of prenataldiagnosis.
Legislation and funding: Reporting is voluntary. Thesystem is run by members of the Department ofMedical Genetics, Alberta Children’s Hospital/Uni-versity of Calgary reporting to Alberta Vital Statis-tics and Alberta Health. Funding is from AlbertaMinistry of Health.
Sources of ascertainment: Reports are obtainedfrom physician’s notice of birth, live birth and still-birth registrations, death registrations and a spe-cial congenital anomalies reporting form (CARF)from hospitals. This is based on discharge diagno-sis, including readmissions for any reason up to oneyear of age. Additional sources are speciality clin-ics, such as medical genetics and cytogeneticslaboratories.
Exposure information: None is routinely.
Background information: Linkage studies are pos-sible with other statistical data from Alberta Health.
Address for further information: R. Brian Lowry, De-partment of Medical Genetics, Alberta Children’sHospital, 1820 Richmond Road S.W., Calgary,Alberta, T2T 5C7, Canada.Phone: 1-403-2297367, Fax: 1-403-2297624E-mail: [email protected]
Australia
Australian Congenital Malformation Monitoring SystemAustralian Congenital Malformation Monitoring SystemAustralian Congenital Malformation Monitoring SystemAustralian Congenital Malformation Monitoring SystemAustralian Congenital Malformation Monitoring System
History: National monitoring of malformations be-gan in 1981, but not all States and Territories werecollecting data at that stage. Subsequently, peri-natal data systems have been introduced in allStates and Territories. The programme became anassociate member of the International Clearing-house in 1982 and a full member in 1984.
Size and coverage: All births in Australia are nowa-days covered, at the present approximately250,000 annual births. Coverage increased fromabout 50% in 1981 to 100% in 1986. Stillbirths of 20weeks or more gestation are registered. Incom-plete data for the Northern Territory were excludedfrom this report.
Legislation and funding: State and Territory healthdepartments report to the central registry. Centralregistration is funded by a grant from the AustralianInstitute of Health, which is a statutory body withinthe national Department of Community Servicesand Health.
Sources of ascertainment: Reports are obtainedfrom birth notifications, referral hospitals, death cer-tificates, pathology departments and cytogeneticlaboratories.
Exposure information: Except in South Australia,exposure information is not routinely recorded buthas to be obtained ad hoc.
Background information: General perinatal statis-tics are obtained from notification of birth to healthdepartments and from birth and perinatal deathregistrations compiled by the Australian Bureau ofStatistics.
Address for further information: Paul A. L. Lancas-ter, National Perinatal Statistics Unit, Building A27,The University of Sydney, Sydney, N.S.W. 2006,Australia.Phone: 61-2-9381014, Fax: 61-2-93821025E-mail: [email protected]
5. Contributing Monitoring Systems
26
China, Beijing
Birth Defect Surveillance System in Thirty Counties of FourBirth Defect Surveillance System in Thirty Counties of FourBirth Defect Surveillance System in Thirty Counties of FourBirth Defect Surveillance System in Thirty Counties of FourBirth Defect Surveillance System in Thirty Counties of FourProvinces, PProvinces, PProvinces, PProvinces, PProvinces, People’s Republic of China (BDSeople’s Republic of China (BDSeople’s Republic of China (BDSeople’s Republic of China (BDSeople’s Republic of China (BDSS - China)S - China)S - China)S - China)S - China)
History: The programme began in 1992. It becamea full member of the International Clearinghousein 1997.
Size and coverage: This is a population basedmonitoring system. Reports were obtained from allhospitals and village health stations which togethercover all geographically defined population. Totalnumber of population in these areas is around 17millions and total number of births per year isaround 150,000.
Legislation and funding: Funding is from ChinaMinistry of Health and local health authorities.
Sources of ascertainment: Reports are obtainedfrom delivery units, paediatric clinics, ultrasounddepartments, pathology departments and perina-tal health care departments of different level hospi-tals, MCH institutes and village health stations inthe participating counties and cites.
Exposure information: Exposure information is ob-tained from the perinatal health care surveillancesystem (PHCSS) in the same areas for all womenand their babies from pre-marital examination tillsix weeks after birth. BDSS data is linked withPHCSS data by using an ID number assigned toeach woman.
Background information: Background informationis also obtained from PHCSS data.
Address for further information: Zhu Li, M.D., M.P.H.,China National Centre for Maternal and InfantHealth, Beijing Medical University, 38 College Road,Beijing 100083, PR China.Phone: 86-10-62091138, Fax: 86-10-62091141E-mail: [email protected]
Canada, National
Canadian Congenital Anomalies Surveillance SystemCanadian Congenital Anomalies Surveillance SystemCanadian Congenital Anomalies Surveillance SystemCanadian Congenital Anomalies Surveillance SystemCanadian Congenital Anomalies Surveillance System
History: The program was started in 1966. The pro-gram was a full member until 1987, when it becamean associate member. The program was discontin-ued as an associate member of the InternationalClearinghouse in the early 1990s, and reinstated itsassociate member status in 1996.
Size and coverage: The system presently monitorsabout 280,000 births annually, which representsabout 70% of all births in Canada. Stillbirths of atleast 20 weeks of gestation are included.
Legislation and funding: Reporting is based on anagreement between the Canadian Institute forHealth Information, an non-profit organization whichcollects and disseminates data on hospital admis-sion/separation in Canada, and the central registry,which is run and funded by Health Canada. AlbertaCongenital Anomalies Surveillance System andManitoba provincial government also provide thetwo Canadian provinces' data.
Sources of ascertainment: Cases are ascertainedfrom hospital admission/separation summaryrecords collected by the Canadian Institute forHealth Information, or by Alberta Congenital Anoma-lies Surveillance System and Manitoba provincialgovernment. Follow-up continues to one year of age.
Exposure information: No exposure information isroutinely collected in the central registry.
Background information: Background informationis based on hospital admission/separation sum-mary records from the Canadian Institute for HealthInformation, or provided by Alberta CongenitalAnomalies Surveillance System and Manitoba pro-vincial government.
Address for further information: Shi Wu Wen, MB,PhD, Senior Epidemiologist, Bureau of Reproduc-tive and Child Health, LCDC Building # 6 First Floor,Tunney's Pasture A-L 0601E2, Ottawa, Ontario,Canada K1A 0L2.Phone: 1-613-9543339, Fax: 1-613-9419927E-mail: [email protected]
Contributing Monitoring Systems
27
China, CBDMN
Chinese Birth Defects Program of SichuanChinese Birth Defects Program of SichuanChinese Birth Defects Program of SichuanChinese Birth Defects Program of SichuanChinese Birth Defects Program of SichuanProvince, China (until 1994)Province, China (until 1994)Province, China (until 1994)Province, China (until 1994)Province, China (until 1994)Chinese Birth Defects Monitoring NetworkChinese Birth Defects Monitoring NetworkChinese Birth Defects Monitoring NetworkChinese Birth Defects Monitoring NetworkChinese Birth Defects Monitoring Network
History: The programme began in 1984. it becamean associate member of InternationalClearinghouse in 1985 and a full member in 1987.
Size and coverage: In 1984, reports were obtainedfrom 100 hospitals but participation has increased.In 1985,205 hospitals participated. At present, theprogramme covers approximately 260,000 birthsannually in 31 provinces.
Legislation and funding: Participation is voluntary.Funding is mainly from local health authorities.
Sources of ascertainment: Reports are obtainedfrom delivery units, paediatric clinics, and pathol-ogy departments of the participating hospitals.
Exposure information: Exposure information is ob-tained by interviews of mothers of the reportedmalformed infants. No information is available onexposures in controls.
Background information: Total number of births fromeach participating hospital is known.
Address for further information: Zhu Jun, NationalCenter for Birth Defects Monitoring, West ChinaUniversity of medical Sciences, No. 17 section 3REN MIN NAN LU , Chengdu-PRC-China.Phone: 86-28-5501363, Fax: 86-28-5501363E-mail: [email protected]
Czech Republic
Congenital Malformations Monitoring ProgrammeCongenital Malformations Monitoring ProgrammeCongenital Malformations Monitoring ProgrammeCongenital Malformations Monitoring ProgrammeCongenital Malformations Monitoring Programmeof the Czech Republicof the Czech Republicof the Czech Republicof the Czech Republicof the Czech Republic
History: A registration of congenital malformationbegan in 1961 and regular monitoring started in1975. The programme was a founding member ofthe International Clearinghouse and is a full mem-ber.
Size and coverage: All births in the Czech Republic(Bohemia, Moravia and Silesia regions) are covered,at present comprising approximately 90,000 annualbirths. Stillbirths weighting at least 1,000g are in-cluded.
Legislation and funding:Reporting is compulsory.The registration is financed and run by the govern-ment in the Institute of Health Information and Sta-tistics of the Czech Republic. Analysis of data issupported by Grant projects of Grant Agency Min-istry of Health of the Czech Republic in the Institutefor Care of Mother and Child.
Sources of ascertainment:Reports are obtainedfrom delivery units, neonatal, pediatric, child sur-gery, pathology departments and cytogenetic labo-ratories. Reporting to the central registry occurs viaRegional Department of Institute of Health Informa-tion and Statistics.
Exposure information: Some exposure informationis available on malformed infants, at present noneon controls.
Background information: Information’s on all birthsare available in the Institute of Health Informationand Statistics of the Czech Republic.
Address for further information: Antonin Sipek,Department of Population Teratology, Institute forCare of Mother and Child, Podolske nabr. 157,147 10 Prague 4, Czech Republic.Phone:420-2-612142410, Fax: 420-2-61213851E-mail: [email protected]
Contributing Monitoring Systems
28
England and Wales
The National Congenital Anomaly SystemThe National Congenital Anomaly SystemThe National Congenital Anomaly SystemThe National Congenital Anomaly SystemThe National Congenital Anomaly System
History: The monitoring programme was started in1964. It was a founding member of the InternationalClearinghouse and is a full member.
Size and coverage: All births in England and Walesare covered, at present approximately 650,000 an-nually. Stillbirths of 24 weeks or more gestation areregistered.
Legislation and funding: Reporting is voluntary. Thesystem is financed by the governmental Office forNational Statistics.
Sources of ascertainment: Reports are mainly basedon notifications of births prepared by attendants atbirth, either physicians or midwives, supplementedby other reports from neonatal intensive care units,special care baby units etc. For Wales and the Trentregion cases are received from the regional regis-ters which use several sources including cytogenticlaboratories, pathology, paediatrics, surgery, etc.
Exposure information: Parents’ occupation isknown. No other information on other exposures isavailable but can be retrieved ad hoc from generalpractitioners.
Background information: Information on all births isavailable from birth certificates.
Address for further information: Beverley J Botting,Office for National Statistics, B5/11, 1 DrummondGate, London SW1V 2QQ, UK.Phone: 44-71-5335195, Fax: 44-71-5335635E-mail: [email protected]
Contributing Monitoring Systems
Finland
The Finnish Register of Congenital MalformationsThe Finnish Register of Congenital MalformationsThe Finnish Register of Congenital MalformationsThe Finnish Register of Congenital MalformationsThe Finnish Register of Congenital Malformations
History: The registry was established in 1963 andregular monitoring started in 1977. It was a found-ing member of the International Clearinghouse andis a full member.
Size and coverage: All births in Finland are cov-ered, at present approximately 60,000 annually.Stillbirths of 22 weeks or more are registered. As aresearch project selective terminations for fetal rea-sons and spontaneous abortions with malformationshave also been included since 1993.
Legislation and funding: Reporting is compulsory.The registry is run and financed by the governmen-tal National Research and Development Centre forWelfare and Health.
Sources and ascertainment: Reports are obtainedfrom delivery units, neonatal, pediatric and pathol-ogy departments, death certificates and cytoge-netic laboratories. Case information is also receivedfrom the national Medical Birth Register, AbortionRegister and Hospital Discharge Register.
Exposure information: Until 1986, extensive expo-sure information was obtained from maternity healthcenters and by personal interview for selected mal-formations and their controls. In 1987-1992 onlyparental occupation was reported. Exposure infor-mation, like maternal occupation, drug use, X-raysand diseases, etc. has been obtained since 1993.Some exposure information on all births is also avail-able in the Medical Birth Register since 1987.
Background information: Epidemiological back-ground data are available on all births in the Medi-cal Births Register and in the Statistics Finland.
Address for further information: Annukka Ritvanen,The National Research and Development Centrefor Welfare and Health, Unit for Statistics and Reg-isters, Siltasaarenkatu 18 A, P. O. Box 220, SF-00531Helsinki, Finland.Phone: 358-9-39672376, Fax: 358-9-39672324E-mail: [email protected]
29
France, Central-East
Central-East France Register of CongenitalCentral-East France Register of CongenitalCentral-East France Register of CongenitalCentral-East France Register of CongenitalCentral-East France Register of CongenitalMalformationsMalformationsMalformationsMalformationsMalformations
History: The registry began in 1973 within the Rhone-Alps area -the Auvergne region was added in 1983,the Jura area in 1985, the Côte d’Or & Nièvre in1989 and Saône-et-Loire in 1990. The programmewas a founding member of the InternationalClearinghouse and is a full member. In 1998 theregistry was split up and the Auvergne region, be-came financially independent, under the responsi-bility of Christine Francannet. The collaborationbetween Auvergne and the rest of the FCE-registryis maintained and common results are published.
Size and coverage: The registry covers all births inthe area approximately 100,000 births annually,which represents about 13%.of all births in France.Stillbirths of 22 weeks or more gestation are in-cluded.
Legislation and funding: Reporting is voluntary. Thesystem is run by a privately funded research organi-sation. It is now officially recognised by the FrenchMinistry of Health and partially supported by an an-nual grant for the National Committee of Registries.
Sources of ascertainment: Reports are receivedfrom delivery units, pediatric and child surgery clin-ics, pathology departments, and cytogenetic labo-ratories. Infants up to the age of one are registered,as well as fetus delivered after medical abortion.
Exposure information: Information on maternal andpaternal occupation, drug use, diseases, etc. arecollected by interviews of the mothers of the mal-formed infants. No controls are interviewed.
Background information: Some background infor-mation is available from the general populationstatistics.
Address for further information: Elisabeth Robert,Institute Européen des Génomutations, 86 RueEdmond Locard, F-69005 Lyon, France.Phone: 33-478-258210, Fax: 33-478-366182E-mail: [email protected]
Contributing Monitoring Systems
FFFFFrance, Prance, Prance, Prance, Prance, Parisarisarisarisaris
France: ParisFrance: ParisFrance: ParisFrance: ParisFrance: Paris
History: The registry was started in 1975 but has beenreally efficient in 1980. It became an associate mem-ber of the International Clearinghouse in 1982.
Size and coverage: All births in Paris are eligible forinclusion, at present approximately 37,000 annu-ally which represents about 6% of the births inFrance. Stillbirths of at least 22weeks gestation areregistered and from 1994, induced terminationsafter prenatal diagnosis of birth defects are system-atically included. On the whole, the estimation ofthe coverage of the registry is 95%.
Legislation and funding: Reporting is voluntary. Theregistry is associated with the NationalInstitute ofHealth and Medical Research (INSERM), officiallyrecognised and partly financially supported by theINSERM and the Ministry of Health (National HealthAuthority Department).
Sources of ascertainment: Reports are actively col-lected from obstetrical and delivery units, pediatricdepartments (up to the age of one month), cytoge-netic laboratories and foetopathological depart-ments and from the Medical Neonatal TransportService. Notifications from delivery units andpediatric departments are linked to the health cer-tificates of the first week and the nine month of life.
Exposure information: Informations on maternaldrug use, maternal and paternal diseases and oc-cupation, outcome of previous pregnancies, arerecorded for the reported malformed cases.
Prenatal diagnosis information: Technics on prena-tal screening (ultrasound, serum markers) and pre-natal diagnosis, the dates which they are performed,are systematically recorded.
Background information: Background data on birthsare available from the National Institute of Statis-tics (INSEE).
Address for further information: Janine Goujard,INSERM U 149, 123 Bd de Port-Royal, 75014 Paris,France.Phone: 33-1-42345575, Fax: 33-1-43268979E-mail: [email protected]
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France, Strasbourg
Strasbourg Prospective Study of CongenitalStrasbourg Prospective Study of CongenitalStrasbourg Prospective Study of CongenitalStrasbourg Prospective Study of CongenitalStrasbourg Prospective Study of CongenitalMalformationsMalformationsMalformationsMalformationsMalformations
History: The registry was started in 1979. The pro-gramme became an associate member of the In-ternational Clearinghouse in 1982.
Size and coverage: All births in an area includingand around Strasbourg and the Bas-Rhin are cov-ered - 13,000 to 13,500 annually, or 1.8% of all birthsin France.
Legislation and funding: The programme is a re-search program, recognized by the local healthauthorities and funded by Social Security. Ministryof Health, and INSERM.
Sources of ascertainment: Reports are obtainedfrom pediatricians examining the newborn infants.A control infant is selected for each malformed one:the next infant of the same sex as the proband bornat that hospital.
Exposure information: Detailed information on vari-ous exposures is obtained by interview of the moth-ers of the malformed infants and their controls. Thechildren are followed to the age of one year.
Background information: General demographic in-formation is obtained from the National Institute ofStatistics. Further information is obtained from So-cial Security Records and Health Sheets.
Address for further information: Claude Stoll, Serv-ice de Génétique Médicale, Hôpital de Hautepierre,Avenue Molière, 67098 Strasbourg Cedex, France.Phone: 33-3-88128120, Fax: 33-3-88128125E-mail: [email protected]
Contributing Monitoring Systems
Hungary
Hungarian Congenital Abnormality RegistryHungarian Congenital Abnormality RegistryHungarian Congenital Abnormality RegistryHungarian Congenital Abnormality RegistryHungarian Congenital Abnormality Registry
History: Centralised registration of congenital ab-normalities was begun in 1962, under our co-ordi-nation in 1970, and monitoring began in 1973. Theprogramme was a founding member of the Interna-tional Clearinghouse and is a full member.
Size and coverage: The registry covers all births inHungary, approximately 120,000 annually. Criteriato define stillbirth was changed in 1998. At present,stillbirths of at least 24 weeks gestation or 500grams are registered. Prenatally diagnosed andterminated fetuses are also registered.
Legislation and funding: Reporting is compulsory.The registry is run and financied by the governmen-tal National Center for Epidemiology (past NationalInstitute of Public Health).
Sources of ascertainment: Reports are obtainedfrom delivery units, neonatal and pediatric surgery,pathology and prenatal diagnostic centres. Abnor-malities detected before the age of one are re-ported. Variations in figures (especially after 1990)compared to the previous years do not necessarilyreflect discipline (the duty of registration), in spiteof that notification is obligatory, in most cases de-creases can be noticed in the rates of birth defects.
Exposure information: Exposure information is avail-able only since 1980, when a case-control systemwas initiated in which mothers of selected mal-formed infants and controls are interviewed.
Background information: General background in-formation on all births is available from centralstatistics.
Address for further information: Csaba Siffel,Department of Human Genetics and Teratology,National Center for Epidemiology, Gyali ut 2-6.,H-1966 Budapest, Pf. 64., Hungary.Phone/fax: 36-1-215 5773E-mail: [email protected]
31
Ireland, Dublin
Dublin EUROCAT RegistryDublin EUROCAT RegistryDublin EUROCAT RegistryDublin EUROCAT RegistryDublin EUROCAT Registry
History: Register began in September 1979 andjoined EUROCAT at the same time. Joined Interna-tional Clearinghouse in 1997.
Size and coverage: The Registry is population-based and situated in the East of Ireland coveringthe counties of Dublin, Wicklow and Kildare. Aboutone third (20,000 births) of all births in Ireland occurin this area.
Legislation and funding: The Registry is locatedwithin the Public Health Department of EasternHealth Board. Staffing includes a full time nurse/researcher and a part time secretary plus a part-time public health specialist and a part-time epi-demiologist. Funding is provided by the Depart-ment of Health through the Eastern Health Board.There is a Steering Committee comprising special-ists from each of Maternity and Paediatric Hospi-tals in the catchment plus a representative from theDepartment of Health.
Sources of ascertainment: All live and still birthsare covered. Abortion is illegal in Ireland.
Address for further information: Zachary Johnson,Eastern Health Board, Dr. Stevens Hospital,Ireland – Dublin.Phone:353-1-635-2752, Fax:353-1-6795061E-mail: [email protected]
Contributing Monitoring Systems
Israel,IBDMS
Israel Birth Defects Monitoring SystemIsrael Birth Defects Monitoring SystemIsrael Birth Defects Monitoring SystemIsrael Birth Defects Monitoring SystemIsrael Birth Defects Monitoring System
History: The programme started in one hospital in1966 and was a founding member of the Interna-tional Clearinghouse. It was a full member until 1986,when it became an associate member.
Size and coverage: Reports are now obtained fromthree hospitals located in the central region of thecountry, with approximately 20,000 annual births(more than 15% of all births in Israel: IBDMS). Still-births of 28 weeks or more gestation are included.The registry of termination of pregnancy beganin 1995.
Legislation and funding: The programme is a re-search programme supported by research grantswithout any governmental support.
Sources of ascertainment: Reporting is voluntary.Reports are obtained from delivery units andneonatal departments in the participating hospi-tals. The three included hospitals are: Rabin Medi-cal Center, Beilinson Campus’ Petah Tikva; KaplanHospital, Rehovot (Dr, Kohan Dr, Shinwell) and LisMedical Center, Tel Aviv (Prof. Mimouni).
Exposure information: Complete anamneses is ob-tained by interviews of mothers of all malformedinfants. All the other women with normal newbornscomplete a similar form at discharge.
Background information: Epidemiological informa-tion on all births occurring in the participating hos-pitals is available.
Address for further information: Paul Merlob,Department of Neonatology, Rabin Medical Center,Beilinson Campus, 49100 Petah Tikva, Israel:IBDMS.Phone: 972-3-9377473/2Fax: 972-3-9220068 / 9219685E-mail: [email protected]
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Italy, BDRCam
Birth Defects Registry of CampaniaBirth Defects Registry of CampaniaBirth Defects Registry of CampaniaBirth Defects Registry of CampaniaBirth Defects Registry of Campania
History: The registry started in 1991.
Size and coverage: The programme is based on re-porting from hospitals distributed in Campania, asouthern Italy region. Naples is main city. Initially 38hospitals reported and the annual number of birthswas 38,000. At the present time, 60 hospitals partici-pate, covering approximately 50.000 annual births orapproximately 75% of all births. Stillbirths are included.The programme become an associate member of theInternational Clearinghouse in 1996.
Legislation and funding: The programme is a sur-veillance programme supported by grants fromRegional Health Authorities. Participation was vol-untary up to 1995. From 1996 participation is man-datory and the programme population based.
Sources of ascertainment: Reports are obtainedfrom delivery units and pediatric clinics at the par-ticipating hospitals. For selected malformationsmultiple sources are used with follow-up to one yearusing specific records from pediatric specialtiesdepartment dealing with malformed infants.
Exposure information: For each malformed infantreported, information is given on certain exposures,including maternal drug usage and parental occu-pation. Up to now no information on controls isavailable.
Background information: Up to now little backgroundinformation is given on certain exposures, includingmaternal drug usage and parental occupation. Up tonow no information on controls is available.
Address for further information: GioacchinoScarano, Registro Campano Difetti Congeniti c/oOsservatorio Epidemiologico Regionale, RegioneCampania, Via S. Lucia, 81-81100 Naples, Italy.Phone: 39-081-7962531/7962532Fax: 39-0825-203455E-mail: [email protected]
Contributing Monitoring Systems
Italy, IMER
Emilia-Romagna Registry of Congenital of MalformationsEmilia-Romagna Registry of Congenital of MalformationsEmilia-Romagna Registry of Congenital of MalformationsEmilia-Romagna Registry of Congenital of MalformationsEmilia-Romagna Registry of Congenital of Malformations
History: The registry started in 1978 in a few hospitalsand has increased in size to now include 44 deliveryunits. The programme joined the InternationalClearinghouse in 1985 as an associate member.
Size and coverage: The programme is population-based (about 95% of all births in the Emilia-Romagna region) and covers approximately 28,000annual births. Stillbirths of 28 weeks or more gesta-tion are included.
Legislation and funding: The programme is recog-nised and financed by the health authorities, theNational Research Council, and the Regional HealthCouncil. Hospital participation is voluntary.
Sources of ascertainment: Reporting is made byneonatologists and pediatricians during the firstweek of the infant’s life. Selected malformations arefollowed up.
Exposure information: Detailed exposure informa-tion is obtained by interviews of the mothers of mal-formed infants. For each malformed infant, a con-trol is chosen (the baby born before or after themalformed case in the same hospital) and its motheris interviewed in a similar way.
Background information: Some general demo-graphic information is known for all births in the area.For each participating hospital, the number oflivebirths and stillbirths are known.
Address for further information: Guido Cocchi,lstituto Clinico di Pediatria Preventiva eNeonatologia, Università di Bologna, Via Massarenti,11, 40138 Bologna, Italy.Phone: 39-051-342754 / 6363654Fax: 39-051-342754E-mail: [email protected]
33
Italy, North-East
North East Italy registry of Congenital MalformationsNorth East Italy registry of Congenital MalformationsNorth East Italy registry of Congenital MalformationsNorth East Italy registry of Congenital MalformationsNorth East Italy registry of Congenital Malformations
History: The Registry was established in 1981 toinclude the Veneto and Friuli Venezia Giulia regions.the Trentino Alto Adige region was added in 1990.The Registry became a member of Eurocat in1985,and an associate member of the InternationalClearinghouse in 1997.
Size and coverage: Reports are obtained from 78participating hospitals, with a total of approximately57,000 annual births; the actual coverage is esti-mated at 99%.
Legislation and funding: Reporting is voluntary. Theprogramme is partly run by privately funded re-search organisations and partly by Regional HealthAuthorities.
Sources of ascertainment: Reports are obtained onspecific forms from delivery units, induced abortionunits, pediatric, cardiology, ophthalmology andpathology departments, regional induced abortiondatabase and cytogenetic laboratories. 32 selectedmalformations are recorded within 7 days from birth(within 3 years of age for cardiovascular and oph-thalmological anomalies only). In terminated fetusesall anomalies are recorded. Two control infants areselected for each malformed one.
Exposure information: Detailed information on vari-ous exposures, including maternal or paternal oc-cupation, diseases and drug use is obtained byinterview of the mothers at the birth of the malformedinfants and their controls.
Background information: Some epidemiologicalbackground data of all births are available. For eachparticipating hospital the number of livebirths andstillbirths by sex and number of twin pairs are known.
Address for further information: Romano Tenconi,Clinical and Epidemiological Genetic Service,Pediatric Department, via Giustiniani 3,35128 Padova, Italy.Phone: 39-049-8213513, Fax: 39-049-8213513E-mail: [email protected]: www.genetica.pedi.unipd.it
Contributing Monitoring Systems
Italy, ISMAC
Sicilian Registry of Congenital MalformationsSicilian Registry of Congenital MalformationsSicilian Registry of Congenital MalformationsSicilian Registry of Congenital MalformationsSicilian Registry of Congenital Malformations
History: The Registry started in 1991 and becamea Clearinghouse associate member in 1996. Sicil-ian Registry is also member of EUROCAT and col-laborates with other Italian Registries under super-vision of Italian National Institut of Health – Rome.
Size and coverage: It is hospital based and actu-ally collaborates with four south-east provinces ofthe nine Sicilian provinces, (with a covering ratehigher than 75%) and with more than 19,000 con-trolled newborns for year.
Legislation and funding: The programme is on avoluntary basis, supported at local level byA.S.MA.C, Sicilian association for congenital mal-formations prevention.
Sources of ascertainment: Reports are obtainedfrom delivery units, pediatric units and otherspecialistic departments.
Exposure information: For each malformed reported(livebirth, stillbirth and voluntary abortion), informa-tion is given on certain exposures, including mater-nal drug usage and parental occupation. Up to nowno information on controls is available.
Address for further information: Sebastiano Biancaand Florindo Mollica, Clinica Pediatrica, Policlinico,Via Santa Sofia, 78 – 95123 Catania, Italy. SalvatoreMeli, I.S.MA.C. Viale A. Doria, 25 - 95125 Catania,Italy.Phone: 39-095-330533, Fax: 39-095-222532E-mail:[email protected]
34
Italy,Tuscany
TTTTTuscany Registry of Congenital Defectsuscany Registry of Congenital Defectsuscany Registry of Congenital Defectsuscany Registry of Congenital Defectsuscany Registry of Congenital Defects
History: The registry started in 1979 in the provinceof Florence and from 1992 in the whole Tuscany re-gion. The programme became a full member of theInternational Clearinghouse in 1998.
Size and coverage: The programme is populationbased, involves all the regional hospitals and thecoverage is around 95% of all births in the Tuscanyregion (approximately 3.5 millions inhabitants and25,000 births/year). Stillbirths of 20 weeks or moregestation and induced abortions after prenatal di-agnosis of birth defects are systematically included.Malformed babies diagnosed within the first year oflife are also registered.
Legislation and funding: The Registry is a surveil-lance programme included in the Regional Statis-tics System; it is formally recognised and supportedby the Tuscany Region Health Authority.
Sources and ascertainment: Multiple sources areused to ascertain malformed infants; records areobtained from all obstetrical and maternity units,pediatric departments, neonatal and pediatric sur-gery units, prenatal diagnostic centers and pathol-ogy services. Mothers are interviewed by using astandardized questionnaire.
Exposure information: Exposure information onmaternal and paternal occupation, life-style, andsocio-economical characteristics are obtained byinterviews of mothers of malformed infants.
Background information: Vital statistics and otherepidemiological information are obtained by thebirth medical records collected by the RegionalBureau of Statistics. Selected information is ob-tained from the control material collected.
Address for further information: Fabrizio Bianchi,Reparto Epidemiologia e Biostatistica, Istituto diFisiologia del Consiglio Nazionale delle Ricerche,Via Trieste, 41, 56126 Pisa, Italy.Phone:39-050-21282, Fax:39-050-503596E-mail: [email protected]
Contributing Monitoring Systems
Japan, JAOG
Japan Association of Maternal Welfare (Until 1994)Japan Association of Maternal Welfare (Until 1994)Japan Association of Maternal Welfare (Until 1994)Japan Association of Maternal Welfare (Until 1994)Japan Association of Maternal Welfare (Until 1994)Japan Association of Obstetricians andJapan Association of Obstetricians andJapan Association of Obstetricians andJapan Association of Obstetricians andJapan Association of Obstetricians andGynecologistsGynecologistsGynecologistsGynecologistsGynecologists
History: The programme started in 1972 and a fullmember of the International Clearinghouse in1988.
Size and coverage: The programme is based onreports from 270 hospitals throughout Japan. Atpresent, approximately 100,000 births are covered,representing about 9 % of all Japanese births. Still-births of 22weeks or more gestation are included.
Legislation and funding: The programme is a re-search programme acknowledged by the Ministryof Welfare and Health and supported by JAOG.
Sources of ascertainment: Reports are obtainedfrom delivery units and pediatric clinics of partici-pating hospitals.
Exposure information: Detailed information on vari-ous exposures including maternal or paternal oc-cupation, chronic diseases and drug use, X-ray andviral infections are available.
Background information: Basic epidemiologicalinformation on all births is available from each par-ticipating hospitals.
Address for further information: Yoshio Sumiyoshi,JAOG, Yokohama City University, Urafune Hospi-tal,3-46, Urafune-cho, Minami-ku, Yokohama,232-0024, Japan.Phone: 81-45-2533668, Fax: 81-45-2533668E-mail: [email protected]
35
Mexico, RYVEMCE
Mexican Registry and Epidemiological Surveil-Mexican Registry and Epidemiological Surveil-Mexican Registry and Epidemiological Surveil-Mexican Registry and Epidemiological Surveil-Mexican Registry and Epidemiological Surveil-lance of External Congenital Malformationslance of External Congenital Malformationslance of External Congenital Malformationslance of External Congenital Malformationslance of External Congenital Malformations
History: The programme was started in 1978. Theprogramme became a full member of the Interna-tional Clearinghouse in 1980.
Size and coverage: Reports are obtained from 15hospitals in 11 cities in Mexico. Participation is vol-untary. The annual number of births is approximately40,000, about 3.5% of all births in Mexico.Stillbnirths of 20 weeks or more gestation and/or atleast 500g birthweight are included.
Legislation and funding: The programme is a re-search programme and is funded by researchgrants.
Sources of ascertainment: Reports are obtainedfrom the delivery units and pediatric departmentsof the participating hospitals.
Exposure information: The mother of each reportedinfant and the mother of a control infant-the nextnon-malformed infant born at that hospital with thesame sex as the proband - are interviewed on vari-ous exposures, including drug usage and parentaloccupation.
Background information: The total number of birthsin the hospitals is known.
Address for further information: Osvaldo Mutchinick,Departamento de Genetica, Instituto Nacional deNutricion, Salvador Zubiran, Vasco de Quiroga 15,Tlalpan, 14000 Mexico, D.F., Mexico.Phone: 52-5-5731200/ 52-5-5730611, 52-5-5737333(ext 2426, 2425)Fax: 52-5-6556138E-mail: [email protected]
Contributing Monitoring Systems
New Zealand
New Zealand Congenital Anomalies MonitoringNew Zealand Congenital Anomalies MonitoringNew Zealand Congenital Anomalies MonitoringNew Zealand Congenital Anomalies MonitoringNew Zealand Congenital Anomalies MonitoringProgrammeProgrammeProgrammeProgrammeProgramme
History: The programme began in 1975 and be-came a full member of the InternationalClearinghouse in 1979.
Size and coverage: The programme covers alllivebirths (approximately 56,000 per year) deliveredin a New Zealand publicly funded hospital. Onlythese data are included in the quarterly and annualreports to the International Clearinghouse. Data onstillbirths are retrospectively added to the databasetogether with additional cases derived from thenational perinatal and mortality databases.
Legislation and funding: The programme is run andfunded by the Central Regional Health Authority.Reporting is compulsory. Reports are obtained de-liveries from public hospitals.
Sources of ascertainment: Reports are based onbirth notification forms for deliveries inside our out-side hospitals and on discharge diagnoses.
Exposure information: No exposure information arecurrently available, but attempts are being madeto obtain such data as well as increase the level ofascertainment.
Background information: General epidemiologicalcharacteristics for all births are available.
Address for further information: Barry Borman,Central Regional Health Authority, Public HealthGroup, 155 The Terrace, PO Box 1 10-097,Wellington, New Zealand.Phone: 64-4-4727633, Fax: 64-4-4727639E-mail: [email protected]
36
Northern Netherlands
EUROCAT registration Northern NetherlandsEUROCAT registration Northern NetherlandsEUROCAT registration Northern NetherlandsEUROCAT registration Northern NetherlandsEUROCAT registration Northern Netherlands
History: The programme started in 1981, and be-came a Clearinghouse member in 1993 as an asso-ciate member.
Size and coverage: In the beginning the programmecovered 7,500 births annually. Coverage wasgradually increased to 19,000 births annually in theprovinces Groningen, Friesland and Drenthe from1989 onwards. Home deliveries (30% of births) areincluded.
Legislation and funding: The programme is fundedby the Dutch Ministry of Public Health, Welfare andSports. The registry is carried out in the Depart-ment of Medical Genetics of the University ofGroningen.
Sources of ascertainment: Obstetricians, paedia-tricians, clinical geneticists, surgeons, general prac-titioners, midwives, well-baby clinics, pathologistsand the national obstetric registry send informationto the registry on a voluntary basis. Informed con-sent of the parents is needed. Registry personnel isactively involved in data collection. No age limitsare applied.
Exposure information: Since 1997 parents areasked to fill out a questionnaire including questionson occupational activities and drug use. Besides,data from community pharmacies are used to col-lect maternal drug exposure data.
Background information: General statistics areavailable from the Dutch Central Bureau of Statis-tics (CBS).
Address for further information: Martina C. Cornel,Department of Medical Genetics, Ant. Deusinglaan4, 9713 AW Groningen, The Netherlands.Phone: 31-50-3633238/3632952Fax: 31-50-3187268E-mail: [email protected]
Norway
Medical Birth Registry of NorwayMedical Birth Registry of NorwayMedical Birth Registry of NorwayMedical Birth Registry of NorwayMedical Birth Registry of Norway
History: The programme was started in 1967. Theprogramme was a founding member of the Interna-tional Clearinghouse and is a full member.
Size and coverage: The programme covers all birthsin Norway, approximately 60,000 annual births. Still-births of 16 weeks or more gestation are included.
Legislation and funding: The programme is run andfunded by the governmental National Institute ofPublic Health. Reporting is compulsory.
Sources of ascertainment: The registry is based onthe notification of births from the delivery units.
Exposure information: Some basic information, suchas maternal disease, is collected on all infants,malformed or not.
Background information: All information availablefor the reported malformed infants is also availablefor the total population of births.
Address for further information: Lorentz M. Irgens,Medical Birth Registry of Norway, Armauer HansenBldg, Haukeland Hospital, N-5021 Bergen, Norway.Phone: 47-5-5974667, Fax: 47-55-974998E-mail: [email protected]
Contributing Monitoring Systems
37
South Africa, SABDSS
South African Birth Defects Surveillance SystemsSouth African Birth Defects Surveillance SystemsSouth African Birth Defects Surveillance SystemsSouth African Birth Defects Surveillance SystemsSouth African Birth Defects Surveillance Systems
History: The programme started in 1988 and be-came a full member of the InternationalClearinghouse in 1992.
Size and coverage: The programme is hospitalbased covering 11 sentinel sites over the countrywith approximately 75,000 annual or 5% of all birthsin South Africa.
Legislation and Funding: The programme is fundedby the Department of National Health. Participa-tion in the programme is voluntary.
Sources of ascertainment: Reports are obtainedfrom delivery units and paediatric units of the par-ticipating hospitals.
Exposure information: No exposure information isroutinely available.
Background information: Total births for some par-ticipating hospitals are not accurately known.
Address for further information: Rauf Sayed, Depart-ment of Community Health, Medical School,University of Cape Town, Observatory 7925,South Africa.Phone: 27-21-4066486, Fax: 27-21-4066163E-mail: [email protected]
Contributing Monitoring Systems
South America, ECLSouth America, ECLSouth America, ECLSouth America, ECLSouth America, ECLAMCAMCAMCAMCAMC
Latin American Collaborative Study of Congeni-Latin American Collaborative Study of Congeni-Latin American Collaborative Study of Congeni-Latin American Collaborative Study of Congeni-Latin American Collaborative Study of Congeni-tal Malformationstal Malformationstal Malformationstal Malformationstal Malformations
History: The programme started in 1967 and hasgrown in size and coverage. The programmebecame a full member of the InternationalClearinghouse in 1977.
Size and coverage: The number of participatinghospitals has grown from 20 in 1977 to 70 at thepresent time, distributed over most South Ameri-cans countries. The annual number of births cov-ered is at present approximately 150,000, less than1% of all births. Stillbirths of at least 500gbirthweight have been included since 1978.
Legislation and funding: The programme is a re-search programme with voluntary participation ofhospitals and funded by research grants providedfrom several sources, mainly the national researchcouncils of Argentina and Brazil..
Sources of ascertainment: Reporting is made bycollaborating pediatricians at the delivery units ofparticipating hospitals.
Exposure information: The mother of each reportedinfant and the mother of a control infant - the nextnon-malformed infant born at that hospital with thesame sex as the proband - are interviewed on vari-ous exposures, including drug usage and parentaloccupation.
Background information: Background informationis obtained partly from summarising tables of birthsin each participating hospitals, partly from thematched control newborns.
Address for further information: Eduardo Castilla,ECLAMC/Dept. Genetica/FIOCRUZ, C.P. 926,20010-970 Rio de Janeiro, Brazil.Phone: 55-21-5984358, Fax: 55-21-2604282E-mail: [email protected]
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Spain, ECEMC
Spanish Collaborative Study of CongenitalSpanish Collaborative Study of CongenitalSpanish Collaborative Study of CongenitalSpanish Collaborative Study of CongenitalSpanish Collaborative Study of CongenitalMalformationsMalformationsMalformationsMalformationsMalformations
History: The programme started in 1976 as a hos-pital-based case-control study and surveillance sys-tem. It became a full member of the InternationalClearinghouse in 1979.
Size and coverage: Reports are obtained from hos-pitals (81 at present) distributed all over Spain. Theannual number of births is approximately 100,000,representing more than 26% of all Spanish births.Stillbirths of at least 500g or 24 weeks have beenincluded since 1980.
Legislation and funding: It is a research programmewith voluntary participation of hospitals and is fi-nanced mainly by the Spanish Administration, andpartially by non-governmental organisations.
Sources of ascertainment: The detection period isthe first 3 days of life, including major and/or minor/mild defects. Reports come from delivery units andpaediatric departments of the participating hospi-tals. Mothers are interviewed directly to fill in theECEMC standard protocols, which include morethan 300 data for each child (family history, demo-graphic and obstetrical data, prenatal exposures,etc), whether case or control (the next non-mal-formed infant born at that hospital with the samesex as the proband). In many instances, photo-graphs, imaging studies, karyotypes and other com-plementary studies are available.
Exposure information: The mother of each reportedinfant (case or control) is interviewed on variousexposures (parental occupation, maternal acute orchronic diseases, drug usage, exposure to otherchemical or physical factors) within the first 3 daysafter delivery.
Background information: Total number of births bysex and number of twin pairs in each participatinghospital are known. Other background informationis obtained from the control material.
Address for further information: Prof. María-LuisaMartínez-Frías, ECEMC, Facultad de Medicina,Universidad Complutense, 28040-Madrid, Spain.Phone: 34-1-3941587, Fax: 34-1-3941592E-mail: [email protected]
Contributing Monitoring Systems
Sweden
The Swedish Registry of Congenital Malforma-The Swedish Registry of Congenital Malforma-The Swedish Registry of Congenital Malforma-The Swedish Registry of Congenital Malforma-The Swedish Registry of Congenital Malforma-tions and the Medical Birth Registrytions and the Medical Birth Registrytions and the Medical Birth Registrytions and the Medical Birth Registrytions and the Medical Birth Registry
History: The Registry of Congenital Malformationsstarted in 1964, the Medical Birth Registry in 1973.The programme was a founding member of the In-ternational Clearinghouse and contributed withdata until 1994. The registry has a new regime from1999 and is since then again a full member of theInternational Clearinghouse.
Size and coverage: All births in Sweden are included,approximately 100,000-120,000 annual births. Thedefinition of stillbirth in Sweden is more than 28 weeks.Since 1999 all fetal deaths with congenital malforma-tions more than 22 weeks are reported to the SwedishRegistry of Congenital Malformations. In 1999 a spe-cial fetal congenital anomalies surveillance systemwas started to include those fetuses with congenitalmalformations who were terminated as a result of pre-natal diagnosis.
Legislation and funding: Reporting is compulsory. Theregistries are run by and funded by the National Boardof Health and Social Welfare (governmental).
Sources of ascertainment: Reports are receivedfrom delivery units, paediatric clinics, pathologydepartments, child cardiology clinics, and cytoge-netic laboratories.
Exposure information: Some exposure informationfor all births is available in the Medical Birth Regis-try; maternal occupation, socio-economic factors,maternal smoking, drug use during pregnancy, con-traceptive usage, maternal diseases.
Background information: Epidemiological back-ground data are available on all birth in the Medi-cal Birth Registry.
Addresses for further information: Anders Ericson,Department of Epidemiology, National Board of Healthand Social Welfare, S-106 30 Stockholm, Sweden.Phone: +48-8-7833265, Fax: +46-8-7833327E-mail: [email protected]öran Annerén, Department of Clinical Genetics,Uppsala University Children’s Hospital, S-751 85Uppsala, Sweden.Phone: +46-18-665942, Fax: +46-18-554025E-mail: [email protected]
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United Arab Emirates
Congenital Abnormality Study GroupCongenital Abnormality Study GroupCongenital Abnormality Study GroupCongenital Abnormality Study GroupCongenital Abnormality Study Group
History: The programme was started in 1992, re-mained dormant for a while but began continuousmonitoring in 1994. It is now as Associate Memberof the International Clearinghouse.
Size and coverage: The programme covers about8000 births a year occurring in three major hospi-tals of the Al Ain Medical District, situated in theeastern part of Abu Dhabi Emirate. It has a popula-tion of about 300,000. Still births with a weight ofonly more than 500 gm are included.
Legislation and funding: The programme is fundedby the Faculty of Medicine and Health Sciences ofthe UAE University. Efforts to procure additionalfunds have not been successful.
Source of ascertainment: In each hospital, there isa neonatologist who examines, identifies the ab-normalities and records at birth in a data collectionform provided. The diagnosis is further assisted bya clinical geneticist/dysmorphologist and Paedia-tricians.
Exposure information: Some basic information onexposure such as maternal disease is collected inall cases.
Background information: General epidemiologicaldata for all births are available.
Address for further information: Lihadh Al-Gazali,Program Director, Congenital Abnormality StudyGroup,Department of Paediatrics, Faculty of Medi-cine, UAE University, Al Ain, PO Box 17666, Al Ain,United Arab Emirates.Phone: 971-3-672000, Fax: 971-3-672022E-mail:(1) [email protected](2) [email protected]
Contributing Monitoring Systems
USA, Atlanta
Metropolitan Atlanta Congenital Defects ProgrammeMetropolitan Atlanta Congenital Defects ProgrammeMetropolitan Atlanta Congenital Defects ProgrammeMetropolitan Atlanta Congenital Defects ProgrammeMetropolitan Atlanta Congenital Defects Programme
History: The programme started in 1967. The pro-gramme was a founding member of the Interna-tional Clearinghouse and is a full member.
Size and coverage: The programme covers all birthsin Metropolitan Atlanta, USA. The approximate an-nual number of births is 35,000. Stillbirths of 20 weeksor more gestation and/or at least 500g birthweightare included.
Legislation and funding: The programme is run andfunded by the governmental Centres for Disease Con-trol (CDC). Data are retrieved by personnel from CDC.
Sources of ascertainment: Multiple sources areused to ascertain malformed infants born in thedefined area with a follow-up to one year’s age us-ing records from delivery units, pediatric depart-ments and other specialities dealind with mal-formed infants.
Exposure information: Through 1980, exposure in-formation was obtained by interviews of mothers ofreported malformed infants
Background information: Number of birth and somebasic epidemiological information are obtainedfrom vital statistics.
Address for further information: J. David Erickson,Centers for Disease Control and Prevention, Divi-sion of Birth Defects and Pediatric Genetics,Mailstop F45, 4770 Buford Highway NE, Atlanta,Georgia 30341, U.S.A.Phone: 1-770-4887160, Fax: 1-770-4887197E-mail: [email protected]
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USA,CaliforniaUSA,CaliforniaUSA,CaliforniaUSA,CaliforniaUSA,California
California Birth Defects Monitoring ProgrammeCalifornia Birth Defects Monitoring ProgrammeCalifornia Birth Defects Monitoring ProgrammeCalifornia Birth Defects Monitoring ProgrammeCalifornia Birth Defects Monitoring Programme
History: The California Birth Defects Monitoring Pro-gram (CBDMP) since its inception 15 years ago, isa public health program devoted to finding causesof birth defects. The Program is funded through theCalifornia Department of Health Services and jointlyoperated with the March of Dimes Birth DefectsFoundation. Programme is a associate member ofthe International Clearinghouse.
Size and coverage: The California Birth DefectsMonitoring Programme’s goal is to find causes ofbirth defects. To do this the programme operates apopulation-based registry among 300,000 birthsper year in California (1/2 of the state’s births) anddoes descriptive and case-control studies.
Legislation and funding: The California Birth De-fects Monitoring Program has been establishedunder Legislature Mandate Statutory Authority: Di-vision 102, Part 2, Chapter 1, Sections 1
Contributing Monitoring Systems
Sources of ascertainment: The CBDMP collects itsdata by sending its medical records abstrators to over200 hospitals and genetic centres in California to iden-tify children with birth defects identified pre-natallyuntil age 1. Birth defects under study include struc-tural congenital anomalies, and cerebral palsy. In 1998CBDMP will begin studying mental retardation andother neuro-developmental abnormalities.
Exposure information: The CBDMP’s large data base(currently 3,000,000 births under surveillance sincethe programme’s inception in 1983) insures adequatesample size to identify risk factors for birth defects.
Background information: A complete CBDMP Pub-lication list is available upon request. Address re-quests to: Jackie Wynne, MOD/CBDMP, 3031 “F”Street, Suite 200, Sacramento, CA 95816-3844.Phone: 1-916-443-0816 Ext 12 Fax: 1-916-443-6657
Address for further information: John A Harris,California Birth Defects, Monitoring Program,1900 Powell Street, Suite 1050, Emeryville,CA 94608, U.S.A.Phone: 1-510 6533303, Fax: 1-510 6531678E-mail: [email protected] or [email protected]