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Congenital Abnormalities and Preterm Birth Related to Maternal Illnesses During Pregnancy · · Nándor Ács Ferenc G. Bánhidy Andrew E. Czeizel Congenital Abnormalities and Preterm Birth Related to Maternal Illnesses During Pregnancy 123 NándorÁcs,MD,PhD FerencG.Bánhidy,MD,PhD SemmelweisUniversity SemmelweisUniversity SecondDepartmentofObstetrics SecondDepartmentofObstetrics andGynecology andGynecology Budapest1082,Üllo˝iút78/a Budapest1082,Üllo˝iút78/a Hungary Hungary [email protected] [email protected] AndrewE.Czeizel,MD,PhD,DSci FoundationoftheCommunityControl ofHereditaryDiseases Budapest1026 Törökvészlejto˝32 Hungary [email protected] ISBN978-90-481-8619-8 e-ISBN978-90-481-8620-4 DOI10.1007/978-90-481-8620-4 SpringerDordrechtHeidelbergLondonNewYork LibraryofCongressControlNumber:2010922898 ©SpringerScience+BusinessMediaB.V.2010 Nopartofthisworkmaybereproduced,storedinaretrievalsystem,ortransmittedinanyformorby anymeans,electronic,mechanical,photocopying,microfilming,recordingorotherwise,withoutwritten permissionfromthePublisher,withtheexceptionofanymaterialsuppliedspecificallyforthepurpose ofbeingenteredandexecutedonacomputersystem,forexclusiveusebythepurchaserofthework. Printedonacid-freepaper SpringerispartofSpringerScience+BusinessMedia(www.springer.com) Contents Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xvii TechnicalNotes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xxi PartI TheStudyPopulationandMethods 1 TheHungarianCongenitalAbnormalityRegistry(HCAR). . . . . 3 1.1 MaterialsandMethods . . . . . . . . . . . . . . . . . . . . . . 4 1.2 TheDataBaseoftheHCAR . . . . . . . . . . . . . . . . . . . 12 1.3 QualityControloftheHCAR . . . . . . . . . . . . . . . . . . 14 1.3.1 StudyPopulationsandSamples . . . . . . . . . . . . . 14 1.3.2 CompletenessofNotification . . . . . . . . . . . . . . 14 1.3.3 TheValidityofCA-Diagnoses . . . . . . . . . . . . . 15 1.4 TheWeaknessesoftheHCAR . . . . . . . . . . . . . . . . . . 18 1.5 TheHungarianCase-ControlSurveillanceofCongenital Abnormalities(HCCSCA) . . . . . . . . . . . . . . . . . . . . 20 1.5.1 StudyGroups . . . . . . . . . . . . . . . . . . . . . . 21 1.5.2 CollectionofExposureandOtherData . . . . . . . . . 21 1.5.3 ClassificationofCA-Groups . . . . . . . . . . . . . . 23 1.6 TheStrengthsandWeaknessesoftheHCCSCA . . . . . . . . . 30 1.6.1 TheMaternalDiseaseItself . . . . . . . . . . . . . . . 30 1.6.2 SourceofExposureInformation . . . . . . . . . . . . 31 1.6.3 TheTimeFactor . . . . . . . . . . . . . . . . . . . . . 32 1.6.4 ConfoundingFactors . . . . . . . . . . . . . . . . . . 38 1.6.5 TheEvaluationofPossibleRisk . . . . . . . . . . . . 42 1.7 PretermBirthandLowBirthWeightNewborns . . . . . . . . . 43 1.7.1 Definitions . . . . . . . . . . . . . . . . . . . . . . . . 45 1.7.2 TheHungarianDataofPretermBirths . . . . . . . . . 45 1.8 TheDataSetoftheHCCSCA,1980–1996 . . . . . . . . . . . 47 1.8.1 MaternalDiseases . . . . . . . . . . . . . . . . . . . . 48 1.8.2 StatisticalAnalysis . . . . . . . . . . . . . . . . . . . 49 1.9 BudapestMonitoringSystemofSelf-PoisoningPregnantWomen 56 1.10 FinalConclusions . . . . . . . . . . . . . . . . . . . . . . . . 57 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57 OwnPublications . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58 v vi Contents PartII ResultsofStudiesandTheirInterpretation 2 CertainInfectiousandParasiticDiseases . . . . . . . . . . . . . . . 65 2.1 Intestinal Infectious Diseases with the Leading SymptomofDiarrhea. . . . . . . . . . . . . . . . . . . . . . . 67 2.1.1 Salmonellosis(SalmonellaGastroenteritis) . . . . . . . 67 2.1.2 InfectiousDiarrhea . . . . . . . . . . . . . . . . . . . 68 2.2 Tuberculosis . . . . . . . . . . . . . . . . . . . . . . . . . . . 73 2.2.1 InterpretationofDataintheHCCSCA . . . . . . . . . 74 2.3 Varicella(Chickenpox)andHerpesZoster . . . . . . . . . . . . 74 2.3.1 ResultsoftheStudy(X). . . . . . . . . . . . . . . . . 75 2.3.2 InterpretationofResults. . . . . . . . . . . . . . . . . 76 2.4 HerpesSimplex . . . . . . . . . . . . . . . . . . . . . . . . . . 77 2.4.1 OrofacialHerpes . . . . . . . . . . . . . . . . . . . . 77 2.4.2 GenitalHerpes . . . . . . . . . . . . . . . . . . . . . 82 2.5 Measles(Rubeola,Morbilli) . . . . . . . . . . . . . . . . . . . 86 2.5.1 InterpretationofDataintheHCCSCA . . . . . . . . . 87 2.6 Rubella . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87 2.6.1 InterpretationofDataintheHCCSCA . . . . . . . . . 88 2.7 ViralHepatitis . . . . . . . . . . . . . . . . . . . . . . . . . . 89 2.7.1 InterpretationofDataintheHCCSCA . . . . . . . . . 91 2.8 Mumps . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91 2.8.1 InterpretationofDataintheHCCSCA . . . . . . . . . 92 2.9 ViralGenitalWarts(CondylomataAcuminata) . . . . . . . . . 92 2.9.1 ResultsoftheStudy(XVII) . . . . . . . . . . . . . . . 93 2.10 Cytomegalovirus . . . . . . . . . . . . . . . . . . . . . . . . . 93 2.10.1 InterpretationofDataintheHCCSCA . . . . . . . . . 95 2.11 OtherorUnspecifiedViralInfections . . . . . . . . . . . . . . 95 2.11.1 InterpretationofDataintheHCCSCA . . . . . . . . . 95 2.12 Syphilis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 98 2.12.1 InterpretationofDataintheHCCSCA . . . . . . . . . 99 2.13 GonococcalInfection . . . . . . . . . . . . . . . . . . . . . . . 99 2.13.1 InterpretationofDataintheHCCSCA . . . . . . . . . 100 2.14 Dermatomycosis . . . . . . . . . . . . . . . . . . . . . . . . . 100 2.14.1 InterpretationofDataintheHCCSCA . . . . . . . . . 100 2.15 Toxoplasmosis . . . . . . . . . . . . . . . . . . . . . . . . . . 101 2.15.1 InterpretationofDataintheHCCSCA . . . . . . . . . 102 2.16 Ascaris . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103 2.16.1 InterpretationofDataintheHCCSCA . . . . . . . . . 103 2.17 Scabies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 104 2.17.1 InterpretationofDataintheHCCSCA . . . . . . . . . 104 2.18 FinalConclusions . . . . . . . . . . . . . . . . . . . . . . . . 104 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105 OwnPublications . . . . . . . . . . . . . . . . . . . . . . . . . . . . 109 Contents vii 3 Neoplasms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111 3.1 BreastCancer . . . . . . . . . . . . . . . . . . . . . . . . . . . 111 3.1.1 InterpretationofDataintheHCCSCA . . . . . . . . . 111 3.2 CervicalCancer. . . . . . . . . . . . . . . . . . . . . . . . . . 112 3.2.1 InterpretationofDataintheHCCSCA . . . . . . . . . 112 3.3 ThyroidCancer . . . . . . . . . . . . . . . . . . . . . . . . . . 112 3.3.1 InterpretationofDataintheHCCSCA . . . . . . . . . 113 3.4 UterineLeiomyoma . . . . . . . . . . . . . . . . . . . . . . . 113 3.4.1 ResultsoftheStudy(I) . . . . . . . . . . . . . . . . . 113 3.4.2 InterpretationofResults. . . . . . . . . . . . . . . . . 114 3.5 Others . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114 3.6 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116 OwnPublications . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116 4 DiseasesoftheBloodandBlood-FormingOrgans . . . . . . . . . . 117 4.1 Anemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117 4.1.1 ResultsoftheStudy(I) . . . . . . . . . . . . . . . . . 117 4.1.2 InterpretationofResults. . . . . . . . . . . . . . . . . 120 4.2 VonWillebrand’sDisease . . . . . . . . . . . . . . . . . . . . 122 4.2.1 InterpretationofDataintheHCCSCA . . . . . . . . . 122 4.3 Others . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122 4.4 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122 OwnPublications . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123 5 Endocrine,NutritionalandMetabolicDiseases . . . . . . . . . . . 125 5.1 ThyroidDiseasesinPregnancy . . . . . . . . . . . . . . . . . . 125 5.2 SimpleGoiter . . . . . . . . . . . . . . . . . . . . . . . . . . . 127 5.2.1 InterpretationofDataintheHCCSCA . . . . . . . . . 127 5.3 Hypothyroidism . . . . . . . . . . . . . . . . . . . . . . . . . 127 5.3.1 InterpretationofDataintheHCCSCA . . . . . . . . . 128 5.4 Hyperthyroidism . . . . . . . . . . . . . . . . . . . . . . . . . 129 5.4.1 ResultsoftheStudy . . . . . . . . . . . . . . . . . . . 129 5.4.2 InterpretationofResults. . . . . . . . . . . . . . . . . 131 5.5 CarbohydrateMetabolism . . . . . . . . . . . . . . . . . . . . 132 5.6 DiabetesMellitus . . . . . . . . . . . . . . . . . . . . . . . . . 132 5.6.1 ResultsoftheStudy(IV,V) . . . . . . . . . . . . . . . 135 5.6.2 InterpretationofResults. . . . . . . . . . . . . . . . . 139 5.7 Obesity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 142 5.7.1 InterpretationofDataintheHCCSCA . . . . . . . . . 142 5.8 Others . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 143 5.8.1 Hyperparathyroidism . . . . . . . . . . . . . . . . . . 143 5.8.2 DiabetesInsipidus . . . . . . . . . . . . . . . . . . . . 143 5.8.3 Cushing’sSyndrome . . . . . . . . . . . . . . . . . . 143 5.8.4 AddisonDisease. . . . . . . . . . . . . . . . . . . . . 144 5.8.5 WilsonDisease . . . . . . . . . . . . . . . . . . . . . 144 viii Contents 5.9 FinalConclusion . . . . . . . . . . . . . . . . . . . . . . . . . 144 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 144 OwnPublications . . . . . . . . . . . . . . . . . . . . . . . . . . . . 146 6 MentalandBehaviouralDisorders . . . . . . . . . . . . . . . . . . 149 6.1 Schizophrenia. . . . . . . . . . . . . . . . . . . . . . . . . . . 149 6.1.1 InterpretationofDataintheHCCSCA . . . . . . . . . 150 6.2 Manic-DepressionDisorders . . . . . . . . . . . . . . . . . . . 150 6.2.1 InterpretationofDataintheHCCSCA . . . . . . . . . 151 6.3 PanicDisorders . . . . . . . . . . . . . . . . . . . . . . . . . . 151 6.3.1 ResultsoftheStudy(I,II). . . . . . . . . . . . . . . . 152 6.3.2 InterpretationoftheResults . . . . . . . . . . . . . . . 156 6.4 OtherAnxietyDisorders . . . . . . . . . . . . . . . . . . . . . 159 6.4.1 InterpretationofDataintheHCCSCA . . . . . . . . . 159 6.5 AlcoholDependenceSyndromeandDrunkenness . . . . . . . . 159 6.5.1 InterpretationofDataintheHCCSCA . . . . . . . . . 159 6.6 MentalRetardation . . . . . . . . . . . . . . . . . . . . . . . . 160 6.6.1 InterpretationofDataintheHCCSCA . . . . . . . . . 160 6.7 FinalConclusions . . . . . . . . . . . . . . . . . . . . . . . . 160 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 160 OwnPublications . . . . . . . . . . . . . . . . . . . . . . . . . . . . 162 7 DiseasesoftheNervousSystem . . . . . . . . . . . . . . . . . . . . 163 7.1 MultipleSclerosis . . . . . . . . . . . . . . . . . . . . . . . . 163 7.1.1 InterpretationofDataintheHCCSCA . . . . . . . . . 163 7.2 Epilepsy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 164 7.2.1 ResultsoftheStudy(I,VI) . . . . . . . . . . . . . . . 166 7.2.2 TheInterpretationofResults . . . . . . . . . . . . . . 171 7.3 Migraine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 174 7.3.1 ResultsoftheStudy(VII,VIII) . . . . . . . . . . . . . 176 7.3.2 InterpretationofResults. . . . . . . . . . . . . . . . . 181 7.3.3 GeneralRecommendationsRegardingtothe TreatmentofPregnantWomenwithMigraine . . . . . 185 7.4 OtherHeadaches . . . . . . . . . . . . . . . . . . . . . . . . . 186 7.4.1 ResultsoftheStudy . . . . . . . . . . . . . . . . . . . 186 7.4.2 InterpretationofResults. . . . . . . . . . . . . . . . . 187 7.5 FinalConclusions . . . . . . . . . . . . . . . . . . . . . . . . 187 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 188 OwnPublications . . . . . . . . . . . . . . . . . . . . . . . . . . . . 191 8 DiseasesoftheEyeandAdnexa . . . . . . . . . . . . . . . . . . . . 193 8.1 InterpretationofDataintheHCCSCA . . . . . . . . . . . . . . 193 9 DiseasesoftheEarandtheMastoidProcess . . . . . . . . . . . . . 195 9.1 OtitisMedia . . . . . . . . . . . . . . . . . . . . . . . . . . . 195 9.1.1 ResultsoftheStudy(I) . . . . . . . . . . . . . . . . . 195 9.1.2 InterpretationofResults. . . . . . . . . . . . . . . . . 198 9.2 OtherDiseases . . . . . . . . . . . . . . . . . . . . . . . . . . 199 Contents ix Reference . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 199 OwnPublication . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 199 10 DiseasesoftheCirculatorySystem . . . . . . . . . . . . . . . . . . 201 10.1 MaternalCardiovascularAdaptationtoPregnancy . . . . . . . 201 10.2 MitralStenosisDuetoRheumaticHeartDisease . . . . . . . . 202 10.2.1 InterpretationofDataintheHCCSCA . . . . . . . . . 202 10.3 Hypertension . . . . . . . . . . . . . . . . . . . . . . . . . . . 202 10.3.1 ResultsoftheStudy(I,II). . . . . . . . . . . . . . . . 203 10.3.2 InterpretationofResults. . . . . . . . . . . . . . . . . 208 10.4 Preeclampsia-Eclampsia . . . . . . . . . . . . . . . . . . . . . 210 10.4.1 ResultsoftheStudy . . . . . . . . . . . . . . . . . . . 211 10.4.2 InterpretationofResults. . . . . . . . . . . . . . . . . 214 10.5 CoronaryArteryDisease . . . . . . . . . . . . . . . . . . . . . 218 10.5.1 ResultsoftheStudy . . . . . . . . . . . . . . . . . . . 218 10.5.2 InterpretationofResults. . . . . . . . . . . . . . . . . 220 10.6 CardiacDysrhythmias . . . . . . . . . . . . . . . . . . . . . . 222 10.7 ParoxysmalSupraventricularTachycardia . . . . . . . . . . . . 222 10.7.1 ResultsoftheStudy . . . . . . . . . . . . . . . . . . . 222 10.7.2 InterpretationofResults. . . . . . . . . . . . . . . . . 224 10.8 ExtrasystolicArrhythmia . . . . . . . . . . . . . . . . . . . . . 225 10.8.1 InterpretationofDataintheHCCSCA . . . . . . . . . 226 10.9 ConductionDisorders . . . . . . . . . . . . . . . . . . . . . . 226 10.9.1 InterpretationofDataintheHCCSCA . . . . . . . . . 226 10.10 Phlebitis,Thrombophlebitis,andPulmonaryEmbolism . . . . . 226 10.10.1 ResultsoftheStudy . . . . . . . . . . . . . . . . . . . 227 10.10.2 InterpretationofResults. . . . . . . . . . . . . . . . . 229 10.11 VaricoseVeinsoftheLowerExtremities . . . . . . . . . . . . . 231 10.11.1 ResultsoftheStudy(VI) . . . . . . . . . . . . . . . . 231 10.11.2 InterpretationoftheResults . . . . . . . . . . . . . . . 233 10.12 Hemorrhoids . . . . . . . . . . . . . . . . . . . . . . . . . . . 234 10.12.1 ResultsoftheStudy . . . . . . . . . . . . . . . . . . . 234 10.12.2 InterpretationofResults. . . . . . . . . . . . . . . . . 237 10.13 Hypotension . . . . . . . . . . . . . . . . . . . . . . . . . . . 239 10.13.1 ResultsoftheStudy . . . . . . . . . . . . . . . . . . . 239 10.13.2 InterpretationofResults. . . . . . . . . . . . . . . . . 241 10.14 Others . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 243 10.14.1 InterpretationofDataintheHCCSCA . . . . . . . . . 243 10.15 GeneralConclusion. . . . . . . . . . . . . . . . . . . . . . . . 243 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 243 OwnPublications . . . . . . . . . . . . . . . . . . . . . . . . . . . . 248 11 DiseasesoftheRespiratorySystem . . . . . . . . . . . . . . . . . . 251 11.1 RespiratorySystemandRespiratoryFunctionDuringPregnancy 251 11.2 CommonCold . . . . . . . . . . . . . . . . . . . . . . . . . . 252 11.2.1 ResultsoftheStudy(I,II). . . . . . . . . . . . . . . . 252 11.2.2 InterpretationofResults. . . . . . . . . . . . . . . . . 256

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No part of this work may be reproduced, stored in a retrieval system, or transmitted in any form or tem, G = genital anomalies, E = ear anomalies and/or deafness) (II), (v) English abstract) Medicus Universalis 1998; 31: 17–21.
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No part of this work may be reproduced, stored in a retrieval system, or transmitted in any form or tem, G = genital anomalies, E = ear anomalies and/or deafness) (II), (v) English abstract) Medicus Universalis 1998; 31: 17–21.

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