cohort and was one of the first studies to include echocardiography as a modality for ascertainment, verification, and classification of cases It also prospectively defined the denominator for the cohort From 1981 to 1989, 4390 infants with congenital heart disease were identified from 906,646 regional live births, giving an estimate of prevalence of 4.84 per 1000 live births The prevalence increased throughout the period of study, with the proportion of cases having diagnostic confirmation with echocardiography increasing, and those confirmed with cardiac catheterization decreasing The prevalence in the past 3 years of the study was 5.5 per 1000 live births The major contributor to the apparent increase in prevalence was an increase in the number of perimembranous and muscular ventricular septal defects, reflecting better ascertainment with increasing use and improvements in echocardiography Ventricular septal defects accounted for 33% of the cases (Table 13.7) Table 13.7 Distribution of Diagnostic Groups in Order of Frequency (n = 4390) Diagnostic Group Ventricular septal defect Pulmonary stenosis Atrial septal defect within oval fossa Atrioventricular septal defect Tetralogy of Fallot Transposition Coarctation of aorta Hypoplastic left heart syndrome Aortic stenosis Patent arterial duct Isomerism of atrial appendages Double-outlet right ventricle Bifoliate aortic valve Cardiomyopathy Pulmonary atresia with intact septum Peripheral pulmonary arterial stenosis Totally anomalous pulmonary venous return Common arterial trunk Congenitally corrected transposition Ebstein malformation Tricuspid atresia Interrupted aortic arch Other left-sided lesionsa Double-inlet ventricle Other right-sided lesionsb Divided left atrium Number 1411 395 340 326 297 208 203 167 128 104 99 86 84 82 73 65 60 51 47 43 32 31 26 18 % 32.1 9.0 7.7 7.4 6.8 4.7 4.6 3.8 2.9 2.4 2.3 2.0 1.9 1.9 1.7 1.5 1.4 1.2 1.1 1.0 0.7 0.7 0.6 0.4 0.2 0.1 aIncludes 13 cases of coronary arterial anomalies, 7 anomalies of the aortic arch, 5 instances of mitral valvar regurgitation, and 1 case with drainage of the superior caval vein to the left atrium bIncludes eight examples of partially anomalous pulmonary venous return and one pulmonary arterial sling The Baltimore-Washington Infant Study (1981–89) From Ferencz C, Rubin JD, Loffredo CA, et al Epidemiology of Congenital Heart Disease: The Baltimore-Washington Infant Study: 1981–1989 Vol 4 Mount Kisco, NY: Futura; 1993 The Baltimore-Washington Infant Study included a case-control study within its design, with control infants randomly selected each year of the study from all live born infants without congenitally malformed hearts in a manner stratified by the hospital managing the births A comprehensive questionnaire was completed by standardized interviews of mothers at home visits The questionnaire collected data regarding demographic, maternal health, nutritional, genetic, and environmental factors The study defined a broad spectrum of familial and genetic factors, which were present in just over 33% of cases Table 13.8 shows the results of a multivariable analysis of potential risk factors without inclusion of maternal reproductive history variables When the number of previous pregnancies is included in the model, three or more pregnancies, as opposed to none, had an adjusted odds ratio of 1.29, and maternal age, race, familial noncardiac malformations, local contraceptives, and increasing number of drugs taken were no longer significantly associated with congenital cardiac disease When associations with environmental risk factors were examined separately for cases with and without genetic risk factors in comparison to controls without genetic risk factors, a greater number of environmental risk factors with stronger associations were noted in the analysis of cases with genetic risk factors, particularly for exposures to therapeutic drugs This suggests that environmental factors may have a greater influence in those with an underlying genetic susceptibility Table 13.8 Multivariable Model of Potential Risk Factors Without Maternal Reproductive History Variables (The Baltimore-Washington Infant Study, 1981–89) Variable GENETIC FACTORS IN NUCLEAR FAMILY Familial congenital heart disease Familial noncardiac malformations Adjusted Odds Ratio 95% CI 2.20 1.27 1.69–2.85 1.02–1.57 MATERNAL FACTORS Diabetes (overt) MATERNAL AGE SCORE 2.97 1.82–4.86 0 (