The BWIS included infants with cardiac defects confirmed in special studies who were residents in a defined Mid-Atlantic region of the United States. This was a case-control study which evaluated all live-born infants with congenital heart disease in comparison to an annually ascertained control population which was representative of all regional live births.

Over a nine year period all regional pediatric cardiology centers enrolled all infants with confirmed congenital heart disease and provided detailed coded diagnoses of all abnormalities as determined by echocardiography, cardiac catheterization, surgery and at autopsy in deceased infants. Cases were also found through searches of pathology records of the 53 regional hospitals, and of death certificates. Controls were selected annually by random selection of resident newborns in all participating hospitals and designated for interview at certain ages to conform to the age-distribution of cases. These controls were representative of the regional birth cohort. All families were visited by a trained interviewer, who obtained the parents’ consent to complete a detailed questionnaire regarding the family history, parental health, maternal reproductive history, medical therapies, occupational and home exposures to potentially harmful substances. About 200 covariates were defined for the analysis of case-control differences.

The first analyses compared the data on all cases to all controls. It was then necessary to examine diagnostic subsets of congenital heart disease to establish whether or not the presumed risk factors affected cardiac development generally or whether they were specific for certain chambers or valves of the heart or for the great vessels. This required a categorization of cardiovascular malformations appropriate for the search for possible causes.

Classification of diagnostic subsets:

Clinical differentiation of cardiovascular anomalies according to the anatomic abnormality of the heart and its great vessels was considered in relation to the presumed embryonic time at which development may have been disturbed.

  • Early anomalies i.e. defects of ‘primary cardiogenesis’ were those in which the four-chambered heart was not properly formed.
  • In presumably ‘late’ anomalies the four-chambered structure of the heart is present, but defects might have occurred during the embryonic growth period.

Case-control analyses of diagnostic groups:

All cases

‘Early’ cardiac defects: ‘Late’ cardiac defects:
Defects of laterality and looping Ventricular septal defect: muscular type
Defects of the cardiac outflow tract Left-sided obstructive lesions
Atrioventricular septal defects Right-sided obstructive lesions
Ventricular septal defects : membranous type Atrial septal defects
Total anomalous pulmonary venous return Patent arterial duct
Ebstein’s malformation of the tricuspid valve

For each of these categories the review included details of the cardiac and non-cardiac anomalies, descriptive analysis of prevalence by time, season and area of residence, gender, race and twinning, and a search for genetic and environmental risk factors, including the family history, maternal age and reproductive history, maternal illnesses and medications, lifestyle exposures to potentially toxic substances of both parents at home and in their work.

The methods and results of the BWIS were published in:

  • Ferencz,C, Rubin, JD, Loffredo,CA, Magee,CM. The Epidemiology of Congenital Heart Disease, The Baltimore-Washington Infant Study (1981-1989), Perspectives in Pediatric Cardiology, vol.4. MountKisco, N.Y: Futura Publishing Co.Inc, 1993.
  • Ferencz,C Loffredo,CA, Correa-Villasenor, Wilson,PD. Genetic and Environmental Risk Factors of Major Cardiovascular Malformations, The Baltimore-Washington Infant Study, (1981-1989), Perspectives in Pediatric Cardiology, vol.5. Armonk, N.Y: Futura Publishing Co.Inc, 1997.

Findings of the Baltimore-Washington Infant Study are shown in the context of the various topics: Occurrence, Mortality and Risk Factors