The multicenter study had a case-control design. There were 560 case infants with PPHN and four controls per case (2240). All controls were drawn from the birth hospitals of cases; half the controls had malformations other than PPHN, and half had normal formations. Cases and controls were identified within five months of birth at 88 birth and tertiary hospitals in the areas surrounding Boston, Philadelphia, and Toronto. Mothers of subjects were interviewed by telephone within six months of delivery; a standardized questionnaire inquired in detail about demographic factors; reproductive, medical, and pregnancy illness histories; medication use (including a detailed focus on use of over-the-counter analgesic/antipyretic medications), smoking, and nutrition. Because of emerging genetic research suggesting an effect of NSAIDs on pathways possibly related to the etiology of PPHN, buccal swabs were also collected and stored for future analyses. Exposure prevalences were compared between mothers of cases and controls and relative risks were estimated, controlling for potential confounding factors.