Persistent pulmonary hypertension of the newborn (PPHN), previously called persistent fetal circulation, is a birth defect affecting approximately 1 in 1250 liveborn term infants; even with complex and high-risk interventions, PPHN results in substantial mortality and morbidity. This defect results from the inappropriate muscularization of fetal pulmonary vessels, and experimental and human evidence consistently suggests that maternal cigarette smoking and antenatal exposure to non-steroidal anti-inflammatory drugs (NSAIDs), particularly aspirin or ibuprofen, may play a role in the etiology of this condition. Because these exposures are quite prevalent (e.g., ibuprofen is currently taken in the first trimester or later in pregnancy by 15% and 3.2% of women, respectively), testing these hypotheses is of considerable public health importance. The investigators propose to conduct a multicenter case-control study of PPHN in relation to maternal exposure to smoking and NSAIDs. They will also assess other potential antenatal risk factors and collect and store buccal cell specimens for future analyses. There will be 560 case infants with PPHN and four controls per case (2240). All controls will be drawn from the birth hospitals of cases; half the controls will have malformations other than PPHN, and half will have normal formations. Cases and controls will be identified within 5 months of birth at 88 birth and tertiary hospitals in the areas surrounding Boston, Philadelphia, and Toronto. Mothers of subjects will be interviewed by telephone within six months of delivery; a standardized questionnaire will inquire 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 will also be collected and stored for future analyses. Exposure prevalences will be compared between mothers of cases and controls and relative risks will be estimated, controlling for potential confounding factors.
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