Risk Factors for Pulmonary Hypertension of the Newborn

BACKGROUND: 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 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 percent and 3.2 percent of women, respectively), testing these hypotheses is of considerable public health importance. DESIGN NARRATIVE: 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. The study completion date listed in this record was obtained from the "End Date" entered in the Protocol Registration and Results System (PRS) record.