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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL058763-03
Application #
6183305
Study Section
Special Emphasis Panel (ZRG4-EDC-1 (01))
Project Start
1998-04-01
Project End
2003-03-31
Budget Start
2000-04-01
Budget End
2001-03-31
Support Year
3
Fiscal Year
2000
Total Cost
$559,264
Indirect Cost
Name
Boston University
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02118
Van Marter, Linda J; Hernandez-Diaz, Sonia; Werler, Martha M et al. (2013) Nonsteroidal antiinflammatory drugs in late pregnancy and persistent pulmonary hypertension of the newborn. Pediatrics 131:79-87
Radin, Rose G; Mitchell, Allen A; Werler, Martha M (2013) Predictors of recall certainty of dates of analgesic medication use in pregnancy. Pharmacoepidemiol Drug Saf 22:25-32
Toh, Sengwee; Mitchell, Allen A; Anderka, Marlene et al. (2011) Antibiotics and oral contraceptive failure - a case-crossover study. Contraception 83:418-25
Louik, Carol; Gardiner, Paula; Kelley, Katherine et al. (2010) Use of herbal treatments in pregnancy. Am J Obstet Gynecol 202:439.e1-439.e10
Hernandez-Diaz, Sonia; Werler, Martha M; Mitchell, Allen A (2007) Gestational hypertension in pregnancies supported by infertility treatments: role of infertility, treatments, and multiple gestations. Fertil Steril 88:438-45
Waller, D Kim; Tita, Alan T N; Werler, Martha M et al. (2003) Association between prepregnancy maternal body mass index and the risk of having an infant with a congenital diaphragmatic hernia. Birth Defects Res A Clin Mol Teratol 67:73-6
Werler, Martha M; Louik, Carol; Mitchell, Allen A (2003) Epidemiologic analysis of maternal factors and amniotic band defects. Birth Defects Res A Clin Mol Teratol 67:68-72
Meyer, Katie A; Werler, Martha M; Hayes, Catherine et al. (2003) Low maternal alcohol consumption during pregnancy and oral clefts in offspring: the Slone Birth Defects Study. Birth Defects Res A Clin Mol Teratol 67:509-14