title: Maternal Antihypertensive Medication Use and Congenital Heart Defects: Updated Results From the National Birth Defects Prevention Study.
abstract: Previous NBDPS (National Birth Defects Prevention Study) findings from 1997 to 2003 suggested that maternal antihypertensive use was associated with congenital heart defects (CHDs). We re-examined associations between specific antihypertensive medication classes and specific CHDs with additional NBDPS data from 2004 to 2011. After excluding mothers missing hypertension information or who reported pregestational diabetes mellitus, a multiple birth, or antihypertensive use but no hypertension, we compared self-reported maternal exposure data on 10 625 CHD cases and 11 137 nonmalformed controls. We calculated adjusted odds ratios [95% confidence intervals] to estimate the risk of specific CHDs associated with antihypertensive use during the month before conception through the third month of pregnancy, controlling for maternal age, race/ethnicity, body mass index, first trimester cigarette smoking, and NBDPS site. Overall, 164 (1.5%) case mothers and 102 (0.9%) control mothers reported early pregnancy antihypertensive use for their hypertension. We observed increased risk of 4 CHD phenotypes, regardless of antihypertensive medication class reported: coarctation of the aorta (2.50 [1.52-4.11]), pulmonary valve stenosis (2.19 [1.44-3.34]), perimembranous ventricular septal defect (1.90 [1.09-3.31]), and secundum atrial septal defect (1.94 [1.36-2.79]). The associations for these phenotypes were statistically significant for mothers who reported β-blocker use or renin-angiotensin system blocker use; estimates for other antihypertensive medication classes were generally based on fewer exposed cases and were less stable but remained elevated. Our results support and expand on earlier NBDPS findings that antihypertensive medication use may be associated with increased risk of specific CHDs, although we cannot completely rule out confounding by underlying disease characteristics.
authors.affiliation: From the Congenital Malformations Registry, New York State Department of Health, Albany (S.C.F., A.R.V.Z., C.M.D., M.L.B.); Department of Epidemiology and Biostatistics, School of Public Health, University at Albany, Rensselaer, NY (A.R.V.Z., C.M.D., M.L.B.); Department of Epidemiology, School of Public Health, Boston University, MA (M.M.W.); Genetics Unit, MassGeneral Hospital for Children, Boston, MA (A.E.L.); Massachusetts Department of Public Health, Massachusetts Center for Birth Defects Prevention, Boston (A.E.L.); and Department of Epidemiology, College of Public Health, University of Iowa, Iowa City (P.A.R.). sarah.fisher@health.ny.gov.
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Fisher
authors.affiliation: From the Congenital Malformations Registry, New York State Department of Health, Albany (S.C.F., A.R.V.Z., C.M.D., M.L.B.); Department of Epidemiology and Biostatistics, School of Public Health, University at Albany, Rensselaer, NY (A.R.V.Z., C.M.D., M.L.B.); Department of Epidemiology, School of Public Health, Boston University, MA (M.M.W.); Genetics Unit, MassGeneral Hospital for Children, Boston, MA (A.E.L.); Massachusetts Department of Public Health, Massachusetts Center for Birth Defects Prevention, Boston (A.E.L.); and Department of Epidemiology, College of Public Health, University of Iowa, Iowa City (P.A.R.).
authors.forename: Alissa R
authors.initials: AR
authors.lastname: Van Zutphen
authors.affiliation: From the Congenital Malformations Registry, New York State Department of Health, Albany (S.C.F., A.R.V.Z., C.M.D., M.L.B.); Department of Epidemiology and Biostatistics, School of Public Health, University at Albany, Rensselaer, NY (A.R.V.Z., C.M.D., M.L.B.); Department of Epidemiology, School of Public Health, Boston University, MA (M.M.W.); Genetics Unit, MassGeneral Hospital for Children, Boston, MA (A.E.L.); Massachusetts Department of Public Health, Massachusetts Center for Birth Defects Prevention, Boston (A.E.L.); and Department of Epidemiology, College of Public Health, University of Iowa, Iowa City (P.A.R.).
authors.forename: Martha M
authors.initials: MM
authors.lastname: Werler
authors.affiliation: From the Congenital Malformations Registry, New York State Department of Health, Albany (S.C.F., A.R.V.Z., C.M.D., M.L.B.); Department of Epidemiology and Biostatistics, School of Public Health, University at Albany, Rensselaer, NY (A.R.V.Z., C.M.D., M.L.B.); Department of Epidemiology, School of Public Health, Boston University, MA (M.M.W.); Genetics Unit, MassGeneral Hospital for Children, Boston, MA (A.E.L.); Massachusetts Department of Public Health, Massachusetts Center for Birth Defects Prevention, Boston (A.E.L.); and Department of Epidemiology, College of Public Health, University of Iowa, Iowa City (P.A.R.).
authors.forename: Angela E
authors.initials: AE
authors.lastname: Lin
authors.affiliation: From the Congenital Malformations Registry, New York State Department of Health, Albany (S.C.F., A.R.V.Z., C.M.D., M.L.B.); Department of Epidemiology and Biostatistics, School of Public Health, University at Albany, Rensselaer, NY (A.R.V.Z., C.M.D., M.L.B.); Department of Epidemiology, School of Public Health, Boston University, MA (M.M.W.); Genetics Unit, MassGeneral Hospital for Children, Boston, MA (A.E.L.); Massachusetts Department of Public Health, Massachusetts Center for Birth Defects Prevention, Boston (A.E.L.); and Department of Epidemiology, College of Public Health, University of Iowa, Iowa City (P.A.R.).
authors.forename: Paul A
authors.initials: PA
authors.lastname: Romitti
authors.affiliation: From the Congenital Malformations Registry, New York State Department of Health, Albany (S.C.F., A.R.V.Z., C.M.D., M.L.B.); Department of Epidemiology and Biostatistics, School of Public Health, University at Albany, Rensselaer, NY (A.R.V.Z., C.M.D., M.L.B.); Department of Epidemiology, School of Public Health, Boston University, MA (M.M.W.); Genetics Unit, MassGeneral Hospital for Children, Boston, MA (A.E.L.); Massachusetts Department of Public Health, Massachusetts Center for Birth Defects Prevention, Boston (A.E.L.); and Department of Epidemiology, College of Public Health, University of Iowa, Iowa City (P.A.R.).
authors.forename: Charlotte M
authors.initials: CM
authors.lastname: Druschel
authors.affiliation: From the Congenital Malformations Registry, New York State Department of Health, Albany (S.C.F., A.R.V.Z., C.M.D., M.L.B.); Department of Epidemiology and Biostatistics, School of Public Health, University at Albany, Rensselaer, NY (A.R.V.Z., C.M.D., M.L.B.); Department of Epidemiology, School of Public Health, Boston University, MA (M.M.W.); Genetics Unit, MassGeneral Hospital for Children, Boston, MA (A.E.L.); Massachusetts Department of Public Health, Massachusetts Center for Birth Defects Prevention, Boston (A.E.L.); and Department of Epidemiology, College of Public Health, University of Iowa, Iowa City (P.A.R.).
authors.forename: Marilyn L
authors.initials: ML
authors.lastname: Browne
mesh_terms: D000328:Adult; D000959:Antihypertensive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D016022:Case-Control Studies; D005260:Female; D006330:Heart Defects, Congenital / Q000139:chemically induced* / Q000517:prevention & control; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D008423:Maternal Age; D018811:Maternal Exposure; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000517:prevention & control; D012307:Risk Factors; D055815:Young Adult
chemical_list: D000959:Antihypertensive Agents
keywords: antihypertensive agents; congenital heart defects; hypertension; pregnancy