Fisher Sarah C, Van Zutphen Alissa R, Werler Martha M, Lin Angela E, Romitti Paul A, Druschel Charlotte M, Browne Marilyn L
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.).
Hypertension. 2017 May;69(5):798-805. doi: 10.1161/HYPERTENSIONAHA.116.08773. Epub 2017 Apr 3.
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.
先前1997年至2003年全国出生缺陷预防研究（NBDPS）的结果表明，母亲使用抗高血压药物与先天性心脏病（CHD）有关。我们利用2004年至2011年NBDPS的额外数据，重新审视了特定抗高血压药物类别与特定先天性心脏病之间的关联。在排除缺失高血压信息的母亲，或报告有孕前糖尿病、多胎妊娠、使用抗高血压药物但无高血压的母亲后，我们比较了10625例先天性心脏病病例和11137例无畸形对照的母亲自我报告的暴露数据。我们计算了调整后的优势比[95%置信区间]，以估计在受孕前一个月至妊娠第三个月期间使用抗高血压药物与特定先天性心脏病相关的风险，并对母亲年龄、种族/民族、体重指数、孕早期吸烟情况和NBDPS研究地点进行了控制。总体而言，164例（1.5%）病例母亲和102例（0.9%）对照母亲报告因高血压在孕早期使用了抗高血压药物。无论报告使用何种抗高血压药物类别，我们均观察到4种先天性心脏病表型的风险增加：主动脉缩窄（2.50[1.52 - 4.11]）、肺动脉瓣狭窄（2.19[1.44 - 3.34]）、膜周部室间隔缺损（1.90[1.09 - 3.31]）和继发孔房间隔缺损（1.94[1.36 - 2.79]）。对于报告使用β受体阻滞剂或肾素 - 血管紧张素系统阻滞剂的母亲，这些表型的关联具有统计学意义；其他抗高血压药物类别的估计值通常基于较少的暴露病例，稳定性较差，但仍有所升高。我们的结果支持并扩展了NBDPS早期的研究发现，即使用抗高血压药物可能与特定先天性心脏病的风险增加有关，尽管我们不能完全排除潜在疾病特征造成的混杂因素影响。
