Maternal hypertensive disorders, antihypertensive medication use, and the risk of birth defects: a case-control study

Objective: To study previously identified associations between specific maternal hypertensive disorders and/or prenatal exposure to antihypertensive medication and birth defects.

Design: Case-control study.

Setting: Slone Birth Defects Study, 1998-2010.

Population: A total of 5568 cases with birth defects and 7253 liveborn infants without malformations as controls.

Methods: Adjusted odds ratios (aORs) for birth defects associated with prenatal exposure to maternal hypertensive disorders and/or antihypertensive medication were calculated using multivariable logistic regression analyses.

Main outcome measures: Specific birth defects previously linked to maternal hypertension or antihypertensive medication use during pregnancy.

Results: Non-pharmacologically managed chronic hypertension was associated with a three-fold risk of oesophageal atresia (95% CI 1.2-8.3), and pre-eclampsia superimposed on non-pharmacologically managed chronic hypertension was associated with ventricular septal defects (aOR 3.9, 95% CI 1.3-11.7) and atrial septal defects (aOR 6.5, 95% CI 1.8-23.7). For chronic hypertension that was pharmacologically treated early in pregnancy, increased risks were observed for first-degree hypospadias (aOR 2.9, 95% CI 1.1-7.4). Non-pharmacologically managed pre-eclampsia was related to second-/third-degree hypospadias and ventricular septal defects. Pharmacological treatment for gestational hypertension was associated with a number of congenital heart defects.

Conclusions: Our results confirm some, but not all, previously identified associations between pharmacologically treated and non-pharmacologically managed hypertensive disorders and specific birth defects. They support the hypothesis that physiological changes early in pregnancy that manifest in gestational hypertension and pre-eclampsia may play a role in the aetiology of major birth defects, including congenital heart defects and hypospadias.