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

ObjectiveTo study previously identified associations between specific maternal hypertensive disorders and/or prenatal exposure to antihypertensive medication and birth defects. DesignCase-control study. SettingSlone Birth Defects Study, 1998-2010. PopulationA total of 5568 cases with birth defects and 7253 liveborn infants without malformations as controls. MethodsAdjusted 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 measuresSpecific birth defects previously linked to maternal hypertension or antihypertensive medication use during pregnancy. ResultsNon-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 (aOR3.9, 95%CI 1.3-11.7) and atrial septal defects (aOR6.5, 95%CI 1.8-23.7). For chronic hypertension that was pharmacologically treated early in pregnancy, increased risks were observed for first-degree hypospadias (aOR2.9, 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. ConclusionsOur 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.