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.


METHODS
Case-control study.


METHODS
Slone Birth Defects Study, 1998-2010.


METHODS
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.


METHODS
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.
Department for Health Evidence, Radboud University Medical Center, Nijmegen, the Netherlands.
M M H J
MM
van Gelder
Slone Epidemiology Center at Boston University, Boston, MA, USA.
C M
CM
Van Bennekom
Slone Epidemiology Center at Boston University, Boston, MA, USA.
C
C
Louik
Slone Epidemiology Center at Boston University, Boston, MA, USA.
M M
MM
Werler
Department for Health Evidence, Radboud University Medical Center, Nijmegen, the Netherlands.|Department of Paediatrics, Radboud University Medical Center, Nijmegen, the Netherlands.
N
N
Roeleveld
Slone Epidemiology Center at Boston University, Boston, MA, USA.
A A
AA
Mitchell
D000014:Abnormalities, Drug-Induced / Q000209:etiology*; D000328:Adult; D000959:Antihypertensive Agents / Q000009:adverse effects*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D046110:Hypertension, Pregnancy-Induced / Q000188:drug therapy*; D011225:Pre-Eclampsia / Q000188:drug therapy; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000188:drug therapy*; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced*; D012307:Risk Factors; D016896:Treatment Outcome; D055815:Young Adult
D000959:Antihypertensive Agents
Antihypertensive agents; cardiovascular abnormalities; congenital malformations; hypertensive disorders in pregnancy; hypospadias; oesophageal atresia