Major congenital malformations following prenatal exposure to serotonin reuptake inhibitors and benzodiazepines using population-based health data.
BACKGROUND
To determine a population-based incidence of congenital anomalies following prenatal exposure to serotonin reuptake inhibitor (SRI) antidepressants used alone and in combination with a benzodiazepines (BZ).


METHODS
Population health data, maternal health, and prenatal prescription records were linked to neonatal records, representing all live births (British Columbia, Canada, N=119,547) during a 39-month period (1998-2001). The incidence and risk differences (RD) for major congenital anomalies (CA) and congenital heart disease (CHD), including ventricular and atrial septal defects (VSD, ASD), from infants of mothers treated with an SRI alone, a benzodiazepine (BZ) alone, or SRI+BZ in combinationcompared to outcomesno exposure.


RESULTS
Risk for a CA or CHD did increase following combined SRI+BZ exposure compared with no exposure. However, using a weighted regression model, controlling for maternal illness characteristics, combination therapy risk remained significantly associated only with CHD. The risk for an ASD was higher following SRI monotherapy compared with no exposure, after adjustment for maternal covariates. Dose/day was not associated with increased risk.


CONCLUSIONS
Infants exposed to prenatal SRIs in combination with BZs had a higher a incidence of CHD compared to no exposure, even after controlling for maternal illness characteristics. SRI monotherapy was not associated with an increased risk for major CA, but was associated with an increased incidence of ASD. Risk was not associated with first trimester medication dose/day.
Oberlander
Tim F
TF
Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada. toberlander@cw.bc.ca
Warburton
William
W
Misri
Shaila
S
Riggs
Wayne
W
Aghajanian
Jaafar
J
Hertzman
Clyde
C
D000328:Adult; D018687:Antidepressive Agents, Second-Generation / Q000009:adverse effects*; D001569:Benzodiazepines / Q000009:adverse effects*; D002170:Canada / Q000453:epidemiology; D000013:Congenital Abnormalities / Q000453:epidemiology* / Q000209:etiology; D011307:Drug Prescriptions / Q000706:statistics & numerical data; D005260:Female; D019538:Health Care Surveys / Q000706:statistics & numerical data; D006330:Heart Defects, Congenital / Q000453:epidemiology; D006801:Humans; D007231:Infant, Newborn; D018811:Maternal Exposure; D011247:Pregnancy; D011256:Pregnancy Outcome / Q000453:epidemiology*; D012307:Risk Factors; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects*
D018687:Antidepressive Agents, Second-Generation; D001569:Benzodiazepines; D017367:Selective Serotonin Reuptake Inhibitors