Major congenital malformations following prenatal exposure to serotonin reuptake inhibitors and benzodiazepines using population-based health data

Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada.
Birth Defects Research Part B Developmental and Reproductive Toxicology (Impact Factor: 0.77). 02/2008; 83(1):68-76. DOI: 10.1002/bdrb.20144
Source: PubMed


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).
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.
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.
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.

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Available from: Jaafar Aghajanian, Dec 16, 2014
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    • "An increased risk of heart defects when SSRIs were combined with benzodiazepines during pregnancy compared with no first trimester exposure to drugs in either class (adjusted rate difference =1.18%, 95% CI 0.18%–2.18%) has also been reported.115 Neither drug class was associated with increased risk of heart defects when given individually. "
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    • "The most consistent pattern examining malformations has been the finding of increased risk for congenital heart defects after first trimester exposure to SRIs (paroxetine in particular). Increased risk after first-trimester exposure to SRIs has been reported in numerous studies, including research by Glaxosmithkline (the manufacturer of paroxetine) [88], and across different populations, including Quebec [52], and British Columbia, Canada [55], Israel, Germany, Italy [70], Sweden [89], and Denmark [90]. The increased risk for congenital heart defects was also reported when women who had received other antidepressants were studied as controls, as a way of reducing the likelihood of confounding by the underlying maternal depression [52] [88]. "
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