The association between use of antidepressants, especially SSRIs, during pregnancy and birth defects has been the topic of much discussion in recent years. As studies have reached conflicting conclusions, there has been a general uncertainty around the safety of antidepressant use during pregnancy.
In the current study the authors sought to provide a more robust estimate of the association between use of individual SSRIs during pregnancy and birth defects. They reviewed published analyses to determine previously reported associations and determined whether these associations were supported by data from the US National Birth Defects Prevention Study (NBDPS).
The final analyses included 17,952 mothers of infants with birth defects and 9,857 mothers of infants without birth defects, born between 1997 and 2009. Use of citalopram, escitalopram, fluoxetine, paroxetine or sertraline at least once in the period from one month before conception through the third month of pregnancy was recorded.
The main findings included the following:
• None of the five previously reported associations between maternal use of sertraline (the most commonly used SSRI) and birth defects were confirmed in this analysis.
• No association between maternal use of citalopram or escitalopram and previously reported associated birth defects was found, except for a marginal association between citalopram and neural tube defects.
• For fluoxetine, associations were seen for ventricular septal defects, right ventricular outflow tract obstruction cardiac defects and craniosynostosis.
• For paroxetine, significant associations with anencephaly, atrial septal defects and right ventricular outflow tract obstruction cardiac defects, all seen in other studies, were confirmed in the NBDPS. In addition two other associations, seen in a previous analysis of the NBDPS, were observed (gastroschisis and omphalocele).
The authors say that their data provide reassuring data for some SSRIs, but suggest that some birth defects may be more frequently seen in women treated during early pregnancy with paroxetine or fluoxetine. They stress however that if these observed associations are causal, then any increase in absolute risk is small. For example the absolute risks in the children of women who are treated with paroxetine early in pregnancy would increase for anencephaly from 2 per 10,000 to 7 per 10,000, and for one of the heart defects from 10 per 10,000 to 24 per 10,000.
They call for additional studies of specific SSRIs during pregnancy "to enable women and their healthcare providers to make more informed decisions about treatment."