While some studies have shown an association between in utero exposure to antidepressants and various pregnancy outcomes, including preterm delivery, low birth weight, and lower Apgar scores, these outcomes have also been linked to untreated maternal depression. Thus, it has been difficult to determine if there is a causal relationship between antidepressant exposure and negative pregnancy outcomes or whether maternal depression is itself responsible for these negative outcomes.

A recent meta-analysis published in JAMA Psychiatry addresses these conflicting results.  The authors searched MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature, PsycINFO, and the Cochrane Library databases from their start dates to June 30, 2010 for English-language studies reporting outcomes associated with pharmacologic treatment during pregnancy. 3074 abstracts were identified and 735 articles were retrieved; 23 studies were included in the final analysis.  The following outcomes were studied:

Risk of spontaneous abortion:  No significant association between antidepressant exposure and spontaneous abortion (odds ratio [OR], 1.47; 95% CI, 0.99 to 2.17; P = .055) was observed.

Gestational age and risk of preterm delivery: Antidepressant exposure was statistically significantly associated with a shorter gestation; the mean difference [MD] in weeks was ?0.45.  The risk of preterm delivery (typically defined as less than 37 weeks) was more common among women taking antidepressants (OR, 1.55; 95% CI, 1.38 to 1.74; P < .001).  Results were very similar for the 5 studies comparing outcomes in women exposed to antidepressants versus depressed with no antidepressant exposure.

Birth weight:  Antidepressant exposure during pregnancy was significantly associated with lower birth weight; the mean difference in grams was ?74.  When this comparison group was limited to depressed mothers with no antidepressant exposure, there was no longer a significant association.

Apgar scores:  Antidepressant exposure was significantly associated with lower Apgar scores at 1 and 5 minutes.

This is the first meta-analysis to examine gestational age, birth weight, and Apgar scores among infants with prenatal exposure to antidepressant medications. One of the strengths of this study is that it has also attempted to assess the impact of maternal depression on these outcomes. However, because few studies provided adequate data to enable this sort of analysis, the statistical power was limited.  Furthermore, it should be noted that the comparison groups typically used (women with depression who do not take antidepressants) may have significant limitations. Most notably, one could easily hypothesize that the women who chose to discontinue or avoid antidepressants during pregnancy are the women with milder illness.  Therefore, we cannot exclude the possibility that more severe depressive symptoms, or comorbid anxiety, may have a greater impact on outcomes.

While the analysis demonstrated statistically significant associations for three of the pregnancy outcomes studied, it is reassuring that the observed effects were small: about 3 days shorter gestational age, 75 g lower birth weight, and less than half a point on the 1- and 5-minute Apgar scores.  Furthermore, these values typically fall within the normal range.  The clinical significance of these findings is unclear. For example, the mean Apgar score of the exposed infants at 1 minute was 7.52 and at 5 minutes was 8.65.  While these scores are lower than in the unexposed infants, Apgar scores of 7 or higher indicate that a neonate’s condition is normal to excellent.

Further studies will need to better assess the impact of maternal illness, especially more severe symptoms, on pregnancy outcomes; however, this study is reassuring, indicating that if antidepressants are, in fact, associated with negative pregnancy outcomes, the effects are small and of questionable clinical significance.

Ruta Nonacs, MD PhD

Ross LE, Grigoriadis S, Mamisashvili L, et al. Selected Pregnancy and Delivery Outcomes After Exposure to Antidepressant Medication:  A Systematic Review and Meta-analysis.  JAMA Psychiatry. 2013; published online.




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