Selected pregnancy and delivery outcomes after exposure to antidepressant medication: A systematic review and meta-analysis

Importance: Untreated depression during pregnancy has been associated with increased morbidity and mortality for both mother and child and, as such, optimal treatment strategies are required for this population. Context: There are conflicting data regarding potential risks of prenatal antidepressant treatment. Objective: To determine whether prenatal antidepressant exposure is associated with risk for selected adverse pregnancy or delivery outcomes. Data Sources: MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature, PsycINFO, and the Cochrane Library were searched from their start dates to June 30, 2010. Study Selection: English-language studies reporting outcomes associated with pharmacologic treatment during pregnancy were included. We reviewed 3074 abstracts, retrieved 735 articles, and included 23 studies in this metaanalysis. Data Extraction: Study design, antidepressant exposure, adjustment for confounders, and study quality were extracted by 2 independent reviewers. Results: There was no significant association between antidepressant medication exposure and spontaneous abortion (odds ratio [OR], 1.47; 95% CI, 0.99 to 2.17; P=.055). Gestational age and preterm delivery were statistically significantly associated with antidepressant exposure (mean difference [MD] [weeks],-0.45; 95% CI, -0.64 to -0.25; P<.001; and OR, 1.55; 95% CI, 1.38 to 1.74; P<.001, respectively), regardless of whether the comparison group consisted of all unexposed mothers or only depressed mothers without antidepressant exposure. Antidepressant exposure during pregnancy was significantly associated with lower birth weight (MD [grams],-74; 95% CI,-117 to-31; P=.001); when this comparison group was limited to depressed mothers without antidepressant exposure, there was no longer a significant association. Antidepressant exposure was significantly associated with lower Apgar scores at 1 and 5 minutes, regardless of whether the comparison group was all mothers or only those who were depressed during pregnancy but not exposed to antidepressants. Conclusions and Relevance: Although statistically significant associations between antidepressant exposure and pregnancy and delivery outcomes were identified, group differences were small and scores in the exposed group were typically within the normal ranges, indicating the importance of considering clinical significance. Treatment decisions must weigh the effect of untreated maternal depression against the potential adverse effects of antidepressant exposure.