Treating maternal depression with selective serotonin reuptake inhibitors (SSRIs) could increase the risk for low birth weight and small for gestational age, according to a study recently published in the Journal of Affective Disorders.

This retrospective cohort study included 1,977,446 participants from 15 research studies. The correlation between the use of SSRIs used to treat maternal depression and deficient fetal growth was significant, with a pooled risk ratio of 1.38 (95% CI, 1.13-1.69; Z=3.14; P =.00) for low birth weight and 1.45 (95% CI, 1.18-1.76; Z=3.62; P =.00) for small for gestational age. Heterogeneity results between studies revealed a significant effect of sample size (I2=70.2%; P =.00), leading to the exclusion of one case-control study on the link between SSRIs and small for gestational age. Sensitivity analyses revealed low quality in 5 studies, creating the potential for unreliable results. After excluding these studies, the overall conclusions were the same: an odds ratio for low birth weight of 1.35 (95% CI, 1.24-1.47; Z=7.09; P =.00) and for small for gestational age of 1.23 (95% CI, 1.15-1.32; Z=6.11; P =.00).

A database search using Web of science, PsyBOOKS PsycARTICLES, PsycINFO, and PubMed was performed to find relevant publications. Inclusion criteria included an examination of the link between fetal growth and SSRIs used to treat prenatal depression as well as the inclusion of effects sizes (e.g. 95% CI, relative risk). Limitations to this study include control sample selection bias, a possible history of exposure to risk factors, an absence of particular statistics, and lower confidence as a result of not being a prospective cohort study, leading to potential false negatives.

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The study researchers concluded that “SSRIs use for maternal depression may increase the risk of [small for gestational age] in retrospective cohort studies and that SSRIs use for maternal depression may increase the risk of [low birth weight]. However, when analyzing prospective cohort studies, no association was found between SSRIs use and [low birth weight]…[Future] studies should consider the timing of exposure to SSRIs, maternal lifestyle throughout pregnancy, differences in SSRIs used, and study design to fully elucidate the maximum benefits for the mother and to minimize the risks to the newborn when using an SSRIs during pregnancy for the treatment of depression.”


Zhao X, Liu Q, Cao S, et al. A meta-analysis of selective serotonin reuptake inhibitors (SSRIs) use during prenatal depression and risk of low birth weight and small for gestational age. J Affect Disord. 2018;241:563-570.

This article originally appeared on Psychiatry Advisor