SSRIs in Pregnancy—What Offspring Brain Volumes Can and Cannot Tell Us

Abstract

To the Editor We read with great interest the publication of Koc and colleagues on prenatal exposure to selective serotonin reuptake inhibitors (SSRIs) and offspring brain trajectories. 1 We applaud the authors for their innovative and well-executed study using data from a prospective population-based cohort, adjusting for confounders, including different comparator groups, and applying advanced neuroimaging techniques and statistical modeling. The authors showed that prenatal SSRI exposure was associated with about 3% reduced brain volumes of regions involved in emotional regulation in offspring. They also demonstrated minor reduced volumes of specific brain regions among offspring of women with depressive symptoms in the prenatal and postnatal life.In their Key Points and conclusion, however, the authors refer only to the findings linked to prenatal SSRI use and not to those linked to depressive symptoms. From a clinical perspective, we are concerned that clinicians or patients may jump to preemptive conclusions and consider these findings discouraging to prescribing or taking SSRIs in pregnancy. We have listed several considerations.First, the clinical relevance of the altered brain volumes is unknown. Second, despite differences in absolute brain volumes across groups, the developmental trajectories of various brain volumes followed similar trends during the follow-up period, regardless of SSRI or depression exposure. Third, the advanced statistical model demonstrating the trajectory of brain volumes following prenatal SSRI exposure is based entirely on 80 data points in 41 participants over a span of 8 years. Overadjustment is a risk and in their illustration, the y-axis starts at 700 000 mm 3 . Fourth, the observations are subject to residual confounding by indication as women receiving SSRIs in pregnancy likely experience more severe disease than any of the comparators. Fifth, some volumetric brain differences did not persist until early adolescence, suggesting adaptability and plasticity of the brain morphology and protective environmental factors during the postnatal life. Sixth, discontinuing prenatal antidepressant treatment is associated with an increased risk of psychiatric emergency and postpartum relapse. 2,3 Seventh, depression is common in pregnancy and associated with important short-and long-term risks if treated insufficiently. 4,5 Although we applaud the authors for not suggesting clinical implications, we remain concerned that these findings will be framed as signals mitigating SSRI use in pregnancy and cause uncertainty and guilt among pregnant women with depression. We do agree that more research on the functional implications and clinical impact of the differences in brain volumes on the developing infant is pivotal.