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

Abstract

COMMENT & RESPONSEIn Reply We appreciate Ceulemans and colleagues' response. We share their concern regarding the potential for misinterpretation and preemptive clinical implications of our study of selective serotonin reuptake inhibitor (SSRI) use during pregnancy. 1 We also agree that discontinuing prenatal SSRI treatment can increase the risk of psychiatric emergencies and postpartum relapse. We certainly did not advocate against SSRI treatment during pregnancy or recommend discontinuation of treatment. At the same time, we recognize that there are effective alternatives to SSRI treatment and that most women taking SSRIs during pregnancy are taking maintenance treatment. 2 In our study, all women had initiated SSRI treatment before conception. Thus, the results should not be generalized to women who consider commencing treatment in pregnancy. We propose further research and discussion of possible risks and unwanted effects of discontinuing or continuing treatment. Our vision is a more personalized treatment, eg, for asymptomatic women on maintenance therapy who are planning a pregnancy.We readily acknowledge that the association between exposure to maternal prenatal depressive symptoms and brain structural differences in offspring should have been mentioned in the key findings despite word count limitations. Several points raised by Ceulemans and colleagues would have deserved more discussion. The sample size concerns are valid and discussed only briefly, although the number of SSRI-exposed participants (partly due to repeated imaging assessment) was sufficient to detect an association with offspring brain morphology.One of the interesting findings that certainly requires further exploration is the clinical relevance of differences in brain volume trajectories. As highlighted in the accompanying Editorial, 3 the clinical significance of the observed changes in brain volume remains unclear. Interestingly, key limbic regions tend to normalize over time. Ideally, we would have been able to incorporate mediation models linking brain trajectories to behavioral and cognitive outcomes. However, in this cohort, Generation R, data that allow careful temporal modeling are not available yet.We certainly recognize the significance of the postnatal environment in shaping the neurodevelopment of the offspring, but we consider it as a downstream factor and not as an antecedent or possible confounder of the effects of prenatal SSRI use. The postnatal environment could mediate the association between intrauterine exposures and brain development; exploring such mechanisms was beyond the scope of our study.