Third Trimester Maternal SSRI Exposure Linked to Depression, Anxiety in Offspring

sad young girl sitting on the couch
sad young girl sitting on the couch
The issue of whether and how prenatal SSRI exposure affects offspring has remained murky.

Maternal exposure to selective serotonin reuptake inhibitors (SSRIs) late in pregnancy may increase the risk for anxiety and depression in offspring, according to the Journal of the American Academy of Child & Adolescent Psychiatry. The findings only applied to late pregnancy (>29 weeks), as opposed to early (0 to 16 weeks) or mid-pregnancy (17 to 28 weeks).

Antidepressants — particularly SSRIs — are often prescribed during pregnancy for various psychiatric disorders, but the issue of whether and how prenatal SSRI exposure affects offspring has remained murky. Because there have been no studies to date that have examined the time-dependent effects of SSRIs on social and behavioral development during early childhood, a team of Norwegian researchers examined the effects of SSRI use during each trimester compared with children born to mothers who were not exposed to antidepressants during pregnancy.

The investigators used data from the Norwegian Mother and Child Cohort Study, a questionnaire-oriented, prospective population-based initiative that recruited participants from 1999 to 2008 from the Medical Birth Registry of Norway. Women who reported anxiety or depression symptoms according to the Hopkins Symptom Checklist-25 prior to or during pregnancy were invited to participate, with 41% agreeing to do so.

The children were assessed at 1.5 years, 3 years, and 5 years via the Child Behavior Checklist for preschool children and the Emotionality, Activity, and Shyness Temperament Questionnaire. Beta coefficients were used to express the mean difference in clinical developmental outcomes between children prenatally exposed to SSRIs and children who were not exposed to any form of antidepressant.

There were 8359 maternal-offspring dyads included, with 4128 children completing the study through age 5. Compared with unexposed children, children with SSRI exposure during late pregnancy were at a significantly elevated risk for depressed/anxious behaviors by 5 years (adjusted β: 0.50; 95% CI, 0.04-0.95).

No such relationship was detected with regard to other developmental outcomes, and was there no association established for mid-pregnancy SSRI exposure. In children exposed to SSRIs during late pregnancy, each year of life saw a 0.06 effect increase as measured on the Child Behavior Checklist for preschool children (adjusted β: 0.06; 95% CI, –0.00-0.16; P = .058).

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Study strengths identified by the investigators included accounting for maternal psychiatric disorders and assessing symptoms twice during pregnancy, dealing with study drop out (using imputation) and confounders, and exploring robustness of their results, via sensitivity analyses.

Study limitations included: the self-reporting nature of questionnaires, a lack of estimates regarding early pregnancy effect of SSRI exposure; potential misclassification of exposure; a lack of dosage information; a low response rate, coupled with possible self-selection skewing towards healthier women; possible selection bias; and small sample size.

While the researchers noted that replication of their results is needed, they felt that their findings were indicative of possible fetal susceptibility to SSRI exposure during certain periods of gestation. The issue for practitioners moving forward will be balancing this risk for future developmental issues in children with the very real impact of maternal depression or anxiety left untreated during pregnancy.


Lupattelli A, Wood M, Ystrom E, Skurtveit S, Handal M, Nordeng H. Effect of time-dependent selective serotonin reuptake inhibitor antidepressants during pregnancy on behavioral, emotional, and social development in preschool-age children [published online December 28, 2017]. J Am Acad Child Adolesc Psychiatry. doi:10.1016/j.jaac.2017.12.010