Prenatal Exposure to Folic Acid and Antidepressants and Language Development A Population-Based Cohort Study

Objective: The aim of the study was to determine the effect of simultaneous use of folic acid supplements and selective serotonin reuptake inhibitors (SSRIs) by pregnant women on language development in their offspring at the age of 3 years. Design: We conducted a cohort study of 45,266 women with 51,747 singleton pregnancies in the population-based Norwegian Mother and Child Cohort study (1999-2008). The association between the use of SSRIs with and without concomitant folic acid and language competence in the offspring was investigated using multinomial logistic regression. Self-reported use of folic acid supplements and SSRIs was prospectively collected in 4-week intervals during pregnancy and validated with prescription data and plasma concentrations, respectively. The children's language competence was measured by a validated language grammar rating scale and classified into 3 categories. Results: Women reported the use of folic acid in 44,417 (85.8%) and SSRI in 372 (0.7%) of the pregnancies, 260 used the 2 simultaneously. Compared with women who used folic acid and no SSRIs, the adjusted relative risk ratio of lower language competence rose with the increased duration of simultaneous use of folic acid and SSRIs. After simultaneous use at 4 to 8 four-week intervals, the relative risk ratio reached 4.5 (95% confidence interval, 2.5-8.0) and 5.7 (2.5-13.0) for the intermediate and most delayed category, respectively, using the best language competence category as the reference. The use of SSRIs without folic acid was not significantly associated with an increased risk. Conclusions: We detected a significant association between long-term use of SSRIs during pregnancy and delayed language competence in the offspring only when folic acid supplementation was used concomitantly. This surprising result warrants further studies.