SSRI Use During Pregnancy and Risk of ASD or Developmental Delay In Children

Background:  Evidence indicates that serotonin is altered in children with an autism spectrum disorder (ASD); however, little is known about the developmental effect of prenatal exposure to medications that act on a child’s serotonin system in utero.

Objectives:  To provide preliminary data about the developmental effects of prenatal maternal use of selective serotonin reuptake inhibitors (SSRIs), a class of antidepressants. Both overall use and timing of use by trimester were assessed.

Methods:  From the Childhood Autism Risks from Genetics and the Environment (CHARGE) study, a large population-based case-control study, we examined mother-child pairs for which self-reported maternal medication history was available (total sample) and a subset consisting of mothers who reported experiencing a mental health disorder at any time prior to their child’s birth (mental health subset). The total sample comprised 479 children with ASD, 152 with developmental delay (DD), and 358 with typical development (TD). The mental health subset had 104 with ASD, 33 with DD, and 60 with TD. Children with ASD had an ADI-R and ADOS confirmed diagnosis; Vineland and Mullen scores were used to classify children as DD or TD. Exposure was defined as mothers who reported taking an SSRI at any time between conception and birth. Bivariate logistic regression was used to examine the association between prenatal SSRI exposure and developmental outcomes in children.  

Results:  

1. In the total sample, SSRIs were used during pregnancy by 29 mothers (6.1%) in the ASD group, 9 (5.9%) in the DD group, and 12 (3.4%) in the TD group. In the subset, SSRI use occurred in 27 mothers (26.0%) in the ASD group, 9 (27.3%) in the DD group, and 11 (18.3%) in the TD group.
2. ASD versus TD: Overall, the crude odds ratio (OR) for SSRI exposure was 1.86 (95% confidence interval (CI): 0.93-3.69). The trimester specific OR’s were 1.45 (95% CI: 0.69-3.04), 1.73 (95% CI: 0.71-4.26) and 2.30 (95% CI: 0.97-5.46) for the 1^st, 2^nd, and 3^rd, respectively.
3. DD versus TD: Overall, the crude OR for SSRI exposure was 1.81 (95% CI: 0.75-4.40). The crude ORs for SSRI exposure were 0.85 (95% CI: 0.27-2.72), 2.42 (95% CI: 0.83-7.02), and 3.18 (95% CI: 1.16-8.71) for the 1^st, 2^nd, and 3^rd trimesters respectively.
4. The trends were similar but attenuated for the mental health subset.

Conclusions:  SSRI exposure was similar in the ASD and DD groups, and was lowest in the TD group. Compared to the TD group, the odds of SSRI exposure became increasingly greater from the first to third trimester for both the ASD and DD groups, although the number of mother-child pairs in some subgroups was small. Odds of exposure did not significantly differ between the ASD and DD groups at any time point. Results were similar among mothers who experienced a mental health disorder prior to their child’s birth. The crude analysis indicates that timing of prenatal exposure to SSRIs is important to consider when investigating their affect on development. Results adjusting for potential confounders will be discussed.