Title:Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin Norepinephrine Reuptake Inhibitors (SNRIs) During Pregnancy and the Risk for Autism spectrum disorder (ASD) and Attention deficit hyperactivity disorder (ADHD) in the Offspring: A True Effect or a Bias? A Systematic Review & Meta-Analysis
Volume: 19
Issue: 6
Author(s): Regina Leshem, Benjamin Bar-Oz, Orna Diav-Citrin, Siham Gbaly, Jessica Soliman, Christel Renoux and Ilan Matok*
Affiliation:
- School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem,Israel
Keywords:
SSRI's, SNRI's, antidepressants, ASD, ADHD, prenatal exposure, pregnancy.
Abstract:
Background and Objective: An inconsistent association between exposure to SSRIs and
SNRIs and the risk for ASD and ADHD in the Offspring was observed in observational studies.
Some suggest that the reported association might be due to unmeasured confounding. We aimed to
study this association and to look for sources of bias by performing a systematic review and meta-analysis.
Methods: Medline, Embase, and the Cochrane Library were searched up to June 2019 for studies
reporting on ASD and ADHD in the Offspring following exposure during pregnancy. We followed
the PRISMA 2009 guidelines for data selection and extraction. Outcomes were pooled using random-
effects models and odds ratios (OR), and 95% confidence intervals (CI) were calculated for
each outcome using the adjusted point estimate of each study.
Results: Eighteen studies were included in the meta-analysis. We found an association between SSRIs/
SNRIs prenatal use and the risk for ASD and ADHD (OR=1.42, 95% CI: 1.23–1.65, I2=58%;
OR=1.26, 95% CI: 1.07-1.49, I2=48%, respectively). Similar findings were obtained in women
who were exposed to SSRIs/SNRIs before pregnancy, representing statistically significant association
with ASD (OR=1.39, 95% CI: 1.24-1.56, I2=33%) and ADHD (OR=1.63, 95% CI: 1.50-1.78,
I2=0%) in the Offspring, although they were not exposed to those medications in utero.
Conclusions: Although we found an association between exposure to SSRIs/SNRIs during pregnancy
and the risk for ASD and ADHD, an association with those disorders was also present for exposure
pre-pregnancy, suggesting that the association might be due to unmeasured confounding.
We are aiming to further assess the role of potential unmeasured confounding in the estimation of
the association and perform a network meta-analysis.
