Autism and Prenatal Exposure to SSRIs

Li-Ching Lee, PhD, ScM Associate Scientist, Departments of Epidemiology and Mental Health Johns Hopkins Bloomberg School of Public Health Baltimore MD Interview with:
Li-Ching Lee, PhD, ScM
Associate Scientist,
Departments of Epidemiology and Mental Health
Johns Hopkins Bloomberg School of Public Health
Baltimore MD 21205 What are the main findings of the study?

Dr. Li-Ching Lee: This population-based case-control study in young children provides evidence that prenatal selective serotonin reuptake inhibitor (SSRI) use may be a risk factor for autism and other developmental delays (DD). Among boys, prenatal SSRI exposure was nearly 3 times as likely in children with autism spectrum disorder (ASD) relative to children with typical development; the strongest association occurred with first-trimester exposure. Exposure was also elevated among boys with DD and was strongest in the third trimester. Were any of the findings different from previous studies?

Dr. Li-Ching Lee: Recent ASD studies using electronic medical records and registries included large samples of pregnant women with prospectively collected medication use. However, ASD diagnoses were not validated. Furthermore, studies by Croen et al (2011) using Kaiser patients and by Hviid et al (2013) using Danish registries were unable to confirm whether dispensed SSRIs were actually taken by mothers, whereas the Rai et al (2013) study from Stockholm, Sweden, only included self-reported use at the first antenatal visit. The Kaiser and Swedish studies reported modestly increased autism spectrum disorder risk among children prenatally exposed to SSRIs, independent of maternal mental health, whereas no significant differences were observed in the Danish cohort. Similar to our results, the Kaiser study found the highest risk with first-trimester use. The Swedish study could not assess timing of use. Neither assessed differences in SSRI effects by child gender. Similar to the Danish cohort results, we found no association when boys and girls were combined. Hviid et al reported no data on gender, nor gender-stratified analyses. What should clinicians and patients take away from your report?

Dr. Li-Ching Lee: Because of low exposure prevalence and possible cofactors influencing susceptibility to autism spectrum disorder from SSRI exposure, any contribution of these medications to the increase in autism diagnoses over time is likely minimal. The reported results must be viewed in the context of the disorder SSRIs are used to treat and, particularly, with the risks associated with failure to treat the condition. Maternal depression during pregnancy has itself been linked to preterm birth, fetal growth restriction, and preeclampsia, as well as increased irritability in newborns and reduced activity and attentiveness compared with infants of nondepressed women. Given these negative consequences, depression during pregnancy and the positive aspects of pharmacologic management present pregnant women and their doctors with complex treatment decisions. The benefits of treating depression with SSRIs during pregnancy should continue to be carefully weighed against any potential risk of harm. What recommendations do you have for future research as a result of this study?

Dr. Li-Ching Lee: Whether the risk of DDs other than autism spectrum disorder is also elevated in association with prenatal SSRI exposure requires confirmation with a larger sample size; research might usefully address how maternal SSRI use is affected by the knowledge of predisposing genetic conditions. Also needed are studies in more girls, sufficient sample sizes to address possible differential effects from specific SSRIs, and attention to mechanisms by which SSRIs might influence autism spectrum disorder and other developmental outcomes. The field would benefit from a deeper understanding of the contribution of maternal and fetal genetics in regulating serotonin.

Prenatal SSRI Use and Offspring With Autism Spectrum Disorder or Developmental Delay

Rebecca A. Harrington, Li-Ching Lee, Rosa M. Crum, Andrew W. Zimmerman, and Irva Hertz-Picciotto

Pediatrics peds.2013-3406; published ahead of print April 14, 2014, doi:10.1542/peds.2013-3406

Last Updated on April 22, 2014 by Marie Benz MD FAAD