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Prenatal SSRI Use and Offspring With Autism Spectrum Disorder or Developmental Delay
Open accessAbstract
OBJECTIVE: To examine associations between prenatal use of selective serotonin reuptake inhibitors (SSRIs) and the odds of autism spectrum disorders (ASDs) and other developmental delays (DDs). METHODS: A total of 966 mother-child pairs were evaluated (492 ASD, 154 DD, 320 typical development [TD]) from the Childhood Autism Risks from Genetics and the Environment (CHARGE) Study, a population-based case-control study. Standardized measures confirmed developmental status. Interviews with biological mothers ascertained prenatal SSRI use, maternal mental health history, and sociodemographic information. RESULTS: Overall, prevalence of prenatal SSRI exposure was lowest in TD children (3.4%) but did not differ significantly from ASD (5.9%) or DD (5.2%) children. Among boys, prenatal SSRI exposure was nearly 3 times as likely in children with ASD relative to TD (adjusted odds ratio [OR]: 2.91; 95% confidence interval [CI]: 1.07–7.93); the strongest association occurred with first-trimester exposure (OR: 3.22; 95% CI: 1.17–8.84). Exposure was also elevated among boys with DD (OR: 3.39; 95% CI: 0.98–11.75) and was strongest in the third trimester (OR: 4.98; 95% CI: 1.20–20.62). Findings were similar among mothers with an anxiety or mood disorder history. CONCLUSIONS: In boys, prenatal exposure to SSRIs may increase susceptibility to ASD or DD. Findings from published studies on SSRIs and ASD continues to be inconsistent. Potential recall bias and residual confounding by indication are concerns. Larger samples are needed to replicate DD results. Because maternal depression itself carries risks for the fetus, the benefits of prenatal SSRI use should be carefully weighed against potential harms.
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“Relationships between DD and prenatal SSRIs were overall similar to those observed with ASD, and in agreement with previous null reports of prenatal SSRI use and ADHD (21, 25, 42), DD (32, 57), and ID (27, 58).”
From Maternal Psychiatric Conditions, Treatment With Selective Serotonin Reuptake Inhibitors, and Neurodevelopmental Disorders (2021) · cites this paper as [32]
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In the citing paper
“These positive findings in other studies persisted even after efforts to reduce confounding by indication through adjustment for maternal psychiatric condition (29, 31, 43, 44), restriction to mothers with psychiatric conditions (27–30, 32), and propensity weighting methods (30).”
From Maternal Psychiatric Conditions, Treatment With Selective Serotonin Reuptake Inhibitors, and Neurodevelopmental Disorders (2021) · cites this paper as [32]
Experimental — accuracy not yet measuredIn the citing paper
“Previous studies have observed associations between prenatal SSRI exposure and specific types of DD, including motor (32, 59) and speech/language delays (57).”
From Maternal Psychiatric Conditions, Treatment With Selective Serotonin Reuptake Inhibitors, and Neurodevelopmental Disorders (2021) · cites this paper as [32]
In the citing paper
“However, reflecting the mixed evidence of this research area, our findings also contradict several other large studies conducted in Sweden,(30, 43) the Netherlands (44), California (31, 32), Canada (29), and Denmark (27, 28).”
From Maternal Psychiatric Conditions, Treatment With Selective Serotonin Reuptake Inhibitors, and Neurodevelopmental Disorders (2021) · cites this paper as [32]
In the citing paper
“For ASD as the outcome, seven case–control studies (involving 291,468 patients and 13,243 cases of ASD) [17, 18, 26–29, 32] and eight cohort studies (involving 3,294,218 patients and 27,342 cases of ASD) [16, 19, 25, 30, 31, 33–35] were included.”
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“there was a total of 15 observational studies measuring ASD as an outcome [16–19, 25–35].”
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Metadata
- Authors
- Harrington, R. A., Lee, L.-C., Crum, R. M., Zimmerman, A. W., & Hertz-Picciotto, I.
- Affiliations
- Johns Hopkins University (US)
- University of Massachusetts Chan Medical School (US)
- Department of Public Health Sciences and the MIND Institute, University of California, Davis, Davis, California
- ORCID
- Zimmerman, Andrew W.
- Venue
- Pediatrics
- Publisher
- American Academy of Pediatrics (AAP)
- Published
- 2014-05-01
- Volume
- 133
- Issue
- 5
- Pages
- e1241-e1248
- ISSN
- 0031-4005 (ISSN-L)
- 1098-4275
- PMC
- PMC4006441
- OpenAlex
- W2105930613
- Cited by
- 174
- References
- 50
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 6 · 2023: 3 · 2022: 6 · 2021: 13 · 2020: 17 · 2019: 15 · 2018: 21 · 2017: 25 · 2016: 34 · 2015: 16 · 2014: 7
- FWCI
- 26.85
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- PEDIATRICS (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Autism Speaks
- National Institutes of Health (ES11269)
- National Institute of Environmental Health Sciences (R01ES015359, P01ES011269)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Pregnancy and Medication Impact
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Maternal Mental Health During Pregnancy and Postpartum
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Substance Exposure Effects
- Keywords
- prenatal SSRI exposure, selective serotonin reuptake inhibitors, autism spectrum disorder, developmental delay, maternal mental health, maternal depression, first trimester exposure, third trimester exposure, sex differences, CHARGE study, maternal medication use
- MeSH terms
- California, Developmental Disabilities, Child Development Disorders, Pervasive, Child, Preschool, Drug Utilization, Female, Humans, Male, Pregnancy, Pregnancy Trimester, First, Pregnancy Trimester, Third, Prenatal Exposure Delayed Effects, Sex Factors, Odds Ratio, Case-Control Studies
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