Prenatal exposure to selective serotonin reuptake inhibitors and social responsiveness symptoms of autism: Population-based study of young children

Marroun, Hanan El; White, Tonya J. H.; van der Knaap, Noortje J. F.; Homberg, Judith R.; Fernández, Guillén; Schoemaker, Nikita K.; Jaddoe, Vincent W. V.; Hofman, Albert; Verhulst, Frank C.; Hudziak, James J.; Stricker, Bruno H. C.; Tiemeier, Henning

doi:10.1192/bjp.bp.113.127746

Cited by 117Maternal Mental Health During Pregnancy and PostpartumPregnancy and Medication ImpactAutism Spectrum Disorder Research

Prenatal exposure to selective serotonin reuptake inhibitors and social responsiveness symptoms of autism: Population-based study of young children

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Marroun, Hanan El, White, Tonya J. H., van der Knaap, Noortje J. F., Homberg, Judith R., Fernández, Guillén, Schoemaker, Nikita K., Jaddoe, Vincent W. V., Hofman, Albert +4 more·2014·British Journal of Psychiatry

DOI 10.1192/bjp.bp.113.127746

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Abstract

Background: Selective serotonin reuptake inhibitors (SSRIs) are considered safe and are frequently used during pregnancy. However, two case–control studies suggested an association between prenatal SSRI exposure with childhood autism. Aims: To prospectively determine whether intra-uterine SSSRI exposure is associated with childhood autistic symptoms in a population-based study. Method: A total of 376 children prenatally exposed to maternal depressive symptoms (no SSRI exposure), 69 children prenatally exposed to SSRIs and 5531 unexposed children were included. Child pervasive developmental and affective problems were assessed by parental report with the Child Behavior Checklist at ages 1.5, 3 and 6. At age 6, we assessed autistic traits using the Social Responsiveness Scale (n= 4264). Results: Prenatal exposure to maternal depressive symptoms without SSRIs was related to both pervasive developmental (odds ratio (OR) = 1.44, 95% CI 1.07–1.93) and affective problems (OR = 1.44, 95% CI 1.15–1.81). Compared with unexposed children, those prenatally exposed to SSRIs also were at higher risk for developing pervasive developmental problems (OR = 1.91, 95% CI 1.13–3.47), but not for affective problems. Children prenatally exposed to SSRIs also had more autistic traits (B= 0.15, 95% CI 0.08–0.22) compared with those exposed to depressive symptoms only. Conclusions: Our results suggest an association between prenatal SSRI exposure and autistic traits in children. Prenatal depressive symptoms without SSRI use were also associated with autistic traits, albeit this was weaker and less specific. Long-term drug safety trials are needed before evidence-based recommendations are possible.

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The literature often reports links between ASD and maternal psychiatric conditions before or during pregnancy, such as depression, schizophrenia, anxiety, and personality disorders.
“Associations between ASD and maternal psychiatric conditions preceding or during pregnancy (20, 45, 46), including depression (24, 43, 44, 47), schizophrenia (48, 49), anxiety (50), and personality disorders (48), are commonly reported in the literature.”
From Maternal Psychiatric Conditions, Treatment With Selective Serotonin Reuptake Inhibitors, and Neurodevelopmental Disorders (2021) · cites this paper as [44]
The null prenatal SSRI-ASD result conflicts with several large studies from Sweden, the Netherlands, California, Canada, and Denmark.
“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 [44]
Other studies' positive results remained after adjustment, restriction, and propensity weighting aimed at confounding by indication.
“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 [44]

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“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).”
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Underrated Diagnosis: Prenatal Depression
Koçak, Ö., & KOÇAK, S. (2023) · Kafkas Journal of Medical Sciences · doi:10.5505/kjms.2023.21033 · Cited by 1 · see citing works

Prenatal exposure to selective serotonin reuptake inhibitors and autistic symptoms in young children: another red herring?
Petersen, I., Evans, S. J. W., & Nazareth, I. (2014) · British Journal of Psychiatry · doi:10.1192/bjp.bp.113.141721 · Cited by 16 · see citing works
Prenatal SSRI use and offspring with autism spectrum disorder or developmental delay
Harrington, R. A., Lee, L.-C., Crum, R. M., Zimmerman, A. W., & Hertz-Picciotto, I. (2014) · Pediatrics · doi:10.1542/peds.2013-3406 · Cited by 174 · see citing works
Highlights of this issue
Dean, K. (2014) · The British Journal of Psychiatry · doi:10.1192/bjp.205.2.a7
Maternal SSRI exposure increases the risk of autistic offspring: a meta-analysis and systematic review.
Andalib, S., Emamhadi, M. R., Yousefzadeh-Chabok, S., Shakouri, S. K., Høilund-Carlsen, P. F., Vafaee, M. S., & Michel, T. M. (2017) · European Psychiatry · doi:10.1016/j.eurpsy.2017.06.001 · Cited by 86 · see citing works
Depression and SSRI use in pregnancy associated with traits of autism in children
Torjesen, I. (2014) · BMJ · doi:10.1136/bmj.g4835 · Cited by 5 · see citing works

Authors: Marroun, H. E., White, T. J. H., van der Knaap, N. J. F., Homberg, J. R., Fernández, G., Schoemaker, N. K., Jaddoe, V. W. V., Hofman, A., Verhulst, F. C., Hudziak, J. J., Stricker, B. H. C., & Tiemeier, H.
Affiliations: Erasmus MC (NL)
University of Vermont (US)
Corresponding author: Tiemeier, Henning
ORCID: Marroun, Hanan El
White, Tonya J. H.
Homberg, Judith R.
Fernández, Guillén
Schoemaker, Nikita K.
Jaddoe, Vincent W. V.
Verhulst, Frank C.
Hudziak, James J.
Stricker, Bruno H. C.
Tiemeier, Henning
Venue: British Journal of Psychiatry
Publisher: Royal College of Psychiatrists
Published: 2014-08
Volume: 205
Issue: 2
Pages: 95-102
ISSN: 0007-1250 (ISSN-L)
1472-1465
DOI: 10.1192/bjp.bp.113.127746
OpenAlex: W1981456496
Cited by: 117
References: 54
Citations by year: 2026: 3 · 2025: 6 · 2024: 1 · 2023: 9 · 2022: 3 · 2021: 7 · 2020: 13 · 2019: 11 · 2018: 16 · 2017: 15 · 2016: 18 · 2015: 11 · 2014: 3
FWCI: 15.52
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.cambridge.org/core/terms (unspecified, 1250 d)
Locations: The British Journal of Psychiatry (publishedVersion)
PubMed (publishedVersion)
EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
Radboud Repository (Radboud University) (submittedVersion)
Topics: Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Maternal Mental Health During Pregnancy and Postpartum
Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Pregnancy and Medication Impact
Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
Keywords: prenatal SSRI exposure, selective serotonin reuptake inhibitors, autism spectrum disorder, autistic traits, social responsiveness, maternal depression, emotional problems, child behavior, drug safety in pregnancy
MeSH terms: Autistic Disorder, Depressive Disorder, Female, Humans, Pregnancy, Prenatal Exposure Delayed Effects, Selective Serotonin Reuptake Inhibitors

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Prenatal exposure to selective serotonin reuptake inhibitors and social responsiveness symptoms of autism: Population-based study of young children

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