Gestational exposure to selective serotonin reuptake inhibitors and offspring psychiatric disorders: A national register-based study

Malm, Heli; Brown, Alan S.; Gissler, Mika; Gyllenberg, David; Hinkka-Yli-Salomäki, Susanna; McKeague, Ian W.; Weissman, Myrna; Wickramaratne, Priya; Artama, Miia; Gingrich, Jay A.; Sourander, Andre

doi:10.1016/j.jaac.2016.02.013

Cited by 206Pregnancy and Medication ImpactMaternal Mental Health During Pregnancy and PostpartumPrenatal Substance Exposure Effects

Gestational exposure to selective serotonin reuptake inhibitors and offspring psychiatric disorders: A national register-based study

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Malm, Heli, Brown, Alan S., Gissler, Mika, Gyllenberg, David, Hinkka-Yli-Salomäki, Susanna, McKeague, Ian W., Weissman, Myrna, Wickramaratne, Priya +3 more·2016·Journal of the American Academy of Child & Adolescent Psychiatry

DOI 10.1016/j.jaac.2016.02.013PMC PMC4851729

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Abstract

Objective To investigate the impact of gestational exposure to selective serotonin reuptake inhibitors (SSRIs) on offspring neurodevelopment.Method This is a cohort study using national register data in Finland between the years 1996 and 2010. Pregnant women and their offspring were categorized into 4 groups: SSRI exposed (n = 15,729); exposed to psychiatric disorder, no antidepressants (n = 9,651); exposed to SSRIs only before pregnancy (n = 7,980); and unexposed to antidepressants and psychiatric disorders (n = 31,394). We investigated the cumulative incidence of offspring diagnoses of depression, anxiety, autism spectrum disorder (ASD), and attention-deficit/hyperactivity disorder (ADHD) for the 4 groups from birth to 14 years, adjusting for confounders.Results The cumulative incidence of depression among offspring exposed prenatally to SSRIs was 8.2% (95% CI = 3.1-13.3%) by age 14.9 years, compared with 1.9% (95% CI = 0.9-2.9%) in the psychiatric disorder, no medication group (adjusted hazard ratio [HR] = 1.78; 95% CI = 1.12-2.82; p = .02) and to 2.8% (95% CI = 1.4-4.3%) in the SSRI discontinued group (HR = 1.84; 95% CI = 1.14-2.97; p = .01). Rates of anxiety, ASD, and ADHD diagnoses were comparable to rates in offspring of mothers with a psychiatric disorder but no medication during pregnancy. Comparing SSRI exposed to unexposed individuals, the HRs were significantly elevated for each outcome.Conclusion Prenatal SSRI exposure was associated with increased rates of depression diagnoses in early adolescence but not with ASD or ADHD. Until confirmed, these findings must be balanced against the substantial adverse consequences of untreated maternal depression.

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The DD-prenatal SSRI pattern resembled the ASD pattern and matched earlier null findings for ADHD, DD, and ID.
“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 [21]
The null result for prenatal SSRIs and ASD agrees with multiple large population studies designed to handle confounding by indication.
“Our findings of no association between prenatal SSRI exposure and ASD are consistent with the conclusions of several large, population-based studies that specifically address confounding by indication (19–26, 42).”
From Maternal Psychiatric Conditions, Treatment With Selective Serotonin Reuptake Inhibitors, and Neurodevelopmental Disorders (2021) · cites this paper as [21]
One observational study reported effect estimates for maternal antidepressant exposure during pregnancy vs. unexposed women with a past medical history of affective disorder for ADHD.
“One observational study reported effect estimates for maternal antidepressant exposure during pregnancy vs. unexposed women with a past medical history of affective disorder [31].”
From Antidepressant use during pregnancy and risk of autism spectrum disorder and attention deficit hyperactivity disorder: Systematic review of observational studies and methodological considerations (2018) · cites this paper as [31]
The definition of exposure to other medicines during pregnancy focused on other psychotropic drugs, anxiolytics and sedatives, or nicotine products, with only one study accounting for all types of medications used.
“However, the definition of exposure to the use of other medicines during pregnancy focused on the use of other psychotropic drugs [35, 36, 38], use of anxiolytics and sedatives [19, 31, 37] or use of nicotine products [29], with only one study accounting for all types of medications used [25].”
From Antidepressant use during pregnancy and risk of autism spectrum disorder and attention deficit hyperactivity disorder: Systematic review of observational studies and methodological considerations (2018) · cites this paper as [31]
For ADHD, three case-control studies involving 51,944 patients and 4,375 cases and four cohort studies involving 2,713,779 patients and 51,938 cases were included.
“For ADHD as the outcome, three case–control studies (involving 51,944 patients and 4,375 cases of ADHD) [17, 18, 36] and four cohort studies (involving 2,713,779 patients and 51,938 cases of ADHD) [31, 33, 37, 38] were included.”
From Antidepressant use during pregnancy and risk of autism spectrum disorder and attention deficit hyperactivity disorder: Systematic review of observational studies and methodological considerations (2018) · cites this paper as [31]

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Authors: Malm, H., Brown, A. S., Gissler, M., Gyllenberg, D., Hinkka-Yli-Salomäki, S., McKeague, I. W., Weissman, M., Wickramaratne, P., Artama, M., Gingrich, J. A., & Sourander, A.
Affiliations: University of Helsinki (FI)
New York State Psychiatric Institute (US)
University of Turku (FI)
Columbia University (US)
Finnish Cancer Registry (FI)
Corresponding author: Malm, Heli
ORCID: Malm, Heli
Brown, Alan S.
Gissler, Mika
Gyllenberg, David
McKeague, Ian W.
Weissman, Myrna
Wickramaratne, Priya
Artama, Miia
Gingrich, Jay A.
Venue: Journal of the American Academy of Child & Adolescent Psychiatry
Publisher: Elsevier BV
Published: 2016-05
Volume: 55
Issue: 5
Pages: 359-366
ISSN: 0890-8567 (ISSN-L)
DOI: 10.1016/j.jaac.2016.02.013
PMC: PMC4851729
OpenAlex: W2290447957
Cited by: 206
References: 27
Citations by year: 2026: 3 · 2025: 15 · 2024: 13 · 2023: 14 · 2022: 22 · 2021: 21 · 2020: 20 · 2019: 25 · 2018: 29 · 2017: 28 · 2016: 16
FWCI: 32.39
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Journal of the American Academy of Child & Adolescent Psychiatry (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Työväentutkimus Vuosikirja (submittedVersion, other-oa)
STM:n Hallinnonalan avoin julkaisuarkisto (Julkari) (submittedVersion)
Columbia Academic Commons (Columbia University)
Funders: John Templeton Foundation
Helsingin Yliopisto
Suomen Lääketieteen Säätiö
National Alliance for Research on Schizophrenia and Depression
University of Oxford
Turun Yliopisto
Lastentautien Tutkimussäätiö
Terveyden ja hyvinvoinnin laitos
National Institutes of Health
National Institute of Mental Health (P50MH090966)
National Institute on Drug Abuse
Mailman School of Public Health, Columbia University
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, maternal antidepressant use, depression, anxiety, autism spectrum disorder, attention deficit hyperactivity disorder, brain development
MeSH terms: Autism Spectrum Disorder, Adolescent, Adult, Anxiety Disorders, Attention Deficit Disorder with Hyperactivity, Bipolar Disorder, Depressive Disorder, Female, Finland, Follow-Up Studies, Humans, Pregnancy, Prenatal Exposure Delayed Effects, Registries, Selective Serotonin Reuptake Inhibitors, Maternal Exposure, Young Adult

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Gestational exposure to selective serotonin reuptake inhibitors and offspring psychiatric disorders: A national register-based study

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