CoChat
Sign Up
Cited by 36Maternal Mental Health During Pregnancy and PostpartumPregnancy and Medication ImpactPharmacological Effects and Toxicity Studies

Maternal Psychiatric Conditions, Treatment With Selective Serotonin Reuptake Inhibitors, and Neurodevelopmental Disorders

Open access
Ames, Jennifer L., Ladd-Acosta, Christine, Fallin, M. Daniele, Qian, Yinge, Schieve, Laura A., DiGuiseppi, Carolyn, Lee, Li-Ching, Kasten, Eric P. +5 more·2021·Biological Psychiatry
DOI 10.1016/j.biopsych.2021.04.002PMC PMC8504533
Open this paper in CoChat — free accountOpen PDF

Abstract

BACKGROUND: This study aims to clarify relationships of maternal psychiatric conditions and selective serotonin reuptake inhibitor (SSRI) use during preconception and pregnancy with risk of neurodevelopmental disorders in offspring. METHODS: We used data from the Study to Explore Early Development, a multisite case-control study conducted in the United States among children born between 2003 and 2011. Final study group classifications of autism spectrum disorder (ASD) (n = 1367), developmental delays or disorders (DDs) (n = 1750), and general population controls (n = 1671) were determined by an in-person standardized developmental assessment. Maternal psychiatric conditions and SSRI use during pregnancy were ascertained from both self-report and medical records. We used logistic regression to evaluate associations of ASD and DDs (vs. population controls) with maternal psychiatric conditions and SSRI treatment in pregnancy. To reduce confounding by indication, we also examined SSRI associations in analyses restricted to mothers with psychiatric conditions during pregnancy. RESULTS: Psychiatric conditions and SSRI use during pregnancy were significantly more common among mothers of children with either ASD or DDs than among population controls. Odds of ASD were similarly elevated among mothers with psychiatric conditions who did not use SSRIs during pregnancy (adjusted odds ratio 1.81, 95% confidence interval 1.44-2.27) as in mothers who did use SSRIs (adjusted odds ratio 2.05, 95% confidence interval 1.50-2.80). Among mothers with psychiatric conditions, SSRI use was not significantly associated with ASD in offspring (adjusted odds ratio 1.14, 95% confidence interval 0.80-1.62). Primary findings for DDs exhibited similar relationships to those observed with ASD. CONCLUSIONS: Maternal psychiatric conditions but not use of SSRIs during pregnancy were associated with increased risk of neurodevelopmental disorders in offspring.

Integrity signals

Registry

Crossref · 10.1016/j.biopsych.2021.04.002

Cites

61 of 61 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 59 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Mothers of children with ASD or DD used SSRIs in pregnancy more frequently than POP controls did.

    “The frequencies of any antidepressant use and SSRI use anytime during preconception or pregnancy were higher among mothers of children with ASD or DD than among mothers of POP controls (Table 2).”
    Quote in the paperSubstantial claim
  • Findingown data

    In every exposure window, maternal psychiatric conditions raised the odds of DD without co-occurring intellectual disability.

    “In all time windows, maternal psychiatric conditions, particularly when combined with SSRI use, were associated with higher odds of DD without co-occurring ID but not DD with co-occurring ID (Supplementary Figure 5).”
    Quote in the paperSubstantial claim
  • Findingown data

    The point estimates for the association with DD were larger for joint exposure to maternal psychiatric condition and SSRI use than for psychiatric condition without SSRI use.

    “though point estimates were larger for the joint exposure.”
    Quote in the paperNot a substantial claim
  • Findingown data

    For ASD and DD alike, maternal psychiatric conditions had stronger associations in subgroups without co-occurring intellectual disability than in those with it.

    “For both ASD and DD outcomes, associations with maternal psychiatric conditions were stronger for child diagnostic subgroups without co-occurring ID than for those with co-occurring ID.”
    Quote in the paperSubstantial claim
  • Findingown data

    Overall, mothers with a psychiatric condition during pregnancy had nearly twice the adjusted odds of having a child with ASD compared with mothers without a psychiatric condition (aOR=1.93, 95% CI 1.59-2.34).

    “The adjusted odds of having a child with ASD were nearly 2-fold higher among mothers with a psychiatric condition during pregnancy, regardless of SSRI use, than among mothers without a psychiatric condition (none of whom used SSRIs, by definition) (Psy Yes vs. Psy No): adjusted odds ratio (aOR)=1.93, 95% confidence interval (CI) 1.59 – 2.34) (Table 4).”
    Quote in the paperSubstantial claim
  • May combine two claims. 17
  • The quote only partly states this claim. 1
  • Classified as probably not a substantial claim. 9

  • May combine two claims.

    Findingown data

    For mothers with psychiatric conditions, SSRI use in trimesters or at any time in pregnancy had modestly raised DD odds, though the intervals included the null.

    “SSRI use by trimester and anytime during pregnancy also showed modestly higher odds of DD, though confidence intervals contained the null.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Secondary results hint that maternal SSRI use might raise DD odds without ID, though the intervals for DD with and without ID overlapped.

    “While secondary findings suggest that maternal SSRI use may be associated with increased odds of DD without ID, the confidence intervals for DD with and without ID overlapped.”
    Quote in the paperNot a substantial claim

  • May combine two claims. The quote only partly states this claim.

    Findingown data

    Associations of maternal psychiatric condition and SSRI exposure with ASD held across preconception and each trimester.

    “These relationships were consistent for exposure across the pre-conception period and all trimesters of pregnancy.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The link between maternal psychiatric condition and ASD, regardless of SSRI treatment, was strongest for children without co-occurring intellectual disability and for multiplex families.

    “Specifically, associations of maternal psychiatric condition both with and without SSRI treatment were strongest among children with ASD without co-occurring ID and in multiplex families (Supplementary Figures 2 and 4).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Secondary analyses found significant links between prenatal SSRIs and DD without co-occurring intellectual disability, which could be a false positive requiring confirmation.

    “However, in secondary analyses, we noted significant associations between prenatal SSRI exposure and DD without co-occurring ID, a possible false-positive finding that needs confirmation in future work.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductown data

    The confidence intervals in the secondary DD analyses were broad and overlapped.

    “However, confidence intervals in these secondary analyses of DD were wide and overlapping.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    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).”
    Quote in the paperSubstantial claim0 of 7 sources checked
    • cites [21] Malm, 2016, Gestational exposure to selective serotonin reuptake inhibitors and offspring psychiatric disorders: A national register-based study, J Am Acad Child Adolesc Psychiatry source

      Not checked in the free run.

    • cites [25] Sujan, 2017, Associations of maternal antidepressant use during the first trimester of pregnancy with preterm birth, small for gestational age, autism spectrum disorder, and attention-deficit/hyperactivity disorder in offspring, JAMA source

      Not checked in the free run.

    • cites [42] Castro, 2016, Absence of evidence for increase in risk for autism or attention-deficit hyperactivity disorder following antidepressant exposure during pregnancy: A replication study, Transl Psychiatry source

      Not checked in the free run.

    • cites [32] Harrington, 2014, Prenatal SSRI use and offspring with autism spectrum disorder or developmental delay, Pediatrics source

      Not checked in the free run.

    • cites [57] Brown, 2016, Association of selective serotonin reuptake inhibitor exposure during pregnancy with speech, scholastic, and motor disorders in offspring, JAMA Psychiatry source

      Not checked in the free run.

    • cites [27] Liu, 2017, Antidepressant use during pregnancy and psychiatric disorders in offspring: Danish nationwide register based cohort study, BMJ source

      Not checked in the free run.

    • cites [58] Viktorin, 2017, Association of antidepressant medication use during pregnancy with intellectual disability in offspring, JAMA Psychiatry source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    Children whose mothers took SSRIs before conception or during pregnancy had higher DD odds, especially DD without co-occurring intellectual disability.

    “however, we observed that odds of DD, particularly DD without co-occurring ID, were higher in children of mothers who used SSRIs during pre-conception and pregnancy.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Earlier work has linked prenatal SSRIs to particular DD types, such as motor and speech/language delays.

    “Previous studies have observed associations between prenatal SSRI exposure and specific types of DD, including motor (32, 59) and speech/language delays (57).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [32] Harrington, 2014, Prenatal SSRI use and offspring with autism spectrum disorder or developmental delay, Pediatrics source

      Not checked in the free run.

    • cites [59] Pedersen, 2010, Fetal exposure to antidepressants and normal milestone development at 6 and 19 months of age, Pediatrics source

      Not checked in the free run.

    • cites [57] Brown, 2016, Association of selective serotonin reuptake inhibitor exposure during pregnancy with speech, scholastic, and motor disorders in offspring, JAMA Psychiatry source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    For mothers with a psychiatric condition in pregnancy, SSRI use was unrelated to ASD, which suggests SSRIs do not increase ASD odds apart from the conditions they treat.

    “Among mothers with psychiatric conditions during pregnancy, SSRI use was not related to ASD, suggesting that SSRIs may not raise odds of ASD independently of their psychiatric indications;”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    A small group (4.5%) lacking sociodemographic data was removed.

    “We further excluded a small subset of participants (4.5%) with missing sociodemographic information.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Information on maternal psychiatric conditions and pregnancy SSRI use came from self-report and medical records.

    “Maternal psychiatric conditions and SSRI use during pregnancy were ascertained from both self-report and medical records.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    To address confounding by indication, SSRI associations were also assessed only among mothers with psychiatric conditions in pregnancy.

    “To reduce confounding by indication, we also examined SSRI associations in analyses restricted to mothers with psychiatric conditions during pregnancy.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductown data

    Restricting SSRI analyses to mothers with psychiatric histories reduced, but did not eliminate, confounding by condition severity.

    “Our analytic strategy of examining the impact of prenatal exposure to SSRIs among mothers with psychiatric histories mitigated but did not completely resolve confounding by condition severity.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductown data

    SEED is a large, sociodemographically varied sample drawn from six US locations.

    “The SEED population, representing six different geographic locations across the US, is large and sociodemographically diverse.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    Including DD children let the authors test whether SSRI effects were specific to ASD or extended to other neurodevelopmental outcomes.

    “Including children with DD further allowed for evaluation of the specificity of impact of SSRI use on non-ASD neurodevelopmental endpoints.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductcitation

    ASD group children satisfied ADOS criteria and either full ADI-R criteria or one of three ADI-R alternatives.

    “Children in the final ASD group (n=1429) met ASD diagnostic criteria on the ADOS and either the full ASD diagnostic criteria on the ADI-R or one of three alternate criteria on the ADI-R, as detailed in Wiggins et al. (34)”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [34] Wiggins, 2015, Using standardized diagnostic instruments to classify children with autism in the study to explore early development, J Autism Dev Disord source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductown data

    An in-person standardized developmental assessment assigned final ASD, DD, or POP classification.

    “Final study group classifications of ASD (n=1367), DD (n= 1750), and general population controls (POP)(n=1671) were determined by an in-person standardized developmental assessment.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductcitation

    Maternal SSRI use in SEED matched other US estimates, which lessens worry about participation selection bias.

    “Additionally, rates of maternal SSRI use in the SEED sample were comparable to other US estimates (5–7), mitigating concerns about selection bias in participation.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [5] Alwan, 2011, Patterns of antidepressant medication use among pregnant women in a United States population, J Clin Pharmacol source

      Not checked in the free run.

    • cites [6] Ailes, 2016, Using insurance claims data to identify and estimate critical periods in pregnancy: An application to antidepressants, Birth Defects Res A Clin Mol Teratol source

      Not checked in the free run.

    • cites [7] Andrade, 2016, Use of selective serotonin reuptake inhibitors (SSRIs) in women delivering liveborn infants and other women of child-bearing age within the U.S. Food and Drug Administration’s Mini-Sentinel program, Arch Womens Ment Health source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductcitation

    SEED did not enroll every invited family, and case and control response rates differed.

    “Nevertheless, as discussed in earlier work, not all invited families enrolled in the study and response rates differed between cases and controls (33).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [33] Schendel, 2012, The Study to Explore Early Development (SEED): A multisite epidemiologic study of autism by the Centers for Autism and Developmental Disabilities Research and Epidemiology (CADDRE) network, J Autism Dev Disord source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    The study did not correct for multiple comparisons.

    “We did not correct for multiple comparisons.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductcitation

    At one site, a responder-non-responder comparison showed that maternal age, education, and race/ethnicity predicted participation, but adjusted risk-factor analyses were largely robust to non-response bias.

    “However, an analysis that compared characteristics of responders and non-responders at one site found that, although maternal age, education, and race/ethnicity predicted study participation, risk factor analyses adjusted for these sociodemographic variables were generally robust to the impact of non-response bias (61).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [61] Schieve, 2018, Assessment of demographic and perinatal predictors of non-response and impact of non-response on measures of association in a population-based case control study: Findings from the Georgia Study to Explore Early Development, Emerg Themes Epidemiol source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductreasoning

    Covariates in the final model were maternal race/ethnicity, education, delivery age, smoking, and pregnancy household income; these related to child outcomes and were not intermediates.

    “We pared down the final adjustment set to covariates associated with child outcomes and not considered intermediates in the pathways of interest; these included maternal race/ethnicity, education level, age at delivery, and smoking, and household income during pregnancy.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Only children whose maternal psychiatric and medication data were complete across all three sources entered the final analysis.

    “The final analytic sample included children with completed maternal psychiatric and medication information available in all three sources (Caregiver Interview, maternal medical history, and medical record data).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductown data

    The study had clinically validated neurodevelopmental diagnoses plus detailed information on exposures around conception and in pregnancy and on potential confounders.

    “Our study benefitted from clinically validated diagnoses of neurodevelopmental disorders and detailed data on pre-conception and pregnancy exposures and potential confounders.”
    Quote in the paperSubstantial claim
25 of 25

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Ames, J. L., Ladd-Acosta, C., Fallin, M. D., Qian, Y., Schieve, L. A., DiGuiseppi, C., Lee, L.-C., Kasten, E. P., Zhou, G., Pinto-Martin, J., Howerton, E. M., Eaton, C. L., & Croen, L. A.
Affiliations
  • Kaiser Permanente (US)
  • Johns Hopkins University (US)
  • Centers for Disease Control and Prevention (US)
  • Colorado School of Public Health (US)
  • Michigan State University (US)
Corresponding author
Ames, Jennifer L.
ORCID
Venue
Biological Psychiatry
Publisher
Elsevier BV
Published
2021-08
Volume
90
Issue
4
Pages
253-262
ISSN
0006-3223 (ISSN-L)
DOI
10.1016/j.biopsych.2021.04.002
PMC
PMC8504533
OpenAlex
W3153199133
Cited by
36
References
61
Citations by year
2026: 4 · 2025: 7 · 2024: 8 · 2023: 4 · 2022: 11 · 2021: 2
FWCI
5.42
Type
journal article
Language
en
Open access
Licence
Locations
  • Biological Psychiatry (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD087915, U10DD000180, U10DD000181, U10DD000182, U10DD000183, U10DD000184, U10DD000498)
  • University of Pennsylvania (R01HD087915, U10DD000180, U10DD000181, U10DD000182, U10DD000183, U10DD000184, U10DD000498)
  • Kaiser Foundation Research Institute (R01HD087915, U10DD000180, U10DD000181, U10DD000182, U10DD000183, U10DD000184, U10DD000498)
  • National Institutes of Health (R01HD087915, U10DD000180, U10DD000181, U10DD000182, U10DD000183, U10DD000184, U10DD000498)
  • Michigan State University (R01HD087915, U10DD000180, U10DD000181, U10DD000182, U10DD000183, U10DD000184, U10DD000498)
  • Centers for Disease Control and Prevention (R01HD087915, U10DD000180, U10DD000181, U10DD000182, U10DD000183, U10DD000184, U10DD000498)
  • Johns Hopkins University (R01HD087915, U10DD000180, U10DD000181, U10DD000182, U10DD000183, U10DD000184, U10DD000498)
  • University of North Carolina at Chapel Hill (R01HD087915, U10DD000180, U10DD000181, U10DD000182, U10DD000183, U10DD000184, U10DD000498)
  • California Department of Public Health (R01HD087915, U10DD000180, U10DD000181, U10DD000182, U10DD000183, U10DD000184, U10DD000498)
  • Pfizer (R01HD087915, U10DD000180, U10DD000181, U10DD000182, U10DD000183, U10DD000184, U10DD000498)
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
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmacological Effects and Toxicity Studies
Keywords
selective serotonin reuptake inhibitors, prenatal SSRI exposure, autism spectrum disorder, developmental delay, neurodevelopmental disorders, offspring risk, maternal mental health, confounding by indication
MeSH terms
Autism Spectrum Disorder, Child, Female, Humans, Mothers, Pregnancy, Pregnancy Complications, Prenatal Exposure Delayed Effects, United States, Case-Control Studies, Selective Serotonin Reuptake Inhibitors, Neurodevelopmental Disorders

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read under definition version 3 (extract-v3) on 2026-09-28.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-09-28.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review