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Perinatal and maternal factors associated with Autism Spectrum Disorder

Edlund, Susanna LU ; Haglund, Nils LU ; Bornehag, Carl Gustaf LU ; Gennings, Chris ; Kiviranta, Hannu ; Kolevzon, Alexander ; Lindh, Christian LU orcid ; Rantakokko, Panu ; Reichenberg, Abraham and Swan, Shanna , et al. (2026) In PLOS ONE 21(3 March).
Abstract

Background Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition influenced by both genetic and environmental factors. Prenatal and perinatal exposures have been implicated in ASD etiology, but their influence may vary across clinical subgroups, including subgroups defined by co-occurring intellectual disability (ID). Methods We conducted a population-based case–control study in southern Sweden including all children diagnosed with ASD before the age of 9, and whose mothers were born in Sweden. Diagnoses were confirmed through detailed medical record review, and information on ASD severity, ID status, and familial ASD were collected for subgroup analyses. A total of 996 ASD cases and 9,960 age- and sex-matched... (More)

Background Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition influenced by both genetic and environmental factors. Prenatal and perinatal exposures have been implicated in ASD etiology, but their influence may vary across clinical subgroups, including subgroups defined by co-occurring intellectual disability (ID). Methods We conducted a population-based case–control study in southern Sweden including all children diagnosed with ASD before the age of 9, and whose mothers were born in Sweden. Diagnoses were confirmed through detailed medical record review, and information on ASD severity, ID status, and familial ASD were collected for subgroup analyses. A total of 996 ASD cases and 9,960 age- and sex-matched controls were identified from a regional perinatal database. Multivariable logistic regression estimated adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for maternal, obstetric, and neonatal factors. Results Higher maternal body mass index (BMI) in early pregnancy was associated with increased likelihood of ASD (adjusted odds ratio [aOR] 1.41–1.76 for overweight and obesity compared with normal weight), with broadly similar associations observed across ASD subgroups defined by severity, intellectual disability, and familial ASD. Maternal smoking in early pregnancy (aOR 1.49, 95% CI 1.22–1.82) and both elective (aOR 1.22, 95% CI 1.01–1.48) and emergency cesarean delivery (aOR 1.40, 95% CI 1.15–1.81) were also associated with higher odds of ASD, with generally stronger associations in children without intellectual disability and in those with less severe ASD. Subgroup-specific associations were observed for maternal epilepsy and gestational diabetes, while prematurity showed weaker associations than anticipated and was mainly observed in severe ASD and non-familial cases. Low Apgar scores at 5 minutes showed no consistent association with ASD. Conclusions Multiple maternal and perinatal factors were associated with ASD in this large Swedish cohort. Stratified analyses by ASD severity, ID status, and familial ASD revealed both shared and subgroup-specific association patterns, underscoring the value of considering ASD heterogeneity in studies of neurodevelopmental variation.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
PLOS ONE
volume
21
issue
3 March
article number
e0316968
publisher
Public Library of Science (PLoS)
external identifiers
  • scopus:105033467968
  • pmid:41849261
ISSN
1932-6203
DOI
10.1371/journal.pone.0316968
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2026 Edlund et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
id
3f59e6b9-43b7-40d2-8b9e-583c8711ad92
date added to LUP
2026-05-05 13:14:57
date last changed
2026-06-02 15:09:42
@article{3f59e6b9-43b7-40d2-8b9e-583c8711ad92,
  abstract     = {{<p>Background Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition influenced by both genetic and environmental factors. Prenatal and perinatal exposures have been implicated in ASD etiology, but their influence may vary across clinical subgroups, including subgroups defined by co-occurring intellectual disability (ID). Methods We conducted a population-based case–control study in southern Sweden including all children diagnosed with ASD before the age of 9, and whose mothers were born in Sweden. Diagnoses were confirmed through detailed medical record review, and information on ASD severity, ID status, and familial ASD were collected for subgroup analyses. A total of 996 ASD cases and 9,960 age- and sex-matched controls were identified from a regional perinatal database. Multivariable logistic regression estimated adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for maternal, obstetric, and neonatal factors. Results Higher maternal body mass index (BMI) in early pregnancy was associated with increased likelihood of ASD (adjusted odds ratio [aOR] 1.41–1.76 for overweight and obesity compared with normal weight), with broadly similar associations observed across ASD subgroups defined by severity, intellectual disability, and familial ASD. Maternal smoking in early pregnancy (aOR 1.49, 95% CI 1.22–1.82) and both elective (aOR 1.22, 95% CI 1.01–1.48) and emergency cesarean delivery (aOR 1.40, 95% CI 1.15–1.81) were also associated with higher odds of ASD, with generally stronger associations in children without intellectual disability and in those with less severe ASD. Subgroup-specific associations were observed for maternal epilepsy and gestational diabetes, while prematurity showed weaker associations than anticipated and was mainly observed in severe ASD and non-familial cases. Low Apgar scores at 5 minutes showed no consistent association with ASD. Conclusions Multiple maternal and perinatal factors were associated with ASD in this large Swedish cohort. Stratified analyses by ASD severity, ID status, and familial ASD revealed both shared and subgroup-specific association patterns, underscoring the value of considering ASD heterogeneity in studies of neurodevelopmental variation.</p>}},
  author       = {{Edlund, Susanna and Haglund, Nils and Bornehag, Carl Gustaf and Gennings, Chris and Kiviranta, Hannu and Kolevzon, Alexander and Lindh, Christian and Rantakokko, Panu and Reichenberg, Abraham and Swan, Shanna and Källén, Karin}},
  issn         = {{1932-6203}},
  language     = {{eng}},
  number       = {{3 March}},
  publisher    = {{Public Library of Science (PLoS)}},
  series       = {{PLOS ONE}},
  title        = {{Perinatal and maternal factors associated with Autism Spectrum Disorder}},
  url          = {{http://dx.doi.org/10.1371/journal.pone.0316968}},
  doi          = {{10.1371/journal.pone.0316968}},
  volume       = {{21}},
  year         = {{2026}},
}