Peer-reviewed article
Maternal stress in pregnancy and child autism spectrum disorder: evaluating putative causal associations using a genetically informed design
Abdelrazek M, Rice F ·
Summary
Written by AI, not yet AICS's view · claude-haiku-4-5-20251001This study investigates whether maternal stress during pregnancy causes autism spectrum disorder (ASD) in children, or whether the association is due to inherited genetic factors. Using a genetically informed design with children born through in-vitro fertilization (some raised by genetically related mothers, others by unrelated mothers), researchers measured prenatal stress and child ASD traits at age 10. The study found that prenatal stress was associated with lower birth weight and shorter gestational age, validating the stress measure. Maternal stress showed similar associations with child ASD traits in both related and unrelated mother-child groups, suggesting an environmental rather than genetic link.
Key points
- Subjective prenatal maternal stress was associated with lower birth weight (β = –0.297, p = 0.005) and reduced gestational age (β = –0.320, p = 0.001)
- Late pregnancy stress was associated with increased offspring ASD traits in unrelated mother-child pairs (β = 0.233, p = 0.029)
- Non-significant interaction terms suggest that mechanisms linking maternal stress to both ASD and birth outcomes are environmentally driven rather than genetically inherited
- The similar pattern of associations in related and unrelated mother-child groups indicates a potential causal environmental effect rather than passive gene-environment correlation
- Sample comprised 365 related and 111 unrelated mother-child pairs with mean child age of 9.84 years
Limitations
The small sample size, particularly for unrelated mother-child pairs (n=111), limits statistical power. Prenatal stress was measured subjectively on a Likert scale rather than using objective biomarkers, and ASD traits were assessed through maternal questionnaire rather than clinical diagnosis, which may introduce measurement error and bias.
Abstract
Aims Prenatal adversity is hypothesized to increase risk of Autism Spectrum Disorder (ASD) via epigenetic changes. Maternal stress in late pregnancy may alter offspring neurodevelopmental outcomes by disrupting a unique period of rapid neurogenesis. Observational studies reporting an environmentally mediated programming pathway face challenges in drawing causal inferences including passive gene-environment correlation. This project aims to use a quasi-experimental genetically informed design to assess if reported correlations between maternal prenatal stress and offspring ASD traits were due to maternally inherited factors or consistent with a potentially causal prenatal exposure effect. No previous cross-fostering studies have assessed the effects of prenatal stress on childhood ASD. Method This study used an in-vitro fertilization cross-fostering sample with pregnant mothers related (n = 365) or unrelated (n = 111) to their offspring (mean age = 9.84 years). Prenatal stress was assessed using a subjective Likert scale during pregnancy. Questionnaires examined maternally rated offspring ASD traits using the Social and Communication Disorders Checklist. Birth weight and gestational age from medical records were used as comparison outcomes to validate the measure of stress as evidence suggests they are influenced by environmental factors. Correlations from multiple regression models were examined in relation to magnitude of effect size as well as significance. This is partly due to small sample size and that cross-fostering designs rely on comparing magnitudes of associations between related and unrelated groups. An interaction term was used to test the difference in the strength of association between related and unrelated mother-child groups. Result Subjective assessment of prenatal maternal stress showed construct validity as it was associated with low birth weight (β = –0.297, p = 0.005) and reduced gestational age (β= –0.320, p = 0.001). Subjective late pregnancy stress was associated with increased offspring ASD traits in the whole sample (β = 0.089, p = 0.073) and in the related (β=0.045, p = 0.424) and unrelated mother-child (β=0.233, p = 0.029) subgroups. Non-significant interaction terms demonstrated that the mechanisms underlying the association between maternal stress and ASD and birth outcomes are likely to be similar and environmentally driven in the different conception groups. Conclusion Findings demonstrate the utility of genetically informed designs in disentangling inherited factors from environmental influences in the study of prenatal risk factors. Correlations between maternal prenatal stress and offspring ASD being present in both related and unrelated mother-child groups indicate an environmental link that is consistent with a potential causal effect. Associations detected are of imperative use for clinicians and policymakers, as they can guide the implementation of early psychosocial care for families at high liability.