Antenatal Psychosocial Stressors Associate with Clinical Severity in Children with Autism Spectrum Disorder

Background Autism Spectrum Disorder (ASD) has multifactorial etiology. Antenatal psychosocial stress may influence neurodevelopmental vulnerability through neuroendocrine and inflammatory mechanisms, though evidence remains inconsistent. This study examined associations between documented antenatal psychosocial stressors and ASD clinical severity while accounting for potential confounders. Methods This mixed retrospective-prospective study at a tertiary care center in India included 120 children diagnosed with ASD (2018–2024) and 120 age-matched controls. ASD severity was assessed using the Childhood Autism Rating Scale-2 (CARS-2) for prospective cases and validated clinical documentation for retrospective cases. Antenatal psychosocial stressors were documented using structured interviews. Multivariable logistic regression examined associations between stressor exposure and ASD severity, adjusting for maternal age, socioeconomic status, obstetric complications, and family psychiatric history. Results Mean age at diagnosis was 3.6 ± 1.3 years; 75% were male. Antenatal psychosocial stressors were documented in 62.5% of ASD cases versus 33.3% of controls (adjusted OR = 2.89, 95% CI: 1.58–5.28, p < 0.001). Among children with ASD, those with documented stressors had higher rates of moderate-severe presentations (58.7% vs 35.6%, adjusted OR = 2.41, 95% CI: 1.15–5.05, p = 0.02). A dose-response relationship was observed: severe stressors (adjusted OR = 3.12, 95% CI: 1.28–7.61, p = 0.01) and chronic duration (adjusted OR = 2.87, 95% CI: 1.19–6.94, p = 0.02) showed stronger associations. Second-trimester exposure showed the strongest association with severity (adjusted OR = 3.45, 95% CI: 1.32–9.01, p = 0.01). Maternal mental health concerns demonstrated the highest risk (adjusted OR = 3.24, 95% CI: 1.25–8.39, p = 0.02). Associations remained significant in sensitivity analyses restricted to prospective cases and after propensity score matching. Conclusions Antenatal psychosocial stressors were associated with both ASD diagnosis and clinical severity in a dose-dependent manner. These findings are consistent with existing recommendations for systematic psychosocial assessment during prenatal care. Prospective studies with biological stress markers are needed to establish causality and identify intervention windows for supporting maternal wellbeing.