Prenatal maternal risk factors associated with autism spectrum disorder (ASD) among children in Palestine: a case–control study

Autism spectrum disorder (ASD) is a multifactorial neurodevelopmental condition. This study aimed to identify prenatal maternal risk factors associated with ASD among children in the West Bank, Palestine. A frequency-matched case-control study was conducted from April 2024 to April 2025. The study included 90 children with confirmed ASD and 180 controls without ASD, matched by age and sex in a 1:2 ratio. Data on maternal prenatal psychosocial, lifestyle, environmental, infectious, obstetric, chronic disease, nutritional, and medication-related exposures were collected through structured face-to-face interviews with mothers or primary caregivers, with medical record review when available. Continuous variables were summarized as means and standard deviations, and categorical variables as frequencies and percentages. Pearson’s chi-square test, Fisher’s exact test, and Monte Carlo exact testing were used as appropriate. Univariate logistic regression estimated crude odds ratios (ORs), and multivariable logistic regression identified independent prenatal factors associated with ASD. Because some exposures were infrequent, we performed Firth’s penalized logistic regression. Sensitivity analyses were performed using alternative model specifications. Child age and sex were identical between cases and controls, indicating successful matching. In univariate analysis, maternal psychological stress, passive smoking, pre-pregnancy obesity, second-trimester infection, late pregnancy bleeding, maternal chronic disease, and immune or inflammatory disease were associated with ASD. In the conventional multivariable model, maternal psychological stress (adjusted OR [aOR] = 2.63, 95% confidence interval [CI]: 1.49–4.63), passive smoking (aOR = 2.27, 95% CI: 1.17–4.39), second-trimester infection (aOR = 10.32, 95% CI: 1.03–104.01), and late pregnancy bleeding (aOR = 3.55, 95% CI: 1.08–11.66) were associated with ASD. In the Firth model, estimates for psychological stress (aOR = 2.53, 95% CI: 1.46–4.41) and passive smoking (aOR = 2.20, 95% CI: 1.15–4.21) were similar. The aOR for second-trimester infection decreased to 6.74 (95% CI: 1.14–71.43), and that for late pregnancy bleeding was 3.32 (95% CI: 1.09–11.06). The infection estimate remained imprecise. Sensitivity analyses supported the stability of these findings. Maternal psychological stress, passive smoking, second-trimester infection, and late pregnancy bleeding were independently associated with ASD among children in Palestine.