99 - Autism risk rises with prematurity: A nationwide matched cohort study

Publication Number: 1091.99

Ariel Israel, Leumit Research Institute, Jerusalem, Yerushalayim, Israel; Francis B. Mimouni, Tel aviv university, Tel Aviv, HaMerkaz, Israel; Shlomo Vinker, Leumit Health Services, Tel Aviv, Tel Aviv, Israel; Joseph Mendlovic, AdventHealth for Children, Tel AVIV, Tel Aviv, Israel

Background: Prematurity is a recognized risk factor for autism spectrum disorder (ASD), but the magnitude of risk across gestational age ranges is not well established.

Objective: We aimed to quantify the dose–response relationship between decreasing gestational age at birth and subsequent ASD risk.

Design/Methods: We conducted a retrospective cohort study using the electronic health records of Leumit Health Services (LHS), a nationwide Israeli HMO serving ~730,000 members. The cohort included children born between 2011–2021 with accessible pregnancy records documenting both last menstrual period and delivery date. Each child with ASD (n = 1,241) was matched to 10 controls without ASD on age, sex, ethnicity, socioeconomic status, and enrollment year. Gestational age was categorized as < 28, 28–31, 32–33, 34–35, 36, 37–42 (term), and ≥42 weeks. Odds ratios (ORs) with 95% confidence intervals (CIs) were computed using Fisher’s exact test.

Results: A strong inverse relationship between gestational age and ASD risk was observed. Compared with term birth (37–42 weeks), ASD risk increased progressively with prematurity:
• < 28 weeks: OR 3.51 [1.25–8.67], P = 0.009
• 28–31 weeks: OR 3.02 [1.44–5.89], P = 0.002
• 32–33 weeks: OR 2.11 [1.27–3.39], P = 0.003
• 34–35 weeks: OR 1.66 [1.19–2.26], P = 0.002
• 36 weeks: OR 1.40 [1.07–1.81], P = 0.011
Post-term birth (≥42 weeks) was not significantly associated (OR 1.45 [0.83–2.39], P = 0.14).

Conclusion(s): Earlier gestational age at birth is strongly and progressively associated with higher ASD risk. The dose-response pattern supports a potential causal link, possibly mediated by white matter injury and neuroinflammation in preterm infants. These findings emphasize the need for tailored neurodevelopmental surveillance and early ASD screening programs proportional to prematurity severity.

Association Between Gestational Age at Delivery and Risk of Autism Spectrum Disorder
autism_forest_plot.pdfForest plot illustrating odds ratios (95 % CI) for autism spectrum disorder (ASD) by gestational age at delivery. Risk increased progressively with decreasing gestational age compared with term birth (37–42 weeks).