Not Positively Coupled at the Country Level: Maternal Sepsis and Other Maternal Infection Burden and Child Autism Disability in 204 Countries and Territories, 1990–2023

Aims Maternal infection during pregnancy is associated with offspring autism spectrum disorder (ASD) in individual-level studies (pooled OR 1.13–1.32; hospitalisation-grade 1.30–1.81), but negative-control and sibling designs attribute most of it to familial confounding (2.4 million Swedish children: pregnancy HR 1.16; pre-pregnancy control HR 1.25; sibling HR 0.94). Whether any country-level coupling exists has never been tested.Methods We conducted an ecological bounding analysis of the Global Burden of Disease Study 2023 (GBD 2023; 204 countries and territories, 1990–2023). Exposure: incident maternal sepsis and other maternal infections per 1,000 live births; outcome: ASD years-lived-with-disability (YLD) rate at ages 5–9 years. Distributed lags aligned exposure to birth cohorts (k=0–9; primary 7); country-and-year fixed effects and first differences were co-primary, with Driscoll–Kraay baseline inference and cluster- and bootstrap-robust variants. Bidirectional negative controls were judged by equivalence testing (TOST; δ=0.02 fixed before result inspection), future-exposure tests (t+3, t+5), and minimum-detectable-effect bounds.Results The within-country association was weakly negative (FE β=−0.0137; 95% CI −0.0234 to −0.0040 under Driscoll–Kraay; −0.0507 to +0.0233 under country clustering) and structurally non-causal: a flat lag profile with no birth-cohort peak at k≈7; future exposure associated at the same sign and two-thirds magnitude (−0.009/−0.008 at t+3/t+5); the main estimate sat below the negative-control background band's lower edge (band |β|≈0.02–0.05); and the association was zero where diagnostic capacity was high and stable (top HAQ tertile +0.0007), driven by middle-HAQ transition countries (−0.071). The conservative bound excludes positive elasticities above +0.023 (exposure doubling → +2.3% ASD YLDs); the individual-literature-implied elasticity (0.005–0.015) lies within it.Conclusions Country-level data bound but cannot adjudicate the maternal infection–autism question. Maternal sepsis reduction is justified by maternal and neonatal outcomes, not measurable ASD benefit, and GBD ASD maps should be read as diagnostic-capacity maps. Bidirectional negative controls with fixed equivalence margins and future-exposure tests offer a portable standard for reporting ecological nulls.