New research from Denmark found that newborns diagnosed with early-onset sepsis were more likely to develop autism spectrum disorder later in life.
The researchers, led by Mads Andersen of the Aarhus University Hospital, also examined attention deficit hyperactivity disorder (ADHD), but the association appeared weaker and was likely influenced by shared familial factors.
They followed nearly 1 million children who were born between 1997 and 2013 and tracked health data until June 2021 using national registries. The cohort included children who were born at or after 35 weeks of gestation and excluded those with major birth defects.
Of the 981,869 children included, 8154 had early-onset sepsis, and 152 were diagnosed with meningitis in the first week of life. Diagnoses were based on clinical codes and, when available, confirmed by positive bacterial cultures.
Pediatric patients with sepsis had higher rates of autism spectrum disorder (ASD) and ADHD than those without infection. Sepsis was associated with a 43% increased likelihood of ASD (adjusted hazard ratio [HR] = 1.43, 95% confidence interval [CI] = 1.30–1.58). For ADHD, the adjusted HR was 1.28 (95% CI = 1.17–1.39). However, in sibling comparisons—where one child had sepsis and the other did not—the association with ADHD was no longer significant (HR = 1.12, 95% CI = 0.93–1.34), though the association with ASD persisted (HR = 1.32, 95% CI = 1.05–1.66). Familial factors that may affect incidence of ASD and ADHD, especially in conjunction with increased gastrointestinal symptoms, continue to be explored, the authors noted.
Rates of neurodevelopmental disorders per 1000 person-years were higher in the exposed group: 4.5 for ADHD and 3.3 for ASD in pediatric patients with sepsis, compared with 3.2 and 2.0, respectively, in unexposed children.
The investigators also assessed the smaller group of pediatric patients with early meningitis. Point estimates suggested higher rates of both ADHD and ASD, though the small sample size limited precision.
Culture-positive sepsis, which was confirmed by blood cultures, was identified in 257 pediatric patients. This group showed no elevated risk for ADHD (incidence rate ratio [IRR] = 0.98, 95% CI = 0.47–1.79), but the researchers observed a nonsignificant increase in ASD risk (IRR = 1.77, 95% CI, 0.91–3.09).
They adjusted for a range of potential confounding factors, including parental age, smoking, education, income, and psychiatric history. Sensitivity analyses using stricter outcome definitions and adjustments for loss to follow-up yielded consistent results.
The findings suggest that sepsis during the first week of life may be associated with an increased likelihood of ASD in children born at term. The observed link to ADHD may be due to shared familial traits, such as genetic or environmental factors.
This study contributes to growing evidence on the long-term effects of early-life infections on brain development and supports further investigation into the biological mechanisms involved.
The authors reported no conflicts of interest.
Source: Paediatric and Perinatal Epidemiology