Early-Onset Neonatal Infection and Cerebral Palsy.

Importance: Cerebral palsy is the leading motor disability in childhood. The potential etiologic contribution of early-onset neonatal infection remains uncertain. Objective: To examine the association between early-onset neonatal infection and cerebral palsy among near-term and full-term children. Design, Setting, and Participants: This nationwide population-based cohort study considered children born in Denmark between 2004 and 2022 with follow-up until 2025. All Danish near-term and full-term liveborn singleton births without major congenital anomalies were included. Data were analyzed from August 1, 2025, to December 31, 2025. Exposures: Early-onset infection was defined as an invasive bacterial infection within the first week after birth. Infections were defined by diagnostic codes of sepsis or meningitis or bacterial pathogens cultured from blood or cerebrospinal fluid. Main Outcomes and Measures: Cerebral palsy was defined as a validated diagnosis in the Danish Cerebral Palsy Registry or the Danish Cerebral Palsy Follow-up Program. The primary analysis estimated the association between sepsis and cerebral palsy. Secondary analyses included the associations between sepsis and cerebral palsy subtypes, neuroimaging findings, and gross motor function; the association between meningitis and cerebral palsy; and the associations between culture-positive infections only and cerebral palsy. The primary analysis was performed using multivariable logistic regression to estimate adjusted odds ratios (ORs) with 95% CI. Results: A total of 1 034 416 children were included (median gestational age at birth, 40 weeks [IQR, 39-41 weeks]; mean birth weight, 3550 g [SD, 502 g]; 528 072 male [51.0%]). A total of 8151 children (0.8%) had sepsis, and 236 (<0.1%) had meningitis. Among these children, 350 of 8151 (4.3%) had culture-positive sepsis, and 41 of 236 (17.4%) had culture-positive meningitis. Sepsis was associated with an increased risk of cerebral palsy with an adjusted OR of 8.13 (95% CI, 6.32-10.45). Sepsis showed a stronger association with nonambulatory status and the bilateral subtypes. The risk estimate increased when only culture-positive sepsis was considered with an OR of 23.58 (95% CI, 11.66-47.65). Meningitis was associated with even higher risks of cerebral palsy with ORs ranging from 49.27 (95% CI, 26.82-90.54) for all children who were exposed to 79.57 (95% CI, 24.52-258.18) for children with a culture-positive infection only. Conclusions and Relevance: In this cohort study of near-term and full-term children, early-onset neonatal sepsis and meningitis were associated with a markedly increased risk of cerebral palsy. Sepsis showed a stronger association with the more severe clinical presentations of cerebral palsy.