Neurological and neurodevelopmental outcomes in neonates and children after maternal chikungunya infection in pregnancy: a systematic review and meta-analysis.

Abstract

Chikungunya virus (CHIKV) is a re-emerging Aedes-borne virus with documented vertical transmission in pregnancy. Neurological and neurodevelopmental outcomes in neonates and children have important clinical and societal implications, yet evidence remains limited and fragmented. We therefore undertook a quantitative meta-analysis and narrative synthesis on neurological and neurodevelopmental outcomes in neonates and children after maternal chikungunya infection in pregnancy. In this systematic review and meta-analysis, we searched PubMed, Embase, Web of Science, and Scopus from inception to January 3, 2026, with no language restrictions. We included observational studies reporting neurological outcomes in neonates and/or children after maternal CHIKV infection during pregnancy. Prespecified exclusion criteria were duplicate records/publications; non-original reports; non-human studies; and reports without useable outcome data for synthesis. Quantitative outcomes were: (1) the pooled proportion of acute neonatal neurological outcomes among neonates with confirmed vertical CHIKV infection (≤28 days), and (2) the relative risk (RR) of adverse neurodevelopmental outcomes (>28 days) in children born to mothers with CHIKV infection compared with children of uninfected mothers. Quantitative outcomes were pooled using random-effects meta-analysis (Freeman-Tukey for proportions; inverse-variance pooling for RRs), with heterogeneity assessed by I². Risk of bias was assessed using the Joanna Briggs Institute (JBI) checklist (case series/cross-sectional) and the Newcastle-Ottawa Scale (NOS) (cohort and case-control studies), and certainty of evidence was appraised with Grading of Recommendations Assessment, Development and Evaluation (GRADE). Qualitative synthesis summarized acute neonatal neurologic manifestations, long-term neurodevelopmental outcomes, and neuroimaging/cerebrospinal fluid (CSF) findings. The protocol was registered in International Prospective Register of Systematic Reviews (PROSPERO) (CRD420251120058). The search identified 1080 records; 26 studies met inclusion criteria. All 26 contributed to the qualitative synthesis and 9 entered the quantitative meta-analysis. Among neonates with confirmed vertical CHIKV infection, the pooled proportion with neurological outcomes was 48.0% (95% CI 24.0-73.0; 7 studies; n = 157 neonates; I² = 88.14%; risk of bias: JBI: 3 high, 4 moderate; GRADE: low) with substantial heterogeneity. In cohort studies, maternal CHIKV infection during pregnancy was associated with a higher risk of adverse post-neonatal neurodevelopmental outcomes (RR 1.87, 95% CI 1.30-2.70; 2 studies, n = 264 mother-child pairs/children; I² = 36.03%; risk of bias: low (NOS 8-9); GRADE: low; predominantly late-pregnancy/peripartum exposure). Qualitative evidence indicated that affected neonates are often asymptomatic at birth but typically develop signs on days 3-7 of life. Severe cases feature encephalopathy, encephalitis/meningoencephalitis, or seizures, and neuroimaging is dominated by white-matter injury, often with splenial diffusion restriction. Our findings suggest that vertical CHIKV infection often causes early neonatal neurological manifestations, and maternal infection in late pregnancy or the perinatal period may be associated with a nearly twofold increase in adverse long-term neurodevelopment in offspring. However, these inferences are based on a small, predominantly observational evidence base with heterogeneous outcome definitions and ascertainment, which limits the precision and comparability of pooled estimates. Despite a limited and heterogeneous evidence base, these findings support proactive identification of high-risk peripartum exposure, targeted diagnostic testing and close observation during the first postnatal week, and longitudinal developmental follow-up. From a public-health perspective, they emphasize the importance of mosquito-bite prevention for pregnant women and robust vector control, as well as strengthened newborn monitoring and timely access to early-intervention and family support services in affected settings. Prevention and Control of Emerging and Major Infectious Diseases-National Science and Technology Major Project; National Natural Science Foundation of China.