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

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

Liyan Zhou, Chenyuan Qin, Jie Deng, Yan Xing, Hongguang Chen, Daniel R. Lucey, Jue Liu 

DOI: 10.1016/j.eclinm.2026.103888

Background

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.

Methods

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).

Results

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.

Fig. 1 Flow diagram of study selection. Flow diagram showing the identification, screening, eligibility assessment, and inclusion of studies in accordance with PRISMA.

Fig. 2 Forest plot of the pooled proportion of neonatal neurological outcomes among neonates with confirmed vertical chikungunya virus infection. Random-effects meta-analysis of proportions (Freeman–Tukey double-arcsine transformation). Squares represent the study-specific proportions (ES), with square size proportional to study weight; horizontal lines indicate 95% confidence intervals. The diamond represents the pooled proportion and its 95% CI, and the vertical dashed line indicates the pooled estimate. Abbreviations: CI, confidence interval; ES, study-specific proportion; I2, Higgins' I-squared statistic.

Fig. 3 Sensitivity analysis of the proportions meta-analysis. Leave-one-out sensitivity analysis showing the pooled proportion after sequential exclusion of each study. Each point shows the pooled proportion after omitting one study; bars show 95% CIs.The dashed line and shaded band indicate the primary pooled estimate and its 95% CI. Abbreviations: CI, confidence interval; I2, Higgins' I-squared statistic.

Fig. 4 Forest plot of the pooled relative risk of adverse post-neonatal neurodevelopmental outcomes associated with maternal chikungunya virus infection during pregnancy. Fixed-effects inverse-variance meta-analysis pooling relative risks, with study-specific and pooled estimates shown with 95% confidence intervals. Squares show study-specific RRs (size ∝ weight) and lines show 95% CIs; the diamond shows the pooled RR. The dashed line at RR = 1.0 indicates no effect. Abbreviations: CI, confidence interval; H2, Cochran's H-squared statistic; I2, Higgins' I-squared statistic; Q, Cochran's Q statistic; RR, relative risk.

Conclusion

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.

Reference

Zhou, L., Qin, C., Deng, J., Xing, Y., Chen, H., Lucey, D.R. and Liu, J. (2026). Neurological and neurodevelopmental outcomes in neonates and children after maternal chikungunya infection in pregnancy: a systematic review and meta-analysis. eClinicalMedicine, [online] 94, p.103888. doi:https://doi.org/10.1016/j.eclinm.2026.103888.