Global epidemiology of neonatal herpes: systematic review, meta-analyses, and meta-regressions

Background Neonatal herpes simplex virus (nHSV) infection, caused by HSV-1 or HSV-2, is a global health concern due to its high mortality and longterm morbidity. In this study, we assessed nHSV global epidemiology, regionvariations, and temporal trends. Methods We conducted a systematic review of PubMed, Embase, and nationsurveillance reports through 12 December 2024, and reported findings in accordance with PRISMA guidelines. We used random-effects meta-analysis estimate pooled mean outcomes and meta-regression analyses to assess associations, temporal trends, and potential sources of heterogeneity. Results We identified 143 relevant publications from three of the six World Health Organization regions, providing 140 nHSV incidence rate measures and 103 proportions of incident nHSV-1 vs. nHSV-2 cases. The global pooled and regional population-weighted mean incidence rate was 8.2 (95% confidence interval (CI) = 5.9-10.7) per 100 000 live births. Incidence rate was highest the Americas (13.3 cases per 100 000 live births; 95% CI = 9.9-17.2), followed by the European Region (5.2 cases per 100 000 live births; 95% CI = 3.4-7.3) and the Western Pacific Region (2.9 cases per 100 000 live births; 95% CI = 2.2-3.6). Globally, nHSV-1 and nHSV-2 accounted for pooled and weighted means of 47.3% (95% CI = 39.5-55.0) and 52.8% (95% CI = 45.2-60.5) of cases, respectively. The highest nHSV-1 proportion was in the Western Pacific Region (57.7%; 95% CI = 49.2-66.1), while the highest nHSV-2 proportion was in the Region of the Americas (60.5%; 95% CI = 55.8-65.1). Meta-regression analyses showed an annual increase of 3.5% (95% CI = 1.5-5.6) in nHSV incidence rate, alongside a yearly 1.4% (95% CI = 0.9-1.9) increase in the proportion of nHSV-1 cases and a 1.1% (95% CI = 0.6-1.6) decrease in the proportion of nHSV-2 cases. Conclusions nHSV affects approximately one in 10 000 newborns, with regional variations and a rising incidence rate. The increasing dominance of nHSV-1 over nHSV-2 reflects shifting HSV epidemiology.