Abstract
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 long-term morbidity. In this study, we assessed nHSV global epidemiology, regional variations, and temporal trends. METHODS: We conducted a systematic review of PubMed, Embase, and national surveillance reports through 12 December 2024, and reported findings in accordance with PRISMA guidelines. We used random-effects meta-analysis to 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 in 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.