The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians · 2026
Maternal genital herpes infection during pregnancy and the risk of preterm delivery, an overlooked and understudied link between maternal infection and adverse fetal outcome.
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Li De-Kun, Ferber Jeannette R, Odouli Roxana, Garzaro Piero, Quesenberry Charles
Аннотация
BACKGROUND: While reproductive tract infections have been associated with preterm delivery (PTD), the specific etiologically-relevant infections remain elusive. Genital herpes simplex virus (GHSV), after initial infection, remains in the body permanently and can cause viral shedding during pregnancy leading to placental inflammation which is one of the major pathogenetic pathways for PTD. However, the direct evidence linking between GHSV infection and PTD has not been well-investigated and reported.
METHODS: A large prospective cohort study with a two-stage study design was conducted among 84,935 pregnant women at Kaiser Permanente Northern California (KPNC). Pregnant women with and without GHSV (exposure) were identified from the KPNC electronic health record (EHR). Gestational age at delivery was also captured for all deliveries EHRs to determine PTD (outcome).
RESULTS: Using Cox regression to control for confounders and account for varying gestational age at delivery, GHSV infection, if not treated during pregnancy, was associated with more than 80% increased risk of PTD compared to no GHSV infection: adjusted hazard ratio (aHR)=1.81, 95% confidence interval (CI)=1.59-2.06). This association was much stronger for women with symptomatic, therefore active, GHSV infection during pregnancy with > 3.5 times higher risk of PTD than women without GHSV infection. In contrast, the association was weaker for women with asymptomatic, therefore inactive, GHSV infection during pregnancy (33% increased risk of PTD). This contrast between symptomatic and asymptomatic infection supports the argument that the association between GHSV infection and increased risk of PTD is likely due to underlying biologic pathogenesis, rather than confounding.
CONCLUSIONS: This study reveals an important, yet modifiable (treatable) infectious risk factor for PTD, and provides potentially actionable findings that could lead to proactive identification of pregnant women with GHSV infection through prenatal screening. The findings could stimulate research to examine the effective treatment of women with GHSV infection during pregnancy to reduce PTD.
METHODS: A large prospective cohort study with a two-stage study design was conducted among 84,935 pregnant women at Kaiser Permanente Northern California (KPNC). Pregnant women with and without GHSV (exposure) were identified from the KPNC electronic health record (EHR). Gestational age at delivery was also captured for all deliveries EHRs to determine PTD (outcome).
RESULTS: Using Cox regression to control for confounders and account for varying gestational age at delivery, GHSV infection, if not treated during pregnancy, was associated with more than 80% increased risk of PTD compared to no GHSV infection: adjusted hazard ratio (aHR)=1.81, 95% confidence interval (CI)=1.59-2.06). This association was much stronger for women with symptomatic, therefore active, GHSV infection during pregnancy with > 3.5 times higher risk of PTD than women without GHSV infection. In contrast, the association was weaker for women with asymptomatic, therefore inactive, GHSV infection during pregnancy (33% increased risk of PTD). This contrast between symptomatic and asymptomatic infection supports the argument that the association between GHSV infection and increased risk of PTD is likely due to underlying biologic pathogenesis, rather than confounding.
CONCLUSIONS: This study reveals an important, yet modifiable (treatable) infectious risk factor for PTD, and provides potentially actionable findings that could lead to proactive identification of pregnant women with GHSV infection through prenatal screening. The findings could stimulate research to examine the effective treatment of women with GHSV infection during pregnancy to reduce PTD.