Abstract and Introduction
Abstract
To examine the risks of genital herpes and antiherpes treatment during pregnancy in relation to preterm delivery (PTD), we conducted a multicenter, member-based cohort study within 4 Kaiser Permanente regions: northern and southern California, Colorado, and Georgia. The study included 662,913 mother-newborn pairs from 1997 to 2010. Pregnant women were classified into 3 groups based on genital herpes diagnosis and treatment: genital herpes without treatment, genital herpes with antiherpes treatment, and no herpes diagnosis or treatment (unexposed controls). After controlling for potential confounders, we found that compared with being unexposed, having untreated genital herpes during first or second trimester was associated with more than double the risk of PTD (odds ratio (OR) = 2.23, 95% confidence interval (CI): 1.80, 2.76). The association was stronger for PTD due to premature rupture of membrane (OR = 3.57, 95% CI: 2.53, 5.06) and for early PTD (≤35 weeks gestation) (OR = 2.87, 95% CI: 2.22, 3.71). In contrast, undergoing antiherpes treatment during pregnancy was associated with a lower risk of PTD compared with not being treated, and the PTD risk was similar to that observed in the unexposed controls (OR = 1.11, 95% CI: 0.89, 1.38). The present study revealed increased risk of PTD associated with genital herpes infection if left untreated and a potential benefit of antiherpes medications in mitigating the effect of genital herpes infection on the risk of PTD.
Introduction
Preterm delivery (PTD), defined as giving birth before 37 completed weeks of gestation, is the leading cause of perinatal mortality and morbidity. In the United States and other developed countries, it is also the leading cause of many debilitating conditions among offspring, including cerebral palsy, blindness, and deafness. In addition, it is the major cause of admission to neonatal intensive care units and a significant contributor to medical expenditure during infancy and early childhood. Each year in the United States, approximately 12% of all births (approximately half a million births) are the result of PTD, and many of those preterm infants are admitted to a neonatal intensive care unit. The economic costs associated with PTD amount to more than $26 billion each year and are rising. PTD is a global crisis as defined by the World Health Organization and the March of Dimes. Despite decades of research, the incidence of PTD has not been reduced, in large part because of a lack of progress in understanding its underlying causes.
Although infection during pregnancy has long been suspected to be an important risk factor for PTD, treating bacterial infections during pregnancy has not been demonstrated to be effective in reducing the rate of PTD. There is, however, little literature examining the potential impact of viral infections of the reproductive tract on PTD. Genital herpes simplex infections are reported to be prevalent in pregnant women based on seropositivity (14%–22%), although the prevalence of primary genital herpes infection during pregnancy is relatively low (≈2%). Among the limited studies in which genital herpes infection during pregnancy was examined, the focus has been on the impact of maternal herpes infection on vertical transmission to offspring. The relationship between genital herpes infection and PTD risk is largely unknown. Consequently, the treatment effect of antiherpes medication on reducing PTD risk has largely not been examined. To examine genital herpes infection and antiherpes medications in relation to the risk of PTD, we conducted a multicenter study among 4 geographically and demographically diverse Kaiser Permanente regions with more than 73,000 births annually: Kaiser Permanente California, including the northern and southern California regions, Kaiser Permanente Colorado, and Kaiser Permanente Georgia.