Maternal pre-pregnancy infection with hepatitis B virus and the risk of preterm birth: a population-based cohort study

BACKGROUND: Preterm birth is the leading cause of child death in children younger than 5 years. Large cohort studies in developed countries have shown that maternal hepatitis B virus infection is associated with preterm birth, but there is little reliable evidence from China and other developing countries, where hepatitis B virus prevalence is intermediate or high. Hence, we designed this study to investigate the association between pre-pregnancy hepatitis B virus infection and risk of preterm and early preterm birth. METHODS: Between Jan 1, 2010, and Dec 31, 2012, we did a population-based cohort study using data from 489 965 rural women aged 21-49 years who had singleton livebirths from 220 counties of China who participated in the National Free Preconception Health Examination Project. Participants were divided into three groups according to their pre-pregnancy status of hepatitis B virus infection: women uninfected with hepatitis B virus (control group), women who were HBsAg positive and HBeAg negative (exposure group 1), and women who were both HBsAg and HBeAg positive (exposure group 2). The primary outcome was preterm birth (gestation at less than 37 weeks). We used log-binomial regression to estimate adjusted risk ratios (aRR) of preterm birth for women with pre-pregnancy hepatitis B virus infection, and risk of early preterm birth (gestation less than 34 weeks). FINDINGS: 489 965 women met inclusion criteria and were included in this study; of these, 20 827 (4·3%) were infected with hepatitis B virus. Compared with women who were not infected with hepatitis B virus, women who were HBsAg positive and HBeAg negative had a 26% higher risk of preterm birth (aRR 1·26, 95% CI 1·18-1·34) and women who were both HBsAg and HBeAg positive had a 20% higher risk of preterm birth (aRR 1·20, 1·08-1·32). Compared with women who were not infected with hepatitis B virus, women who were HBsAg positive and HBeAg negative manifested an 18% higher risk of early preterm birth (gestation less than 34 weeks; aRR 1·18, 1·04-1·34) and women who were both HBsAg and HBeAg positive had a 34% higher risk of early preterm birth (aRR 1·34, 1·10-1·61). Maternal pre-pregnancy hepatitis B virus infection was independently associated with higher risk of preterm birth and early preterm birth. These associations were similar in subgroups of participants as defined by baseline characteristics. INTERPRETATION: Besides mother-to-child transmission, the risk of preterm birth in women infected with hepatitis B virus should not be neglected. Comprehensive programmes that focus on early detection of hepatitis B virus infection before pregnancy and provide appropriate medical intervention for women infected with hepatitis B virus before and during pregnancy would be helpful in improving maternal and neonatal outcomes and reducing child mortality. FUNDING: Chinese Association of Maternal and Child Health Studies.