Maternal hepatitis B virus infection and risk of preterm birth in China
Authors: Qi-Tao Huang, Mei Zhong
Journal: The Lancet Global Health (2017)

Preterm births represent a heavy economic and social burden worldwide. However, the association between hepatitis B virus infection and preterm births remains controversial. Several large, population-based cohort studies in developed countries have shown that maternal hepatitis B virus infections are associated with a high risk of preterm birth. However, there is little reliable evidence from China, where the rate of hepatitis B virus infection is high. In this issue of The Lancet Global Health, Jue Liu and colleagues1Liu J Zhang S Liu M Wang Q Shen H Zhang Y Maternal pre-pregnancy infection with hepatitis B virus and the risk of preterm birth: a population-based cohort study.Lancet Glob Health. 2017; 5: e624-e632Summary Full Text Full Text PDF PubMed Scopus (86) Google Scholar investigate the association between maternal pre-pregnancy infection with hepatitis B virus and the risk of preterm birth in a population-based cohort in China. They find that maternal pre-pregnancy hepatitis B virus infection is independently associated with an increased risk of preterm birth. Conversely, three meta-analyses2Huang QT Chen JH Zhong M et al.Chronic hepatitis B infection is associated with decreased risk of preeclampsia: a meta-analysis of observational studies.Cell Physiol Biochem. 2016; 385: 1860-1868Crossref Scopus (21) Google Scholar, 3Huang QT Chen JH Zhong M et al.The risk of placental abruption and placenta previa in pregnant women with chronic hepatitis B viral infection: a systematic review and meta-analysis.Placenta. 2014; 358: 539-545Summary Full Text Full Text PDF Scopus (15) Google Scholar, 4Huang QT Wei SS Zhong M et al.Chronic hepatitis B infection and risk of preterm labor: a meta-analysis of observational studies.J Clin Virol. 2014; 611: 3-8Summary Full Text Full Text PDF Scopus (21) Google Scholar have indicated that hepatitis B virus infection is not associated with an increased risk of adverse pregnancy outcomes (eg, preterm birth, placenta previa, and placental abruption). The discrepancy between the findings of these studies and the study by Liu and colleagues might be related to the different characteristics of the study populations, research methods, sample sizes, and regional differences; some studies were retrospective, observational, or done with small sample sizes, which might be more susceptible to bias in data analysis. Moreover, almost all previous studies investigating the relation between pregnancy-related complications and hepatitis B virus infection have not taken account of hepatitis B virus load. It is well known that hepatitis B virus load represents a key factor in determining disease prognosis, from immune tolerance, to chronic inflammation, to life-threatening complications, through induction of inappropriate immunological reactions.5Ganem D Prince AM Hepatitis B virus infection—natural history and clinical consequences.N Engl J Med. 2004; 350: 1118-1129Crossref PubMed Scopus (1941) Google Scholar Although information on hepatitis B virus DNA load was not available in the databases Liu and colleagues studied, the authors showed that, compared with women who were not infected with hepatitis B virus, women who were hepatitis B surface antigen (HBsAg) positive and hepatitis B e antigen (HBeAg) negative had an 18% higher risk of preterm birth, and women who were both HBsAg and HBeAg positive had a 34% higher risk of preterm birth. Given that individuals with HBeAg-positive chronic infection usually have high amounts of hepatitis B virus DNA, the degree of influence on adverse pregnancy outcomes could be associated with hepatitis B virus DNA load. A dose–response relation between hepatitis B virus DNA load and preterm birth could not be ascertained with certainty. Pregnant women with a high hepatitis B virus DNA load are also at increased risk of mother-to-child transmission. Standard passive-active immunoprophylaxis with the hepatitis B virus vaccine and with hepatitis B virus immune globulin has a high failure rate in neonates, with the rate of intrauterine infections being approximately 15%, because of the high hepatitis B virus DNA load.6Patton H Tran TT Management of hepatitis B during pregnancy.Nat Rev Gastroenterol Hepatol. 2014; 117: 402-409Crossref Scopus (48) Google Scholar Clinical trials have reported that antiviral treatment in women with a high hepatitis B virus load during the second or third trimester of pregnancy could decrease the incidence of mother-to-child transmission.7Pan CQ Duan Z Dai E et al.Tenofovir to prevent hepatitis B transmission in mothers with high viral load.N Engl J Med. 2016; 374: 2324-2334Crossref PubMed Scopus (380) Google Scholar If a high hepatitis B virus DNA load could increase the risk of adverse pregnancy outcomes, anti-hepatitis B virus therapy might be more beneficial than prevention of perinatal hepatitis B virus transmission. Liu and colleagues' findings could have several clinical applications. First, since maternal pre-pregnancy hepatitis B virus infection was independently associated with an increased risk of preterm birth, the risk of preterm birth and other adverse pregnancy outcomes (besides mother-to-child transmission) in women infected with hepatitis B virus should not be neglected. It is worthwhile to further explore whether hepatitis B virus DNA load is associated with other pregnancy-related complications (eg, premature rupture of the membrane, pre-eclampsia, and placental abruption, among others). Second, HBeAg status might represent a simple marker and risk predictor of adverse pregnancy-related outcomes in chronic hepatitis B virus-infected populations. Early detection of hepatitis B virus infection before pregnancy, monitoring the risk of preterm birth, and providing appropriate medical intervention might help in improving maternal and neonatal outcomes. In the future, larger, prospective cohort studies, with adequate measurement of viral load in pregnant women infected with hepatitis B virus, might be worthwhile to explore the dose–response relation between hepatitis B virus DNA load and preterm birth, as well as other pregnancy-related complications. Moreover, it would be helpful to investigate whether anti-hepatitis B virus therapy could have additional health benefits, such as lowering the risk of preterm birth. We declare no competing interests. Maternal pre-pregnancy infection with hepatitis B virus and the risk of preterm birth: a population-based cohort studyBesides 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. Full-Text PDF Open Access