Maternal infection with hepatitis B virus before pregnancy and risk of congenital malformations in offspring: a record-linkage study of a large national sample from ChinaResearch in context

Abstract

Summary: Background: Whether hepatitis B virus (HBV) infection of women prior to pregnancy can influence risk of congenital malformations in offspring remains controversial. We assessed the association between them by considering congenital malformations in the aggregate as well as risk of organs systems using a large national sample of Chinese women. Methods: We performed a record-linkage cohort study of women who participated in National Free Preconception Health Examination Project, between January 1, 2010, and December 31, 2019 for whom data on congenital malformations in their offspring were available from the National Population-Based Birth Defects Surveillance Network. A total of 498,968 linked records were obtained, of which 127,371 were excluded because HBV status before pregnancy was unknown, the records involved multiple pregnancies, or pre-pregnancy examinations were conducted after conception. Based on pre-pregnancy status, mothers were assigned to two categories of HBsAg− or HBsAg+ and, in certain analyses, to three categories of HBsAg−, HBsAg+/HBeAg− or HBsAg+/HBeAg+. Potential associations of serological status with risk of congenital malformations, considered separately or in aggregate, were explored using multilevel logistic regression. Factors that might influence such associations were also explored. Findings: Among the 371,597 women analyzed, 21,482 (5.78%) were HBsAg+ before pregnancy, and 8333 (2.24%) had a fetus or child diagnosed with congenital malformations, composed of 7744 HBsAg− women and 589 HBsAg+ women. HBsAg+ status was associated with increased risk of congenital malformations in the aggregate (OR 1.14, 95% CI 1.03–1.25) and of cardiovascular malformations specifically (OR 1.18, 95% CI 1.03–1.35). HBsAg+/HBeAg− status was associated with significantly higher risk of cardiovascular malformations (OR 1.19, 95% CI 1.01–1.39) as well as reproductive malformations (OR 1.51, 95% CI 1.02–2.23). Associations between HBsAg+ status before pregnancy and risk of congenital malformations was modified by alanine aminotransferase activity (Pinteraction < 0.05). Interpretation: Prepregnancy HBV infection might be associated with fetal malformations. This association needs further investigation to confirm whether it is a causal association, and assess whether antiviral therapy of women with HBsAg+ planning to conceive might reduce the risk of fetal malformations. Funding: The National Health Commission of the People's Republic of China, China; Science and Technology Department of Sichuan Province, China; and the Ministry of Science and Technology of the People's Republic of China.

Keywords

• Maternal infection
• Hepatitis B virus
• Fetus
• Congenital malformations