Maternal Preconception Hepatitis B Virus Infection and Risk of Congenital Heart Diseases in Offspring Among Chinese Women Aged 20 to 49 Years

Importance: Maternal hepatitis B virus (HBV) infection during early pregnancy has been related to congenital heart diseases (CHDs) in offspring. However, no study to date has evaluated the association of maternal preconception HBV infection with CHDs in offspring. Objective: To explore the association of maternal preconception HBV infection with CHDs in offspring. Design, Setting, and Participants: This retrospective cohort study used nearest-neighbor (1:4) propensity score matching of 2013 to 2019 data from the National Free Preconception Checkup Project (NFPCP), a national free health service for childbearing-aged women who plan to conceive throughout mainland China. Women aged 20 to 49 years who got pregnant within 1 year after preconception examination were included, and those with multiple births were excluded. Data were analyzed from September to December 2022. Exposures: Maternal preconception HBV infection statuses, including uninfected, previous, and new infection. Main Outcomes and Measures: The main outcome was CHDs, which were prospectively collected from the birth defect registration card of the NFPCP. Logistic regression with robust error variances was used to estimate the association between maternal preconception HBV infection status and CHD risk in offspring, after adjusting for confounding variables. Results: After matching with a 1:4 ratio, there were 3 690 427 participants included in the final analysis, where 738 945 women were infected with HBV, including 393 332 women with previous infection and 345 613 women with new infection. Approximately 0.03% (800 of 2 951 482) of women uninfected with HBV preconception and women newly infected with HBV carried an infant with CHDs, whereas 0.04% (141 of 393 332) of women with HBV infection prior to pregnancy carried an infant with CHDs. After multivariable adjustment, women with HBV infection prior to pregnancy had a higher risk of CHDs in offspring compared with women who were uninfected (adjusted relative risk ratio [aRR], 1.23; 95% CI, 1.02-1.49). Moreover, compared with couples who were uninfected with HBV prior to pregnancy (680 of 2 610 968 [0.026%]), previously infected women with uninfected men (93 of 252 919 [0.037%]) or previously infected men with uninfected women (43 of 95 735 [0.045%]) had a higher incidence of CHDs in offspring and were significantly associated with a higher risk of CHDs in offspring (previously infected women with uninfected men: aRR, 1.36; 95% CI, 1.09-1.69; previously infected men with uninfected women: aRR, 1.51; 95% CI, 1.09-2.09) with multivariable adjustment, while no significant association was observed between maternal new HBV infection and CHDs in offspring. Conclusions and Relevance: In this matched retrospective cohort study, maternal preconception previous HBV infection was significantly associated with CHDs in offspring. Moreover, among women with HBV-uninfected husbands, significantly increased risk of CHDs was also observed in previously infected women prior to pregnancy. Consequently, HBV screening and getting HBV vaccination-induced immunity for couples prior to pregnancy are indispensable, and those with previous HBV infection prior to pregnancy should also be taken seriously to decrease the CHDs risk in offspring.