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

Abstract

ImportanceMaternal 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.ObjectiveTo explore the association of maternal preconception HBV infection with CHDs in offspring.Design, Setting, and ParticipantsThis 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.ExposuresMaternal preconception HBV infection statuses, including uninfected, previous, and new infection.Main Outcomes and MeasuresThe 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.ResultsAfter 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 RelevanceIn 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.

Maternal Hepatitis B Virus Infection and Risk of Congenital Heart Diseases—Reply

“…The authors of the letter argue that the prevalence of hepatitis B virus infection varies by nearly 25% between our study and another study cited, a difference that might influence the associations observed in our study. However, it should be noted that the nationwide cross-sectional study by Liu et al was conducted among pregnant Chinese women.…”

“…Overall, these comments on our study help us better interpret our conclusions. In the future, we plan to conduct a study with more detailed extending data to explore the effect of maternal preconception hepatitis B virus infection on the different subtypes of congenital heart disease in offspring.…”

“…In Reply We appreciate the thoughtful comments on our study and thank the authors for their suggestions. Although there are some limitations to the study, we still believe that hepatitis B virus screening and hepatitis B virus vaccination–induced immunity prior to pregnancy are indispensable and that prepregnancy hepatitis B virus infection should be taken seriously.…”

“…However, it should be noted that the nationwide cross-sectional study by Liu et al was conducted among pregnant Chinese women. In contrast, the current study, based on National Free Preconception Checkup Project (NFPCP), was conducted among reproductive-aged women planning to conceive, rather than pregnant women with or without pregnancy intention. Therefore, with the different target populations, the prevalence of women with hepatitis B virus infection might vary.…”

Maternal Hepatitis B Virus Infection and Risk of Congenital Heart Diseases

“…Second, propensity score matching was used to balance the distribution of comorbidity and confounding conditions between exposed and control groups . In the study by Wu et al, women with hepatitis B infection were initially considered as a group of participants to match control individuals, which is appropriate to explore the association between maternal hepatitis B infection (as a group) and congenital heart disease in offspring. However, women with hepatitis B infection were divided into previous infection and new infection, resulting in important differences in the comparison of basic characteristics of the 3 groups of participants.…”