Maternal Preconception Hepatitis B Increases Offspring’s Risk of Congenital Heart Diseases

Maternal hepatitis B virus (HBV) infection early in pregnancy has been linked to congenital heart diseases in offspring. However, a new study, published in JAMA Pediatrics, was the first to analyze the association between maternal preconception HBV infection and congenital heart diseases (CHD) in newborn infants.

The retrospective cohort study used nearest-neighbor (1:4) propensity score matching of 2013-2019 data, obtained from the National Free Preconception Checkup Project (NFPCP). The NTPCP is a national free health service for mainland Chinese women of childbearing age who intend to conceive.

The cohort included women 20-49 years of age who became pregnant within 1 year of a preconception examination. Multiple births were excluded, and data were analyzed from September-December 2022. The investigators recorded maternal preconception HBV infection statuses, categorized as either uninfected, previous, or new infection.

The primary study outcome was CHDs, which were collected prospectively from the birth defect registration card of the NFPCP. After adjusting for confounding variables, the investigators used logistic regression with robust error variances to estimate the correlation between maternal preconception HBV infection status and CHD risk in offspring.

After propensity score matching with a 1:4 ratio, 3690427 participants were included in the final analysis. Of this cohort, 738945 women were infected with HBV, including 393332 with a previous infection and 345613 with a new infection.

An estimated 0.03% (n = 800 of 2951482) of women uninfected with HBV preconception and women newly infected with HBV had an infant with CHDs. Comparatively, 0.04% (n = 141 of 393332) of women infected with HBV prior to pregnancy had an infant with CHDs.

Multivariable adjustment revealed women with HBV infection prior to pregnancy had a higher risk of CHDs in offspring, compared to offspring of uninfected women. Additionally, compared to couples who were uninfected with HBV prior to pregnancy (n = 680 of 2610968), previously infected women coupled with uninfected men (n = 93 of 252919) or previously infected men coupled with uninfected women (n = 43 of 95735) had a higher incidence of CHDs in offspring.

The investigators concluded that maternal preconception previous HBV infection was significantly associated with CHDs in infant offspring. Among women coupled with HBV-uninfected men, there was a significantly increased risk of CHDs observed in women previously infected before pregnancy.

These findings, the study authors argued, heighten the importance of HBV testing and hepatitis B vaccination. Individuals previously infected with HBV should take serious precautions to decrease the risk of congenital heart diseases in their offspring.