Hep B Prior to Pregnancy Tied to Congenital Heart Diseases in Infants

Maternal hepatitis B virus (HBV) infection prior to pregnancy was significantly associated with congenital heart diseases (CHDs) in offspring, a retrospective cohort study from China showed.

Compared with uninfected women, those with HBV infection before pregnancy had a higher risk of CHDs in offspring, with an adjusted relative risk ratio (aRR) of 1.23 (95% CI 1.02-1.49), reported Ying Yang, PhD, of the National Research Institute for Family Planning in Beijing, and colleagues in JAMA Pediatrics.

In addition, compared with couples who were both uninfected with HBV prior to pregnancy, previously infected women with uninfected men had a higher risk of CHDs in offspring (aRR 1.36, 95% CI 1.09-1.69), as did previously infected men with uninfected women (aRR 1.51, 95% CI 1.09-2.09), after multivariable adjustment.

No significant association was seen between new maternal HBV infection and CHDs in offspring.

"Our study provided new evidence of associations between maternal preconception HBV infection and risk of CHDs in offspring among Chinese childbearing-aged women, indicating the necessity of HBV screening in preparation for pregnancy, and the importance of staying free of HBV infection for women," Yang and team wrote. "For those women with previous HBV infection, even if they were not contagious, they should also be taken seriously to decrease the risk of CHDs in offspring."

CHD accounts for about one-third of all birth defects, Yang and colleagues noted. Since HBV affects 3% to 10% of reproductive-age women in China, screening should be recommended in this population, as well as for their partners.

"HBV infection has been reported to affect not only oocytes but also sperm, and there may be an interaction effect of spouses' preconception HBV infection statuses," the authors explained.

They pointed to previous studies that showed that HBV DNA sequences were able to integrate into chromosomes and be active during embryo development, "which might result in abnormal embryonic heart development consequently."

"Maternal preconception HBV infection may alter the epigenome profile in newborns, which could influence embryonic heart development," they added.

Yang and team also recommended that HBV status be monitored in this population.

"In China, although HBV vaccination has been incorporated into the Chinese immunization program since the early 1990s, considering the serum HBsAb titers may decrease gradually with age, both women and men are recommended to regularly monitor their HBV infection status, and HBV-related health education should be strengthened, especially for couples who plan to conceive, to lower the risk of CHDs in offspring," they wrote.

In the U.S., all adults are recommended to undergo HBV screening and receive vaccination. In guidance updated last week, the CDC recommended that pregnant women be screened for HBV during their first trimester regardless of vaccination status or history of testing.

For this study, Yang and colleagues included 3,690,427 women ages 20 to 49, of whom 738,945 were infected with HBV, including 393,332 with previous infection and 345,613 with new infection.

They used 1:4 propensity score matching of data from 2013 to 2019 from the National Free Preconception Checkup Project, a national free health service for childbearing-age women who plan to conceive throughout mainland China.

Approximately 0.03% of uninfected women and newly infected women carried an infant with CHDs, while 0.04% of women with HBV infection before pregnancy carried an infant with CHDs.

CHDs included atrial septal defect, ventricular septal defect, atrioventricular septal defect, patent ductus arteriosus, Tetralogy of Fallot, pulmonary stenosis, and transposition of the great arteries.

Yang and colleagues said that missing diagnoses of CHDs within 28 days of delivery was possible, and CHD subtypes were not recorded, which were both limitations to their study. Furthermore, the association of different HBV DNA loads with the risk of CHDs in offspring could not be assessed.

In addition, the study did not take into account pregnancy complications, such as gestational diabetes, which may have led to a potentially biased estimation of the association of maternal HBV infection before pregnancy with CHDs in offspring.

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