Heart Defects in Kids Linked to Dads’ Hepatitis B History Too

A child’s risk of congenital heart disease (CHD) may be related to a past hepatitis B virus (HBV) infection in either parent, according to a retrospective cohort study.

Paternal preconception HBV infection was linked to significantly greater odds of CHD in offspring (adjusted relative risk 1.40, 95% CI 1.11-1.76) among Chinese couples who had undergone prepregnancy testing, reported Yihua He, MD, of Beijing Anzhen Hospital at Capital Medical University in Beijing, and colleagues.

These results mirror those from a separate analysis from the same research group that showed that maternal HBV infection during prepregnancy or pregnancy was associated with CHD in offspring.

“The findings suggest that personalized reproductive guidance regarding HBV screening and staying free of HBV infection should be provided for both wives and husbands,” He’s group wrote in JAMA Pediatrics.

The authors cited “possible mechanisms for HBV creating congenital biologic effects, such as the integration of the HBV genome into the sperm cell genome inducing chromosomal aberrations and the expression of HBV S protein, impairing sperm quality and function.”

However, H. Nina Kim, MD, MSc, an infectious diseases and liver specialist at the University of Washington in Seattle, urged interpreting these findings with caution, noting that they need further confirmation before any change in policy or guidelines.

She told MedPage Today that false signals may arise when studying rare outcomes such as birth defects. “Statistically significant does not necessarily mean it is true or clinically relevant,” said Kim, who was not involved with the study.

“In the field, we don’t really consider HBV to be transmissible to the fetus from the father through the male germ line so a priori I would not have expected an association with congenital heart disease,” she added.

The CDC estimates that 580,000 to 2.4 million Americans have HBV infection, with two-thirds likely unaware of their infection.

Last year, the agency started recommending that all adults should be tested for HBV infection at least once in their lifetime, and many should get periodic retesting. Screening should include HBV surface antigen, antibodies to them, and total hepatitis B core antibody.

For their study, He and colleagues relied on data from the Chinese National Free Preconception Checkup Project conducted from 2010 to 2018. The study enrolled couples, namely men (median age 27 years) with wives who were ages 20 to 49 years and were uninfected with HBV.

As part of prepregnancy examinations, serum samples from couples were collected by investigators. Participants were stratified by HBV status: uninfected, previous infection (both serum hepatitis B surface antigen and hepatitis B envelope antigen negative), and new infection (serum hepatitis B surface antigen positive).

The authors used propensity score matching to compare men with and without preconception HBV infection. Over 3 million couples were thus matched and included in the study.

Information about CHD among their offspring was recorded from birth registers. These conditions included atrial septal defect, ventricular septal defect, atrioventricular septal defect, tetralogy of Fallot, pulmonary stenosis, and transposition of the great arteries.

There was no evidence of interaction between maternal immune status and paternal preconception HBV infection for CHD in children.

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