medwireNews: The risk for congenital heart disease (CHD) is elevated in children whose fathers are infected with the hepatitis B virus (HBV) before their conception, suggests research published in JAMA Pediatrics.
Noting that maternal HBV infection before or during pregnancy has previously been shown to increase the risk for CHD in children, the investigators now advise that “personalized reproductive guidance regarding undergoing HBV screening and staying free of HBV infection should be provided for both wives and husbands, which might be helpful for the reduction of congenital malformation risk and improvement of neonatal outcomes.”
Yihua He (Capital Medical University, Beijing, China) and co-authors collated data for 3,047,924 couples included in the Chinese National Free Preconception Checkup Project between 2010 and 2018. All the wives were 20–49 years old without HBV infection at time of enrolment and conceived within a year of enrolling into the study. The husbands were aged a median of 27 years.
In all, 610,978 of the men were diagnosed with HBV prior to pregnancy, of whom 61.1% were newly infected (positive for serum HBsAg) and 38.4% were previously infected (negative for serum HBsAg and HBeAg).
CHD was detected in the children of 0.025% of the couples overall, and in 0.023%, 0.028%, and 0.036% of children born to couples where the husband had any HBV infection, new HBV infection, or earlier HBV infection, respectively.
After adjusting for risk factors including paternal and maternal age, alcohol and smoking habits, and family history of CHD, men with an earlier HBV infection were a significant 1.4 times more likely to have a child with CHD than those with no infection, but there was not a significant association among men with a new infection.
However, the researchers acknowledge that the differences in the risks for CHD in the children of men with a previous infection and newly diagnosed men may be due to couples with newly identified paternal infection choosing to delay conception or terminate a pregnancy, or perhaps experiencing a greater risk for miscarriage.
He et al also found that the rate of CHD was “consistently lower” among the children of men not infected with HBV compared with those of fathers with new or earlier HBV infection regardless of whether their wives were susceptible to HBV infection (0.022 vs 0.023 and 0.036%, respectively) or immune to HBV (0.026 vs 0.033 and 0.037%, respectively).
Among wives susceptible to HBV, there was an increased risk for CHD in their children if their husband had a previous HBV infection versus no infection (adjusted relative risk [aRR]=1.46), but again this was not the case when only looking at new paternal infection. And among wives with HBV immunity, neither earlier nor new paternal HBV infection status was associated with increased CHD risk in the children.
The risk for CHD in children was higher for couples where the man had been previously infected, regardless of maternal immune status, than for couples where both the man and the woman had no history of HBV infection (aRR=1.49).
A significantly higher CHD risk was also found for the children of couples with newly infected men and immune women (aRR=1.38) but not for couples where the husband was newly infected and the wife was susceptible.
He and co-authors suggest that “maternal immunity against HBV may not be able to mitigate the teratogenic associations of paternal HBV infection with risk of CHDs in offspring,” and that the paternal risk associated with HBV infection may be similar to that of smoking, alcohol, and the impact of age on sperm.
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