Study reveals association between maternal prenatal infections and risk of biliary atresia in offspring

The case-control study of 447 infants with a BA diagnosis and 2912 controls revealed offspring born to mothers with prenatal intestinal infection and genitourinary tract infection had a significantly greater risk of BA development compared to offspring who were not exposed to such maternal infections.

Biliary atresia is a rare, devastating hepatobiliary disease which is the primary cause of pediatric liver transplant. The underlying aetiology of BA remains elusive despite substantial research. According to current theories, the principal pathomechanism of BA involves fibrosis and inflammation of cholangiocytes and hepatocytes, particularly after exposure to viral infections during the early neonatal period. However, studies have shown that BA may begin in utero. There is no clear understanding of the association of maternal infections during pregnancy with the development of BA in offspring.

To fill this knowledge gap, Wei-Hao Wang, Department of Pediatrics, Changhua Christian Hospital, Changhua, Taiwan, and colleagues aimed to examine the association between prenatal infections in mothers and the development of biliary atresia in their offspring.

For the population-based case-control study, the researchers obtained administrative data from the Taiwan National Health Insurance Research Database with linkage to the Taiwan Maternal and Child Health Database, capturing medical and demographic information on the nearly 23 million Taiwanese population.

The cohort included 2 905 978 singleton live births among mother-infant dyads between 2004 and 2020 in Taiwan. The case group of BA infants was identified from the use of International Classification of Diseases diagnostic codes for BA and subsequent liver transplant or Kasai procedure. The control group was randomly selected from infants without BA, representing about 1 in 1000 study population.

Prenatal maternal infections included influenza, intestinal infection, pneumonia, soft-tissue infection, upper airway infection, and genitourinary tract infection.

The study's primary outcome was exposure to prenatal maternal infections. Inverse probability weighting analysis was performed by building a logistic regression model to estimate the probability of the exposure observed for a particular infant and using the estimated probability as a weight in subsequent analyses. The risk of BA in offspring after prenatal maternal infections was assessed using the weighted odds ratio (OR) estimated by logistic regressions.

Based on the study, the researchers reported the following findings:

• Among the mother-infant dyads included, 447 infants with BA were cases (51.9% females) and 2912 infants without BA were controls (52.0% males). The mean maternal age at childbirth was 30.7 years.
• Offspring exposed to prenatal intestinal infection (weighted OR, 1.46) and genitourinary tract infection (weighted OR, 1.22) in mothers exhibited a significantly higher risk of BA.
• Maternal intestinal infection (weighted OR, 6.05) and genitourinary tract infection (weighted OR, 1.55) that occurred during the third trimester were associated with an increased risk of BA in offspring.

"We observed an association between prenatal intestinal infection and genitourinary tract infection in mothers and BA occurrence in their offspring," the researchers wrote. "the exact underlying mechanism for which warrants further exploration."

"The findings also suggest the importance of additional BA surveillance in the offspring of pregnant women with these diseases," they concluded.

Reference:

Wang W, Chiu F, Kuo T, Shao YJ. Maternal Prenatal Infections and Biliary Atresia in Offspring. JAMA Netw Open. 2024;7(1):e2350044. doi:10.1001/jamanetworkopen.2023.50044