Background: This study aimed to investigate the potential causal association between chronic hepatitis B (CHB) infection and the risk of pre-eclampsia/eclampsia using a Mendelian randomisation (MR) design.
Methods: We conducted a two-sample MR analysis using genome-wide association study (GWAS) summary statistics from three large-scale datasets. For CHB infection, we used data from 351,885 individuals UK Biobank. For pre‑eclampsia/eclampsia, we analysed two FinnGen datasets with sample sizes of 118,291 and 126,760 individuals, respectively. Genetic variants strongly associated with CHB infection (p < 5 × 10-8) were selected as instrumental variables. The inverse-variance weighted (IVW) method was employed as the primary analysis. Sensitivity analyses included MR-Egger regression, weighted median, weighted mode and MR-PRESSO. Cochran's Q test and MR-Egger intercept tests were performed to assess heterogeneity and horizontal pleiotropy, respectively.
Results: MR analysis revealed significant positive genetic associations between CHB infection and increased risk of pre-eclampsia (OR = 1.154, 95%CI = 1.014-1.313, p = .029) and eclampsia (OR = 1.561, 95%CI = 1.030-2.366, p = .035). Findings were robust across sensitivity analyses for both outcomes.
Conclusions: Our study provides genetic evidence that CHB infection increases the risk of both pre-eclampsia and eclampsia. These findings suggest that considering CHB status as a risk factor and implementing targeted HBV screening programmes may be beneficial for pregnant women.
Keywords: Chronic hepatitis B; Mendelian randomisation; eclampsia; pre-eclampsia; pregnancy outcome.
This study explored the link between long-term hepatitis B infection (chronic hepatitis B, CHB) and two serious pregnancy complications: pre-eclampsia and eclampsia. Chronic hepatitis B is a persistent liver infection. Pre-eclampsia and eclampsia cause high blood pressure in pregnant women; eclampsia also involves seizures, posing risks to both mother and baby. We used genetic information to investigate whether having a higher genetic chance of getting CHB also increases the risk of developing these pregnancy problems. Our results consistently show that women with a genetic predisposition to CHB infection appear to have a higher risk of developing both pre-eclampsia and eclampsia. This suggests that being aware of a woman’s hepatitis B status during pregnancy could be important. Close monitoring for early signs of pre-eclampsia or eclampsia might be beneficial for pregnant women with CHB to help ensure their safety and the health of their baby.