Abstract:Objective To investigate the associations between virological characteristics of hepatitis B virus (HBV) infection and antiviral therapy with adverse pregnancy outcomes. Methods A total of 3 355 hepatitis B surface antigen (HBsAg)-positive pregnant women who were hospitalized for delivery at Hunan Provincial Maternal and Child Health Hospital from January 2020 to June 2024 were included in the exposed group, and 3 600 HBsAg-negative pregnant women were included in the unexposed group in this unmatched retrospective cohort study. Univariate analyses, multivariable logistic regression, and stratified analysis were performed. Odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated to analyze the associations of HBsAg status, hepatitis B e antigen (HBeAg) status, HBV DNA load, and antiviral therapy with adverse pregnancy outcomes. Results Multivariable analysis showed that HBsAg-positivity was an independent risk factor for intrahepatic cholestasis of pregnancy, preterm birth, threatened miscarriage, fetal distress and neonatal respiratory distress syndrome, with adjusted odds ratios (aORs) (95%CIs) of 2.46(1.67-3.61), 1.45(1.19-1.78), 7.68(3.95-14.93), 1.65(1.40-1.98), and 5.71(2.54-12.81), respectively. Stratified analysis showed that the risks of preeclampsia and fetal growth restriction were higher in the HBeAg-positive group than in the HBeAg-negative group, with aORs of 2.53 and 3.11, respectively. An HBV DNA load >2.0×105 IU/mL was an independent risk factor for fetal growth restriction (aOR=4.07). Among women with high viral loads, antiviral therapy was a protective factor against gestational diabetes mellitus, preterm birth, and fetal growth restriction, with aORs of 0.44, 0.28, and 0.35, respectively (all adjusted P<0.05). Conclusion HBsAg positivity was an independent risk factor for multiple adverse pregnancy outcomes. HBeAg positivity and a high HBV DNA load can further increase the risk of adverse pregnancy outcomes. Antiviral therapy in pregnant women with high viral loads can reduce the risk of some adverse pregnancy outcomes. Enhanced screening and management during pregnancy are recommended for HBsAg-positive pregnant women, and timely intervention for high-risk populations.