Background <p>Pregenomic RNA (pgRNA) has been utilized as an early predictive marker for antiviral therapy, an indicator for the emergence of drug resistance in hepatitis B virus (HBV), or a marker for safe discontinuation of nucleoside analog therapy. However, its role during pregnancy has rarely been reported. We aimed to evaluate the pgRNA profiles and its dynamic changes among pregnant, postpartum, and non-pregnant women with chronic HBV infection (CHB).</p> Methods <p>We conducted a study involving 479 women with CHB, including 235 during pregnancy, 90 postpartum, and 154 non-pregnant women of childbearing age. pgRNA was detected using the HBV-SAT method. Additionally, we followed up 39 women in mid-pregnancy, 21 in late pregnancy, 20 within 0–3 months postpartum, and 20 non-pregnant women of childbearing age with different treatment regimens for two times.</p> Results <p>Significant differences were observed in clinical indicators such as HBV DNA, ALT, AST, and pgRNA among CHB women during pregnancy, postpartum, and non-pregnant periods. Pregnant and postpartum women with positive pgRNA had higher levels of DNA, HBeAg, HBsAg, and ALT. Moreover, the detection rates of pgRNA, DNA, and HBeAg varied significantly across the three stages and different treatment regimens in CHB women. pgRNA was highly correlated with HBeAg, and a moderate correlation was found between pgRNA and HBV DNA levels. This study also revealed the patterns of viral activity changes during pregnancy and postpartum, and the first three months postpartum represent a critical period for viral activity changes. This unique immune adjustment phase may offer new opportunities for the treatment of hepatitis B.</p> Conclusion <p>CHB women have different pgRNA and clinical characteristics during pregnancy, postpartum, and the non-pregnant childbearing period.</p>