Abstract: Objective The serological characteristics and pre S1 gene sequencing in hepatitis B virus (HBV) infected pregnant women with negative Pre-S1 antigen (Pre-S1Ag) were analyzed to provide a basis for explaining the negative Pre-S1Ag in HBV-infected pregnant women and preventing vertical transmission. Methods Pregnant women who underwent health examination in Shandong Maternal and Child Health Hospital from July 2021 to December 2022 were selected as the study objects. Five tests of hepatitis B and Pre-S1Ag were detected. A total of 14 cases with positive hepatitis B surface antigen (HBsAg) and negative Pre-S1Ag were selected as the experimental group, and 20 cases with both positive HBsAg and Pre-S1Ag were randomly selected as the control group. HBV DNA was detected, and PreS/S gene was amplified and sequencing was performed. Results In HBV-infected pregnant women, Pre-S1Ag negative was found only in five serologic patterns of hepatitis B with positive HBsAg, anti-HBe and anti-HBC, accounting for 4.17%, but not in other serologic patterns of HBV infection. There were significant differences in the positive rates of HBeAg and anti-HBe between the experimental group and the control group (P<0.001). Compared with the control group, HBsAg detection were （29±91） IU/mL and （2 070.6±714.8） IU/mL, respectively. HBV DNA were （1.63±0.05） lg IU/mL and （5.79±1.53） lg IU/mL, and the differences was statistically significant (P<0.001). The sequencing results showed 3 genotype B cases and 17 genotype C cases in the control group. The 14 samples in the experimental group were all genotype C. There was no significant difference in the positive rates of Pre-S1 protein between the two groups (P>0.05). Conclusion The no reactivity of Pre-S1Ag in HBV-infected pregnant women was not related to PreS gene mutations, but was related to the low HBV DNA load resulting in the expression level of Pre-S1Ag below the detection limit. The possibility of vertical transmission in HBV-infected pregnant women with negative Pre-S1Ag cannot be ignored.

Key words: Hepatitis B virus, Pregnant woman, Hepatitis B surface antigen, Pre-S1 antigen, Pre-S /S gene