| Objective To observe the effect of hepatitis B vaccine combined with hepatitis B immunoglobulin(HBIG)on blocking mother-to-child transmission of hepatitis B virus(HBV)in a mother-to-child blocking cohort,and to analyze the incidence and influencing factors of breakthrough HBV infection in children born to hepatitis B surface antigen(HBs Ag)positive mothers who underwent successful mother-to-child blocking of hepatitis B vaccine combined with hepatitis B immunoglobulin(HBIG).Methods A total of 463 newborns delivered by HBs Ag-positive mothers from September 2009 to January 2011 in Huai’an District,Huai’an City were immunized with hepatitis B vaccine and HBIG for mother-infant blocking,and a cohort was established and followed up for five times at 7 months,12 months,2 years,3 to 4 years,and 8 to 10 years of age.During follow-up,venous blood was collected from children to detect their hepatitis B virus serological markers,and the influencing factors of maternal and fetal blocking failure and the incidence of HBV breakthrough infection in children with successful blocking and its influencing factors were analyzed.Results A total of 450 children were followed up for maternal and fetal blocking effect analysis,7 cases of blocking failure,blocking failure rate was 1.56%.All but one of the seven mothers did not test for HBV genotype,and the other mothers were HBV genotype C.In children whose mothers were HBe Ag-positive or negative,the failure rate of mother-infant blocking was 4.9%and 0.0%,respectively(P<0.0001);in children whose mothers were HBV high or low viral load,the failure rate of blocking was 6.4%and 0.0%,respectively(P<0.0001).There were no significant differences in the failure rate of maternal and fetal blocking in the groups with different gender,birth weight,Apar score,and HBIG inoculation dose in children,and there were also no significant differences in the failure rate of maternal and fetal blocking in the groups with different age of delivery and mode of delivery in mothers(P>0.05).A total of 390 children were included for HBV breakthrough infection analysis.By September 2019,a total of 3348.3 person-years were observed.Twelve patients had breakthrough infection,with a cumulative incidence rate of3.08%and an incidence density of 0.36/100 person-years.There were 5 females and 7males,all of whom were anti-HBc positive,and no HBs Ag positive individuals were found.The age at the time of breakthrough infection ranged from 29 to 117 months,including 3 patients(25.0%)aged 2 years,4 patients(33.3%)aged 3 to 4 years,and the other 5 patients(41.7%)were>9 years.HBV breakthrough infection occurred in15.8%and 2.6%of children whose mothers were infected with HBV genotype B or C,respectively(P=0.003).HBV breakthrough infection occurred in 25.0%,6.7%,2.6%,and 1.0%of children with non-response,low response,normal response,and high response to primary immunization,respectively(x~2=16.513,P<0.05),and showed an increasing trend with increasing level of response to primary immunization(x~2trend=10.187,P=0.001),with a mean antibody level of 460.68 m IU/m L in those with breakthrough infection and 51.90 m IU/m L in those without breakthrough infection(t=2.469,P<0.05).Breakthrough infections occurred in 9.8%of children whose mothers were HBe Ag-positive and none of the children whose mothers were HBe Ag-negative(x~2=23.432,P<0.05).HBV breakthrough infection occurred in0.3%and 12.0%of children born to mothers with low and high viral loads,respectively(P<0.0001).There were no significant differences in HBV breakthrough infection rate among children with different gender,birth weight,Apar score,and HBIG inoculation dose groups,and there were also no significant differences in HBV breakthrough infection rate among children with different maternal age of delivery and mode of delivery groups(P>0.05).Multivariate Cox regression analysis of the risk of HBV breakthrough infection showed that high maternal viral load level(HR=44.970,95%CI:5.773 to 350.280,P<0.0001)and low or no response to primary immunization in children(HR=5.921,95%CI:1.871 to 18.738,P=0.002)were risk factors for HBV breakthrough infection.Conclusion Hepatitis B vaccine combined with HBIG blocks mother-to-child transmission of HBV with high success rate.Maternal HBe Ag positive and maternal high viral load levels are risk factors for blocking failure.The incidence of HBV breakthrough infection in children with successful mother-to-child blocking is low.Maternal HBe Ag positive,maternal high viral load levels and low or no response to primary immunization in children are risk factors for HBV breakthrough infection.With the extension of time after immunization,the risk of breakthrough infection in children increases. |
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