Since the nationwide hepatitis B vaccination program was launched in 1984, the seropositive rate of hepatitis surface antigen (HBsAg), the incidence/mortality rate of fulminant hepatitis and the incidence rate of hepatocellular carcinoma in Taiwanese children have declined significantly. However, active/passive immunoprophylaxis against hepatitis B virus (HBV) can not eradicate transmission completely. Less than 10% infants born to HBsAg positive mothers, especially e antigen (HBeAg) positive ones, will still be infected and become victims of chronic hepatitis B. Possible causes of immunoprophylaxis failure (IF) include: intrauterine infection, surface gene mutant HBV infection, high level of maternal viremia and the host factors that lead to non-response to the vaccine. The aim of the study is to compare the IF rate of the younger child of HBeAg positive mothers, whose elder child is a case of IF, to that of other HBeAg positive mothers, whose elder child is not a case of IF, to see if there is any familial cause of failed immunoprophylaxis.

HBsAg positive mothers with more than one child were enrolled from mothers of HBV carrier children followed-up in our hospital and women delivered in our hospital. The mothers were HBeAg positive when the children were born. Those children who did not receive hepatitis B immunoglobulin (HBIG), or did not receive HBIG within 24 hrs after birth, or did not complete hepatitis B vaccine injection, were excluded. If more than two children in the same family fulfilled the criteria, only the first two were recruited. The HBsAg status, age, sex, delivery mode, maternal age at delivery, and paternal HBsAg status of these children were analyzed.

A total of 98 families were collected. In 9 of the 98 families, both children were cases of IF. In 28 families, only the elder one was HBsAg positive. In 15, only the younger one was HBsAg positive, and in 46, both were HBsAg negative. The IF rate of the elder child (37/98, 37.8%) was significantly higher than that of the younger one (24/98, 24.5%) (p = 0.0474). However, the IF rate of the younger child in the families with an elder child who was a case of IF (9/37, 24.3%), did not differ from that in the families with an elder child who was a not case of IF (15/61, 24.6%) (p = 0.976).

In addition, the maternal age at delivery was significantly younger in those families (N=52) with children infected by HBV than that in the families (N=46) without children infected by HBV (p < 0.05).

We also reported other 8 cases of IF. Their mothers were HBeAg negative at delivery and there 8 cases received HBV vaccines but no HBIG. More than half of them have siblings born within 3 years of their births and the mothers were HBeAg positive when the siblings were born. It is possible that these 8 cases were born at the HBeAg seroconversion stage of their mothers and the maternal HBV DNA amount was still high although the maternal HBeAg was negative.

In conclusion, our present result did not find differences between the IF rates of the younger child in the families with an elder child who was a case of IF and that in the families with an elder child who was a not case of IF. Our present finding indicated that the IF rate was higher in the older children than in the younger ones of HBeAg positive mothers. A younger maternal age at delivery was also noted in those families with children infected by HBV than that in the families without children infected by HBV. A younger maternal age at delivery may be associated with a heavier viral load and then result in failed immunoprophylaxis.