To investigate the efficacy of antepartum administration of three doses of hepatitis B immunoglobulin (HBIg), currently being used in China, 250 pregnant women who were seropositive for hepatitis B e antigen (HBeAg) were randomly divided into study (117 cases) and control groups (133 cases). Subjects in the study group received HBIg 400 IU intramuscularly once a month at the third, second and first month before delivery; subjects in the control group received no antepartum treatment. All neonates received passive-active immunization after birth. The maternal hepatitis B virus (HBV) markers, hepatitis B surface antigen (HBsAg) titres and HBV deoxyribonucleic acid (DNA) levels were measured at week 28 of gestation (before the antepartum treatment) and at labour; the neonatal serum HBV markers were detected at birth and at 12 months after birth. No side-effects were found in any of the women or their neonates. No statistical differences were seen between the maternal HBsAg and HBV DNA levels of the study and control groups at labour nor the protective efficacy rates of postnatal immunoprophylaxis at 12 months after birth (P > 0.05, respectively). To conclude, antepartum administration of three doses of HBIg for the HBeAg-positive women is inefficacious.
In areas where hepatitis B virus (HBV) is epidemic, such as China, South-east Asia, and Africa, perinatal infection is the predominant mode of HBV transmission. Postnatal hepatitis B immunization is by far the only effective treatment recommended by the Advisory Committee on Immunization Practices (http://www.cdc.gov/nip/ACIP/) for preventing perinatal transmission of HBV. However, the protective efficacy rate (PER) is suboptimal, resulting in the HBV infections of some babies born to the chronic hepatitis B (CHB) mothers. About 90% of these early infected individuals will become persistent chronic carriers and be immunotolerant to HBV, which accounts for the very low rates of spontaneous and treatment-related clearance of hepatitis B e antigen (HBeAg). Moreover, babies carrying HBV can horizontally transmit it to other children, together, they serve as a reservoir of HBV in the community for continuous spread later in their lives. Therefore, it is necessary to develop new treatments to improve the PER of postnatal immunoprophylaxis.
In 1995 and 1997, an original antepartum treatment that could significantly and safely reduce the failure of postnatal passive-active hepatitis B immunization was reported in China. This treatment involved the administration of hepatitis B immunoglobulin (HBIg) 200 IU intramuscularly once a month at the third, second and first month before delivery for CHB pregnant women. Since then, similar studies (the dose of HBIg was 200 IU per injection or 400 IU per injection) highlighting the efficacy of this regimen were published in China, indicating that this treatment is becoming a standard regimen in China. Undoubtedly, this regimen is very important if it is effective.
One mechanism of this regimen was reported that the injected HBIg could reduce the maternal viraemia levels. As prelabour HBV deoxyribonucleic acid (DNA) level is the most important risk factor for perinatal transmission, this regimen seems reasonable. Another reported possible mechanism was that the injected HBIg could be transferred to the foetus, but this hypothesis has not been confirmed yet. In these studies, most of the CHB pregnant women were seronegative for HBeAg, while the efficacies and mechanisms have not been evaluated separately according to the maternal HBeAg status. As the viraemia level is strongly related to the complications of CHB, this regimen should be potentially valuable for all the CHB patients if it is effective. To date, monotherapy of HBIg is not one of the current standard regimens for CHB.
It has been demonstrated that perinatal infections of babies born to HBeAg-negative mothers could be satisfactorily prevented by postnatal hepatitis B immunization. In previous studies on nonpregnant CHB patients, neutralization of hepatitis B surface antigen (HBsAg) by HBIg was achieved only in patients with low HBsAg levels. Therefore, antenatal treatment of HBIg should emphasize on the HBeAg-positive women; however, it is questionable that this regimen can significantly reduce the viraemia levels of the HBeAg-positive women.
The aims of this study were to investigate whether this regimen is effective for the HBeAg-positive pregnant women and whether there is an effective adoptive immunoprophylaxis in the foetus. Although a higher dose of HBIg might be more effective, we repeated the reported regimen in this study because no information on how to determine the dose and the frequency of this regimen is available. As perinatal transmission of HBV from the HBeAg-negative mothers could be satisfactorily prevented by the postnatal immunoprophylaxis, no HBeAg-negative pregnant women were enrolled into this trial.