Elsevier

Vaccine

Volume 36, Issue 2, 4 January 2018, Pages 256-263
Vaccine

The efficacy of two different dosages of hepatitis B immunoglobulin combined with hepatitis B vaccine in preventing mother-to-child transmission of hepatitis B virus: A prospective cohort study

https://doi.org/10.1016/j.vaccine.2017.11.037Get rights and content

Abstract

Background/aims

A birth dose of hepatitis B immunoglobulin (HBIG), in combination with hepatitis B vaccine (HepB), is recommended for infants born to hepatitis B surface antigen (HBsAg)-positive mothers. However, the optimal dosage of HBIG remains to be resolved. This prospective cohort study aimed to compare the efficacy of two dosages of HBIG combined with HepB to prevent mother-to-child transmission (MTCT) of HBV.

Methods

From 2009 to 2011, we prospectively enrolled mother-infant pairs with positive maternal HBsAg in China. Infants were assigned to receive one dose of 100 IU or 200 IU HBIG within 12 h of birth according to maternal numbering, followed by completion of the 3-dose 10 μg HepB series. At 7 months, post-vaccination serologic testing (PVST) was performed in 545 and 632 infants in 100 IU and 200 IU HBIG groups, respectively, among whom, 451 and 529 were followed up to 12 months.

Results

Maternal and birth characteristics were comparable between infants in 100 IU and 200 IU HBIG groups. At 7 months, the rates of perinatal infection were 1.5% (8/545) and 1.9% (12/632) in 100 IU and 200 IU HBIG groups, respectively (p = .568). One non-responder infant in 200 IU HBIG group became newly infected at 12 months. The antibody to hepatitis B surface antigen (anti-HBs) positive rates were 98.5% (529/537) and 98.2% (609/620) in 100 IU and 200 IU HBIG groups at 7 months, respectively (p = .704), and the corresponding figures were 98.2% (431/439) and 97.1% (496/511) at 12 months (p = .266). The anti-HBs geometric mean concentrations were comparable between two groups at 7 months (707.95 mIU/mL vs. 602.56 mIU/mL, p = .062) and 12 months (245.47 mIU/mL vs. 229.09 mIU/mL, p = .407).

Conclusions

One birth dose of 100 IU HBIG, combined with the HepB series, might be enough for preventing MTCT of HBV in infants born to HBsAg-positive mothers.

Introduction

Chronic hepatitis B virus (HBV) infection is mainly acquired from mother-to-child transmission (MTCT) during perinatal period in areas with high prevalence of HBV, notably Asia. In the absence of proper immunoprophylaxis, 85.0–90.0% of infants born to hepatitis B surface antigen (HBsAg)-positive and hepatitis B e antigen (HBeAg)-positive mothers and 30.0–40.0% of infants born to HBsAg-positive and HBeAg-negative mothers will become chronically infected [1], who are at a significantly increased lifetime risk for cirrhosis and hepatocellular carcinoma (HCC) and serve as the main reservoir for continued HBV transmission. Therefore, prevention of HBV MTCT will be meaningful to eventually eliminate the burden of HBV infection.

Hepatitis B immunoglobulin (HBIG) is a blood product extracted from donor's plasma with high concentrations of antibody to hepatitis B surface antigen (anti-HBs), after screening to eliminate those positive for HBsAg, antibodies to human immunodeficiency virus (HIV) and hepatitis C virus (HCV), and HCV RNA [2]. HBIG is typically given within 12 h of birth as an adjunct to three doses of hepatitis B vaccine (HepB) to prevent MTCT of HBV. Studies have proved that passive-active immunoprophylaxis is the most safe and effective means to prevent MTCT of HBV currently [3], [4], [5], which further reduces the incidence of MTCT to as low as 5.0% [6], even to as low as 1.0% [7], [8]. Accordingly, a birth dose of HBIG has been recommended for infants born to HBsAg-positive mothers by the United States Advisory Committee on Immunization Practice (ACIP) in 2005 [2], and also by World Health Organization (WHO) [9] and Chinese Society of Hepatology and Chinese Society of Infectious Diseases, Chinese Medical Association in 2015 [10]. Generally, the routine dosages of HBIG for use in neonates were between 100 IU and 200 IU. Current guidelines for preventing chronic HBV infection in China recommend that the dosage of HBIG for infants born to HBsAg-positive mothers should be equal to or greater than 100 IU at birth [10]. In the United States, 0.5 mL HBIG (HepaGam B: >312 IU/mL; HyperHEP B: 220 IU/mL; Nabi-HB: >312 IU/mL) is given to such infants at birth to prevent MTCT of HBV [11]. In Australia, the dosage of HBIG provided for infants of HBV-infected mothers at birth is 100 IU [12]. However, various dosages have been used in studies as well as in clinical practice, with the optimal dosage of HBIG at birth remaining unresolved. In some studies, even two doses of 200 IU HBIG were given to infants [13], [14], [15], [16]. So far, no explicit consensus has been reached on the optimal dosage of HBIG in this setting.

Despite excellent efficacy for preventing MTCT of HBV, the limited source, complicated extraction process, potential biological safety concerns and high cost of HBIG are the barriers that can not be ignored in its promotion of use. It was reported that since 2008, plasma pharmaceuticals have leapt from $ 4 billion to a more than $ 11 billion annual market. Except voluntary donors, the donors’ thirst for the cash incentive from high-frequency blood donation may be putting their health and also the public's health at risk. In real-world settings, HBIG is largely unavailable and unaffordable, especially in developing countries in Asia and Africa with a limited budget. Results from a study showed that only 38% of the infants of HBsAg-positive mothers received HBIG after birth in 14 districts in China [17]. This percentage was even lower, about 13%, as revealed in a survey in Guizhou Province [18]. Similarly, in a Nigerian study, the cost of 100 IU and 200 IU HBIG could be afforded by 82.6% and 10.9% of the parents, respectively, with the other 6.5% getting none [19].

For all the above reasons, the rational use of HBIG should be addressed, especially in resource-limited settings. But evidence from prospective studies on this issue is lacking. Given that the current dosage of HBIG used at birth ranges from 100 IU to 200 IU in most cases, in this study, we prospectively compared the efficacy of 100 IU and 200 IU HBIG at birth combined with the HepB series for preventing MTCT of HBV, with the objective of delineating an optimal dosage of HBIG in this context.

Section snippets

Study subjects and design

During August 2009 to June 2011, pregnant women recruited from Maternal and Child Health Care Centers in Jiangsu and Henan Provinces underwent screening for HBV infection during the first prenatal visit by 12 weeks of gestation. HBsAg-positive pregnant women were enrolled after signing informed consent forms, and serum alanine aminotransferase (ALT) levels were monitored every one to two months during pregnancy. All pregnant women were comprehensively evaluated for treatment during pregnancy by

Enrollment and follow-up of infants

At birth, as shown in Fig. 1, 668 and 780 infants were assigned in 100 IU and 200 IU HBIG groups, respectively. At 7 months of age, 545 (81.6%) and 632 (81.0%) infants in 100 IU and 200 IU HBIG groups returned for PVST, respectively. All of them received the first dose of HepB and HBIG within 12 h of birth, and completed the three-dose HepB series. The rates of loss to follow-up were comparable between two groups (p = .785). Therefore, 545 mother-infant pairs in 100 IU group and 632 in 200 IU

Discussion

Timely passive-active immunoprophylaxis significantly reduces the occurrence of MTCT. Similar to what has been reported in the United States [8], in this prospective cohort study, with a relatively large number of participants, timely post-exposure prophylaxis protected up to 98.3% of infants born to HBsAg-positive mothers from being perinatally infected.

In this study, the rates of immunoprophylaxis failure did not vary by the dosage of HBIG given to neonates born to HBsAg-positive mothers

Acknowledgements

This work was supported by National Major Scientific and Technological Special Project during the Twelfth Five-year Plan Period [grant number 2012ZX10002001-001].

Conflict of interest

None.

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