Author: Dou Xiaoguang Source: China Medical Tribune Date: 2011-08-02 Among HBsAg-positive pregnant women, how many are HBV DNA-positive? And how many are high viral loaders? Does discontinuation of antiviral drugs lead to an increased risk of disease flares in pregnant women? Is there an increased risk of drug resistance in pregnant women? Will it make follow-up treatment difficult? Is breastfeeding safe for mothers with hepatitis B? Theoretically, the virus in breast milk may enter the body through the baby’s broken oral cavity or digestive tract mucosa, which may cause the baby to develop HBV infection. Therefore, some scholars believe that breast milk is dangerous and oppose breastfeeding. However, there are also many clinical studies that show that even though HBV DNA can be detected in breast milk, it does not actually cause HBV infection in newborns, thus advocating that breastfeeding can be performed. The current consensus is that newborns can be breastfed regardless of whether the mother is HBeAg positive or negative, as long as they receive hepatitis B immunoglobulin (HBIG) and hepatitis B vaccine within 12 hours of birth. This is also recommended in our 2010 guidelines (Editor’s note: A recent meta-analysis completed by Zheng Yingjie et al, scholars at Fudan University in Shanghai, showed that mothers who are HBV-infected can breastfeed their infants who have been routinely vaccinated against hepatitis B, regardless of their infectiousness. (For details, see China Medical Tribune, July 21, 2011, page A2). Can HBIG injections in late pregnancy prevent mother-to-child transmission? In China, medical practitioners, mainly obstetricians and gynecologists and maternal and child health workers, have concluded after research that HBIG injections given to pregnant women with chronic HBV infection in late pregnancy can reduce the risk of mother-to-child transmission of HBV. Therefore, some scholars advocate that pregnant women receive HBIG injections in late pregnancy. However, these relevant literatures are all studies from China and these studies are not randomized controlled studies. In addition, neither the World Health Organization nor our Ministry of Health recommends this method to prevent mother-to-child transmission of HBV. Is it true that HBIG injections in pregnant women can neutralize the virus? Does this lead to the development of an immune escape strain of HBV? If this immune escape strain is transmitted in the population, is it possible that the current hepatitis B vaccine will not be successful in preventing HBV infection? There is insufficient research evidence to answer these questions, and therefore it is not recommended to interrupt mother-to-child transmission of HBV. Can antiviral therapy during pregnancy prevent mother-to-child transmission? It is controversial whether oral administration of antiviral drugs such as lamivudine (LAM) in pregnant women with high viral load can improve the rate of MTCT blockade. The failure of PMTCT was among women with high viral load pregnancies A multicenter study published by Swiss scholars in 2010 showed that PMTCT was 100% among 141 newborns whose mothers were HBsAg-positive and received co-immunization between 2005 and 2006. A study published this year by scholars at the Fourth Military Medical University showed that among 214 pregnant women who were HBsAg-positive, the failure rate of HBIG combined with hepatitis B vaccination for mother-to-child transmission of HBV was 4.7% (10/214 cases); in the failure group, all mothers had high HBV DNA loads. In the United States, it was reported that 90% of newborns born to HBsAg-positive mothers could be infected with HBV without co-immunization blockade of the newborn, and the failure rate of mother-to-child transmission blockade with co-immunization was 3% to 7%, with the main reason for failure being high viral load (>108 copies/ml) in pregnant women. A national prospective study conducted by Australian scholars included 313 HBSAg-positive pregnant women, of whom 213 (68%) were HBV DNA-positive and 92 (29%) were HBeAg-positive. The results showed that 138 infants delivered by HBV DNA-positive mothers were tested for HBV DNA 9 months after birth, and only 4 infants were positive for both HBsAg and HBV DNA. The main reason for the failure of mother-to-child transmission interruption was the occurrence of immune escape of the virus from the vaccine and HBIG. However, in the group of mothers with HBV DNA <108 copies/ml, the success rate of mother-to-child transmission interruption was 100%. Antiviral therapy can block mother-to-child transmission, but the level of evidence from relevant studies is low A multicenter, randomized, placebo-controlled study conducted by our scholars included 150 pregnant women with high viral load (HBV DNA >109 copies/ml), 56 of whom started oral LAM at 26-30 weeks of gestation and 59 of whom did not receive antiviral therapy (control group). All newborns delivered by these women received HBIG and hepatitis B vaccination. The results showed that infants delivered in the antiviral treatment group had HBsAg positivity, HBsAb positivity and HBV DNA positivity rates of 18% and 84% and 20%, respectively, at 52 weeks after birth, compared with 39%, 46% and 61%, respectively, in the control group. However, the study shed too many cases, 13% in the treatment group and 31% in the control group, and the level of evidence of the study was compromised. Dutch scholars reported a failure rate of 12.5% (1/8 cases) for mother-to-child transmission blockade in pregnant women with HBV DNA >1.2 × 109 copies/ml who received oral LAM in the last month of pregnancy, compared with 28% (7/25 cases) in the group not receiving antiviral therapy. However, the study sample size was small. A meta-analysis last year (including 37 randomized controlled studies with a total of 5900 newborns) showed that the success rate of mother-to-child transmission interruption with co-immunization was >90% and that oral antiviral drugs were safe and effective in women with high viral load pregnancies. ▪ Other issues and controversies Can cesarean delivery prevent perinatal mother-to-child transmission of HBV? In terms of the effect of delivery method on the risk of perinatal HBV transmission, different studies have shown different results. Our scholars conducted a study in 301 HBsAg-positive pregnant women. In that study, all infants received standardized co-immunization. The results showed no difference in the effect of vaginal delivery, use of forceps or vacuum suction, or cesarean delivery on the risk of HBV infection in infants [Chinese Medical Journal (English Edition) 2002, 115:1510]. However, there have been contrary findings. A meta-analysis of randomized controlled studies showed that elective cesarean delivery reduced the incidence of mother-to-child transmission of HBV compared with the transvaginal delivery group (28% versus 10.5%), but the difference was not significant [Virol J 2008, 5:100]. Most international obstetric guidelines do not recommend the use of cesarean delivery to prevent perinatal mother-to-child transmission of HBV. How to determine the timing of antiviral therapy in late pregnancy? For pregnant women with high HBV DNA load, antiviral may be administered in late pregnancy, but the evidence on the benefits and risks of treatment is far from adequate. One strategy is to decide whether to initiate antiviral therapy in late pregnancy based on the viral load of the pregnant woman, but what the viral load threshold is to initiate therapy is inconclusive. It has been suggested that this threshold correlates with whether mother-to-child transmission of HBV has occurred in a pregnant woman at a previous delivery. The threshold for initiating antiviral therapy should be lower (HBV DNA >106 copies/ml) if the previously delivered infant tested positive for the virus; if the previously delivered infant was negative for the virus, the HBV DNA threshold for antiviral therapy can be set at >108 copies/ml [Cleveland Clin J Med 2009 , 76(S3):S25]. Authors: Dou Xiaoguang, Shengjing Hospital, China Medical University