Abstract: All 36 included trials originated from China and were at overall high risk of bias. The trials included 6044 pregnant women who were HBsAg, HBeAg, or hepatitis B virus DNA (HBV-DNA) positive. Only seven trials reported inclusion of HBeAg-positive mothers. All 36 trials compared HBIG versus no intervention. None of the trials used placebo. Most of the trials assessed HBIG 100 IU (two trials) and HBIG 200 IU (31 trials). The timing of administration of HBIG varied; 30 trials administered three doses of HBIG 200 IU at 28, 32, and 36 weeks of pregnancy. None of the trials reported all-cause mortality or other serious adverse events in the mothers or babies. Serological signs of hepatitis B infection of the newborns were reported as HBsAg, HBeAg, and HBV-DNA positive results at end of follow-up. Twenty-nine trials reported HBsAg status in newborns (median 1.2 months of follow-up after birth; range 0 to 12 months); seven trials reported HBeAg status (median 1.1 months of follow-up after birth; range 0 to 12 months); and 16 trials reported HBV-DNA status (median 1.2 months of follow-up; range 0 to 12 months). HBIG reduced mother-to-child transmission (MTCT) of HBsAg when compared with no intervention (179/2769 (6%) with HBIG versus 537/2541 (21%) with no intervention; RR 0.30, TSA-adjusted CI 0.20 to 0.52; I2 = 36%; 29 trials; 5310 participants; very low quality evidence). HBV-DNA reduced MTCT of HBsAg (104/1112 (9%) with HBV-DNA versus 382/1018 (38%) with no intervention; RR 0.25, TSA-adjusted CI 0.22 to 0.27; I2 = 84%; 16 trials; 2130 participants; low quality evidence). TSA supported both results. Meta-analysis showed that maternal HBIG did not decrease HBeAg in newborns compared with no intervention (184/889 (21%) with HBIG versus 232/875 (27%) with no intervention; RR 0.68, TSA-adjusted CI 0.04 to 6.37; I2 = 90%; 7 trials; 1764 participants; very low quality evidence). TSA could neither support nor refute this observation as data were too sparse. None of the trials reported adverse events of the immunoglobulins on the newborns, presence of local and systemic adverse events on the mothers, or cost-effectiveness of treatment. Due to very low to low quality evidence found in this review, we are uncertain of the effect of benefit of antenatal HBIG administration to the HBV-infected mothers on newborn outcomes, such as HBsAg, HBV-DNA, and HBeAg compared with no intervention. The results of the effects of HBIG on HBsAg and HBeAg are surrogate outcomes (raising risk of indirectness), and we need to be critical while interpreting the findings. We found no data on newborn mortality or maternal mortality or both, or other serious adverse events. Well-designed randomised clinical trials are needed to determine the benefits and harms of HBIG versus placebo in prevention of MTCT of HBV.

Plain-language summary: After searching the medical literature for relevant trials, we identified 36 clinical trials that recruited 6044 pregnant women with signs of HBV infection. All trials originated from China. All trials and trial results were at high risks of bias, which makes potential overestimation of benefits and underestimation of harms more likely. The studies assessed only hepatitis B surface antigen (HBsAg) (proteins on the surface of the HBV that cause immune system of the body to make antibodies when exposed to HBV), hepatitis B virus DNA (HBV-DNA) (self-dividing material of the HBV which carries its genetic information), and hepatitis B envelope antigen (HBeAg) (blood proteins that shows that the virus is still active in the liver) status in newborns. There was no information about the effects of HBIG on death from all causes (newborn or mother), antibodies to hepatitis B core antigen (proteins made by the immune system which bind to HBV and cause them to be destroyed), cost-effectiveness of HBIG, and side effects. Antenatal (before birth) HBIG might have an effect on preventing mother-to-child transmission of HBV as more treated babies than non-treated babies had no HBsAg or HBV-DNA; however, both results could have been affected by the way the trials were conducted and were at high risk of bias. The authors could draw no conclusions about the side effects of HBIG for pregnant women with HBV infection. Well-designed clinical trials with low risks of bias are needed to establish the benefits and harms of HBIG compared with no treatment in pregnant women with HBV. Due to the very low to low quality evidence in this review, we do not know if antenatal HBIG administration has an effect on the proportion of newborns with HBsAg and HBV-DNA compared with no treatment. We could draw no conclusions about death of newborns or mothers as we found no data.