阻断乙型肝炎病毒宫内传播的随机对照研究

A randomized controlled trial on interruption of HBV transmission in uterus

目的 最近 10多年的研究表明 ,用乙肝疫苗主被动联合免疫能阻断母婴间乙肝病毒(HBV)传播 ,保护效果达到 70 %～ 90 % ,而宫内已感染HBV是生后免疫接种失败的主要原因 ,我们研究用乙肝免疫球蛋白 (HBIG)多次产前注射 ,观察阻断HBV宫内传播的效果。方法 980例携带HBsAg孕妇随机分成两组 ,一组孕妇产前 3个月 (妊娠 2 8周起 )每 4周肌注HBIG 2 0 0IU～ 4 0 0IU ,直至临产 ,称HBIG组 ;另一组不注射为对照 ,称对照组。所有对象和其所生孩子出生时即采外周血 ,检测HBsAg、HBeAg ,部分测HBVDNA ,所有新生儿随访 1年。结果 4 96例新生儿为对照组母亲所生 ,生后仅接种乙肝疫苗和HBIG ;4 91例新生儿为HBIG组母亲所生 ,生后同样给予主被动联合免疫。结果显示对照组婴儿的宫内感染率为 14 .3% ;而HBIG组婴儿的宫内感染率为 5 .7% (χ2 =2 0 .11,P <0 .0 0 1) ,宫内感染HBV的高危因素是母亲呈HBsAg、HBeAg双阳性或HBVDNA阳性。结论 研究提出产前多次肌注HBIG可有效减少HBV的宫内传播 。

Objective Mother to infant transmission is the major reason for high HBV carrier rates in China. HBIG plus hepatitis B vaccine is highly effective in preventing perinatal transmission of HBV infection. However, such a means of prevention still fails in 10%-20% of neonates born to HBV carrier mothers. Intrauterine infection of HBV is the major cause of failure of vaccination against hepatitis B in neonates born to HBV carrier mothers. We studied the interruptive effect of HBV specific immunoglobulin (HBIG) before delivery in the prevention of intrauterine transmission of HBV. Methods Nine hundred and eighty healthy pregnant women who were asymptomatic HBsAg carriers at the ages of 19-35 years (averaging 24) were selected by the obstetric department of Zhongshan Hospital, Fudan university, the obstetric department of Shanghai Ninth People′s Hospital, Shanghai Second Medical University and International Peace Maternity and Child Health Care Hospital in Shanghai from January 1995 to October 1999. A total of 980 pregnant women were randomly divided into an HBIG group and a control group according a random number table. Each subject in the HBIG group received 200 IU or 400 IU of HBIG intramuscularly (IM) at 3, 2 and 1 month before delivery. The subjects in the control group did not receive any specific treatment. All newborn infants received 100 IU of HBIG per dose IM after venous blood sample was taken at birth, followed by 30 μg of HBV vaccine IM at 1, 2 and 7 months of age. Blood tests were performed for all subjects and their neonates. Blood specimens were tested for HBsAg and HBeAg by enzyme immunoassay (Abbott kits). Total HBV DNA was tested by nested PCR to employ for HBV S gene amplification. The liver function was regarded as abnormal when ALT was >40 IU/L. All infants were followed up for 1 year.Results In this randomized controlled trial, HBsAg was found positive in 107 of 987 neonates (7 twins) in venous blood specimens within 16 hours after birth. HBsAg was found persistently positive in 99 of the 107 neonates for more than 6 months, which may be the evidence of HBV intrauterine transmission. In the HBIG group, 491 neonates were born to HBV carrier mothers and in the control group 496 neonates were born to HBV carrier mothers. The rates of intrauterine transmission in the two groups were 14.3% and 5.7%, respectively (χ 2=20 280, P <0.001). The levels of serum ALT in the 47 out of 99 infants with intrauterine HBV infection were>40 IU/L, which persisted for more than 6 months, which signifies chronic hepatitis B (CHB). The rates of CHB in HBIG group and control group were 2.2% and 7.3%, respectively (χ 2=13.696, P <0.001). The high risk factors of HBV intrauterine infection (HII) included HBsAg, HBeAg double positive, and HBV DNA positive in peripheral blood of pregnant women. The study also showed that the serum HBsAg and/or HBeAg, HBV DNA became negative in 32 out of 99 HII infants during the one year follow up period.Conclusions The results of the present study suggested that the HBV infection in the uterus may be interrupted by using multiple intramuscular HBIG before delivery without any side effects. The neonates born to HBV carrier mothers should be vaccinated against HBV starting at birth, even if they are already infected with HBV in uterus.