HBsAg阳性母亲所生婴儿的母婴阻断及全程接种乙型肝炎疫苗后免疫应答状态

目的 了解HBsAg阳性母亲所生婴儿的母婴阻断及全程接种乙型肝炎疫苗后免疫应答状态及变化规律.方法 对249例HBsAg阳性母亲的新生儿予以联合母婴阻断措施,并全程接种乙型肝炎疫苗,用微粒化学发光法跟踪测定婴儿生后7、12、24、36个月的HBsAg和抗-HBs水平.组间比较采用卡方检验.结果 HBsAg阳性母亲所生婴儿母婴阻断后不同时间免疫应答状态不同,7月龄婴儿无应答率为8.0%(20/249),低应答率为11.7%(29/249),强应答率为80.3%(200/249);12月龄婴儿无应答率为10.8%(13/120),低应答率为26.7%(32/120),强应答率为62.5%(75/120);24月龄婴儿无应答率14.8%(4/27),低应答率为33.3%(9/27),强应答率为51.9%(14/27),36月龄婴儿无应答率为14.3%(1/7),低应答率为28.6%(2/7),强应答率为57.1%(4/7);7月龄组与其他月龄组同等应答状态间比较,差异有统计学意义(x2=21.98,P＜0.01).强应答组婴幼儿抗-HBs效价出生7个月后出现逐渐下降的趋势,效价越高,其下降的例数越少,下降出现的时间越晚.抗-HBs效价＞1000 mIU/mL时,在36个月内下降比率为57.6%(19/33),下降高峰为24个月(57.9%,11/19);抗-HBs效价为100～1000 mIU/mL时,在36个月内下降比率为73.8%(31/42),下降高峰为12个月(54.8%,17/31).HBsAg阳性婴儿7月龄多表现为无应答状态,占全部无应答婴儿的70%(14/20,x2=128.61,P＜0.01),99%(189/191)HBsAg阴性婴儿多为强应答.HBeAg同时阳性母亲的婴儿无应答率有高于HBeAg阴性母亲婴儿的趋势,但差异无统计学意义(9.1%比5.5%,x2=0.24,P＞0.05).结论 HBsAg阳性母亲新生婴儿的母婴阻断及全程接种乙型肝炎疫苗后不同时间免疫应答状态不同,且呈动态变化;无应答状态多见于HBsAg阳性的免疫失败婴儿;HBsAg阴性婴儿大多呈强应答;HBeAg同时阳性的母亲婴儿更易呈低应答.建议完善母婴阻断后管理流程,特别是生后7个月～2年的积极随访监测.

Immune responses of infants born to HBsAg positive mothers after combined passive immunoprophylaxis and active immunoprophylaxis

Objective To evaluate the immune responses and its dynamic changes of the babies born to hepatitis B surface antigen (HBsAg) positive mothers after combined passive immunoprophylaxis and active immunoprophylaxis. Methods Two hundred and forty-nine infants born to HBsAg positive mothers were enrolled. All of these infants have received both passive immunoprophylaxis by injecting hepatitis B immunoglobuin (HBIG) and active immunoprophylaxis by vaccinated with hepatitis B vaccine simultaneously 12 hours after birth. After that, all infantscompleted the whole vaccination program. The titers of serum HBsAg and hepatitis B surface antibody (HBsAb) of the infants were checked at 7, 12, 24 and 36 months after birth. The data was analyzed by chi square test. Results Infants born to HBsAg positive mothers showed various immune response modes. The no response rate, low response rate and strong response rate were 8.0% (20/249),11.7% (29/249) and 80.3% (200/249) respectively in the 7-month infants, which were 10.8% (12/120), 26.7% (32/120) and 62.5% (75/120) respectively in 12-month infants. The results from further follow-up showed that no response rate, low response rate and strong response rate were 14.8% (4/27), 33.3% (9/27) and 51.9% (14/27) respectively in the 24-month babies and were 14.3 (1/7), 28. 6% (2/7) and 57.1% (4/7) respectively in the 36-month babies. There were statistically significant difference between the 7-month infants group and other groups (x2= 21.98,P＜0.01). The HBsAb titers of high-response infants group declined over time. The infants with higher antibody titers tended to not decline or decline more slowly. In infants who have even achieved HBsAb titers higher than 1000 mIU/mL, 57.6% (19/33) of them showed decreased titers in 36 months. The titer decrease peaked at 24 month after birth (57.9%, 11/19). In infants who have achieved HBsAb titers of 100 to 1000 mIU/mL, 73.8% (31/42) of them showed decreased titers in 36 months. The titer decrease peaked at 12 month after birth (54.8%, 17/31). HBsAg positive infants usually showed no response at 7 month, who accounted for 70% (14/20,x2 = 128.61, P＜0.01) of all no response infants. Ninety-nine percent (189/191) of HBsAg negative infants showed strong responses. The infants born to both HBsAg positive and hepatitis B e antigen (HBeAg)positive mothers tended to show no response. However, the difference between these infants and others was not statistically significant (9.1% vs 5.5%,x2 =0.24,P＞0.05). Conclusions The immune responses of infants born to HBsAg positive mothers after combined passive and active immunoprophylaxis change over time. The non-response status is usually found in HBsAg positive infants. HBsAg negative infants usually show strong response. Infants born to both HBsAg positive and HBeAg positive mothers tend to show low response. It is recommended to follow standard immunoprophylaxis procedure. The follow-up and active monitor are very important during 7 months to 2 years after birth.