基于双生子样本的婴儿乙肝疫苗低/无免疫应答的围生期相关因素分析

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目的探讨围生期环境因素如喂养方式、生命早期营养状况等对婴儿乙肝疫苗低/无免疫应答的影响,为研究乙肝疫苗免疫失败机制提供依据。方法采用病例对照研究设计,纳入来自5家协作医院儿童保健科参加常规体检的1周岁的双生子和无关个体组成两个独立样本,排除无关个体样本中低出生体重儿及两样本中乙肝表面抗原(HBsAg)阳性及母亲有乙肝病史的研究对象。通过病案调查及现场访谈,收集研究对象的父母健康状况、母亲孕产史、婴儿出生状况及1岁以内体检信息等可能的暴露因素资料。在分析乙肝疫苗低/无免疫应答的相关影响因素时,双生子样本采用XTGEE广义估计模型,无关个体样本采用Logistic回归模型和Tobit回归模型进行分析。结果纳入分析的双生子样本为370人,无关个体样本为300人。19.2%(71例)双生子和11.7%(35例)无关个体在接种乙肝疫苗后发生低/无免疫应答。在双生子样本中,父亲吸烟(OR=4.50,95%CI:2.52~8.03)和低出生体重(OR=2.55,95%CI:1.33~4.87)可能增加乙肝疫苗低/无免疫应答风险,Apgar评分高和0~1周岁体重增长量大可能降低乙肝疫苗低/无免疫应答的风险。但在出生体重正常的无关个体样本中未发现上述因素与乙肝疫苗低/无免疫应答的相关性。结论按照0-1-6方案接种乙肝疫苗后,低出生体重、父亲吸烟、Apgar评分和0~1周岁体重增长量与婴儿发生乙肝疫苗低/无免疫应答相关。 Objective To investigate the impact of perinatal environmental factors such as feeding mode and nutritional status on the low / non-immune response of hepatitis B vaccine in infants and to provide basis for studying the mechanism of immune failure of hepatitis B vaccine. Methods A case-control study was designed and included two independent samples of one-year-old twins and unrelated individuals who participated in routine physical examinations from five collaborating hospitals in children’s health department to exclude two unrelated individuals from low birth weight infants and two samples of hepatitis B surface antigen (HBsAg) positive mother and the history of hepatitis B subjects. Through the medical record investigation and the on-the-spot interview, we collected the possible exposure factors such as the parents’ health condition, the mother’s mother’s history of pregnancy, the baby’s birth condition and the medical information within 1 year of age. In analyzing the influencing factors of low / no immune response of hepatitis B vaccine, twins samples were estimated by XTGEE generalized estimation model, and unrelated individual samples were analyzed by Logistic regression model and Tobit regression model. Results Twelve pairs of samples were included in the analysis and 300 unrelated individuals. 19.2% (71) twins and 11.7% (35) unrelated individuals developed a low / no immune response after hepatitis B vaccination. Fetal smoking (OR = 4.50, 95% CI: 2.52 to 8.03) and low birth weight (OR = 2.55, 95% CI: 1.33 to 4.87) in doubanated subjects may increase the risk of hepatitis B vaccine low / no immune response, Apgar High ratings and large weight gain from 0 to 1 year of age may reduce the risk of low / no immune response to hepatitis B vaccine. However, no correlation was found between the above factors and HBV vaccine low / no immune response in unrelated individuals with normal birth weight. Conclusion Low birth weight, fatal smoking, Apgar score and weight gain of 0-1 year-old children were associated with low / no immune response to hepatitis B vaccine in infants after vaccination with hepatitis B vaccine according to 0-1-6 protocol.
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