乙型肝炎病毒父婴垂直传播的危险因素分析

Risk factors for paternal vertical transmission of hepatitis B virus

目的探讨乙型肝炎病毒（HBV）父婴垂直传播的危险因素及HBV DNA载量对HBV父婴垂直传播的影响。方法选择2007年9月～2008年12月在福建省妇幼保健院行产前初诊检查的161例HBsAg阴性而丈夫HBsAg阳性的孕妇，以HBsAg阳性丈夫及其新生儿作为研究对象。观察指标包括一般情况、HBV携带时间、父亲乙型肝炎一级家族史、HBV标志物、HBV DNA载量、孕妇HBsAb状态、新生儿临床结局。分娩时收集新生儿脐带血进行HBVDNA定量检测，以脐带血HBV DNA载量≥1．0×10^3copy／ml为病例组，脐带血HBV DNA〈1．0×10^3copy／ml为对照组。结果（1）HBV父婴垂直传播率：161例父亲HBsAg阳性的新生儿中，有36例脐带血HBV DNA检测呈阳性，即HBV父婴垂直传播率为22．4％（36／161），其中父亲乙型肝炎e抗原（HBeAg）阳性的传播率为32．0％（23／72），父亲HBeAg阴性的传播率为14．6％（13／89）。（2）单因素分析结果：父亲HBeAg阳性、父亲HBV DNA阳性、父亲有乙型肝炎一级家族史及父亲HBV携带时间为父婴垂直传播的危险因素，x^2值及OR值分别为6．892及2．7、29．916及5．2、29．499及8．3、23．821及1．4，差异均有统计学意义（P〈0．01）。（3）多因素分析结果：父亲血清HBVDNA阳性及父亲有乙型肝炎一级家族史是HBV父婴垂直传播的危险因素，OR值及95％CI值分别为11．1及4．6～27．1、17．1及3．5～82．6。（4）父亲血清HBV DNA载量与HBV父婴垂直传播的关系：随着父亲血清HBV DNA载量的升高，新生儿脐带血HBV DNA阳性率也逐渐升高，父亲血清HBV DNA载量〈1．0×10。copy／ml时，新生儿脐带血HBV DNA阳性率为0；载量≥1．0×10^4copy／ml时，新生儿阳性率为100％。两者呈剂量反应关系。（5）新生儿临床结局：两组新生儿平均出生体重均为（3．3±0．4）kg。两组新生儿分娩方式、分娩孕周、身长、1分钟Apgar评分、新生儿病理性黄疸及合并其他内外科疾病情况进行比较，差异均无统计学意义（P〉0．05），HBV父婴垂直传播与新生儿临床结局无相关性（P〉0．05）。结论父亲血清HBV DNA载量及乙型肝炎一级家族史是HBV父婴垂直传播的危险因素；当父亲HBV DNA载量≥1．0×10^7copy／ml时，HBV父婴垂直传播率增加。

Objective To explore the risk factors of and the influence of different hepatitis B virus （HBV） DNA load on paternal vertical transmission of HBV. Methods Totally, 161 HBsAg negative women, whose husband was HBsAg positive, attended the antenatal clinics of the Provincial Maternity and Child Health Hospital of Fujian from September 2007 to December 2008 and their newborns were selected, and the epidemiologic information, the duration of being a HBV carrier, the first class HBV family history of the fathers, HBV markers, HBV DNA load, HBsAb of the gravidas, the outcomes of the newborns were all collected. Cord blood was sampled after delivery for HBV DNA quantification and those with HBV DNA load ≥ 1.0 ×10^3 copy/ml were chosen as the case group and those 〈 1.0 ×10^3 copy/ml as control. Results （1） Among the 161 newborns, 36 HBV DNA positive cord blood samples were detected, giving a rate of 22.4% （36/161） for paternal vertical transmission of HBV. The HBV DNA positive rate in cord blood was 32. 0% （23/72） in HBeAg-positive fathers and 14. 6% （13/89） in HBeAg-negative fathers. （2） Univariate analysis showed that HBeAg-positive, HBV DNA positive, first class family history of HBV and the duration of being a HBV cartier of the fathers were risk factors of paternal HBV vertical transmission [ X^2 = 6. 892, 29. 916, 29. 499 and 23. 821, OR = 2. 7, 5.2, 8.3 and 1.4 （ P 〈 0. 01 ） ]. （3） Multivariate analysis found that paternal serum HBV DNA positive and the first class family history of HBV of the father side were risk factors of paternal vertical transmission of HBV （ OR = 11. 1,95% Cl： 4. 6-27.1 ; OR = 17.1, 95% CI： 3.5- 82.6）. （4） According to the different serum HBV DNA load of the HBsAg-positive father, 7 groups were divided. A dose dependent effect was found that the HBV DNA positive rate of the cord blood increased with the rising of HBV DNA load. No HBV DNA positive cord blood was detected when paternal HBV DNA load was 〈 1.0 ×10^4 copy/ml, while 100% of the cord blood were positive when paternal tlBV DNA load ≥1.0×10^8 copy/mh （5） The average birth weight of the newborns in the two groups was the same （3.3 ± 0.4） kg. And the delivery mode, gestational age at delivery, height and Apgar score of the newborns at 1 minute, neonatal pathological jaundice and other complications had no significant difference between the two groups （P 〉 0. 05 ）. No relationship was tbund between the neonatal outcomes and the paternal HBV vertical transmission （P 〉0. 05）. Conclusions HBV DNA load in the serum of HBsAg-positive father, and the paternal first class family history of HBV are risk factors of paternal HBV vertieal transmission. When the serum HBV DNA load in HBsAg-positive father is ≥ 1.0 ×10^7copy/ml, the possibility of paternal vertical transmission of HBV would increase.