羊膜腔穿刺对乙型肝炎病毒母婴传播的影响

Influence of amniocentesis on risk of mother-to-child transmission of hepatitis B virus

目的探讨羊膜腔穿刺是否增加乙型肝炎病毒（hepatitisBvirus，HBV）母婴传播的风险。方法回顾性调查2010年1月至2013年12月在南京大学医学院附属鼓楼医院行羊膜腔穿刺的40例乙型肝炎表面抗原（hepatitis Bsurfaceantigen，HBsAg）阳性孕妇及其子女，其中3例（7．5％）孕妇乙型肝炎e抗原（hepatitis Beantigen，HBeAg）阳性。随访时询问孕妇抗病毒治疗史，记录儿童预防措施，并采集儿童外周血，检测HBV血清标记物。同时检测同期采集的、于-80℃保存的HBsAg阳性孕妇的共48例羊水标本中的HBV标记物。采用χ2检验或Fisher精确概率法进行统计分析。结果40例孕妇行羊膜腔穿刺时平均年龄（31．5±5．5）岁（21～41岁），平均孕周（21．2±1．6）周（18．4～24．9周）。穿刺指征主要为唐氏综合征筛查高风险（26例、65．0％）和高龄（4例、10．0％），14例（35．0％）孕妇经胎盘穿刺。所有孕妇穿刺前均未接受抗病毒治疗，新生儿出生时均正规接种乙型肝炎疫苗和使用乙型肝炎免疫球蛋白。获得随访且保存羊水标本的28例孕妇中，2例（7．1％）HBsAg阳性，其中1例（3．6％）HBVDNA同时阳性。40例获随访的子代中，男性23例（57．5％），平均年龄（2．0±1．0）岁（7个月～4岁）。HBsAg阳性孕妇羊水HBsAg和HBVDNA阳性率大于HBsAg阴性者[4．7％（2／43）与3／5，χ2=14．705；0／43与2／5，χ2=17．948；P值均〈0．05]。37例HBsAg阳性而HBeAg阴性孕妇的子代无一例HBsAg阳性，乙型肝炎核心抗体（hepatitisBcoreantibody，抗-HBc）亦均阴性，另3例HBsAg和HBeAg同时阳性孕妇的子代HBsAg和抗-HBc均阴性。子代乙型肝炎表面抗体阳性率90．0％（36／40）。结论对HBeAg阴性孕妇，羊膜腔穿刺不增加其子代感染HBV的风险，经胎盘穿刺亦不增加HBV母婴传播的风险。对HBeAg阳性孕妇，羊膜腔穿刺是否增加HBV母婴传播尚需进一步研究。羊水HBsAg或HBVDNA阳性不能诊断为宫内感染。

Objective To investigate whether amniocentesis may increase the risk for mother-to- child transmission of hepatitis B virus （HBV）. Methods Totally 40 children born to HBV-infeeted mothers who had amnioccntesis performed in Nanjing Drum Tower Hospital, Nanjing University Medical School from January 2010 to December 2013, were followed up and screened for HBV markers. Amniotie fluid samples were collected and stored at -- 80 ℃ were tested for HBV markers. Among the 40 carrier mothers, three （7.5%） were hepatitis B e antigen （HBeAg）-positive. Relevant data such as antiviral history, administration of hepatitis B vaccine and hepatitis B immunoglobulin （HBIG） in infants were collected. Chi-square test or Fisher＇s exact test was used for statistical analysis. Results The mothers were 21-41 years old, with a mean age of （31.5±5.5） years at the time of amniocentesis and mean gestational age of （21.2±1.6） weeks （18.4-24.9 weeks）. Indications for amniocentesis were mainly abnormal maternal serum alpha-fetoprotein levels （65.0%, 26/40） and maternal age over 35 years （10.0%, 4/40）. None of the mothers received antiviral therapy and 14 （35.0%） underwent transplacental amniocentesis. Among 28 cases who had a store of amniotic fluid sample and were followed-up, one （7.1%） was positive for both hepatitis B surface antigen （HBsAg） and HBV DNA, and another was positive for HBsAg only. The average age of 40 children at follow-up was （2.0± 1.0） years （seven months to four years old）, among which 23 were boys and 17 were girls. All of them received hepatitis B vaccine and HBIG. Positive rate of HBsAg and HBV DNA in HBeAg（＋） mothers are higher than those in HBeAg（-） mothers [4.7%（2/43） vs 3/5, χ2=14.705; 0/43 vs 2/5, χ2=17.948; both P 〈 0.05]. Thirty-seven children born to HBsAg（＋）/HBeAg（-） mothers were negative for both HBsAg and hepatitis B core antibody （anti-HBc）, and the other three born to HBsAg（＋）/HBeAg（＋） mothers were also negative for HBsAg and anti-HBc. Additionally, the positive rate of hepatitis B surface antibody in children was 90.0% （36/40）. Conclusions For those HBsAg（＋）/HBeAg（-） mothers, amniocentesis does not elevate the risk for mother-to-child transmission of HBV, even performed transplacentally. However, further studies are needed for HBeAg-positive mothers. HBsAg or HBV DNA positive in amniotic fluid should be diagnosed as intrauterine infection of HBV.