妊娠中期唐氏综合征筛查血清标志物异常与不良妊娠结局

Maternal serum markers for Down syndrome screening in second-trimester and its relations with adverse pregnant outcomes

目的探讨妊娠中期唐氏综合征筛查血清标志物异常与不良妊娠结局的关系。方法2009年1月1日至2011年1月31日在北京协和医院产科门诊进行妊娠中期三联筛查、在本院分娩并随访到妊娠结局者，共1935例。采用时间分辨荧光免疫分析技术测定妊娠中期（妊娠15～20＋6周）孕妇血清甲胎蛋白（alpha fetoprotein，AFP）、游离β-人绒毛膜促性腺激素（phuman chorionic gonadotropin，β-hCG）及游离雌三醇（unconjugated estriol，uE3）水平。分析血清标志物正常者与异常者之间不良妊娠结局发生率的差异。采用t检验和7。检验进行统计学分析。结果（1）1935例孕妇中，血清标志物正常者（正常组）1255例；异常者680例，包括单项异常者577例，2项异常者89例以及3项异常者14例。根据血清标志物异常的情况，将577例单项异常者分为AFP升高组17例、AFP降低组114例、β—hCG升高组242例、13～hCG降低组139例及uE。降低组65例。AFP降低组妊娠中期体重及β-hCO降低组的分娩孕龄大于正常组[分别为（61．3±9．1）kg与（59．5±8．3）kg、（272．6±11．8）d与（274．4±10．1）d，t=2．21和1．99，P均〈0．01]。（2）正常组不良妊娠结局发生率为42．8％（537／1255），与血清标志物异常者（43．7％，297／680）相比，差异无统计学意义（RR=1．02，P=0．71）。与正常组相比，AFP升高组前置胎盘及胎盘形态异常发生率[分别为25．5％（32／1255）与2／17、4．1％（51／1255）与5／17，RR=4．61和7。24]、AFP降低组妊娠期糖尿病（gestational diabetes mellitus，GDM）发生率[8．1％（101／1255）与14．4％（16／114），RR=1．74]、phCG升高组胎盘胎膜滞留发生率E3．5％（44／1255）与6．2％（15／242），RR=1．773及phCG降低组子痫前期发生率[1．7％（21／1255）与6．5％（9／139），RR=3．87]均升高，差异均具有统计学意义（P均〈0．05）。（3）血清标志物2项异常者共89例。AFP低G—hCG高组小于胎龄儿、羊水过少和胎盘早剥发生率均高于正常组[小于胎龄儿：6．9％（2／29）与1．8％（22／1255），RR=3．94；羊水过少：20．7％（6／29）与6．4％（80／1255），RR=3．24]；AFP低uE。低组羊水过少发生率高于正常组[3／14与6．4％（80／1255），RR=3．363；a-hCG低uE。低组早产和GDM发生率高于正常组[早产：2／6与4．3％（54／；255），RR=7．75；GDM：3／6与8．0％（101／1255），RR=6．21]；差异均具有统计学意义（P均〈0．05）。（4）血清标志物3项异常者共14例，这些孕妇的血清标志物异常与妊娠不良结局的关系没有统计学意义。结论唐氏综合征筛查血清标志物异常与不良妊娠结局有较为密切的关系，妊娠期应密切监测。

Objective To investigate the relationship between abnormalities of maternal serum markers in Down syndrome screening in second trimester and adverse pregnancy outcome. Methods Totally, 1935 pregnant women were screened for Down syndrome with maternal serum tri-marker with time resolved fluorescence assay, including alpha-fetoprotein （AFP）, free β-human chorionic gonadotropin （β-hCG） and unconjugated estriol （uE3）, between 15 and 20±6 gestational weeks at Peking Union Hospital from January 1, 2009 to January 31, 2011, and were followed up till delivery. The relationship between incidence of adverse pregnancy outcomes and women with normal or abnormal levels of serum markers in Down syndrome screening was investigated. T-test or Chi ／0square test were applied for statistical comparison. Results （1） Among the 1935 pregnant women, normal levels of serum markers were found in 1255（normal group） and 680 were abnormal（abnormal group）, in which 577 with only one abnormal serum marker, 89 with two and 14 with three abnormal serum markers. According to the serum marker level, the 577 women with one abnormal serum marker were further divided into five groups, including high AFP group （n=17）, low AFP group （n=114）, high β-hCG group （n=242）, low β-hCG group （n=139） and low uE3 group （n=65）. The birth weight of infants in lower AFP group and the gestational age at delivery in low β-hCG group were greater than those in normal group [（61.3±9.1） kg vs （59.5±8.3） kg, （272.6±11.8） d vs （274.4±10.1） d, t 2.21 and 1.99, both P〈0.01]. （2） The incidence of adverse pregnancy outcome in normal group was 42.8%（537/1255）, while comparing with the abnormal group（43.7%,297/680）, no statistical significance was shown （RR = 1.02, P = 0.71）. While comparing with the normal group, the incidences of placenta previa [25.5% （32/1255） vs 2/17, RR=4.61, P〈±0.05] and abnormal placental morphology were higher in high AFP group [4.1% （51/1255） vs 5/17, RR=7.24, P〈0. 05], the incidence of gestational diabetes mellitus （GDM） was higher in low AFP group [8. 1% （101/1255） vs 14.4% （16/114）, RR 1.74,P〈0.05], the incidence of placenta and membrane retention was higher in high ±hCG group [3.5% （44/1255） vs 6.2±（15/242）, RR 1.77,P〈 0.05], the incidence of pre eclampsia was higher in low β-hCG group [1.7%（21/1255） vs 6.5%（9/ 139）, RR=3.87,P〈0. 05]. （3） There were 89 women with two abnormal serum markers. Comparing with the normal group, the incidences of small for gestional age （SGA） infants, oligohydramnios, abruptio placenta were higher in women with low AFP but high β-hCG [SGA infants： 6.9%（2/29） vs 1.8%（22/1255）, RR=3.94; oligohydramnios： 20.7%（6/29） vs 6.4%（80/ 1255）, RR=3.24; both P〈0.05], the incidences of oligohydramnios was higher in women with both low AFP and low uE3[3/14 vs 6.4% （80/1255）, RR=3.36, P〈0.05], the incidence of premature birth and GDM were higher in women with both low β- hCG and low uE3 [premature birth： 2/6 vs 4.3%（54/1255）, RR= 7.75; GDM： 3/6 vs 8.0± （101/1255）, RR= 6.21; both P〈0.05]. （4） There were 14 women with three abnormal serum markers. The relationship between adverse outcome and abnormal serum markers did not show any statistical significance. Conclusions The abnormality of serum markers of Down syndrome screening is closely related to adverse pregnancy outcomes, and women with abnormal serum markers should be carefully monitored during pregnancy.