连结静　　程兆俊　　宁雯雯　　陈益明

[摘要] 目的 了解早孕期血清產前筛查标志物妊娠相关性蛋白A（PAPP-A）和游离人绒毛膜促性腺激素β亚基（free β-hCG）预测晚期自然流产的价值。 方法 回顾性分析2017年1月至2019年12月在杭州市妇产科医院参加早孕期产前筛查且随访结局为发生晚期自然流产的209例孕妇为自然流产组，并随机选择374例同期生育正常胎儿的孕妇作为对照组，比较两组孕妇的早孕期血清free β-hCG和PAPP-A水平。采用二元Logistic回归分析对早孕筛查标志物是否为自然流产的保护和危险因素进行筛选，利用ROC曲线确定截断值、曲线下面积（AUC），对自然流产的诊断价值进行评价。 结果 自然流产组孕妇的血清PAPP-A水平为0.90（0.21，2.39）MoM，低于对照组的0.97（0.43，2.38）MoM，差异有统计学意义（P<0.05）;二元Logistic回归分析结果显示，PAPP-A MoM 升高是自然流产的保护因素，其OR值为0.659，95%CI：0.463～0.937;自然流产组的free β-hCG为0.93（0.30，2.69）MoM，低于对照组的1.07（0.33，3.61）MoM，差异有统计学意义（P=0.048）。但free β-hCG MoM不是自然流产的危险或保护因素（OR=0.811，P=0.112）。 结论 PAPP-A对晚期自然流产有预测价值，PAPP-A结合预产年龄、孕龄和体重可以提高预测价值，但free β-hCG对晚期自然流产的预测价值有待进一步探讨。

[关键词] 早孕期;产前筛查;PAPP-A;free β-hCG;晚期自然流产

[中图分类号] R714.24          [文献标识码] B          [文章编号] 1673-9701（2021）13-0069-04

Value of serological prenatal screening indexes in early pregnancy in predicting late spontaneous

LIAN Jiejing1， 2   CHENG Zhaojun3   NING Wenwen2   CHEN Yiming1， 2

1.Prenatal Diagnosis Center， Hangzhou Obstetrics and Gynecology Hospital， Hangzhou   310008， China; 2.The Fourth Clinical Medical College， Zhejiang Chinese Medical University， Hangzhou   310003， China; 3.Reproductive Medicine Center， Hangzhou Obstetrics and Gynecology Hospital， Hangzhou   310008， China

[Abstract] Objective To understand the value of serum prenatal screening markers（PAPP-A） and free beta subunit-human chorionic gonadotropin （free β-hCG）in predicting late spontaneous abortion during early pregnancy. Methods A total of 209 pregnant women who participated in prenatal screening during early pregnancy in Hangzhou Obstetrics and Gynecology Hospital from January 2017 to December 2019 and whose follow-up results showed late spontaneous abortion were randomly selected as the spontaneous abortion group， and 374 pregnant women who were given birth to normal fetuses at the same time were selected as the control group. The serum free β-hCG and PAPP-A levels of the two groups of pregnant women during early pregnancy were compared. Binary logistic regression analysis was used to screen whether early pregnancy screening markers were protective and risk factors for spontaneous abortion. ROC curve was used to determine truncation value and area under curve to evaluate the diagnostic value of spontaneous abortion. Results The serum PAPP-A level of pregnant women was 0.90（0.21， 2.39） MoM in the spontaneous abortion group， which was lower than that in the control group （0.97 [0.43， 2.38] MoM）. The difference between the two groups was statistically significant（P<0.05）. The results of binary logistic regression analysis showed that the increase of PAPP-A MoM was the protective factor for spontaneous abortion， and its OR value was 0.659 and 95%CI： 0.463-0.937. The free β-hCG was（0.93 [0.30， 2.69]） MoM in the spontaneous abortion group， which was lower  than that of（1.07[0.33， 3.61] MoM） in the control group， and the difference between the two groups was statistically significant（P=0.048）. However， free β-hCG MoM was not a risk or protective factor for spontaneous abortion（OR=0.811， P=0.112）. Conclusion PAPP-A bears a predictive value for late spontaneous abortion. PAPP-A combined with pre-delivery age，gestational age and body weight can improve the predictive value， but the predictive value of free β-hCG for late spontaneous abortion needs to be further discussed.

[Key words] Early pregnancy; Prenatal screening; PAPP-A; free β-hCG; Late spontaneous abortion

流产是指孕龄不足28周，胎儿体重不足1000 g而终止妊娠者，发生在孕12周以前的流产为早期流产，孕12周以上至不足28周的流产为晚期流产[1]。在自然状态（非人为因素）发生的流产称为自然流产，是妊娠期间常见的并发症，在所有临床妊娠中的发生率约为15%，主要由胎儿染色体异常[2]、母体内分泌失调、感染、环境射线以及不健康的生活方式等因素引起[3]。早期自然流产中超过50%是由染色体异常引起[4]，而引起晚期自然流产的因素比较复杂，主要有子宫病变、全身性疾病、胎盘发育不良、内分泌功能失调、染色体异常、遗传因素缺陷等[5]。晚期自然流产对孕妇的身心健康造成很大的影响，其影响程度与孕龄大小呈正相关[6]。……