探讨早孕期(胎龄为11～13^＋6孕周)胎儿颈项透明层(NT)超声检测联合胎儿DNA无创产前检测(NIPT)，对于高龄(≥35岁)孕妇胎儿性别发育异常(DSD)的临床诊断价值。

根据孕妇入院时的顺序编号，采用随机数字表简单随机抽样方法，选取2016—2018年于中国人民解放军联勤保障部队第901医院最终活产的198例高龄孕妇的单胎妊娠胎儿为研究对象。198例高龄孕妇接受早孕期胎儿NT超声检测与胎儿DNA的NIPT。以多学科协作诊疗团队(MDT)专家根据新生儿临床表现及相关检查结果做出诊断，作为诊断胎儿DSD的"金标准"，计算早孕期胎儿NT、胎儿DNA的NIPT及二者联合检测对于诊断高龄孕妇胎儿DSD的敏感度、特异度及准确度。本研究遵循的程序符合2013年新修订的《世界医学协会赫尔辛基宣言》要求。所有受试儿监护人知情同意，并且签署临床研究知情同意书。

本组198例胎儿中，28例经MDT综合评估，最终被诊断为DSD。①早孕期胎儿NT超声检测对诊断高龄孕妇胎儿DSD的敏感度为89.3%，特异度为71.2%，准确度为73.7%。②胎儿DNA的NIPT对于诊断高龄孕妇胎儿DSD的敏感度为85.7%，特异度为78.2%，准确度为79.3%。③早孕期胎儿NT超声检测联合胎儿DNA的NIPT对于诊断高龄孕妇胎儿DSD的敏感度为96.4%，特异度为88.2%，准确度为89.4%。

早孕期胎儿NT超声检测联合胎儿DNA的NIPT，对诊断高龄孕妇胎儿DSD具有一定价值。由于本研究仅为单中心研究，纳入样本量较小，早孕期胎儿NT联合胎儿DNA的NIPT对诊断高龄孕妇胎儿DSD的价值，尚待大样本、多中心、随机对照试验进一步证实。

To investigate the clinical diagnostic value of ultrasonic testing of fetal nuchal translucency (NT) in the first trimester pregnancy (11-13^{+ 6} gestational weeks) combined with noninvasive prenatal test (NIPT) of fetal DNA in screening fetal disorders of sex development (DSD) of pregnant women with advanced age (≥35-year old).

According to the subsequence number on admission of pregnant women, 198 fetuses of singleton pregnancy with live birth of pregnant women with advanced age in the 901th Hospital of Joint Logistic Support Force of PLA from 2016 to 2018 were selected as research subjects by simple random sampling method of random number table. All pregnant women received ultrasonic testing of fetal NT in the first trimester pregnancy and NIPT of fetal DNA. Taking the diagnosis result made by multi-disciplinary team (MDT) experts according to the clinical manifestations and relevant examination results of neonates as " gold standard" for diagnosis of fetal DSD, the sensitivity, specificity and accuracy of ultrasonic testing of fetal NT in the first trimester pregnancy, NIPT of fetal DNA and the combination of these two methods in diagnosis of fetal DSD of pregnant women with advanced age were calculated, respectively. The procedures followed in this study were in line with the requirements of World Medical Association Declaration of Helsinki revised in 2013. The guardians of all subjects had informed consent and signed the informed consent form of clinical research.

Among the 198 fetuses, 28 cases were finally diagnosed as DSD after comprehensive evaluation by MDT. ① The sensitivity, specificity and accuracy of ultrasonic testing of fetal NT in the first trimester pregnancy in diagnosis of fetal DSD of pregnant women with advanced age were 89.3%, 71.2% and 73.7%, respectively. ② The sensitivity, specificity and accuracy of NIPT of fetal DNA in diagnosis of fetal DSD of pregnant women with advanced age were 85.7%, 78.2% and 79.3%, respectively. ③ The sensitivity, specificity and accuracy of ultrasonic testing of fetal NT in the first trimester pregnancy combined with NIPT of fetal DNA in diagnosis of fetal DSD of pregnant women with advanced age were 96.4%, 88.2% and 89.4%, respectively.

Fetal NT in the first trimester pregnancy combined with NIPT of fetal DNA has a certain value for diagnosis of fetal DSD of pregnant women with advanced age. As this study is just a single center study with small sample size, the value of fetal NT in the first trimester pregnancy combined with NIPT of fetal DNA in diagnosis of fetal DSD of pregnant women with advanced age still needs to be further confirmed by large-sample, multi-center and randomized controlled trials.