双胎减胎、双胎与血清free β-hCG 和AFP水平的相关性
投稿时间:2025-07-04  修订日期:2025-09-05  点此下载全文
引用本文:吴晓霞,董文静,陈益明.双胎减胎、双胎与血清free β-hCG 和AFP水平的相关性[J].医学研究杂志,2026,55(1):95-102, 121
DOI: 10.11969/j.issn.1673-548X.2026.01.017
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作者单位
吴晓霞 浙江中医药大学第四临床医学院 杭州,310053
平湖市第一人民医院检验科 314200 
董文静 浙江中医药大学第四临床医学院 杭州,310053
杭州市余杭区第一人民医院检验科 311113 
陈益明 浙江中医药大学第四临床医学院 杭州,310053
杭州市妇产科医院 
基金项目:浙江省自然科学基金-联合基金资助项目(LBY23H200009)
中文摘要:目的 评估双胎减胎、双胎与中孕期血清游离人绒毛膜促性腺激素β亚基(free beta human chorionic gonadotropin,free β-hCG)和甲胎蛋白(alpha fetoprotein,AFP)水平的相关性及影响因素。方法 采用回顾性病例对照研究,分析2015年1月~2024年6月于杭州市妇产科医院进行中孕期产前筛查后住院分娩的496例孕妇资料,其中,双胎减胎组60例、双胎组239例和单胎组197例。采用独立样本Mann-Whitney H检验对各组定量资料进行比较,以受试者工作特征(receiver operating characteristic,ROC)曲线评价free β-hCG和AFP水平对双胎及双胎减胎的诊断价值。结果 双胎减胎组、双胎组孕妇的中孕期血清AFP中位数倍数(multiple of median,MoM)[1.68(0.73,32.17)MoM、1.97(0.80,3.71)MoM vs 1.02(0.60,1.76)MoM]、free β-hCG MoM水平[1.55(0.60,3.99)MoM、1.74(0.67,5.98)MoM vs 1.08(0.44,3.53)MoM]均高于单胎组,差异有统计学意义(P<0.05)。多元Logistic回归分析结果显示,AFP MoM升高、体外受精、死产和既往病史与双胎减胎相关(OR=9.357、48.609、9.992和118.129)。AFP MoM升高、体外受精、子宫瘢痕史、早产、选择性剖宫产和死产与双胎相关(OR=7.225、10.099、0.314、6.815、3.748和27.689)。ROC曲线显示,free β-hCG、AFP及AFP + free β-hCG对双胎减胎组和双胎组的曲线下面积(area under the curve,AUC)分别为0.614(95%CI:0.529~0.698)、0.773(95%CI:0.697~0.850)和0.776(95%CI:0.701~0.851);0.703(95%CI:0.654~0.752)、0.867(95%CI:0.832~0.901)和0.871(95%CI:0.836~0.905)。AFP对双胎减胎的阴性预测值(negative predictive value,NPV)(0.693)、假阴性率(false negative rate,FNR)(0.400)和阴性似然比(negative likelihood ratio,-LR)(0.442)最佳,AFP对双胎的阳性预测值(positive predictive value,PPV)(0.893)、假阳性率(false positive rate,FPR)(0.091)和阳性似然比(positive likelihood ratio,+LR)(8.374)最佳;而AFP + free β-hCG对双胎减胎的PPV(0.893)、FPR(0.066)和+LR(8.333)最佳,对双胎的NPV(0.808)、FNR(0.213)和-LR(0.237)最佳。结论 与单胎比较,双胎减胎和双胎的中孕期母血清AFP MoM水平分别增高1.65倍(1.68/1.02)和1.93倍(1.97/1.02)。而free β-hCG MoM水平分别增高1.44倍(1.55/1.08)和1.61倍(1.74/1.08)。双胎减胎和双胎的中孕期母血清AFP MoM升高明显,AFP + free β-hCG双指标联合检测的诊断价值优于free β-hCG或AFP标志物的单独检测,因此,有必要在双胎减胎和双胎孕妇的中孕期筛查前,对单胎唐氏筛查风险模型进行校准。
中文关键词:双胎 双胎减胎 游离人绒毛膜促性腺激素β亚基 甲胎蛋白 产前筛查
 
Correlation between Twin Reduction, the Presence of Twins, and the Levels of Serum Free β-hCG and AFP.
Abstract:Objective To evaluate the correlation and influencing factors between twin reduction, twin pregnancies and the levels of free β-human chorionic gonadotropin (free β-hCG) and alpha-fetoprotein (AFP) in mid-pregnancy serum. Methods A retrospective cohort study was conducted to analyze the data of 496 pregnant women who participated in mid-trimester maternal serum prenatal screening at Hangzhou Women′s Hospital from January 2015 to June 2024 and subsequently delivered in the hospital. Among these, there were 60 cases in the twin reduction group, 239 cases in the twin group, and 197 cases in the singleton group. The independent sample Mann–Whitney H test was used to compare the quantitative data of each groups, and receiver operating characteristic (ROC) curve was used to assess the diagnostic value of free β-hCG and AFP for identifying twins and twin reduction. Results The median levels of multiple of median (MoM) of mid-trimester serum AFP and free β-hCG MoM in the twin reduction group and the twin group were significantly higher than those in the singleton group [1.68 (0.73,32.17) MoM, 1.97 (0.80,3.71) MoM vs 1.02 (0.60,1.76) MoM] and [1.55 (0.60,3.99) MoM, 1.74 (0.67,5.98) MoM vs 1.08 (0.44,3.53) MoM], with statistically significant differences between groups (P<0.05). Multivariate Logistic regression analysis showed that increased AFP MoM levels, in vitro fertilisation (IVF), stillbirth, and previous medical history were associated with twin reduction (OR=9.357,48.609,9.992, and 118.129). Increased AFP MoM levels, IVF, history of uterine scarring, preterm birth, elective cesarean section, and stillbirth were associated with twin pregnancies (OR=7.225,10.099,0.314,6.815,3.748, and 27.689). The ROC curve analysis demonstrated that the area under the curve (AUC) values for free β-hCG, AFP, and the combination of AFP + free β-hCG in the twin reduction group were 0.614 (95% CI:0.529-0.698), 0.773 (95% CI:0.697-0.850), and 0.776 (95% CI:0.701-0.851), respectively. In the twin group, the corresponding AUC were 0.703 (95% CI:0.654-0.752), 0.867 (95% CI:0.832-0.901), and 0.871 (95% CI:0.836-0.905). The results showed that AFP had the best negative predictive value (NPV) (0.693), false negative rate (FNR) (0.400), and negative likelihood ratio (-LR) (0.442) for predicting twin reduction, while AFP had the best positive predictive value (PPV) (0.893), false positive rate (FPR) (0.091), and positive likelihood ratio (+LR) (8.374) for predicting twin pregnancies. In contrast, the combination of AFP and free β-hCG demonstrated the best PPV (0.893), FPR (0.066), and +LR (8.333) for predicting twin reduction, and the best NPV (0.808), FNR (0.213), and -LR (0.237) for predicting twin pregnancies. Conclusion Compared with singleton pregnancies, serum MoM levels of AFP in mid-trimester maternal increased by 1.65-fold (1.68/1.02) in twin reduction and 1.93-fold (1.97/1.02) in twin pregnancies cases. The free β-hCG MoM levels increased by 1.44-fold (1.55/1.08) in twin reduction and 1.61-fold (1.74/1.08) in twin pregnancies cases. The serum AFP MoM levels in pregnant women undergoing twin reduction and carrying twins significantly increased during pregnancy. The diagnostic value of combined detection of AFP + free β-hCG is superior to that of individual detection of AFP or free β-hCG marker. Therefore, it is essential to calibrate the screening risk model for Down′s syndrome in singleton pregnancies before the reduction of twin pregnancies and the mid-pregnancy screening of twin pregnant women.
keywords:Twin pregnancy  Twin reduction  Free beta human chorionic gonadotropin  Alpha-fetoprotein  Prenatal screening
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