Construction and predictive value of risk models of maternal serum alpha-fetoprotein variants and fetal open neural tube defects

Abstract

The correlation of maternal serum alpha-fetoprotein (AFP) variants (AFP-L2, AFP-L3), free beta-human chorionic gonadotropin (free β-hCG), and open neural tube defects (ONTDs) during the second trimester, and the screening efficiency of different risk models remain indistinct. We conducted a retrospective case-control study, and studied 57 pregnant women with ONTD fetuses and 569 pregnant women with normal fetuses. The receiver operating characteristic curve method indicated the best cutoff value and area under the curve (AUC). The predictive value of ONTD risk models by free β-hCG, AFP, AFP-L2, and AFP-L3 was investigated via integrated discrimination improvement (IDI), net reclassification improvement (NRI), and decision curve analysis (DCA). Compared to the control group, AFP, AFP-L2, and AFP-L3 levels were significantly higher, while free β-hCG level was significantly lower in the study group. The triple-index model of free β-hCG + AFP-L2 + AFP-L3 and the dual-index model of AFP-L2 + AFP-L3 showed the best predictive values, respectively (AUC = 0.905; AUC = 0.885). The order of the single-index model AUCs was AFP-L3 > AFP-L2 > AFP > free β-hCG. The negative predictive value, false positive rate, and negative likelihood ratio of AFP-L2, AFP-L3 alone, or combined with free β- hCG were better than those of AFP alone; however, the positive likelihood ratio was the opposite. The replacement of AFP by AFP-L2 or AFP-L3 combined with free β-hCG increased the IDI and NRI for predicting ONTD. The top five DCAs were AFP-L2 + free β-hCG, free β-hCG, AFP-L3, AFP + free β-hCG, and AFP. Indicators of maternal serum free β-hCG, AFP-L2, and AFP-L3 in the second trimester exhibited high sensitivity and specificity screening for ONTD fetuses. Risk models constructed using AFP-L2 + AFP-L3 and AFP-L2 + AFP-L3 + free β-hCG demonstrated better screening efficiency.