Effectiveness of Alpha-Fetoprotein Variants L2 and L3 as Substitutes of Alpha-Fetoprotein in Screening for Fetal Trisomy 18

Abstract Purpose To evaluate the effectiveness of alpha-fetoprotein variants (AFP-L2, AFP-L3) for fetal screening of Trisomy 18 in place of alpha fetoprotein (AFP). Methods A case-control study was conducted. The case group included 39 pregnant women diagnosed by karyotype analysis of amniotic fluid cells as bearing Trisomy 18 fetuses. The control group included 48 pregnant women with clinically normal and healthy fetal development. The serum AFP-L2 and AFP-L3 concentrations were detected. Receiver operating characteristic (ROC) curves were used to determine the optimal cutoff value, area under the curve (AUC), and assess the screening performance of AFP-L2 and AFP-L3. Results The AFP-L2 and AFP-L3 concentrations in pregnant women with Trisomy 18 fetuses were 7.95±3.57 ng/mL , and 2.53±1.80 ng/mL, respectively, which was significantly higher than those of the control group (3.73±1.63 ng/mL [3.26~4.20], t=6.820, P<0.001, and 0.84±0.60 ng/mL [0.66~1.01], t=5. 588, P<0.001, respectively). The AUC for AFP-L2 and AFP-L3 in screened Trisomy 18 fetuses was 0.848 (95% CI: 0.767-0.930, P < 0.001) and 0.806 (95% CI: 0.707-0.905, P < 0.001), respectively. The optimal cutoff values of AFP-L2 and AFP-L3 for Trisomy 18 fetuses were determined to be 6.340 ng/mL and 1.705 ng/mL, respectively. The corresponding sensitivity, specificity, and Youden index values were 0.615, 1.000, 0.615; 0.6410, 0.958, and 0.599, respectively. Comparisons across multiple modeling methods showed that the highest AUC of screened Trisomy 18 fetuses (0.992 and 0.986) was yielded by AFP-L2 + AFP-L3 + free β-HCG, and AFP-L2 + free β-HCG, with 1.000 sensitivity indicated in both instances. The sensitivities of the four Trisomy 18 screening combinations were all 1.000. In the control group, false positive rates of 22.92%, 8.33%, 12.50%, and 12.50% were observed. The series test showed that the sensitivities of Trisomy 18 screening was 69.23%, 61.54%, 64.10%, and 43.59%, respectively, while a 3.28% false positive rate was found in the control group AFP + free β-HCG marker combination. Conclusion AFP-L2 and AFP-L3 showed high sensitivity and specificity in the screening of fetuses for Trisomy 18. The new indicators did not bring about a significant improvement in screening efficiency but false positive rate was reduced compared to AFP.