Effectiveness of alpha-fetoprotein variants L2 and L3 as substitutes of alpha-fetoprotein in screening for fetal Trisomy 18

Abstract

Objective

To evaluate the effectiveness of alpha-fetoprotein variants (AFP-L2, AFP-L3) in fetal screening for Trisomy 18 in place of alpha fetoprotein (AFP).

Methods

A retrospective case-control study was conducted. Collectively, 39 pregnant women bearing Trisomy 18 fetuses and 48 pregnant women with clinically normal and healthy fetuses were included. The serum AFP-L2 and AFP-L3 concentrations were detected by enzyme-linked immunosorbent assays. The likelihood ratio method and Python software were used to construct the risk model with AFP, free β-hCG, AFP-L2, and AFP-L3 to predict Trisomy 18. Receiver operating characteristic (ROC) curves were used to determine the optimal cutoff value, while the area under the curve (AUC) was used to assess the screening performance of AFP-L2 and AFP-L3 for fetal Trisomy 18.

Results

Compared to values observed for the control group, AFP-L2 and AFP-L3 concentrations which were significantly higher (both p< .001) in pregnant women with Trisomy 18 fetuses were 7.95 ± 3.57 ng/mL and 2.53 ± 1.80 ng/mL, respectively. Comparisons across multiple modeling methods showed that the highest AUC of screened Trisomy 18 fetuses (0.992, 0.986, and 0.976) was yielded by AFP-L2 + AFP-L3 + free β-hCG, AFP-L2 + free β-hCG, and AFP-L3 + free β-hCG, with a sensitivity of 1.000 indicated in both instances. In different modeling methods, the order of AUC values was AFP-L2 + AFP-L3 + free β-hCG > AFP-L2 + free β-hCG > AFP-L3 + free β-hCG > AFP + free β-hCG.

Conclusions

AFP-L2 and AFP-L3 showed higher sensitivity and specificity as substitutes for AFP in screening Trisomy 18. These two markers indeed improved the screening efficiency and reduced the false positive rate, when compared with AFP only.

Keywords:

• Second trimester
• maternal serum screening
• alpha-fetoprotein variants L2
• L3
• Trisomy 18
• risk modeling

Acknowledgments

The authors are grateful to all participants and contributors. Thanks to Linyuan Gu and Xuelian Chu from the Maternity and Child Health Care Hospital in the Yuhang District of Hangzhou for assistance in collecting the data and the cases of confirmed diagnosis. We thank Ran Xin, Shaolei Lv, and Xiaoying Wang of Data Analysis Department of Zhejiang Biosan Biochemical Technologies Co., Ltd. for their great contribution to this project in patients follow-up and data analysis, and modeling for this project. We also thank International Science Editing (http://www.internationalscienceediting.com) for editing this manuscript.

Statement of ethics

The study was approved by Hangzhou Women’s Hospital (Hangzhou Maternity and Child Health Care Hospital) ethics committee, in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. The approval number was [2018] medical ethics (004) No. 01. Consent obtained from study participants was written.

Disclosure statement

The authors have no conflicts of interest to declare.

Additional information

Funding

This work is funded by Zhejiang Public Welfare Technology Research Program/Social Development (Grant number LGF19H040006); Hangzhou Science and Technology Plan Guidance Project (Grant number 20181228Y13); Hangzhou Health Science and Technology Plan Project (Grant number 2017A55).