Abstract
Non-invasive prenatal testing (NIPT) as a first-tier screening approach at population scale warrants close evaluation of its accessibility, affordability and extended application value. Here we present insights from a fully publicly funded NIPT programme for the pregnant population in Hebei province, China (July 2019–June 2022), with the latest NIPT coverage of 93.3%. Among 1,185,416 pregnant women, the incidences of fetal chromosome aneuploidies were 0.105% (trisomy 21), 0.026% (trisomy 18), 0.005% (trisomy 13), 0.056% (47,XXY), 0.043% (45,X), 0.039% (47,XYY) and 0.034% (47,XXX). Parental advanced age (≥35 years old) was related to a 4.31-fold risk for fetal trisomy 21 compared to parental non-advanced age. An elevated risk for small vulnerable newborns was observed in NIPT false-positive (relative risk: 1.49 (1.31, 1.68)) and NIPT high-risk without invasive prenatal diagnosis (relative risk: 1.85 (1.57, 2.18)) cases. NIPT reduced prenatal diagnosis by 97.4% compared to maternal serum screening, with better cost-effectiveness. Our findings indicate that first-tier NIPT for all pregnant women could be a feasible and cost-effective alternative to traditional maternal serum screening. NIPT positive results may be an early indicator of more adverse pregnancy outcomes beyond fetal aneuploidies.
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Data availability
The primary data from this study are not publicly available owing to restrictions in the informed consent obtained from study participants, which do not allow for public data sharing. De-identified data may be made available from J.G. upon reasonable request and following approval by the relevant institutional and ethics committees. Requests will be considered, reviewed and actioned within 1 month of receipt. The data that support the findings of this study have been deposited in the CNGB Sequence Archive (CNSA) of the China National GeneBank DataBase (CNGBdb) under accession number CNP0006003.
Code availability
The code used for participant selection, data processing and analysis can be made available from J. Zhang upon reasonable request within 1 month of receipt.
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Acknowledgements
We thank all the pregnant women who participated in the project. We thank the related staff of the 12 specified PD institutions and 288 specified prenatal testing institutions. We thank the leading group and technical expert group of Hebei NIPT project. This study was supported by the S&T Program of Hebei (grant nos. 215A9907D to S.H. and 21377722D to Y. Zhou) and the S&T Program of Shijiazhuang (grant no. 235790429H to D.T.). The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript.
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J. Zhang, L.Z., J.G., B.Z. and J. Zhu are joint senior authors and designed the study. J.L., M.W., S.H., B.Z. and J. Zhang drafted the paper. M.W., L.Y., L.T., G.H., H.J. and B.Z. contributed to the data analysis. C.Z., Yunfang Wang, Y. Zhang, Yuzhen Wang, L.C., C.G., H.L., H.X. and B.Y. contributed to the implementation of the project. S.H., Y.L., Y. Zhou, Q.H., R.D., D.T. and S.G. contributed to the data collection. J.L., J. Zhao, Y.C., J. Zhang, L.Z., J.G., B.Z. and J. Zhu contributed to the organization and supervision of the project. All authors were responsible for reviewing and revising the article. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted.
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Extended data
Extended Data Fig. 1 First-tier NIPT coverage for detecting fetal common trisomies.
PD: prenatal diagnosis. Regions were categorized by socioeconomic statuses based on GDP per capita from nationwide and regional public data in 2019 (cities of top3 GDP were defined as advantaged, cities of last 3 GDP were defined as disadvantaged, and the remaining cities were defined as intermediate). The sample size for estimating NIPT coverage (left figure) was 1,529,416 (all registered pregnancies). The sample size for PD rate (right figure) was 2,309 (NIPT high-risk cases on T21, T18, T13).
Extended Data Fig. 2 Distribution of NIPT high-risk for rare autosomal aneuploidies.
n = 953. The number of NIPT high-risk cases on each autosomal chromosome (except chromosome 13, 18, 21) was labeled above the bar. The black bar presented the prenatal diagnosis confirmed fetal RAA, and the gray bar was women without prenatal diagnosis.
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Liu, J., Wu, M., He, S. et al. Large-scale implementation of non-invasive prenatal testing for fetal aneuploidies. Nat. Health (2026). https://doi.org/10.1038/s44360-026-00104-2
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DOI: https://doi.org/10.1038/s44360-026-00104-2
