Identifying occult maternal malignancies from 1.93 million pregnant women undergoing noninvasive prenatal screening tests

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Multiple chromosomal aneuploidies may be associated with maternal malignancies and can cause failure of noninvasive prenatal screening (NIPS) tests. However, multiple chromosomal aneuploidies show poor specificity and selectivity for diagnosing maternal malignancies.


This multicenter retrospective analysis evaluated 639 pregnant women who tested positive for multiple chromosomal aneuploidies on initial NIPS test between January 2016 and December 2017. Women were assessed using genome profiling of copy-number variations, which was translated to cancer risk using a novel bioinformatics algorithm called the cancer detection pipeline (CDP). Sensitivity, specificity, and positive predictive value (PPV) of diagnosing maternal malignancies were compared for multiple chromosomal aneuploidies, the CDP model, and the combination of CDP and plasma tumor markers.


Of the 639 subjects, 41 maternal malignant cancer cases were diagnosed. Multiple chromosomal aneuploidies predicted maternal malignancies with a PPV of 7.6%. Application of the CDP algorithm to women with multiple chromosomal aneuploidies allowed 34 of the 41 (83%) cancer cases to be identified, while excluding 422 of 501 (84.2%) of the false positive cases. Combining the CDP with plasma tumor marker testing gave PPV of 75.0%.


The CDP algorithm can diagnose occult maternal malignancies with a reasonable PPV in multiple chromosomal aneuploidies–positive pregnant women in NIPS tests. This performance can be further improved by incorporating findings for plasma tumor markers.

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The study was supported by the National Key Research & Development Program of China (grant number 2016YFC0905400); Young Scientists Fund of the National Natural Science Foundation of China (grant number 81601293); Natural Science Foundation of Guangdong Province, China (2017A030306026); the Fund for Distinguished Young Scholars of South China University of China (2017JQ017); the Guangzhou Science and Technology Project (201400000004-5, 201508020247); the Pearl River Nova Program of Guangzhou (201506010065); National Key R&D Program of China (grant number 2018YFC1002900, 2018YFC1002901); and High-level Talents of Guangdong (grant number 2016TX03R171).

Author information

XJ, JL, YHH, PLS, and YYY are joint first authors. XJ, YW C and MM are joint corresponding authors on this study. All authors were involved in designing the study; following up with patients; collecting, analyzing, and interpreting the data; and writing the manuscript. All genomic data for all participants and computer codes from this study are deposited at China Nucleotide Sequence Archive (accession ID CNP0000067,

Correspondence to Xin Jin PhD or Yingwei Chen MD or Mao Mao MD, PhD.

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The authors declare no conflicts of interest.

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Ji, X., Li, J., Huang, Y. et al. Identifying occult maternal malignancies from 1.93 million pregnant women undergoing noninvasive prenatal screening tests. Genet Med 21, 2293–2302 (2019) doi:10.1038/s41436-019-0510-5

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  • Noninvasive prenatal screening test
  • Maternal malignancy
  • Multiple chromosomal aneuploidies
  • Cancer detection
  • Plasma tumor marker

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