Retrospective details of false-positive and false-negative results in non-invasive prenatal testing for fetal trisomies 21, 18 and 13

Suzumori, Nobuhiro; Sekizawa, Akihiko; Takeda, Eri; Samura, Osamu; Sasaki, Akira; Akaishi, Rina; Wada, Seiji; Hamanoue, Haruka; Hirahara, Fumiki; Sawai, Hideaki; Nakamura, Hiroaki; Yamada, Takahiro; Miura, Kiyonori; Masuzaki, Hiroaki; Nakayama, Shinichi; Kamei, Yoshimasa; Namba, Akira; Murotsuki, Jun; Yamaguchi, Masayuki; Tairaku, Shinya; Maeda, Keisuke; Kaji, Tatsuru; Okamoto, Yoko; Endo, Masayuki; Ogawa, Masaki; Kasai, Yasuyo; Ichizuka, Kiyotake; Yamada, Naoki; Ida, Akinori; Miharu, Norio; Kawaguchi, Satoshi; Hasuo, Yasuyuki; Okazaki, Taro; Ichikawa, Masao; Izumi, Shun-ichiro; Kuno, Naohiko; Yotsumoto, Junko; Nishiyama, Miyuki; Shirato, Nahoko; Hirose, Tatsuko; Sago, Haruhiko

doi:10.1016/j.ejogrb.2020.10.050

Cited by 25 publications

(33 citation statements)

References 18 publications

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“…Several reports ( Hartwig et al, 2017 ; Chatron et al, 2019 ; Suzumori et al, 2021 ) showed that the accuracy of NIPS might be affected by confined placental mosaicism (CPM); vanishing twin, single, or multiple pregnancies; maternal tumors; concentration of cf-DNA; and chromosomal GC content. These effects were reflected in the accuracy of Z-scores.…”

Section: Discussionmentioning

confidence: 99%

The Optimal Cutoff Value of Z-scores Enhances the Judgment Accuracy of Noninvasive Prenatal Screening

Zhou

Zhang

et al. 2021

Front. Genet.

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ObjectiveTo evaluate the accuracy of Z-scores of noninvasive prenatal screening (NIPS) in predicting 21, 18 trisomy, and X chromosome aneuploidy.MethodsA total of 39,310 prenatal women were recruited for NIPS from September 2015 to September 2020. Interventional prenatal diagnosis was applied to verify the diagnosis of NIPS-positive results. Logistic regression analysis was employed to relate the Z-scores to the positive predictive value (PPV) of NIPS-positive results. Using receiver operating characteristic (ROC) curves, we calculated the optimal cutoff value of Z-scores to predict fetal chromosome aneuploidy. According to the cutoff value, NIPS-positive results were divided into the medium Z-value (MZ) and high Z-value (HZ) groups, and PPV was calculated to access the accuracy of Z-scores.ResultsA total of 288 effective values of Z-scores were used as the final data set. The logistics regression analysis revealed that Z-scores were significantly associated with true-positive results for 21 trisomy (T21) and 18 trisomy (T18) (P < 0.05), whereas the same was not observed for X chromosome aneuploids (P > 0.05). The optimal cutoff value of the Z-score for T21, T18, XO, XXX, and XXY indicated by ROC curve analysis were 5.79, 6.05, −9.56, 5.89, and 4.47, and the area under the curve (AUC) were 0.89, 0.80, 0.48, 0.42, and 0.45, respectively. PPV in the HZ group was higher than that in the MZ group, and the application of the cutoff value reduced the false discovery rate (FDR), which was only 2.9% in the HZ group compared with 61.1% in the MZ group for T21 and T18. The difference in total PPV between the MZ and HZ groups for X chromosome aneuploids was statistically significant. Moreover, the PPV for XXX and XXY seemed to increase with Z-scores but not for XO.ConclusionThe Z-score is helpful for the accurate judgment of NIPS results and for clinical prenatal counseling. Especially for T21 and T18, Z-scores have an excellent clinical association, which is superior to that seen with X chromosome aneuploids. In addition, using Z-scores to judge NIPS results offers a certain reference value for XXX and XXY but not for XO.

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Section: Discussionmentioning

confidence: 99%

The Optimal Cutoff Value of Z-scores Enhances the Judgment Accuracy of Noninvasive Prenatal Screening

Zhou

Zhang

et al. 2021

Front. Genet.

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“…16 The Japan NIPT Consortium reported that FP and FN rates were lower than those reported abroad. 31 In this study, three FN and 59 FP cases were observed. Although only a limited number of cases were analyzed, six CPM cases were confirmed among the FP cases.…”

Section: Discussionmentioning

confidence: 59%

“…These are related to CPMs and maternal malignant neoplasm. 31 In particular, CPM was predicted to generate a 1% FN and 0.025-0.1% FP results. 16 The Japan NIPT Consortium reported that FP and FN rates were lower than those reported abroad.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the clinical performance of noninvasive prenatal testing at a Japanese laboratory

Sasaki¹,

Yamada²,

Tanaka³

et al. 2021

J of Obstet and Gynaecol

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Aim: We aimed to evaluate the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of noninvasive prenatal testing (NIPT) in high-risk pregnant women. Methods: Pregnant women who underwent GeneTech NIPT, the most commonly used NIPT in Japan, between January 2015 and March 2019, at Japan NIPT Consortium medical sites were recruited for this study. The exclusion criteria were as follows: pregnant women with missing survey items, multiple pregnancy/vanishing twins, chromosomal abnormalities in the fetus other than the NIPT target disease, and nonreportable NIPT results. Sensitivity and specificity were calculated from the obtained data, and maternal age-specific PPV and NPV were estimated. Results: Of the 45 504 cases, 44 263 cases fulfilling the study criteria were included. The mean maternal age and gestational weeks at the time of procedure were 38.5 years and 13.1 weeks, respectively. Sensitivities were 99.78% (95% confidence interval [95% CI]: 98.78-99.96), 99.12% (95% CI: 96.83-99.76), and 100% (95% CI: 88.30-100) for trisomies 21, 18, and 13, respectively. Specificities were more than 99.9% for trisomies 21, 18, and 13, respectively. Maternal age-specific PPVs were more than 93%, 77%, and 43% at the age of 35 years for trisomies 21, 18, and 13, respectively. Conclusion:The GeneTech NIPT data showed high sensitivity and specificity in the detection of fetal trisomies 21, 18, and 13 in high-risk pregnant women, and maternal age-specific PPVs were obtained. These results could provide more accurate and improved information regarding NIPT for genetic counseling in Japan.

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“…Under the approval and registration system of the Japanese Medical Association, more than 80 000 screenings were conducted in that time. 33,34 In NIPT, maternal blood is subjected to comprehensive genetic analysis, and the results of the analysis are disclosed as "negative" or "positive" (high-risk of detection group) for the presence of trisomy in fetal chromosomes 21, 18, and 13; positive cases require a definitive diagnosis using amniotic fluid/chorionic villus sampling. According to domestic data, the truepositive predictive rates for fetal chromosomes 21, 18, and 13 were 96%, 87%, and 53%, respectively, while the true-negative predictive rate was more than 99.99%, with a false-negative rate of less than 0.008%.…”

Section: Social Factors For Prenatal Screeningmentioning

confidence: 99%

“…According to domestic data, the truepositive predictive rates for fetal chromosomes 21, 18, and 13 were 96%, 87%, and 53%, respectively, while the true-negative predictive rate was more than 99.99%, with a false-negative rate of less than 0.008%. 33 However, general prenatal screening using NIPT is currently pending because of disability discrimination issues. The current number of legitimate elective abortions for a variety of reasons, which are most reasons other than fetal abnormality, before 22 weeks of gestation currently exceeds 14% of all pregnancies annually in Japan (the Ministry of Health, Labor and Welfare [MHLW] database in 2018).…”

Section: Social Factors For Prenatal Screeningmentioning

confidence: 99%

What are the ethical issues involved in noninvasive prenatal testing in Japan?

Suzumori

2021

J of Obstet and Gynaecol

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Aims: Noninvasive prenatal testing (NIPT) of pregnant women has been performed worldwide since 2011, and it is currently performed in more than 90 countries. However, the rate of adoption in Japan remains at less than 2%. This review seeks to identify the ethical and practical issues surrounding noninvasive prenatal screening-including the purpose of the test, its pros and cons, issues surrounding fair treatment, and social factors-to better understand why the adoption rate remains low. Methods: This study examines the complex ethical issues surrounding noninvasive prenatal testing, including the purpose of the test, its pros and cons, issues related to fair treatment, and social factors. Results: Although cell-free DNA analysis for common fetal trisomies using maternal blood is highly accurate, lack of access to such testing and discriminatory attitudes in society remain important barriers. Personal choices such as whether to undergo noninvasive prenatal screening and whether to continue a pregnancy are sometimes criticized by those who believe that it leads to the "selection of life" or discrimination against people with disabilities. Conclusions: Obstetrics has changed dramatically in recent years, and prenatal diagnosis technology has also advanced. To keep up with these advances, better information should be provided to ensure the public has a more nuanced understanding of the screening beyond the overused argument that it leads to "selection of life."

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Retrospective details of false-positive and false-negative results in non-invasive prenatal testing for fetal trisomies 21, 18 and 13

Cited by 25 publications

References 18 publications

The Optimal Cutoff Value of Z-scores Enhances the Judgment Accuracy of Noninvasive Prenatal Screening

The Optimal Cutoff Value of Z-scores Enhances the Judgment Accuracy of Noninvasive Prenatal Screening

Evaluation of the clinical performance of noninvasive prenatal testing at a Japanese laboratory

What are the ethical issues involved in noninvasive prenatal testing in Japan?

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