Classification of factors involved in nonreportable results of noninvasive prenatal testing (NIPT) and prediction of success rate of second NIPT

Nobuhiro Suzumori; Akihiko Sekizawa; Eri Takeda; Osamu Samura; Aiko Sasaki; Rina Akaishi; Seiji Wada; Haruka Hamanoue; Fumiki Hirahara; Hiroko Kuriki; Hideaki Sawai; Hiroaki Nakamura; Takahiro Yamada; Kiyonori Miura; Hideaki Masuzaki; Takahiro Yamashita; Yoshimasa Kamei; Akira Namba; Jun Murotsuki; Tomohiro Tanemoto; Akimune Fukushima; Kazufumi Haino; Shinya Tairaku; Keiichi Matsubara; Kazutoshi Maeda; Takashi Kaji; Masanobu Ogawa; Hisao Osada; Haruki Nishizawa; Yoko Okamoto; Takeshi Kanagawa; Aiko Kakigano; Masayuki Endo; Michihiro Kitagawa; Masaki Ogawa; Shunichiro Izumi; Yukiko Katagiri; Naoki Takeshita; Yasuyo Kasai; Katsuhiko Naruse; Reiko Neki; Hisashi Masuyama; Maki Hyodo; Yukie Kawano; Takashi Ohba; Kiyotake Ichizuka; Takeshi Nagamatsu; Atsushi Watanabe; Naomi Nishikawa; Naoki Hamajima; Nahoko Shirato; Junko Yotsumoto; Miyuki Nishiyama; Keiko Koide; Tatsuko Hirose; Haruhiko Sago

doi:10.1002/pd.5408

Classification of factors involved in nonreportable results of noninvasive prenatal testing (NIPT) and prediction of success rate of second NIPT

Prenat Diagn. 2019 Jan;39(2):100-106. doi: 10.1002/pd.5408. Epub 2019 Jan 10.

Authors

Nobuhiro Suzumori^{1

2}, Akihiko Sekizawa³, Eri Takeda^{1

2}, Osamu Samura⁴, Aiko Sasaki⁵, Rina Akaishi⁵, Seiji Wada⁵, Haruka Hamanoue⁶, Fumiki Hirahara⁶, Hiroko Kuriki⁶, Hideaki Sawai⁷, Hiroaki Nakamura⁸, Takahiro Yamada⁹, Kiyonori Miura¹⁰, Hideaki Masuzaki¹⁰, Takahiro Yamashita¹¹, Yoshimasa Kamei¹², Akira Namba¹², Jun Murotsuki¹³, Tomohiro Tanemoto⁴, Akimune Fukushima¹⁴, Kazufumi Haino¹⁵, Shinya Tairaku¹⁶, Keiichi Matsubara¹⁷, Kazutoshi Maeda¹⁸, Takashi Kaji¹⁹, Masanobu Ogawa²⁰, Hisao Osada²¹, Haruki Nishizawa²², Yoko Okamoto²³, Takeshi Kanagawa²³, Aiko Kakigano²⁴, Masayuki Endo²⁴, Michihiro Kitagawa²⁵, Masaki Ogawa²⁶, Shunichiro Izumi²⁷, Yukiko Katagiri²⁸, Naoki Takeshita²⁸, Yasuyo Kasai²⁹, Katsuhiko Naruse³⁰, Reiko Neki³¹, Hisashi Masuyama³², Maki Hyodo³³, Yukie Kawano³⁴, Takashi Ohba³⁵, Kiyotake Ichizuka³⁶, Takeshi Nagamatsu³⁷, Atsushi Watanabe³⁸, Naomi Nishikawa³⁹, Naoki Hamajima³⁹, Nahoko Shirato³, Junko Yotsumoto⁴⁰, Miyuki Nishiyama⁵, Keiko Koide³, Tatsuko Hirose³, Haruhiko Sago⁵

Affiliations

¹ Department of Obstetrics and Gynecology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
² Division of Clinical and Molecular Genetics, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
³ Department of Obstetrics and Gynecology, Showa University School of Medicine, Tokyo, Japan.
⁴ Department of Obstetrics and Gynecology, Jikei University School of Medicine, Tokyo, Japan.
⁵ Division of Fetal Medicine, Center for Maternal-Fetal, Neonatal and Reproductive Medicine, National Center for Child Health and Development, Tokyo, Japan.
⁶ Department of Clinical Genetics, Yokohama City University Hospital, Yokohama, Japan.
⁷ Department of Obstetrics and Gynecology, Hyogo College of Medicine, Nishinomiya, Japan.
⁸ Department of Obstetrics, Osaka City General Hospital, Osaka, Japan.
⁹ Clinical Genetics Unit, Kyoto University Hospital, Kyoto, Japan.
¹⁰ Department of Obstetrics and Gynecology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
¹¹ Department of Obstetrics and Gynecology, Maternal and Child Health Center, Aiiku Hospital, Tokyo, Japan.
¹² Departments of Obstetrics and Gynecology, Saitama Medical University School of Medicine, Saitama, Japan.
¹³ Department of Maternal and Fetal Medicine, Tohoku University Graduate School of Medicine, Miyagi Children's Hospital, Sendai, Japan.
¹⁴ Department of Clinical Genetics, School of Medicine, Iwate Medical University, Morioka, Japan.
¹⁵ Department of Obstetrics and Gynecology, Niigata University Medical and Dental Hospital, Niigata, Japan.
¹⁶ Department of Obstetrics and Gynecology, Kobe University Graduate School of Medicine, Kobe, Japan.
¹⁷ Department of Obstetrics and Gynecology, Ehime University School of Medicine, Matsuyama, Japan.
¹⁸ Department of Obstetrics and Gynecology, Shikoku Medical Center for Children and Adults, Kagawa, Japan.
¹⁹ Department of Obstetrics and Gynecology, The University of Tokushima Faculty of Medicine, Tokushima, Japan.
²⁰ Department of Obstetrics and Gynecology, Clinical Research Institute, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan.
²¹ Department of Gynecology, Chiba University Graduate School of Medicine, Chiba, Japan.
²² Department of Obstetrics and Gynecology, Fujita Health University, Aichi, Japan.
²³ Department of Obstetrics, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan.
²⁴ Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Osaka, Japan.
²⁵ Department of Obstetrics and Gynecology, Sanno Hospital, Tokyo, Japan.
²⁶ Division of Obstetrics, Perinatal Medical Center, Tokyo Women's Medical University Hospital, Tokyo, Japan.
²⁷ Department of Obstetrics and Gynecology, Tokai University School of Medicine, Kanagawa, Japan.
²⁸ Department of Obstetrics and Gynecology, School of Medicine, Faculty of Medicine, Toho University, Tokyo, Japan.
²⁹ Department of Obstetrics and Gynecology, Japanese Red Cross Medical Center, Tokyo, Japan.
³⁰ Department of Obstetrics and Gynecology, Nara Medical University, Nara, Japan.
³¹ Department of Perinatology and Gynecology, National Cerebral and Cardiovascular Center, Osaka, Japan.
³² Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Okayama, Japan.
³³ Department of Obstetrics and Gynecology, Hiroshima University Graduate School of Medicine, Hiroshima, Japan.
³⁴ Department of Molecular Pathology, Faculty of Medicine, Oita University, Oita, Japan.
³⁵ Department of Obstetrics and Gynecology, Kumamoto University, Kumamoto, Japan.
³⁶ Department of Obstetrics and Gynecology, Showa University Northern Yokohama Hospital, Yokohama, Japan.
³⁷ Departments of Obstetrics and Gynecology, Tokyo University Hospital, Tokyo, Japan.
³⁸ Division of Clinical Genetics, Nippon Medical School Hospital, Tokyo, Japan.
³⁹ Division of Clinical Genetics, Nagoya City West Medical Center, Nagoya, Japan.
⁴⁰ Departments of Genetic Counseling, Ochanomizu University, Tokyo, Japan.

PMID: 30586157
DOI: 10.1002/pd.5408

Abstract

Objective: To evaluate the reasons for nonreportable cell-free DNA (cfDNA) results in noninvasive prenatal testing (NIPT), we retrospectively studied maternal characteristics and other details associated with the results.

Methods: A multicenter retrospective cohort study in pregnant women undergoing NIPT by massively parallel sequencing (MPS) with failed cfDNA tests was performed between April 2013 and March 2017. The women's data and MPS results were analyzed in terms of maternal characteristics, test performance, fetal fraction (FF), z scores, anticoagulation therapy, and other details of the nonreportable cases.

Results: Overall, 110 (0.32%) of 34 626 pregnant women had nonreportable cfDNA test results after an initial blood sampling; 22 (20.0%) cases had a low FF (<4%), and 18 (16.4%) cases including those with a maternal malignancy, were found to have altered genomic profile. Approximately half of the cases with nonreportable results had borderline z score. Among the women with nonreportable results because of altered genomic profile, the success rate of retesting using a second blood sampling was relatively low (25.0%-33.3%). Thirteen (11.8%) of the women with nonreportable results had required hypodermic heparin injection.

Conclusions: The classification of nonreportable results using cfDNA analysis is important to provide women with precise information and to reduce anxiety during pregnancy.

Publication types

Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

Adult
False Negative Reactions
Female
Genetic Testing / methods*
High-Throughput Nucleotide Sequencing* / methods
High-Throughput Nucleotide Sequencing* / standards
High-Throughput Nucleotide Sequencing* / statistics & numerical data
Humans
Predictive Value of Tests
Pregnancy
Pregnancy Trimester, First / blood
Pregnancy Trimester, First / genetics
Pregnancy Trimester, Second / blood
Pregnancy Trimester, Second / genetics
Prenatal Diagnosis / methods*
Reproducibility of Results
Research Design* / standards
Research Design* / statistics & numerical data
Retrospective Studies
Risk Factors
Trisomy / diagnosis*
Trisomy / genetics