Genomics-based non-invasive prenatal testing for detection of fetal chromosomal aneuploidy in pregnant women

• Published in: Cochrane database of systematic reviews 2017-11, Vol.11 (11), p.CD011767
• Main Authors: Badeau, Mylène, Lindsay, Carmen, Blais, Jonatan, Nshimyumukiza, Leon, Takwoingi, Yemisi, Langlois, Sylvie, Légaré, France, Giguère, Yves, Turgeon, Alexis F, Witteman, William, Rousseau, François
• Format: Article
• Language: English
• Subjects: Aneuploidy; Cell-Free Nucleic Acids - blood; Chromosome Disorders - diagnosis; Chromosome Disorders - genetics; Disorders of Sex Development - diagnosis; Disorders of Sex Development - genetics; Female; Fetal assessment before labour; Fetal Diseases - diagnosis; Fetal Diseases - genetics; High-Throughput Nucleotide Sequencing - methods; Humans; Pregnancy; Pregnancy & childbirth; Pregnancy, High-Risk; Prenatal Diagnosis - methods
• ISSN: 1469-493X; 1469-493X
• DOI: 10.1002/14651858.CD011767.pub2

Common fetal aneuploidies include Down syndrome (trisomy 21 or T21), Edward syndrome (trisomy 18 or T18), Patau syndrome (trisomy 13 or T13), Turner syndrome (45,X), Klinefelter syndrome (47,XXY), Triple X syndrome (47,XXX) and 47,XYY syndrome (47,XYY). Prenatal screening for fetal aneuploidies is standard care in many countries, but current biochemical and ultrasound tests have high false negative and false positive rates. The discovery of fetal circulating cell-free DNA (ccfDNA) in maternal blood offers the potential for genomics-based non-invasive prenatal testing (gNIPT) as a more accurate screening method. Two approaches used for gNIPT are massively parallel shotgun sequencing (MPSS) and targeted massively parallel sequencing (TMPS). To evaluate and compare the diagnostic accuracy of MPSS and TMPS for gNIPT as a first-tier test in unselected populations of pregnant women undergoing aneuploidy screening or as a second-tier test in pregnant women considered to be high risk after first-tier screening for common fetal aneuploidies. The gNIPT results were confirmed by a reference standard such as fetal karyotype or neonatal clinical examination. We searched 13 databases (including MEDLINE, Embase and Web of Science) from 1 January 2007 to 12 July 2016 without any language, search filter or publication type restrictions. We also screened reference lists of relevant full-text articles, websites of private prenatal diagnosis companies and conference abstracts. Studies could include pregnant women of any age, ethnicity and gestational age with singleton or multifetal pregnancy. The women must have had a screening test for fetal aneuploidy by MPSS or TMPS and a reference standard such as fetal karyotype or medical records from birth. Two review authors independently carried out study selection, data extraction and quality assessment (using the QUADAS-2 tool). Where possible, hierarchical models or simpler alternatives were used for meta-analysis. Sixty-five studies of 86,139 pregnant women (3141 aneuploids and 82,998 euploids) were included. No study was judged to be at low risk of bias across the four domains of the QUADAS-2 tool but applicability concerns were generally low. Of the 65 studies, 42 enrolled pregnant women at high risk, five recruited an unselected population and 18 recruited cohorts with a mix of prior risk of fetal aneuploidy. Among the 65 studies, 44 evaluated MPSS and 21 evaluated TMPS; of these, five studies also compared gNIPT with a tradi