The accuracy of cell‐free fetal DNA‐based non‐invasive prenatal testing in singleton pregnancies: a systematic review and bivariate meta‐analysis

Abstract

Background Cell-free fetal DNA (cffDNA) non-invasive prenatal testing (NIPT) is rapidly expanding, and is being introduced at varying rates depending on country and condition.Objectives Determine accuracy of cffDNA-based NIPT for all conditions. Evaluate influence of other factors on test performance.Search strategy Medline, Embase, CINAHL, Cochrane Library, from 1997 to April 2015.Selection criteria Cohort studies reporting cffDNA-based NIPT performance in singleton pregnancies.Data collection and analysis Bivariate or univariate meta-analysis and subgroup analysis performed to explore influence of test type and population risk. False and inconclusive results were poorly reported across all conditions. Although the test type affected both sensitivity and specificity, there was no evidence that population risk had any effect.Conclusion Performance of cffDNA-based NIPT is affected by condition under investigation. For fetal sex and rhesus D status, NIPT can be considered diagnostic. For trisomy 21, 18, and 13, the lower sensitivity, specificity, and disease prevalence, combined with the biological influence of confined placental mosaicism, designates it a screening test. These factors must be considered when counselling patients and assessing the cost of introduction into routine care.Keywords Cell-free fetal DNA, diagnostic accuracy, non-invasive prenatal testing.Tweetable abstract cffDNA NIPT accuracy high, can be diagnostic for fetal sex and rhesus D, but only screening test in aneuploidy.

Prenatal Diagnosis

“…26 Food and Drug Administration–approved cell-free DNA technology for anti-Kell and other sources of isoimmunization is not yet available in the United States. Several laboratories have begun to report on other autosomal aneuploidies or for microdeletions; however, these tests are not currently validated and are not recommended at present.…”

Noninvasive Prenatal Testing - When Is It Advantageous to Apply

“…The sensitivity to detect trisomy 21 is as high as 99%, but for trisomy 13 and 18 it is “only” 90 and 95%, respectively [57]; while this is a significant improvement over combined or first-trimester screening, it is not at the level to be considered a diagnostic test.…”

New technologies and trends of prenatal diagnostics

“…Чувствительность неинвазивного пренатального тестирования по выявлению частых трисомий на основе метаанализа 117 исследований [15] Table 2 Detection rate of NIPT for common trisomies using meta-analysis data from 117 studies [15] [3][4], начиная с 2017 г. в ряде стран предполагается официаль-но включить НИПТ в систему пренатального скрининга беременных с высоким риском хро-мосомной патологии у плода. Так, в Дании, где пренатальное обследование, согласно мнению Международного общества по пренатальной диагностике (ISPD), организовано наиболее полно и грамотно, государство обеспечивает бесплатный пренатальный комбинированный скрининг 1-го триместра [22].…”

“…С одной сторо-ны, чувствительность НИПТ по выявлению наиболее частых типов анеуплодии достигает 96-99 % при серьезном снижении числа лож-ноположительных результатов (табл. 2) [15]. Однако в 4-5 % случаев НИПТ невозможно из-за низкой концентрации фетальной ДНК в крови беременных, а при повторном заборе крови в более поздние сроки (около 17 недель беременности) 10 % пациенток этой группы не получат ответ [16,17].…”