Single-Nucleotide Polymorphism–Based Noninvasive Prenatal Screening in a High-Risk and Low-Risk Cohort

Abstract

Objective To estimate performance of a single-nucleotide-polymorphism–based noninvasive prenatal screen for fetal aneuploidy in high-risk and low-risk populations upon single venopuncture. Methods One thousand sixty-four maternal blood samples from 7 weeks of gestation and beyond were included; one thousand fifty-one were within specifications, 518 (49.3%) low-risk. Cell-free DNA was amplified, sequenced, and analyzed using the Next-generation Aneuploidy Test Using SNPs algorithm. Samples were called as trisomies 21, 18, 13, or monosomy X, or euploid, and male or female. Results Nine hundred sixty-six samples (91.9%) successfully generated a cell-free DNA result. Among these, sensitivity was 100% for trisomy 21 (58/58, CI: 93.8–100%), trisomy 13 (12/12, CI: 73.5–100%), and fetal sex (358/358 female, CI:99.0–100%; 418/418 male, CI: 99.1–100%), 96.0% for trisomy 18 (24/25, CI: 79.7–99.9%), and 90% for monosomy X (9/10, CI: 55.5–99.8%). Specificity for trisomies 21 and 13 was 100% (905/905 [CI: 99.6–100%] and 953/953 [CI: 99.6–100%], respectively) and for trisomy 18 and monosomy X was 99.9% (938/939 [CI: 99.4–100%] and 953/954 [CI: 99.4–100%], respectively). However, 16% (20/125) of aneuploid samples did not return a result; 50% (10/20) had a fetal fraction below the 1.5th percentile of euploid pregnancies. Aneuploidy rate was significantly higher in these samples (p<0.001, odds ratio: 9.2, CI: 4.4–19.0). Sensitivity and specificity did not differ in low-risk and high-risk populations. Conclusions This noninvasive prenatal screen performed with high sensitivity and specificity in high-risk and low-risk cohorts. Aneuploid samples were significantly more likely to not return a result; the number of aneuploidy samples was especially increased among samples with low fetal fraction. This underscores the importance of redraws or, in rare cases, invasive procedures based on low fetal fraction.

Noninvasive prenatal screening for fetal aneuploidy, 2016 update: a position statement of the American College of Medical Genetics and Genomics

“…In two prospective studies including more than 16,000 pregnancies, a low fetal fraction in maternal circulation was associated with an increased risk of fetal aneuploidies. 24,45 The biologic mechanism of low fetal fraction and its association with aneuploidies is speculative. Interestingly, triploidy was most common (31%); however, trisomy 21 was seen in 23% of cases of low fetal fraction.…”

A National Referral Laboratory’s Experience with the Implementation of SNP-Based Non-invasive Prenatal Screening for Fetal Aneuploidy and Select Microdeletion Syndromes

“…Peripheral blood specimens were collected and sent by 2-day air transportation to the Natera laboratory without plasma separation prior to shipment. Laboratory procedures were as described elsewhere [7,11,[15][16][17][18][19][20]. Following the NIPS analyses, all patient reports were communicated electronically to Echevarne and to the individual referring physicians and clinics.…”

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].…”

“…За последние три года опубликованы данные многочисленных испытаний и кли-нических наблюдений, проведенных в разных странах. Ажиотаж вокруг НИПТ-технологий постепенно стихает, уступая место взвешенным и проверенным решениям, поддерживаемым научным сообществом [3,4]. Однако до сих пор НИПТ и НИПД не сертифицированы в орга-нах здравоохранения ни в одной стране мира, а высокая стоимость исследований не позволя-ет рекомендовать их к широкому применению, в том числе НИПТ, в качестве скрининга «пер-вой линии» [5].…”