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

Abstract

To retrospectively evaluate the successful test rate and performance of non-invasive prenatal screening (NIPS) for aneuploidies and microdeletions with international transportation of samples. Blood samples from Iberian women with singleton pregnancies were sent to a US laboratory for NIPS for aneuploidy and microdeletion syndromes (22q11.2, 1p36, Cri-du-chat, Prader Willi and Angelman). The NIPS methodology involved the analysis of single nucleotide polymorphisms in cell-free DNA in maternal plasma. Women with high-risk results were offered karyotyping and/or microarray confirmatory studies. Based on 14,175 women with successful testing (98.76% of all referrals), the overall test positive rate was 2.37% (1.9% for aneuploidy and 0.47% for microdeletion syndromes). Based on cases with known outcome, the positive predictive values (PPVs) were: for trisomy 21, 98.6%; trisomy 18, 85.7%; trisomy 13, 71.4%; monosomy-X, 87.5%; other sex chromosome aneuploidies, 100%; 22q11.2 deletion, 15.4%; and other microdeletions combined, 20%. With a protocol change that involved selective use of resequencing at a higher depth of read, the PPV for 22q11.2 deletion increased to 33.3 and 75% for the other microdeletions. Effective NIPS for both aneuploidies and select microdeletion syndromes can be provided even when this involves international transportation of blood specimens.

The accuracy of cell‐free DNA screening for fetal segmental copy number variants: A systematic review and meta‐analysis

“…15,26,28,29,31,35,37,39,41,42,45,51,54,56,57,59,60,62,65,67,71,[73][74][75]78 Six inclusions (9.5%) were validation studies assessing novel cfDNA technologies or algorithms. 15,29,31,39,47,49 Seventeen studies (27.0%) reported cfDNA screening outcomes for 22q.11.2 syndrome (16 reporting PPV 12,14,26,27,30,38,40,47,56,60,65,68,69,73,76,83 and three reporting sensitivity and specificity 39,60,76 ), including seven which exclusively assessed 22q.11.2 syndrome and no other CNVs.…”

“…15,29,31,39,47,49 Seventeen studies (27.0%) reported cfDNA screening outcomes for 22q.11.2 syndrome (16 reporting PPV 12,14,26,27,30,38,40,47,56,60,65,68,69,73,76,83 and three reporting sensitivity and specificity 39,60,76 ), including seven which exclusively assessed 22q.11.2 syndrome and no other CNVs. 27,30,39,60,68,69,76 Six studies (9.5%) included results for 15q microdeletion, 12,14,26,38,40,73 and eight (12.7%) for 5psyndrome. 12,14,26,38,40,47,73 A summary of the characteristics of included studies is provided in Table S1.…”

“…27,30,39,60,68,69,76 Six studies (9.5%) included results for 15q microdeletion, 12,14,26,38,40,73 and eight (12.7%) for 5psyndrome. 12,14,26,38,40,47,73 A summary of the characteristics of included studies is provided in Table S1.…”

Assessment of a change of protocol of prenatal screening by inclusion of non-invasive prenatal diagnosis

“…A drawback to this technique is its high cost and limited availability, as not all laboratories perform this test [23]. In many countries, NIPS requires international shipping of samples, which may alter test results due to delays in preanalytical phase [8,24].…”

“…This strategy involves non-invasive prenatal screening (NIPS). NIPS analyzes fetal DNA in maternal blood to assess the genetic characteristics of the fetus without entering the uterus; therefore, this method does not entail any risk for fetal loss [8].…”