ObjectiveThe primary goal of this study was to provide clinically relevant information for appropriate patient counseling.MethodDemographics and test metrics were reviewed for 86 658 clinical cases. Outcome information was requested for samples reported as aneuploidy detected or suspected for chromosomes 21, 18, or 13; voluntary outcome reporting was encouraged for all discordant outcomes.ResultsOf 86 658 cases, 85 298 (98.4%) met inclusion criteria for result reporting. Of the 1360 (1.6%) cancellations, only 101 (0.1%) were for technical reasons. Average time to result was 3.3 business days. Aneuploidy was detected or suspected in 2142 (2.5%) samples. For aneuploidy detected cases with known clinical outcomes, the overall positive predictive value (PPV) was 83.5% (608/728); observed PPVs for trisomies 21, 18, and 13 ranged from 50.0 to 92.8%. As individual PPVs are determined by a patient's prior risk, we developed a chart for counseling patients on positive predictive value based on maternal age.ConclusionThis large‐scale report reinforces that noninvasive prenatal testing is a highly accurate screen for fetal aneuploidy in the general obstetric population. Test improvements have facilitated a reduction in failure rates, time to result, and borderline results/unclassifiable results. We have developed a positive predictive value counseling tool to ensure appropriate patient education, counseling, and clinical utilization. © 2015 Illumina. Prenatal Diagnosis published by John Wiley & Sons, Ltd.

Objective: The aim of this study was to evaluate clinical use of NIPT at gestational ages of 23 weeks and above. Methods: A cohort of 5579 clinical patients with singleton gestations of 23 weeks or greater submitting a blood sample for NIPT in an 18-month period were selected for this study. Clinical outcomes were requested for samples with NIPT results indicating fetal aneuploidy and compared with NIPT findings to confirm concordance or discordance. Results: A review of clinical indications revealed that a significantly (p50.0001) larger proportion of late-gestation samples indicated abnormal ultrasound findings with or without other indications, 6.2% and 42.1%, compared with early-gestation samples, 1.8% and 6.0%, respectively. Of 5372 reported late-gestation samples, 151 (2.8%) were reported as aneuploidy detected or suspected. In late-gestation samples, the overall observed positive predictive value (PPV) for NIPT was 64.7%, with an observed PPV of 100% in the subset of cases with multiple clinical indications including abnormal ultrasound findings. Conclusions: NIPT is a highly accurate prenatal screening option for women after 23 weeks of gestation. Women who presented for NIPT in the latter stages of pregnancy more frequently specified clinical indications of abnormal ultrasound findings than women who entered screening earlier in pregnancy.

The article contains the results of the research, which set two main goals. The first is the determination of the actual indicators of the effectiveness of noninvasive prenatal studies and the development of counseling tools about the predictability of a positive outcome, taking into account certain clinical indicators and the a priori age risk of the mother. The second is the assessment of changes in the clinical and demographic population after the introduction of testing.Objective: The primary goal of this study was to provide clinically relevant information for appropriate patient counseling.Method: Demographics and test metrics were reviewed for 86 658 clinical cases. Outcome information was requested for samples reported as aneuploidy detected or suspected for chromosomes 21, 18, or 13; voluntary outcome reporting was encouraged for all discordant outcomes.Results: Of 86 658 cases, 85 298 (98.4%) met inclusion criteria for result reporting. Of the 1360 (1.6%) cancellations, only 101 (0.1%) were for technical reasons. Average time to result was 3.3 business days. Aneuploidy was detected or suspected in 2142 (2.5%) samples. For aneuploidy detected cases with known clinical outcomes, the overall positive predictive value was 83.5% (608/728); observed positive predictive values for trisomies 21, 18, and 13 ranged from 50.0 to 92.8%. As individual positive predictive values are determined by a patient’s prior risk, we developed a chart for counseling patients on positive predictive value based on maternal age.Conclusion: This large-scale report reinforces that noninvasive prenatal testing is a highly accurate screen for fetal aneuploidy in the general obstetric population. Test improvements have facilitated a reduction in failure rates, time to result, and borderline results/unclassifiable results. We have developed a positive predictive value counseling tool to ensure appropriate patient education, counseling, and clinical utilization.Funding sources: This study was funded by Illumina.Conflicts of interest: Authors of article are employees of and hold equity in Illumina.

Conclusions: This study shows that gestational age has a significant effect on the accuracy of fetal gender determination ultrasound in the first trimester. Identification male 11 weeks (CRL <57 mm) is difficult and prone to a high rate of errors. OP05.04Non-invasive diagnosis of RhD status and fetal gender from maternal plasma: our results from years 2008 to 2014Objectives: The aim of the study was to perform non-invasive prenatal detection of fetal RhD gene (RHD) from plasma of RhD-negative pregnant women to detect RhD materno-fetal incompatibility together with fetal sex. Methods: We tested 354 plasma samples of RhD negative mothers (range 10-38 wks). In the first pilot phase (2008-2012) 281 samples were tested for RHD exon 10 only. In the second phase (2012-2014) 73 samples were tested for three RHD exons (5, 7 and 10) together with DNA from buccal swabs of RhD negative mothers. 40 samples of maternal blood (range 7-32 wks) were also tested for fetal gender since 2012. Fetal DNA was isolated from 1 ml of maternal plasma by QIAamp Circulating Nucleic Acid Kit (Qiagen, Germany) and fetal status was determined by RT-PCR method. Results: In the first phase (exon 10 only), 175 RhD+ and 97 RhD-results were detected, 9 plasma samples (3,3%) were non-informative. 144 samples were postnatally verified (52,9%) and 5 (3,47%) false RhD negative (FN) and 4 (2,77%) false RhD positive (FP) cases were then registered. In the second period (2012-2014) 73 samples were tested for three RHD exons (5, 7 and 10) together with DNA from buccal swabs of RhD negative mothers. 44 samples were RhD+, 28 RhD-and 1 sample (1,37%) non-informative. No FN and FP results were recorded postanatally. 21 cases of 40 gender determination were medically indicated due to gonosomal recessive diseases risk -mostly Hemophilia A (8x) and Duchenne muscular dystrophy (5x). Male gender was determined in 21 tested fetuses. All cases were verified postnatally, no FP neither FN results were found. Six cases of gender determination before 10wks of pregnancy (2x7,4x9) were proven correct (4x male), but the small number does not allow to draw any conclusions of testing accuracy. Conclusions: Non-invasive RhD determination with three exons (5, 7, 10) together with DNA from buccal swabs of RhD negative mothers and fetal gender determination from 10th week of pregnancy provides diagnostic accuracy.