OP17.08: Prenatal diagnosis using combined qf‐PCR and array CGH analysis as a first line test: results from over 1000 consecutive cases

Abstract

Short oral presentation abstractsSupporting information can be found in the online version of this abstract OP17.07 Development of auditable standards in the first trimester ultrasound assessment of fetal blood flow through the ductus venosus and the tricuspid valve Objectives: To develop reference ranges for the ductus venosus (DV) and tricuspid valve (TV) waveforms at 11-14 weeks to define auditable standards to assess operator measurement performance. Methods: A single operator utilising the FMF criteria, prospectively obtained quantitative measurements for DV (pulsatility index for veins [PIV], pre-load index [PLI] and peak velocity for veins [PVIV]) and TV (E-wave peak velocity [EWPV], A-wave peak velocity [AWPV] and E-A ratio) to develop medians and 90% reference intervals. Measurement agreement studies between two experienced operators were also performed. The measurement bias of 3 additional operators was subsequently assessed using these auditable standards. Results: Doppler measurements were obtained in 292 patients (DV) and 321 patients (TV). Highly correlated DV indices indicated that only one reference range (for PIV) was necessary with a mean PIV measurement of 1.06 (90% RI 0.86 -1.23). As both EWPV and AWPV changed reliably over gestation, only the E-A ratio reference range was computed.Intra-observer and inter-observer studies on 30 additional patients of the DV PI and TV E-A ratio showed the within-operator agreement was almost perfect for DV PIV (ICC 0.82 -0.86) and strong for TV E-A ratio (ICC 0.68 -0.78) whilst the betweenoperator agreement was good for both DV PIV and TV E-A ratio measurements (ICC 0.46 for both).Preliminary audit using central tendency and dispersion of the measurements by 3 trained operators showed a tendency to overestimate DV PI (0.97, 1.07 and 1.09 MoM respectively; SD log PI 0.03-0.06) whilst the TV E-A ratio distribution met expectation (0.97, 0.98 and 0.98 MoM respectively; SD log E-A ratio 0.04 -0.1). Conclusions: Measurements of DV PIV and TV E-A ratio by experienced operators were found to be reproducible. Development of local reference ranges enabled the definition of quantitative auditable standards that can be utilized in assessment of operator training and ongoing Doppler measurement quality assurance.

Is high fetal nuchal translucency associated with submicroscopic chromosomal abnormalities on array CGH?

“…In the combined data of four studies of array CGH in pregnancies undergoing prenatal diagnosis for advanced maternal age or maternal anxiety in the absence of fetal defects, the incidence of pathogenic CNVs was 0.5% (19/3671). Similarly, combining the data of our study and those from the three previous studies, in a total of 371 cases with high fetal NT and no other sonographically detected defect, the incidence of pathogenic CNVs was 0.8%, which may therefore not be higher than in the general population.…”

“…These incidences of pathogenic CNVs in fetuses with sonographically detected abnormalities are higher than are incidences reported in prenatal studies in which array CGH was performed in women undergoing prenatal diagnosis for advanced maternal age or maternal anxiety in the absence of fetal defects. In four such studies, the incidence of pathogenic CNVs was 0.7% (6/852) 17 , 0.2% (1/431) 18 , 0.7% (3/422) 6 and 0.5% (9/1966) 19 .…”

“…There have been three previous studies investigating the potential value of array CGH in fetuses with high NT and normal karyotype. Leung et al .…”

“…Scott et al 6 examined 90 fetuses with high NT and reported a pathogenic CNV in one of 41 (2.4%; 95% CI, 0.4-12.6) cases with normal karyotype. There was one case of ventricular septal defect (pers.…”

“…Fetal nuchal translucency thickness (NT) above the 99 th percentile (≥ 3.5 mm) is associated with a high risk for chromosomal abnormalities, major fetal defects and a wide range of genetic syndromes 1 -3 . Recent studies have investigated the possible association between high NT thickness with normal karyotype and submicroscopic chromosomal abnormalities detected by comparative genomic hybridization (CGH) 4 or array CGH 5,6 , reporting pathogenic copy number variants (CNVs) in 0 of 100 fetuses with NT ≥ 3.5 mm and normal karyotype 4 , in four of 48 with NT > 3.5 mm 5 and in one of 41 with NT > 3.5 mm 6 .…”