A two-year prospective study assessing the performance of fetal chromosomal microarray analysis and next-generation sequencing in high-risk pregnancies.

BACKGROUND: Introduction of cell-free fetal DNA (cff-DNA) testing in maternal blood opened possibilities to improve the performance of combined first-trimester screening (cFTS) in terms of better detection of trisomies and lowering invasive testing rate. The use of new molecular methods, such as chromosomal microarray analysis (CMA) and next-generation sequencing (NGS), has shown benefits in prenatal diagnosis of chromosomal and genetic diseases, which are not detectable with cff-DNA screening, but require an invasive procedure. METHODS: The objective of this study was to evaluate prospectively during two years performance of CMA and NGS in high-risk pregnancies. Initially, we investigated 14,566 singleton pregnancies with cFTS. A total of 334 high-risk pregnancies were selected for CMA diagnostic performance evaluation and 28 cases of highly dysmorphic fetuses for NGS analysis. CMA study group was divided into two groups based on the indications for testing; group A patients with high-risk for trisomies after cFTS, but normal ultrasound and group B patients who met criteria for CMA as a first-tier diagnostic test. RESULTS: The diagnostic yield of CMA was overall 3.6% (1.6% in Group A and 6.0% in Group B). In NGS analysis group, we report diagnostic yield of 17.9%. CONCLUSION: The use of CMA in high-risk pregnancies is justified and provides relevant clinical information in 3.6% of the cases. NGS analysis in fetuses with multiple anomalies shows promising results, but more investigations are needed for a better understanding of practical applications of this molecular diagnosis method in prenatal settings.

Prospective experience with contingent screening strategy for Down syndrome in Estonia.

The purpose of this study was to establish the first-trimester screening for Down syndrome (DS) in Estonia and to evaluate the potential of a contingent screening in the population of pregnant women. A prospective cohort study included non-selected pregnancies during the programme of first-trimester screening for DS in a 4-year period at a single centre. The following screening tests were evaluated: measurement of nuchal translucency (NT) and serum screening [pregnancy-associated plasma protein A and free beta subunit of human chorionic gonadotropin (fß-HCG)]; results were given as combined screening. After first-trimester screening, contingent screening protocol was used, and women were divided into three groups: high risk, low risk and an intermediate risk group. In the last group, a second-trimester triple test (AFP; total HCG and uE3) was also performed. The study group consisted of 3,194 non-selected pregnancies. In 1,387 (43.4%) women, first-trimester serum screening showed low risk (risk ≤ 1:5,000), and no future testing was performed, in 30 (0.9%) women screening test showed high risk (risk ≥ 1:50) and a diagnostic test was offered, and in 1,777 (55.7%) women repeated risk calculation in the second trimester was done. During the study period, there were 17 cases of trisomy 21, of which 15 (88.3%) were detected with the described screening programme. In conclusion, two-step contingent sequential screening is a better choice for Down syndrome screening in Estonia instead of previously used second-trimester screening, and it offers the advantage of earlier diagnosis.

Developmental changes in cerebral and visceral blood flow velocity in healthy neonates and infants.

OBJECTIVE: The purpose of this study was to evaluate the changes in Doppler blood flow velocity (BFV) in cerebral and visceral arteries during infancy. METHODS: The BFV was measured in 37 healthy term neonates in the anterior cerebral artery (ACA), middle cerebral artery (MCA), basilar artery, internal carotid artery (ICA), celiac artery (CA), superior mesenteric artery (SMA), and renal artery (RA). RESULTS: The mean BFV increased and the resistive index decreased (P < .05) in all cerebral arteries, SMA, and CA by the age of 12 to 23.9 hours and in the RA by the age of 24 to 35.9 hours compared with 2 to 11.9 hours. A further significant increase (P < .05) of the mean BFV occurred in all arteries except the ICA and CA by the age of 72 to 120 hours compared with 12 to 23.9 hours. By the age of 21 to 59 days, the mean BVF doubled in all investigated arteries compared with 2 to 11.9 hours, with a further significant increase (P < .05) by the age of 150 to 240 days in cerebral and renal arteries. There was no correlation between the mean blood pressure (BP) and mean BFV in the ACA and MCA. However, there was a positive correlation (r > or = 0.5; P < .05) between the BP and BFV in the RA and SMA at the age of 12 to 23.9 hours. CONCLUSIONS: A significant increase in the cerebral and visceral BFV occurs normally throughout infancy, with the visceral BFV affected by BP changes during the first day of life.