Utility of noninvasive genome-wide screening: a prospective cohort of obstetric patients undergoing diagnostic testing.

PURPOSE: Copy-number variant (CNV) assessment is recommended for patients undergoing prenatal diagnostic testing. Noninvasive screening tests have not been extensively validated for CNV detection. The objective of this study was to compare the ability of genome-wide noninvasive prenatal screening (NIPS) to chromosomal microarray to detect clinically significant findings. METHODS: We prospectively enrolled 198 subjects at the time of consent for diagnostic prenatal testing. Genome-wide NIPS results were compared with diagnostic testing results to assess NIPS test performance (n = 160, 38 subjects without microarray results excluded). Cohen's kappa statistic was used to assess test agreement. RESULTS: Genome-wide NIPS did not detect clinically significant chromosomal abnormalities at the same rate as diagnostic testing, κ = 0.75 (95% confidence interval [CI], 0.62-0.87). When excluding CNVs <7 Mb and findings outside the limits of genome-wide NIPS, test agreement improved, κ = 0.88 (0.79-0.97) driven by agreement for common aneuploidies (κ = 1.0). However, among patients with an abnormal fetal survey, agreement was only fair, κ = 0.38 (0.08-0.67). CONCLUSION: While NIPS is an excellent screening test for common aneuploidies, genome-wide NIPS misses clinically significant findings detected on routine diagnostic testing. False positive and false negative cases highlight the importance of pretest counseling regarding NIPS limitations, especially in the setting of fetal anomalies.

Is the starting section for 3D volume acquisition in the first trimester relevant in the post hoc analysis of aneuploidy screening markers and fetal anatomy?

OBJECTIVE: To determine the ability to assess the fetal anatomy and ultrasound screening markers using three-dimensional (3D) volumes acquired during the 11th to 13th week scan, in relation to whether a fetal profile could be used as a starting section. METHODS: Post hoc analysis of 3D ultrasound volumes acquired at 11 to 13 weeks in 223 pregnancies was performed to identify the appropriate sections for evaluation of three screening markers and ten fetal anatomy landmarks. When possible, the fetal profile was used as the starting section for volume acquisition. RESULTS: When the fetal profile was used, satisfactory images for assessment were obtained in 90% of cases for nuchal translucency and 72% for the nasal bone, whereas successful evaluation of the ten anatomical landmarks ranged from 0 to 99%. In alternative starting sections, the corresponding success rates were 65%, 48%, and 0-95%. CONCLUSION: Although performance of post hoc analysis of 3D volumes is best when carried out from a profile starting section and quicker than two-dimensional analysis, it appears to be not ready for clinical use because nuchal translucency could not be examined in 10% of the fetuses.

Reciprocal expression of peroxisome proliferator-activated receptor-gamma and cyclooxygenase-2 in human term parturition.

OBJECTIVE: The objective of this study was to test the hypothesis that peroxisome proliferator activated receptor-gamma (PPAR-gamma) is expressed in intrauterine tissues before active term human parturition, and that its repression is associated with up-regulation of cyclooxygenase-2 (COX-2). STUDY DESIGN: Specimens were collected from women with term singleton pregnancies after spontaneous labor or cesarean section before labor, prepared for immunoblot and immunohistochemical analysis, and probed for PPAR-gamma or COX-2. RESULTS: PPAR-gamma expression was prominent in fetal membranes and placenta before active labor. After labor, PPAR-gamma expression was significantly reduced in fetal membranes, but not in placenta. The ratio of COX-2:PPAR-gamma was significantly elevated in fetal membranes with labor. PPAR-gamma immunostaining was prominent in syncytiotrophoblast, extravillous cytotrophoblasts, and cells of the amnion and chorion. COX-2 immunostaining was abundant in the amnion and rare in the placenta. CONCLUSION: PPAR-gamma is highly expressed in term intrauterine tissues. In fetal membranes, PPAR-gamma levels are reduced once active labor commences, coincidental with a relative increase in COX-2 expression.