Objective To assess the performance of cell-free DNA (cfDNA) testing in maternal blood for detection of fetal aneuploidy of chromosomes 13, 18, 21, X, and Y using targeted sequencing of single-nucleotide polymorphisms.Methods Prospective study in 242 singleton pregnancies undergoing chorionic villus sampling at 11 to 13 weeks.Maternal blood was collected before chorionic villus sampling and sent to Natera (San Carlos, CA, USA). cfDNA was isolated from maternal plasma, and targeted multiplex PCR amplification followed by sequencing of 19 488 polymorphic loci covering chromosomes 13, 18, 21, X, and Y was performed. Sequencing data were analyzed using the NATUS algorithm that determines the copy number and calculates a sample-specific accuracy for each of the five chromosomes tested. Laboratory personnel were blinded to fetal karyotype.Results Results were provided for 229 (94.6%) of the 242 cases. Thirty-two cases were correctly identified as aneuploid, including trisomy 21 [n = 25; sensitivity = 100% (CI: 86.3-100%), specificity = 100% (CI: 98.2-100%)], trisomy 18 (n = 3), trisomy 13 (n = 1), Turner syndrome (n = 2), and triploidy (n = 1), with no false positive or false negative results. Median accuracy was 99.9% (range: 96.0-100%).Conclusions cfDNA testing in maternal blood using targeted sequencing of polymorphic loci at chromosomes 13, 18, 21, X, and Y holds promise for accurate detection of fetal autosomal trisomies, sex chromosome aneuploidies, and triploidy.
What are the novel findings of this work?This prospective multicenter study of screening for pre-eclampsia (PE) in 29 677 singleton pregnancies at 35 + 0 to 36 + 6 weeks' gestation by means of the competing-risks model with a combination of maternal risk factors, mean arterial pressure, serum placental growth factor and serum soluble fms-like tyrosine kinase-1 has validated a previously reported algorithm. There was very high discrimination between affected and unaffected pregnancies and good agreement between the predicted risk and observed incidence of PE. What are the clinical implications of this work?Effective screening for PE at 36 weeks' gestation provides an opportunity for the development of strategies to reduce the incidence or adverse consequences of term PE.
Objectives First, to validate a previously developed model for screening for pre‐eclampsia (PE) by maternal characteristics and medical history in twin pregnancies; second, to compare the distributions of mean arterial pressure (MAP), uterine artery pulsatility index (UtA‐PI), serum placental growth factor (PlGF) and serum pregnancy‐associated plasma protein‐A (PAPP‐A) in twin pregnancies that delivered with PE to those in singleton pregnancies and to develop new models based on these results; and, third, to examine the predictive performance of these models in screening for PE with delivery at < 32 and < 37 weeks' gestation. Methods Two datasets of prospective non‐intervention multicenter screening studies for PE in twin pregnancies at 11 + 0 to 13 + 6 weeks' gestation were used. The first dataset was from the EVENTS (Early vaginal progesterone for the preVention of spontaneous prEterm birth iN TwinS) trial and the second was from a previously reported study that examined the distributions of biomarkers in twin pregnancies. Maternal demographic characteristics and medical history from the EVENTS‐trial dataset were used to assess the validity of risks from our previously developed model. The combined data from the first and second datasets were used to compare the distributional properties of log10 multiples of the median (MoM) values of UtA‐PI, MAP, PlGF and PAPP‐A in twin pregnancies that delivered with PE to those in singleton pregnancies and develop new models based on these results. The competing‐risks model was used to estimate the individual patient‐specific risks of delivery with PE at < 32 and < 37 weeks' gestation. Screening performance was measured by detection rates (DR) and areas under the receiver‐operating‐characteristics curve. RESULTS The EVENTS‐trial dataset comprised 1798 pregnancies, including 168 (9.3%) that developed PE. In the validation of the prior model based on maternal characteristics and medical history, calibration plots demonstrated very good agreement between the predicted risks and the observed incidence of PE (calibration slope and intercept for PE < 32 weeks were 0.827 and 0.009, respectively, and for PE < 37 weeks they were 0.942 and −0.207, respectively). In the combined data, there were 3938 pregnancies, including 339 (8.6%) that developed PE and 253 (6.4%) that delivered with PE at < 37 weeks' gestation. In twin pregnancies that delivered with PE, MAP, UtA‐PI and PlGF were, at earlier gestational ages, more discriminative than in singleton pregnancies and at later gestational ages they were less so. For PAPP‐A, there was little difference between PE and unaffected pregnancies. The best performance of screening for PE was achieved by a combination of maternal factors, MAP, UtA‐PI and PlGF. In screening by maternal factors alone, the DR, at a 10% false‐positive rate, was 30.6% for delivery with PE at < 32 weeks' gestation and this increased to 86.4% when screening by the combined test; the respective values for PE < 37 weeks were 24.9% and 41.1%. Conclusions In the as...
Key Clinical MessageBardet–Biedl syndrome (BBS) is a ciliopathy that is responsible for multiple visceral abnormalities. This disorder is defined by a combination of clinical signs, many of which appear after several years of development. BBS may be suspected antenatally based on routine ultrasound findings of enlarged hyperechogenic kidneys and postaxial polydactyly.
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