Antenatal screening for Down's syndrome: Revised nuchal translucency upper truncation limit due to improved precision of measurement.

Objective: To determine whether the improved precision of nuchal translucency (NT) measurement used in antenatal screening for Down's syndrome observed over time as evidenced by a decrease in the multiple of the median (MoM) standard deviation requires a modification to the NT MoM truncation limits to maintain accurate risk estimation.

Methods: Probability plots were derived from the measurements of NT MoM values used in a 2018 audit of 22,362 unaffected pregnancies. The plots were used to determine whether the NT MoM upper truncation limit should be lowered.

A simple method to allow for guanine-cytosine amplification error in prenatal DNA screening for trisomy 18.

Background: A source of error in prenatal screening for trisomies is PCR amplification error associated with guanine-cytosine (GC) content of DNA fragments in maternal plasma. We describe a simple method of allowing for this.

Methods: Data from a Reflex DNA screening programme (67 trisomy 18 and 83 unaffected pregnancies) were used to compare the ratio of chromosome 18 DNA fragment counts to chromosome 8 DNA fragment counts (because chromosome 8 has a similar GC content to chromosome 18) with the percentage of chromosome 18 DNA counts using counts from all autosomes in the denominator, with and without an all autosome correction for the GC content of the DNA fragments.

Prenatal screening for Down syndrome in twin pregnancies: Estimates of screening performance based on 61 affected and 7302 unaffected twin pregnancies.

The aims of this study were to determine whether assumptions used in prenatal screening for Down syndrome in twin pregnancies are valid and derive estimates of risk and screening performance in twin pregnancies using observed data. Data were collected on nuchal translucency, chorionicity, pregnancy associated plasma protein-A (PAPP-A), and free ß human chorionic gonadotrophin (free ß-hCG) from 61 twin pregnancies with Down syndrome and 7302 unaffected twin pregnancies. Distribution parameters were determined and used to estimate screening performance.

Serum marker truncation limits in first trimester antenatal screening for trisomy 18.

Objective: To assess whether the accuracy of risk estimation in antenatal screening for trisomy 18 using the Combined test can be improved by revising the truncation limits of two serum markers.

Methods: In an audit of data from 420 trisomy 18 and 573,754 unaffected singleton pregnancies screened at the Wolfson Institute of Preventive Medicine, London (March 2003 to June 2017), the accuracy of risk estimation was assessed by inspection of a validation plot (the median predicted late first trimester Combined test risk plotted against observed prevalence within categories of predicted risk estimates). Using validation and probability plots, we assessed whether the revised pregnancy-associated plasma protein A (PAPP-A) and free β-human chorionic gonadotrophin (free β-hCG) truncation limits led to more accurate risk estimation and improved screening performance.

Specifying a Gold Standard for the Validation of Fetal Fraction Estimation in Prenatal Screening.

Background: An estimate of fetal fraction (FF) is needed for DNA-based screening for trisomy 21 and other aneuploidies, but there is no gold standard to validate FF measurement methods. We specify a gold standard and use it to validate a method of measuring FF (SeqFF) in singleton pregnancies.

Methods: The gold standard was a formula derived from 2 elements: () an estimate of the percentage of DNA fragments in maternal plasma from chromosome 21 (%Ch21) in pregnancies without trisomy 21, 18, or 13 (P) and () calculation of %Ch21 with increasing FF in trisomy 21 pregnancies (P).

Prenatal reflex DNA screening for trisomies 21, 18, and 13.

Purpose: The purpose of the study was to determine the screening performance of prenatal reflex DNA screening for trisomies 21 (T21), 18 (T18), and 13 (T13) as part of a routine service at five hospitals.

Methods: Women who accepted screening had a first-trimester combined test (pregnancy-associated plasma protein A, free β-human chorionic gonadotropin, nuchal translucency interpreted with maternal age). Those with a risk of having an affected pregnancy ≥1 in 800 were reflexed to a DNA sequencing test using stored plasma from the original blood sample, thereby avoiding the need to recall them.

The estimation of median nuchal translucency values between 10 and 14 weeks of pregnancy.

Nuchal translucency (NT) is a useful marker in antenatal screening for Down's syndrome in the late first trimester of pregnancy. NT measurements increase with increasing crown rump length (CRL) so multiple of the median (MoM) values are used to allow for this. Log-linear and log-quadratic regressions of NT in relation to CRL have previously been proposed to calculate MoM values.

Prevention of neural tube defects: a cross-sectional study of the uptake of folic acid supplementation in nearly half a million women.

Background: Taking folic acid supplements before pregnancy to reduce the risk of a neural tube defect (NTD) is especially important in countries without universal folic acid fortification. The extent of folic acid supplementation among women who had antenatal screening for Down's syndrome and NTDs at the Wolfson Institute of Preventive Medicine, London between 1999 and 2012 was assessed.

Methods And Findings: 466,860 women screened provided details on folic acid supplementation.

Detection of trisomy 18 and trisomy 13 using first and second trimester Down's syndrome screening markers.

Objective: To estimate the detection rates (DRs) and false-positive rates (FPRs) in the incidental identification of trisomy 18 (T18) and trisomy 13 (T13) as part of antenatal screening for Down's syndrome (DS) using the Combined, Quadruple and Integrated test markers.

Methods: Screening marker levels on 224 T18 and 67 T13 pregnancies screened for DS were evaluated. Estimated means, standard deviations and correlation coefficients were used with published estimates for unaffected pregnancies to derive detection algorithms for the two disorders.

Antenatal screening for Down syndrome using serum placental growth factor with the combined, quadruple, serum integrated and integrated tests.

Objective: To estimate the value of first or second trimester placental growth factor (PlGF) as an additional antenatal screening marker for Down syndrome.

Design: Nested case-control study.

Setting: Antenatal screening service.

Effect of interrupting prenatal Down syndrome screening due to a large nuchal translucency.

Objective: The aim of this study is to determine the effect of interrupting prenatal Down syndrome screening for women with large nuchal translucency (NT) measurements on the performance of combined and integrated tests.

Design: Distribution of large NT at 11-13 weeks of gestation was determined from a screening programme (204,982 pregnancies, 509 with Down syndrome). Monte Carlo simulation was used to estimate the effects of interrupting screening on the detection rate (DR) and false-positive rate (FPR) in (i) the remaining women and (ii) all women.

First trimester Down's syndrome screening marker values and cigarette smoking: new data and a meta-analysis on free beta human chorionic gonadotophin, pregnancy-associated plasma protein-A and nuchal translucency.

Objectives: To examine the effect of smoking on three first trimester screening markers for Down's syndrome that constitute the Combined test, namely nuchal translucency (NT), pregnancy-associated plasma protein-A (PAPP-A) and free beta human chorionic gonadotophin (free beta-hCG) and to use the results to determine which of these markers need to be adjusted for smoking and by how much.

Methods: The difference in the median multiple of the median (MoM) values in smokers compared to non-smokers was determined for NT, PAPP-A and free beta-hCG in 12,517 unaffected pregnancies that had routine first trimester Combined test screening. These results were then included in a meta-analysis of published studies and the effect of adjusting for smoking on screening performance of the Combined test was estimated.

Prenatal screening for Down syndrome: the problem of recurrent false-positives.

Objectives: It has been reported that, in prenatal screening programmes for Down syndrome, women who have false-positive results in one pregnancy have an increased risk of a false-positive result in a subsequent pregnancy. We examined the effect of this in the screening programme conducted from the Wolfson Institute of Preventive Medicine with a view to determining the magnitude of the effect, and to describe a method of avoiding the problem.

Methods: Six thousand four hundred and forty-eight women were identified who had had two singleton pregnancies without Down syndrome in the screening programme based at the Wolfson Institute of Preventive Medicine, in which both pregnancies were screened using a Quadruple test (maternal age with alphafetoprotein (AFP), unconjugated oestriol (uE(3)), total or free beta-human chorionic gonadotrophin (hCG) and either free alpha-hCG or inhibin-A as the fourth serum marker).

Antenatal screening for Down's syndrome with the quadruple test.

Second trimester screening for Down's syndrome is widely practised throughout the world. We assessed the performance of antenatal serum screening for Down's syndrome with the quadruple test in 46193 pregnancies from 14 hospitals over 5 years. Women who screened positive (risk > or =1 in 300) were offered diagnostic amniocentesis or chorionic villus sampling.