Combined Screening For Down Syndrome Research Articles

DEPIST 21: Information and knowledge of pregnant women about screening strategies including non-invasive prenatal testing for Down syndrome

ObjectiveTo evaluate the knowledge of pregnant women and provide information about Down syndrome (DS) screening, including non-invasive prenatal testing (NIPT). Materials and methodsA prospective unicenter study of pregnant women recruited during their first trimester foetal ultrasound was carried out. Single pregnancies from 11 to 17 + 6 weeks of amenorrhoea (SA) without a history of DS were included. “Pre” and “post” questionnaire were fulfilled before and after the consultation. Patient characteristics, prior information, information provided during the consultation, and patient satisfaction were also analysed. ResultsA total of 273 were included in the study, and 147 completed surveys (pre and post) were examined. In pre-consultation, 82 % of women know that integrated screening includes maternal serum markers and nuchal translucency (n = 103). Concerning NIPT for DS, 8% (n = 11) of women declare having been informed before the ultrasound. A minority of patients know modalities of reimbursement (n = 33, 26 %) and invasive sampling is mandatory for diagnosis when NIPT is positive (n = 37, 28 %). Significant improvement in right answers was obtained for three questions: “nuchal translucency is included in the combined screening test for DS” (p = 0,007); “blood serum markers is included in the combined screening for DS” (p = 0,009) and advanced maternal age increases risk for DS” (p = 0,004). Total score in the post questionnaire was significantly higher than the “pre” consultation questionnaire (14,7 ± 2.8 versus 14,1 ± 2.9; p = 0.01). ConclusionPatients show a high level of knowledge on screening strategies for DS in pre-consultation. They benefit from the consultation on global knowledge, NIPT, and ultrasound notions.

EP06.16: Preliminary study on the consequences of the implementation of the DNAf technique for the screening of Trisomy 21 in a hospital of the public network of Madrid, Spain

To evaluate the consequences, following the implantation of the ADNf determination as a second step after a high risk combined screening. We compare the first 8 months (year 2016) in which the DNAf was available for detection of Trisomy 21 (T21) after a combined high-risk screening (contingent screening) (PERIOD II), with a previous 2 years (years 2012 and 2013) in which after combined high-risk screening, invasive test (IT) (chorionic villus sampling or amniocentesis) was offered (PERIOD I). Changing the strategy did not affect the detection rate of T21 and ITs were reduced by 60.5%. In the period I, 15% of the IT performed detected a chromosomopathy compared to 50% in period II. The ITs for maternal anxiety were reduced, since the patients were informed about the possibility of determining DNAf, despite the fact that the DNAf was not financed by public health under this indication. The implantation of DNAf in a hospital in the Spanish public network has caused a drastic reduction of the invasive tests generated by the combined screening for Down syndrome. We also observed a decrease in invasive tests performed by maternal anxiety in the population served.

Nuchal translucency measurement, freeβ-hCG and PAPP-A concentrations in IVF/ICSI pregnancies: systematic review and meta-analysis

So far, data on the effect of assisted reproductive technologies (ART) on the components of first trimester combined screening for Down syndrome are still controversial. A systematic search of the literature was performed in order to identify the effect of ART, particularly in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) with fresh embryo transfer, on the nuchal translucency, free beta-human chorionic gonadotrophin and pregnancy-associated plasma protein-A measurements. Moreover, a meta-analysis and a descriptive graphical representation of the ratios between ART and spontaneous pregnancies (controls) values of median of the multiple of median (m0 MoM) were performed. Free beta-human chorionic gonadotrophin test showed slightly higher values in the ICSI group than controls (RR=1.09, 95%CI: 1.03-1.16) but not in the IVF group (RR=1.03, 95%CI: 0.94-1.12). Pregnancy-associated plasma protein-A values for IVF/ICSI, IVF and ICSI showed lower values in comparison with controls (RR, 95%CI 0.85, 0.80-0.90; 0.82, 0.74-0.89 and 0.83, 0.79-0.86, respectively). The nuchal translucency measurement did not show any statistical differences between study groups (IVF and ICSI) and controls (RR=1.00, 95%CI: 0.94-1.08 and RR=1.01, 95%CI: 0.97-1.05, respectively). These results may be due to alterations in the placentation of ART pregnancies. Differentiating further subgroups of ART pregnancies may explain the differences in biomarker concentrations, in prenatal behavior and in obstetric outcomes between ART and spontaneous pregnancies. © 2017 John Wiley & Sons, Ltd.

Non-invasive prenatal testing for Down syndrome in general maternity services

Since its discovery in 1997, the presence of cell-free fetal DNA in the maternal bloodstream has been put to clinical use to detect variety of fetal conditions, in the antenatal period. The use of fetal DNA can offer a highly accurate screen for the presence of Down syndrome (trisomy 21). This has numerous advantages over standard first trimester combined screening for Down syndrome; for example, a reduction in miscarriages due to its non-invasive nature. This article considers a number of issues that need to be resolved before widespread implication of this type of screening into standard NHS practice.

First-trimester combined screening for trisomy 21 in women with renal disease.

To evaluate the results of first-trimester combined screening for Down syndrome in women with chronic renal disease. Fifty-five pregnant women with renal disease were compared with 110 patients matched for maternal age, maternal weight, smoking status, and gestational age. Maternal renal function was assayed at the time of the combined screening, and renal insufficiency was defined by serum creatinine >90 µmol/L and renal clearance <80 mL/min. We defined three groups: kidney disease and normal renal function (group 1), kidney disease and renal insufficiency (group 2), and a control group (group 3). The values of nuchal translucency, pregnancy-associated plasma protein A, human β-chorionic gonadotrophin (hCGβ), and false-positive rates for Down syndrome screening were compared. There were 39 (71%) and 16 (29%) cases in groups 1 and 2, respectively. Nuchal translucency and multiple of the median (MoM) pregnancy-associated plasma protein A were similar in the three groups. However, MoM hCGβ levels were higher in group 2 than in groups 1 and 3 (5.37 vs 1.1 vs 0.98 MoM, p = 0.0001). The resulting screen-positive rate was also higher in group 2 than in groups 1 and 3 (43.7% vs 10.2% vs 5.5%, p = 0.0001). Trisomy 21 first-trimester screening using hCGβ is not suitable in the case of maternal renal failure. © 2014 John Wiley & Sons, Ltd.

204: Utilization of a 1/1000 cutoff in combined screening for Down syndrome (DS) in younger AMA patients provides cost advantages compared with NIPS

We evaluate whether NIPS or 1st TM combined screening (CS) followed by NIPS was more cost effective in the AMA population and whether incorporating an expanded 1/1000 cutoff (vs. 1/300) would provide any cost advantages.

P07.02: Can we predict who will choose invasive testing after a positive first trimester combined screening for Down syndrome?

P07.02: Can we predict who will choose invasive testing after a positive first trimester combined screening for Down syndrome?

Analysis of Quality of Nuchal Translucency Measurements: Its Role in Prenatal Diagnosis

Objective. Quantitative analysis of the quality of nuchal translucency (NT) measurements. Methods. First-trimester combined screening for Down syndrome was performed to all pregnant women attended in our Department from October 2003 to November 2009. NT was measured according to the Fetal Medicine Foundation (FMF) criteria by 20 trained obstetricians. The performance of NT measurements was retrospectively analyzed with regard to several quality control standards. Accuracy according to experience, professional profile, crown rump length (CRL) values, and FMF certification was statistically tested. Results. A total of 14978 NT measurements were assessed. (1) The mean operator-specific median NT-MoM values was 0,98. (2) Mean percentage of cases >95th and <5th centiles were 5,0% and 4,2%, respectively. (3) Logarithmic mean and SD of the NT MoM values were 0,00 and 0,13, respectively. (4) The DR for trisomy 21 at screening time was 90,7% for a FPR of 6,7% for standard screening strategy. (5) According to Cumulative SUM (CUSUM) figures, the performance was more acceptable in FMF-certified operators. Conclusion. Overall, quality standards show optimal NT measurements in our unit. Operator experience, a dedicated profile to fetal medicine, CRL over 60 mm, and FMF certification have a significant positive impact on the quality standards.

Erroneous production of PAPP‐A kits: the impact of a downward shift in PAPP‐A concentration on the test performance of first‐trimester combined screening for Down syndrome

To evaluate a 20% downward shift in the pregnancy-associated plasma protein A (PAPP-A) concentration on the test performance of first-trimester combined screening (FTS) for Down syndrome (DS) following a flaw in the production of PAPP-A kits on FTS for DS. A retrospective re-evaluation of PAPP-A in stored sera. Inclusion criteria were a maternal weight-corrected PAPP-A multiple of the median value ≥ 0.9 and a biochemical risk of DS ≤ 1:200 at the time of testing. Of the 3100 women, 473 (15%) fulfilled the inclusion criteria. After combining the biochemical risk based on the incorrect PAPP-A values with nuchal translucency findings, an increased risk for DS was initially found in 107 women [false positive rate (FPR): 3.1]. Eighty-two (77%) of the 107 women opted for invasive testing. Following re-analysis of PAPP-A, the biochemical risk and the combined risk were statistically significantly different from the initial risk estimates (p < 0.001.). We noticed that 25 women (30%) had invasive testing, while this was unjustified given the re-analysed PAPP-A. Erroneous PAPP-A kits resulted in an increase in the FPR by 1.2%. There were no reports of iatrogenic miscarriage. The occurrence of this problem reaffirms the importance of continuous monitoring of quality in FTS.

Auditing ultrasound assessment of fetal nuchal translucency thickness: A review of Australian national data 2002–2008

Nuchal translucency (NT) measurement is the ultrasound component of first trimester combined screening for Down syndrome. In 2002, a NT ultrasound education and monitoring program was established in Australia. Between 2002 and 2008, a total of 728,502 NT scans were audited through this process. OVERALL AIM: To audit the availability and performance of certified operators measuring NT following implementation of the Australian education and monitoring program in 2002. Retrospective review of the central database that is used to monitor performance of individuals and practices performing NT scans in both public and private practice settings throughout Australia between 2002 and 2008. The performance of operators was assessed by a widely used international standard - that 40-60% of NT measurements should be above the median value for gestational age. The number of certified operators has increased (from 184 in 2002 to 477 in 2008). There is wide variation between states in the number of operators per birth. The percentage of certified operators with a measurement distribution meeting the international standard has increased from 40% in 2002 to 55% in 2008. Greatest improvement has been seen in operators performing 30-199 scans per year. There has been no overall improvement in performance over the last three audit cycles. The number of operators certified to perform the NT scan has increased since 2002, although availability in some states remains low. An initial improvement in performance of operators appears to have reached a plateau. It is time to become more proactive in engaging operators in the audit cycle.

Early vaginal bleeding has no impact on markers used in first trimester aneuploidy screening

To assess the impact of early vaginal bleeding on the levels of markers used in first trimester screening for aneuploidy. A retrospective analysis was carried out on the free beta human chorionic gonadotrophin (beta-hCG) and pregnancy associated plasma protein-A (PAPP-A) levels and nuchal translucency thickness in 49 653 women with a normal singleton fetus who had first trimester combined screening for Down Syndrome in three centres. Median MoMs and the distribution of log MoMs of the two markers were compared in two groups-7470 women who self-reported vaginal bleeding and 42 183 women who reported no vaginal bleeding at any stage prior to the screening test. The overall median MoM free beta-hCG and that in the bleeding and non-bleeding group were 0.9854, 1.0012 and 0.9832, and for PAPP-A were 1.0407, 1.0413 and 1.037. There was no significant difference between the bleeding and non-bleeding group by median test (p = 0.080) or by t-test comparing log MoMs (p = 0.1305) for free beta-hCG and for PAPP-A with median test (p = 0.5071) or by t-test comparing log MoMs (p = 0.1740). For delta nuchal translucency (NT) there was also no significant difference between the bleeding and non-bleeding group (p = 0.055). Vaginal bleeding has little or no impact on first trimester marker levels and no correction is necessary.

ADAM 12 may be used to reduce the false positive rate of first trimester combined screening for Down syndrome

ADAM12 has been shown to be an efficient maternal serum marker for Down syndrome (DS) in the first trimester; but recent studies, using a second generation assay, have not confirmed these findings. We examined the efficiency of a second generation assay for ADAM12. ADAM12 concentrations were determined in 28 first trimester DS and 503 control pregnancies using a novel Research Delfia ADAM12 kit. Log10MoM distributions of ADAM12 and correlations with other markers were established. Population performance of screening was estimated by Monte Carlo simulation. ADAM12 was significantly reduced in the first trimester in DS pregnancies with a log10MoM of -0.1621 (equivalent to 0.68 MoM) (p < 0.001). The reduction decreased with advancing gestational age. ADAM12 used with PAPP-A + hCG beta + NT (CUB screening) increased the detection rate (DR) from 86% to 89% for a false positive rate (FPR) of 5%. When used for a fixed DR of 90%, the addition of ADAM12 resulted in a 25% reduction of the FPR. ADAM12 is a moderately effective DS marker. It is not a cost-effective addition to CUB screening, but may be used to reduce the FPR in selected high-risk cases.

P11.11: True value of the biochemical tests of genetic screening in the first trimester combined with highly-trained ultrasound personnel

Background: First-trimester Down syndrome screening may have a higher false positive rate in pregnancies achieved by in-vitro fertilization (IVF). Objective: To determine the levels of first-trimester screening markers and to assess the false-positive rate for first-trimester combined screening for Down syndrome in pregnant women after invitro fertilization (IVF), including IVF with intracytoplasmic sperm injection (IVF-ICSI), compared with those observed in spontaneously pregnancies. Methods: A retrospective cohort study of 638 pregnancies achieved after IVF was compared with a control group of 9756 pregnancies conceived spontaneously. All women completed a first-trimester combined screening program. Results: In chromosomally normal pregnancies conceived after IVF, the median value of pregnancy-associated plasma protein-A multiples of the median (MoM) was significantly decreased when compared with pregnancies conceived spontaneously (0.87 vs 1.05), whereas the median free β-human chorionic gonadotropin MoM value was significantly increased (0.90 vs 0.86). The median nuchal translucency thickness MoM was similar in both groups. The false-positive rate of first-trimester combined screening in the overall IVF group, adjusted for maternal age, was significantly higher when compared with controls (9.0% vs. 3.9%). Conclusions: It seems advisable to establish specific median curves for the first-trimester serum screening parameters for IVF pregnancies, as reported in other series.

The impact of crown–rump length measurement error on combined Down syndrome screening: a simulation study

To evaluate the impact of a 5-mm error in the measurement of crown-rump length (CRL) in a woman undergoing ultrasound and biochemistry sequential combined screening for Down syndrome. Based on existing risk calculation algorithms, we simulated the case of a 35-year-old-woman undergoing combined screening based on nuchal translucency (NT) measurement and early second-trimester maternal serum markers (human chorionic gonadotropin (hCG) and alpha-fetoprotein (AFP) expressed as multiples of the median (MoM)). Two measurement errors were considered (+ or - 5 mm), for four different CRLs (50, 60, 70 and 80 mm), with five different NT measurements (1, 1.5, 2, 2.5 and 3 mm) in a patient undergoing biochemistry testing at 14 + 4, 15, 16, 17 or 18 weeks' gestation. Four different values for each maternal serum marker were tested (1, 1.5, 2 and 2.5 MoM for hCG, and 0.5, 0.8, 1 and 1.5 MoM for AFP), leading to a total of 3200 simulations of the impact of measurement error. In all cases the ratio between the risk as assessed with or without the measurement error was calculated (measurement error-related risk ratio (MERR)). Over 3200 simulated cases, MERR ranged from 0.53 to 2.14. In 586 simulations (18.3%), it was < 0.66 or > 1.33. Based on a risk cut-off of 1/300, women would have been misclassified in 112 simulations (3.5%). This would go up to 33 (27.5%) out of the 120 simulations in women with 'borderline' risk, with 1.5 MoM for hCG and 0.5 MoM for AFP, and NT measurement of 1 or 2mm. Down syndrome screening may be highly sensitive to measurement errors in CRL. Quality control of CRL measurement should be performed together with quality control of NT measurement in order to provide the highest standard of care.

Medians and correction factors for biochemical and ultrasound markers in Chinese women undergoing first‐trimester screening for trisomy 21

To establish normative values and distribution parameters of first-trimester maternal serum free beta-human chorionic gonadotropin (beta-hCG), pregnancy-associated plasma protein-A (PAPP-A) and fetal nuchal translucency (NT) thickness in Chinese women and to examine the effects of covariates on their levels. Maternal serum free beta-hCG, PAPP-A and fetal NT were measured in 9762 women presenting for first-trimester combined screening for Down syndrome at 11 to 14 weeks of gestation. Individuals' markers were converted to multiples of the median (MoM) using expected medians estimated by performing a weighted regression analysis. Multivariate regression analysis was performed to assess the influence of maternal weight, parity, ethnicity, chorionicity in twin pregnancies, smoking, insulin-dependent diabetes and mode of conception on individual marker MoM levels. Both free beta-hCG and PAPP-A median values demonstrated an exponential relationship with gestational age in days. Multivariate regression analysis indicated that free beta-hCG MoM was statistically significantly dependent on maternal weight (P < 0.0001) and chorionicity in twin pregnancy (both monochorionic and dichorionic P < 0.0001), that PAPP-A MoM was dependent on maternal weight (P < 0.0001), parity (P < 0.0001), chorionicity in twin pregnancy (both monochorionic and dichorionic P < 0.0001) and mode of conception (P = 0.002), and that fetal NT-MoM was dependent on maternal weight (P = 0.0006) and mode of conception (P = 0.012). Normative values have been generated to allow conversion of NT, free beta-hCG and PAPP-A to their MoM equivalents and correction factors have been determined to adjust for maternal and pregnancy characteristics for use in ethnic Chinese women undergoing first-trimester screening for aneuploidy.

First‐trimester screening markers are altered in pregnancies conceived after IVF/ICSI

To determine the levels of first-trimester screening markers and to assess the false-positive rate for first-trimester combined screening for Down syndrome in a large national population of women pregnant after assisted reproductive technology (ART), in order to decide whether or not to correct risk calculation for mode of conception. A national prospective cohort study of 1000 pregnancies achieved after ART was compared with a control group of 2543 pregnancies conceived spontaneously. All women completed a first-trimester combined screening program. Risk calculation was performed retrospectively based on the screening parameters to avoid bias due to the use of different algorithms of risk calculation. In chromosomally normal pregnancies conceived after in-vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), the pregnancy-associated plasma protein-A multiples of the median value was significantly decreased when compared with that of pregnancies conceived spontaneously (0.78 and 0.79 vs. 0.98), while there was no difference in the group treated by frozen embryo replacement. There was no difference in the level of free beta-human chorionic gonadotropin between groups. The median nuchal translucency thickness was smaller in the overall ART group compared with controls. The false-positive rate of first-trimester combined screening in the overall ART group, adjusted for maternal age, was significantly higher when compared with controls (9.0% vs. 6.0%). It seems advisable to use a population of IVF/ICSI pregnancies to establish median curves for the first-trimester serum screening parameters and perhaps also for nuchal translucency thickness. However, care must be taken, as different ART treatment methods and aspects of medical history seem to alter the screening parameters in different ways.

First‐trimester combined screening for Down syndrome: prediction of low birth weight, small for gestational age and pre‐term delivery in a cohort of non‐selected women

To establish the relationship between the first-trimester screening markers [pregnancy-associated plasma protein A (PAPP-A), free human chorionic gonadotrophin-beta (beta-hCG), nuchal translucency (NT)], the Down syndrome (DS) risk estimate, and the adverse outcomes such as low birth weight, small for gestational age (SGA) and pre-term delivery. A retrospective cohort study including 1,734 non-selected singleton pregnancies consecutively enrolled into the programme of first-trimester combined screening for DS in a 12-month period at a single centre. Data from the Prenatal Patient Registry in ASTRAIA were combined with the Danish National Newborn Screening Registry and Danish Birth Registry. There was a significant relation between low PAPP-A MoM, low beta-hCG MoM, increased risk estimate for DS and low birth weight and SGA. Low PAPP-A MoM and increased NT showed a significant relation to pre-term and spontaneous pre-term delivery. Low PAPP-A MoM showed a significant relation to early pre-term delivery. First-trimester screening markers exhibited a significant relation to low birth weight, SGA and to some extent, to pre-term and early pre-term delivery. The screening performance of individual markers was poor.

Prediction of birth weight by fetal crown–rump length and maternal serum levels of pregnancy‐associated plasma protein‐A in the first trimester

To determine whether the first trimester crown-rump length (CRL), maternal serum levels of pregnancy-associated plasma protein A (PAPP-A) and free beta-human chorionic gonadotropin (fbeta-hCG) are independent predictors of birth weight. This was an observational study over 1.5 years in Chinese patients who underwent first-trimester combined screening for Down syndrome in a University fetal medicine unit. After excluding cases with multiple pregnancies, congenital malformations and in-utero deaths, the relationship between fetal CRL (expressed as standardized Z-score (Z-CRL)), maternal PAPP-A and fbeta-hCG levels (expressed as log(10) of multiples of the median) and birth weight (Z-BW) were analyzed by Pearson's correlation test followed by multiple regression to check for their independency. The predictive power of the independent predictors for small-for-gestational age (SGA, defined as birth weight < 10(th) centile) was then assessed using receiver-operating characteristics (ROC) curves, and the likelihood ratios were derived. A total of 2760 cases were included. Z-CRL, log(10) PAPP-A(MoM), and log(10) fbeta-hCG were positively correlated with Z-BW (P < 0.0001), but only Z-CRL and log(10) PAPP-A(MoM) were independent predictors (P < 0.0001). The areas under the ROC curves of PAPP-A(MoM) and Z-CRL were 0.608 and 0.593, respectively (P < 0.0001). Likelihood ratios increased with decreasing PAPP-A(MoM) and Z-CRL, but were around 1 when the markers were at or above the mean. First-trimester CRL and PAPP-A are independent factors that influence final birth weight. The lower the PAPP-A and the smaller the CRL, the higher the risk of a fetus becoming SGA. However, their predictive powers are not sufficiently good for them to be used alone for SGA screening.

Maternal serum free ß‐hCG and PAPP‐A in patients with habitual abortion‐influence on first‐trimester screening for chromosomal abnormalities

To explore if maternal serum free beta-hCG and pregnancy-associated plasma protein A (PAPP-A) levels in the first-trimester of pregnancy are altered in patients with habitual abortions and if there is an effect on first-trimester screening for Down syndrome. A retrospective study was conducted on 913 normal singleton fetuses that underwent first-trimester combined screening for Down syndrome. Maternal serum PAPP-A and free beta-hCG were compared between patients with (n = 64) and without habitual abortions (n = 849). The medians +/- SD log(10) MoM of PAPP-A and free beta-hCG +/- SD in patients with and without habitual abortions were 0.063 +/- 0.28 versus - 0.014 +/- 0.27 and - 0.001 +/- 0.27 versus - 0.018 +/- 0.31, with a p value of 0.042 and 0.87, respectively. The screen positive rate setting the cut off at 1:350 looking at the background risk for trisomy 21 was 71.4% in women with and 81.2% in women without habitual abortion, after combined first-trimester screening it was 7.8% in women with and 10.1% in women without recurrent abortion. Patients with habitual abortions have slightly increased maternal serum PAPP-A levels in the first-trimester. This marginal difference seems not to effect risk calculation in combined first-trimester screening for trisomy 21.

Follow up and evaluation of the Victorian first‐trimester combined screening programme for Down syndrome and trisomy 18

The objective of this study was to follow up and evaluate the statewide first-trimester combined screening programme for Down syndrome and trisomy 18 at Genetic Health Services Victoria, Australia. Retrospective population cohort. Maternal Serum Screening Laboratory records. All women screened between February 2000 and June 2002 (16,153 pregnancies). Screening results were matched to Victorian perinatal and birth defect data via record linkage, with an ascertainment of 96.8% of pregnancy outcomes. Manual follow up with health professionals increased ascertainment to more than 99%. Fetal Down syndrome or trisomy 18, and combined screen results, to calculate test characteristics. Using a risk threshold of 1 in 300 at time of ultrasound, the sensitivities for standard first-trimester combined screening and augmented 13-week combined screening for Down syndrome were 87.3 and 90.5% and the false-positive rates (FPR) were 4.1 and 3.9%, respectively. The sensitivity for trisomy 18 was 66.7% (10/15, 95% CI 42.8-90.5%) with a 0.4% FPR and 15.2% positive predictive value (1 in 250 risk threshold). The combined use of record linkage and manual follow-up techniques was effective in ascertaining more than 99% of pregnancy outcomes for calculations of accurate test characteristics of the combined screen. The sensitivity for Down syndrome at Genetic Health is comparable to similar populations. However, the sensitivity for trisomy 18 is lower than that elsewhere, which may reflect the overall low birth prevalence of trisomy 18 and associated small numbers in this particular cohort.