Syndrome Maternal Serum Screening Research Articles

Cost-effectiveness threshold of first-trimester Down syndrome maternal serum screening for the use of cell-free DNA as a second-tier screening test.

We aimed to identify the most relevant cost-effectiveness threshold of first-trimester Down syndrome (DS) maternal serum screening (T21T1) for the use of cell-free DNA (cfDNA) as a second-tier test in the French context. A cost-effectiveness analysis was performed on 108,121 singleton pregnancies using a simulation model. The threshold of T21T1 screening was ranged from 1/51 to 1/1,000 in steps of 1/50. The most relevant threshold was based on cost-effectiveness ratio (CER; costs =direct medical costs after T21T1 screening/ effectiveness =number of DS cases identified). In the sample, 161cases of DS were identified. At the threshold of ≥1/50, 47.2% of total DS cases were diagnosed. In the simulation model, for a threshold ≥ 1/250, 73.9% of total DS cases were diagnosed, for ≥ 1/500, 78.8% and for ≥ 1/1,000, only two additional cases were diagnosed. The slope of the cost increase was slight from threshold ≥ 1/250 (978,634€), then steep up to 1/500 (1,966,576€) and increased exponentially to 1/1,000 (3,980,216€). The CER was 38,560 for a threshold ≥ 1/500. The most cost-effective threshold for cfDNA as a second-tier test seems to be ≥1/500. For higher thresholds, costs increase dramatically for only a few additional cases of DS identified.

Impact on spina bifida screening of shifting prenatal Down syndrome maternal serum screening from the second trimester to the first.

Shifting screening for trisomy 21 to the first trimester has resulted in the loss of maternal serum alpha-fetoprotein screening for spina bifida. The aim of this study was to study the impact on open spina bifida prenatal screening. We reviewed prenatally diagnosed cases of spina bifida over three years: 2009 (only second-trimester screening, MSM2T), 2010 (transient period) and 2011 (majority first-trimester screening, MSM1T). Cases were assigned to three groups based on maternal serum markers (MSM2T, MSM1T and 'not performed'). Gestational age at diagnosis of spina bifida was compared between these three groups and between the years 2009 and 2011. Median gestational ages at diagnosis of the 742 spina bifida cases between the three groups were 22weeks [18+6 -23], 22+1 weeks [21+3 -23] and 21+4 weeks [14+1 -23], respectively (P<0.005). The diagnosis was made at 14-20weeks in 34.7% for MSM2T group versus 8.5% for MSM1T (P<0.001). Spina bifida diagnosis at 14-20weeks declined from 38.8% in 2009 to 13.3% in 2011 (P<0.001). Loss of maternal serum alpha-fetoprotein had a tangible effect on the gestational age at diagnosis of spina bifida and resulted in a decrease of 25% of cases of spina bifida detected before 20weeks. © 2017 John Wiley & Sons, Ltd.

Preanalytical stability of maternal serum markers hCGβ and PAPP-A

Down syndrome maternal serum marker screening is based on a risk calculation including the free β - human chorionic gonadotropin (hCGβ) and pregnancy-associated placenta protein type A (PAPP-A). The aim of this study was to define the pre-analytical conditions of stability of these markers both in whole blood at 15-25̊C and, after centrifugation, in serum at 4-8̊C. 158 patients were included in the study. Two automated workstations were used for assays, Cobas 8000e602, Roche Diagnostics (58 patients tested) and DELFIAXpress, PerkinElmer (100 patients tested). The stability of markers was studied in whole blood (15-25̊C) 2, 4, 6 and 8 hours after sampling and in serum stored after centrifugation at 4-8̊C at 24, 72 and 120 hours. Variations were defined by (CT - C2)/C2, C2 being the marker concentration at 2 hours and CT the concentration at time T. In whole blood kept for 8 hours at 15-25̊C, hCGβ increased by a mean 2.4%, whereas the mean increase of PAPP-A was < 1%. In the serum kept for 5 days at 4-8̊C, the mean increase of hCGβ was 4.2%, with no change in PAPP-A. The impact of these variations on risk calculation is low. In conclusion, maternal serum can be store 8 hours at 15-25̊C in whole blood and 5 days at 4-8̊C after centrifugation and serum separation for Down syndrome maternal serum screening.

PMM.88 Screening for Down’s Syndrome in Women with Renal Disease

IntroductionIn 2001, the UK National Screening Committee advised that all pregnant mothers should be offered a screening test for Down’s syndrome (DS). This is performed at first (biomarkers and ultrasound)...

Down syndrome maternal serum marker screening after 18 weeks of gestation: a countrywide study

The objective of the study was to evaluate the efficacy of maternal serum markers in detecting Down syndrome after 18 weeks of gestation in women who book late for maternity care in a large national retrospective study. During the period 2007-2012, 27,648 women, regardless of maternal age (17.4% were 35 years old and over), were included in a late Down syndrome screening program (18(+0) to 35(+6) weeks) using the maternal serum markers alpha-fetoprotein and human chorionic gonadotrophin-beta. Samples were assayed in a single laboratory. A dataset of median markers previously established in our laboratory was used for risk calculation. The control group consisted of 27,648 women (14(+0) to 17(+6) weeks) randomly selected from the routine database. When the later screening group was compared with the standard second-trimester control group, the median multiples of medians (1.01 vs 0.98 for alpha-fetoprotein, 1.03 vs 0.98 for human chorionic gonadotrophin-beta), median risks (1 of 2414 vs 1 of 2720), false-positive rates (11.1% vs 11.6%), and trisomy 21 detection rates (83.3% vs 85.7%) did not differ significantly. Late Down syndrome maternal serum screening is feasible with a good sensitivity/specificity compromise throughout gestation and is of clinical value in late-booking women.

Down syndrome maternal serum screening in patients with renal disease

The objective of the study was to determine the value of maternal serum Down syndrome screening in patients affected by renal disease. A study group of 54 pregnant women with renal diseases defined before pregnancy, was compared with a control group of 108 patients matched for maternal age, maternal weight, smoking status, and gestational age. Maternal serum markers (free beta-human chorionic gonadotropin [hCG], total hCG, alpha-fetoprotein) expressed in multiple of median and maternal renal function markers (creatinine, beta2-microglobulin, alpha1-microglobulin) were assayed. The percentage of patients in the Down syndrome at-risk group (>1:250) using free beta-hCG was significantly higher (P < .02) in the renal disease group (48%) than in the control group (12%). No significant difference was observed for total hCG (25% vs 15%). Down syndrome screening using free beta-hCG is not applicable in patients with renal disease whatever the maternal serum creatinine and can be used with caution when total hCG is used.

Dépistage prénatal de la trisomie 21 : les nouvelles recommandations

Summary Down syndrome maternal serum screening is organized in France since 1997 and is performed at a national scale. Due to ethic implication, this screening is strictly regulated (maternal information and signed consent, authorized laboratories, software and reagents designed). During these 10 years, new tools were developed, such as nucal translucency measurement and first trimester maternal serum markers. Three major modifications are included in the new policies (JO 3rd July 2009): the maternal age cut-off of 38 years for fetal karyotyping is of no value; first-trimester screening combining nucal translucency measurement and biochemical markers must be routinely proposed; ultrasonography must be performed with quality control.

Trends in state/population-based Down syndrome screening and invasive prenatal testing with the introduction of first-trimester combined Down syndrome screening, South Australia, 1995-2005

The purpose of this study was to review trends in the us of maternal serum Down syndrome screening and invasive prenatal testing before and after the introduction of a state-based first-trimester combined Down syndrome screening program. A retrospective population-based study was performed on first- and second-trimester Down syndrome screening, invasive prenatal testing, and prenatal detection of Down syndrome from 1995 to 2005 in South Australia with data from state-based registers. Chi-square tests were used to evaluate trends. There was a significant decrease in the use of second-trimester Down syndrome maternal serum screening (from 75% in 1995 to 25% in 2005; P < .001) and a corresponding significant increase in first-trimester combined screening (from 0.8% in 2000 to 49% in 2005; P < .001). The proportion of all confinements that involved invasive prenatal testing fell (from 9.3% in 1995 to 7.6% in 2005; P < .001). There was a significant decrease in the number of invasive prenatal tests that were needed to detect 1 Down syndrome fetus (from 86 tests in 1995 to 40 tests in 2005; P < .001), with no significant change in the proportion of Down syndrome cases that were detected prenatally. The introduction and increased use of first-trimester combined Down syndrome screening has been associated with more efficient use of invasive prenatal testing in South Australia and has maintained a high level of overall prenatal detection.

Prenatal diagnosis and molecular characterization of an interstitial 1q24.2q25.2 deletion

We report on the observation of an interstitial deletion of the long arm of chromosome 1 diagnosed prenatally in a 28 weeks gestation fetus by standard karyotype. Amniocentesis was performed because of an increased Down syndrome maternal serum screening and ultrasonographic abnormalities. Fetus autopsy showed an intrauterine growth retardation, dysmorphic features and limbs abnormalities. Using fluorescent in situ hybridization technique (FISH), we characterized the deletion boundaries corresponding to the bacterial artificial chromosomes (BAC) RP11-193J5 and RP11-162L13. Molecular studies identified the deletion of paternal origin. Therefore the karyotype was interpreted as 46,XY,del(1)(q24.2q25.2). This is the smallest deletion of the long arm of chromosome 1 reported prenatally and characterized at the molecular level. Its phenotype is compared to other similar cases described in the literature.

Medically assisted reproduction and second-trimester maternal serum marker screening for Down syndrome.

To evaluate the effect of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) on total hCG, free ss-hCG, AFP and unconjugated estriol (uE3) used as markers for second-trimester Down syndrome maternal serum screening. Second-trimester maternal sera from 1515 singleton pregnancies (970 by IVF, 545 by ICSI) were compared with control sera (21 014 cases). Free ss-hCG, total hCG, AFP and uE3 were compared between the control group and the medically assisted reproduction groups. The percentages of at-risk patients (>/=1/250) were also compared. No differences in values of the maternal serum markers were observed between the medically assisted and control groups. When maternal age was taken into account, the screen-positive rate for Down syndrome screening did not differ between the two groups. Patients undergoing assisted reproduction techniques can be counseled for maternal serum Down syndrome screening with the same efficacy as patients with naturally conceived pregnancies.

Very low alpha-fetoprotein in Down syndrome maternal serum screening.

To establish the frequency of very low maternal serum AFP and to differentiate congenital AFP deficiency from those diseases known to be associated with low AFP. AFP values below 2 microg/L and borderline values up to 3 microg/L were retrospectively analysed in 839 773 singleton pregnancies included in a programme for routine screening of trisomy 21 maternal serum markers. Serum AFP was undetectable (< or =2 microg/L) in 8 cases, giving a frequency of 1/105 000. The calculated risk of Down syndrome was > or =1/250 in 5 cases. Fetal karyotype was normal. Seven of these pregnancies went to term (39-41 weeks) uneventfully, and birth weight was normal (3050-4110 g). In the 8th case, fetal death occurred at 35 weeks due to severe maternal diabetes. AFP levels between 2.1 and 3.0 microg/L were noted in 7 other cases. The calculated risk of Down syndrome was > or =1/250 in 5 cases, and fetal karyotype was normal. Pregnancies went to term in 4 cases (33-41 weeks), and birth weight was normal (3000-3380 g). In 3 cases, low hCG (<0.6 MoM) was associated with low AFP, and fetal death occurred at 15 to 16 weeks. Once technical errors have been excluded (repeat assay in a second run, calcium assayed to exclude the interference of EDTA for fluorimetric methods, dilution to exclude interfering antibodies, running on an alternative analyser, checking a second sample), very low second-trimester maternal serum AFP should prompt ultrasound examination in order to check fetal viability. Congenital AFP deficiency, an extremely rare disorder (1/100 000), should be suspected. It has no consequences for fetal and infant development, and parents should be reassured.

Second-trimester Down syndrome maternal serum screening in twin pregnancies: impact of chorionicity.

To evaluate the diagnostic value of second-trimester maternal serum screening for Down syndrome in twin pregnancies. On the basis of a prospective study of second-trimester maternal serum screening, we studied the distribution of alpha-fetoprotein (AFP) and free ss hCG in 3043 twin pregnancies with known outcome. There were 1561 dichorionic and 244 monochorionic pregnancies. The placental type was not available in 1238 cases. We compared 5 screening policies with the same risk, 1/250, cut-off: maternal age, maternal age corrected for the risk of having at least one affected twin in dichorionic pregnancies, maternal serum marker screening using observed AFP and free ss-hCG values divided by a factor of 2, by using the median values actually observed in the global twin population, or by the median values specific to mono- or dichorionic twins. When expressed in singleton-derived MoMs, the median was 2.10 for AFP and 2.11 for free ss-hCG. The median AFP did not differ between monochorionic and dichorionic pregnancies. The distribution of free ss-hCG was significantly shifted towards greater values in monochorionic (2.16 MoM) compared to dichorionic (2.07) pregnancies (p < 0.0001). Screened-positive and detection rates were, respectively, 6.6% and 27.3% using maternal age alone, 24.6% and 54.5% using maternal age corrected for the risk of having at least one affected twin in dichorionic pregnancies, 7.75% and 54.5% using observed AFP and free beta-hCG values divided by a factor of 2, 8.05% and 54.5% using the median values actually observed in the global twin population, and 7.75% and 54.5% using the median values specific to mono- or dichorionic twins. Trisomy 21 second-trimester maternal serum screening is feasible in twins, and is better than a policy based on maternal age alone.

Risk of amniocentesis in women screened positive for Down syndrome with second trimester maternal serum markers.

In routine obstetrical practice, prior to offering invasive prenatal diagnosis, it is crucial to weigh the risks attendant on amniocentesis against the individual's risk of aneuploidy. We took advantage of a policy of follow-up of patients undergoing Down syndrome maternal serum screening to compare the rates of fetal loss before 24 weeks and of early premature delivery at 24-28 weeks between women who underwent amniocentesis and women who did not. A total of 54 902 patients entered the study, of whom 4039 (7.35%) were lost to follow-up and 387 were excluded because of a severe fetal abnormality. Of the 50 476 remaining patients, 3472 had an amniocentesis whereas 47 004 had not and served as controls. In the amniocentesis group, the fetal loss rate before 24 weeks was 1.12% (95% CI=1.08-1.15) and the 24-28 weeks premature delivery rate was 0.40% (95% CI=0.39-0.41) which was significantly higher than in controls (0.42% with 95% CI 0.41-0.43 and 0.24% with 95% CI 0.23-0.25, respectively). The 0.86% difference in adverse outcome rates between the amniocentesis and control groups may be attributable to amniocentesis and compares favourably with the positive predictive value of maternal serum markers (1.70%) observed in the present study.

Dimeric Inhibin A as a Fourth Marker for Down's Syndrome Maternal Serum Screening in Native Japanese Women

This study was conducted to assess the usefulness of dimeric inhibin A as a fourth marker for Down's syndrome screening in addition to AFP, hCG and uE3 markers for native Japanese women. Serum specimens from 367 native Japanese women in the second trimester were assayed for dimeric inhibin A levels. Day specific dimeric inhibin A medians were established for gestational ages 15.0-21.9. Weekly median values for the native Japanese were compared with those of a U.S. population. Selected Japanese specimens from 15 diagnosed Down's syndrome and 3 trisomy 18 cases were also assayed for dimeric inhibin A. Dimeric inhibin A levels did not vary greatly over the gestational age range as expected. Median value comparison showed that native Japanese dimeric inhibin A medians are higher than the U.S. population medians by an average of 7.95%. Native Japanese dimeric inhibin A median values in this study are 1.77 times higher in Down's syndrome cases than in unaffected pregnancies. Trisomy 18 dimeric inhibin A levels show no significant difference from the unaffected pregnancies. This report shows for the first time that dimeric inhibin A can be informative as a fourth marker for Down's syndrome screening in native Japanese women. We expect the addition of dimeric inhibin A to a triple marker protocol will increase the accuracy of predicted risk for all pregnancies screened and increase the detection rate of Down's syndrome affected pregnancies.