Combined Screening For Down Syndrome Research Articles

Influence of maternal systemic lupus erythematosus on first‐trimester combined screening for chromosomal abnormalities

To explore the effect of maternal systemic lupus erythematosus (SLE) on first-trimester screening markers for Down syndrome. A retrospective study was conducted on 1150 normal singleton fetuses that underwent first-trimester combined screening for Down syndrome. Fetal delta nuchal translucency (NT), maternal serum PAPP-A and free beta-hCG were compared between pregnancies with SLE (n = 10) and without preexisting maternal disease (n = 1140). The medians +/- SD for delta NT, log(10) MoM of PAPP-A and free beta-hCG +/- SD in pregnancies with SLE and without maternal disease were - 0.18 +/- 0.29 versus - 0.18 +/- 0.33, 0.005 +/- 0.32 versus 0.02 +/- 0.26, and 0.22 +/- 0.19 versus - 0.014 +/- 0.28, with a p value of 0.7, 0.98 and 0.03, respectively. Patients with preexisting SLE have increased maternal serum-free beta-hCG levels in the first-trimester. But, because of the multimodal procedure of risk calculation there is no significant difference in the screen-positive rate after the combined first-trimester screening for trisomy 21.

Dépistage de la trisomie 21 par le test combiné du premier trimestre suivi par l'échographie du second trimestre en population générale

Background Recent studies have reported the efficacy of first trimester combined screening for Down Syndrome based on maternal age, serum markers (human chorionic gonadotropin, pregnancy-associated plasma protein A), and ultrasound measurement of fetal nuchal translucency. However, those do not incorporate the value of the widely accepted routine 20–22 week anomaly scan. Study design We carried out a multi-centre, interventional study in the unselected population of a single health authority in order to assess the performance of first trimester combined screening, followed by routine second trimester ultrasound examination and/or screening by maternal serum markers (free β-hCG and alpha-fetoprotein measurement or total hCG, alpha-fetoprotein and unconjugated estriol measurement) when incidentally performed. Detection and screen positive rates were estimated using a correction method for non verified issues. A cost analysis was also performed. Results During the study period, 14,934 women were included. Fifty-one cases of Down Syndrome were observed, giving a prevalence of 3.4 per 1000 pregnancies. Of these, 46 were diagnosed through first ( N = 41) or second ( N = 5) trimester screening. Among the 5 screen-negative Down syndrome cases, all were diagnosed postnatally after an uneventful pregnancy. Detection and screen positive rates of first trimester combined screening were 79.6% and 2.7%, respectively. These features reached 89.7 and 4.2%, respectively when combined with second trimester ultrasound screening. The average cost of the full screening procedure was 108 € (120 $) per woman and the cost per diagnosed Down syndrome pregnancy was 7,118 € (7,909 $). Conclusion Our findings suggest that one pragmatic interventional two-step approach using first-trimester combined screening followed by second trimester detailed ultrasound examination is a suitable and acceptable option for Down syndrome screening in pregnancy.

Does vaginal bleeding influence first‐trimester markers for Down syndrome?

To examine the effect of early vaginal bleeding on first-trimester screening markers for Down syndrome. A retrospective study was conducted on 1755 normal singleton fetuses that underwent first-trimester combined screening for Down syndrome on the basis of ultrasound and maternal serum markers. Fetal delta-nuchal translucency (NT), maternal serum pregnancy-associated plasma protein A (PAPP-A) and free beta-hCG were compared between pregnancies with (n = 252) and without (n = 1503) an episode of vaginal bleeding. Subgroup analysis for the intensity of bleeding (spotting n = 191; light n = 32; heavy n = 29) was performed. The median +/- SD (log(10)) for delta-NT, multiple of medians (MoM) PAPP-A and MoM free beta-hCG (corrected for maternal weight, smoking and ethnicity) was - 0.17 +/- 0.62, 1.10 +/- 0.28, 1.1 +/- 0.28 and - 0.15 +/- 0.51, 0.98 +/- 0.26, 0.94 +/- 0.3 in pregnancies with and without a history of early vaginal bleeding, which were not significantly different. Exclusion of patients with spotting from the vaginal bleeding group revealed significantly higher maternal serum free beta-hCG MoM values (median +/- SD (log(10))) compared to patients without bleeding, 1.29 +/- 0.27 vs 0.96 +/- 0.3(p = 0.011). Screen-positive (cut off of 1:350) rate after combined first-trimester screening was 28.1% in patients with light vaginal bleeding and 8.4% in patients without bleeding (p = 0.001). Light vaginal bleeding before first-trimester combined screening for Down syndrome leads to a higher screen-positive rate after combined first trimester screening, without a significant difference in serum levels of the screening markers.

Screening for Down syndrome using first-trimester combined screening followed by second-trimester ultrasound examination in an unselected population

Recent studies have reported the efficacy of first-trimester combined screening for Down syndrome based on maternal age, serum markers (human chorionic gonadotropin, pregnancy-associated plasma protein A), and ultrasound measurement of fetal nuchal translucency. However, those do not incorporate the value of the widely accepted routine 20-22 weeks' anomaly scan. We carried out a multicenter, interventional study in the unselected population of a single health authority in order to assess the performance of first-trimester combined screening, followed by routine second trimester ultrasound examination and/or screening by maternal serum markers (free beta-hCG and alpha-fetoprotein measurement or total hCG, alpha-fetoprotein, and unconjugated estriol measurement) when incidentally performed. Detection and screen positive rates were estimated using a correction method for nonverified issues. A cost analysis was also performed. During the study period, 14,934 women were included. Fifty-one cases of Down syndrome were observed, giving a prevalence of 3.4 per 1000 pregnancies. Of these, 46 were diagnosed through first (n = 41) or second (n = 5) trimester screening. Among the 5 screen-negative Down syndrome cases, all were diagnosed postnatally after an uneventful pregnancy. Detection and screen positive rates of first-trimester combined screening were 79.6% and 2.7%, respectively. These features reached 89.7%, and 4.2%, respectively, when combined with second-trimester ultrasound screening. The average cost of the full screening procedure was 108 euros (120 dollars) per woman and the cost per diagnosed Down syndrome pregnancy was 7,118 euros (7909 dollars). Our findings suggest that 1 pragmatic interventional 2-step approach using first-trimester combined screening followed by second-trimester detailed ultrasound examination is a suitable and acceptable option for Down syndrome screening in pregnancy.

First-trimester maternal serum levels of placental hormones are independent predictors of second-trimester fetal growth parameters

To determine whether first-trimester maternal serum levels of pregnancy-associated plasma protein-A (PAPP-A) and free beta-human chorionic gonadotropin (fbeta-hCG) are independent predictors of second-trimester fetal growth parameters. This was a cohort study over a 1-year period involving 594 Chinese women who underwent both first-trimester combined screening for Down syndrome and a routine second-trimester ultrasound examination. Maternal PAPP-A and fbeta-hCG levels (expressed in log(10) of multiples of median (MoM)), crown-rump length (CRL) (expressed in standardized Z-score (Z-CRL)), and maternal height and weight, were correlated with the Z-score of biparietal diameter (Z-BPD), femur length (Z-FL) and abdominal circumference (Z-AC) measured in the second trimester, using the Pearson test, followed by multiple regression analysis. Z-BPD, Z-FL and Z-AC were positively correlated with log(10) PAPP-A MoM, CRL and maternal height (all P < 0.05), while log(10) fbeta-hCG MoM was negatively correlated with Z-AC (P < 0.05). After controlling for the effects of CRL, maternal height and weight, log(10) PAPP-A MoM was found to be an independent positive predictor of Z-FL (r = 0.797, P < 0.001) and Z-AC (r = 0.305, P = 0.049), and log(10) fbeta-hCG MoM was an independent negative predictor of Z-FL (r = -0.381, P = 0.023) and Z-AC (r = -0.418, P = 0.002). Neither hormonal level was related to Z-BPD. First-trimester PAPP-A and fbeta-hCG are independent factors that influence subsequent fetal growth. PAPP-A level is positively correlated with FL and AC in the second trimester, while fbeta-hCG level is negatively correlated with them. However, BPD is not affected by either of the hormones.

Expectation and knowledge of women undergoing first-trimester combined screening for Down syndrome in a Chinese population

To study the preference of pregnant women regarding the time taken to report the results of first-trimester combined screening for Down syndrome and their knowledge about it. A questionnaire survey was conducted on a cohort of 325 pregnant participants who attended our first-trimester combined nuchal translucency and biochemical screening programme for fetal Down syndrome. This service was operated in a one-stop setting and the result of the screening test was available within 1 to 2 h after the collection of blood sample. The majority of participants: (1) could recall the quoted detection rate correctly (96.6%); (2) understood that a negative test does not exclude Down syndrome (91.1%); (3) understood that a positive test does not equate to an affected fetus (91.0%), and (4) could decide on the need for further invasive tests on the basis of the screening test results (98.1%). Twenty-nine percent of participants considered that a one-stop setting was very important because any delay in releasing the results made a significant difference to them, while 48.9% considered it acceptable if the results were available on the same day. The percentage dropped dramatically to 6.3% (within 2 days), 6.7% (within 3 days), 5.7% (within 1 week), and 3.1% (more than 1 week). The majority of the pregnant women in our test considered same day reporting of screening test results to be no different from a one-stop clinic. This would have important implications for the organisation and structuring of our service provision, since the operation of a one-stop clinic imposes significant stresses on the clinical staff involved.

Early vaginal bleeding and first-trimester markers for Down syndrome.

To assess the effect of early vaginal bleeding on first-trimester markers for Down syndrome. A retrospective study was conducted on 2330 normal singleton fetuses who underwent first-trimester combined screening for Down syndrome based on ultrasound and maternal serum markers. Fetal nuchal translucency (NT), maternal serum pregnancy-associated plasma protein A (PAPP-A), free beta-hCG and the false-positive rate of the test were compared between pregnancies with (n = 253) and without (n = 2077) a history of early vaginal bleeding. The mean +/- SD log(10) MoM for NT, PAPP-A and free beta-hCG was -0.024 +/- 0.101, 0.007 +/- 0.244, 0.047 +/- 0.273 and -0.011 +/- 0.108, -0.006 +/- 0.223, 0.008 +/- 0.264 in pregnancies with and without a history of early vaginal bleeding, with a p value of 0.07, 0.40 and 0.03 respectively. The false-positive rate was 2.4% and 3.6% (p = 0.33). An earlier episode of vaginal bleeding is associated with an increase in maternal serum free beta-hCG levels at first-trimester combined screening for Down syndrome. However, this phenomenon is unlikely to significantly affect the false-positive rate of the test.