First-trimester Screening For Trisomy Research Articles

Combined first trimester screening for trisomy 21: Assessment of excess risk in case of free ß-human chorionic gonadotrophin between 5 and 10 multiples of the median.

The first trimester combined risk of trisomy 21 is obtained by multiplying the risk related to maternal age by the likelihood ratios of nuchal translucency, free beta-human chorionic gonadotrophin (β-hCG) and placenta associated plasma protein-A. Beyond five multiples of the median (MoM) of β-hCG, the risk of trisomy 21 is truncated. The objective of the present study was to evaluate the evolution of the first trimester combined risk of trisomy 21 in individuals with first-trimester free-β-hCG levels between 5 and 10 MoM. We conducted a non-interventional cohort study from a 6-year database of combined first-trimester trisomy 21 screening of all individuals who underwent the screening in a French specialized medical analysis center. We included all pregnant individuals who had a serum-free β-hCG between 5 and 10 MoM. Patients for whom the status of the fetus, with or without trisomy 21, was not identified by the outcome of the pregnancy or by a karyotype result were excluded from the study. The discriminatory capacity of free-β-hCG above 5 MoM was studied by a receiver operating characteristic curve. We used an orthogonal polynomial regression to represent the evolution of likelihood ratios according to free-β-hCG in MoM. Among 413 216 combined first-trimester screens of trisomy 21, 2239 (0.5%) screens met the inclusion criteria. In the selected population, 801 (35.8%) were excluded from the study because of missing fetal or neonatal status, and 46 (3.2%) fetuses out of 1438 included were diagnosed with trisomy 21. For free β-hCG values between 5 and 10 MoM, the area under the curve is 0.56 (0.46-0.65). The scatterplot of the likelihood ratio of β-hCG showed an increasing parabolic pattern: the likelihood of trisomy 21 increases with the free-β-hCG threshold. To override the truncated risk of trisomy 21 in case of free β-hCG values between 5 and 10 MoM, the study has allowed us to estimate the adjusted risk of trisomy 21, enabling health professionals to offer appropriate prenatal counseling.

SY10-3. Complement Activation and Regulation in Preeclampsia and HELLP Syndrome

To evaluate the potential of maternal serum placental growth factor (PlGF) as a marker for Trisomy 21 in Chinese pregnant women.Serum samples were collected and stored from 600 women who have a viable singleton pregnancy and underwent first trimester screening for Trisomy 21 between 2011 and 2014. Serum concentration of PlGF was measured using the automated time-solved immunofluorometric assay and expressed as Multiples of the expected median (MoM) from the 600 women available stored serum samples (558 Euploidy and 42 Trisomy 21). The levels of PlGF MoM were compared between Trisomy 21 cases and Euploid pregnancies. Expected median PlGF levels in Chinese were also compared to that published for Caucasians. Multivariate Gaussian modeling was performed to predict detection and false-positive rates.In euploid pregnancies the concentrations of PlGF increased with Crown Rump Length(CRL) and decreased with maternal weight. The overall median MoM of PlGF in Chinese was higher than that of Caucasian. The median PlGF level was 0.63 MoM in the cases and 1.00 MoM in the controls (p < 0.0001). The prediction of Trisomy 21 has been slightly improved by the addition of PlGF to the standard screening test in China. The detection rate of screening after adding PlGF data was increased from 93.4% to 94.6% at a false-positive rate of 3% and the false positive rate decreased from 0.23% to 0.17% for a detection rate of 80%.The median PlGF concentrations in Chinese is higher than those of Caucasians. Results suggest adding PlGF may substantially improve the performance of current first trimester screening strategy for Trisomy 21 in Chinese pregnant women.

Performance of first trimester screening for Trisomy 21 in twin pregnancies.

To assess the performance of the Danish first trimester screening program in twin pregnancies. Retrospective, nation-wide, cohort study with data collected from the Danish Fetal Medicine Database (DFMD) and The Danish Central Cytogenetic Registry (DCCR). The cohort included all women with twin pregnancies participating in the national first trimester screening program for Trisomy 21. Risk assessment was based on maternal age, nuchal translucency (NT) thickness and, if available, biochemical markers (β-hCG and PAPP-A). 8812 twin pregnancies including 42 pregnancies with Trisomy 21 had a risk assessment between 2009 and 2017. The detection rate (DR) for pregnancies with a risk assessment based on maternal age and NT only (missing data on biochemical markers, n = 4693) was 69.6% (95% CI: 50.8%-88.4%) for a 6.3% false positive rate (FPR) (95% CI: 5.6%-7.0%), whereas for pregnancies with a risk assessment based on all three parameters (n = 4119) the DR was 89.5% (95% CI: 76.7%-100.0%) for a 7.2% FPR (95% CI: 6.4%-8.0%). The DR of Trisomy 21 in twin pregnancies, seems as high as for singleton pregnancies, when using optimal screening techniques, but the FPR is nearly twice as high.

VP03.04: First trimester aneuploidy screening using maternal characteristics, serum biochemical markers and nuchal translucency in a low‐risk population

To evaluate the performance of a first trimester screening for aneuploidy in detecting Trisomy 21, 18 and 13 using maternal charateristics, serum biochemical markers and fetal nuchal translucency measurement in a low-risk population. It also aims to determine the maternal variables associated with risk of Trisomy 21, 18 and 13. The FTS aneuploidy program was introduced in our institution on January 2014. This is a retrospective review of patients referred for FTS between January 2014 to June 2018 to determine the performance of our FTS program. The final risk for aneuploidy was obtained using the LifecycleTM prenatal screening software (Perkin Elmer, USA), with a cut-off value of 1:250. Pregnancy variables and outcomes were determined by reviewing delivery records. The incidence of aneuploidy in our institution was 3 per 1,000 livebirths. 134 women were included with age range 21–44 years (mean 34.79 years). Pre-pregnancy BMI showed 48 (35.8%) overweight and 14 (10.4%) obese mothers. 55 (41.0%) had associated comorbidities including DM, hypothyroidism, hypertension, APAS, pre-eclampsia. 14 (10.4%) women screened high risk for T21 and all neonates were karyotype negative. 120 (89.6%) women screened low risk and all neonates were karyotype negative. One woman screened high risk for T18 and T13 and the neonate was karyotype negative. Multivariate analysis showed that maternal age and NT MoM were significantly associated with risk for T21 (p < 0.05). For every increase in age, there is 1.35x increase risk for T21 (OR = 1.35; 95% CI:1.10–1.67; p = 0.005). For every increase in NT MoM, there is 13x increased risk for T21 (OR = 12.99; 95% CI:1.82–92.76; p = 0.01). The first trimester screening for Trisomy 21 in this low-risk population has a specificity of 89% and negative predictive value of 100% at a false-positive rate of 10%. Maternal age, nuchal translucency MoM and nasal bone were significantly associated with risk for Trisomy 21.

First-trimester screening for trisomies in pregnancies with vanishing twin.

To examine multiples of the median (MoM) values of serum free beta-human chorionic gonadotropin (β-hCG) and pregnancy-associated plasma protein-A (PAPP-A) in a large series of pregnancies with a vanishing twin, determine the association of these values with the interval between embryonic death and blood sampling, and develop a model that would allow incorporation of these metabolites in first-trimester combined screening for trisomy. This was a retrospective study comparing maternal serum free β-hCG and PAPP-A levels at 11-13 weeks' gestation in 528 dichorionic pregnancies with a vanishing twin, including 194 (36.7%) with an empty gestational sac and 334 (63.3%) with a dead embryo, with those in 5280 normal singleton pregnancies matched for method of conception and date of examination. In vanishing-twin pregnancies with a dead embryo, marker levels were examined in relation to the estimated time between embryonic death and maternal blood sampling. First, in pregnancies with a vanishing twin, median free β-hCG MoM was not significantly different from that in normal singleton pregnancies (1.000; 95% CI, 0.985-1.016 vs 0.995; 95% CI, 0.948-1.044; P = 0.849). Second, PAPP-A MoM was higher in vanishing-twin pregnancies than in normal singleton pregnancies (1.000; 95% CI, 0.985-1.015), both in the group with an empty gestational sac (1.165; 95% CI, 1.080-1.256; P = 0.0001) and in that with a dead embryo (1.175; 95% CI, 1.105-1.249; P < 0.0001). Third, in vanishing-twin pregnancies with a dead embryo, PAPP-A MoM was related inversely to the interval between estimated gestational age at embryonic demise and blood sampling (P < 0.0001). Fourth, in first-trimester screening for trisomy 21 in singleton pregnancies, the estimated detection rate, at a 5% false-positive rate, was 82% in screening by a combination of maternal age and fetal nuchal translucency thickness, and this increased to 86% with the addition of serum free β-hCG and to 91% with the addition of serum PAPP-A. Fifth, similar performance of screening can be achieved in pregnancies with a vanishing twin, provided the appropriate adjustments are made to the level of PAPP-A for the interval between estimated gestational age at embryonic demise and blood sampling. First-trimester screening for trisomy in pregnancies with a vanishing twin should rely on a combination of maternal age, fetal nuchal translucency thickness and serum free β-hCG, as in singleton pregnancy, without the use of serum PAPP-A. Alternatively, PAPP-A can be included but only after appropriate adjustment for the interval between estimated gestational age at fetal demise and blood sampling. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

First trimester uterine artery pulsatility index levels in euploid and aneuploid pregnancies.

To examine whether the uterine artery PI is different in aneuploid and euploid pregnancies. Retrospective case-matched study at the department of prenatal medicine at the University of Tuebingen, Germany. The study involved patients with complete data on first trimester screening for trisomies and preeclampsia except PlGF. For each case with trisomy 21 we randomly selected 50 cases with a euploid fetus where complete data on screening for aneuploidy and preeclampsia were also available. The uterine artery pulsatility index and the corresponding MoM values of euploid and the aneuploid population were compared with a Man-Whitney U test. The dataset consisted of 4591 singleton pregnancies. The karyotype was normal in 4500 cases and was abnormal in the remaining 91 pregnancies. There were 50 pregnancies with trisomy 21, 31 with trisomy 18 and 13, and 10 with triploidy. In the group with euploid fetuses, median uterine artery PI was 1.55 (0.99 MoM). In the group with trisomy 21, the median PI (1.42) and MoM (0.89) levels were both significantly lower than in the euploid (p < 0.001). However, the measurements in the trisomy 18 and 13 [1.61 (0.93 MoM)] and in the triploidy [1.99 (1.13 MoM)] groups were not significantly different from those in the euploid group (p = 0.468 and p = 0.632, respectively). In conclusion, uterine artery PI levels in the first trimester are slightly lower in pregnancies with trisomy 21. This knowledge may prove to be useful in cases where a low PAPP-A level is seen on the first trimester maternal serum biochemical evaluation to differentiate whether the more likely cause for this finding is placental dysfunction or aneuploidy, specifically trisomy 21.

OC02.01: Performance of first trimester screening for Trisomy 21 in twin pregnancies

OC02.01: Performance of first trimester screening for Trisomy 21 in twin pregnancies

First trimester combined screening in patients with systemic lupus erythematosus: impact of pre-analytical variables on risk assessment

BackgroundPrenatal diagnosis of fetal trisomy 21 and other chromosomal abnormalities is based on invasive tests, such as amniocentesis and chorionic villus sampling, which are carried out in women identified through screening as being at high risk for these abnormalities. The most widely used method of screening is the first-trimester combined test which utilizes maternal age, and measurements of fetal nuchal translucency thickness (NT) and maternal serum pregnancy-associated plasma protein-A (PAPP-A) and free β-human chorionic gonadotropin (hCG).ObjectivesTo assess the influence of SLE on the levels of NT, PAPP-A, and β-hCG and whether any alterations in such levels may increase the rate of false positives and the subsequent number of invasive tests.MethodThis was a prospective first-trimester screening study for trisomies 21, 18, and 13 by a combination of maternal age, fetal nuchal translucency thickness, and serum PAPP-A and β-hCG at King’s College Hospital, London, between March 2006 and February 2011. The study population included 47 cases with maternal SLE and 45,493 without SLE. The results of biomarkers in the SLE and non-SLE groups were compared.ResultsIn the SLE group, compared to the non-SLE group, there were no significant differences in median maternal age, fetal NT, or serum PAPP-A MoM, but serum free β-hCG MoM was increased (1.402, IQR 0.872–2.290 vs 0.994, IQR 0.676–1.508).ConclusionIn first trimester screening for trisomies, the measured value of free ß-hCG should be adjusted for maternal SLE to avoid false positive results and overuse of invasive tests.

Maternal serum PlGF (placental growth factor) in Chinese women in the first trimester undergoing screening for Down syndrome

ObjectiveTo evaluate the potential of maternal serum placental growth factor (PlGF) as a marker for Trisomy 21 in Chinese pregnant women. Study designSerum samples were collected and stored from 600 women who have a viable singleton pregnancy and underwent first trimester screening for Trisomy 21 between 2011 and 2014. Serum concentration of PlGF was measured using the automated time-solved immunofluorometric assay and expressed as Multiples of the expected median (MoM) from the 600 women available stored serum samples (558 Euploidy and 42 Trisomy 21). The levels of PlGF MoM were compared between Trisomy 21 cases and Euploid pregnancies. Expected median PlGF levels in Chinese were also compared to that published for Caucasians. Multivariate Gaussian modeling was performed to predict detection and false-positive rates. ResultsIn euploid pregnancies the concentrations of PlGF increased with Crown Rump Length(CRL) and decreased with maternal weight. The overall median MoM of PlGF in Chinese was higher than that of Caucasian. The median PlGF level was 0.63 MoM in the cases and 1.00 MoM in the controls (p<0.0001). The prediction of Trisomy 21 has been slightly improved by the addition of PlGF to the standard screening test in China. The detection rate of screening after adding PlGF data was increased from 93.4% to 94.6% at a false-positive rate of 3% and the false positive rate decreased from 0.23% to 0.17% for a detection rate of 80%. ConclusionThe median PlGF concentrations in Chinese is higher than those of Caucasians. Results suggest adding PlGF may substantially improve the performance of current first trimester screening strategy for Trisomy 21 in Chinese pregnant women.

OC05.03: Preliminary results of contingent first trimester screening for Trisomy 21 with non‐invasive prenatal testing in a Danish cohort

OC05.03: Preliminary results of contingent first trimester screening for Trisomy 21 with non‐invasive prenatal testing in a Danish cohort

P14.10: Evaluation of PLGF on the first trimester of pregnancy on a Brazilian fetal medicine unit and its correlation to fetal birthweight and time of delivery

The aim of this study was to evaluate plasma levels of placental growth factor (PlGF) on the first trimester of pregnancy and its correlation to fetal birthweight and time of delivery. In order to validate the PlGF for clinical use on screening for pre-eclampsia on our fetal medicine unit, plasma levels of PlGF were determined by commercial Delfia-Xpress on a hundred random stored serum of patients screened for first trimester screening for trisomy 21 over the year of 2013.The serum concentration of PlGF were compared to fetal birthweight at delivery and gestational age of delivery. Plasma concentration of PlGF was available on 75 cases. Fetal births weigh and completed follow up obstetric history were available on 63 cases. All of these patients were normotensive during pregnancies. The median of plasma concentration was 30,9 pg/ml, the median for gestational age of delivery was 38,6 weeks and 3187 g for birth weigh. Considering only the normotensive pregnancies the PlGF concentration showed a positive increase with gestational age (r = 0,3865) but a slight positive correlation with fetal weight (r = 0,1441) and the gestational age of delivery (r = 0,1874). Serum PlGF concentration increases on the first trimester of pregnancy and showed a slight positive correlation with fetal birthweight and gestational age of delivery on normotensive pregnancies.

First trimester detection of trisomy 16 using combined biochemical and ultrasound screening

What's already known about this topic? Four previously reported cases of trisomy 16 have shown reduced levels of pregnancy‐associated plasma protein‐A during first trimester screening for trisomy 21. Isolated increases in free β human chorionic gonadotrophin and nuchal translucency were observed in these four cases.What does this study add? During first trimester screening for aneuploidy, we observed a further 28 cases of trisomy 16, all of which had reduced levels of pregnancy‐associated plasma protein‐A consistent with previous reported cases. Increased free β human chorionic gonadotrophin and increased nuchal translucency were not a consistent finding in our 28 cases.

OC05.05: The Danish Fetal Medicine Database: establishment and quality assessment of first trimester screening for trisomy 21 in the period 2008–2010

OC05.05: The Danish Fetal Medicine Database: establishment and quality assessment of first trimester screening for trisomy 21 in the period 2008–2010

P07.04: First trimester screening for trisomy 21 by maternal age, nuchal translucency and fetal nasal bone in 13,049 unselected pregnancies in Slovenia

P07.04: First trimester screening for trisomy 21 by maternal age, nuchal translucency and fetal nasal bone in 13,049 unselected pregnancies in Slovenia

OP07.04: Effect of bias in the CRL measurement on first trimester screening for trisomy 21

OP07.04: Effect of bias in the CRL measurement on first trimester screening for trisomy 21

Validation of First Trimester Screening for Trisomy 21 in Singapore with Reference to Performance of Nasal Bone

Introduction: The aim of this study is to describe the performance of first trimester screening (FTS) for trisomy 21 using maternal age, serum biochemistry and fetal nuchal translucency (NT) in a single center and to evaluate the effect of nasal bone on screening performance. Material and Methods: In 12,585 singleton pregnancies, the NT and nasal bone were examined. The majority of these mothers also had their serum biochemical markers analyzed. Risk was computed using different combinations of maternal age, biochemistry, NT and nasal bone. Down syndrome cases were confirmed by karyotyping. Results: There were 12,519 normal pregnancies, 31 with trisomy 21 and 35 with other chromosomal abnormalities. Without considering the nasal bone, the combined FTS detected 87.1% of trisomy 21 fetuses (false positive rate 5.1%), using 1:300 as the risk threshold, and this was further improved to 96.8% with the policy that classifies all fetuses with an absent nasal bone as high risk. Subgroup analysis showed that the detection rate would be 90.9%, with a false positive rate of 3.7%, if nasal bone was incorporated in the risk algorithm, compared to 81.8% and a false positive rate of 5.4% if it was not used. Discussion: FTS is very effective in early detection of trisomy 21 in Singapore. The nasal bone is a useful marker that can substantially improve the screening performance.

Chorangiocarcinoma of the placenta: A case report and clinical review

ObjectiveWe describe a case of chorangiocarcinoma, a complex lesion consisting of a trophoblastic proliferation within a chorangioma, presenting in a term placenta. Materials and methodsThe lesion was diagnosed by ultrasound at a second trimester check-up after amniocentesis, performed because of increased combined risk at first trimester screening for trisomy 21. After uncomplicated vaginal delivery, a healthy child was born and the placenta was expelled spontaneously. ResultsGross examination of the placenta showed a well-demarcated mass, bulging paracentrally from the fetal surface. Histology revealed a trophoblastic proliferation inside a chorangioma, consisting of multiple nodules with characters of focal multinucleation and pleomorphic cell nuclei, extensive central necrosis and high mitotic activity. Immunohistochemical staining showed strong intensity for hCG; Ki-67 (MIB-1) demonstrated a high proliferation index.Histopathological and immunohistochemical profile was compatible with a malignant trophoblastic proliferation. ConclusionsThis is only the fifth reported case of so-called “chorangiocarcinoma” of the placenta (Table 1). However, histopathologically only one reported case was identical to ours. A proliferation of atypical trophoblast was observed inside a chorangioma, which formed as it were a shield around the trophoblast. No extravascular stromal invasion was present. Follow-up revealed no metastases, either in the mother or the child, up to 3 months after birth.

Prediction of pre-eclampsia with PAPP-A and mean uterine artery pulsatility index (UTAPI) in first trimester

ObjectiveTo assess the association between pre-eclampsia (PE) and levels of PAPP-A and UtaPI in first trimester.MethodsRetrospective study of singleton pregnancies attending for first trimester screening for trisomy 21. PAPP-A was...

P17.06: Screening for trisomies and fetal anomalies in the second trimester after first trimester genetic scan. What are the benefits?

To investigate the performance of the first trimester screening for trisomies and also for fetal morphologic anomalies, and the performance of subsequent scanning in the second trimester. We performed a prospective study in singleton pregnancies, between 11 weeks 0 days and 13 weeks 5 days. The first trimester the genetic scan (247 cases) included measurement of NT, IT, the NB presence, the FMF angle, the tricuspid and DV Doppler, after FMF recommendations. All additional parameters were included in the combined test. At 16–19 weeks, the genetic sonogram included cardiac morphology. Complete evaluation was obtained at 165 (66.8%) cases. Just one major morphologic anomaly was discovered in the second scan. There were 2 cases of ventricular septal defects, a case of hipoplastic left heart syndrome and 1 case of unilateral arm lesion. In the first trimester, 16 (6.47%) pregnancies were included in the high risk group or in the intermediate risk (from 1 in 51 to 1 in 1000). Of all these cases, only 8 maintained soft markers for chromosomal anomalies in the second trimester. These patients were offered amniocentesis with QFPCR. In 6 cases trisomy 21 was confirmed. There was also a case of partial trisomy 13. It is likely that both trimester assessment could improve the detection rate for chromosomal anomalies, but it is cost effective low and time consuming. It must be established the importance of each additional markers in modifying the risk calculation, both in the first, and in the second trimester. Supporting information can be found in the online version of this abstract. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

The significance of fetal maxillary length in the first trimester screening for trisomy 21

The present study aims to specify the significance of fetal maxillary length by establishing a nomogram for a Turkish population and by investigating its relationship with the ultrasonographic and biochemical parameters which are commonly used to screen trisomy 21 in the first trimester of pregnancy. The present observational study investigates 1,308 Turkish women who had 11- to 14-week-old singleton healthy pregnancies. Fetal crown-rump length (CRL), nuchal translucency (NT), nasal bone length (NBL) and maxillary length are measured by ultrasonography and maternal serum concentrations of pregnancy-associated plasma protein-A (PAPP-A) and free beta-human chorionic gonadotropin (HCG) are determined. A positive and significant correlation was detected between the fetal maxillary length and gestational age (r = 0.309, P < 0.001) as was the case with fetal CRL (r = 0.357, P < 0.001) and NBL (r = 0.487, P < 0.001). Although there was a significant and positive correlation between fetal maxillary length and maternal serum PAPP-A levels (r = 0.201, P < 0.001), a significant and negative correlation was found between fetal maxillary length and the maternal serum concentrations of free beta-HCG (r = -0.238, P < 0.001). Fetal maxillary length increased in accordance with the advancing gestational age and increasing CRL. Maternal serum PAPP-A concentrations and fetal CRL and NBL were addressed as independent predictors of fetal maxillary length. The length of fetal maxillary bone is a promising biometrical parameter which can be reliably and efficiently used to screen trisomy 21 in first trimester. Fetal maxillary length is also found to correlate with gestational age, CRL, NBL and PAPP-A significantly. It would be rational to use a combination of nasal and maxillary bone length measurements in case serum concentrations of PAPP-A or beta-HCG cannot be assessed.