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Objective To provide data on how screen-positive and detection rates of first trimester prenatal screening for fetal Down syndrome vary with changes in the risk cut-off and maternal age to inform contingency criteria for publicly funded noninvasive prenatal testing. Materials and Methods First trimester screening and diagnostic data were collected for all women attending for first trimester fetal aneuploidy screening in Western Australia between 2005 and 2009. Prenatal screening and diagnostic data were linked to pregnancy outcomes, including data from the Midwives' Notification System and the Western Australian Registry of Developmental Anomalies. The prevalence of Down syndrome and performance of screening by risk cut-off and/or for women >35 years were analysed. Results The current screening risk cut-off of 1:300 has screen-positive and detection rates of 3.5% and 82%. The screen-positive rate increases by 0.7-0.8% for each 100 point change in risk, up to 19.2% at 1:2500 (96% detection rate). Including all women >35 years as screen positive would increase the screen-positive rate and detection rates to 30.2% and 97.2%. Conclusion Variation in screening risk cut-off and the use of maternal age to assess eligibility for noninvasive testing could significantly impact the demand for, and cost of, the test. A contingent first trimester screening approach for risk assessment is superior to the use of a combination of screening and maternal age alone. These data will inform decisions regarding the criteria used to determine eligibility for publicly funded noninvasive prenatal testing. [ABSTRACT FROM AUTHOR]

Résumé Objectif Évaluer les résultats du dépistage de la trisomie 21 par le risque combiné du 1 er trimestre (tel qu’il a été défini par l’arrêté du 23 juin 2009) dans la structure Prima facie. Méthodes Étude monocentrique portant sur l’ensemble des patientes ayant consulté à Prima facie avec une grossesse monofœtale évolutive, non issue de don d’embryon, entre le 1 er janvier 2009 et le 31 décembre 2014. Résultats Dix-huit mille deux cent cinquante-et-une patientes ont été incluses, parmi lesquelles 17 267 ont effectué le dépistage de la trisomie 21 par le risque combiné. Mille quarante-six de ces patientes (6,1 %) ont eu un risque supérieur à 1/250. Soixante-quinze fœtus étaient porteurs d’une trisomie 21, dont 65 dans le groupe à risque accru. La sensibilité et la spécificité du dépistage sont de 86,7 et 94,4 %. La médiane de la clarté nucale était de 0,98 MoM. Conclusions Le dépistage de la trisomie 21 par le calcul du risque combiné du 1 er trimestre a permis de dépister 86,7 % des trisomies 21 avec un taux de faux-positifs de 5,6 %. Objective To evaluate the results of screening for trisomy 21 by the combined risk of first trimester (as defined by the decree of June 23, 2009) in the Prima facie structure. Methods Single center study involving all patients that were seen for first trimester screening at Prima facie with singleton living pregnancy, not obtained by embryo donation, between 1 January 2009 and 31 December 2014. Results Eighteen thousand two hundred and fifty-one patients were included, of which underwent screening for trisomy 21 by the combined risk. One thousand and forty-six (6.1%) had a calculated risk higher than 1/250. Seventy-five were affected by trisomy 21, of whom 65 in the high risk group. The sensitivity and specificity of screening are 86.7% and 94.4%. The median nuchal translucency was 0.98 MoM. Conclusions Screening for trisomy 21 by calculating the combined risk of first trimester enabled to detect 86.7% of trisomy 21 with a false positive rate of 5.6%. [ABSTRACT FROM AUTHOR]

The objective was to determine the strength of relationship between maternal free beta human chorionic gonadotropin (β-hCG) concentrations and rates of adverse pregnancy outcomes. Consecutive records of the database of our Down screening project were assessed for free β-hCG levels and pregnancy outcomes. Pregnancies with foetal chromosomal or structural anomalies and those with underlying disease were excluded. Free β-hCG levels of < 0.5, > 0.5 and < 2.0, and ≥ 2.0 MoM were categorised as low, normal and high, respectively. Of 17,082 screened women, 13,620 were available for analysis. In the first trimester (n= 8150), low β-hCG levels significantly increased risk for intrauterine growth restriction (IUGR), preterm birth, low birth weight (LBW) and low Apgar score with relative risk of 1.66, 1.43, 1.83 and 2.89; whereas high β-hCG group had a significant decreased risk of preterm birth and GDM with relative risk of 0.73 and 0.62. In the second trimester (n= 5470), both low and high β-hCG groups had significant increased risks of the most common adverse outcomes, i.e. spontaneous abortion, IUGR and preterm birth. In conclusion, abnormally low (< 0.5MoM) or high (> 2.0 MoM) free β-hCG levels are generally associated with an increased risk of adverse pregnancy outcomes. Nevertheless, high free β-hCG levels in the first trimester may possibly decrease risk of preterm delivery and GDM. [ABSTRACT FROM PUBLISHER]

Objective To investigate whether first-trimester biochemical markers of placentation, including pregnancy-associated plasma protein-A (PAPP-A) and placental growth factor (PLGF), are altered in women that subsequently develop gestational diabetes mellitus (GDM) and to examine their potential value in improving the performance of screening for GDM by maternal characteristics and medical history. Methods The study population of 31,225 singleton pregnancies, including 787 cases that developed GDM, was drawn from women undergoing routine prospective screening for pregnancy complications at 11–13 weeks’ gestation. Maternal serum PAPP-A and PLGF were measured and the levels were expressed as multiples of the median (MoM) after adjustment for maternal characteristics and medical history. The performance of screening for GDM by maternal factors and MoM values of PAPP-A and PLGF was evaluated by receiver operating characteristic (ROC) curves. Results In the GDM group, compared to the unaffected group, the median PAPP-A was reduced (0.949, 95% CI 0.913–0.987 MoM) (p = 0.0009) and median PLGF was increased (1.053, 95% CI 1.023–1.083 MoM) (p = 0.004). The performance of screening for GDM by maternal factors was not improved by the addition of PAPP-A and/or PLGF. Conclusions First trimester maternal serum PAPP-A and PLGF are not useful in screening for GDM. [ABSTRACT FROM AUTHOR]

Objectives: To determine whether brachial artery flow-mediated dilation (FMD) assessed by ultrasonography during the late first trimester is able to predict the occurrence of hypertensive disorders during pregnancy. Methods: Maternal endothelial function was assessed by flow-mediated dilation (FMD) of the brachial artery in 487 pregnant women at 11-13+6 weeks' gestation. Subjects were prospectively followed and grouped according to the outcomes related to hypertensive disorders. We determined the areas under receiver operating characteristic (ROC) curve with their respective 95% confidence intervals (CI) for using low FMD results to predict the occurrence of hypertensive disorders during pregnancy. Results: Among 487 women, 9 (1.8%) were diagnosed with early-onset preeclampsia, 22 (4.5%) were diagnosed with late-onset preeclampsia, 47 (9.7%) developed gestational hypertension, and the remaining 409 (84%) pregnancies were unaffected by hypertensive disorders. Area under ROC curve analyses demonstrated that FMD was not able to predict pregnancies that developed hypertensive disorders. Conclusions: We conclude that FMD should not be considered a potential first-trimester marker of hypertensive disorders during pregnancy. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

ABSTRACT We present the nature of pathogenic SNP array findings in pregnancies without ultrasound ( US) abnormalities and show the additional diagnostic value of SNP array as compared with rapid aneuploidy detection and karyotyping. 1,330 prenatal samples were investigated with a 0.5-Mb SNP array after the exclusion of the most common aneuploidies. In 2.7% (36/1,330) of the cases, pathogenic chromosome aberrations were found; a microscopically detectable abnormality in 0.7% and a submicroscopic aberration in 2%. Our results show that in addition to the age- or screening-related aneuploidy risk, in pregnancies without US abnormalities, there is a risk of 1:148 (9/1,330) for a (sub)microscopic abnormality associated with an early-onset often severe disease, 1:222 (6/1,330) for a submicroscopic aberration causing an early-onset disease, 1:74 (18/1,330) for carrying a susceptibility locus for a neurodevelopmental disorder, and 1:443 (3/1,330) for a late-onset disorder (hereditary neuropathy with liability to pressure palsies in all three cases). These risk figures are important for adequate pretest counseling so that prospective parents can make informed individualized choices between targeted prenatal testing and broad testing with SNP array. Based on our results, we believe if invasive testing is performed, SNP array should be the preferred cytogenetic technique irrespective of the indication. [ABSTRACT FROM AUTHOR]

INTRODUCTION First trimester screening (FTS) is a validated screening tool that has been shown to achieve detection rates of 84%-90% for trisomies 21, 18 and 13. However, its effectiveness for different maternal ages has not been assessed. The present study aimed to assess the performance of FTS in an Asian population, and to compare its effectiveness in older (= 35 years) and younger (< 35 years) women. The potential use of noninvasive prenatal test (NIPT) as a contingent screening test is also examined. METHODS Data on cases of FTS performed on singleton pregnancies over a six-year period was collated from two Singapore maternal centres, National University Hospital and Singapore General Hospital. Cases that had a 1:250 risk of trisomy were considered to be screen-positive. Pregnancy outcomes were obtained from birth records or karyotype test results. RESULTS From 10,289 FTS cases, we obtained a sensitivity of 87.8%, a specificity of 97.6%, a false positive rate of 2.4% and a false negative rate of 0.06% for the detection of aneuploidy. The overall detection rate for trisomy 21 was 86.5%-85.7% for older women and 87.5% for younger women. The mean number of invasive tests required per case of trisomy 21 was 9.3 in younger women, 8.6 in older women and 13.5 in women with intermediate risk (1:250-1,000). CONCLUSION While the performance of FTS was similar in younger and older women, more invasive procedures were required to diagnose trisomy 21 in women with intermediate risk. It may be advantageous to offer contingent NIPT to this group of women to reduce the risk of iatrogenic fetal loss. [ABSTRACT FROM AUTHOR]

Objective: In this study, we aimed to evaluate the distribution and mean values of fetal nuchal translucency (NT) in singleton pregnancies with low risk in Manisa city. It was also aimed to evaluate relationship between NT values and week of gestation, crown-rump length (CRL), parity and maternal weight. Methods: A total of 351 singleton pregnancy cases who admitted to our perinatology clinic in between March 2013 and May 2014 for screening at 11-14 weeks of gestation were included in the study. Fetal NT, CRL measurements, week of gestation, maternal weight and parity were evaluated. Three hundred and fifty-one cases that were included in the study were separated into four groups according to their CRL measurements: Those with CRL between 45 and 54 mm were determined as Group 1 (n=62), those with CRL between 55 and 64 mm were determined as Group 2 (n=133), those with CRL between 65 and 74 mm were determined as Group 3 (n=115), and those with CRL between 75 and 84 mm were determined as Group 4 (n=41). The groups were compared in terms of maternal age and mean NT value. Results: Mean age of the cases was 28.76±5.51, mean week of gestation was 12.29±0.69, mean CRL value was 63.69±9.07 mm, and mean NT value was 1.23±0.48 mm. No significant difference was observed among the groups in terms of maternal age and NT measurement (p=0.817 and 0.072, respectively). In the correlation analysis, it was seen that NT value was significantly correlated with CRL (r=0.232; p=0.001) and week of gestation (r=0.203; p=0.001) statistically. No relationship was found between NT and gravida, parity and maternal age. Conclusion: First trimester screening is a method becoming more common in terms of prenatal diagnosis. Fetal NT is a part of this screening procedure. Fetal NT measurement should be carried out in accordance with the standards and pregnancy management should be planned according to the algorithms. [ABSTRACT FROM AUTHOR]

Objective: To assess the possible changes in first trimester screening test parameters in pregnancies complicated with placenta previa and to determine whether there is an association between hyperemesis gravidarum and placenta previa. Material and Methods: A total of 131 singleton spontaneously conceived pregnancies that were complicated by placenta previa and delivered between May 2006 and May 2013 were evaluated from birth charts. Ninety patients without placenta previa were selected amongst patients who delivered within the same period of time as the control group. Cases of low lying placenta (n=52) within the study group were assessed as a separate group. The rest of the cases was considered to be in a different group. Results: Beta human chorionic gonadotropin (BhCG) multiples of medians (MoMs) and nuchal translucency (NT) MoMs were significantly higher in the placenta previa group in comparison with the low lying placenta and control groups. Apgar scores at both the 1st and 5th minutes were significantly lower in the placenta previa group. Hyperemesis gravidarum was found to be significantly more frequent in the placenta previa group. Conclusion: The prevalence of hyperemesis gravidarum in the first trimester is higher in pregnancies complicated by placenta previa. Paying more attention to the development of placenta previa in the routine pregnancy follow-up of patients with hyperemesis gravidarum could be considered. [ABSTRACT FROM AUTHOR]

Copyright of Medizinische Genetik is the property of De Gruyter and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective To examine maternal serum concentrations of placental growth factor (PlGF) at 11–14 gestational weeks in pregnancies that developed gestational diabetes mellitus (GDM) and to create first trimester prediction models for GDM. Methods Case control study including 40 GDM cases and 94 controls. PlGF, biophysical and biochemical markers and maternal–pregnancy characteristics were analyzed. Results Log 10 transformed PlGF (log 10 PlGF) was not related to maternal factors. Log 10 PlGF was increased (p = 0.008) in the GDM group compared to the control group. Log 10 PlGF was associated with fasting glucose levels (p = 0.04) in the oral glucose tolerance test. Log 10 PlGF had a strong relation with birth weight adjusted for gestational age in the control but not in the GDM group. Maternal weight and maternal age were the only predictors of GDM among the maternal factors [area under the curve (AUC) = 0.73, p < 0.001]. Log 10 PlGF alone was a significant predictor of GDM (AUC = 0.63, p < 0.001). Combination of maternal weight, maternal age and log 10 PlGF resulted in an improved prediction (DR = 71.4%, for 25% FPR, AUC = 0.78, Model R 2 = 0.17, p < 0.001). Conclusion At 11–14 weeks in pregnancies that develop GDM, the maternal serum levels of PlGF are increased. Measurement of serum PlGF at 11–14 weeks improves the performance of early screening for GDM provided by maternal factors alone. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study is to investigate the predictive value of low levels of pregnancy associated plasma protein-A (PAPP-A) during the first trimester on adverse pregnancy outcomes, namely pregnancy induced hypertension (PIH), preeclampsia (PE), intrauterine growth restriction (IUGR), and fetal loss., Methods: This is a prospective cohort study including 2636 women with singleton pregnancies that attended the Prenatal Diagnosis Unit of the First Department of Obstetrics and Gynecology of National and Kapodistrian University of Athens in "Alexandra Hospital" between 2017 and 2019 for the first trimester combined screening routine scan. The study population was divided into two groups according to their PAPP-A levels. The cut-off value of the PAPP-A level was defined as the 0.4 multiple of median (MoM) which is in correspondence with the fifth centile. The women were followed-up prospectively until delivery and the primary outcome measures were the incidence of PIH, PE, IUGR (<10th centile), and fetal loss.  Results: PAPP-A levels of ≤0.4 MoM were associated with increased maternal body mass index (BMI), increased uterine arteries pulsatility index (PI), and lower birth weight. Women with PAPP-A levels ≤0.4 MoM were more likely to develop PE (2.3% vs. 0.2%, p<0.001), PE or PIH (2.3% vs. 0.4%, p=0.003), IUGR (2.3% vs. 0.4%, p=0.003), and combined adverse outcome (25.5% vs. 1.9%, p<0.001) compared to women with PAPP-A>0.4 MoM., Conclusions: This study confirms that among women with PAPP-A levels ≤0.4 MoM in the first trimester, there are increased odds for PE or PIH, IUGR, and combined composite pregnancy outcome., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Papamichail et al.)

Introduction: First trimester screening by dual test is the most preferred method of antenatal screening. The detection rate of foetal aneuploidy using dual test is 95%. This test uses maternal serum free ß human Chorionic Gonadotropin (free ß hCG) and Pregnancy Associated Plasma Protein A (PAPP-A) along with maternal demographic and foetal sonographic indices to calculate risk for foetal aneuploidy. PAPP-A is a zinc binding metalloproteinase which is also responsible for placental development and foetal growth. So, zinc might also have some role in first trimester screening. No studies are available substantiating the role of zinc in first trimester screening. Aim: To measure and correlate maternal serum zinc with PAPP-A and calculated risk ratio of first trimester screening. Materials and Methods: PAPP-A and zinc were measured from the serum of 84 pregnant women aged 20-40 years in 11th-13th weeks+6 days of gestation who underwent dual test during their antenatal check-up. Risk calculation was done using Screening Software for Downs Windows Lab (SSDWL). Results: Maternal serum PAPP-A showed a significant positive correlation with maternal serum zinc (p-value <0.001). Maternal serum PAPP-A and zinc both showed a significant positive correlation with calculated risk ratio (p-value<0.01). Conclusion: As PAPP-A is a zinc binding metalloproteinase, zinc showed significant pattern of correlation with aneuploidy risk as shown by PAPP-A. So there could be a possible role for serum zinc in first trimester of screening. [ABSTRACT FROM AUTHOR]

Objective: To assess 2D and 3D frontomaxillary facial angle (FMFA) measurements in euploid and trisomy 21 fetuses. Materials and Methods: Over a 2-year period, women with singleton pregnancies attending a private prenatal screening and diagnosis practice in Sydney, Australia, were invited to participate in this study where 2D images and 3D volumes of the fetal face were collected during routine first trimester screening. In pregnancies where trisomy 21 was confirmed, FMFA measurements were performed in 2D and 3D and compared with those from a euploid cohort. Results: Overall, 250 women carrying euploid and 22 women carrying trisomy 21 fetuses participated. Trisomy 21 fetuses had significantly larger FMFA measurements than euploid fetuses in both 2D and 3D assessments. 95% of 3D and 100% of 2D FMFA measurements for the trisomy 21 fetuses were above the mean FMFA measurement of the euploid fetuses. There was no relationship between increasing crown-rump length and FMFA measurement. Conclusion: 2D and 3D FMFA measurements in trisomy 21 fetuses are statistically greater (p < 0.001) than those in euploid fetuses. This supports FMFA as a possible additional marker for trisomy 21 for first trimester screening. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objectives: to assess the performance of a combined first-trimester screening for trisomy 21 in an unselected Italian population referred to a specialized private center for prenatal medicine. Methods: a retrospective validation of firsttrimester screening algorithms [risk calculation based on maternal age and nuchal translucency (NT) alone, maternal age and serum parameters (free β-hCG and PAPP-A) alone and a combination of both] for fetal aneuploidies evaluated in an unselected Italian population at Artemisia Fetal-Maternal Medical Centre in Rome. All measurements were performed between 11+0 and 13+6 weeks of gestation, between April 2007 and December 2008. Results: of 3,610 single fetuses included in the study, we had a complete follow-up on 2,984. Fourteen of 17 cases of trisomy 21 were detected when a cut-off of 1:300 was applied [detection rate (DR) 82.4%, 95% confidence interval (CI) 64.2-100; false-positive rate (FPR) 4.7%, 95% CI 3.9-5.4; false-negative rate (FNR) 17.6%, 95% CI 0-35.8%]. Conclusion: in our study population the detection rate for trisomy 21, using the combined risk calculation based on maternal age, fetal NT, maternal PAPP-A and free β-hCG levels, was superior to the application of either parameter alone. The algorithm has been validated for first trimester screening in the Italian population. [ABSTRACT FROM AUTHOR]

We report on our experience of studying amniotic fluid cells by cytogenetic analysis (CA) of the first 2 clones. We investigated the incidence and types of chromosome aberrations detected by CA of 196 amniocenteses performed on pregnant women at high risk. Of these cases, 178 were analysed by QF-PCR (risk group A). The results were compared with the data obtained by CA of 1,263 amniocenteses carried out in patients with other indications. QF-PCR was used to investigate 1,030 of these cases (risk group B). The combined average turnaround time for a CA result of the first 2 clones in both risk groups was within 9 ± 2 days. The final CA results (≥6 clones) were obtained within 12 ± 4 days. In risk group A, CA was not possible in 2 cases due to cell culture failure. The foetal karyotype was abnormal in 13.8% of the cases by CA of ≥6 clones and in 13.5% of the cases by QF-PCR. Together, CA of ≥6 clones and QF-PCR detected chromosome aberrations in 14.8% of the cases. With the exception of 2 cases of in vitro culture failure and 1 case with low gonosomal mosaicism, CA of the first 2 clones detected all cases with chromosome aberrations. Five cases with clinically significant chromosome aberrations were not detected by QF-PCR. In risk group B, the foetal karyotype was found to be abnormal in 2.2% of the cases by CA of ≥6 clones and in 1.0% of the cases by QF-PCR. Together, CA of ≥6 clones and QF-PCR revealed chromosome aberrations in 2.2% of the cases. With the exception of 1 case with low gonosomal mosaicism, CA of the first 2 clones detected all other cases with chromosome aberrations. The majority of these cases were inherited chromosome aberrations. Eighteen cases with chromosome aberrations were not detected by QF-PCR. Based on our results, CA of ≥6 clones, together with QF-PCR as a first test, should be performed in all prenatal cases with abnormal ultrasound findings. In pregnancies with other indications, CA of the first 2 clones alone is sufficient to identify all clinically significant (and inherited) chromosome aberrations. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Summary: There have been tremendous advancements over the past three decades in prenatal screening for aneuploidy and we have changed our practice from screening by maternal age alone to ‘combined’ first trimester screening and circulating cell-free fetal DNA. We currently use the nuchal translucency and biochemical markers of free β-hCG and PAPP-A to determine the risk of fetal aneuploidy. The primary goal is to identify higher risk women for fetal aneuploidy early in pregnancy and give them the option to pursue invasive testing in a timely manner if desired. [Copyright &y& Elsevier]

Background: The aim of this study was to compare pregnancy-associated plasma protein A (PAPP-A) and the β-subunit of human chorionic gonadotropin (hCGβ) measured in maternal plasma at the first trimester screening, in women who later developed early or late pre-eclampsia (PE) to women with normal pregnancies. Methods: In the study were included 161 cases with PE and 88 controls with uncomplicated pregnancies. Plasma PAPP-A and hCGβ were measured between gestational age (GA) 8+2 and 14+0, and cases with early and late onset PE were compared with controls. Results: Median of hCGβ (MoM) was lower in women with early (p<0.05) and late PE (p<0.05) compared to healthy pregnant women. Median (range) of hCGβ (MoM) for women with early onset PE, late onset PE, and women with healthy pregnancies, were 0.75 (0.30-1.21), 0.93 (0.26-3.18), and 0.97 (0.33-4.12), respectively. No significant difference in the median of PAPP-A (MoM) was found between the groups. Conclusions: hCGβ was significantly lower in pregnancies that subsequently developed PE and might be of use in the effort of trying to find ways to predict PE. No significant difference was found for PAPP-A in our study. [ABSTRACT FROM AUTHOR]

Copyright of Ginecología y Obstetricia de México is the property of Federacion Mexicana de Ginecologia y Obstetricia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: We investigated the prognostic relevance of ultrasound visibility of distendend jugular lymphatic sacs (JLS) in fetuses with aberrant karyotypes in First-trimester-screening. Furthermore we tried to differentiate between increased nuchal translucency (NT) and cystic hygroma colli. Methods: We performed a retrospective single center study in 1874 patients presenting for First-trimester-screening between 2009 and 2013. All fetuses with an abnormal risk calculation and NT > 2.5 mm (95th percentile) were reviewed for ultrasound visibility of JLS. A group of 30 fetuses with normal risk calculation served as control. Karyotyping was performed by chorionic-villi-sampling or amniocentesis, respectively. Results: In a total of 2030 fetuses 70 (3.44%) with pathologic first-trimester-screening results showed either aberrant karyotypes or severe ultrasound pathologies. Main aberrant karyotypes were trisomy 21 (25), trisomy 18 (16), trisomy 13(six), Monosomy X (four), 47, XYY or 47, XXX (three) and Noonan' syndrome (two). Distended JLS were visible in 47% of all cases. Statistical anaylsis found a significant correlation between NT and JLS size for the fetuses with trisomies 21, 18 and 13 ( r = 0.53, p < 0.002). Cystic hygroma colli was present in all Turner and Noonan syndromes. Conclusions: Distended JLS have a strong correlation with abnormal karyotypes and increased nuchal translucency. Karyotyping should be offered in these cases. [ABSTRACT FROM AUTHOR]

Background The aim of this study is to validate the Fetal Medicine Foundation ( FMF) multiple logistic regression algorithm for prediction of risk of pre-eclampsia in an Australian population. This model, which predicts risk using the population rate of pre-eclampsia, a variety of demographic factors, mean maternal arterial blood pressure ( MAP), uterine artery PI ( UtA PI) and pregnancy-associated plasma protein A ( PAPP- A), has been shown to predict early-onset pre-eclampsia (delivery prior to 34 weeks) in 95% of women at a 10% false-positive rate. Methods All women who attended first trimester screening at the Royal Prince Alfred Hospital had their body mass index ( BMI), MAP and UtA PI assessed in addition to factors traditionally used to assess aneuploidy (including PAPP- A MoM). After delivery, risks of early-onset (delivery prior to 34 weeks) pre-eclampsia, late pre-eclampsia and gestational hypertension were calculated using the FMF risk algorithm. Results A total of 3099 women were screened and delivered locally. 3066 (98.9%) women had all data to perform pre-eclampsia screening available. This included 3014 (98.3%) women with a live birth, where risks of early pre-eclampsia were calculated. Twelve women were delivered before 34 weeks because of early pre-eclampsia with a prevalence of early pre-eclampsia of 1 in 256 pregnancies. Risks generated through the use of maternal history, MAP, UtA PI and PAPP- A detected 41.7 and 91.7% of early pre-eclampsia at a false-positive rate of 5 and 10%, respectively. Conclusions This study shows that the FMF early pre-eclampsia algorithm is effective in an Australian population. [ABSTRACT FROM AUTHOR]

Aim The aim of this retrospective study was to investigate the relation between perinatal complications in twin pregnancies and the combination of first-trimester maternal serum pregnancy-associated plasma protein- A ( PAPP- A) and free beta-human chorionic gonadotrophin (β- hCG) levels. Material and Methods The study was conducted at the Perinatology Department of Baskent University between January 2005 and December 2011. In total, 104 patients with twin pregnancies were recruited. The association of first-trimester maternal serum-screening markers with perinatal complications was investigated for small-for-gestational-age ( SGA) fetuses or intrauterine growth restriction ( IUGR), preterm delivery (before 34 weeks of gestation), pregnancy-induced hypertension ( PIH), and growth discordance between fetuses. Results Low serum PAPP- A (below 10th percentile) levels were not correlated with preterm labor, PIH, or IUGR in twin gestations. Elevated free β- hCG levels (>90th percentile) were linked to increased rates of PIH and small-for-gestational-age fetuses or IUGR. Conclusion Elevated first-trimester free β- hCG was related to adverse pregnancy outcomes in twin pregnancies, whereas low PAPP- A levels were not linked to adverse pregnancy outcomes. [ABSTRACT FROM AUTHOR]

Objectives: To find the best early predictor model for fetal growth and large for gestational age (LGA) infants considering clinical, ultrasonographic and biochemical variables. Method: In 2097 singleton pregnancies at first trimester, we evaluated maternal characteristics, PAPP-A and ß-HCG proteins, fetal nuchal translucency thickness and uterine artery pulsatility index (UtA-PI). At second trimester fetal ultrasound biometry and UtA-PI were then measured. The relationships between birth weight and LGA and maternal characteristics, first and second trimester variables, and all variables combined, were studied. The performance of screening was determined by receiver operating characteristic curves analysis. Results: Stepwise regression analysis showed that in the prediction of birthweight percentile there were significant contributions from all maternal factors, PAPP-A and Ut-A PI in the first trimester, and fetal biometric variables in the second trimester. Maternal charateristics combined with PAPP-A, β-hCG, fetal NT and uterine artery PI identified 30.2 % LGA (FPR 10%). The combined model reached a sensitivity of 41.2% (FPR 10%) and 56.2% (FPR 20%). Conclusions: Sensitivity of the screening for LGA improves significantly after addition of second trimester ultrasound measurements to first trimester variables and maternal characteristics. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate different cut-off values of first trimester pregnancy associated plasma protein-A (PAPP-A) in screening for adverse pregnancy outcomes in a retrospective cohort study., Methods: During the study period of 1.1.2014-31.12.2018, total of 23,482 women with singleton pregnancies participated in first trimester combined screening for chromosomal abnormalities. Maternal serum PAPP-A multiple of medians (MoM) levels were measured, and study population was divided into three study groups of PAPP-A ≤0.40 (n=1,030), ≤0.35 (n=630) and ≤0.30 (n=363) MoM., Results: Small for gestational age (SGA), preterm birth (PTB) and composite outcome (SGA, hypertensive disorder of pregnancy (HDP) and/or PTB) were more frequent in all three PAPP-A MoM study groups and pre-eclampsia in ≤0.40 and ≤0.35 study groups than in their control groups (p < 0.05). The odds ratio (OR) for SGA varied from 3.7 to 5.4 and sensitivity and specificity from 6.9 to 13.8% and from 95.9 to 98.6%, between study groups. Using PAPP-A ≤0.30 MoM as a screening cut-off instead of PAPP-A ≤0.40 MoM, resulted in approximately 50% reduction in screening detection of SGA and PTB., Conclusions: PAPP-A ≤0.40 MoM should be considered as a primary screening cut-off for adverse pregnancy outcomes as approximately 23% will develop either SGA, HDP or PTB. It seems to be the best cut-off to screen for SGA., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)

Objective To investigate the uptake of different components of first trimester screening (FTS) and the impact on invasive diagnostic testing (IPT) since the introduction of non-invasive prenatal testing (NIPT) at a level III center. Methods Retrospective data analysis was conducted for singleton pregnancies that presented for FTS between 01/2019-12/2019 (group 1, n = 990). Patients were categorized into three risk groups: low risk for trisomy 21 (< 1 : 1000), intermediate risk (1 : 101-1 : 1000) and high risk (≥ 1 : 100). Uptake of NIPT and IPT was analyzed for each of the risk groups. Results were compared to a previous cohort from 2012/2013 (immediately after the introduction of NIPT, group 2, n = 1178). Results Group 1 showed a significant increase in the use of NIPT as part of FTS (29.5% vs. 3.7% for group 2, p = 0.001) in all three risk groups. Overall IPT rates were lower in group 1 (8.6%) vs. group 2 (11.3%, p = 0.038), mainly due to a significant reduction of IPT in the intermediate risk group. IPT rates in the high-risk group remained stable over time. Conclusion Appropriate clinical implementation of NIPT is still currently a challenge for prenatal medicine experts. Our data suggest that widespread uptake of NIPT is becoming more common these days; however, a contingent approach might prevent redundant uptake., Competing Interests: Conflict of Interest The authors declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Abstract: Aims: To assess pregnancy-associated plasma protein A (PAPP-A) correlation with GDM and its usefulness in predicting GDM in primiparous women. Methods: First trimester data related to 307 pregnant women affected by GDM and 366 control pregnant women were retrieved from a computer data base and integrated with ad hoc data. Clinical data were recorded at delivery. A logistic model was used to analyze the association between first trimester data and subsequent clinical outcomes. We derived a risk score using both classical risk factors for GDM and PAPP-A. Results: Diabetic and control women were significantly different in terms of age (p <0.001), BMI (p <0.001), weight (p <0.001), family history of diabetes (p <0.001), PAPP-A concentration and PAPP-A corrected multiple of the median (MoM) (p <0.001). The ROC-AUC of the clinical risk score was 0.60 (95%CI 0.56–0.64), the adjusted score including PAPP-A MoM was 0.70 (95%CI 0.66–0.74). Conclusions: Low PAPP-A was strongly associated with GDM and lower values were found in diabetic women needing insulin therapy. Adding PAPP-A to first trimester screening could improve the prediction of women at high risk who will develop GDM. Further studies are needed to validate the applicability of our findings in different populations and settings. [Copyright &y& Elsevier]

In this study, we investigated whether the concentrations of pregnancy-associated plasma protein-A (PAPP-A) or free β-hCG (fβhCG) in the first trimester can identify women at increased risk of subsequent preterm delivery in the absence of hypertensive disorders. Preterm and early preterm deliveries are defined as those deliveries before completing 37 and 34 weeks, respectively. A total of 868 women were enrolled into this study. According to the level of the markers, the patients were evaluated in three groups: 1 - maternal serum level ≤5th percentile, 2 - between 5th and 95th percentiles, 3 - ≥95th percentile. In the group of patients with a PAPP-A level ≤5th percentile [≤0.35 multiples of the median (MoM)], mean gestational age (GA) at delivery, mean birth weight and the number of the cases with early preterm delivery were significantly lower than the others. Mean level of PAPP-A was significantly lower in cases with early preterm than term deliveries (0.58 ± 0.32 versus1.09 ± 0.69; p = 0.01). Maternal serum level of fβhCG did not show significant difference between these groups (0.84 ± 0.45 versus 1.17 ± 0.77; p = 0.15). Low levels of maternal serum PAPP-A (≤0.35 MoM) (Odds ratio = 7; 95% confidence interval 1.8-27.7; p = 0.0048) significantly predicted early preterm delivery in normotensive pregnancies. Women with low levels of PAPP-A at first trimester have a higher risk of early preterm delivery even in the absence of hypertensive disorders. [ABSTRACT FROM AUTHOR]

This review of literature describes the first-trimester nuchal translucency (NT) which forms the basis of new form of screening which can lead to a significant improvement in detection of congenital anomalies as compared to second trimester screening programs, the so called genetic-sonogram. A growing body of evidence-based studies has demonstrated that fetal NT can be a powerful prenatal screening tool and combined with first trimester serum markers, it can be incredibly promising in near future. It should be expressed as Multiple of median (MoM) and maintained and monitored like any laboratory analyte. The aim of this review was to investigate the different hypotheses on the aetiology of increased NT. Using a computerized database (PubMed), articles on the aetiology of first-trimester NT were retrieved. Furthermore, the cited references of the retrieved articles were used to find additional articles. Based on ultrasonography, the associations of increased NT fetuses are described in relation with Down syndrome, Cardiac anomalies, and a diverse range of other anomalies. The review concludes that first trimester NT ultrasound has the potential to be used as an important tool for the detection of various congenital abnormalities and an early management can be implemented to reduce the mental trauma of expecting mothers by proper counseling and early diagnosis. For the precise measurements, it should be implemented in a meticulous and coherent manner. [ABSTRACT FROM AUTHOR]

Objectives: The intention of this study is to analyze the impact of the single parameters NT, PAPP-A and free β-hCG used in combined first trimester screening and to determine their contribution in the risk assessment. Methods: A retrospective risk assessment on the advanced first trimester screening (AFS) algorithm was made to determine the effect of a particular parameter while the remaining ones were fixed for calculation. Afterward data were recalculated by the AFS module. Test performance was measured by receiver operating characteristics (ROC) curves and their area under curve (AUC). Results: Among the 14,862 cases are 14,748 healthy fetuses, 86 with trisomy 21, 22 with trisomy 18 and 6 with trisomy 13. Some settings obtain at default cut-off a very high sensitivity. However, a lack of specificity, as a high false-positive rate, too. The ROC analysis was best for NT, followed by PAPP-A. Free β-hCG showed the lowest AUC. Combining PAPP-A and free β-hCG offered a better AUC than each parameter alone. Best test performance was obtained by including all three parameters. Discussion: A detection rate of 69 % for testing NT discretely is in order with present study data. PAPP-A is following and free β-hCG is not useful with a test positive rate of about a third. The detection rate of the biochemical parameters combined is higher than for NT alone, but results in a five times higher punctuation rate. All parameters together in the AFS provide the best test performance. The impact of each parameter NT, PAPP-A and free-β-hCG in a combined test strategy is nearly a third. Thus, every single parameter is needed to provide a high detection rate for all of the trisomies and minimize the number of unnecessary invasive diagnostics. [ABSTRACT FROM AUTHOR]

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Objective: To screen for chromosomal defects on the basis of maternal age and fetal nuchal translucency thickness at 10 to 14 weeks of gestation. Method: Fetal nuchal translucency thickness was measured by ultrasound examination at 10-14 weeks of gestation in living singleton pregnancies in women attending routine antenatal care at Prince Ali Bin Hussein. Amman Jordan. The risks for trisomy 21 and other chromosomal defects by ultrasound measurment of fetal nuchal translucency thickness and maternal age were calculated, using the software provided by The Fetal Medicine Foundation. Results: Chromosomal defects were diagnosed in 10 cases, including 4 cases of trisomy 21 and 6 cases with other chromosomal abnormalities (trisomy 18, 13, triploidy, Turner). The estimated risk based on maternal age and fetal NT was 1 in 300 .Conclusion: The combination of maternal age and fetal nuchal translucency thickness was an effective method of screening for chromosomal defects. [ABSTRACT FROM AUTHOR]

Objective: To compare the predictive performance for preterm-pre-eclampsia (PE) in first-trimester screening by serum placental growth factor (PlGF) versus pregnancy associated plasma protein-A (PAPP-A), in combination with maternal risk factors, mean arterial pressure (MAP) and uterine artery pulsatility index (UtA-PI), after adjustment for the effect of aspirin in women receiving this treatment., Design: Non-intervention multicentre screening studies for PE in singleton pregnancies., Setting: Maternity hospitals., Population: Two independent prospective studies of 8775 and 16 451 women with singleton pregnancies attending for routine assessment at 11 +0 -13 +6 weeks' gestation., Methods: The competing risks model was used to estimate patient-specific risks of delivery with PE at <37 weeks' gestation based on maternal risk factors and combinations with MAP, UtA-PI and either PlGF or PAPP-A. McNemar's test was used to compare the detection rate (DR) of preterm-PE of screening utilising PlGF versus PAPP-A, after adjustments for the effects of aspirin., Main Outcome Measure: Predictive performance for preterm-PE., Results: In the combined data of 25 226 women, including 678 (2.7%) who developed PE, there were 194(0.8%) with preterm-PE. Addition of PlGF improved the DR of preterm-PE, at 10% screen positive rate, by 18.4% (95% CI 12.2-24.6) in screening by maternal risk factors, by 19.9% (95% CI 13.6-26.2) in screening by maternal factors and MAP, and by 7.0% (95% CI 2.3-11.6) in screening by maternal factors, MAP and UtA-PI. PAPP-A did not significantly improve the DR provided by any combination of biomarkers., Conclusion: The predictive performance of first trimester PlGF for preterm-PE is superior to that of PAPP-A., (© 2022 John Wiley & Sons Ltd.)

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. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to evaluate population parameters (medians, standard deviations and coefficients of correlation) different from those used by the commercial software Elipse® v3.0 (Perkin Elmer) in the calculation of prenatal risk of trisomy 18. Moreover, the truncation limits used for extreme values of free β-human chorionic gonadotropin (fβ-hCG), pregnancy associated plasma protein-A (PAPP-A) and nuchal translucency (NT) were revised. Methods: A calculation engine for the prenatal risk of trisomy 18 was developed [called FMF (Fetal Medicine Foundation) calculator]. Recently, published population parameters for fβ-hCG and PAPP-A as well as new truncation limits were included in this calculator. The patient-specific risks obtained by Elipse® v3.0 and FMF calculators, were compared in 18,801 pregnant women, including 13 cases of trisomy 18, four cases of trisomy 13 and one case of triploidy. Results: Using a cut-off point of 1:250, FMF calculator increased the detection rate of trisomy 18 from 62% to 100% with a 0.31% increase in the false-positive rate (FPR). When the detection rate was fixed at 100%, the FPR generated by Elipse v3.0 (1.52%) was significantly higher (p<0.0001) than that generated by the FMF calculator (0.36%). Moreover, an improved detection in cases of trisomy 13 and triploidy was observed. Conclusions: It is recommended that each laboratory reviews the population parameters and truncation limits used in the risk calculation of trisomy 18, in order to obtain an adequate performance in the screening. [ABSTRACT FROM AUTHOR]

Objective: To evaluate whether gestational diabetes mellitus (GDM) requiring insulin treatment (White's classification A2) is associated with an alteration of pregnancy-associated plasma protein-A (PAPP-A) serum levels at first-trimester screening between 11 and 14 weeks of gestation. Methods: We collected data (2007-2010) of all women who developed GDM requiring insulin treatment and completed first-trimester combined screening program including the determination of serum PAPP-A and free β-human chorionic gonadotropin (β-hCG). A total of 288 women were included in this study. Each of the 72 women who developed GDM was matched with three unaffected controls. Results: Women with GDM were significantly older (34.2 ± 5.9 vs. 32.3 ± 5.5 years, P = 0.007) and delivered significantly earlier (38.40 ± 2.25 vs. 39.1 ± 2.2 gestational weeks, P = 0.01). Multiple regression analysis revealed, that PAPP-A and β-hCG were independently associated with each other ( P = 0.04) but there was no association between GDM/no GDM and the first-trimester serum markers ( P = 0.77). Conclusion: Our data suggest that women who are developing GDM needing insulin treatment do not have altered PAPP-A levels at 11-14 weeks. [ABSTRACT FROM AUTHOR]

Objective: To describe early ultrasound findings in Meckel-Gruber syndrome (MKS) in first and second trimester of three families, detailed ultrasound findings have been documented in addition to pathoanatomical findings and results of DNA studies. A splice site mutation in the MKS4 gene could be detected. Clinical management accounting risk assessment for future pregnancies is discussed and early ultrasound markers in MKS are described. Methods: All cases were examined in a tertiary center for prenatal diagnosis by ultrasound. Necroscopy confirmed the clinical diagnosis. Fetal DNA analysis was accomplished in a reference center for MKS. In addition, ultrasound findings in early pregnancy of two further cases are described. Results: Three couples presented with pregnancies complicated by MKS. The earliest diagnosis was suspected in 11 + 6 weeks of gestation and was confirmed in 13 + 0 weeks by ultrasound revealing a large occipital encephalocele and polycystic kidneys. Another case with recurrent MKS in two consecutive pregnancies was diagnosed in 20 weeks and 14 weeks of gestation, respectively. Here a close molecular genetic follow-up was performed leading to the detection of two mutations in the MKS4 gene in both fetuses. The third case was diagnosed in 15 weeks of gestation. Ultrasound findings in all pregnancies were doubtless and autopsies confirmed the diagnosis. Conclusion: Detection of MKS is already possible in the first trimester. Knowledge of the underlying genetic defect helps counseling the couples with recurrence of MKS and chorionic villi sampling in the first trimester of pregnancy can be offered. [ABSTRACT FROM AUTHOR]