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Objective: Concordance-analysis and evaluation of existing algorithms detecting late-onset preeclampsia during first trimester screeningMethods: Retrospective cohort study investigating risk algorithms of late-onset preeclampsia during first trimester screening in a German prenatal center. Three previously developed algorithms including anamnestic factors (Apriori) and biophysical markers (BioM) were investigated by using detection rates (DR) with fixed FPR 10% and fixed cutoff >1:100. Furthermore, we set up a concordance-analysis of test results in late-onset preeclampsia cases to examine the effect of influencing factors and to detect potential weaknesses of the algorithms. Therefore, we modeled the probability of discordances as a function of the influencing factors based on a logistic regression, that was fitted using a Bayesian approach.Results: 6,113 pregnancies were considered, whereof 700 have been excluded and 5,413 pregnancies were analyzed. 98 (1.8%) patients developed preeclampsia (79 late-onsets, 19 early-onsets). The Apriori-algorithm reaches a DR of 34.2%, by adding BioM (MAP and UtA-PI) the DR improves to 57.0% (FPR of 10%). In concordance-analysis of Apriori algorithm and Apriori+BioM algorithms, influencing factor BMI<25 increases the chance of discordances sigificantly. Additional, in the subgroup of late-onset preeclampsias with BMI<25 the DR is higher in Apriori+BioM algorithms than in Apriori algorithm alone. If both compared algorithms include BioM, influencing factor MAP decreases the chance of discordances significantly. All other tested influencing factors do not have a statistically significant effect on discordancesConclusion: Normal-weight patients benefit more from the integration of MAP and UtA-PI compared to overweight/obese patients. [ABSTRACT FROM AUTHOR]

Objective: To increase the detection rate of preterm preeclampsia (PE) first trimester combined screening tests are being developed. The aim of this review is to create an overview of the currently investigated screening markers, algorithms and their validations.Methods: Comprehensive review of the literature concerning first trimester screening for PEResults and conclusions: Studies investigating a total of 160 biochemical, 6 biophysical and 14 ultrasound markers could be identified. Of the 21 algorithms published, mainly the algorithm published by the Fetal Medicine Foundation London has been validated. This algorithm performes significantly better than screening by anamnestic risk factors only. [ABSTRACT FROM AUTHOR]

We previously reported a logistic regression model for prediction of GDM from maternal characteristics and medical history in 75,161 singleton pregnancies. In this study of 1376 twin and 13,760 singleton pregnancies recruited at 11–13 weeks’ gestation, we extend the model to include terms for twin pregnancies. We found the respective odds of GDM in dichorionic and monochorionic twin pregnancies to be 1.36 (95% CI: 1.02–1.81) and 2.78 (95% CI: 1.72–4.48) times higher than in singleton pregnancies. In both singleton and twin pregnancies, the risk for GDM increased with maternal age and weight and birth weight z-score of a baby in a previous pregnancy and is higher in women with a previous pregnancy complicated by GDM; in those with a first- or second-degree relative with diabetes mellitus; in women of Black, East Asian, and South Asian racial origin; and in pregnancies conceived through the use of ovulation-induction drugs. In singleton pregnancies, at 10% and 20% false-positive rate, the detection rate was 43% and 58%, respectively. In twin pregnancies, using risk cut-offs corresponding to 10% and 20% false-positive rates in singletons, the respective false-positive rates were 27% and 47%, and the detection rates were 63% and 81%.

Objective: To investigate the performance of first trimester Down syndrome (DS) screening markers in Iranian pregnancies.Although sonographic and serum markers are currently recommended for the first trimester screening of Down syndrome, the screening performance of the markers depends on the race and ethnicity. Materials and methods: A retrospective case-control study using first trimester screening results recorded with the prenatal diagnostic multi-centers in Iran. A total of 6,384 pregnant women were examined from March 2012 to February 2017. Totally 100 Down syndrome cases and 266 matched controls were selected and the maternal characteristics, sonographic and biochemical screening data were collected. Statistical analysis was performed using logistic regression and descriptive statistics. A decision tree model was designed using the chi-squared automatic interaction detection method based on serum markers. Results: For screening of DS pregnancies, PAPP-A (cut-off 0.795 MoM) yielded the highest sensitivity (86%) and NB marker presented highest specificity (96.24%). combination of the biochemical markers PAPP-A and β-hCG (cut-off: 1.55 MoM) showed the highest sensitivity over other combined markers. The decision-tree model based on serum markers improved (91% DR For a 5% FPR) first trimester screening performance. Conclusion: The novel decision-tree model base on serum markers revealed a better predictive value to achieve high sensitivity and specificity of first trimester Down syndrome screening in Iranian population.

Introduction: Switzerland was amongst the first countries to offer cell-free fetal DNA (cffDNA) testing covered by the health insurance to pregnant women with a risk ≥ 1:1000 for trisomies at first trimester combined screening (FTCS). The aim of this study is to evaluate the implementation of this contingent model in a single tertiary referral centre and its effect on gestational age at diagnosing trisomy 21., Materials and Methods: Between July 2015 and December 2020 all singleton pregnancies at 11-14 weeks of gestation without major fetal malformation were included and stratified according to their risk at FTCS. Statistical analysis was performed by GraphPad Version 9.1 for Windows., Results: 4424 pregnancies were included. Of 166 (3.8%) pregnancies with a NT ≥ 3.5 mm and/or a risk ≥ 1:10 at FCTS, 130 (78.3%) opted for direct invasive testing. 803 (18.2%) pregnancies had an intermediate risk, 692 (86.2%) of them opted for cffDNA first. 3455 (78.1%) pregnancies had a risk < 1:1000. 63 fetuses were diagnosed with trisomy 21, 47 (74.6%) directly by invasive procedures after FTCS, 16 (25.4%) by cffDNA first., Conclusions: Most women choose cffDNA or invasive testing as second tier according to national guidelines. Despite the delay associated with cffDNA testing after FCTS, 75% of all trisomy 21 are still diagnosed in the first trimester with this contingent screening model., Competing Interests: Conflict of Interest Florent Badiqué and Lorenz Risch work in one of the laboratories providing the cffDNA results, however they were not involved in the analysis of the results., (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/).)

Background: The Fetal Medicine Foundation developed a multiple logistic regression algorithm for risk prediction of delivering a small for gestational age neonate. Aim: To validate this algorithm in an Australian population. Methods: At the combined first trimester screen participants' medical histories, demographic data, mean arterial pressure, uterine artery pulsatility index and pregnancy‐associated plasma protein‐A were assessed. After delivery, risk of delivering a small for gestational age neonate at <37 or ≥37 weeks gestation was retrospectively calculated using the Fetal Medicine Foundation algorithm. Results: Three thousand and eight women underwent prediction of risk for delivering a small for gestational age neonate. The algorithm detected 15.0% (95% CI: 3.2–37.9) of small for gestational age neonates delivered <37 weeks gestation at a fixed 10% false positive rate (or 35.0% (95% CI: 15.4–59.2) at a fixed 20% false positive rate). It detected 23.4% (95% CI: 16.1–30.7) of small for gestational age neonates delivered ≥37 weeks gestation at a fixed 10% false positive rate (or 39.1% (95% CI: 30.7–47.5) at a fixed 20% false positive rate). The algorithm performed significantly better than individual parameters (P < 0.05). The area under the receiver operating characteristic curve was 0.68 (95% CI: 0.56–0.80) and 0.70 (95% CI: 0.65–0.74) for small for gestational age neonates at <37 and ≥37 weeks gestation, respectively. Conclusions: The Fetal Medicine Foundation algorithm for first trimester prediction of small for gestational age neonates does not perform as well in an Australian population as in the original United Kingdom cohort. However, it performs significantly better than any individual test parameter in both preterm and term neonates. Incorporation of further variables may help improve screening efficacy. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the performance of first trimester biochemical markers, pregnancy-associated plasma protein-A (PAPP-A), free beta human chorionic gonadotropin (fβ-hCG), and nuchal translucency (NT) in detection of severe congenital heart defects (CHDs). Methods: During the study period from 1 January 2008 to 31 December 2011, biochemical markers and NT were measured in 31,144 women as part of voluntary first trimester screening program for Down's syndrome in Northern Finland. Data for 71 severe CHD cases and 762 controls were obtained from the hospital records and from the National Medical Birth Register, which records the birth of all liveborn and stillborn infants, and from the National Register of Congenital Malformations that receives information about all the CHD cases diagnosed in Finland. Results: Both PAPP-A and fβ-hCG multiple of median (MoM) values were decreased in all severe CHDs: 0.71 and 0.69 in ventricular septal defects (VSDs), 0.58 and 0.88 in tetralogy of Fallot cases (TOFs), 0.82 and 0.89 in hypoplastic left heart syndromes (HLHSs), and 0.88 and 0.96 in multiple defects, respectively. NT was increased in all study groups except of VSD group. ROC AUC was 0.72 for VSD when combining prior risk with PAPP-A and fβ-hCG. Adding NT did not improve the detection rate. With normal NT but decreased (<0.5 MoM) PAPP-A and fβ-hCG odds ratios for VSD and HLHS were 19.5 and 25.6, respectively. Conclusions: Maternal serum biochemistry improves the detection of CHDs compared to NT measurement only. In cases with normal NT measurement but low concentrations of both PAPP-A and fβ-hCG, an alert for possible CHD, especially VSD, could be given with thorough examination of fetal heart in later ultrasound scans. [ABSTRACT FROM AUTHOR]

Objective: We aimed to compare the first trimester screening profiles of spontaneous (n=972) and in in vitro fertilization (IVF) pregnancies (n=339) in a population of patients who had uncomplicated singleton pregnancies comparable for maternal age, gestation, body mass index, and ethnicity. Material and Methods: A non-interventional analysis of retrospective cohort data and review of the literature. Results: All IVF pregnancies were achieved via intracytoplasmic sperm injection using the same ovarian stimulation protocol with recombinant follicle-stimulating hormone and a gonadotropin-releasing hormone antagonist, cetrorelix acetate. The means of the multiple of median (MoM) of pregnancy-associated plasma protein-A (PAPP-A) were slightly lower in the fresh (1.19±0.6 vs 1.33±0.7, respectively; p=0.056) and frozen embryo transfer (1.03±0.5 vs 1.33±0.7, respectively; p=0.036) IVF pregnancies compared with natural conceptions. However, when the medians of the MoMs of PAPP-A and beta-human chorionic gonadotrophin (β-hCG), and their distributions were compared across the mode of conception, there were no differences between IVF pregnancies spontaneous pregnancies. Furthermore, the scatterplot diagram and curve fitting regression analyses revealed no difference in the temporal relations of β-hCG and PAPP-A with each other and gestational age between spontaneous and IVF pregnancies. Conclusion: These results support the notion that uncomplicated singleton IVF pregnancies have similar first trimester screening profiles to spontaneous conceptions. [ABSTRACT FROM AUTHOR]

Objective  To determine if patients with a history of low pregnancy-associated plasma protein A (PAPP-A) in an initial pregnancy are at higher risk for adverse obstetric outcomes in a subsequent pregnancy. Study Design  This was a retrospective cohort study in patients who underwent first trimester screening for PAPP-A in two consecutive pregnancies. Two groups were examined: patients who had low PAPP-A in the first pregnancy followed by normal PAPP-A in the second pregnancy and patients who had recurrent low PAPP-A. Maternal and neonatal outcomes were compared between the groups, with the primary outcome being intrauterine growth restriction (IUGR) or preeclampsia. Results  A total of 124 patients were included, representing 248 pregnancies. Ninety-two (74.2%) patients had normal PAPP-A in the second pregnancy, and 32 (12.9%) patients had recurrent low PAPP-A. Patients with recurrent low PAPP-A had a higher rate of IUGR or preeclampsia compared with patients with normal PAPP-A in the second pregnancy but this was not significantly different (12.5 vs. 10.9%, p  = 0.51). There were no significant differences for all other outcomes. Conclusion  Among patients with a history of low PAPP-A, patients with normal PAPP-A in the subsequent pregnancy have a similar risk of adverse neonatal outcomes compared with patients with recurrent low PAPP-A. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the impacts of maternal risk factors described by the Fetal Medicine Foundation's 2012 algorithm (FMF2012) in a Brazilian population. Methods: All singleton pregnancies submitted to first-trimester preeclampsia (PE) screening using the FMF2012 algorithm were considered for study inclusion. Maternal factors, recorded via a patient questionnaire, were described and compared between PE outcome groups. A Gaussian regression model was derived to measure the effects of maternal factors, and to identify factors that contributed significantly (p < .05) to the alteration of gestational age at delivery, in pregnancies with PE. Results: Of the 1934 cases considered for study inclusion, the final sample consisted of 1531 cases. The sample included 120 (7.8%) cases of PE, of which 26 (1.7%) were preterm PE (PE < 37 weeks) and 11 (0.72%) were early PE (PE < 34 weeks). The PE rate did not differ according to ethnicity, smoking, family history of PE, or use of assisted reproductive technology. Significant differences (p < .05) between the normal and PE groups in maternal age, maternal weight, previous history of PE, chronic hypertension, and types 1 and 2 diabetes were detected. Conclusions: The significance and magnitude of associations of maternal factors in our sample differed from those incorporated in the FMF2012 model, implying the need to derive a fitted model for our population. [ABSTRACT FROM AUTHOR]

Objective: To better adjust the risk for preeclampsia, multifactorial models in first trimester of pregnancy have found the way in clinical practice. This study compares the available test algorithms.Study Design: In a cross-sectional study between November 2013 and April 2016 we compared the tests results of three first trimester testing algorithms for preeclampsia in 413 women. Risk for preterm preeclampsia was calculated with three different algorithms: Preeclampsia Predictor™ Software by PerkinElmer (PERK), ViewPoint® Software by GE Healthcare (VP) and the online calculator of the Fetal Medicine Foundation (FMF).We analyzed the data descriptively and determined Cohen's Kappa to assess the agreement among the algorithms.Results: VP classified 89(21.5%) women, PERK 43(10.4%) women and FMF 90 (21.8%) women as having high risk for preterm preeclampsia (<34 weeks of gestation for VP and PERK and <37 weeks of gestation for FMF). Agreement between tests ranged from moderate to substantial (PERK/VP: κ = 0.56, PERK/ FMF: κ = 0.50, and VP/ FMF: κ = 0.72).Conclusion: The three algorithms are similar but not equal. This may depend on chosen cut off, but also on test properties. This study cannot decide which algorithm is the best, but differences in results and cut offs should be taken into account. [ABSTRACT FROM AUTHOR]

Pre‐eclampsia is a common condition that affects 2–5% of pregnancies and is associated with significant maternal and perinatal morbidity, and cost to the healthcare system. In those at high risk for pre‐eclampsia, interventions such as aspirin intake have been shown to reduce prevalence of disease. However, to implement these interventions, it is essential that high‐risk women be identified early in pregnancy. A combined first trimester screening model for pre‐eclampsia that includes maternal history, mean arterial pressure, uterine artery Doppler and PlGF has been shown to be the most effective at identifying the population at greatest risk of pre‐eclampsia. This article will explore the most appropriate methods of measuring the components of first trimester screening and discuss the use of aspirin for prevention of pre‐eclampsia in pregnancy. [ABSTRACT FROM AUTHOR]

Introduction. Screening for congenital heart defects (CHD) in the first trimester has been shown to be effective in low risk populations. However, it is usually not per formed routinely. Our aim was to assess the feasibility of the fetal heart assessment and screening for major CHD by routine first trimester scan. Materials and method. This was a retrospective two year study of 1423 uncomplicated pregnancies, examined during the first trimester screening for chromosomal and fetal structural abnormalities. To improve the fetal heart visualization on anatomic survey, we have performed the scans starting from 12 gestational weeks. The four chamber view (4CV) and three vessels and trachea view (3VTV) of fetal hearts were assessed by grayscale and color or directional power Doppler imaging. The final diagnosis of the suspected CHD was based on the second trimester and third trimester fetal and postnatal echocardiography or autopsy. Results and conclusions. The median crown rump length was 61.7 mm. The 4CV and the 3VTV were considered normal in 95% of cases (1352/1423), in 2% of cases (29/1423) unfeasible, and in 3% of cases (42/1423) abnormal. Overall, on the first trimester scan we identified 42 cases of CHD, and among them there were 33 (2.32%) confirmed major CHD, as fol lows: eight cases of double outlet right ventricle (DORV); eight atrioventricular septal defects (AVSD); five cases of pulmonary atresia; four cases of tetralogy of Fallot (TOF); four cases of hypoplastic left heart syndrome; two cases of pulmonary stenosis; two cases of mitral atresia and one mitral stenosis; one case of tricuspid atresia; one case of transposition of great arteries (TGA), one aortic hypoplasia, one case of critical stenosis of the aorta, and three cases of right atrial isomerism. Among the confirmed congenital heart defects, seven were complex cardiac anomalies. In four cases, the diagnosis was slightly modified later in gestation. In addition, 14 congenital heart defects were missed in the first trimester, as follows: four cases of aortic hypoplasia, two TOF, two TGA, two DORV, two cases of coarctation of the aorta, one pulmonary atresia and one right aortic arch. The assessment by the 4CV and the 3VTV for major congenital heart defects had a sensitivity and specificity of 70.2% and 99.3%, respectively, with a positive and negative predictive value of 78.5% and 98.9%, respectively. Among 33 fetuses with CHD, seven fetuses (20.6%) had other structural abnormalities. In 15 fetuses (44.11%), the NT was above the 95th centile. Eleven fetuses (32.35%) showed reversed flow in ductus venosus and/or tricuspid regurgitation. First trimester cardiac screening and the detection of major congenital heart defects are feasible during the routine first trimester scan. However, the early detailed assessment of the fetal heart requires expertise in fetal echocardiography and complementary scans in both the second and the third trimester, since there are many defects that evolve over time which are best assessed later in gestation. [ABSTRACT FROM AUTHOR]

COVID-19 has been shown to affect pregnant women. Since pregnant women are at risk of this infection, vaccination against COVID-19 has been suggested as an imperative way to diminish rate of COVID-19 in this population. In the current observational study, we have collected data of first and second trimester screening (FTS and STS) from pregnant women who were infected with SARS-CoV-2 and/or vaccinated against COVID-19 during their pregnancy, and compared this data with a group of control pregnant women. The cohort included 4612 and 2426 women referred for FTS and STS, respectively. There was no significant difference in median values of Pregnancy-associated plasma protein A (PAPP-A) and human chorionic gonadotropin-beta subunit (βHCG) between infected women and controls. Moreover, these levels were not different between "Infected + vaccinated" and "Only vaccinated" groups. However, median values of PAPP-A and βHCG were higher in "Infected + vaccinated" and "Only vaccinated" groups compared with "Infected" and "Control" groups (P < 0.001). Median values of unconjugated Estriol (uE3) and βHCG markers were not different between "Only vaccinated" and "Control" groups, yet both markers were elevated in "Infected" and "Infected + vaccinated" groups compared with other groups. AFP values were higher in "Infected" group (P = 0.012). However, multiple of the median (MoM) and risk of open spina bifida (OSB) were not affected. Finally, median of calculated risk of trisomy 18 was lower in "Infected" and "Vaccinated" groups compared with controls (P = 0.007). Moreover, AstraZeneca and Sinopharm vaccines were associated with elevation of the calculated risk values of trisomy 21 and trisomy 18 (P < 0.001). While Sinopharm did not affect nuchal translucency (NT) and NT MoM (P = 0.13), AstraZeneca and Barakat increased and decreased these values, respectively (P values = 0.0027 and 0.015, respectively). Taken together, COVID-19 during pregnancy might be associated with some adverse obstetric outcomes. Besides, vaccination against this infection might affect the results of STS or FTS. [ABSTRACT FROM AUTHOR]

Introduction: In Denmark, first trimester screening has a very high uptake (>90%). If Down syndrome is diagnosed, termination rates are high (>95%). The aim of this study was to investigate the timing of the decision to terminate pregnancy following a diagnosis of Down syndrome and the factors influencing this decision.Material and Methods: Semi-structured, qualitative interview study with 21 couples who had received a prenatal diagnosis of Down syndrome and decided to terminate the pregnancy. Participants were recruited from obstetric departments between February 2016 and July 2017. Data were analyzed using thematic analysis.Results: Five themes were identified: "initial decision-making", "consolidating the decision", "reasons and concerns shaping the termination of pregnancy decision", "the right decision is also burdensome", and "perceived influences in decision-making". For most couples, the initial decision to terminate pregnancy was made before or during the diagnostic process, but it was re-addressed and consolidated following the actual diagnosis. Imagining a family future with a severely affected Down syndrome child was the main factor influencing the termination of pregnancy decision. The decision was articulated as "right" but also as existentially burdensome for some, due to fear of regret and concern about ending a potential life. The decision to terminate pregnancy was considered a private matter between the couple, but was refined through interactions with clinicians and social networks.Conclusion: All couples made an initial decision prior to receiving the Down syndrome diagnosis. Knowledge of the couple's initial decision may facilitate patient-centered communication during and after the diagnostic process. Couples may benefit from counseling to deal with grief and existential concerns. [ABSTRACT FROM AUTHOR]

Objective: To investigate the performance of first trimester Down syndrome (DS) screening markers in Iranian pregnancies.Although sonographic and serum markers are currently recommended for the first trimester screening of Down syndrome, the screening performance of the markers depends on the race and ethnicity. Materials and methods: A retrospective case-control study using first trimester screening results recorded with the prenatal diagnostic multi-centers in Iran. A total of 6,384 pregnant women were examined from March 2012 to February 2017. Totally 100 Down syndrome cases and 266 matched controls were selected and the maternal characteristics, sonographic and biochemical screening data were collected. Statistical analysis was performed using logistic regression and descriptive statistics. A decision tree model was designed using the chi-squared automatic interaction detection method based on serum markers. Results: For screening of DS pregnancies, PAPP-A (cut-off 0.795 MoM) yielded the highest sensitivity (86%) and NB marker presented highest specificity (96.24%). combination of the biochemical markers PAPP-A and β-hCG (cut-off: 1.55 MoM) showed the highest sensitivity over other combined markers. The decision-tree model based on serum markers improved (91% DR For a 5% FPR) first trimester screening performance. Conclusion: The novel decision-tree model base on serum markers revealed a better predictive value to achieve high sensitivity and specificity of first trimester Down syndrome screening in Iranian population. [ABSTRACT FROM AUTHOR]

Objective: To determine intersonographer, intersampling site pulsatility index differences in the ascending branch of the uterine artery (UtA-PI) and their effect on detection rates (DR) for early onset preeclampsia (PE).Methods: A prospective observational study was conducted including 52 women with singleton viable pregnancy at 11-13 weeks' gestation. Consecutive bilateral UtA-PI measurements were performed by two sonographers. Both sonographers hold the Fetal Medicine Foundation (FMF) uterine artery Doppler assessment competency certificates. Sonographer "A" underwent mentorship-based specialist training at the FMF; whilst sonographer "B" is a fetal maternal specialist who was deemed competent to measure UtA-PI based on completion of the FMF online course. Both sonographers were unaware of each other's UtA-PI and peak systolic velocity (PSV) measurements throughout the study. UtA-PI was measured by sonographer "A" at 1, 2 and 3 cm distally from the internal os. UtA-PI minimum ("Low-PI") and mean ("Mean-PI") were determined. Intraclass correlation (ICC), Bland-Altman analysis and Wilcoxon signed rank test were performed to determine bias, 95% limits of agreement (LOA) for intersonographer and intersampling site differences. Simulation studies were performed to determine the effect on early onset PE screening DR.Results: (1) Intersite assessment indicated that UtA-PI and PSV decreased by 7-8% per centimeter relative to the measurement taken at the internal os; (2) Sonographer "B" UtA-PI measurements were significantly lower than those of sonographer "A" for "Low-PI" (p = .001), "Mean-PI" (p = .002) and PSV (p = .004) determined by Wilcoxon signed rank test. The mean reduction in "Low-PI", "Mean-PI" and PSV of sonographer "B" relative to sonographer "A" were 14.04%, 11.09% and 10.99%, respectively; (3) Measurements taken by sonographer "B" at the level of the internal os were comparable to measurements taken by sonographer "A" at 2 cm distal to the internal os (low-PI: p = .98, Mean-PI: p = .49 and PSV: p = .24); (4) Between sonographer ICC for UtA-PI was asymmetrical strong (left ICC = 0.72, 95%CI: 0.51-0.84) to fair (right ICC = 0.38, 95%CI: -0.08-0.64); and (5) The 14% mean intersonographer difference in lowest UtA-PI would have resulted in an 7% difference in PE screening performance.Conclusions: The measurement of UtA-PI is sampling site dependent with the potential for significant intersonographer differences despite the availability of a prescriptive measurement protocol. This is an important observation as it implies that sonographer "B" inadvertently measured the UtA-PI at a distal site, not at the level of internal os, compared to those measured by sonographer "A", resulting in a lower DR for early onset PE. [ABSTRACT FROM AUTHOR]

Objective: We examined whether first trimester aneuploidy and pre-eclampsia screening markers predict gestational diabetes mellitus (GDM) in a large multi-ethnic cohort and the influence of local population characteristics on markers.Methods: Clinical and first trimester markers (mean arterial pressure (MAP), uterine artery pulsatility index (UtA PI), pregnancy associated plasma protein A (PAPP-A), free-β human chorionic gonadotropin (free-hCGβ)) were measured in a case-control study of 980 women (248 with GDM, 732 controls) at 11 to 13 + 6 weeks' gestation. Clinical parameters, MAP-, UtA PI-, PAPP-A-, and free-hCGβ-multiples-of-the-median (MoM) were compared between GDM and controls; stratified by ethnicity, parity, and GDM diagnosis <24 versus ≥24 weeks' gestation. GDM model screening performance was evaluated using AUROC.Results: PAPP-A- and UtA PI-MoM were significantly lower in GDM versus controls (median ((IQR) PAPP-A-MoM 0.81 (0.58-1.20) versus 1.00 (0.70-1.46); UtA PI-MoM 1.01 (0.82-1.21) versus 1.05 (0.84-1.29); p < .05). Previous GDM, family history of diabetes, south/east Asian ethnicity, parity, BMI, MAP, UtA PI, and PAPP-A were significant predictors in multivariate analysis (p < .05). The AUC for a model based on clinical parameters was 0.88 (95%CI 0.85-0.92), increasing to 0.90 (95%CI 0.87-0.92) with first trimester markers combined. The combined model best predicted GDM <24 weeks' gestation (AUC 0.96 (95%CI 0.94-0.98)).Conclusions: Addition of aneuploidy and pre-eclampsia markers is cost-effective and enhances early GDM detection, accurately identifying early GDM, a high-risk cohort requiring early detection, and intervention. Ethnicity and parity modified marker association with GDM, suggesting differences in pathophysiology and vascular risk. [ABSTRACT FROM AUTHOR]

Abstract: The benefit of the early administration of aspirin to reduce preterm pre‐eclampsia among screened positive European women from multivariate algorithmic approach (ASPRE trial) has opened an intense debate on the feasibility of universal screening. This review aims to assess the new perspectives in the combined screening of pre‐eclampsia in the first trimester of pregnancy and the chances for prevention using low‐dose aspirin with special emphasis on the particularities of the Asian population. PubMed, CENTRAL and Embase databases were searched from inception until 15 November 2017 using combinations of the search terms: preeclampsia, Asian, prenatal screening, early prediction, ultrasonography, pregnancy, biomarker, mean arterial pressure, soluble fms‐like tyrosine kinase‐1, placental growth factor, pregnancy‐associated plasma protein‐A and pulsatility index. This is not a systematic review or meta‐analysis, so the risk of bias of the selected published articles and heterogeneity among the studies need to be considered. The prevalence of pre‐eclampsia and serum levels of biochemical markers in Asian are different from Caucasian women; hence, Asian ethnicity needs to be corrected for in the algorithmic assessment of multiple variables to improve the screening performance. Aspirin prophylaxis may still be viable in Asian women, but resource implication needs to be considered. Asian ethnicity should be taken into account before implementing pre‐eclampsia screening strategies in the region. The variables included can be mixed and matched to achieve an optimal performance that is appropriate for economical restriction in individual countries. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to investigate the attitude (view, likely uptake and preferred strategy) towards cell-free fetal DNA (cfDNA) testing among pregnant women before a first-trimester risk assessment for trisomy 21 (unselected women) and after obtaining a high risk.Material and Methods: Unselected and high-risk women attending first-trimester screening (Rigshospitalet, Copenhagen University Hospital) were invited to fill out the questionnaire Antenatal testing for Down syndrome as an online survey.Results: The survey included 203 unselected and 50 high-risk women (response rates of 74.8% and 84.7%, respectively). Nearly all considered cfDNA testing a positive development in antenatal care, and 97.2% would like it to be offered. Offering cfDNA testing as an alternative to invasive testing would increase the uptake of follow-up testing compared with invasive testing alone (98.8% vs. 90.7%, p < 0.001). Women who would only accept follow up by cfDNA testing were more likely to continue an affected pregnancy (30.0% vs. 3.6%, p < 0.001) or have doubts about termination (50.0% vs. 32.1%, p < 0.001).Conclusions: Offering cfDNA testing would likely increase the uptake of follow-up testing without a corresponding rise in the termination rate of affected fetuses as some women test for information only. However, both unselected and high-risk women had overwhelmingly positive views underlining attention to avoid routinization. [ABSTRACT FROM AUTHOR]

Prenatal screening for aneuploidies is done using maternal serum and sonographic markers. Although many screening tests are available, their correct application still does not have uniformity. This review will give insight into the existing screening protocols, their merits and demerits, interpretation of results and the relevance of these tests in low resource settings. Cell free fetal DNA and its exciting role in non invasive prenatal testing along with its advantages and drawbacks is also taken up. We have further considered the role of counseling and its importance before embarking on the screening tests. The upcoming role of maternal serum markers for prediction of adverse obstetrical outcomes is also discussed. [ABSTRACT FROM AUTHOR]

Objective: To assess the potential of screening for pre-eclampsia (PE) in a Chinese population.Design: Case-control study.Setting: Teaching hospital in Hong Kong.Population: A total of 3330 women having a viable singleton pregnancy attending first-trimester Down-syndrome screening.Methods: Mean arterial pressure (MAP), bilateral uterine artery pulsatility index (UtA-PI), and placental growth factor (PlGF) were measured. Screening markers were transformed to multiples of the gestational median (MoM) and adjusted for maternal and pregnancy characteristics. MoM distributions in PE and non-PE pregnancies were compared with published expected values. PE screening performance was assessed using area under receiver operating curves (AUROC).Main Outcome Measures: PE detection rate.Results: A total of 30 (0.9%) women developed either early (<34 weeks) or late (≥34 weeks) onset PE. MAP was dependent on maternal BMI, UtA-PI on fetal crown rump length, uterine artery peak systolic velocity (UtA-PSV) on maternal age and gestation, and PlGF on gestation in non-PE pregnancies. MoM distributions determined using published Fetal Medicine Foundation models deviated significantly from one for both MAP (P < 0.0001) and PI (P < 0.0001), but not PlGF (P = 0.52) in non-PE pregnancies, whilst PlGF MoM distributions in those who developed early as opposed to late onset PE were significantly higher (P = <0.05). AUROC for any PE using multiple markers was 0.72 (95% CI: 0.64-0.81) with detection rates of 72 and 55% for early and late PE, respectively, for a 10% false positive rate.Conclusion: Detection rates for PE in our Chinese population were lower than the expected 90-95% even after adjusting MoM for local women's characteristics.Funding: General Research Fund (Project number 470513).Tweetable Abstract: Pre-eclampsia screening in the Chinese population had detection rates lower than previously published results. [ABSTRACT FROM AUTHOR]

The objective of this study was to test three measurements: brain stem (BS), intracranial translucency (IT) and brain stem to occipital bone distance (BSOB), as well as one landmark: cisterna magna (CM) visibility, for early diagnosis of open spina bifida (OSB) in a low risk population. A prospective observational study was undertaken in a university hospital. A sample of 1479 women consented to participate between 20 September 2013 and 30 June 2015. Measurements were performed from the mid-sagittal view, as is routinely used for nuchal thickness assessment. CM visibility was assessed qualitatively as the third anechoic band in the posterior cranial fossa (PCF). All pregnancies were screened with a combination of maternal serum alpha-fetoprotein and second trimester anomaly scan and followed until delivery. Predictive values were calculated for each marker. We were able to diagnose two OSB cases and highly suspect one Dandy-Walker malformation case at the first trimester scan by the observation of PCF. PCF characteristics of OSB cases were increased BS diameter, increased BS-BSOB ratio and non-visualization of the CM. All the markers demonstrated high sensitivity and specificity but CM visibility reached the highest positive predictive value. Due to relatively high false positive rates, PCF measurements could not reach a satisfactory performance to validate their clinical use as a single marker. CM visibility has the advantage of being a qualitative marker and reduces the need for sophisticated and time-consuming measurements. Intracranial translucency and BS-BSOB ratio measurements should be used when the CM visibility is absent or in doubt. [ABSTRACT FROM AUTHOR]

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 β human Chorionic Gonadotropin (free β 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

Objective: To investigate whether maternal serum pregnancy associated plasma protein-A (PAPP-A), total β human chorionic gonadotropin (hCG) levels and nuchal translucency (NT) measurements differ in women with pre-gestational diabetes mellitus (PGDM) compared to non-diabetic controls and to assess whether correction factors are needed for diabetic women in calculation of aneuploidy risks. Study Design: We performed a retrospective study of all women who underwent first trimester aneuploidy screening (11 + 0 to 13 + 6 weeks) from 2005 to 2011. The primary study outcome was the difference in PAPP-A, β-hCG and NT multiples of median between women with PGDM and non-diabetic women. Results: Of 6741 eligible patients, 103 patients with PGDM were using insulin and 4 patients were using oral hypoglycemic agents; the latter were excluded due to small number. There was 12% reduction of median PAPP-A (p = 0.001) and 18% reduction of median hCG (p = 0.006) in women with PGDM receiving insulin. There was no difference in NT. Conclusions: In women with PGDM receiving insulin, PAPP-A and β-hCG levels are significantly lower compared to non-diabetic women. This suggests that when calculating risks for aneuploidy, correction factors should be considered to adjust PAPP-A and β-hCG concentrations to those seen in non-diabetic women.

Purpose: First trimester risk assessment plays a major role in the contemporary pregnancy care. It has evolved significantly since its introduction in the 1990s when it essentially consisted of just the nuchal translucency measurement. Today, it involves the measurement of several biophysical and biochemical markers and can assess the risk for a wide array of major chromosomal and non-chromosomal defects as well as other pregnancy-related complications.Methods: A search of the Medline and Embase databases was done looking for articles about first trimester screening. We performed a detailed review of the literature to evaluate the screening tests currently available and their respective test performance.Results: The detailed ultrasound examination results in the detection of about half of major structural defects, determination of a very accurate gestational age, and identification of multiple pregnancies as well as their chorionicity. In addition, risk assessment for preeclampsia and early IUGR can be established at this stage. In case of an increased risk, the daily use of low-dose aspirin can be offered at a point in pregnancy when it still can have a positive impact. Additional screening tests for gestational diabetes and macrosomia are available.Conclusion: Contemporary first trimester screening is essential to establish an individual risk profile and can be used to tailor the pregnancy care. [ABSTRACT FROM AUTHOR]

Purpose: First trimester risk assessment for chromosomal abnormalities plays a major role in the contemporary pregnancy care. It has evolved significantly since its introduction in the 1990s, when it essentially consisted of just the nuchal translucency measurement. Today, it involves the measurement of several biophysical and biochemical markers and it is often combined with a cell-free DNA (cfDNA) analysis as a secondary test.Methods: A search of the Medline and Embase databases was done looking for articles about first trimester aneuploidy screening. We performed a detailed review of the literature to evaluate the screening tests currently available and their respective test performance.Results: Combined screening for trisomy 21 based on maternal age, fetal NT, and the serum markers free beta-hCG and PAPP-A results in a detection rate of about 90% for a false positive of 3-5%. With the addition of further ultrasound markers, the false positive rate can be roughly halved. Screening based on cfDNA identifies about 99% of the affected fetuses for a false positive rate of 0.1%. However, there is a test failure rate of about 2%. The ideal combination between combined and cfDNA screening is still under discussion. Currently, a contingent screening policy seems most favorable where combined screening is offered for everyone and cfDNA analysis only for those with a borderline risk result after combined screening.Conclusion: Significant advances in screening for trisomy 21 have been made over the past 2 decades. Contemporary screening policies can detect for more than 95% of affected fetuses for false positive rate of less than 3%. [ABSTRACT FROM AUTHOR]

Objective: To assess the adverse outcome in pregnancies with raised Nuchal translucency measurement.Methods: This retrospective study was conducted at the Aga Khan University Hospital, Karachi, Pakistan between January 2001 and December 2015. Women attending the Fetal Medicine unit for first trimester screening by Nuchal translucency were included in the study. All pregnancies were followed up till delivery. Those with incomplete information about the delivery were excluded from the analysis. Pregnancy outcome was observed in normal Nuchal translucency measurements and in raised Nuchal translucency measurements.Results: Out of the 1941 fetuses, there were 54 (2.8%) with raised Nuchal translucency measurement. Adverse pregnancy outcome was found in 32 (59.3%) of fetuses with raised Nuchal translucency measurement. Invasive testing was done in 15 (27.8%) of pregnancies with raised Nuchal translucency measurement. Among them there were nine (16.7%) cases with abnormal karyotype. It included six (11.1%) cases of trisomy 21, three (5.6%) cases of trisomy 13 and 18.Conclusion: Raised Nuchal translucency measurement is associated with adverse pregnancy outcome. One in three fetuses are affected by it. Live birth in this group where there is no aneuploidy is around 3.7%. [ABSTRACT FROM AUTHOR]

Prenatal diagnostics has been impacted by technological changes in the past decade, which have affected the diagnostic yield. The aim of this study was to evaluate the impact of SNP array and noninvasive prenatal testing (NIPT) on the diagnostic yield and the number of invasive tests in our center. The frequency of pathogenic fetal unbalanced chromosome aberrations was studied in 10,005 cases referred for prenatal testing in 2009-2015. Chromosomal SNP microarray analysis replaced karyotyping in all invasively tested pregnancies and since 2014 a choice between NIPT and diagnostic testing with microarray was offered to women with an increased risk for common aneuploidy. The introduction of microarray led to an additional yield of submicroscopic pathogenic chromosome aberrations: 3.6% in fetuses with ultrasound anomalies and 1.9% in fetuses without ultrasound anomalies. The introduction of NIPT led to a decrease of invasive tests and of diagnostic yield. Moreover, a diagnostic delay in about 1:350 cases was observed. Since 20%-33% of pathogenic fetal chromosome aberrations are different from the common aneuploidies and triploidy, whole-genome analysis should be offered after invasive sampling. Because NIPT (as a second screening) has led to a decreased diagnostic yield, it should be accompanied by an appropriate pretest counseling. [ABSTRACT FROM AUTHOR]

Purpose: Maternal age is a crucial factor in fetal aneuploidy screening, resulting in an increased rate of false-positive cases in older women and false-negative cases in younger women. The absolute risk (AR) is the simplest way to eliminate the background maternal age risk, as it represents the amount of improvement of the combined risk from the maternal background risk. The aim of this work is to assess the performance of the AR in the combined first-trimester screening for aneuploidies.Materials and Methods: A retrospective validation of the AR in the combined first-trimester screening for fetal aneuploidies, in an unselected population at Altamedica Fetal-Maternal Medical Center in Rome, between March 2007 and December 2008.Results: Of 3845 women included in the study, we had a complete follow-up on 2984. We evaluated that an AR < 3 would individuate 22 of 23 cases of aneuploidy with a detection rate of 95.7% (95%CI 87.3-100), a false-positive rate of 8.7% (95%CI 7.7-9.7) and a false-negative rate of 4.3% (95%CI 0-12.7).Conclusions: In our study, the AR ameliorates the detection rate for aneuploidy. Further research and a prospective study on a larger population would help us to improve the AR in detecting most cases of aneuploidy. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the utility of first-trimester placental volume and vascular flow indices to predict intrauterine growth retardation (IUGR).Study Design: In 1004 singleton pregnancies attending routine care we recorded maternal characteristics, biophysical and biochemical factors included in the first trimester screening for aneuploidy (FTSA) and uterine artery pulsatility index (PI). Placental volume, Vascularization Index, Flow Index and Vascularization Flow Index were obtained. Customized curves were used to define IUGR. We compared pregnancies with and without IUGR. The performance of different predictive models was described by the areas under the receiver operator characteristic (AUROC) curve. Predictive models of IUGR were compared using a two by two approach and subset analysis was performed.Results: Placental volume and all vascular indices were significantly lower (p<0.001, p≤0.01), and uterine artery PI higher (p<0.001), in pregnancies with IUGR, with and without associated pre-eclampsia.Results: obtained in the analysis of homogeneous subsets showed that the effectiveness of combined predictive models for IUGR improved significantly after adding vascular indices or placental volume to maternal characteristics, FTSA variables and uterine artery PI (AUROC curve value 0.703 (95% CI 0.663-0.744) versus 0.720 (95% CI 0.681-0.759) and 0.735 (95% CI 0.696-0.733), respectively). The most effective model at first trimester was that which included only maternal characteristics, uterine a-PI and placental volume, similar to that of the most complex model built with all the factors analyzed in this study AUROC curve value 0.735 (95% CI 0.696-0.773).Conclusions: Placental volume and vascular indices were predictors factors of IUGR at first trimester. The effectiveness of combined predictive models for IUGR increased significantly after adding these factors, but the sensitivity of these models was too low for them to be considered useful in clinical practice. [ABSTRACT FROM AUTHOR]

Introduction: An impact of maternal obesity on ultrasound dating of pregnancy at 11-14 gestational weeks is possible and was investigated.Material and Methods: A prospective cohort study based on the Danish national population during a 4-year period in which we entered all mothers with singleton pregnancies who had a known last menstrual period (LMP), a recorded booking of body mass index (BMI), and a late first trimester ultrasound dating scan using crown-rump-length measurement (gestational age 11+0 -13+6  weeks). Almost all scans were performed transabdominally. Transvaginal ultrasound was only performed in the case of limited visibility by transabdominal scanning. Differences between LMP and ultrasound estimated date of delivery (EDD) were stratified by BMI classes. Odds ratios (ORs) were calculated and adjusted for maternal age, parity and smoking.Results: In total, 187 486 women were analyzed: 21.8% were overweight and 12.3% obese. Ultrasound EDD was ≥7 days later than by LMP in 5.8% of normal-weight women, 7.3% of obese women, and 10.0% of women with morbid obesity. Compared with normal BMI (18.5-24.9), the OR for postponing EDD increased with increasing BMI; BMI 25-29.9 [OR 0.97, 95% confidence interval (CI) 0.93-1.02], BMI 30-34.9 (OR 1.14, 95% CI 1.07-1.23), BMI 35-39.9 (OR 1.28, 95% CI 1.15-1.42), and BMI 40+ (OR 1.73, 95% CI 1.50-1.98). Lean pregnant women (BMI <18.5) also had a higher chance of having EDD postponed 7 days or more (OR 1.11, 95% CI 1.01-1.22).Conclusion: Rising maternal BMI appears to be associated with postponement of ultrasound EDD. [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.

Aim: Both previous versions of the German PRC algorithm developed by our group for routine first-trimester screening relied on the assumption that maternal blood sampling and fetal ultrasonography are performed at the same visit of a pregnant women. In this paper we present an extension of our method allowing also for constellations where this synchronization is abandoned through preponing blood sampling to dates before 11 weeks of gestation. Methods: In contrast to the directly measured concentrations of the serum parameters PAPP-A and free ß-hCG, the logarithmically transformed values could be shown to admit the construction of reference bands covering the whole range from 16 to 84 mm CRL [corresponding to 63 to 98 days of gestation]. Prior to determining reference limits from which the DoEs for each individual patient had to be calculated, the log concentrations of all PAPP-A and free ß-hCG values were transformed once more using the calibration approach established in 1 for the elimination of the influence of maternal weight. Results: Although that part of the database which was available for estimating the reference bands for blood sampling times prior to 11 weeks of gestation was comparatively sparse (898 out of 186 215 pregnancies with euploid outcome), the key statistical characteristics of the extended risk-calculation procedure turned out to be very satisfactory. Using the same cutoff value of 1:150 for the posterior risks of trisomy 21 and 13/18, the overall FPR (false positive rate) for diagnosing a T21 was found to be 3.42%. The corresponding DTR (detection rate) was obtained to be 86.8% and thus exceeded the DTR attained by PRC 2.0 for trisomy 21. For trisomies 13 and 18, the proportions of patients with calculated posterior risks exceeding the cutoff value of 1:150 were obtained to be 1.60% (=FPR) and 86.4% (=DTR). Conclusion: Transforming the measured concentrations of PAPP-A and free ß-hCG to the logarithmic scale allows one to extend the DoE-based algorithm developed by the FMF Germany for diagnosing trisomies 21 and 13/18 in such a way that it can be applied to constellations where blood sampling is done before 11 weeks of gestation.

In this paper the authors examined the most important factors that in the pre-conception period can interfere in the evolution of pregnancy. They also reported a method that since the first trimester of pregnancy is able to identify women at higher risk of developing preeclampsia. Proceedings of the 11th International Workshop on Neonatology and Satellite Meetings · Cagliari (Italy) · October 26th-31st, 2015 · From the womb to the adult Guest Editors: Vassilios Fanos (Cagliari, Italy), Michele Mussap (Genoa, Italy), Antonio Del Vecchio (Bari, Italy), Bo Sun (Shanghai, China), Dorret I. Boomsma (Amsterdam, the Netherlands), Gavino Faa (Cagliari, Italy), Antonio Giordano (Philadelphia, USA)

Background: It is well documented that pregnant women experience increased worry and uncertainty following a high-risk prenatal screening result. While waiting for diagnostic results this worry continues to linger. It has been suggested that high-risk women put the pregnancy mentally 'on hold' during this period, however, not enough is known about how high-risk women and their partners cope while waiting for diagnostic results. The aim of this study was to identify the strategies employed to cope with worry and uncertainty. Methods: Qualitative, semi-structured interviews with 16 high-risk couples who underwent diagnostic testing. The couples were recruited at a university hospital fetal medicine unit in Denmark. Data were analysed using thematic analysis. Results: All couples reported feeling worried and sad upon receiving a high-risk screening result. While waiting for diagnostic results, the couples focused on coming to their own understanding of the situation and employed both social withdrawal and social engagement as strategies to prevent worry from escalating. Additionally, couples used gratitude, reassuring reasoning and selective memory as means to maintain hopes for a good outcome. Discussions about what to do in case of an abnormal test result were notably absent in the accounts of waiting. This bracketing of the potential abnormal result allowed the couples to hold on to a 'normal' pregnancy and to employ an 'innocent-till-proven-guilty' approach to their worries about the fetus's health. None of the interviewed couples regretted having prenatal screening and all of them expected to have prenatal screening in a future pregnancy. Conclusions: The couples in this study did not put the pregnancy mentally 'on hold'. Worry and uncertainty must be understood as managed through a diverse range of practical and emotional strategies that change and overlap in the process of waiting. Clinicians may support appropriate ways of coping with worry and waiting through empathetic and empowering clinical communication. In addition to providing adequate information and presenting options available, clinicians may support high-risk women/couples by encouraging them to seek their own personal understandings and management strategies as a way to gain some control in an uncertain situation. [ABSTRACT FROM AUTHOR]

Objective: To establish a structured review process to facilitate the identification of the fetal nasal bone (NB) in the first trimester ultrasound scan to improve the quality images.Methods: We conducted a retrospective observational study in fetal NB images obtained during ultrasound exams of singleton pregnancies that underwent first trimester screening (crown-rump length 45-84 mm). When the images were obtained the examiner was not aware of the study. Audit was conducted by an examiner according criteria established by the Fetal Medicine Foundation. Fetal NB images were assessed regarding adequate magnification, mid-sagittal view and transducer held parallel to the direction of the nose. The transvaginal and transabdominal as well as anterior and posterior fetal back groups were compared using χ(2) test.Results: We considered 874 fetal NB images for auditing. Fetal NB was considered present in 865 images (99%). During the audit process, we identified 72 (8.2%) cases of disagreement between examiner and auditor assessments. Disagreement was higher when image quality was poor (62 cases = 7%). Transvaginal approach performed better in the following criteria: adequate magnification (p < 0.001), midline (p < 0.001) and completely adequate (p < 0.001).Conclusion: A peer reviewed audit program for fetal NB is feasible in a clinical scenario. Image quality appears to play an important role in compliance to image standards audited and in agreement between examiner and auditor. [ABSTRACT FROM AUTHOR]

Study Question: Are maternal first trimester levels of serum free-beta hCG associated with the development of hypospadias or undescended testis (UDT) in boys?Summary Answer: Overall, first trimester maternal levels of serum free-beta hCG are not associated with hypospadias or UDT. However, elevated levels were found in severe phenotypes (proximal hypospadias and bilateral UDT) suggesting an altered pathway of hormonal release in early pregnancy.What Is Known Already: Human chorionic gonadotrophin peaks in first trimester of pregnancy stimulating fetal testosterone production, which is key to normal male genital development. Endocrine-disrupting insults early in pregnancy have been associated with increased risk of common genital anomalies in males such as hypospadias and UDT. One plausible etiological pathway is altered release of hCG.Study Design, Size, Duration: We conducted a record-linkage study of two separate populations of women attending first trimester aneuploidy screening in two Australian states, New South Wales (NSW) and Western Australia (WA), in 2006-2009 and 2001-2003, respectively.Participants/materials, Setting, Methods: Included were women who gave birth to a singleton live born male infant. There were 12 099 boys from NSW and 10 518 from WA included, of whom 90 and 77 had hypospadias; and 107 and 109 UDT, respectively. Serum levels of free-beta hCG were ascertained from laboratory databases and combined with relevant birth outcomes and congenital anomalies via record linkage of laboratory, birth, congenital anomalies and hospital data. Median and quartile levels of gestational age specific free-beta hCG multiple of the median (MoM) were compared between affected and unaffected boys. Logistic regression was used to evaluate the association between levels of free-beta hCG MoM and hypospadias or UDT, stratified by suspected placental dysfunction and co-existing anomalies. Where relevant, pooled analysis was conducted.Main Results and the Role Of Chance: There was no difference in median hCG levels amongst women with an infant with hypospadias (NSW = 0.88 MoM, P = 0.83; WA = 0.84 MoM, P = 0.76) or UDT (NSW = 0.89 MoM, P = 0.54; WA = 0.95 MoM, P = 0.95), compared with women with an unaffected boy (NSW = 0.92 MoM; WA = 0.88 MoM). Low (<25th centile) or high (>75th centile) hCG levels were not associated with hypospadias or UDT, nor when stratifying by suspected placental dysfunction and co-existing anomalies. However, there was a tendency towards high levels for severe types, although confidence intervals were wide. When combining NSW and WA results, high hCG MoM levels (>75th centile) were associated with increased risk of proximal hypospadias (odds ratio (OR) 4.34; 95% CI: 1.08-17.4) and bilateral UDT (OR 2.86; 95% CI: 1.02-8.03).Limitations, Reasons For Caution: There were only small numbers of proximal hypospadias and bilateral UDT in both cohorts and although we conducted pooled analyses, results reported on these should be interpreted with caution. Gestational age by ultrasound may have been inaccurately estimated in small and large for gestational age fetuses affecting hCG MoM calculation in those pregnancies. Despite the reliability of our datasets in identifying adverse pregnancy outcomes, we did not have pathology information to confirm tissue lesions in the placenta and therefore our composite outcome should be considered as a proxy for placental dysfunction.Wider Implications Of the Findings: This is one of the largest population-based studies examining the association between maternal first trimester serum levels of free-beta hCG and genital anomalies-hypospadias and UDT; and the first to compare specific phenotypes by severity. Overall, our findings does not support the hypothesis that alteration in maternal hCG levels is associated with the development of male genital anomalies; however, high hCG free-beta levels found in severe types suggest different underlying etiology involving higher production and secretion of hCG. These findings require further exploration and replication.Study Funding/competing Interests: This work was funded by the National Health and Medical Research Council (NHMRC) grant APP1047263. N.N. is supported by a NHMRC Career Development Fellowship APP1067066. C.B. was supported by a NHMRC Principal Research Fellowship #634341. The funding agencies had no role in the design, analysis, interpretation or reporting of the findings. There are no competing interests.Trial Registration Number: Not applicable. [ABSTRACT FROM AUTHOR]

Objective: To conduct a literature review to assess the effectiveness of first trimester ultrasonographic markers of spina bifida (SB) integrating data with our prospective experience. Methods: The analysis of the SB cases that we prospectively detected in the first trimester, between January 2012 and February 2014, and a systematic review of all the papers evaluating the effectiveness of SB ultrasonographic markers at 11-14 weeks, namely brain stem diameter (BS), fourth ventricle/intracranial translucency (IT), cisterna magna (CM), brain stem/occipital bone distance (BSOB), the ratio between BS and BSOB. Some studies assess only the effectiveness of IT, others include more parameters, and few include them all. Results: We prospectively detected four SB cases, three open (OSB) and one closed (CSB), in a low risk population undergoing first trimester screening. In the three OSB, CM (in 2/3 cases) and BSOB (3/3) distance were below the 5th percentile, BS and BS/BSOB ratio (3/3) were above the 95th percentile. In the CSB, all the measurements were within normal limits. Conclusion: The literature and our data agree that most fetuses with OSB demonstrate in the first trimester positive sonographic markers in the posterior fossa, but additional prospective studies are needed to establish the best protocol for OSB screening. [ABSTRACT FROM AUTHOR]

Objective: Prenatal screening tests have been developed to detect fetal aneuploidies. These tests and their combinations which are applied in first and second trimester and have different rates for detection of Down's syndrome. The aim of this study was to compare the results of first and second trimester screening tests which were conducted independently in the same pregnancies. Material and Methods: The files of 1136 pregnant women having first and second screening tests independently were examined retrospectively. Patient's ages, gestational weeks, first trimester CRL ve NT measurements were registered with their first and second trimester trisomy risk scores. Collected data were analysed with SPSS (Statistical Package for Social Sciences). Results: Mean age of the pregnant women were calculated as 26.6±5.8. %0.7 (n:8) of first trimester tests and %6.8 (77) of second trimester tests were reported as having high risk for trisomy 21. When the first and second trimester screening results in the same pregnancies were compared in terms of trisomy 21 risk scores; case numbers in terms of equal, decreased and increased risk were calculated as 55 (4.8%), 468 (41.2%) ve 613 (54.4%), respectively. While 11% (n:125) of those having decreased and increased risk were above 35 years old, this rate was just %0.1 (n:1) in those having no difference. Conclusion: In our study, 76 of 1128 patients detected as having low risk (<1\250) for trisomy 21 at the first trimester were encountered as having high risk (>1\250) at the second trimester test. Interpreting the tests independently will cause false positive results because of this we think that it is necessary to evaluate first and second trimester test results as entegrated. [ABSTRACT FROM AUTHOR]

Objective: Pregnancy-associated plasma protein A (PAPP-A) is a macromolecular glycoprotein. The peritoneal fluid of women affected by endometriosis shows a significant increase of PAPP-A levels. Given the important role of PAPP-A in first trimester screening test, we wondered if its presence in the peritoneal fluid of women with endometriosis could affect biochemical parameters of the test performed during pregnancy. Methods: A prospective study enrolled 78 women with singleton pregnancy who performed combined test between 11 + 0 and 13 + 6 weeks of gestation: 25 women with previous histological diagnosis of endometriosis and 53 women without. All patients were sampled to determine PAPP-A concentrations. Serum levels of PAPP-A were expressed in UI/L and in MoM (multiples of median). The two groups - endometriosis women and non-endometriosis women - were compared in order to find a possible different concentration of serum PAPP-A. Results: We found an increased concentration of both PAPP-A UI/L and PAPP-A MoM in deep endometriosis patients versus ovarian endometriosis with significant difference in PAPP-A MoM (p = 0.018). We also found a significant association between the stage of the disease and PAPP-A UI/L and MoM levels (PAPPA UI/L p = 0.05, PAPP-A MoM p = 0.01). Conclusions: Women with deep endometriosis show increased serum PAPP-A concentrations compared to women with ovarian endometriosis. Likewise, women with moderate or severe stage of the disease show increased serum PAPP-A concentrations compared to women with minimum or mild disease. This increase could affect first trimester aneuploidy screening test and endometriosis could represent a confounding factor in the calculation of aneuploidy risk. [ABSTRACT FROM AUTHOR]

The early detection of foetal growth restriction and macrosomia is an important goal of modern obstetric care. Aberrant foetal growth is an important cause of perinatal morbidity and mortality. Current modalities for detecting the abnormal foetal growth are often inadequate. Pulse wave analysis using applanation tonometry is a simple and non-invasive test that provides information about the cardiovascular system. Arterial elasticity has previously been implicated in the pathophysiology of pre-eclampsia and cardiovascular disease. Our study examined the relationship between maternal arterial elasticity and birthweight by using pulse wave analysis. We discovered that increased large artery elasticity predicted a larger baby at birth. Large artery elasticity therefore has the potential to act as a useful screening tool which may help in the prediction of women who are at risk of aberrant foetal growth. [ABSTRACT FROM PUBLISHER]

Objective: To explore in women with late-onset preeclampsia (PE) the association between maternal levels of angiogenic/antiangiogenic factors in the first trimester of pregnancy and histological findings attributable to placental underperfusion (PUP).Methods: A nested case-control cohort study was conducted in 73 women with pregnancies complicated by late-onset PE (>34 weeks at delivery) matched with controls. First trimester uterine artery Doppler (UtA); maternal levels of placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) were retrieved. Placentas were histologically evaluated using a hierarchical and standardized classification system. One-way ANOVA with linear polynomial contrast or linear-by-linear association test was performed to test the hypothesis of a linear association across study groups (controls, PE without PUP and PE with PUP).Results: In 54 (74%) placentas, 89 placental histological findings qualifying for PUP were found. Across study groups, significant values were observed in maternal levels of decreased PlGF (MoM values: 1.53, 1.41 and 1.37; p < 0.001), increased sFlt-1 (MoM values: 3.11, 3.11 and 3.22; p = 0.002), increased sFlt-1/PlGF ratio (MoM values: 2.3, 2.3 and 2.44; p < 0.001), abnormal UtA Doppler (MoM values: 1, 1.26 and 1.32; p < 0.001), and worse perinatal outcomes in terms of gestational age at delivery, cesarean section for not reassuring fetal status, birth weight and neonatal acidosis.Discussion: In late-onset PE an imbalance of circulating angiogenic and anti-angiogenic factors already present at 8-10 weeks of pregnancy was associated with histological findings reflecting placental insufficiency. An early first trimester screening by angiogenic factors might help to identify patients with placental involvement among late-onset PE cases.Conclusion: In late-onset preeclampsia, first-trimester uterine Doppler and circulating levels of angiogenic/antiangiogenic factors are associated with placental underperfusion. [ABSTRACT FROM AUTHOR]

Objective To examine the potential role of maternal serum levels of tumor necrosis factor-α (TNF-α) and high sensitivity C-reactive protein (Hs-CRP) in the first trimester of pregnancy in the prediction of gestational diabetes mellitus (GDM). Methods Maternal serum TNF-α and Hs-CRP concentrations were measured in a case–control study of singleton pregnancies at 11–13 weeks' gestation, which included 200 cases that subsequently developed GDM and 800 unaffected controls. Measured levels of TNF-α and Hs-CRP were expressed as multiples of the median (MoM) after adjustment for maternal characteristics and history. The performance of screening for GDM by maternal factors and MoM values of TNF-α and Hs-CRP was evaluated by the area under the receiver operating characteristic curves (AUROC). Results In the GDM group, compared to the normal group, the median TNF-α was significantly increased (1.303 MoM, interquartile range [IQR] 1.151–1.475 vs. 1.0 MoM, IQR 0.940–1.064; p = 0.031) and the median Hs-CRP was not significantly different (1.113 MoM, IQR 0.990–1.250 vs. 1.0 MoM, IQR 0.943–1.060; p = 0.084). In the prediction of GDM, the AUROC for maternal characteristics with TNF-α or Hs-CRP was not significantly different than the AUROC for maternal characteristics alone (p = 0.5055 and p = 0.2197, respectively). Conclusions In pregnancies that develop GDM there is no evidence of an inflammatory response at 11–13 weeks’ gestation and the levels of serum TNF-α and Hs-CRP are not useful in first-trimester screening for GDM. [ABSTRACT FROM AUTHOR]