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Background: Maternal gestational diabetes (GDM), small (SGA) and large (LGA) for gestational age neonates are associated with increased morbidity in both mother and child. We studied how different levels of first trimester pregnancy associated plasma protein-A (PAPP-A) and free beta human chorionic gonadotropin (fβ-hCG) were associated with SGA and LGA in GDM pregnancies and controls. Methods: Altogether 23 482 women with singleton pregnancies participated in first trimester combined screening and delivered between 2014 and 2018 in Northern Finland and were included in this retrospective case-control study. Women with GDM (n = 4697) and controls without GDM (n = 18 492) were divided into groups below 5th and 10th or above 90th and 95th percentile (pc) PAPP-A and fβ-hCG MoM levels. SGA was defined as a birthweight more than two standard deviations (SD) below and LGA more than two SDs above the sex-specific and gestational age-specific reference mean. Odds ratios were adjusted (aOR) for maternal age, BMI, ethnicity, IVF/ICSI, parity and smoking. Results: In pregnancies with GDM the proportion of SGA was 2.6% and LGA 4.5%, compared to 3.3% (p = 0.011) and 1.8% (p < 0.001) in the control group, respectively. In ≤ 5th and ≤ 10th pc PAPP-A groups, aORs for SGA were 2.7 (95% CI 1.5–4.7) and 2.2 (95% CI 1.4–3.5) in the GDM group and 3.8 (95% CI 3.0–4.9) and 2.8 (95% CI 2.3–3.5) in the reference group, respectively. When considering LGA, there was no difference in aORs in any high PAPP-A groups. In the low ≤ 5 percentile fβ-hCG MoM group, aORs for SGA was 2.3 (95% CI 1.8–3.1) in the control group. In fβ-hCG groups with GDM there was no association with SGA and the only significant difference was ≥ 90 percentile group, aOR 1.6 (95% CI 1.1–2.5) for LGA. Conclusion: Association with low PAPP-A and SGA seems to be present despite GDM status. High PAPP-A levels are not associated with increased LGA risk in women with or without GDM. Low fβ-hCG levels are associated with SGA only in non-GDM pregnancies. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this cross‐sectional questionnaire study was to investigate motivation to participate in a possible new screening for preeclampsia in the first trimester of pregnancy among Danish pregnant women through a questionnaire based on Theory of Planned Behavior developed for this specific purpose. The new screening combines maternal characteristics with mean arterial pressure, uterine artery pulsatility index and biochemical markers to predict the risk of preeclampsia, whereas the current Danish screening uses maternal characteristics alone. Material and methods: Participation was offered to a proportion of women attending a first or a second trimester screening scan at two University Hospitals in Copenhagen. The questionnaire was set up in REDCap® and answers were entered directly into the database, which was accessed via a QR‐code. Results: We invited 772 pregnant women to participate in the questionnaire survey between November 2021 and April 2022 at Copenhagen University Hospital Rigshospitalet (study site one) (n = 238) and Copenhagen University Hospital Hvidovre (study site two) (n = 534). The response rate was 71.8% (171/238) at study site one and 33.9% (181/534) at study site two. A total of 352 women were included in the study (total participation rate 45.6%). Most women had a positive attitude towards preeclampsia screening in pregnancy, and 99.4% said they would participate in a risk assessment for preeclampsia if given the opportunity. A total of 97.4% answered "yes" to whether a first trimester preeclampsia screening should be offered to all pregnant women in Denmark. Positive motivation to participate in preeclampsia screening was correlated with having a network with a positive attitude towards preeclampsia screening. Conclusions: The results of this study indicate that Danish pregnant women have a positive attitude towards participation in a first trimester screening for preeclampsia. This observation might be useful in relation to possible future implementation in Denmark. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [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: In this study, we report the indications for prenatal cytogenetic diagnosis of triploid cases, in an attempt to identify clues to early diagnosis.Study Design: This was a retrospective analysis of prenatal cases of triploidy during a 9-year period at mainland China. Clinical data were reviewed for these cases, including maternal demographics, indications for invasive testing, fetal ultrasound findings, and pregnancy outcomes.Results: A total of 22 singleton pregnancies affected with triploid fetuses were detected. The fetal karyotype included 69,XXX (72.7%) and 69,XXY (27.3%). Eighteen cases were identified by the first trimester screening program. One case was missed by maternal cell-free DNA testing, but detected by second trimester anatomy scan. Three cases escaped the first trimester screening and were detected by second trimester anatomy scan.Conclusions: The present study demonstrates that most triploid cases can be diagnosed prenatally during the first trimester. The early asymmetrical fetal growth restriction, structural anomalies, and extremely high risk serum screening result for trisomy 21 or 18 should alert the physicians to the investigation of triploidy.Key Message: Ultrasound-based first-trimester screening plays a major role in early diagnosis of fetal triploidy. Future replacement of routine first-trimester screening by cell-DNA testing might miss the chance of early diagnosis and management of triploid pregnancies. [ABSTRACT FROM AUTHOR]

Objectives: Early identification of preeclampia in the first trimester of pregnancy represents one of the major challenges of modern fetal medicine. The primary aim of our study was to evaluate the effectiveness of implementation of preeclampsia screening in Tuscany, Italy. The secondary aim was to evaluate pregnancy/neonatal outcome in the positive screening group compared with the negative screening group.Study Design: Retrospective study including singleton pregnancies undergoing screening for preeclampsia. The screening test was a multiparametric algorithm based on maternal history, biochemical and biophysical parameters (Fetal Medicine Foundation algorithm).Main Outcome Measures: The overall performance of the test was calculated, in terms of sensitivity, specificity, positive and negative predictive value and in relation to gestational age at onset (primary aim). Pregnancy and neonatal outcomes were then compared between the positive and negative population at preeclampsia screening test (secondary aim).Results: Of the 5719 patients enrolled, 4797 were included in the analysis. The sensitivity for early onset of preeclampsia (≤34 weeks) was 0.75 (CI:0.41-0.93) and specificity 0.93 (CI:0.92-0.94) for a false positive rate of 7%. The population that tested positive for preeclampsia screening showed a higher incidence of deliveries at lower gestational ages (p < 0.001), preeclampsia onset despite prophylaxis with aspirin (p < 0.001), emergency caesarean section (p < 0.001), low fetal birth weight (p < 0.001) and neonatal admission in intensive care unit (p < 0.001).Conclusions: Our data confirm the validity of first trimester screening test in identifying a category of patients at greatest risk for preeclampsia even in the presence of a post-test pharmacological prophylaxis. [ABSTRACT FROM AUTHOR]

To identify the most common ultrasound patterns of markers and anomalies associated with Patau syndrome (PS), to explore the efficacy of multiparameter sonographic protocols in detecting trisomy 13 (T13) and to analyze the influence of maternal age (MA) on screening performance. The project was a prospective study based on singleton pregnancies referred for a first-trimester screening examination. The scan protocol included nuchal translucency (NT), fetal heart rate (FHR), secondary ultrasound markers [nasal bone (NB), tricuspid regurgitation (TR), ductus venosus reversed a-wave (revDV)] and major anomaly findings. The study population comprised 6133 pregnancies: 6077 cases of euploidy and 56 cases of T13. Statistically significant differences were found in MA, FHR, NT, absence of NB, presence of revDV, TR and single umbilical artery. Fourteen cases of T13 (25%) demonstrated no markers of aneuploidy. The best general detection rate (DR) (DR of 78.6% with an false positive rate (FPR) of 1.2%) was obtained for a cutoff of 1/300 utilizing the "NT+T13" algorithm. The logistic regression model revealed that the central nervous system (CNS) anomalies had the greatest odds ratio (of 205.4) for T13. The effectiveness of the multiparameter sonographic protocol used for T13 screening showed promising results in patients older than 36 years and suboptimal results in patients between 26 and 36 years old. When screening for T13 left heart defects, CNS anomalies, abdominal anomalies, FHR above the 95th percentile, increased NT, revDV and lack of NB should receive specific attention. [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.)

Introduction: Preeclampsia affects about 10% of twin pregnancies and significantly increases the risk of adverse pregnancy outcomes. However, screening models for preeclampsia in twin pregnancies remain elusive. The present study aimed to evaluate the performance of a multi-marker first trimester preeclampsia screening model in low-risk twin pregnancies.Material and Methods: Between 2014 and 2017, we prospectively assessed first trimester biomarkers for preeclampsia in a 'low-risk' twin pregnancy cohort at a single center. Multiple logistic regression was used to determine significant predictors for early preeclampsia (occurring prior to 34 weeks) and late preeclampsia (occurring after 34 weeks). The performance of the screening models fitted using the significant predictors was calculated using receiver operating characteristics curves, and internal validation was performed using bootstrapping.Results: A total of 769 twin pregnancies were included in the study. Early preeclampsia and late preeclampsia developed in 27 (3.5%) and 59 (7.7%) cases, respectively. Logistic regression analyses showed that maternal age, body mass index, mean artery pressure and placental growth factor were significant predictors for early preeclampsia. Maternal age, body mass index, mean artery pressure and pregnancy-associated plasma protein A were significant for late preeclampsia. Uterine artery pulsatility index was not predictive of either early or late preeclampsia. For the fitted screening model of early and late preeclampsia, the areas under receiver operating characteristics curves were 0.82 (95% confidence interval [CI] 0.76-0.88) and 0.66 (95% CI 0.59-0.73), which were expected to decrease to 0.77 and 0.60, respectively, based on bootstrapping; the positive predictive values were 10.2% and 12.5%; and the estimated detection rates were 40.7% and 22.0%, respectively, at a false-positive rate of 10%.Conclusions: A multi-marker screening model for preeclampsia in low-risk twin pregnancies, using a modified version of Fetal Medicine Foundation predictors in singletons, does not perform well. Uterine artery pulsatility index is of little value in screening for preeclampsia in low-risk twin pregnancies. [ABSTRACT FROM AUTHOR]

Objective: To evaluate whether neutrophil-to-lymphocyte ratio (NLR), a well-established inflammatory marker, can be used as an early predictor for small-for-gestational-age (SGA) neonates and other adverse pregnancy outcomes.Methods: A case-control study compared first-trimester hematological biomarkers in pregnancies of patients with and without SGA (n=149, n=151, respectively). Demographic, clinical, and obstetrical characteristics and first-trimester complete blood count were retrieved. Woman with singleton pregnancies who delivered at Soroka University Medical Center between January 2015 and December 2016 were included. Patients with known maternal infections, relevant medications, hematological conditions, and chronic diseases that may alter the blood count, those with multiple pregnancies, and those with congenital or chromosomal abnormalities were excluded. After univariate analysis, a linear regression model was constructed to assess the association between hematological indices and SGA. Receiver operating curves were constructed to evaluate the sensitivity and specificity of NLR.Results: First-trimester NLR values of the SGA group were significantly higher compared to controls (3.03 ± 1.68 vs 2.63 ± 1.2, P=0.016). Significantly higher levels of NLR were noted among the severely (<3%) SGA neonates (3.12 ± 1.62 vs 2.62 ± 1.2; P=0.034).Conclusion: NLR may be an early, clinically useful marker in the prediction of SGA. As blood samples are routinely collected, correct implication of this result may serve as a valuable non-invasive, low-cost, readily available predicting tool. [ABSTRACT FROM AUTHOR]

Background: We hypothesized that earlier gestational diabetes mellitus (GDM) diagnosis and treatment of high-risk women would reduce gestational weight gain (GWG) in the first trimester and overall. Materials and Methods: We evaluated timing of GDM diagnosis among 5,391 pregnant women who delivered singleton births 2010–2013 in a large diverse health maintenance organization (HMO). All GDM screening was by the same oral glucose tolerance testing protocol; GDM treatment protocols were also consistent irrespective of timing of diagnosis. Women without risk factors were universally screened at 24–28 weeks gestation (Usual). Early screening was recommended in obese and other high-risk women at the first prenatal visit; those who screened negative Early were rescreened at 24–28 weeks (Early+Usual). Results: Average GWG for all women was 12.8 kg; 10.7% of women were diagnosed with GDM. Average GWG for all women diagnosed with GDM was 10.7 kg, adjusted for gestational age. Women with EarlyGDM averaged 2.4 kg less GWG than women diagnosed with UsualGDM (p < 0.0001). Among obese women, only women diagnosed with EarlyGDM averaged overall GWG within Institute of Medicine (IOM) weight guidelines (mean 8.1 kg) and were weight neutral in the first trimester (-0.2 kg). Overall, 43% of all pregnant women exceeded IOM GWG guidelines (gained more total weight than recommended); 60% of obese women exceeded guidelines. Obese women diagnosed with GDM were less likely to exceed IOM guidelines if diagnosed earlier in pregnancy (35% EarlyGDM vs. 59% UsualGDM exceeded guidelines, p < 0.0001). Conclusion: Our results suggest that EarlyGDM diagnosis (and thus treatment) in high-risk women is beneficial for optimizing GWG. [ABSTRACT FROM AUTHOR]

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]

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 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: 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]

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]

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]

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]

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: 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]

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]

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]

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]

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: 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]

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]

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]

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]

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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]

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]