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Objective: To compare the predictive performance of three different mathematical models for first‐trimester screening of pre‐eclampsia (PE), which combine maternal risk factors with mean arterial pressure (MAP), uterine artery pulsatility index (UtA‐PI) and serum placental growth factor (PlGF), and two risk‐scoring systems. Methods: This was a prospective cohort study performed in eight fetal medicine units in five different regions of Spain between September 2017 and December 2019. All pregnant women with singleton pregnancy and a non‐malformed live fetus attending their routine ultrasound examination at 11 + 0 to 13 + 6 weeks' gestation were invited to participate in the study. Maternal characteristics and medical history were recorded and measurements of MAP, UtA‐PI, serum PlGF and pregnancy‐associated plasma protein‐A (PAPP‐A) were converted into multiples of the median (MoM). Risks for term PE, preterm PE (< 37 weeks' gestation) and early PE (< 34 weeks' gestation) were calculated according to the FMF competing‐risks model, the Crovetto et al. logistic regression model and the Serra et al. Gaussian model. PE classification was also performed based on the recommendations of the National Institute for Health and Care Excellence (NICE) and the American College of Obstetricians and Gynecologists (ACOG). We estimated detection rates (DR) with their 95% CIs at a fixed 10% screen‐positive rate (SPR), as well as the area under the receiver‐operating‐characteristics curve (AUC) for preterm PE, early PE and all PE for the three mathematical models. For the scoring systems, we calculated DR and SPR. Risk calibration was also assessed. Results: The study population comprised 10 110 singleton pregnancies, including 32 (0.3%) that developed early PE, 72 (0.7%) that developed preterm PE and 230 (2.3%) with any PE. At a fixed 10% SPR, the FMF, Crovetto et al. and Serra et al. models detected 82.7% (95% CI, 69.6–95.8%), 73.8% (95% CI, 58.7–88.9%) and 79.8% (95% CI, 66.1–93.5%) of early PE; 72.7% (95% CI, 62.9–82.6%), 69.2% (95% CI, 58.8–79.6%) and 74.1% (95% CI, 64.2–83.9%) of preterm PE; and 55.1% (95% CI, 48.8–61.4%), 47.1% (95% CI, 40.6–53.5%) and 53.9% (95% CI, 47.4–60.4%) of all PE, respectively. The best correlation between predicted and observed cases was achieved by the FMF model, with an AUC of 0.911 (95% CI, 0.879–0.943), a slope of 0.983 (95% CI, 0.846–1.120) and an intercept of 0.154 (95% CI, –0.091 to 0.397). The NICE criteria identified 46.7% (95% CI, 35.3–58.0%) of preterm PE at 11% SPR and ACOG criteria identified 65.9% (95% CI, 55.4–76.4%) of preterm PE at 33.8% SPR. Conclusions: The best performance of screening for preterm PE is achieved by mathematical models that combine maternal factors with MAP, UtA‐PI and PlGF, as compared to risk‐scoring systems such as those of NICE and ACOG. While all three algorithms show similar results in terms of overall prediction, the FMF model showed the best performance at an individual level. © 2024 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the diagnostic accuracy of the Fetal Medicine Foundation (FMF) competing‐risks model, incorporating maternal characteristics, mean arterial pressure (MAP), uterine artery pulsatility index (UtA‐PI) and placental growth factor (PlGF) (the 'triple test'), for the prediction at 11–13 weeks' gestation of preterm pre‐eclampsia (PE) in a Spanish population. Methods: This was a prospective cohort study performed in eight fetal medicine units in five different regions of Spain between September 2017 and December 2019. All pregnant women with a singleton pregnancy and a non‐malformed live fetus attending a routine ultrasound examination at 11 + 0 to 13 + 6 weeks' gestation were invited to participate. Maternal demographic characteristics and medical history were recorded and MAP, UtA‐PI, serum PlGF and pregnancy‐associated plasma protein‐A (PAPP‐A) were measured following standardized protocols. Treatment with aspirin during pregnancy was also recorded. Raw values of biomarkers were converted into multiples of the median (MoM), and audits were performed periodically to provide regular feedback to operators and laboratories. Patient‐specific risks for term and preterm PE were calculated according to the FMF competing‐risks model, blinded to pregnancy outcome. The performance of screening for PE, taking into account aspirin use, was assessed by calculating the area under the receiver‐operating‐characteristics curve (AUC) and detection rate (DR) at a 10% fixed screen‐positive rate (SPR). Risk calibration of the model was assessed. Results: The study population comprised 10 110 singleton pregnancies, including 72 (0.7%) that developed preterm PE. In the preterm PE group, compared to those without PE, median MAP MoM and UtA‐PI MoM were significantly higher, and median serum PlGF MoM and PAPP‐A MoM were significantly lower. In women with PE, the deviation from normal in all biomarkers was inversely related to gestational age at delivery. Screening for preterm PE by a combination of maternal characteristics and medical history with MAP, UtA‐PI and PlGF had a DR, at 10% SPR, of 72.7% (95% CI, 62.9–82.6%). An alternative strategy of replacing PlGF with PAPP‐A in the triple test was associated with poorer screening performance for preterm PE, giving a DR of 66.5% (95% CI, 55.8–77.2%). The calibration plot showed good agreement between predicted risk and observed incidence of preterm PE, with a slope of 0.983 (95% CI, 0.846–1.120) and an intercept of 0.154 (95% CI, −0.091 to 0.397). Conclusions: The FMF model is effective in predicting preterm PE in the Spanish population at 11–13 weeks' gestation. This method of screening is feasible to implement in routine clinical practice, but it should be accompanied by a robust audit and monitoring system, in order to maintain high‐quality screening. © 2023 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

This article compares the predictive performance of three different mathematical models for screening pre-eclampsia (PE) in the first trimester of pregnancy. The models combine maternal risk factors with mean arterial pressure (MAP), uterine artery pulsatility index (UtPI), and serum placental growth factor (PlGF). The study, conducted in eight Spanish hospitals, included 10,110 singleton pregnancies. The results showed that all three models had similar overall prediction results and outperformed the scoring systems. However, the FMF model demonstrated the best performance at the individual level. [Extracted from the article]

This article evaluates the accuracy of using fetal biparietal diameter (BPD) at 11-13 weeks for pregnancy dating compared to the measurement of Crown-rump length (CRL). The study was conducted in Spain, UK, Belgium, and Bulgaria and included women with singleton, non-malformed fetus/neonate. The researchers developed a formula for pregnancy dating based on BPD and validated it against commonly used formulas. The results showed that pregnancy dating based on ultrasound measurement of fetal BPD is a reliable alternative to dating based on CRL. [Extracted from the article]

Objective: Effective first‐trimester screening for pre‐eclampsia (PE) can be achieved using a competing‐risks model that combines risk factors from the maternal history with multiples of the median (MoM) values of biomarkers. A new model using artificial intelligence through machine‐learning methods has been shown to achieve similar screening performance without the need for conversion of raw data of biomarkers into MoM. This study aimed to investigate whether this model can be used across populations without specific adaptations. Methods: Previously, a machine‐learning model derived with the use of a fully connected neural network for first‐trimester prediction of early (< 34 weeks), preterm (< 37 weeks) and all PE was developed and tested in a cohort of pregnant women in the UK. The model was based on maternal risk factors and mean arterial blood pressure (MAP), uterine artery pulsatility index (UtA‐PI), placental growth factor (PlGF) and pregnancy‐associated plasma protein‐A (PAPP‐A). In this study, the model was applied to a dataset of 10 110 singleton pregnancies examined in Spain who participated in the first‐trimester PE validation (PREVAL) study, in which first‐trimester screening for PE was carried out using the Fetal Medicine Foundation (FMF) competing‐risks model. The performance of screening was assessed by examining the area under the receiver‐operating‐characteristics curve (AUC) and detection rate (DR) at a 10% screen‐positive rate (SPR). These indices were compared with those derived from the application of the FMF competing‐risks model. The performance of screening was poor if no adjustment was made for the analyzer used to measure PlGF, which was different in the UK and Spain. Therefore, adjustment for the analyzer used was performed using simple linear regression. Results: The DRs at 10% SPR for early, preterm and all PE with the machine‐learning model were 84.4% (95% CI, 67.2–94.7%), 77.8% (95% CI, 66.4–86.7%) and 55.7% (95% CI, 49.0–62.2%), respectively, with the corresponding AUCs of 0.920 (95% CI, 0.864–0.975), 0.913 (95% CI, 0.882–0.944) and 0.846 (95% CI, 0.820–0.872). This performance was achieved with the use of three of the biomarkers (MAP, UtA‐PI and PlGF); inclusion of PAPP‐A did not provide significant improvement in DR. The machine‐learning model had similar performance to that achieved by the FMF competing‐risks model (DR at 10% SPR, 82.7% (95% CI, 69.6–95.8%) for early PE, 72.7% (95% CI, 62.9–82.6%) for preterm PE and 55.1% (95% CI, 48.8–61.4%) for all PE) without requiring specific adaptations to the population. Conclusions: A machine‐learning model for first‐trimester prediction of PE based on a neural network provides effective screening for PE that can be applied in different populations. However, before doing so, it is essential to make adjustments for the analyzer used for biochemical testing. © 2023 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objective: Epidemiological studies have established that women with pre‐eclampsia (PE) are at increased long‐term cardiovascular risk. Mild cardiac functional changes have been documented during pregnancy in women with PE, but their evolution from presentation to the postpartum period remains poorly defined. The aim of this study was to assess biventricular cardiovascular indices using novel and sensitive two‐dimensional and three‐dimensional (3D) echocardiographic modalities in pregnancy and to track alterations in both risk factors and cardiovascular indices in the postpartum period. Methods: A total of 59 women with PE were examined at 34 (interquartile range, 31–37) weeks' gestation and at 2–3 days, 3 months and 6 months postpartum. During pregnancy, 118 women with a normotensive pregnancy were also recruited as controls. Biventricular ejection fraction and left ventricular mass were measured by 3D echocardiography. Biventricular global longitudinal strain and strain of the left atrium were assessed using speckle‐tracking imaging. Results: In women with PE, compared with controls, there was lower left ventricular diastolic function (left atrial reservoir strain, 44.1% vs 49.2%) and increased left ventricular mass index (148 vs 128 g/m2), but there was no significant difference in right ventricular functional indices. These alterations in cardiac indices were mostly explained by differences in maternal risk factors. In the postpartum period, most cardiac indices improved by 3 months. Multivariable linear mixed‐model analysis demonstrated that this improvement was mostly attributed to reduction in weight and blood pressure. Conclusion: In women with PE, there is postpartum improvement in cardiac functional and structural indices in parallel with improvement in their risk factor profile. © 2023 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

This article, published in the journal Ultrasound in Obstetrics & Gynecology, examines the effectiveness of the cerebro-placental ratio (CPR) in predicting adverse perinatal outcomes in uncomplicated singleton pregnancies attending a 40-42 week appointment. The study analyzed data from 3143 pregnancies and found that maternal age, body mass index, racial origin, parity, and labor induction were significant predictors of adverse perinatal outcomes. However, the addition of the CPR did not improve the predictive performance, and the CPR alone had a low detection rate. Therefore, the study concludes that the CPR is not a reliable predictor of adverse perinatal outcomes in post-term pregnancies. [Extracted from the article]

Objective: To estimate the risk of fetal loss associated with chorionic villus sampling (CVS) in twin pregnancy, using propensity score analysis. Methods: This was a multicenter cohort study of women with twin pregnancy undergoing ultrasound examination at 11–13 weeks' gestation, performed in eight fetal medicine units in which the leadership were trained at the Harris Birthright Research Centre for Fetal Medicine in London, UK, and in which the protocols for screening, invasive testing and pregnancy management are similar. The risk of death of at least one fetus was compared between pregnancies that had and those that did not have CVS, after propensity score matching (1:1 ratio). This procedure created two comparable groups by balancing the maternal and pregnancy characteristics that lead to CVS being performed, similar to how randomization operates in a randomized clinical trial. Results: The study population of 8581 twin pregnancies included 445 that had CVS. Death of one or two fetuses at any stage during pregnancy occurred in 11.5% (51/445) of pregnancies in the CVS group and in 6.3% (515/8136) in the non‐CVS group (P < 0.001). The propensity score algorithm matched 258 cases that had CVS with 258 non‐CVS cases; there was at least one fetal loss in 29 (11.2%) cases in the CVS group and in 35 (13.6%) cases in the matched non‐CVS group (odds ratio (OR), 0.81; 95% CI, 0.48–1.35; P = 0.415). However, there was a significant interaction between the risk of fetal loss after CVS and the background risk of fetal loss; when the background risk was higher, the risk of fetal loss after CVS decreased (OR, 0.46; 95% CI, 0.23–0.90), while, in pregnancies with a lower background risk of fetal loss, the risk of fetal loss after CVS increased (OR, 2.45; 95% CI, 0.95–7.13). The effects were statistically significantly different (P‐value of the interaction = 0.005). For a pregnancy in which the background risk of fetal loss was about 6% (the same as in our non‐CVS population), there was no change in the risk of fetal loss after CVS, but, when the background risk was more than 6%, the posterior risk was paradoxically reduced, and when the background risk was less than 6%, the posterior risk increased exponentially; for example, if the background risk of fetal loss was 2.0%, the relative risk was 2.8 and the posterior risk was 5.6%. Conclusion: In twin pregnancy, after accounting for the risk factors that lead to both CVS and spontaneous fetal loss and confining the analysis to pregnancies at lower prior risk, CVS seems to increase the risk of fetal loss by about 3.5% above the patient's background risk. © 2021 International Society of Ultrasound in Obstetrics and Gynecology. Linked article: There is a comment on this article by Li and Li. Click here to view the Correspondence. [ABSTRACT FROM AUTHOR]

Objectives: Gestational diabetes mellitus (GDM) is associated with premature cardiovascular disease and adverse cardiovascular outcome in the mother. Subclinical cardiac functional changes in the left ventricle have been reported during pregnancy in women with GDM using conventional echocardiography, but results are inconsistent. The aims of the current study were to assess whether GDM is associated with biventricular systolic dysfunction in the mother and whether these cardiac changes can be detected using the novel echocardiographic modalities of strain imaging and three‐dimensional (3D) echocardiography. Methods: This was a cross‐sectional study in women with GDM and controls examined at 26–40 weeks of gestation. All women underwent echocardiography, and 3D volumes of the left and right ventricles and left atrium were collected. Ejection fraction and left ventricular mass were measured using 3D echocardiography. Left ventricular mass was indexed to body surface area. Speckle‐tracking echocardiography was used to assess global longitudinal strain of the left and right ventricles and strain of the left atrium. Results: The study population included 123 women with GDM and 246 controls. Women with GDM, compared to controls, were older (35.1 ± 5.2 vs 32.4 ± 5.5 years; P < 0.001), had higher body mass index (30.6 (interquartile range (IQR), 26.2–35.2) vs 27.5 (IQR, 24.7–30.7) kg/m2; P < 0.001) and had higher systolic blood pressure (119.9 ± 11.2 vs 116.4 ± 12.0 mmHg; P = 0.007). In all women with GDM, there was good glycemic control. In women with GDM, compared to controls, there was lower global longitudinal strain of the left ventricle (−19.3% (IQR, −21.4 to −17.6%) vs −20.1% (IQR, −22.1 to −18.7%); P = 0.002) and right ventricle (−22.2% (IQR, −26.1 to −19.8%) vs −24.1% (IQR, −27.0 to −21.9%); P < 0.001). There was no significant difference between the groups in ejection fraction, left ventricular mass, diastolic function assessed by left atrial strain, or 3D functional indices. Conclusions: Women with GDM, compared to women with uncomplicated pregnancy, have lower left and right ventricular myocardial deformation. Volumetric assessment using 3D echocardiography does not provide additional information about maternal cardiac function. Strain imaging is a sensitive echocardiographic modality to detect early cardiac functional changes in women with GDM. Further studies are needed to assess the pattern of deterioration of cardiac function with advancing age in women with a history of GDM. © 2021 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objective: To estimate the chorionic villus sampling (CVS)-related risk of fetal loss in twin pregnancy after adjustment for chorionicity, nuchal translucency thickness (NT), intertwin discordance in crown-rump length (CRL), maternal demographic characteristics and serum pregnancy-associated plasma protein-A (PAPP-A) and free β-human chorionic gonadotropin (β-hCG).Methods: This was a multicenter study from eight fetal medicine units in which the leadership were trained at the Harris Birthright Research Centre for Fetal Medicine in London, UK, and in which the protocols for screening, invasive testing and pregnancy management are similar. Data were obtained prospectively from women with twin pregnancy undergoing routine ultrasound examination at 11-13 weeks' gestation. Multivariable logistic regression analysis with backward stepwise elimination was used to examine whether CVS provided a significant independent contribution to the prediction of risk of fetal loss after adjusting for maternal and pregnancy characteristics, including maternal age, racial origin and weight, method of conception, smoking status, parity, chorionicity, intertwin discordance in CRL, fetal NT ≥ 95th percentile and free β-hCG and PAPP-A multiples of the median. Similarly, within the CVS group, multivariable logistic regression analysis was used to investigate the effect of the number of intrauterine needle insertions and size of the needle on the risk of fetal loss.Results: The study population of 8581 twin pregnancies undergoing ultrasound examination at 11-13 weeks' gestation included 316 dichorionic and 129 monochorionic twins that had CVS. First, in twin pregnancies undergoing CVS, compared to those not undergoing CVS, there was a 2-fold increased risk of fetal loss at < 24 weeks' gestation and of loss at any stage in pregnancy. Second, the factors providing a significant independent contribution to the prediction of miscarriage or fetal loss in twin pregnancy were increased maternal weight, black racial origin, monochorionicity, and more so monoamnionicity, large intertwin discordance in CRL and increased fetal NT, and, in the case of fetal loss at any stage, there was also a contribution from assisted conception and low serum PAPP-A. Third, after adjustment for maternal and pregnancy characteristics, CVS did not provide a significant contribution to the risk of fetal loss. Fourth, in twin pregnancies that had CVS, there was no significant contribution to fetal loss from the number of intrauterine needle insertions or needle size.Conclusion: The 2-fold increased risk of fetal loss following CVS in twin pregnancy can, to a great extent, be explained by maternal and pregnancy characteristics rather than the invasive procedure itself. © 2021 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objectives: To assess differences in cardiac morphology and function in fetuses of mothers with gestational diabetes mellitus (GDM) compared to controls, and to assess whether, in women with GDM, fetal cardiac changes are accentuated with advancing gestational age.Methods: We studied 112 women with GDM and 224 women with uncomplicated pregnancy at 24-40 weeks' gestation. In all fetuses, a standard four-chamber oblique view was obtained and offline speckle-tracking analysis was performed to measure right and left endocardial global longitudinal strain (GLS) and tricuspid and mitral annular plane systolic excursion. Global sphericity index was also calculated. Echocardiographic parameters were compared between GDM fetuses and controls at two gestational time periods of 24 + 0 to 32 + 0 weeks and 32 + 1 to 40 + 1 weeks.Results: At 24 + 0 to 32 + 0 weeks, we phenotyped 43 fetuses from mothers with GDM and 71 from uncomplicated pregnancies, and, at 32 + 1 to 40 + 1 weeks, we phenotyped 69 fetuses from mothers with GDM and 153 from women with uncomplicated pregnancy. In fetuses of mothers with GDM, compared to controls, right ventricular functional indices were consistently lower both at 24 + 0 to 32 + 0 weeks and at 32 + 1 to 40 + 1 weeks. Right ventricular GLS was reduced in the GDM group at 24 + 0 to 32 + 0 weeks (adjusted mean difference, 0.7%; 95% CI, 0.3-1.1%) and at 32 + 1 to 40 + 1 weeks (adjusted mean difference, 0.9%; 95% CI, 0.6-1.1%). Fetal left ventricular global longitudinal function was similar in GDM pregnancies compared with controls, with the exception of the contractility of the left ventricular basal segment, which was reduced. Global sphericity index was reduced in GDM pregnancies only at 32 + 1 to 40 + 1 weeks (adjusted mean difference, -0.4; 95% CI, -0.7 to 0.1).Conclusions: The offspring of women with GDM are at high risk for development of cardiovascular disease in childhood and early adulthood. Our study demonstrates that GDM is associated with a reduction mainly in fetal right ventricular function, compared to controls, and this response is not exaggerated with increasing gestational age. Further studies are needed to determine whether fetuses with the observed alterations in cardiac function are those at highest risk for subsequent development of cardiovascular disease. © 2020 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objective: To estimate the risk of miscarriage associated with chorionic villus sampling (CVS).Methods: This was a retrospective cohort study of women attending for routine ultrasound examination at 11 + 0 to 13 + 6 weeks' gestation at one of eight fetal-medicine units in Spain, Belgium and Bulgaria, between July 2007 and June 2018. Two populations were included: (1) all singleton pregnancies undergoing first-trimester assessment at Hospital Clínico Universitario Virgen de la Arrixaca in Murcia, Spain, that did not have CVS (non-CVS group); and (2) all singleton pregnancies that underwent CVS following first-trimester assessment at one of the eight participating centers (CVS group). We excluded pregnancies diagnosed with genetic anomalies or major fetal defects before or after birth, those that resulted in termination and those that underwent amniocentesis later in pregnancy. We used propensity score (PS) matching analysis to estimate the association between CVS and miscarriage. We compared the risk of miscarriage of the CVS and non-CVS groups after PS matching (1:1 ratio). This procedure creates two comparable groups balancing the maternal and pregnancy characteristics that are associated with CVS, in a similar way to that in which randomization operates in a randomized clinical trial.Results: The study population consisted of 22 250 pregnancies in the non-CVS group and 3613 in the CVS group. The incidence of miscarriage in the CVS group (2.1%; 77/3613) was significantly higher than that in the non-CVS group (0.9% (207/22 250); P < 0.0001). The PS algorithm matched 2122 CVS with 2122 non-CVS cases, of which 40 (1.9%) and 55 (2.6%) pregnancies in the CVS and non-CVS groups, respectively, resulted in a miscarriage (odds ratio (OR), 0.72 (95% CI, 0.48-1.10); P = 0.146). We found a significant interaction between the risk of miscarriage following CVS and the risk of aneuploidy, suggesting that the effect of CVS on the risk of miscarriage differs depending on background characteristics. Specifically, when the risk of aneuploidy is low, the risk of miscarriage after CVS increases (OR, 2.87 (95% CI, 1.13-7.30)) and when the aneuploidy risk is high, the risk of miscarriage after CVS is paradoxically reduced (OR, 0.47 (95% CI, 0.28-0.76)), presumably owing to prenatal diagnosis and termination of pregnancies with major aneuploidies that would otherwise have resulted in spontaneous miscarriage. For example, in a patient in whom the risk of aneuploidy is 1 in 1000 (0.1%), the risk of miscarriage after CVS will increase to 0.3% (0.2 percentage points higher).Conclusions: The risk of miscarriage in women undergoing CVS is about 1% higher than that in women who do not have CVS, although this excess risk is not solely attributed to the invasive procedure but, to some extent, to the demographic and pregnancy characteristics of the patients. After accounting for these risk factors and confining the analysis to low-risk pregnancies, CVS seems to increase the risk of miscarriage by about three times above the patient's background risk. Although this is a substantial increase in relative terms, in pregnancies without risk factors for miscarriage, the risk of miscarriage after CVS remains low and similar to, or slightly higher than, that in the general population. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Background: We have proposed previously that the competing-risks model for prediction of pre-eclampsia (PE) based on maternal characteristics and medical history (prior model), developed in singleton pregnancies, can be extended to risk assessment for twins; in dichorionic (DC) and monochorionic (MC) twin pregnancies with the same characteristics as in singleton pregnancies, the distribution of gestational age at delivery with PE was shifted to the left by 8 and 10 weeks, respectively. However, in a subsequent validation study, we found that, in both the training and validation datasets, the observed incidence of PE was lower than the predicted one and such overestimation of risk was particularly marked for early PE.Objectives: First, to develop a new extension of the competing-risks prior model in screening for PE by maternal demographic characteristics and medical history in twin pregnancies in a training dataset. Second, to examine the predictive performance of this model in screening for PE with delivery < 34 weeks (early PE), < 37 weeks (preterm PE) and at any gestational age (all PE) in twins in a validation dataset. Third, to demonstrate the application of screening in a mixed population of singleton and twin pregnancies.Methods: The data for this study were obtained from two prospective non-intervention multicenter screening studies for PE in twin pregnancies at 11 + 0 to 13 + 6 weeks' gestation. The training and validation datasets consisted of 2219 and 2999 women, respectively. We used the training dataset to fit a model in which the effect of twins on shifting the distribution of gestational age at delivery with PE in singletons to the left should not be the same for all gestational ages but the shift should depend on the singleton prior mean; the effect increases with increasing prior mean. We examined the predictive performance of the model in the training and validation datasets using the area under the receiver-operating characteristics curve (AUC) and calibration plots. Data on 16 747 singleton pregnancies obtained from the Screening ProgRamme for prE-Eclampsia (SPREE) study were included to examine the performance of screening in a mixed population of singleton and twin pregnancies.Results: Calibration plots and calibration intercept and slope demonstrate superior predictive performance of the new model in the validation dataset. Although the AUC for twin pregnancies is lower than in singleton pregnancies, performance of screening in a mixed population of singleton and twin pregnancies is superior to that in singletons (AUC of 0.790 in a mixed population comprising 2% twins and 98% singletons compared to 0.775 in singletons). For the risk cut-offs likely to be used in practice, all twin pregnancies screen positive using maternal characteristics and medical history.Conclusions: A new competing-risks model in screening for PE by maternal risk factors in twin pregnancy has been developed and, using this model, the predicted risks for early PE, preterm PE and all PE are in relatively good agreement with the observed incidence of the disease. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To examine the predictive performance of the competing-risks model in screening for pre-eclampsia (PE) by maternal demographic characteristics and medical history in twin pregnancy, in a training dataset used for development of the model and a validation dataset.Methods: The data for this study were derived from two prospective non-intervention multicenter screening studies for PE in twin pregnancies at 11 + 0 to 13 + 6 weeks' gestation. The first study of 2219 women, which was reported previously, was used to develop the competing-risks model for prediction of PE and is therefore considered to be the training set. The validation study comprised 2999 women. Patient-specific risks of delivery with PE at < 34 (early), < 37 (preterm) and < 41 + 3 (all) weeks' gestation were calculated using the competing-risks model and the performance of screening for PE in the training and validation datasets was assessed. We examined the predictive performance of the model by, first, its ability to discriminate between the PE and no-PE groups using the area under the receiver-operating characteristics curve (AUC) and, second, calibration, which assesses agreement between the predicted risk and observed incidence of PE.Results: The incidence of early PE, preterm PE and all PE in the training and validation datasets was similar (1.8% vs 1.4%, 5.6% vs 5.6% and 7.7% vs 7.2%, respectively) and this was substantially higher than in our previous studies in singleton pregnancies. The training and validation datasets had similar AUCs for early PE (0.670 (95% CI, 0.593-0.747) vs 0.677 (95% CI, 0.594-0.760)), preterm PE (0.666 (95% CI, (0.617-0.715) vs 0.652 (95% CI, 0.609-0.694)) and all PE (0.656 (95% CI, 0.615-0.697) vs 0.644 (95% CI, 0.606-0.682)). Calibration plots of the predictive performance of the competing-risks model demonstrated that, in both the training and validation datasets, the observed incidence of PE was lower than the predicted one and such overestimation of risk was particularly marked for early PE.Conclusions: Discrimination and calibration of the competing-risks model for PE in a validation dataset are consistent with those in the training dataset. However, the model needs to be adjusted to correct the observed overestimation of risk for early PE. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objectives: To examine the effect of first-trimester screening for pre-eclampsia (PE) on the prediction of delivering a small-for-gestational-age (SGA) neonate and the effect of prophylactic use of aspirin on the prevention of SGA.Methods: The data for this study were derived from two multicenter studies. In SPREE, we investigated the performance of screening for PE by a combination of maternal characteristics and biomarkers at 11-13 weeks' gestation. In ASPRE, women with a singleton pregnancy identified by combined screening as being at high risk for preterm PE (> 1 in 100) participated in a trial of aspirin (150 mg/day from 11-14 until 36 weeks' gestation) compared to placebo. In this study, we used the data from the ASPRE trial to estimate the effect of aspirin on the incidence of SGA with birth weight < 10th , < 5th and < 3rd percentile for gestational age. We also used the data from SPREE to estimate the proportion of SGA in the pregnancies with a risk for preterm PE of > 1 in 100.Results: In SPREE, screening for preterm PE by a combination of maternal factors, mean arterial pressure, uterine artery pulsatility index and serum placental growth factor identified a high-risk group that contained about 46% of SGA neonates < 10th percentile born at < 37 weeks' gestation (preterm) and 56% of those born at < 32 weeks (early); the overall screen-positive rate was 12.2% (2014 of 16 451 pregnancies). In the ASPRE trial, use of aspirin reduced the overall incidence of SGA < 10th percentile by about 40% in babies born at < 37 weeks' gestation and by about 70% in babies born at < 32 weeks; in babies born at ≥ 37 weeks, aspirin did not have a significant effect on incidence of SGA. The aspirin-related decrease in incidence of SGA was mainly due to its incidence decreasing in pregnancies with PE, for which the decrease was about 70% in babies born at < 37 weeks' gestation and about 90% in babies born at < 32 weeks. On the basis of these results, it was estimated that first-trimester screening for preterm PE and use of aspirin in the high-risk group would potentially reduce the incidence of preterm and early SGA by about 20% and 40%, respectively.Conclusion: First-trimester screening for PE by the combined test identifies a high proportion of cases of preterm SGA that can be prevented by the prophylactic use of aspirin. © 2018 Crown copyright. Ultrasound in Obstetrics & Gynecology © 2018 ISUOG. [ABSTRACT FROM AUTHOR]

Objective: To examine the performance of screening for preterm and term pre-eclampsia (PE) in the study population participating in the ASPRE (Combined Multimarker Screening and Randomized Patient Treatment with Aspirin for Evidence-Based Preeclampsia Prevention) trial.Methods: This was a prospective first-trimester multicenter study on screening for preterm PE in 26 941 singleton pregnancies by means of an algorithm that combines maternal factors, mean arterial pressure, uterine artery pulsatility index and maternal serum pregnancy-associated plasma protein-A and placental growth factor at 11-13 weeks' gestation. Eligible women with an estimated risk for preterm PE of > 1 in 100 were invited to participate in a double-blind trial of aspirin (150 mg per day) vs placebo from 11-14 until 36 weeks' gestation, which showed that, in the aspirin group, the incidence of preterm PE was reduced by 62%. In the screened population, the detection rates (DRs) and false-positive rates (FPRs) for delivery with PE < 37 and ≥ 37 weeks were estimated after adjustment for the effect of aspirin in those receiving this treatment. We excluded 1144 (4.2%) pregnancies because of loss to follow-up or study withdrawal (n = 716), miscarriage (n = 243) or termination (n = 185).Results: The study population of 25 797 pregnancies included 180 (0.7%) cases of preterm PE, 450 (1.7%) of term PE and 25 167 (97.6%) without PE. In combined first-trimester screening for preterm PE with a risk cut-off of 1 in 100, the DR was 76.7% (138/180) for preterm PE and 43.1% (194/450) for term PE, at screen-positive rate of 10.5% (2707/25 797) and FPR of 9.2% (2375/25 797).Conclusion: The performance of screening in the ASPRE study was comparable with that of a study of approximately 60 000 singleton pregnancies used for development of the algorithm; in that study, combined screening detected 76.6% of cases of preterm PE and 38.3% of term PE at a FPR of 10%. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To compare the performance of screening for pre-eclampsia (PE) based on risk factors from medical history, as recommended by NICE and ACOG, with the method proposed by The Fetal Medicine Foundation (FMF), which uses Bayes' theorem to combine the a-priori risk from maternal factors, derived by a multivariable logistic model, with the results of various combinations of biophysical and biochemical measurements.Methods: This was a prospective multicenter study of screening for PE in 8775 singleton pregnancies at 11-13 weeks' gestation. A previously published FMF algorithm was used for the calculation of patient-specific risk of PE in each individual. The detection rates (DRs) and false-positive rates (FPRs) for delivery with PE < 32, < 37 and ≥ 37 weeks were estimated and compared with those derived from application of NICE guidelines and ACOG recommendations. According to NICE, all high-risk pregnancies should be offered low-dose aspirin. According to ACOG, use of aspirin should be reserved for women with a history of PE in at least two previous pregnancies or PE requiring delivery < 34 weeks' gestation.Results: In the study population, 239 (2.7%) cases developed PE, of which 17 (0.2%), 59 (0.7%) and 180 (2.1%) developed PE < 32, < 37 and ≥ 37 weeks, respectively. Screening with use of the FMF algorithm based on a combination of maternal factors, mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI) and serum placental growth factor (PlGF) detected 100% (95% CI, 80-100%) of PE < 32 weeks, 75% (95% CI, 62-85%) of PE < 37 weeks and 43% (95% CI, 35-50%) of PE ≥ 37 weeks, at a 10.0% FPR. Screening with use of NICE guidelines detected 41% (95% CI, 18-67%) of PE < 32 weeks, 39% (95% CI, 27-53%) of PE < 37 weeks and 34% (95% CI, 27-41%) of PE ≥ 37 weeks, at 10.2% FPR. Screening with use of ACOG recommendations detected 94% (95% CI, 71-100%) of PE < 32 weeks, 90% (95% CI, 79-96%) of PE < 37 weeks and 89% (95% CI, 84-94%) of PE ≥ 37 weeks, at 64.2% FPR. Screening based on the ACOG recommendations for use of aspirin detected 6% (95% CI, 1-27%) of PE < 32 weeks, 5% (95% CI, 2-14%) of PE < 37 weeks and 2% (95% CI, 0.3-5%) of PE ≥ 37 weeks, at 0.2% FPR.Conclusion: Performance of screening for PE at 11-13 weeks' gestation by the FMF algorithm using a combination of maternal factors, MAP, UtA-PI and PlGF, is by far superior to the methods recommended by NICE and ACOG. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To examine the diagnostic accuracy of a previously developed model for prediction of pre-eclampsia (PE) by a combination of maternal factors and biomarkers at 11-13 weeks' gestation.Methods: This was a prospective first-trimester multicenter study of screening for PE in 8775 singleton pregnancies. A previously published algorithm was used for the calculation of patient-specific risk of PE in each individual. The detection rates (DRs) and false-positive rates (FPRs) for delivery with PE < 32, < 37 and ≥ 37 weeks were estimated and compared with those for the dataset used for development of the algorithm.Results: In the study population, 239 (2.7%) cases developed PE, of which 17 (0.2%), 59 (0.7%) and 180 (2.1%) developed PE < 32, < 37 and ≥ 37 weeks, respectively. With combined screening by maternal factors, mean arterial pressure, uterine artery pulsatility index and serum placental growth factor, the DR was 100% (95% CI, 80-100%) for PE < 32 weeks, 75% (95% CI, 62-85%) for PE < 37 weeks and 43% (95% CI, 35-50%) for PE ≥ 37 weeks, at a 10% FPR. These DRs were similar to the estimated rates for the dataset used for development of the model: 89% (95% CI, 79-96%) for PE < 32 weeks, 75% (95% CI, 70-80%) for PE < 37 weeks and 47% (95% CI, 44-51%) for PE ≥ 37 weeks.Conclusion: Assessment of a combination of maternal factors and biomarkers at 11-13 weeks provides effective first-trimester screening for preterm PE. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]