Search

Objective: To determine whether serum placental growth factor (PlGF) at 19–23 weeks of gestation can improve the identification of risk for adverse outcomes. Design: Prospective observational cohort study. Setting: Two English maternity units. Population: Unselected singleton pregnancies attending routine ultrasound at 19–23 weeks of gestation. Methods: Outcomes ascertained by health record review. Diagnostic test properties evaluated clinical risk factors for pre‐eclampsia (according to National Institute of Care Excellence) or fetal growth restriction (according to Royal College of Obstetricians and Gynaecologists), low PlGF at 19–23 weeks of gestation (<5th percentile) or both. Main outcome measures: Pre‐eclampsia, gestational hypertension, stillbirth, birthweight below third percentile or neonatal intensive care unit (NICU) admission for ≥48 h. Results: In 30 013 pregnancies, risk factors were present in 9941 (33.1%), low PlGF was present in 1501 (5.0%) and both ('two‐stage' screening) were present in 547 (1.8%) pregnancies. Risk factors detected 41.7%–54.7% of adverse outcomes, and could not meaningfully revise the risk (all positive likelihood ratios, +LR, <5.0; all negative likelihood ratios, −LR, ≥0.2). Low PlGF detected 8.5%–17.4% of adverse outcomes, but meaningfully increased risks (other than NICU admission) associated with delivery <37 weeks of gestation (+LR = 5.03–15.55); all −LRs were ≥0.2. 'Two‐stage' screening detected 4.2%–8.9% of adverse outcomes, with meaningful +LRs (6.28–18.61) at <37 weeks of gestation, except for NICU admission of ≥48 h, which had an +LR of 7.56 at <34 weeks of gestation; all −LRs were ≥0.2. No screening strategy meaningfully increased or decreased the detection of adverse outcome risk at term. Conclusions: Clinical risk factor screening has a high screen‐positive rate and a poor detection of adverse outcomes. False positives cannot be reduced by PlGF testing at 19–23 weeks of gestation; therefore, this cannot be recommended as a useful strategy on its own. [ABSTRACT FROM AUTHOR]

Objective: To report the predictive performance for preterm birth (PTB) of the Fetal Medicine Foundation (FMF) triple test and National Institute for health and Care Excellence (NICE) guidelines used to screen for pre‐eclampsia and examine the impact of aspirin in the prevention of PTB. Design: Secondary analysis of data from the SPREE study and the ASPRE trial. Setting: Multicentre studies. Population: In SPREE, women with singleton pregnancies had screening for preterm pre‐eclampsia at 11–13 weeks of gestation by the FMF method and NICE guidelines. There were 16 451 pregnancies that resulted in delivery at ≥24 weeks of gestation and these data were used to derive the predictive performance for PTB of the two methods of screening. The results from the ASPRE trial were used to examine the effect of aspirin in the prevention of PTB in the population from SPREE. Methods: Comparison of performance of FMF method and NICE guidelines for pre‐eclampsia in the prediction of PTB and use of aspirin in prevention of PTB. Main outcome measure: Spontaneous PTB (sPTB), iatrogenic PTB for pre‐eclampsia (iPTB‐PE) and iatrogenic PTB for reasons other than pre‐eclampsia (iPTB‐noPE). Results: Estimated incidence rates of sPTB, iPTB‐PE and iPTB‐noPE were 3.4%, 0.8% and 1.6%, respectively. The corresponding detection rates were 17%, 82% and 25% for the triple test and 12%, 39% and 19% for NICE guidelines, using the same overall screen positive rate of 10.2%. The estimated proportions prevented by aspirin were 14%, 65% and 0%, respectively. Conclusion: Prediction of sPTB and iPTB‐noPE by the triple test was poor and poorer by the NICE guidelines. Neither sPTB nor iPTB‐noPE was reduced substantially by aspirin. [ABSTRACT FROM AUTHOR]

Objectives: The mechanism by which aspirin prevents pre‐eclampsia is poorly understood, and its effects on biomarkers throughout pregnancy are unknown. We aimed to investigate the effects of aspirin on mean arterial pressure (MAP) and mean uterine artery pulsatility index (UtA‐PI) using repeated measures from women at increased risk of preterm pre‐eclampsia. Methods: This was a longitudinal secondary analysis of the Combined Multimarker Screening and Randomized Patient Treatment with Aspirin for Evidence‐Based Pre‐eclampsia Prevention (ASPRE) trial using repeated measures of MAP and UtA‐PI. In the trial, 1620 women at increased risk of preterm pre‐eclampsia were identified using the Fetal Medicine Foundation algorithm at 11 + 0 to 13 + 6 weeks, of whom 798 were randomly assigned to receive 150 mg/day aspirin and 822 were assigned to receive placebo daily from 11–14 weeks to 36 weeks of gestation or delivery, whichever came first. MAP and UtA‐PI were measured at baseline and follow‐up visits at 19–24, 32–34 and 36 weeks of gestation. Generalized additive mixed models with treatment by gestational age interaction terms were used to investigate the effects of aspirin on MAP and UtA‐PI trajectories over time. Results: Among 798 participants in the aspirin group and 822 in the placebo group, there were 5951 MAP and 5942 UtA‐PI measurements. Trajectories of raw and multiples of the median (MoM) values of MAP did not differ significantly between the two groups (MAP MoM analysis: P‐value for treatment by gestational age interaction, 0.340). In contrast, trajectories of raw and MoM values of UtA‐PI showed a significantly steeper decline in the aspirin group than in the placebo group, with the difference mainly driven by a more pronounced reduction before 20 weeks of gestation (UtA‐PI MoM analysis: P‐value for treatment by gestational age interaction, 0.006). Conclusions: In women at increased risk of preterm pre‐eclampsia, 150 mg/day aspirin initiated in the first trimester does not affect MAP but is associated with a significant decrease in mean UtA‐PI, particularly before 20 weeks of gestation. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objective: To determine the relative burdens of maternal and perinatal complications for preterm and term pre‐eclampsia. Design: Prospective observational cohort study. Setting: Two English maternity units. Population: Unselected women with singleton pregnancies who developed pre‐eclampsia (International Society for the Study of Hypertension in Pregnancy definition). Methods: Outcomes were ascertained by health record review and compared between pregnancies with preterm (versus term) pre‐eclampsia. Main outcome measures: Severe maternal hypertension, maternal mortality or major maternal morbidity, perinatal mortality or major neonatal morbidity, neonatal unit (NNU) admission ≥48 hours, and birthweight <3rd percentile. Results: Among 40 241 singleton pregnancies, 298 (0.7%, 95% confidence interval [CI] 0.66–0.83) and 1194 (3.0%, 95% CI 2.8–3.1) developed preterm and term pre‐eclampsia, respectively. Women with preterm (versus term) pre‐eclampsia more commonly experienced adverse maternal or perinatal events: severe hypertension 18.5% (95% CI 14.5–23.3) versus 13.6% (95% CI 11.7–15.6); maternal mortality/major morbidity 7.4% (95% CI 4.9–10.9) versus 2.2% (95% CI 1.5–3.2); perinatal mortality/major neonatal morbidity 29.5% (95% CI 24.6–34.9) versus 2.2% (95% CI 1.5–3.2); and birthweight <3rd percentile 54.4% (95% CI 48.7–59.9) versus 14.2% (95% CI 12.4–16.3). However, in absolute terms, most maternal complications occurred in women with term pre‐eclampsia, as did a large proportion of perinatal complications: severe hypertension 74.7% (95% CI 68.5–80.0); maternal mortality/major morbidity 54.2% (95% CI 40.3–67.4); perinatal mortality/major neonatal morbidity 22.8% (95% CI 16.1–31.3); NNU admission ≥48 hours 38.1% (95% CI 32.4–44.1); and birthweight <3rd percentile 51.2% (95% CI 45.8–56.5). Conclusions: Although adverse event risks are greater with preterm (versus term) pre‐eclampsia, term disease is associated with at least equivalent total numbers of maternal, and a significant proportion of perinatal, adverse events. Increased efforts should be made to decrease the incidence of term pre‐eclampsia. This article includes Author Insights, a video abstract presented by Laura A. Magee available at: https://vimeo.com/790715868 [ABSTRACT FROM AUTHOR]

Objective: To evaluate the accuracy of predicting the risk of developing pre-eclampsia (PE) according to first-trimester maternal demographic characteristics, medical history and biomarkers using artificial-intelligence and machine-learning methods.Methods: The data were derived from prospective non-interventional screening for PE at 11-13 weeks' gestation at two maternity hospitals in the UK. The data were divided into three subsets. The first set, including 30 437 subjects, was used to develop the training process, the second set of 10 000 subjects was utilized to optimize the machine-learning hyperparameters and the third set of 20 352 subjects was coded and used for model validation. An artificial neural network was used to predict from the demographic characteristics and medical history the prior risk that was then combined with biomarker values to determine the risk of PE and preterm PE with delivery at < 37 weeks' gestation. An additional network was trained without including race as input. Biomarkers included uterine artery pulsatility index (UtA-PI), mean arterial blood pressure (MAP), placental growth factor (PlGF) and pregnancy-associated plasma protein-A. All markers were entered using raw values without conversion into standardized multiples of the median. The prediction accuracy was estimated using the area under the receiver-operating-characteristics curve (AUC). We further computed the detection rate at 10%, 20% and 40% false-positive rates (FPR). The impact of taking aspirin was also added. Shapley values were calculated to evaluate the contribution of each parameter to the prediction of risk. We used a non-parametric test to compare the expected AUC with the one obtained when we randomly scrambled the labels and kept the predictions. For the general prediction, we performed 10 000 permutations of the labels. When the AUC was higher than the one obtained in all 10 000 permutations, we reported a P-value of < 0.0001. For the race-specific analysis, we performed 1000 permutations. When the AUC was higher than the AUC in permutations, we reported a P-value of < 0.001.Results: The detection rate for preterm PE vs no PE, at a 10% FPR, was 53.3% when screening by maternal factors only, and the corresponding AUC was 0.816; these increased to 75.3% and 0.909, respectively, with the addition of biomarkers into the model. Information on race was important for the prediction accuracy; when race was not used to train the model, at a 10% FPR, the detection rate of preterm PE vs no PE decreased to 34.5-45.5% (for different races) when screening by maternal factors only and to 55.0-62.1% when biomarkers were added. The major predictors of PE were high MAP and UtA-PI, and low PlGF. The accuracy of prediction of all PE cases was lower than that for preterm PE. Aspirin use was recommended for cases who were at high risk of preterm PE. The AUC of all PE vs no PE was 0.770 when screening by maternal factors and 0.817 when the biomarkers were added; the respective detection rates, at a 10% FPR, were 41.3% and 52.9%.Conclusions: Screening for PE using a non-linear machine-learning-based approach does not require a population-based normalization, and its performance is similar to that of logistic regression. Removing race information from the model reduces its prediction accuracy, especially for the non-white populations when only maternal factors are considered. © 2022 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objective: The competing-risks model for assessment of risk for pre-eclampsia (PE) at 35-37 weeks' gestation identifies the majority of women who are at high risk of subsequent delivery with PE. We aimed to examine the incidence and relative risk of adverse pregnancy outcomes in patient groups stratified according to the estimated risk of delivery with PE.Methods: This was a prospective non-interventional, observational study in women with a singleton pregnancy attending for a routine hospital visit at 35 + 0 to 36 + 6 weeks' gestation. The risk of delivery with PE for each patient in the study population was estimated using the competing-risks model, combining the prior distribution of gestational age at delivery with PE and the likelihood from multiples of the median values of mean arterial pressure, placental growth factor and soluble fms-like tyrosine kinase-1. The patients were assigned to one of the following five risk categories: Group A, ≥ 1 in 2; Group B, 1 in 5 to 1 in 3; Group C, 1 in 20 to 1 in 6; Group D, 1 in 50 to 1 in 21; and Group E, < 1 in 50. The outcome measures were delivery with PE, gestational hypertension (GH), small-for-gestational age (SGA) at birth, delivery by Cesarean section, stillbirth, neonatal death, perinatal death and admission to the neonatal unit (NNU) for at least 48 h. In each risk category, the proportion of women with each adverse outcome was determined and relative risks (RR) were calculated as compared with the lowest-risk Group E.Results: In the study population of 29 035 women, 1.6%, 2.7%, 8.2%, 9.8% and 77.8% were categorized into Groups A, B, C, D and E, respectively. Compared with women in Group E, women in the higher-risk groups were more likely to have an adverse outcome. The RR of delivery with PE in Group A compared with Group E was 65.5 (95% CI, 54.1-79.1) and the respective values were 11.9 (95% CI, 9.1-15.5) for GH, 1.8 (95% CI, 1.5-2.1) for delivery by emergency Cesarean section, 1.5 (95% CI, 1.2-1.8) for delivery by elective Cesarean section, 8.9 (95% CI, 7.4-10.8) for SGA with birth weight < 3rd percentile, 4.8 (95% CI, 4.3-5.4) for SGA with birth weight < 10th percentile, 5.3 (95% CI, 1.4-20.5) for stillbirth and 3.4 (95% CI, 2.8-4.2) for NNU admission for ≥ 48 h. The RR for these pregnancy complications in higher-risk groups (vs Group E) was particularly high for cases with delivery within 2 weeks after assessment. In terms of SGA, both for birth weight < 10th and < 3rd percentiles, the trend in all cases was stronger than that observed when the analysis was confined to normotensive pregnancies. The rates of neonatal death were too small to allow meaningful comparisons between risk groups.Conclusion: Pregnant women identified by the competing-risks model to be at high risk of PE are also at increased risk of GH, Cesarean section, stillbirth, SGA and NNU admission for ≥ 48 h. © 2022 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objective: To examine the performance of a model combining maternal risk factors, uterine artery pulsatility index (UtA-PI) and estimated fetal weight (EFW) at 19-24 weeks' gestation, for predicting all antepartum stillbirths and those due to impaired placentation, in a training dataset used for development of the model and in a validation dataset.Methods: The data for this study were derived from prospective screening for adverse obstetric outcome in women with singleton pregnancy attending for routine pregnancy care at 19 + 0 to 24 + 6 weeks' gestation. The study population was divided into a training dataset used to develop prediction models for placental dysfunction-related antepartum stillbirth and a validation dataset to which the models were then applied. Multivariable logistic regression analysis was used to develop a model based on a combination of maternal risk factors, EFW Z-score and UtA-PI multiples of the normal median. We examined the predictive performance of the model by, first, the ability of the model to discriminate between the stillbirth and live-birth groups, using the area under the receiver-operating-characteristics curve (AUC) and the detection rate (DR) at a fixed false-positive rate (FPR) of 10%, and, second, calibration by measurements of calibration slope and intercept.Results: The study population of 131 514 pregnancies included 131 037 live births and 477 (0.36%) stillbirths. There are four main findings of this study. First, 92.5% (441/477) of stillbirths were antepartum and 7.5% (36/477) were intrapartum, and 59.2% (261/441) of antepartum stillbirths were observed in association with placental dysfunction and 40.8% (180/441) were unexplained or due to other causes. Second, placental dysfunction accounted for 80.1% (161/201) of antepartum stillbirths at < 32 weeks' gestation, 54.2% (52/96) at 32 + 0 to 36 + 6 weeks and 33.3% (48/144) at ≥ 37 weeks. Third, the risk of placental dysfunction-related antepartum stillbirth increased with increasing maternal weight and decreasing maternal height, was 3-fold higher in black than in white women, was 5.5-fold higher in parous women with previous stillbirth than in those with previous live birth, and was increased in smokers, in women with chronic hypertension and in parous women with a previous pregnancy complicated by pre-eclampsia and/or birth of a small-for-gestational-age baby. Fourth, in screening for placental dysfunction-related antepartum stillbirth by a combination of maternal risk factors, EFW and UtA-PI in the validation dataset, the DR at a 10% FPR was 62.3% (95% CI, 57.2-67.4%) and the AUC was 0.838 (95% CI, 0.799-0.878); these results were consistent with those in the dataset used for developing the algorithm and demonstrate high discrimination between affected and unaffected pregnancies. Similarly, the calibration slope was 1.029 and the intercept was -0.009, demonstrating good agreement between the predicted risk and observed incidence of placental dysfunction-related antepartum stillbirth. The performance of screening was better for placental dysfunction-related antepartum stillbirth at < 37 weeks' gestation compared to at term (DR at a 10% FPR, 69.8% vs 29.2%).Conclusions: Screening at mid-gestation by a combination of maternal risk factors, EFW and UtA-PI can predict a high proportion of placental dysfunction-related stillbirths and, in particular, those that occur preterm. Such screening provides poor prediction of unexplained stillbirth or stillbirth due to other causes. © 2021 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objectives: To examine the performance of the routine 11-13-week scan in detecting fetal defects in twin pregnancies and to examine if, in pregnancies with a fetal defect, compared to those with normal fetuses, there is increased incidence of nuchal translucency thickness (NT) ≥ 95th and ≥ 99th percentiles or intertwin discordance in crown-rump length (CRL) ≥ 10% and ≥ 15%.Methods: This was a retrospective analysis of prospectively collected data in twin pregnancies undergoing routine ultrasound examination for fetal anatomy, according to standardized protocols, at 11-13 weeks' gestation between 2002 and 2019. Pregnancies with known chromosomal abnormality were excluded. The final diagnosis of fetal defect was based on the results of postnatal examination in cases of live birth and on the findings of the last ultrasound examination in cases of pregnancy termination, miscarriage or stillbirth. The performance of the 11-13-week scan in the detection of fetal defects was determined.Results: The study population of 6366 twin pregnancies with two live fetuses at 11-13 weeks' gestation included 4979 (78.2%) dichorionic (DC) and 1387 (21.8%) monochorionic (MC) twin pregnancies. The main findings were: first, the overall incidence of fetal defects was higher in MC than in DC twins (2.8% vs 1.3%); second, the proportion of defects diagnosed in the first trimester was higher in MC than in DC twins (52.6% vs 27.1%); third, the pattern of defects in relation to detectability at the 11-13-week scan (always detectable, sometimes detectable and never detectable) was similar to that reported previously in singleton pregnancies; fourth, always-detectable defects included acrania, alobar holoprosencephaly, encephalocele, pentalogy of Cantrell, exomphalos, body-stalk anomaly, twin reversed arterial perfusion sequence and conjoined twins; fifth, the incidence of fetal NT ≥ 95th percentile was higher in those with than in those without a defect (16.5% vs 4.5% in DC twins and 19.2% vs 5.9% in MC twins) and this was also true for NT ≥ 99th percentile (8.3% vs 1.0% in DC twins and 15.4% vs 2.0% in MC twins); and sixth, the incidence of CRL discordance ≥ 10% was higher in those with than in those without a defect (20.2% vs 7.9% in DC twins and 33.8% vs 9.3% in MC twins) and this was also true for CRL discordance ≥ 15% (10.1% vs 1.9% in DC twins and 28.2% vs 2.8% in MC twins).Conclusions: First, fetal defects are more common in MC than in DC twin pregnancies. Second, first-trimester detection of fetal defects in DC twin pregnancies is similar to that in singleton pregnancies. Third, first-trimester detectability of defects in MC twins is higher than in DC twins. Fourth, in twin pregnancies with a fetal defect, there is higher intertwin discordance in CRL and incidence of increased NT, but the predictive performance of screening by these markers is poor. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objectives: First, to compare the incidence of single and double fetal death between monochorionic (MC) and dichorionic (DC) twin pregnancies with two live fetuses at 11-13 weeks' gestation and no major abnormalities. Second, to investigate the relationship between gestational age at single fetal death and interval to delivery of the cotwin. Third, to determine the rate of early preterm birth in DC and MC twin pregnancies with two live fetuses and those with single fetal death.Methods: This was a retrospective analysis of prospectively collected data on twin pregnancies undergoing routine ultrasound examination at 11-13 weeks' gestation between 2002 and 2019. The outcome measures, which were stratified by chorionicity, were: first, death of both fetuses at presentation or death of one fetus followed by delivery of a live or dead cotwin within the subsequent 3 days at < 34 weeks' gestation; second, in pregnancies with single fetal death at < 34 weeks' gestation and a live cotwin ≥ 3 days later, the subsequent risk of fetal death and gestational-age distribution at birth of the cotwin; and, third, the gestational-age distribution at birth in pregnancies with two live fetuses.Results: The main findings of this study of 4896 DC and 1329 MC twin pregnancies with two live fetuses at 11-13 weeks' gestation were: first, the rate of death of both twins or death of one fetus and delivery of the live or dead cotwin within 3 days was higher in MC than in DC twin pregnancies; second, the rate of single fetal death with a live cotwin ≥ 3 days later was higher in MC than in DC twin pregnancies, but the rate of subsequent cotwin death in MC twin pregnancies was not significantly different from that in DC twin pregnancies; third, in pregnancies with two live fetuses, the rate of early preterm birth was significantly higher in MC than in DC twin pregnancies; fourth, the rate of early preterm birth in pregnancies with single fetal death and a live cotwin ≥ 3 days later was not significantly different between MC and DC twin pregnancies but the rates were substantially higher than in those with two live fetuses; and, fifth, in both MC and DC pregnancies with single fetal death and a live cotwin ≥ 3 days later, there was a significant inverse association between gestational age at death and interval to delivery (mean interval of 19 weeks for death at 15 weeks and mean interval of 2.5 weeks for death at 30 weeks).Conclusions: First, in MC twin pregnancies, the risk of single or double fetal death is higher than in DC twins. Second, in both MC and DC twin pregnancies, the rate of early preterm birth is higher in those with one fetal death than in those with two live fetuses. Third, in both MC and DC twins with one fetal death, the interval to delivery is related inversely to gestational age at fetal death. These data should be useful in counseling parents as to the likely outcome of their pregnancy after single fetal death and in defining strategies for surveillance in the management of these types of twin pregnancy. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To investigate the value of increased fetal nuchal translucency thickness (NT) at the 11-13-week scan in the prediction of adverse outcome in dichorionic (DC), monochorionic diamniotic (MCDA) and monochorionic monoamniotic (MCMA) twin pregnancies.Methods: This was a retrospective analysis of prospectively collected data on twin pregnancies undergoing routine ultrasound examination at 11-13 weeks' gestation between 2002 and 2019. In pregnancies with no major defects or chromosomal abnormalities, we examined the value of increased NT ≥ 95th percentile in one or both fetuses in the prediction of, first, miscarriage or death of one or both fetuses at < 20 and < 24 weeks' gestation in DC, MCDA and MCMA twin pregnancies, second, death of one or both fetuses or neonates at ≥ 24 weeks in DC, MCDA and MCMA twin pregnancies, third, development of twin-twin transfusion syndrome (TTTS) or selective fetal growth restriction (sFGR) treated by endoscopic laser surgery at < 20 and ≥ 20 weeks' gestation in MCDA pregnancies, and, fourth, either fetal loss or laser surgery at < 20 weeks' gestation in MCDA pregnancies.Results: The study population of 6225 twin pregnancies included 4896 (78.7%) DC, 1274 (20.5%) MCDA and 55 (0.9%) MCMA pregnancies. The incidence of NT ≥ 95th percentile in one or both fetuses in DC twin pregnancies was 8.3%; in MCDA twins the incidence was significantly higher (10.4%; P = 0.016), but in MCMA twins it was not significantly different (9.1%; P = 0.804) from that in DC twins. In DC twin pregnancies, the incidence of high NT was not significantly different between those with two survivors and those with adverse outcome. In MCMA twin pregnancies, the number of cases was too small for meaningful assessment of the relationship between high NT and adverse outcome. In MCDA twin pregnancies with at least one fetal death or need for endoscopic laser surgery at < 20 weeks' gestation, the incidence of NT ≥ 95th percentile was significantly higher than in those with two survivors (23.5% vs 9.8%; P < 0.0001). Kaplan-Meier analysis in MCDA twin pregnancies showed that, in those with NT ≥ 95th percentile, there was significantly lower survival at < 20 weeks' gestation than in those with NT < 95th percentile (P = 0.001); this was not the case for survival at ≥ 20 weeks (P = 0.960). The performance of screening by fetal NT ≥ 95th percentile for prediction of either fetal loss or need for endoscopic laser surgery at < 20 weeks' gestation was poor, with a detection rate of 23.5% at a false-positive rate of 8.9%, and the relative risk, in comparison to fetal NT < 95th percentile, was 2.640 (95% CI, 1.854-3.758; P < 0.0001). In MCDA twin pregnancies, the overall rate of fetal loss or need for laser surgery at < 20 weeks' gestation was 10.7% but, in the subgroups with NT ≥ 95th and NT ≥ 99th percentiles, which constituted 10.4% and 3.3% of the total, the rates increased to 24.1% and 40.5%, respectively.Conclusions: In MCDA twin pregnancies with no major fetal abnormalities, measurement of NT at the 11-13-week scan is a poor screening test for adverse pregnancy outcome. However, the finding in one or both fetuses of NT ≥ 95th percentile, and more so ≥ 99th percentile, is associated with a substantially increased risk of fetal loss or need for endoscopic laser surgery at < 20 weeks' gestation. The extent to which closer monitoring and earlier intervention in the high-risk group can reduce these complications remains to be determined. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To investigate the value of intertwin discordance in fetal crown-rump length (CRL) at the 11-13-week scan in the prediction of adverse outcome in dichorionic (DC), monochorionic diamniotic (MCDA) and monochorionic monoamniotic (MCMA) twin pregnancies.Methods: This was a retrospective analysis of prospectively collected data on twin pregnancies undergoing routine ultrasound examination at 11-13 weeks' gestation between 2002 and 2019. In pregnancies with no major abnormalities, we examined the value of intertwin discordance in fetal CRL in DC, MCDA and MCMA twins in the prediction of fetal loss at < 20 and < 24 weeks' gestation, perinatal death at ≥ 24 weeks, preterm delivery at < 32 and < 37 weeks, birth of at least one small-for-gestational-age (SGA) neonate with birth weight < 5th percentile and intertwin birth-weight discordance of ≥ 20% and ≥ 25%.Results: First, the study population of 6225 twin pregnancies included 4896 (78.7%) DC, 1274 (20.4%) MCDA and 55 (0.9%) MCMA twin pregnancies. Second, median CRL discordance in DC twin pregnancies (3.2%; interquartile range (IQR), 1.4-5.8%) was lower than in MCDA twins (3.6%; IQR, 1.6-6.2%; P = 0.0008), but was not significantly different from that in MCMA twins (2.9%; IQR, 1.2-5.1%; P = 0.269). Third, compared to CRL discordance in DC twin pregnancies with two non-SGA live births at ≥ 37 weeks' gestation, there was significantly larger CRL discordance in both DC and MCDA twin pregnancies complicated by fetal death at < 20 and < 24 weeks' gestation, perinatal death at ≥ 24 weeks, preterm birth at < 32 and < 37 weeks, birth of at least one SGA neonate and birth-weight discordance ≥ 20% and ≥ 25%, and in MCDA twin pregnancies undergoing endoscopic laser surgery. Fourth, the predictive performance of CRL discordance for each adverse pregnancy outcome was poor, with areas under the receiver-operating-characteristics curves ranging from 0.533 to 0.624. However, in both DC and MCDA twin pregnancies with large CRL discordance, there was a high risk of fetal loss. Fifth, in DC twin pregnancies, the overall rate of fetal loss at < 20 weeks' gestation was 1.3% but, in the small subgroup with CRL discordance of ≥ 15%, which constituted 1.9% of the total, the rate increased to 5.3%. Sixth, in MCDA twin pregnancies, the rate of fetal loss or endoscopic laser surgery at < 20 weeks was about 11%, but, in the small subgroups with CRL discordance of ≥ 10%, ≥ 15% and ≥ 20%, which constituted 9%, < 3% and < 1% of the total, the risk was increased to about 32%, 49% and 70%, respectively. Seventh, in MCMA twin pregnancies, there were no significant differences in CRL discordance for any of the adverse outcome measures, but this may be the consequence of the small number of cases in the study population.Conclusions: In both DC and MCDA twin pregnancies, increased CRL discordance is associated with an increased risk of fetal death at < 20 and < 24 weeks' gestation, perinatal death at ≥ 24 weeks, preterm birth at < 37 and < 32 weeks, birth of at least one SGA neonate and birth-weight discordance ≥ 20% and ≥ 25%, but CRL discordance is a poor screening test for adverse pregnancy outcome. However, in DC twins, CRL discordance of ≥ 15% is associated with an increased risk of fetal loss at < 20 and < 24 weeks' gestation and, in MCDA twins, CRL discordance of ≥ 10%, and more so discordance of ≥ 15% and ≥ 20%, is associated with a very high risk of fetal loss or endoscopic laser surgery at < 20 and < 24 weeks and this information is useful in counseling women and defining the timing for subsequent assessment and possible intervention. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objectives: To report and compare pregnancy outcome in dichorionic (DC), monochorionic diamniotic (MCDA) and monochorionic monoamniotic (MCMA) twin pregnancies with two live fetuses at 11-13 weeks' gestation and to examine the impact of endoscopic laser surgery for severe twin-twin transfusion syndrome (TTTS) and/or selective fetal growth restriction (sFGR) on the outcome of MCDA twins.Methods: This was a retrospective analysis of prospectively collected data on twin pregnancies undergoing routine ultrasound examination at 11-13 weeks' gestation between 2002 and 2019. In pregnancies with no major abnormalities, we compared overall survival, fetal loss at < 24 weeks' gestation, perinatal death at ≥ 24 weeks, delivery at < 37 and < 32 weeks, and birth weight < 5th percentile between DC, MCDA and MCMA twins.Results: The study population of 6225 twin pregnancies with two live fetuses at 11-13 weeks' gestation with no major abnormalities included 4896 (78.7%) DC, 1274 (20.5%) MCDA and 55 (0.9%) MCMA twins. In DC twins, the rate of loss at < 24 weeks' gestation in all fetuses was 2.3%; this rate was higher in MCDA twins (7.7%; relative risk (RR), 3.258; 95% CI, 2.706-3.923) and more so in MCMA twins (21.8%; RR, 9.289; 95% CI, 6.377-13.530). In DC twins, the rate of perinatal death at ≥ 24 weeks in all twins that were alive at 24 weeks was 1.0%; this rate was higher in MCDA twins (2.5%; RR, 2.456; 95% CI, 1.779-3.389) and more so in MCMA twins (9.3%; RR, 9.130; 95% CI, 4.584-18.184). In DC twins, the rate of preterm birth at < 37 weeks' gestation in pregnancies with at least one liveborn twin was 48.6%; this rate was higher in MCDA twins (88.5%; RR, 1.824; 95% CI, 1.760-1.890) and more so in MCMA twins (100%; RR, 2.060; 95% CI, 2.000-2.121). In DC twins, the rate of preterm birth at < 32 weeks was 7.4%; this rate was higher in MCDA twins (14.2%; RR, 1.920; 95% CI, 1.616-2.281) and more so in MCMA twins (26.8%; RR, 3.637; 95% CI, 2.172-6.089). In DC twin pregnancies with at least one liveborn twin, the rate of a small-for-gestational-age neonate among all liveborn twins was 31.2% and in MCDA twins this rate was higher (37.8%; RR, 1.209; 95% CI, 1.138-1.284); in MCMA twins, the rate was not significantly different (33.3%; RR, 1.067; 95% CI, 0.783-1.455). Kaplan-Meier analysis showed a significant difference in survival in MCDA and MCMA twins, compared to DC twins, for both the interval of 12 to < 24 weeks' gestation (log-rank test, P < 0.0001 for both) and that of ≥ 24 to 38 weeks (log-rank test, P < 0.0001 for both). Endoscopic laser ablation of intertwin communicating placental vessels was carried out in 127 (10.0%) MCDA twin pregnancies for TTTS and/or sFGR and, in 111 of these, surgery was performed at < 24 weeks; both fetuses survived in 62 (55.9%) cases, one fetus survived in 25 (22.5%) cases and there were no survivors in 24 (21.6%) cases. On the extreme assumption that, had laser surgery not been carried out in these cases, all fetuses would have died, the total fetal loss rate at < 24 weeks' gestation in MCDA twins would have been 13.5%.Conclusions: The rates of fetal loss at < 24 weeks' gestation, perinatal death at ≥ 24 weeks and preterm birth are higher in MCDA and more so in MCMA twins than in DC twins. In MCDA twins, the rate of fetal loss may have been reduced by endoscopic laser surgery in those that developed early TTTS and/or sFGR. These data would be useful in counseling parents as to the likely outcome of their pregnancy and in defining strategies for surveillance and interventions in the management of the different types of twin pregnancy. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To investigate the potential value of routine ultrasound examination at 35-37 weeks' gestation in the diagnosis of previously unknown fetal abnormalities.Methods: This was a prospective study of 52 400 singleton pregnancies attending for a routine ultrasound examination at 35 + 0 to 36 + 6 weeks' gestation; all pregnancies had a previous scan at 18-24 weeks and 47 214 also had a scan at 11-13 weeks. We included pregnancies resulting in live birth or stillbirth but excluded those with known chromosomal abnormality. Abnormalities were classified according to the affected major organ system, and the type and incidence of new abnormalities were determined.Results: In the study population, the incidence of fetal abnormality was 1.9% (995/52 400), including 674 (67.7%) that had been diagnosed previously during the first and/or second trimester, 247 (24.8%) that were detected for the first time at 35-37 weeks and 74 (7.4%) that were detected for the first time postnatally. The most common abnormalities that were diagnosed during the first and/or second trimester and that were also observed at 35-37 weeks included ventricular septal defect, talipes, unilateral renal agenesis and/or pelvic kidney, hydronephrosis, duplex kidney, unilateral multicystic kidney, congenital pulmonary airway malformation, ventriculomegaly, cleft lip and palate, polydactyly and abdominal cyst or gastroschisis. The most common abnormalities first seen at 35-37 weeks were hydronephrosis, mild ventriculomegaly, ventricular septal defect, duplex kidney, ovarian cyst and arachnoid cyst. The incidence of abnormalities first seen at 35-37 weeks was 0.5% and those that were detected exclusively for the first time at this examination were ovarian cyst, microcephaly, achondroplasia, dacryocystocele and hematocolpos. The incidence of abnormalities first seen postnatally was 0.1% and the most common were isolated cleft palate, polydactyly or syndactyly and ambiguous genitalia or hypospadias; prenatal examination of the genitalia was not a compulsory part of the protocol.Conclusions: A high proportion of fetal abnormalities are detected for the first time during a routine ultrasound examination at 35-37 weeks' gestation. Such diagnosis and subsequent management, including selection of timing and place for delivery and postnatal investigations, could potentially improve postnatal outcome. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of diet and/or exercise in overweight or obese pregnant women on the risk of preeclampsia (PE). Methods: We performed a systematic review and meta-analysis of randomized controlled trials examining the effect of diet and/or exercise interventions in overweight and obese pregnant women on the risk of PE and hypertensive disorders. We completed a literature search through PubMed, Embase, Cinahl, Web of science, Cochrane CENTRAL Library from their earliest entries to November 2017 and from references of other systematic reviews. No language restrictions were applied. Relative risks (RR) with random effect were calculated with their 95% confidence intervals (CI). Results: There were 23 eligible trials (7236 participants), including 11 (5023 participants) investigating the effect of diet and three (387 participants) investigating the effect of exercise on risk of PE, 14 (4345 participants) investigating the effect of diet, five (884 participants) investigating the effect of exercise and one (304 participants) investigating the effect of diet and exercise on risk of hypertensive disorders. Most studies were considered to be at low risk of bias for random sequence allocation and incomplete outcome data but at high risk of bias for blinding of participant and personnel. The heterogeneity of the studies on PE was low (I2 = 0-11%), but the heterogeneity of the studies on hypertensive disorders was variable (I2 = 0-53%). In women randomized to diet and/or exercise, compared to expectant management, there was no significant difference in the risk of PE (RR 1.01, 95% CI 0.80-1.27; p = .96) or hypertensive disorders of pregnancy (RR 0.87, 95% CI 0.70-1.06; p = .17). In the intervention group, compared to expectant management, gestational weight gain was significantly lower (-1.47 kg, 95% CI -1.97 to -0.97; p < .00001). Metaregression weighted by the size of the studies showed no significant association between gestational weight gain and the risk of PE or hypertensive disorders (p = .314 and p = .124, respectively). Conclusions: Diet and exercise in overweight or obese pregnant women are beneficial in reducing gestational weight gain. However, these interventions do not reduce the risk of PE or hypertensive disorders of pregnancy. [ABSTRACT FROM AUTHOR]

Background: Stillbirth remains a major problem in both developing and developed countries. Omics evaluation of stillbirth has been highlighted as a top research priority. Objective: To identify new putative first-trimester biomarkers in maternal serum for stillbirth prediction using metabolomics-based approach. Methods: Targeted, nuclear magnetic resonance (NMR) and mass spectrometry (MS), and untargeted liquid chromatography-MS (LC-MS) metabolomic analyses were performed on first-trimester maternal serum obtained from 60 cases that subsequently had a stillbirth and 120 matched controls. Metabolites by themselves or in combination with clinical factors were used to develop logistic regression models for stillbirth prediction. Prediction of stillbirths overall, early (<28 weeks and <32 weeks), those related to growth restriction/placental disorder, and unexplained stillbirths were evaluated. Results: Targeted metabolites including glycine, acetic acid, L-carnitine, creatine, lysoPCaC18:1, PCaeC34:3, and PCaeC44:4 predicted stillbirth overall with an area under the curve [AUC, 95% confidence interval (CI)] = 0.707 (0.628-0.785). When combined with clinical predictors the AUC value increased to 0.740 (0.667-0.812). First-trimester targeted metabolites also significantly predicted early, unexplained, and placental-related stillbirths. Untargeted LC-MS features combined with other clinical predictors achieved an AUC (95%CI) = 0.860 (0.793-0.927) for the prediction of stillbirths overall. We found novel preliminary evidence that, verruculotoxin, a toxin produced by common household molds, might be linked to stillbirth. Conclusions: We have identified novel biomarkers for stillbirth using metabolomics and demonstrated the feasibility of first-trimester prediction. [ABSTRACT FROM AUTHOR]

Objective: To examine the performance of the routine 11-13-week scan in detecting fetal non-chromosomal abnormalities.Methods: This was a retrospective study of prospectively collected data from 100 997 singleton pregnancies attending for a routine ultrasound examination of fetal anatomy, performed according to a standardized protocol, at 11-13 weeks' gestation. All continuing pregnancies had an additional scan at 18-24 weeks and 71 754 had a scan at either 30-34 or 35-37 weeks. The final diagnosis of fetal abnormality was based on the results of postnatal examination in cases of live birth and on the findings of the last ultrasound examination in cases of pregnancy termination, miscarriage or stillbirth. The performance of the 11-13-week scan in the detection of fetal abnormalities was determined.Results: The study population contained 1720 (1.7%) pregnancies with a fetal abnormality, including 474 (27.6%) detected on the first-trimester scan, 926 (53.8%) detected on the second-trimester scan and 320 (18.6%) detected in the third trimester or postnatally. At 11-13 weeks' gestation, we diagnosed all cases of acrania, alobar holoprosencephaly, encephalocele, tricuspid or pulmonary atresia, pentalogy of Cantrell, ectopia cordis, exomphalos, gastroschisis and body-stalk anomaly and > 50% of cases of open spina bifida, hypoplastic left heart syndrome, atrioventricular septal defect, complex heart defect, left atrial isomerism (interrupted inferior vena cava with normal intracardiac anatomy), lower urinary tract obstruction, absence of extremities, fetal akinesia deformation sequence and lethal skeletal dysplasia. Common abnormalities that were detected in < 10% of cases at 11-13 weeks included ventriculomegaly, agenesis of the corpus callosum, isolated cleft lip, congenital pulmonary airway malformation, ventricular septal defect, abdominal cysts, unilateral renal agenesis or multicystic kidney, hydronephrosis, duplex kidney, hypospadias and talipes.Conclusions: A routine 11-13-week scan, carried out according to a standardized protocol, can identify many severe non-chromosomal fetal abnormalities. A summary statistic of the performance of the first-trimester scan is futile because some abnormalities are always detectable, whereas others are either non-detectable or sometimes detectable. To maximize prenatal detection of abnormalities, additional scans in both the second and third trimesters are necessary. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To assess the additive value of fetal growth velocity between 32 and 36 weeks' gestation to the performance of ultrasonographic estimated fetal weight (EFW) at 35 + 0 to 36 + 6 weeks' gestation for prediction of delivery of a small-for-gestational-age (SGA) neonate and adverse perinatal outcome.Methods: This was a prospective study of 14 497 singleton pregnancies undergoing routine ultrasound examination at 30 + 0 to 34 + 6 and at 35 + 0 to 36 + 6 weeks' gestation. Multivariable logistic regression analysis was used to determine whether addition of growth velocity, defined as the difference in EFW Z-score or abdominal circumference (AC) Z-score between the early and late third-trimester scans divided by the time interval between the scans, improved the performance of EFW Z-score at 35 + 0 to 36 + 6 weeks in the prediction of, first, delivery of a SGA neonate with birth weight < 10th and < 3rd percentiles within 2 weeks and at any stage after assessment and, second, a composite of adverse perinatal outcome, defined as stillbirth, neonatal death or admission to the neonatal unit for ≥ 48 h.Results: Multivariable logistic regression analysis demonstrated that significant contributors to the prediction of a SGA neonate were EFW Z-score at 35 + 0 to 36 + 6 weeks' gestation, fetal growth velocity, by either AC Z-score or EFW Z-score, and maternal risk factors. The area under the receiver-operating characteristics curve (AUC) and detection rate (DR), at a 10% screen-positive rate, for prediction of a SGA neonate < 10th percentile born within 2 weeks after assessment achieved by EFW Z-score at 35 + 0 to 36 + 6 weeks (AUC, 0.938 (95% CI, 0.928-0.947); DR, 80.7% (95% CI, 77.6-83.9%)) were not significantly improved by addition of EFW growth velocity and maternal risk factors (AUC, 0.941 (95% CI, 0.932-0.950); P = 0.061; DR, 82.5% (95% CI, 79.4-85.3%)). Similar results were obtained when growth velocity was defined by AC rather than EFW. Similarly, there was no significant improvement in the AUC and DR, at a 10% screen-positive rate, for prediction of a SGA neonate < 10th percentile born at any stage after assessment or a SGA neonate < 3rd percentile born within 2 weeks or at any stage after assessment, achieved by EFW Z-score at 35 + 0 to 36 + 6 weeks by addition of maternal factors and either EFW growth velocity or AC growth velocity. Multivariable logistic regression analysis demonstrated that the only significant contributor to adverse perinatal outcome was maternal risk factors. Multivariable logistic regression analysis in the group with EFW < 10th percentile demonstrated that significant contribution to prediction of delivery of a neonate with birth weight < 10th and < 3rd percentiles and adverse perinatal outcome was provided by EFW Z-score at 35 + 0 to 36 + 6 weeks, but not by AC growth velocity < 1st decile.Conclusion: The predictive performance of EFW at 35 + 0 to 36 + 6 weeks' gestation for delivery of a SGA neonate and adverse perinatal outcome is not improved by addition of estimated growth velocity between 32 and 36 weeks' gestation. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the incidence of antepartum stillbirth in relation to the distribution of neonatal/fetal weight for different gestational ages. Design: Prospective observational cohort study. Setting: Obstetric ultrasound departments in two UK maternity hospitals. Population: 168 966 women with singleton pregnancies attending for routine antenatal care. Methods: We examined the incidence of antepartum stillbirths, within different birthweight and fetal weight percentile subgroups, conditioning for gestational age. Main outcome measures: Incidence of antepartum stillbirth. Results: The risk of stillbirth progressively increased for lower birthweight. Considering the 25–75th percentile as the reference category, the relative risks for stillbirth at <37 weeks' gestation were 7.6 (95% confidence interval [CI] 5.7–10.2) <1st percentile, 2.6 (95% CI 1.8–3.7) 1 to 10th percentile, 1.4 (95% CI 0.9–2.1) 10 to 25th percentile, 0.8 (95% CI 0.4–1.5) 75 to 90th percentile, 0.8 (95% CI 0.4–1.7) 90 to 99th percentile, 0.9 (95% CI 0.3–2.5) >99th percentile. The respective values for births at ≥37 weeks' gestation were 5.0 (95% CI 2.9–8.9), 2.1 (95% CI 1.4–3.3), 1.4 (95% CI 0.9–2.1), 1.2 (95% CI 0.7–1.8), 1.0 (95% CI 0.6–1.8) and 4.0 (95% CI 1.8–9.3). The incidence of stillbirth in ongoing low‐risk singleton pregnancies gradually increases for smaller fetuses at any gestational point. The higher incidence (5.56%) was evident for fetal weight <1st percentile between 24 and 28 weeks' gestation. Conclusion: Fetal weight and the weight of the stillborn have a continuous association with the incidence of antepartum stillbirth which is affected by gestational age. [ABSTRACT FROM AUTHOR]

Objectives: First, to examine the predictive performance of maternal serum glycosylated fibronectin (GlyFn) at 35 + 0 to 36 + 6 weeks' gestation in screening for delivery with pre‐eclampsia (PE) and delivery with gestational hypertension (GH) at ≥ 37 weeks' gestation, both within 3 weeks and at any time after the examination. Second, to compare the predictive performance for delivery with PE and delivery with GH of various combinations of biomarkers, including GlyFn, mean arterial pressure (MAP), uterine artery pulsatility index (UtA‐PI), serum placental growth factor (PlGF) and soluble fms‐like tyrosine kinase‐1 (sFlt‐1). Third, to compare the predictive performance for delivery with PE and delivery with GH by serum PlGF concentration, sFlt‐1/PlGF concentration ratio and the competing‐risks model with different combinations of biomarkers as above. Fourth, to compare the predictive performance of screening at 11 + 0 to 13 + 6 weeks vs 35 + 0 to 36 + 6 weeks for delivery with PE and delivery with GH at ≥ 37 weeks' gestation. Methods: This was a case–control study in which maternal serum GlyFn was measured in stored samples from a non‐intervention screening study in singleton pregnancies at 35 + 0 to 36 + 6 weeks' gestation using a point‐of‐care device. We used samples from women who delivered at ≥ 37 weeks' gestation, including 100 who developed PE, 100 who developed GH and 600 controls who did not develop PE or GH. In all cases, MAP, UtA‐PI, PlGF and sFlt‐1 were measured during the routine visit at 35 + 0 to 36 + 6 weeks. We used samples from patients that had been examined previously at 11 + 0 to 13 + 6 weeks' gestation. Levels of GlyFn were transformed to multiples of the expected median (MoM) values after adjusting for maternal demographic characteristics and elements from the medical history. Similarly, the measured values of MAP, UtA‐PI, PlGF and sFlt‐1 were converted to MoM. The competing‐risks model was used to combine the prior distribution of the gestational age at delivery with PE, obtained from maternal risk factors, with various combinations of biomarker MoM values to derive the patient‐specific risks of delivery with PE. The performance of screening of different strategies was estimated by examining the detection rate (DR) at a 10% fixed false‐positive rate (FPR) and McNemar's test was used to compare the DRs between the different methods of screening. Results: The DR, at 10% FPR, of screening by the triple test (maternal risk factors plus MAP, PlGF and sFlt‐1) was 83.7% (95% CI, 70.3–92.7%) for delivery with PE within 3 weeks of screening and 80.0% (95% CI, 70.8–87.3%) for delivery with PE at any time after screening, and this performance was not improved by the addition of GlyFn. The performance of screening by a combination of maternal risk factors, MAP, PlGF and GlyFn was similar to that of the triple test, both for delivery with PE within 3 weeks and at any time after screening. The performance of screening by a combination of maternal risk factors, MAP, UtA‐PI and GlyFn was similar to that of the triple test, and they were both superior to screening by low PlGF concentration (PE within 3 weeks: DR, 65.3% (95% CI, 50.4–78.3%); PE at any time: DR, 56.0% (95% CI, 45.7–65.9%)) or high sFlt‐1/PlGF concentration ratio (PE within 3 weeks: DR, 73.5% (95% CI, 58.9–85.1%); PE at any time: DR, 63.0% (95% CI, 52.8–72.4%)). The predictive performance of screening at 35 + 0 to 36 + 6 weeks' gestation for delivery with PE and delivery with GH at ≥ 37 weeks' gestation was by far superior to screening at 11 + 0 to 13 + 6 weeks. Conclusion: GlyFn is a potentially useful biomarker in third‐trimester screening for term PE and term GH, but the findings of this case–control study need to be validated by prospective screening studies. © 2023 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objective: To estimate the patient-specific risk of pre-eclampsia (PE) at 19-24 weeks' gestation by maternal factors and combinations of mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), serum placental growth factor (PlGF) and serum soluble fms-like tyrosine kinase-1 (sFlt-1). On the basis of the risk of PE, the women would be stratified into high-, intermediate- and low-risk management groups. The high-risk group would require close monitoring for high blood pressure and proteinuria at 24-31 weeks. The intermediate-risk group, together with the undelivered pregnancies from the high-risk group, would have reassessment of risk for PE at 32 weeks to identify those who would require close monitoring for high blood pressure and proteinuria at 32-35 weeks. All pregnancies would have reassessment of risk for PE at 36 weeks to define the plan for further monitoring and delivery.Methods: This was a prospective observational study of women attending for an ultrasound scan at 19-24 weeks as part of routine pregnancy care. Patient-specific risks of delivery with PE at < 32 and at < 36 weeks' gestation were calculated using the competing-risks model to combine the prior distribution of gestational age at delivery with PE, obtained from maternal characteristics and medical history, with multiples of the median (MoM) values of MAP, UtA-PI, PlGF and sFlt-1. Different risk cut-offs were used to vary the proportion of the population stratified into high-, intermediate- and low-risk groups, and the performance of screening for delivery with PE at < 32 weeks' gestation and at 32 + 0 to 35 + 6 weeks was estimated.Results: The study population of 16 254 singleton pregnancies included 467 (2.9%) that subsequently developed PE (23 delivered at < 32 weeks, 58 delivered at 32 + 0 to 35 + 6 weeks and 386 delivered at ≥ 36 weeks). Using a risk of > 1 in 25 for PE at < 32 weeks' gestation and risk of > 1 in 150 for PE at < 36 weeks, the proportion of the population stratified into the high-risk group was about 1% of the total, and the proportion of cases of PE at < 32 weeks' gestation contained within this high-risk group varied from about 35% with screening by maternal factors and MAP, to 78% with maternal factors, MAP and UtA-PI, and up to 100% with maternal factors, MAP, UtA-PI and PlGF, with or without sFlt-1. Similarly, the proportion of the population requiring reassessment of risk at 32 weeks' gestation and the proportion of cases of PE at 32 + 0 to 35 + 6 weeks contained within this population varied, respectively, from about 18% and 79% with screening by maternal factors and MAP, to 10% and 90% with maternal factors, MAP, UtA-PI and PlGF, with or without sFlt-1.Conclusion: In the new pyramid of pregnancy care, assessment of risk for PE at 19-24 weeks' gestation can stratify the population into those requiring intensive monitoring at 24-31 weeks and those in need of reassessment at 32 weeks. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To examine the performance of screening for early, preterm and term pre-eclampsia (PE) at 11-13 weeks' gestation by maternal factors and combinations of mean arterial pressure (MAP), uterine artery (UtA) pulsatility index (PI), serum placental growth factor (PlGF) and serum pregnancy-associated plasma protein-A (PAPP-A).Methods: The data for this study were derived from three previously reported prospective non-intervention screening studies at 11 + 0 to 13 + 6 weeks' gestation in a combined total of 61 174 singleton pregnancies, including 1770 (2.9%) that developed PE. Bayes' theorem was used to combine the prior distribution of gestational age at delivery with PE, obtained from maternal characteristics, with various combinations of biomarker multiples of the median (MoM) values to derive patient-specific risks of delivery with PE at < 37 weeks' gestation. The performance of such screening was estimated.Results: In pregnancies that developed PE, compared to those without PE, the MoM values of UtA-PI and MAP were increased and those of PAPP-A and PlGF were decreased, and the deviation from normal was greater for early than late PE for all four biomarkers. Combined screening by maternal factors, UtA-PI, MAP and PlGF predicted 90% of early PE, 75% of preterm PE and 41% of term PE, at a screen-positive rate of 10%; inclusion of PAPP-A did not improve the performance of screening. The performance of screening depended on the racial origin of the women; on screening by a combination of maternal factors, MAP, UtA-PI and PlGF and using a risk cut-off of 1 in 100 for PE at < 37 weeks in Caucasian women, the screen-positive rate was 10% and detection rates for early, preterm and term PE were 88%, 69% and 40%, respectively. With the same method of screening and risk cut-off in women of Afro-Caribbean racial origin, the screen-positive rate was 34% and detection rates for early, preterm and term PE were 100%, 92% and 75%, respectively.Conclusion: Screening by maternal factors and biomarkers at 11-13 weeks' gestation can identify a high proportion of pregnancies that develop early and preterm PE. © 2018 Crown copyright. Ultrasound in Obstetrics & Gynecology © 2018 ISUOG. [ABSTRACT FROM AUTHOR]

Objective: To compare the predictive performance for delivery with pre‐eclampsia (PE) within 2 weeks of assessment in women with chronic hypertension at 24–41 weeks' gestation between serum glycosylated fibronectin (GlyFn) concentration, serum placental growth factor (PlGF) concentration and soluble fms‐like tyrosine kinase‐1 (sFlt‐1) to PlGF concentration ratio. Methods: This was a prospective study of 104 women with a singleton pregnancy and chronic hypertension presenting at 24–41 weeks' gestation. Twenty‐six (25.0%) cases developed superimposed PE within 2 weeks of sampling. We compared the predictive performance for superimposed PE between GlyFn, PlGF and the sFlt‐1/PlGF ratio at a fixed screen‐positive rate of approximately 10%. Results: The median gestational age at sampling was 34.1 (interquartile range, 31.5–35.6) weeks and 84.6% (88/104) of cases were sampled at < 36 weeks. The predictive performance for superimposed PE of the three methods of screening was similar, with detection rates of about 23–27%, at a screen‐positive rate of 11% and a false‐positive rate of about 5%. Conclusions: Measurement of GlyFn is a simple point‐of‐care test that can be carried out without need for a laboratory and provide results within 10 min of testing. In this respect, it could potentially replace the angiogenic markers that are used currently in the prediction of imminent PE in high‐risk women. However, neither GlyFn nor angiogenic factors are likely to improve the management of women with chronic hypertension because their predictive performance for superimposed PE is poor. © 2023 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objective: To examine the association between chronic hypertension (CH) and a wide range of adverse pregnancy outcomes after adjustment for confounding factors in obstetric history and maternal characteristics.Methods: This was a prospective screening study for adverse pregnancy outcomes in women with singleton pregnancy attending their first routine hospital visit at 11 + 0 to 13 + 6 weeks' gestation. Data on maternal characteristics, medical and obstetric history and pregnancy outcome were collected. Regression analysis was performed to examine the association between CH and adverse pregnancy outcomes, including late miscarriage, stillbirth, pre-eclampsia (PE), gestational diabetes mellitus (GDM), spontaneous and iatrogenic preterm birth (PTB), small-for-gestational-age (SGA) neonate, large-for-gestational-age (LGA) neonate and elective and emergency Cesarean section (CS).Results: The study population of 109 932 pregnancies included 1417 (1.3%) women with CH. After adjusting for potential confounding variables from maternal characteristics, medical and obstetric history, CH was associated with increased risk of stillbirth (odds ratio (OR), 2.38 (95% CI, 1.51-3.75)), PE (OR, 5.76 (95% CI, 4.93-6.73)), SGA (OR, 2.06 (95% CI, 1.79-2.39)), GDM (OR, 1.61 (95% CI, 1.27-2.05)), iatrogenic PTB < 37 weeks (OR, 3.73 (95% CI, 3.07-4.53)) and elective CS (OR, 1.79 (95% CI, 1.52-2.11)), decreased risk of LGA (OR, 0.65 (95% CI, 0.53-0.78)) and had no significant effect on late miscarriage, spontaneous PTB or emergency CS.Conclusion: CH should be combined with other maternal characteristics and medical and obstetric history when calculating an individualized adjusted risk for adverse pregnancy complications. CH increases the risk of stillbirth, PE, SGA, GDM, iatrogenic PTB and elective CS and reduces the risk for LGA. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

ABSTRACT: Objectives: To examine the prevalence of alobar holoprosencephaly, exomphalos, megacystis and nuchal translucency thickness (NT) ≥ 3.5 mm, the incidence and types of chromosomal abnormalities associated with these conditions and their overall impact on the rate of invasive testing and performance of screening at 11–14 weeks. Methods: This was a prospective screening study for trisomies 21, 18 and 13 by the first‐trimester combined test at three maternity units in England. Results: In the study population of 108 982 singleton pregnancies, 870 (0.8%) had abnormal karyotype, including 654 (75.2%) with trisomies 21, 18 or 13 and 216 (24.8%) with other chromosomal abnormalities. The prevalence of alobar holoprosencephaly, exomphalos, megacystis and NT ≥ 3.5 mm was 1 in 2945, 1 in 419, 1 in 1345 and 1 in 119, respectively. Chromosomal abnormalities were observed in 78.4% of cases of holoprosencephaly, 40.8% of exomphalos, 18.5% of megacystis and 48.5% of those with NT ≥ 3.5 mm. The most common chromosomal abnormality associated with holoprosencephaly was trisomy 13, with exomphalos and megacystis was trisomy 18 and with increased NT was trisomy 21. Fetal karyotyping of cases with major fetal defects or increased NT would potentially detect 57% of all chromosomal abnormalities at an invasive testing rate of 1.1%. Conclusion: Major fetal defects and increased NT at 11–13 weeks' gestation are associated with a high risk of chromosomal abnormalities and merit invasive fetal testing. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objectives: To examine the prevalence of alobar holoprosencephaly, exomphalos, megacystis and nuchal translucency thickness (NT) ≥ 3.5 mm, the incidence and types of chromosomal abnormalities associated with these conditions and their overall impact on the rate of invasive testing and performance of screening at 11-14 weeks.Methods: This was a prospective screening study for trisomies 21, 18 and 13 by the first-trimester combined test at three maternity units in England.Results: In the study population of 108 982 singleton pregnancies, 870 (0.8%) had abnormal karyotype, including 654 (75.2%) with trisomies 21, 18 or 13 and 216 (24.8%) with other chromosomal abnormalities. The prevalence of alobar holoprosencephaly, exomphalos, megacystis and NT ≥ 3.5 mm was 1 in 2945, 1 in 419, 1 in 1345 and 1 in 119, respectively. Chromosomal abnormalities were observed in 78.4% of cases of holoprosencephaly, 40.8% of exomphalos, 18.5% of megacystis and 48.5% of those with NT ≥ 3.5 mm. The most common chromosomal abnormality associated with holoprosencephaly was trisomy 13, with exomphalos and megacystis was trisomy 18 and with increased NT was trisomy 21. Fetal karyotyping of cases with major fetal defects or increased NT would potentially detect 57% of all chromosomal abnormalities at an invasive testing rate of 1.1%.Conclusion: Major fetal defects and increased NT at 11-13 weeks' gestation are associated with a high risk of chromosomal abnormalities and merit invasive fetal testing. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: Our primary objective was to apply metabolomic pathway analysis of first trimester maternal serum to provide an insight into the pathogenesis of late-onset preeclampsia (late-PE) and thereby identify plausible therapeutic targets for PE.Methods: NMR-based metabolomics analysis was performed on 29 cases of late-PE and 55 unaffected controls. In order to achieve sufficient statistical power to perform the pathway analysis, these cases were combined with a group of previously analyzed specimens, 30 late-PE cases and 60 unaffected controls. Specimens from both groups of cases and controls were collected in the same clinical centers during the same time period. In addition, NMR analyses were performed in the same lab and using the same techniques.Results: We identified abnormalities in branch chain amino acids (valine, leucine and isoleucine) and propanoate, glycolysis, gluconeogenesis and ketone body metabolic pathways. The results suggest insulin resistance and metabolic syndrome, mitochondrial dysfunction and disturbance of energy metabolism, oxidative stress and lipid dysfunction in the pathogenesis of late PE and suggest a potential role for agents that reduce insulin resistance in PE.Conclusions: Branched chain amino acids are known markers of insulin resistance and strongly predict future diabetes development. The analysis provides independent evidence linking insulin resistance and late-PE and suggests a potentially important therapeutic role for pharmacologic agents that reduce insulin resistance for late-PE. [ABSTRACT FROM AUTHOR]

Objectives: To assess Congo red urine test in the first trimester for preeclampsia (PE) prediction.Sample: A Congo red test was developed with a cohort of 81 pregnant women in Bnai Zion hospital, Israel, at 26-41 weeks of gestation (12 PE cases). The test was then applied to a first-trimester cohort of 642 women at King's College Hospital, UK (105 subsequently developed PE, 21 early, i.e., <34 weeks; 537 controls).Methods: Urine samples were spotted onto nitrocellulose membranes, stained with Congo red, de-stained, dried and quantified with imager and densitometry.Results: At PE signs and symptoms, the detection rate (DR) was 93% and the false-positive rate (FPR) 4%. However, with first-trimester urine samples, the DR was 33.3%, 16.1% and 20% for early, late and all PE cases, respectively, at 12.8% FPR. The odds ratio (OR) for PE by Congo red alone (including adjusted OR) was superior to body mass index and mean arterial blood pressure (MAP) but inferior to previous PE and black ethnicity. Combining all five parameters generated an adjusted OR of 13.92 for PE (p < 0.001).Conclusion: Congo red urine test at PE verifies the disorder. In the first trimester, it adds accuracy for PE prediction in obese, black women, who had previous PE and over-average MAP. [ABSTRACT FROM AUTHOR]

Background: Preterm birth is the leading cause of neonatal and infant death and of disability among survivors. It is unclear whether a pessary inserted around the cervix reduces the risk of preterm singleton birth.Methods: We conducted a multicenter, randomized, controlled trial comparing pessary placement with expectant management (control) in girls and women who were pregnant with singletons (singleton pregnancies) and who had a cervical length of 25 mm or less at 20 weeks 0 days to 24 weeks 6 days of gestation. Participants in either group who had a cervical length of 15 mm or less, at randomization or at subsequent visits, received treatment with vaginal progesterone. The primary outcome was spontaneous delivery before 34 weeks of gestation.Results: In an intention-to-treat analysis, there was no significant difference between the pessary group (465 participants) and the control group (467 participants) in the rate of spontaneous delivery before 34 weeks (12.0% and 10.8%, respectively; odds ratio in the pessary group, 1.12; 95% confidence interval, 0.75 to 1.69; P=0.57). There were no significant differences in the rates of perinatal death (3.2% in the pessary group and 2.4% in the control group, P=0.42), adverse neonatal outcome (6.7% and 5.7%, respectively; P=0.55), or neonatal special care (11.6% and 12.9%, respectively; P=0.59). The incidence of new or increased vaginal discharge was significantly higher in the pessary group than in the control group.Conclusions: Among girls and women with singleton pregnancies who had a short cervix, a cervical pessary did not result in a lower rate of spontaneous early preterm delivery than the rate with expectant management. (Funded by the Fetal Medicine Foundation; Current Controlled Trials number, ISRCTN01096902.). [ABSTRACT FROM AUTHOR]

Objective: To develop a model based on maternal characteristics and medical history (maternal factors) for the prediction of delivery of large-for-gestational-age (LGA) neonates, and to examine the potential value of first-, second- and third-trimester fetal biometry and biomarkers in improving such a model. Methods: This was a screening study in 76 300, 54 999, 25 727 and 6181 singleton pregnancies at 11-13, 19-24, 30-34 and 35-37 weeks' gestation, respectively. The a-priori risk for LGA with birth weight > 95(th) percentile (LGA > 95(th) ) was calculated using multivariable logistic regression analysis to determine which of the maternal factors had a significant contribution. Regression analysis was then used to determine whether screening by a combination of maternal factors, fetal biometry and various biophysical and biochemical markers had significant contribution in predicting delivery of LGA neonates. Results: The likelihood of LGA > 95(th) increased with increasing maternal weight and height and was lower in women of Afro-Caribbean and South Asian racial origins, in cigarette smokers and in nulliparous women. The risk was higher in women with pre-existing diabetes mellitus Type I and lower in those with chronic hypertension. In parous women, the risk increased with birth-weight Z-score in previous pregnancy and prior history of gestational diabetes and decreased with interpregnancy interval. Screening by maternal factors at 11-13 weeks predicted 32%, 44% and 60% of LGA > 95(th) at false-positive rates (FPRs) of 5%, 10% and 20%, respectively. With the addition of fetal biometry, the detection rates improved to 37%, 51% and 68% at 19-24 weeks, 50%, 65% and 81% at 30-34 weeks and 60%, 73% and 85% at 35-37 weeks at FPRs of 5%, 10% and 20%, respectively. The addition of biomarkers did not improve the detection rates achieved when screening by a combination of maternal factors and fetal biometry. Conclusion: Combined screening by maternal factors and fetal biometry can predict a high proportion of pregnancies that will deliver LGA neonates. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Background: Obesity is associated with an increased risk of adverse pregnancy outcomes. Lifestyle-intervention studies have not shown improved outcomes. Metformin improves insulin sensitivity and in pregnant patients with gestational diabetes it leads to less weight gain than occurs in those who do not take metformin.Methods: In this double-blind, placebo-controlled trial, we randomly assigned pregnant women without diabetes who had a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of more than 35 to receive metformin, at a dose of 3.0 g per day, or placebo (225 women in each group) from 12 to 18 weeks of gestation until delivery. The BMI was calculated at the time of study entry (12 to 18 weeks of gestation). The primary outcome was a reduction in the median neonatal birth-weight z score by 0.3 SD (equivalent to a 50% reduction, from 20% to 10%, in the incidence of large-for-gestational-age neonates). Secondary outcomes included maternal gestational weight gain and the incidence of gestational diabetes and of preeclampsia, as well as the incidence of adverse neonatal outcomes. Randomization was performed with the use of computer-generated random numbers. The analysis was performed according to the intention-to-treat principle.Results: A total of 50 women withdrew consent during the trial, which left 202 women in the metformin group and 198 in the placebo group. There was no significant between-group difference in the median neonatal birth-weight z score (0.05 in the metformin group [interquartile range, -0.71 to 0.92] and 0.17 in the placebo group [interquartile range, -0.62 to 0.89], P=0.66). The median maternal gestational weight gain was lower in the metformin group than in the placebo group (4.6 kg [interquartile range, 1.3 to 7.2] vs. 6.3 kg [interquartile range, 2.9 to 9.2], P<0.001), as was the incidence of preeclampsia (3.0% vs. 11.3%; odds ratio, 0.24; 95% confidence interval, 0.10 to 0.61; P=0.001). The incidence of side effects was higher in the metformin group than in the placebo group. There were no significant between-group differences in the incidence of gestational diabetes, large-for-gestational-age neonates, or adverse neonatal outcomes.Conclusions: Among women without diabetes who had a BMI of more than 35, the antenatal administration of metformin reduced maternal weight gain but not neonatal birth weight. (Funded by the Fetal Medicine Foundation; ClinicalTrials.gov number, NCT01273584; EudraCT number, 2008-005892-83.). [ABSTRACT FROM AUTHOR]

Objectives: To develop and validate a prediction model for gestational diabetes mellitus (GDM) at 11-13 weeks' gestation based on maternal characteristics and history and to compare its performance with the method recommended by the National Institute of Health and Care Excellence (NICE) and five other published prediction models. Methods: A predictive logistic regression model for GDM was developed from 1,827 cases (2.4%) who developed GDM and 73,334 unaffected controls. A 5-fold cross-validation study was performed to validate this model and to compare its performance with those of the NICE guidelines and the previously published models. Results: In the logistic regression model, maternal age, weight, height, racial origin, family history of diabetes, use of ovulation drugs, birth weight, and previous history of GDM were found to be significant predictors of GDM. In screening for GDM in the 5-fold cross-validation study, detection rates (DRs) were higher (p < 0.0001) for the proposed model (DR = 83.2%) than for the NICE guidelines (DR = 77.5%) for a false positive rate of approximately 40% (determined by NICE). The area under the receiver operating characteristic curve of the new model was higher (p < 0.0001) than that of the previous five models (0.823 vs. 0.688-786). Conclusions: Early effective screening for GDM can be achieved based on maternal characteristics and history. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective To investigate the potential value of cerebroplacental ratio (CPR) at 36 weeks' gestation in the prediction of adverse perinatal outcome. Methods This was a screening study in 6178 singleton pregnancies at 35-37 weeks' gestation. Umbilical artery (UA) and fetal middle cerebral artery (MCA) pulsatility index (PI) were measured and the values were converted to multiples of the median (MoM) after adjustment from variables in maternal characteristics and medical history that affect the measurements. CPR was calculated by dividing MCA-PI MoM by UA-PI MoM. Multivariable logistic regression analysis was used to determine if measuring CPR improved the prediction of adverse perinatal outcome provided by maternal characteristics, medical history and obstetric factors. The detection rate (DR) and false-positive rate (FPR) of screening by CPR were estimated for stillbirth, Cesarean section for fetal distress, umbilical arterial cord blood pH ≤7.0, umbilical venous cord blood pH≤7.1, 5-min Apgar score<7 and admission to the neonatal unit (NNU) and neonatal intensive care unit (NICU). Results There was a linear association between CPR and both birth-weight Z-score and arterial or venous umbilical cord blood pH, but the steepness of the regression lines was inversely related to the interval from assessment to delivery. The performance of low CPR<5th percentile in screening for each adverse outcome was poor, with DRs of 6-15% and a FPR of about 6%. In the small subgroup of the population delivering within 2 weeks of assessment, the DRs improved to 14-50%, but with a simultaneous increase in FPR, to about 10%. Conclusion The performance of CPR in routine screening for adverse perinatal outcome at 36 weeks' gestation is poor. [ABSTRACT FROM AUTHOR]

Objectives: To develop and validate a prediction model for gestational diabetes mellitus (GDM) at 11-13 weeks' gestation based on maternal characteristics and history and to compare its performance with the method recommended by the National Institute of Health and Care Excellence (NICE) and five other published prediction models.Methods: A predictive logistic regression model for GDM was developed from 1,827 cases (2.4%) who developed GDM and 73,334 unaffected controls. A 5-fold cross-validation study was performed to validate this model and to compare its performance with those of the NICE guidelines and the previously published models.Results: In the logistic regression model, maternal age, weight, height, racial origin, family history of diabetes, use of ovulation drugs, birth weight, and previous history of GDM were found to be significant predictors of GDM. In screening for GDM in the 5-fold cross-validation study, detection rates (DRs) were higher (p < 0.0001) for the proposed model (DR = 83.2%) than for the NICE guidelines (DR = 77.5%) for a false positive rate of approximately 40% (determined by NICE). The area under the receiver operating characteristic curve of the new model was higher (p < 0.0001) than that of the previous five models (0.823 vs. 0.688-786).Conclusions: Early effective screening for GDM can be achieved based on maternal characteristics and history. [ABSTRACT FROM AUTHOR]

Objective: To estimate the proportion of other chromosomal abnormalities that could be missed if combined testing was replaced by cell-free (cf) DNA testing as the method of screening for trisomies 21, 18 and 13.Methods: The prevalence of trisomies 21, 18 or 13, sex chromosome aneuploidies, triploidy and other chromosomal abnormalities was examined in pregnancies undergoing first-trimester combined screening and chorionic villus sampling (CVS).Results: In 1,831 clinically significant chromosomal abnormalities in pregnancies with combined risk for trisomies 21, 18 and 13≥1:100, the contribution of trisomies 21, 18 or 13, sex chromosome aneuploidies, triploidy and other chromosomal abnormalities at high risk of adverse outcome was 82.9, 8.2, 3.9 and 5.0%, respectively. Combined screening followed by CVS for risk≥1:10 and cfDNA testing for risk 1:11-1:2,500 could detect 97% of trisomy 21 and 98% of trisomies 18 and 13. Additionally, 86% of monosomy X, half of 47,XXY, 47,XYY or 47,XXX, half of other chromosomal abnormalities and one third of triploidies, which are currently detected by combined screening and CVS for risk≥1:100, could be detected.Conclusions: Screening by cfDNA testing, contingent on results of combined testing, improves detection of trisomies, but misses a few of the other chromosomal abnormalities detected by screening with the combined test. [ABSTRACT FROM AUTHOR]

Objective: To examine potential performance of screening for trisomies by cell-free (cf) DNA testing in maternal blood contingent on results of first-line testing by combinations of fetal translucency thickness (NT), fetal heart rate (FHR), ductus venosus pulsatility index (DV PIV), and serum-free β-human chorionic gonadotropin (β-hCG), pregnancy-associated plasma protein-A (PAPP-A), placental growth factor (PLGF) and α-fetoprotein (AFP).Methods: Performance was estimated for firstly, screening by cfDNA in all pregnancies and secondly, cfDNA testing contingent on results of first-line testing by combinations of ultrasound and biochemical markers.Results: In first-line screening by cfDNA testing, the detection rate for trisomy 21 and trisomies 18 or 13 would be 99 and 96%, respectively, after invasive testing in 1% of the population. In contingent screening, a detection rate of 98% for trisomy 21 and 96% for trisomy 18 or 13, at an invasive testing rate of 0.7%, can be achieved by carrying out cfDNA testing in about 35, 20 and 11% of cases identified by first-line screening with the combined test alone (age, NT, FHR, β-hCG, PAPP-A), the combined test plus PLGF and AFP and the combined test plus PLGF, AFP and DV PIV, respectively.Conclusions: Effective first-trimester screening for trisomies can be achieved by contingent screening incorporating biomarkers and cfDNA testing. [ABSTRACT FROM AUTHOR]

Objective: To examine the performance of screening for trisomies 21, 18 and 13 at 11-13 weeks' gestation using specific algorithms for these trisomies based on combinations of fetal nuchal translucency thickness (NT), fetal heart rate (FHR), ductus venosus pulsatility index for veins (DV PIV), and serum free β-human chorionic gonadotropin (β-hCG), pregnancy-associated plasma protein A (PAPP-A), placental growth factor (PLGF) and α-fetoprotein (AFP). Methods: Model-based estimates of screening performance were produced for the distribution of maternal ages in England and Wales in 2011, and prospectively collected data on fetal NT, FHR, DV PIV, β-hCG, PAPP-A, PLGF and AFP from singleton pregnancies undergoing aneuploidy screening. Results: In screening by NT, FHR, free β-hCG and PAPP-A, using specific algorithms for trisomy 21 and trisomies 18 and 13 at the risk cutoff of 1:100, the estimated detection rate (DR) was 87.0% for trisomy 21 and 91.8% for trisomies 18 and 13, at a false-positive rate (FPR) of 2.2%. Addition of PLGF, AFP and DV PIV increased the DR to 93.3% for trisomy 21 and 95.4% for trisomies 18 and 13 and reduced the FPR to 1.3%. Conclusions: Effective screening for trisomies can be achieved using specific algorithms based on NT, FHR, DV PIV, β-hCG, PAPP-A, PLGF and AFP. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

ABSTRACT Objective To examine the association between maternal age and a wide range of adverse pregnancy outcomes after adjustment for confounding factors in obstetric history and maternal characteristics. Methods This was a retrospective study in women with singleton pregnancies attending the first routine hospital visit at 11 + 0 to 13 + 6 weeks' gestation. Data on maternal characteristics, and medical and obstetric history were collected and pregnancy outcomes ascertained. Maternal age was studied, both as a continuous and as a categorical variable. Regression analysis was performed to examine the association between maternal age and adverse pregnancy outcome including pre-eclampsia, gestational hypertension, gestational diabetes mellitus ( GDM), preterm delivery, small-for-gestational age ( SGA) neonate, large-for-gestational age ( LGA) neonate, miscarriage, stillbirth and elective and emergency Cesarean section. Results The study population included 76 158 singleton pregnancies with a live fetus at 11 + 0 to 13 + 6 weeks. After adjusting for potential maternal and pregnancy confounding variables, advanced maternal age (defined as ≥ 40 years) was associated with increased risk of miscarriage (odds ratio ( OR), 2.32 (95% CI, 1.83-2.93); P < 0.001), pre-eclampsia ( OR, 1.49 (95% CI, 1.22-1.82); P < 0.001), GDM ( OR, 1.88 (95% CI, 1.55-2.29); P < 0.001), SGA ( OR, 1.46 (95% CI, 1.27-1.69); P < 0.001) and Cesarean section ( OR, 1.95 (95% CI, 1.77-2.14); P < 0.001), but not with stillbirth, gestational hypertension, spontaneous preterm delivery or LGA. Conclusions Maternal age should be combined with other maternal characteristics and obstetric history when calculating an individualized adjusted risk for adverse pregnancy complications. Advanced maternal age is a risk factor for miscarriage, pre-eclampsia, SGA, GDM and Cesarean section, but not for stillbirth, gestational hypertension, spontaneous preterm delivery or LGA. Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

ABSTRACT Objectives To assess first-trimester placental perfusion, reflected in the uterine artery ( UtA) pulsatility index ( PI), in pregnancies complicated by gestational diabetes mellitus ( GDM), with or without pre-eclampsia ( PE), compared with those unaffected by GDM. Methods UtA-PI was measured at 11 + 0 to 13 + 6 weeks' gestation in 1037 singleton pregnancies that subsequently developed GDM and in 56 649 normoglycemic controls. The measured mean UtA-PI was converted to multiples of the expected normal median ( MoM), corrected for maternal weight, racial origin and gestational age, and the median MoM values in the two groups were compared. Results The incidence of PE was higher in pregnancies with GDM than in controls (4.0% vs 2.3%, respectively; P = 0.001). However, there were no significant differences in the median UtA-PI MoM between the groups (1.00 (interquartile range ( IQR), 0.82-1.21) vs 1.00 ( IQR, 0.81-1.21); P = 0.73). The median UtA-PI in patients who developed PE was higher than in those who did not develop PE, regardless of the development of GDM. Conclusions First-trimester placental perfusion, as assessed by UtA Doppler examination, is not impaired in women who subsequently develop GDM. The increased prevalence of PE in women with GDM cannot be attributed to impaired placentation. Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective To investigate the relationship between fetal heart defects and maternal serum placental growth factor ( PlGF), a marker of placental angiogenesis. Methods Maternal serum PlGF, pregnancy-associated plasma protein-A ( PAPP-A) and uterine artery pulsatility index ( UtA-PI) at 11-13 weeks' gestation were compared in 68 cases of isolated fetal major heart defects and 340 normal controls. Variables were converted into multiples of the median ( MoM) after adjustment for gestational age, maternal age, racial origin, weight, parity and method of conception, and then compared between groups. The cardiac defects included 11 cases of obstruction of the left ventricular outflow tract ( LVOT), 25 conotruncal abnormalities and 32 valve defects. Results The median PlGF-MoM in the heart defect group was lower than in controls (0.80 (interquartile range ( IQR), 0.57-1.08) vs 1.00 ( IQR, 0.79-1.32); P < 0.0001). Low PlGF levels were observed in the presence of conotruncal and valve defects but not in the presence of LVOT defects. There was no significant difference between the group with fetal heart defects and controls in PAPP-A- MoM (0.95 ( IQR, 0.68-1.28) vs 1.01 ( IQR, 0.70-1.39); P = 0.292) or UtA-PI-MoM (1.01 ( IQR, 0.84-1.28) vs 0.99 ( IQR, 0.80-1.20); P = 0.396). Conclusion In pregnancies with isolated fetal heart defects there is evidence of impaired placental angiogenesis in the absence of impaired placental perfusion and function. Copyright © 2012 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To investigate the potential value of maternal serum concentration of soluble endoglin (sEng) at 30-33 weeks' gestation in the prediction of preeclampsia (PE) developing at or after 34 weeks. Methods: Serum sEng was measured at 11-13 and at 30-33 weeks' gestation in a case-control study of 50 cases that developed PE at or after 34 weeks and 250 unaffected controls. Regression analysis was used to determine which of the factors amongst the maternal characteristics were significant predictors of first- and third-trimester log10 sEng in the control group. The measured values of sEng were converted into multiples of the unaffected median (MoM) and the MoM values in the PE and controls were compared. Results: The median sEng MoM at 30-33 weeks was significantly higher in the PE group (1.39, IQR 0.94-2.18) than in the controls (0.95, IQR 0.77-1.19), but at 11-13 weeks there was no significant difference between the groups. In screening by a combination of maternal characteristics and third-trimester sEng, the detection rates of intermediate- and late-PE, at a false-positive rate of 10%, were 64.3 and 50.0%, respectively. Conclusion: Screening by maternal characteristics and sEng at 30-33 weeks could identify most pregnancies that will subsequently develop PE. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Emotion processing difficulties are observed in antisocial individuals exhibiting serious antisocial behavior. This study examined emotion processing in 40 male juvenile offenders (JOs) and 52 male controls by measuring startle reflex responses to aversive sounds during the passive viewing of affective and neutral images. JOs as a group exhibited reduced startle-elicited blinks across all slide categories compared to normal controls. Moreover, within the offender group those with more conduct disorder symptoms and higher levels of psychopathic traits displayed reduced startle amplitudes compared to lower-scoring offenders. The finding that startle magnitudes were inversely related to severity of conduct problems supports a dimensional or continuous approach to understanding externalizing disorders. Reductions in amygdala activity could lead to blunted startle magnitudes. The current findings not only provide further evidence that antisocial children have a general defensive motivational system dysfunction and present with impairments in neural systems that subserve emotion processing, but also show for the first time that those with more severe conduct problems have reduced startle responses compared to those who are less severely affected. The implications of these findings for interventions with JOs are discussed. [ABSTRACT FROM AUTHOR]

Objective: To develop models for prediction of preeclampsia (PE) based on maternal characteristics, biophysical and biochemical markers at 11-13 weeks' gestation in which the gestation at the time of delivery for PE is treated as a continuous variable. Methods: This was a screening study of singleton pregnancies at 11-13 weeks including 1,426 (2.4%) that subsequently developed PE and 57,458 that were unaffected by PE. We developed a survival time model for the time of delivery for PE in which Bayes' theorem was used to combine the prior information from maternal characteristics with uterine artery pulsatility index (PI), mean arterial pressure (MAP), serum pregnancy-associated plasma protein-A (PAPP-A) and placental growth factor (PLGF) multiple of the median (MoM) values. Results: In pregnancies with PE, there was a linear correlation between MoM values of uterine artery PI, MAP, PAPP-A and PLGF with gestational age at delivery and therefore the deviation from normal was greater for early than late PE for all four biomarkers. Screening by maternal characteristics, biophysical and biochemical markers detected 96% of cases of PE requiring delivery before 34 weeks and 54% of all cases of PE at a fixed false-positive rate of 10%. Conclusions: A new model has been developed for effective first-trimester screening for PE. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: To combine a specific algorithm for small for gestational age (SGA) without preeclampsia (PE) and another algorithm for PE in the prediction of SGA and PE. Methods: This was a screening study of singleton pregnancies at 11-13 weeks including 1,426 (2.3%) that subsequently developed PE, 3,168 (5.1%) that delivered SGA neonates and 57,458 that were unaffected by PE and SGA. We developed a prediction algorithm for SGA requiring delivery before 37 weeks' gestation (preterm-SGA) from maternal characteristics, uterine artery pulsatility index, mean arterial pressure, serum pregnancy-associated plasma protein-A and placental growth factor multiple of the median values. We then examined the performance of this algorithm individually and in combination with a previously reported algorithm for early-PE in the prediction of SGA and PE. Results: When screen positivity was defined by risk cutoff of 1:200 using the algorithm for early-PE and the risk cutoff of 1:150 using the algorithm for preterm-SGA, the false positive rate was 10.9% and the detection rates of early-PE, late-PE, preterm-SGA and term-SGA were 95.3, 45.6, 55.5 and 44.3%, respectively. Conclusions: Effective first-trimester screening for early-PE and preterm-SGA can be provided by the combined use of the specific algorithms. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective To assess the performance of chromosome-selective sequencing of maternal plasma cell-free DNA ( cfDNA) in non-invasive prenatal testing for trisomy 13. Methods Two-phase case-control study on a single plasma sample per case. The first phase was used to optimize the trisomy 13 algorithm, which was then applied to a second dataset to determine the risk score for trisomy 13 by laboratory personnel who were blinded to the fetal karyotype. Results In the first phase, trisomy 13 risk scores were given for 11 cases of trisomy 13 and 145 euploid cases at 11-13 weeks' gestation. The test identified seven (63.6%) cases of trisomy 13 with no false positives. The trisomy 13 algorithm was subsequently modified and the trisomy 13 risk score was > 99% in all 11 cases of trisomy 13 and < 0.01% in all 145 euploid cases. In the second phase, the new algorithm was used to generate trisomy 13 risk scores for 10 cases of trisomy 13 and 1939 euploid cases. The trisomy 13 risk scores were > 99% in eight (80.0% (95% confidence interval ( CI), 49.0-94.3%)) cases of trisomy 13. In the 1939 euploid cases the risk score for trisomy 13 was < 0.01% in 1937 (99.9%), 0.79% in one, and > 99% in one. Therefore, at the predefined risk cut-off of 1% for classifying a sample as high or low risk, the false-positive rate ( FPR) was 0.05% (95% CI, 0.0-0.3%). Conclusions Chromosome-selective sequencing of cfDNA can detect the majority of cases of trisomy 13 at an FPR of less than 0.1%. [ABSTRACT FROM AUTHOR]

Objective To examine the possible effects of maternal and fetal characteristics on the fetal fraction in maternal plasma cell-free (cf) DNA at 11-13 weeks' gestation and estimate the proportion of pregnancies at high risk of non-invasive prenatal testing (NIPT) failure because the fetal fraction is less than 4%. Methods In 1949 singleton pregnancies at 11-13 weeks' gestation cf-DNA was extracted from maternal plasma. Chromosome-selective sequencing of non-polymorphic and polymorphic loci, where fetal alleles differ from maternal alleles, was used to determine the proportion of cf-DNA that was of fetal origin. Multivariable regression analysis was used to determine significant predictors of the fetal fraction among maternal and fetal characteristics. Results The fetal fraction decreased with increased maternal weight, it was lower in women of Afro-Caribbean origin than in Caucasians and increased with fetal crown-rump length, serum pregnancy-associated plasma protein-A, serum free β-human chorionic gonadotropin, smoking and trisomy 21 karyotype. The median fetal fraction was 10.0% (interquartile range, 7.8-13.0%) and this decreased with maternal weight from 11.7% at 60 kg to 3.9% at 160 kg. The estimated proportion with fetal fraction below 4% increased with maternal weight from 0.7% at 60 kg to 7.1% at 100 kg and 51.1% at 160 kg. Conclusions Fetal fraction in maternal plasma cf-DNA is affected by maternal and fetal characteristics.Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Poor fear conditioning is a correlate of violent offending in adults, but there is no evidence concerning juvenile offenders. Our aim was to compare emotional learning in juvenile offenders and controls and establish whether crime rate is related to seriousness of emotional learning problems. To this end, emotional learning was assessed in 42 juvenile offenders by measuring skin conductance responding ( SCR) during fear conditioning. Compared to controls, juvenile offenders showed lower conditioned SCRs to visual stimuli associated with a subsequent aversive stimulus and the magnitude of the SCR during fear acquisition was inversely associated with the number of their recorded offences. These findings suggest that juvenile offenders have impairments in the neural systems that subserve emotional learning. The implication is that using punitive measures to control persistent offenders is unlikely to be effective in an identifiable group of juvenile offenders. [ABSTRACT FROM AUTHOR]

Objectives: To examine the relationship between the English index of multiple deprivation (IMD) and the incidence of pre‐eclampsia (PE), evaluate the distribution of IMD in a cohort of ethnically diverse pregnant women in South East England and assess whether IMD improves the prediction of PE compared with that provided by the 'history‐only' competing‐risks model (based on maternal characteristics and medical history). Methods: This was a prospective, observational study of 159 125 women with a singleton pregnancy who attended their first routine hospital visit at 11 + 0 to 13 + 6 weeks' gestation in two maternity hospitals in the UK. The inclusion criteria were delivery at ≥ 24 weeks' gestation of babies without major abnormality. Participants completed a questionnaire on demographic characteristics and obstetric and medical history, which was then reviewed by a doctor together with the woman. Patients were asked to self‐identify as white, black, South Asian, East Asian or mixed race. IMD was used as a measure of socioeconomic status, which takes into account income, employment, education, skills and training, health and disability, crime, barriers to housing and services, and living environment. Each neighborhood is ranked according to their level of deprivation relative to that of other areas into one of five equal groups, with Quintile 1 containing the 20% most deprived areas and Quintile 5 containing the 20% least deprived areas. IMD was assigned based on a woman's postcode. Risk factors for PE and its incidence were assessed across IMD using chi‐square test or t‐test, as appropriate. The relationship between IMD and gestational age at delivery with PE was evaluated by fitting parametric survival models for IMD alone, IMD combined with race and IMD combined with the Fetal Medicine Foundation history‐only competing‐risks model. Results: The incidence of PE (n = 4088, 2.6%) increased progressively across IMD quintiles, from 2.0% in Quintile 5 (least deprived) to 3.0% in Quintile 1 (most deprived). Compared with white women and those in other racial groups, black women had a higher incidence of PE (4.8%), were less often in IMD Quintiles 4 and 5, and were more often in IMD Quintiles 1 and 2. None of the IMD quintiles improved the prediction of PE compared with that provided by the history‐only competing‐risks model (which includes race). The history‐only competing‐risks model with vs without IMD had a similar detection rate for delivery with PE at < 37 weeks' gestation (44.1% (95% CI, 41.1–47.2%) vs 43.9% (95% CI, 40.1–47.0%)) and at any gestational age (35.2% (95% CI, 33.8–36.7%) vs 35.1% (95% CI, 33.7–36.6%)), at a 10% screen‐positive rate. Conclusions: The incidence of PE is higher in women living in the most deprived areas in South East England and in black women (vs those of other racial groups), who also live in areas of higher deprivation. However, in screening for PE, inclusion of IMD does not improve the prediction of PE provided by race and other maternal characteristics and elements of medical history. © 2022 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]