Combination Of Maternal Risk Factors Research Articles

Comparison of competing-risks model with angiogenic factors in midgestation screening for preterm growth-related neonatal morbidity.

First, to evaluate the predictive performance for preterm growth-related neonatal morbidity of a high soluble fms-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PlGF) ratio or low PlGF at midgestation and, second, to compare the performance of a high sFlt-1/PlGF ratio or low PlGF with that of the competing-risks model for small-for-gestational age (SGA), utilizing a combination of maternal risk factors, sonographic estimated fetal weight and uterine artery pulsatility index. This was a prospective observational study in women attending for a routine hospital visit at 19-24 weeks' gestation in two maternity hospitals in England. The visit included recording of maternal demographic characteristics and medical history, carrying out an ultrasound scan and measuring serum PlGF and sFlt-1. The primary outcome was delivery < 32 and < 37 weeks' gestation of a SGA neonate with birth weight < 10th or < 3rd percentile, combined with neonatal unit (NNU) admission for ≥ 48 h or a composite of major neonatal morbidity. The detection rates in screening by PlGF < 10th percentile, sFlt-1/PlGF ratio > 90th percentile and the competing-risks model for SGA were estimated and then compared using McNemar's test. In the study population of 40 241 women, prediction of preterm growth-related neonatal morbidity provided by the competing-risks model for SGA was superior to that of screening by low PlGF concentration or high sFlt-1/PlGF ratio. For example, at a screen-positive rate of 10.0%, as defined by the sFlt-1/PlGF ratio > 90th percentile, the competing-risks model predicted 70.1% (95%CI, 61.0-79.2%) of SGA < 10th percentile and 76.9% (95%CI, 67.6-86.3%) of SGA < 3rd percentile with NNU admission for ≥ 48 h delivered < 32 weeks' gestation. The respective values for SGA with major neonatal morbidity were 73.8% (95%CI, 64.4-83.2%) and 77.9% (95%CI, 68.0-87.8%). These were significantly higher than the respective values of 35.1% (95%CI, 25.6-44.6%), 35.9% (95%CI, 25.3-46.5%), 38.1% (95%CI, 27.7-48.5%) and 39.7% (95%CI, 28.1-51.3%) achieved by the application of the sFlt-1/PlGF ratio > 90th percentile (all P < 0.0001). At midgestation, the prediction of growth-related neonatal morbidity by the competing-risks model for SGA is superior to that of a high sFlt-1/PlGF ratio or low PlGF. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

First trimester risk of preeclampsia and rate of spontaneous birth in patients without preeclampsia

First-trimester screening for preeclampsia using a combination of maternal risk factors and mean arterial pressure, uterine artery pulsatility index, and placental growth factor, as proposed by the Fetal Medicine Foundation, provides effective prediction of preterm preeclampsia. Placental dysfunction is a potential precursor of spontaneous birth. The objective of this study was to examine if the estimated risk of preeclampsia is associated with the gestational age at onset of spontaneous delivery in the absence of preeclampsia. This was a secondary analysis of the data from the Screening programme for pre-eclampsia trial in which there was a comparison of the performance of first-trimester screening for preterm preeclampsia using the Fetal Medicine Foundation model vs a traditional history-based risk scoring system. A subgroup of women from the trial with spontaneous onset of delivery (labor with intact membranes or preterm prelabor rupture of membranes) was included in this study and was arbitrarily divided into 3 groups according to the risk for preterm preeclampsia as determined by the Fetal Medicine Foundation model at 11 to 13 weeks' gestation as follows: group 1 low risk (˂1/100); group 2 intermediate risk (1/50 to 1/100); and group 3 high risk (˃1/50). A survival analysis was carried out using a Kaplan-Meier estimator and a Cox regression analysis with stratification by the 3 preeclampsia risk groups. Occurrence of spontaneous birth in the study groups was compared using log-rank tests and hazard ratios. The study population comprised 10,820 cases with delivery after spontaneous onset of labor among the 16,451 cases who participated in the Screening programme for pre-eclampsia trial. There were 9795 cases in group 1, 583 in group 2, and 442 in group 3. The gestational age at delivery was <28, <32, <35, <37, and <40 weeks in 0.29%, 0.64%, 1.68%, 4.52%, and 44.97% of cases, respectively, in group 1; 0.69%, 1.71%, 3.26%, 7.72%, and 55.23% of cases, respectively, in group 2; and 0.45%, 1.81%, 5.66%, 13.80%, and 63.12% of cases, respectively, in group 3. The curve profile of gestational age at spontaneous birth in the 3 study groups was significantly different overall and in pairwise comparisons (P values <.001). The Cox regression analysis showed that risks increased for spontaneous birth by 18% when the intermediate-risk group was compared with the low-risk group (P˂.001) and by 41% when the high-risk group was compared with the low-risk group (P˂.001). In this study that investigated birth after spontaneous onset of labor in women without preeclampsia, there were 2 major findings. First, the duration of pregnancy decreased with increasing first-trimester risk for preeclampsia. Second, in the high-risk group, when compared with the low-risk group, the risk for spontaneous birth was 4 times higher at a gestational age of 24 to 26 weeks, 3 times higher at 28 to 32 weeks, and 2 times higher at 34 to 39 weeks. These differences present major clinical implications for antepartum counselling, monitoring, and interventions in these pregnancies.

Screening for pre-eclampsia by maternal serum glycosylated fibronectin and angiogenic markers at 36 weeks' gestation.

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. 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. 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. 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.

Maternal vascular indices at 36 weeks’ gestation in the prediction of preeclampsia

Epidemiological studies have shown that women with preeclampsia (PE) are at increased long term cardiovascular risk. This risk might be associated with accelerated vascular ageing process but data on vascular abnormalities in women with PE are scarce. This study aimed to identify the most discriminatory maternal vascular index in the prediction of PE at 35 to 37 weeks' gestation and to examine the performance of screening for PE by combinations of maternal risk factors and biophysical and biochemical markers at 35 to 37 weeks' gestation. This was a prospective observational nonintervention study in women attending a routine hospital visit at 35 0/7 to 36 6/7 weeks' gestation. The visit included recording of maternal demographic characteristics and medical history, vascular indices, and hemodynamic parameters obtained by a noninvasive operator-independent device (pulse wave velocity, augmentation index, cardiac output, stroke volume, central systolic and diastolic blood pressures, total peripheral resistance, and fetal heart rate), mean arterial pressure, uterine artery pulsatility index, and serum concentration of placental growth factor and soluble fms-like tyrosine kinase-1. The performance of screening for delivery with PE at any time and at <3 weeks from assessment using a combination of maternal risk factors and various combinations of biomarkers was determined. The study population consisted of 6746 women with singleton pregnancies, including 176 women (2.6%) who subsequently developed PE. There were 3 main findings. First, in women who developed PE, compared with those who did not, there were higher central systolic and diastolic blood pressures, pulse wave velocity, peripheral vascular resistance, and augmentation index. Second, the most discriminatory indices were systolic and diastolic blood pressures and pulse wave velocity, with poor prediction from the other indices. However, the performance of screening by a combination of maternal risk factors plus mean arterial pressure was at least as high as that of a combination of maternal risk factors plus central systolic and diastolic blood pressures; consequently, in screening for PE, pulse wave velocity, mean arterial pressure, uterine artery pulsatility index, placental growth factor, and soluble fms-like tyrosine kinase-1 were used. Third, in screening for both PE within 3 weeks and PE at any time from assessment, the detection rate at a false-positive rate of 10% of a biophysical test consisting of maternal risk factors plus mean arterial pressure, uterine artery pulsatility index, and pulse wave velocity (PE within 3 weeks: 85.2%; 95% confidence interval, 75.6%-92.1%; PE at any time: 69.9%; 95% confidence interval, 62.5%-76.6%) was not significantly different from a biochemical test using the competing risks model to combine maternal risk factors with placental growth factor and soluble fms-like tyrosine kinase-1 (PE within 3 weeks: 80.2%; 95% confidence interval, 69.9%-88.3%; PE at any time: 64.2%; 95% confidence interval, 56.6%-71.3%), and they wereboth superior to screening by low placental growth factor concentration (PE within 3 weeks: 53.1%; 95% confidence interval, 41.7%-64.3%; PE at any time: 44.3; 95% confidence interval, 36.8%-52.0%) or high soluble fms-like tyrosine kinase-1-to-placental growth factor concentration ratio (PE within 3 weeks: 65.4%; 95% confidence interval, 54.0%-75.7%; PE at any time: 53.4%; 95% confidence interval, 45.8%-60.9%). First, increased maternal arterial stiffness preceded the clinical onset of PE. Second, maternal pulse wave velocity at 35 to 37 weeks' gestation in combination with mean arterial pressure and uterine artery pulsatility index provided effective prediction of subsequent development of preeclampsia.

Prediction of spontaneous preterm birth and preterm prelabor rupture of membranes using maternal factors, obstetric history and biomarkers of placental function at 11-13 weeks.

To determine whether first-trimester biomarkers of placental function can be used to screen for spontaneous preterm birth (sPTB), and to develop prediction models using maternal factors, obstetric history and biomarkers of placental function at 11-13 weeks for the calculation of patient-specific risk for sPTB. This was a retrospective secondary analysis of data derived from a prospective cohort study on first-trimester screening for pre-eclampsia in singleton pregnancies attending for routine Down syndrome screening at 11 + 0 to 13 + 6 weeks' gestation at a tertiary obstetric unit between December 2016 and September 2019. A split-sample internal validation method was used to explore and develop prediction models for all sPTB at < 37 weeks and for PTB at < 37 weeks after preterm prelabor rupture of membranes (PPROM) using maternal risk factors, uterine artery Doppler indices, serum placental growth factor (PlGF), pregnancy-associated plasma protein-A (PAPP-A) and β-human chorionic gonadotropin (β-hCG). Screening performance was assessed using receiver-operating-characteristics (ROC)-curve analysis, with calculation of the areas under the ROC curves (AUCs). A total of 9298 singleton pregnancies were included in this study. sPTB at < 37 weeks occurred in 362 (3.89%) cases, including 231 (2.48%) cases of PPROM. sPTB at < 34 weeks occurred in 87 (0.94%) cases, including 39 (0.42%) cases of PPROM. Identified maternal risk factors for sPTB at < 37 weeks included chronic hypertension, conception using in-vitro fertilization and history of PTB. Maternal risk factors for PPROM at < 37 weeks included conception using in-vitro fertilization and history of PTB. Median PlGF multiples of the median (MoM) and PAPP-A MoM were significantly reduced in women with sPTB at < 37 weeks, as well as in those who had PPROM, compared to those who delivered at term. Screening by a combination of maternal risk factors, PAPP-A and PlGF achieved better performance in predicting sPTB at < 37 weeks (AUC, 0.630 vs 0.555; detection rate (DR), 24.8% vs 16.6% at a false-positive rate (FPR) of 10%; P ≤ 0.0001) and PPROM at < 37 weeks (AUC, 0.643 vs 0.558; DR, 28.1% vs 17.0% at a FPR of 10%; P ≤ 0.0001) than using maternal risk factors alone. Both models were successfully applied to the internal validation dataset, with AUCs of 0.628 and 0.650, respectively. We demonstrated that low levels of maternal serum PAPP-A and PlGF in the first trimester are associated with increased risks of sPTB and PPROM at < 37 weeks. However, further research is needed to identify additional biomarkers to improve the screening performance of the combined model that includes maternal risk factors, PAPP-A and PlGF before clinical application. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Comparison of ophthalmic artery Doppler with PlGF and sFlt-1/PlGF ratio at 35-37 weeks' gestation in prediction of imminent pre-eclampsia.

To compare the predictive performance for delivery with pre-eclampsia (PE) at < 3 weeks and at any stage after assessment at 35 + 0 to 36 + 6 weeks' gestation of serum placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1)/PlGF ratio with that of a competing-risks model utilizing maternal risk factors, mean arterial pressure (MAP) and ophthalmic artery peak systolic velocity (PSV) ratio. This was a prospective observational study of women attending for a routine hospital visit at 35 + 0 to 36 + 6 weeks' gestation. This visit included recording of maternal demographic characteristics and medical history, ultrasound examination of fetal anatomy and growth, assessment of flow velocity waveforms from the maternal ophthalmic arteries and measurement of MAP, serum PlGF and serum sFlt-1. The performance of screening for delivery with PE at < 3 weeks and at any time after the examination was assessed using areas under the receiver-operating-characteristics curves and detection rates (DRs), at a 10% false-positive rate (FPR). McNemar's test was used to compare DRs, at a 10% FPR, between screening by PlGF concentration, the sFlt-1/PlGF concentration ratio and the competing-risks model utilizing maternal risk factors, MAP and ophthalmic artery PSV ratio. Model-based estimates of screening performance for different methods of screening were also produced. The study population of 2338 pregnancies contained 75 (3.2%) cases that developed PE, including 30 (1.3%) that delivered with PE at < 3 weeks from assessment, and 2263 cases unaffected by PE. The DR of PE at < 3 weeks from assessment, at a 10% FPR, of sFlt-1/PlGF ratio (70.0% (95% CI, 50.6-85.3%)) was superior to that of PlGF (50.0% (95% CI, 31.3-68.7%)) or PSV ratio (56.7% (95% CI, 37.4-74.5%)) but inferior to that of the combination of maternal risk factors, MAP multiples of the median (MoM) and PSV ratio delta (96.7% (95% CI, 82.8-99.9%)). Similarly, the DR of PE at any stage after assessment of sFlt-1/PlGF ratio (62.7% (95% CI, 50.7-73.6%)) was superior to that of PlGF (52.0% (95% CI, 40.2-63.7%)) or PSV ratio (41.3% (95% CI, 30.1-53.3%)) but inferior to that of the combination of maternal risk factors, MAP MoM and PSV ratio delta (78.7% (95% CI, 67.7-87.3%)). The empirical results for DR at a 10% FPR were consistent with the modeled results, both for delivery with PE at < 3 weeks and at any time after assessment. Ophthalmic artery Doppler in combination with maternal risk factors and blood pressure could potentially replace measurement of PlGF and sFlt-1/PlGF ratio in the prediction of imminent PE. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Estimated fetal weight at mid-gestation in prediction of pre-eclampsia in singleton pregnancy.

To examine the distribution of birth weight according to gestational age in pregnancies complicated by pre-eclampsia (PE) and assess the potential value of sonographic estimated fetal weight (EFW) at mid-gestation as a predictor of PE. The data for this study were derived from prospective screening for adverse obstetric outcome in 93 911 women with a singleton pregnancy attending for routine pregnancy care at 19 + 0 to 24 + 6 weeks' gestation in two UK maternity hospitals. This visit included recording of maternal demographic characteristics and medical history, sonographic EFW and measurement of mean arterial pressure (MAP) and uterine artery pulsatility index (UtA-PI). The distribution of birth weight of pregnancies with and those without PE was assessed. The competing-risks model was used to estimate the individual, patient-specific risk of delivery with PE at < 32 and < 37 weeks' gestation and at any gestational age. The areas under the receiver-operating-characteristics curves and detection rates (DRs) of delivery with PE, at a 10% false-positive rate (FPR), were assessed for various combinations of maternal risk factors, EFW, MAP and UtA-PI. McNemar's test was used to determine the significance of difference in DR at a 10% FPR between screening with vs without EFW. The study population contained 2843 (3.0%) pregnancies that subsequently developed PE, including 148 (0.2%) that delivered with PE at < 32 weeks' gestation and 654 (0.7%) that delivered with PE at < 37 weeks. Birth weight was < 10th percentile in 82% of pregnancies with PE delivering at < 32 weeks' gestation and this decreased to 21% of those with PE delivering at ≥ 37 weeks. In screening for delivery with PE at < 32 and < 37 weeks' gestation, the DR, at a 10% FPR, achieved by maternal risk factors (51% and 46%, respectively) was improved by addition of EFW (69% and 51%, respectively). Similarly, addition of EFW improved the performance of screening by a combination of maternal risk factors and MAP from 72% to 80% for PE < 32 weeks and from 57% to 60% for PE < 37 weeks. EFW did not improve the predictive performance of screening by a combination of maternal risk factors, MAP and UtA-PI. In pregnancies complicated by preterm PE, a high proportion of neonates are small-for-gestational age, and sonographic EFW at mid-gestation can improve the prediction of early and preterm PE provided by maternal risk factors and MAP but not the prediction provided by a combination of maternal risk factors, MAP and UtA-PI. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Second-trimester contingent screening for small-for-gestational-age neonate.

First, to investigate the additive value of second-trimester placental growth factor (PlGF) for the prediction of a small-for-gestational-age (SGA) neonate. Second, to examine second-trimester contingent screening strategies. This was a prospective observational study in women with singleton pregnancy undergoing routine ultrasound examination at 19-24 weeks' gestation. We used the competing-risks model for prediction of SGA. The parameters for the prior model and the likelihoods for estimated fetal weight (EFW) and uterine artery pulsatility index (UtA-PI) were those presented in previous studies. A folded-plane regression model was fitted in the dataset of this study to describe the likelihood of PlGF. We compared the prediction of screening by maternal risk factors against the prediction provided by a combination of maternal risk factors, EFW, UtA-PI and PlGF. We also examined the additive value of PlGF in a policy that uses maternal risk factors, EFW and UtA-PI. The study population included 40 241 singleton pregnancies. Overall, the prediction of SGA improved with increasing degree of prematurity, with increasing severity of smallness and in the presence of coexisting pre-eclampsia. The combination of maternal risk factors, EFW, UtA-PI and PlGF improved significantly the prediction provided by maternal risk factors alone for all the examined cut-offs of birth weight and gestational age at delivery. Screening by a combination of maternal risk factors and serum PlGF improved the prediction of SGA when compared to screening by maternal risk factors alone. However, the incremental improvement in prediction was decreased when PlGF was added to screening by a combination of maternal risk factors, EFW and UtA-PI. If first-line screening for a SGA neonate with birth weight < 10th percentile delivered at < 37 weeks' gestation was by maternal risk factors and EFW, the same detection rate of 90%, at an overall false-positive rate (FPR) of 50%, as that achieved by screening with maternal risk factors, EFW, UtA-PI and PlGF in the whole population can be achieved by reserving measurements of UtA-PI and PlGF for only 80% of the population. Similarly, in screening for a SGA neonate with birth weight < 10th percentile delivered at < 30 weeks, the same detection rate of 90%, at an overall FPR of 14%, as that achieved by screening with maternal risk factors, EFW, UtA-PI and PlGF in the whole population can be achieved by reserving measurements of UtA-PI and PlGF for only 70% of the population. The additive value of PlGF in reducing the FPR to about 10% with a simultaneous detection rate of 90% for a SGA neonate with birth weight < 3rd percentile born < 30 weeks, is gained by measuring PlGF in only 50% of the population when first-line screening is by maternal factors, EFW and UtA-PI. The combination of maternal risk factors, EFW, UtA-PI and PlGF provides effective second-trimester prediction of SGA. Serum PlGF is useful for predicting a SGA neonate with birth weight < 3rd percentile born < 30 weeks after an inclusive assessment by maternal risk factors and biophysical markers. Similar detection rates and FPRs can be achieved by application of contingent screening strategies. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Predictive performance for placental dysfunction related stillbirth of the competing risks model for small-for-gestational-age fetuses.

To examine the predictive performance for placental dysfunction related stillbirths of the competing risks model for small-for-gestational-age (SGA) fetuses based on a combination of maternal risk factors, estimated fetal weight (EFW) and uterine artery pulsatility index (UtA-PI); and second, to compare the performance of this model with that of a stillbirth-specific model using the same biomarkers and with the Royal College of Obstetricians and Gynecologists (RCOG) guideline for the investigation and management of the SGA fetus. Prospective observational study. Two UK maternity hospitals. A total of 131514 women with singleton pregnancies attending for routine ultrasound examination at 19-24weeks of gestation. The predictive performance for stillbirth achieved by three models was compared. Placental dysfunction related stillbirth. At 10% false-positive rate, the competing risks model predicted 59%, 66% and 71% of placental dysfunction related stillbirths, at any gestation, at <37weeks and at <32weeks, respectively, which were similar to the respective figures of 62%, 70% and 73% for the stillbirth-specific model. At a screen positive rate of 21.8%, as defined by the RCOG guideline, the competing risks model predicted 71%, 76% and 79% of placental dysfunction related stillbirths at any gestation, at <37weeks and at <32weeks, respectively, and the respective figures for the RCOG guideline were 40%, 44% and 42%. The predictive performance for placental dysfunction related stillbirths by the competing risks model for SGA was similar to that of the stillbirth-specific model and superior to that of the RCOG guideline. The competing risks approach for SGA is superior to the RCOG guideline in the prediction of placental dysfunction related stillbirths.

Development and validation of model for prediction of placental dysfunction-related stillbirth from maternal factors, fetal weight and uterine artery Doppler at mid-gestation.

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. 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. 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%). 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.

STATIN trial: predictive performance of competing-risks model in screening for pre-eclampsia at 35-37 weeks' gestation.

To examine the predictive performance of a previously reported competing-risks model of screening for pre-eclampsia (PE) at 35-37 weeks' gestation by combinations of maternal risk factors, 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) in a validation dataset derived from the screened population of the STATIN study. This was a prospective third-trimester multicenter study of screening for PE in singleton pregnancies by means of a previously reported algorithm that combines maternal risk factors and biomarkers. Women in the high-risk group were invited to participate in a trial of pravastatin vs placebo, but the trial showed no evidence of an effect of pravastatin in the prevention of PE. Patient-specific risks of delivery with PE were calculated using the competing-risks model, and the performance of screening for PE by maternal risk factors alone and by various combinations of risk factors with MAP, UtA-PI, PlGF and sFlt-1 was assessed. The predictive performance of the model was examined by, first, the ability of the model to discriminate between the PE and no-PE groups using the area under the receiver-operating-characteristics curve (AUC) and the detection rate at a fixed false-positive rate of 10%, and, second, calibration by measurements of calibration slope and calibration-in-the-large. The study population of 29 677 pregnancies contained 653 that developed PE. In screening for PE by a combination of maternal risk factors, MAP, PlGF and sFlt-1 (triple test), the detection rate at a 10% false-positive rate was 79% (95% CI, 76-82%) and the results were consistent with the data used for developing the algorithm. Addition of UtA-PI did not improve the prediction provided by the triple test. The AUC for the triple test was 0.923 (95% CI, 0.913-0.932), demonstrating very high discrimination between affected and unaffected pregnancies. Similarly, the calibration slope was 0.875 (95% CI, 0.831-0.919), demonstrating good agreement between the predicted risk and observed incidence of PE. The competing-risks model provides an effective and reproducible method for third-trimester prediction of term PE. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Impact of new definitions of pre-eclampsia on incidence andperformance of first-trimester screening.

The traditional definition of pre-eclampsia (PE) is based on the development of hypertension and proteinuria. This has been revised recently to include cases without proteinuria but with evidence of renal, hepatic or hematological dysfunction. The aim of this study was to examine the impact of new definitions of PE on, first, the incidence and severity of the disease and, second, the performance of the competing-risks model for first-trimester assessment of risk for PE. This was a retrospective study of 66 964 singleton pregnancies that were classified as having PE, gestational hypertension (GH) or no PE or GH, according to the traditional criteria of the International Society for the Study of Hypertension in Pregnancy (ISSHP-old), which defines PE as the presence of both hypertension and proteinuria. We reviewed the records of pregnancies with GH, and those cases with high creatinine or liver enzymes or low platelet count were reclassified as having PE, according to the new criteria of ISSHP (ISSHP-new) and the new criteria of the American College of Obstetricians and Gynecologists (ACOG). The groups of PE according to the traditional and new criteria were compared for, first, gestational age at delivery, birth-weight percentile and incidence of a small-for-gestational-age (SGA) neonate with birth weight < 10th percentile and perinatal death, and, second, the predictive performance for preterm PE of the competing-risks model based on the combination of maternal risk factors, uterine artery pulsatility index, mean arterial pressure and serum placental growth factor at 11-13 weeks' gestation (triple test). According to ISSHP-old, 1870 (2.8%) cases had PE, 2182 (3.3%) had GH and 62 912 (94.0%) had no PE or GH. The incidence of PE according to ACOG was 3.0% (2029/66 964) and ISSHP-new was 3.4% (2301/66 964). Median gestational age at delivery in the extra cases of PE according to ACOG (difference, 1.3 weeks; 95% CI, 0.71-1.71 weeks) and in the extra cases of PE according to ISSHP-new (difference, 1.5 weeks; 95% CI, 1.29-1.71 weeks) was higher than in cases with PE according to ISSHP-old (38.4 weeks). The incidence of a SGA neonate in the extra cases of PE according to ACOG (relative risk, 0.57; 95% CI, 0.42-0.79) and in the extra cases of PE according to ISSHP-new (relative risk, 0.52; 95% CI, 0.42-0.65) was lower than in the cases of PE according to ISSHP-old (33.64%). In first-trimester screening for preterm PE by the triple test, the detection rate, at a 10% false-positive rate, was 75.9% (95% CI, 70.8-80.6%) for ISSHP-old, 74.3% (95% CI, 69.2-79.0%) for ACOG and 74.0% (95% CI, 68.9-78.6%) for ISSHP-new. The new definitions of PE resulted in, first, an increase in pregnancies classified as having PE but the additional cases had milder disease, and, second, a non-significant decrease in the performance of first-trimester screening for PE. © 2019 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

The International Federation of Gynecology and Obstetrics (FIGO) initiative on pre-eclampsia: A pragmatic guide for first-trimester screening and prevention.

The International Federation of Gynecology and Obstetrics (FIGO) initiative on pre-eclampsia: A pragmatic guide for first-trimester screening and prevention.

Marcadores clínicos, biofísicos y bioquímicos para la predicción de preeclampsia

La preeclampsia es una causa importante de morbilidad y mortalidad materna alrededor del mundo. La incidencia de preeclampsia ha aumentado en la última década, lo cual ha sido atribuido a varios factores. A pesar de las décadas de investigación de esta condición, la capacidad de los clínicos para predecir antes de la aparición de los síntomas no ha mejorado en forma significativa. Ninguna prueba de predicción en solitario ha logrado la aceptación generalizada en la práctica clínica. Las combinaciones de marcadores bioquímicos y ecográficos mejoran la predicción temprana de la preeclampsia. La pesquisa con una combinación de factores de riesgo maternos, Doppler de las arterias uterinas, presión arterial media, concentraciones plasmáticas de proteína A relacionada al embarazo y factor de crecimiento placentario, puede identificar cerca del 95% de los casos de preeclampsia de aparición temprana. En forma interesante, la creciente investigación ha revelado los nombres de algunas bio-moléculas importantes que pueden tener un papel importante en la vasculogénesis de la placentación temprana. Existen preguntas si un único grupo de parámetros puede diagnosticar un síndrome que es complejo. En esta revisión, se examina la fisiopatología subyacente de la preeclampsia y se analiza los potenciales marcadores clínicos, biofísicos y bioquímicos para la predicción temprana.

The use of ultrasound and other markers for early detection of preeclampsia.

Preeclampsia (PE) is a multisystem disorder of pregnancy classically characterized with the onset of hypertension after 20 weeks gestation in the presence of proteinuria. PE typically affects 2-8% of pregnancies and is a leading cause of maternal and perinatal morbidity and mortality. This article reviews the most effective biomarkers used in first trimester screening for PE. It explores their use both in isolation and as part of an algorithm to yield the best detection rates. Screening by a combination of maternal risk factors, uterine artery Doppler, mean arterial pressure, maternal serum PAPP-A and PlGF can identify about 75% of cases of preterm PE for a false-positive rate of 10%. By identifying these patients at high risk for PE, appropriately tailored antenatal surveillance can be instigated and prophylactic pharmacological interventions can be prescribed to improve placentation and ultimately, the outcome for both the mother and fetus.

OP12.11: Combination of maternal risk factors and first trimester biochemical and ultrasound markers for the prediction of early pre‐eclampsia

<scp>OP</scp>12.11: Combination of maternal risk factors and first trimester biochemical and ultrasound markers for the prediction of early pre‐eclampsia

First‐trimester maternal factors and biomarker screening for preeclampsia

Preeclampsia (PE), which affects about 2% of pregnancies, is a major cause of maternal and perinatal morbidity and mortality. PE can be subdivided into early onset PE with delivery <34 weeks' gestation and late onset PE with delivery ≥34 weeks. Early onset PE is associated with a higher incidence of adverse outcome. This review illustrates that effective screening for the development of early onset PE can be provided in the first-trimester of pregnancy. Screening by a combination of maternal risk factors, mean arterial pressure, uterine artery Doppler, maternal serum pregnancy-associated plasma protein-A and placental growth factor can identify about 95% of cases of early onset PE for a false-positive rate of 10%.

Early prediction of preeclampsia.

Effective screening for the development of early onset preeclampsia (PE) can be provided in the first-trimester of pregnancy. Screening by a combination of maternal risk factors, uterine artery Doppler, mean arterial pressure, maternal serum pregnancy-associated plasma protein-A, and placental growth factor can identify about 95% of cases of early onset PE for a false-positive rate of 10%.

OP09.04: First trimester prediction of pre‐eclampsia by maternal brachial artery flow‐mediated dilatation

care in a tertiary Brazilian hospital. The base-cohort population was 487 singleton pregnancies, including 9 case subjects who developed PE requiring delivery before 34 weeks (early PE) and 22 with late PE, 47 with gestational hypertension, and 409 cases subjects (84%) who were unaffected by PE or gestational hypertension. Maternal history, body mass index (BMI), mean arterial pressure (MAP), and uterine artery pulsatility index were recorded in all of the cases. Univariate and logistic regression analysis was used to derive algorithms for the prediction of hypertensive disorders. Results: The maternal characteristics selected by regression analysis to be part of the final predictive model were nulliparity, previous personal and family history of PE. MAP was higher (86 versus 78 mmHg) in patients who developed PE (P < 0.01). The uterine artery percentile of mean PI was higher in the PE than in the control group (50.3% ± 31.7% versus 37.4% ± 30.0%; P < 0.01). It was estimated that, with the algorithm for PE, 78%, 45%, and 26% of early PE, late PE, and gestational hypertension, respectively, could be detected with a 10% false-positive rate. Conclusions: The traditional approach to screening for PE, which is based on maternal demographic characteristics and medical history, identifies ∼60% of cases destined to develop early PE for a falsepositive rate of 10%. This study proposes that a combination of maternal risk factors, mean arterial blood pressure, and uterine artery Doppler, for the same false-positive rate of 10%, could identify 78% of cases of early PE.

PP114. First trimester multi-parameter prediction of pre-eclampsia

Pre-eclampsia (PE), which affects about 3-5% of pregnant women, is the most frequent serious medical complication in pregnancy and a major cause of maternal and perinatal morbidity and mortality. During the past three decades, numerous clinical, biophysical, and biochemical screening tests have been proposed for the early detection of PE. Literature shows large variations in the sensitivity and predictive value of these tests. No single screening test used for PE prediction has gained widespread acceptance into clinical practice. Instead, panels of tests, which combine several clinical measurements, seem to be of more value for increasing the predictive value for PE. The aim of this study was to examine a combination of maternal risk factors, mean arterial blood pressure, and uterine artery Doppler for pre-eclampsia prediction during the first trimester of pregnancy. Prospective study with singleton pregnancies examined at 11-14 weeks of gestation, presenting consecutively for antenatal care in a tertiary Brazilian hospital. The base-cohort population was 487 singleton pregnancies, including nine case subjects who developed PE requiring delivery before 34 weeks (early PE) and 22 with late PE, 47 with gestational hypertension, and 409 cases subjects (84%) who were unaffected by PE or gestational hypertension. Maternal history, body mass index (BMI), mean arterial pressure (MAP), and uterine artery pulsatility index were recorded in all of the cases. Univariate and logistic regression analysis was used to derive algorithms for the prediction of hypertensive disorders. The maternal characteristics selected by regression analysis to be part of the final predictive model were nulliparity, previous personal and family history of PE. MAP was higher (86 versus 78 mmHg) in patients who developed PE (p<0.01). The uterine artery percentile of mean PI was higher in the PE than in the control group (50.3%±31.7% versus 37.4%±30.0%; p<0.01). It was estimated that, with the algorithm for PE, 78%, 45%, and 26% of early PE, late PE, and gestational hypertension, respectively, could be detected with a 10% false-positive rate. The traditional approach to screening for PE, which is based on maternal demographic characteristics and medical history, identifies ∼60% of cases destined to develop early PE for a false-positive rate of 10%. This study proposes that a combination of maternal risk factors, mean arterial blood pressure, and uterine artery Doppler, for the same false-positive rate of 10%, could identify 78% of cases of early PE.