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Objectives: 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. Methods: 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. Results: 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). Conclusion: 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. [ABSTRACT FROM AUTHOR]

Objectives: First, to describe the distribution of biomarkers of impaired placentation in small‐for‐gestational‐age (SGA) pregnancies with neonatal morbidity; second, to examine the predictive performance for growth‐related neonatal morbidity of a high soluble fms‐like tyrosine kinase‐1 (sFlt‐1)/placental growth factor (PlGF) ratio or low PlGF; and, third, to compare the performance of a high sFlt‐1/PlGF ratio or low PlGF with that of the competing‐risks model for SGA in predicting growth‐related neonatal morbidity. Methods: This was a prospective observational study of women attending for a routine hospital visit at 35 + 0 to 36 + 6 weeks' gestation in two maternity hospitals in England. The visit included recording of maternal demographic characteristics and medical history, an ultrasound scan and measurement of serum PlGF and sFlt‐1. The primary outcome was delivery within 4 weeks after assessment and at < 42 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, sFlt‐1/PlGF ratio > 38 and the competing‐risks model for SGA, using combinations of maternal risk factors and Z‐scores of estimated fetal weight (EFW) with multiples of the median values of uterine artery pulsatility index, PlGF and sFlt‐1, were estimated. The detection rates by the different methods of screening were compared using McNemar's test. Results: In the study population of 29 035 women, prediction of growth‐related neonatal morbidity at term provided by the competing‐risks model was superior to that of screening by low PlGF concentration or a high sFlt‐1/PlGF concentration ratio. For example, at a screen‐positive rate (SPR) of 13.1%, as defined by the sFlt‐1/PlGF ratio > 38, the competing‐risks model using maternal risk factors and EFW predicted 77.5% (95% CI, 71.7–83.3%) of SGA < 10th percentile and 89.3% (95% CI, 83.7–94.8%) of SGA < 3rd percentile with NNU admission for ≥ 48 h delivered within 4 weeks after assessment. The respective values for SGA with major neonatal morbidity were 71.4% (95% CI, 56.5–86.4%) and 90.0% (95% CI, 76.9–100%). These were significantly higher than the respective values of 41.0% (95% CI, 34.2–47.8%) (P < 0.0001), 48.8% (95% CI, 39.9–57.7%) (P < 0.0001), 37.1% (95% CI, 21.1–53.2%) (P = 0.003) and 55.0% (95% CI, 33.2–76.8%) (P = 0.035) achieved by the application of the sFlt‐1/PlGF ratio > 38. At a SPR of 10.0%, as defined by PlGF < 10th percentile, the competing‐risks model using maternal factors and EFW predicted 71.5% (95% CI, 65.2–77.8%) of SGA < 10th percentile and 84.3% (95% CI, 77.8–90.8%) of SGA < 3rd percentile with NNU admission for ≥ 48 h delivered within 4 weeks after assessment. The respective values for SGA with major neonatal morbidity were 68.6% (95% CI, 53.1–83.9%) and 85.0% (95% CI, 69.4–100%). These were significantly higher than the respective values of 36.5% (95% CI, 29.8–43.2%) (P < 0.0001), 46.3% (95% CI, 37.4–55.2%) (P < 0.0001), 37.1% (95% CI, 21.1–53.2%) (P = 0.003) and 55.0% (95% CI, 33.2–76.8%) (P = 0.021) achieved by the application of PlGF < 10th percentile. Conclusion: At 36 weeks' gestation, the prediction of growth‐related neonatal morbidity by the competing‐risks model for SGA, using maternal risk factors and EFW, is superior to that of a high sFlt‐1/PlGF ratio or low PlGF. © 2023 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objective: To compare the performance at 35 + 0 to 36 + 6 weeks' gestation of screening for delivery with pre‐eclampsia (PE) at various timepoints, using one of three approaches: placental growth factor (PlGF) concentration, soluble fms‐like tyrosine kinase‐1 (sFlt‐1) to PlGF concentration ratio, or the competing‐risks model, which combines maternal risk factors with biomarkers to estimate patient‐specific risk. Methods: This was a prospective observational study of women attending for a routine hospital visit at 35 + 0 to 36 + 6 weeks' gestation at one of two maternity hospitals in England between 2016 and 2022. During the visit, maternal demographic characteristics and medical history were recorded and serum PlGF, serum sFlt‐1 and mean arterial pressure (MAP) were measured. Detection rates (DRs) were evaluated for delivery with PE (defined as per American College of Obstetricians and Gynecologists 2019 criteria) within 1 week, within 2 weeks or at any time after screening, using the following strategies: (i) low PlGF (< 10th percentile); (ii) high sFlt‐1/PlGF ratio (> 90th percentile); or (iii) the competing‐risks model, in which maternal factors were combined with multiples of the median values of PlGF ('single test'), PlGF and sFlt‐1 ('double test') or PlGF, sFlt‐1 and MAP ('triple test'). Risk cut‐offs corresponded to a screen‐positive rate of 10%. DRs were compared between tests. Results: Of 34 782 pregnancies, 831 (2.4%) developed PE. In screening for delivery with PE at any time from assessment, the DR at 10% screen‐positive rate was 47% by low PlGF alone, 54% by the single test, 55% by high sFlt‐1/PlGF ratio, 61% by the double test and 68% by the triple test. In screening for delivery with PE within 2 weeks from assessment, the respective values were 67%, 74%, 74%, 80% and 87%. In screening for delivery with PE within 1 week from assessment, the respective values were 77%, 81%, 85%, 88% and 91%. For prediction of PE at any time, the DR was significantly higher with the triple test compared to PlGF alone or the sFlt‐1/PlGF ratio, with a DR difference (95% CI) of 20.1% (16.7–23.0%) and 12.4% (9.7–15.3%), respectively. Similar results were seen for prediction of PE within 2 weeks (20.6% (14.9–26.8%) and 12.9% (7.7–17.5%), respectively) and prediction of PE within 1 week (13.5% (5.4–21.6%) and 5.4% (0.0–10.8%), respectively). The double test was superior to the sFlt‐1/PlGF ratio and the single test was superior to PlGF alone in the prediction of PE within 2 weeks and at any time from assessment, but not within 1 week of assessment. Conclusion: At 35 + 0 to 36 + 6 weeks' gestation, the performance of screening for PE by the competing‐risks model triple test is superior to that of PlGF alone or the sFlt‐1/PlGF ratio for the development of disease within 1 week, within 2 weeks and at any time from screening. © 2023 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Background: Several cross-sectional studies have investigated the incidence of urinary Congo-red dye positivity in women with preeclampsia (PE), compared to unaffected pregnancies, and reported very high sensitivity and low false positive rate in the diagnosis of PE. Objective: To determine the performance of the urinary Congo-red dot paper test at 35–37 weeks’ gestation in the prediction of delivery with PE at ≤2 and >2 weeks after assessment. Methods: This was a prospective observational study in women attending for a routine hospital visit at 35+0 to 36+6 weeks’ gestation in a maternity hospital in England. Urine samples were collected and the Congo-red dot paper test was used to assess the degree of Congo-red dye positivity. The test uses a scoring system from 1 to 8 and the higher the score the greater the degree of Congo-red dye positivity. We examined and compared the degree of Congo-red dye positivity in the groups that delivered with PE at ≤2 and >2 weeks with those that remained normotensive. Reproducibility was assessed by examining the inter- and intra-observer reliability of scoring on stored images with the researchers blinded to previous results. Results: The study population of 2140 women included 46 (2.1%) that subsequently developed PE (2.1%). The urinary Congo-red dot test was positive in 8.3% (1/12) and 2.9% (1/34) that delivered with PE at ≤2 and >2 weeks from assessment and in 0.2% (4/2094) of the unaffected pregnancies when the cutoff for Congo-red dye positivity was ≥5. The respective values when the cutoff used was ≥3 were 66.7%, 23.5%, and 16.5%, respectively. The intraclass correlation coefficient for the inter-observer reliability was 0.926 (95% CI 0.890–0.953, p<.0001) and Cohen's kappa coefficient for the intra-observer reliability was 0.904, p<.0001. Conclusions: The performance of the urinary Congo-red dot paper test at 35–37 weeks’ gestation in the prediction of PE is very poor. [ABSTRACT FROM AUTHOR]

Objectives: To examine the association between race and pre‐eclampsia and gestational hypertension after adjustment for factors in maternal characteristics and medical history in a screening study from the Fetal Medicine Foundation (FMF) in England, and to perform a systematic review and meta‐analysis of studies on pre‐eclampsia. Design: Prospective observational study and systematic review with meta‐analysis. Setting: Two UK maternity hospitals. Population: A total of 168 966 women with singleton pregnancies attending for routine ultrasound examination at 11–13 weeks of gestation without major abnormalities delivering at 24 weeks or more of gestation. Methods: Regression analysis examined the association between race and pre‐eclampsia or gestational hypertension in the FMF data. Literature search to December 2021 was carried out to identify peer‐reviewed publications on race and pre‐eclampsia. Main outcome measure: Relative risk of pre‐eclampsia and gestational hypertension in women of black, South Asian and East Asian race by comparison to white women. Results: In black women, the respective risks of total‐pre‐eclampsia and preterm‐pre‐eclampsia were 2‐fold and 2.5‐fold higher, respectively, and risk of gestational hypertension was 25% higher; in South Asian women there was a 1.5‐fold higher risk of preterm pre‐eclampsia but not of total‐pre‐eclampsia and in East Asian women there was no statistically significant difference in risk of hypertensive disorders. The literature search identified 19 studies that provided data on several million pregnancies, but 17 were at moderate or high‐risk of bias and only three provided risks adjusted for some maternal characteristics; consequently, these studies did not provide accurate contributions on different racial groups to the prediction of pre‐eclampsia. Conclusion: In women of black and South Asian origin the risk of pre‐eclampsia, after adjustment for confounders, is higher than in white women. In women of black and South Asian origin the risk of pre‐eclampsia, after adjustment for factors in maternal characteristics and medical history, is higher than in white women. This article includes Author Insights, a video abstract available at: https://vimeo.com/bjogabstracts/authorinsights17240 [ABSTRACT FROM AUTHOR]

Objective: Serum pregnancy-associated plasma protein-A (PAPP-A) and placental growth factor (PlGF) at 11-13 weeks' gestation are reduced in pregnancies with fetal trisomy and in those that subsequently develop pre-eclampsia (PE). In screening for trisomy, the established biochemical marker is PAPP-A, whereas in screening for PE, the preferred marker is PlGF. The objective of this study was to examine the impact of replacing PAPP-A by PlGF in first-trimester screening for trisomies 21, 18 and 13 by maternal age, fetal nuchal translucency thickness (NT) and free β-human chorionic gonadotropin (β-hCG).Methods: This was a prospective screening study in singleton pregnancies for trisomies 21, 18 and 13 by a combination of maternal age, fetal NT and serum PAPP-A and free β-hCG at 11-13 weeks' gestation in which we also measured PlGF. Multiples of the median (MoM) values were calculated for PAPP-A, free β-hCG and PlGF. The dataset was split randomly into training and test datasets of roughly equal size, and the parameters for PlGF obtained from the training dataset were used in risk calculation for the test dataset. Standardized detection rates were computed by obtaining the likelihood ratios for biochemistry and fetal NT for trisomy-21, -18 and -13 pregnancies in the sample and then applying these to each year of maternal age from 12 to 50 to estimate the age-specific detection rates. These were then weighted according to the maternal age distributions of trisomy-21, -18 and -13 pregnancies in England and Wales in 2018. Similarly, standardized false-positive rates (FPR) were computed by obtaining the likelihood ratios for biochemistry and NT, as appropriate, in normal pregnancies in the sample and then applying these to each year of maternal age from 12 to 50 to estimate the age-specific FPRs. A modeling approach was used to assess the performance of screening according to gestational age at biochemical testing.Results: The study population of 71 266 pregnancies included 70 858 (99.4%) with normal fetal karyotype or birth of a phenotypically normal neonate and 263 with trisomy 21, 109 with trisomy 18 and 36 with trisomy 13. There are five main findings of this study. First, the performance of screening for trisomy by the first-trimester combined test or the combined test in which PAPP-A is replaced by PlGF is substantially better at 11 than at 13 weeks' gestation; for example, the detection rates of trisomy 21 by the combined test were 94%, 90% and 84%, at 5% FPR, when testing was carried out at 11, 12 and 13 weeks, respectively, and the corresponding values in screening by a test in which PAPP-A is replaced by PlGF were 90%, 87% and 86%, respectively. Second, in trisomy-21 pregnancies, the deviation of median PAPP-A MoM from normal decreases with increasing gestational age, whereas the deviation in PlGF does not change with gestational age. Third, the performance of screening for trisomy 21 during the 11th and 12th gestational weeks is superior if screening includes PAPP-A rather than PlGF, whereas during the 13th week the performance is slightly higher with the use of PlGF rather than PAPP-A. Fourth, in our population with mean gestational age at testing of 12.7 weeks, screening by maternal age, fetal NT, serum free β-hCG and serum PAPP-A predicted 88%, 96% and 97% of cases of fetal trisomies 21, 18 and 13, respectively, at a FPR of 5%; the respective values in screening by a test in which PAPP-A is replaced by PlGF were 85%, 96% and 96%. Fifth, addition of serum PlGF does not improve the prediction of trisomy provided by maternal age, fetal NT and serum free β-hCG and PAPP-A.Conclusion: In first-trimester screening for trisomy, the preferred biochemical marker is PAPP-A rather than PlGF, especially when biochemical testing is carried out during the 11th week of gestation or earlier. However, if PlGF was to be used rather than PAPP-A, the same detection rate can be achieved but at a higher FPR. This may be an acceptable compromise to minimize cost and achieve effective screening for both trisomy and PE. © 2020 International Society of Ultrasound in Obstetrics and Gynecology. [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 test the hypothesis that the performance of first‐trimester screening for pre‐eclampsia (PE) by a method that uses Bayes' theorem to combine maternal factors with biomarkers is superior to that defined by current National Institute for Health and Care Excellence (NICE) guidelines. Methods: This was a prospective multicenter study (screening program for pre‐eclampsia (SPREE)) in seven National Health Service maternity hospitals in England, of women recruited between April and December 2016. Singleton pregnancies at 11–13 weeks' gestation had recording of maternal characteristics and medical history and measurements of mean arterial pressure (MAP), uterine artery pulsatility index (UtA‐PI), serum placental growth factor (PlGF) and serum pregnancy‐associated plasma protein‐A (PAPP‐A). The performance of screening for PE by the Bayes' theorem‐based method was compared with that of the NICE method. Primary comparison was detection rate (DR) using NICE method vs mini‐combined test (maternal factors, MAP and PAPP‐A) in the prediction of PE at any gestational age (all‐PE) for the same screen‐positive rate determined by the NICE method. Key secondary comparisons were DR of screening recommended by the NICE guidelines vs three Bayes' theorem‐based methods (maternal factors, MAP and PAPP‐A; maternal factors, MAP and PlGF; and maternal factors, MAP, UtA‐PI and PlGF) in the prediction of preterm PE, defined as that requiring delivery < 37 weeks. Results: All‐PE developed in 473 (2.8%) of the 16 747 pregnancies and preterm PE developed in 142 (0.8%). The screen‐positive rate by the NICE method was 10.3% and the DR for all‐PE was 30.4% and for preterm PE it was 40.8%. Compliance with the NICE recommendation that women at high risk for PE should be treated with aspirin from the first trimester to the end of pregnancy was only 23%. The DR of the mini‐combined test for all‐PE was 42.5%, which was superior to that of the NICE method by 12.1% (95% CI, 7.9–16.2%). In screening for preterm PE by a combination of maternal factors, MAP and PlGF, the DR was 69.0%, which was superior to that of the NICE method by 28.2% (95% CI, 19.4–37.0%) and with the addition of UtA‐PI the DR was 82.4%, which was higher than that of the NICE method by 41.6% (95% CI, 33.2–49.9%). Conclusions: The performance of screening for PE as currently recommended by NICE guidelines is poor and compliance with these guidelines is low. The performance of screening is substantially improved by a method combining maternal factors with biomarkers. © 2018 Crown copyright. Ultrasound in Obstetrics & Gynecology © 2018 ISUOG. [ABSTRACT FROM AUTHOR]

Objective: To compare the degree of impaired placentation in women with and those without chronic hypertension (CH) who develop pre-eclampsia (PE) in pregnancy.Methods: Data were derived from prospective screening for adverse pregnancy outcomes in women with singleton pregnancy attending their first routine hospital visit at 11 + 0 to 13 + 6 weeks' gestation. This visit included recording of maternal characteristics and medical history and measurement of mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), serum placental growth factor (PlGF) and serum pregnancy-associated plasma protein-A (PAPP-A). The measured biomarkers were converted to multiples of the median (MoM) after adjustment for pregnancy characteristics. MoM values in women with CH who developed PE (n = 283) were compared to those of women without CH who developed PE (n = 2236).Results: In both groups with and without CH, measurements of MAP and UtA-PI were increased, whereas those of PlGF and PAPP-A were decreased and the deviation from normal in all biomarkers decreased with advancing gestational age at delivery with PE. There was no significant difference between women with and those without CH in the slope of the regression line of log10 MoM biomarker values against gestational age at delivery with PE for any of the biomarkers. However, there was a significant difference in the intercepts and coefficients of biomarkers in the two groups; compared to those without CH, MAP MoM, PlGF MoM and PAPP-A MoM were higher and UtA-PI MoM was lower in the CH group (all P < 0.01).Conclusion: In pregnancies that develop PE, the degree of impaired placentation, reflected in high UtA-PI and low PlGF and PAPP-A at 11-13 weeks' gestation, is less in women with CH than in those without CH. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To examine the effect of chronic hypertension (CH), with and without superimposed pre-eclampsia (PE), on the incidence of a small-for-gestational-age (SGA) neonate and to explore the possible mechanism for such association.Methods: Data for this study were derived from prospective screening for adverse pregnancy outcomes in women with singleton pregnancy attending their first routine hospital visit at 11-13 weeks' gestation, which included recording of maternal characteristics and medical history and measurement of mean arterial pressure (MAP). Birth-weight Z-score, adjusted for gestational age and maternal and pregnancy characteristics, and incidence of SGA were compared between those with and those without CH in the total population and in the subgroups of pregnancies with and without PE. Regression analysis was used to examine the relationship between MAP and birth-weight Z-score and incidence of SGA and PE in those with and those without CH.Results: The study population constituted 74 226 pregnancies, including 1052 (1.4%) with CH and 73 174 without CH. PE developed in 233 (22.1%) cases of the group with CH and in 1662 (2.3%) of those without CH. In the group that developed PE, there was no significant difference for either median birth-weight Z-score or incidence of SGA between those with CH and those without CH. In the group without PE, the incidence of SGA was twice as high in those with CH than in those without. There was a significant association between log10 MAP multiples of the median and incidence of SGA and PE, which was more marked in those with CH than in those without.Conclusion: CH is associated with an increased risk of SGA and PE and this is related to MAP at 11-13 weeks' gestation. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. [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]

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 gestational age at delivery in dichorionic (DC) and monochorionic (MC) twin pregnancies, with and without pre-eclampsia (PE), and to determine the relative risk of total and preterm PE compared with that in singleton pregnancies.Methods: This was a screening study for PE in twin pregnancies undergoing first-trimester combined screening for aneuploidy and subsequently delivering two phenotypically normal live or stillborn babies at ≥ 24 weeks' gestation. The distribution of gestational age at delivery in DC and MC twins was determined and compared with that in singleton pregnancies from the same population. The relative risk for total and preterm PE in twins compared with singleton pregnancies was determined. Kaplan-Meier estimates of the cumulative incidence of PE in twin and singleton pregnancies, assuming no other cause for delivery, were determined and hazard ratios for twins relative to singletons were obtained from a Cox proportional hazards regression model.Results: The incidence of PE in singletons was 2.3% (2162/93 297), in DC twin pregnancies was 8.1% (145/1789) and in MC twin pregnancies was 6.0% (26/430). Compared with singletons, the relative risk of total PE was 3.5 for DC twins and 2.6 for MC twins. Delivery < 37 weeks' gestation occurred in 5.5% of singletons, 46.5% of DC twins and 91.4% of MC twins. The incidence of preterm PE was 0.6%, 5.5% and 5.8% for singletons, DC twins and MC twins, respectively. Compared with singletons, the relative risk of preterm PE was 8.7 for DC twins and 9.1 for MC twins. In the Cox proportional hazards regression model, the hazard ratios for DC and MC twin pregnancies relative to singleton pregnancies were 14 and 23, respectively.Conclusions: The relative risk of preterm PE in DC and MC twins is similar and substantially higher than in singleton pregnancies. In ongoing twin pregnancies, the high relative risk of PE may merit a higher intensity of monitoring than is routine for singleton pregnancies. © 2017 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Background: Preeclampsia is associated with increased risks of life-threatening, -altering, and -ending complications. Assessment of risk for preeclampsia at 35 to 36 weeks' gestation by the Fetal Medicine Foundation 36-week competing-risk model identifies approximately 75% of women who will develop term preeclampsia, at a 10% screen-positive rate.Objective: This study aimed to assess whether the Fetal Medicine Foundation 36-week model can provide personalized guidance to women about the probable timing of their delivery, whether or not they develop pregnancy hypertension.Study Design: In this prospective nonintervention screening study at 2 maternity hospitals in England, women who did not have preeclampsia (American College of Obstetricians and Gynecologists definition) and were attending a routine hospital visit at 35 0/7 to 36 6/7 weeks' gestation underwent assessment of risk for preeclampsia, including maternal demographic characteristics, medical history, mean arterial pressure, and serum placental growth factor and soluble fms-like tyrosine kinase-1. Fetal Medicine Foundation 36-week model risk categories for subsequent preeclampsia were defined as: A, ≥0.500; B, 0.20 to 0.499; C, 0.05 to 0.199; D, 0.020 to 0.049; and E, <0.020. Obstetrical records were examined for all women to identify their gestational age at delivery, and whether they experienced a spontaneous onset of labor (irrespective of mode of delivery) or had a medically indicated birth (either induction of labor or unlabored cesarean delivery). The cumulative incidence of delivery and risk ratios, for all deliveries and for spontaneous deliveries, was assessed.Results: Among 29,035 women with singleton pregnancies, 1.0%, 2.9%, 3.3%, 5.0%, 9.9%, and 77.9% were in A, B, C, D, and E risk strata, respectively. In the A (vs E) stratum, 71.95% (vs 33.52%) of births were medically indicated. Compared with women in stratum E, women in higher risk strata were more likely to deliver, and to deliver following spontaneous labor, before their due date. For example, of the women in stratum A (vs E), 14.2% (vs 1.1%; risk ratio, 12.5 [95% confidence interval, 9.45-15.35]), 48.5% (vs 5.1%; risk ratio, 8.47 [7.48-9.35]), 69.6% (vs 15.5%; risk ratio, 3.86 [3.59-4.08]), and 90.1% (vs 44.8%; risk ratio, 6.72 [4.53-9.95]) gave birth before 37 0/7, 38 0/7, 39 0/7, and 40 0/7 weeks, respectively. For women in stratum A (vs E), when censored for medically indicated births, spontaneous labor occurred more commonly before 37 0/7 (risk ratio, 4.31 [1.99-6.57]), 38 0/7 (risk ratio, 3.71 [2.48-4.88]), 39 0/7 (risk ratio, 2.87 [2.22-3.46]), and 40 0/7 (risk ratio, 1.42 [1.14-1.77]) weeks.Conclusion: Women in higher-risk strata gave birth earlier, and more frequently following medically indicated delivery, compared with those in lower-risk strata. Importantly, the proportion of women who gave birth following spontaneous onset of labor before their due date was also greater in higher-risk than in lower-risk women. The Fetal Medicine Foundation 36-week competing-risk model incorporates biomarkers of placental aging, including angiogenic imbalance; these results imply that a fetoplacental response to placental aging may be an important trigger for the onset of labor at term. [ABSTRACT FROM AUTHOR]

Background: A definition of preeclampsia that incorporates the assessment of maternal, fetal, and uteroplacental status would optimize the identification of pregnancies at risk of complications at term gestational age. This definition would include "carrying forward" angiogenic test results from 35 to 36 weeks of gestation to term gestational age. Would this approach still be useful if testing is performed earlier or at a routine midgestation scan and the result is used to inform the diagnosis of preeclampsia that developed thereafter?Objective: This study aimed to evaluate whether fetoplacental assessment at a 19- to 23-week scan could be "carried forward" to contribute to the classification of preeclampsia and improve the detection of women and fetuses at risk of adverse outcomes associated with hypertension.Study Design: In this prospective cohort study of singleton pregnancies at 2 maternity hospitals in England (October 2011 to March 2020), women attending a routine hospital visit at 19 to 23 weeks of gestation underwent an assessment that included history, ultrasonographic estimated fetal weight, Doppler measurements of the pulsatility index in uterine arteries, and serum placental growth factor. Preeclampsia was defined according to various definitions: (1) traditional, based on new-onset proteinuria at ≥20 weeks of gestation; (2) 2013 American College of Obstetricians and Gynecologists; (3) 2018 International Society for the Study of Hypertension in Pregnancy maternal factor; (4) 2018 International Society for the Study of Hypertension in Pregnancy maternal-fetal factor (death or growth restriction), based on ultrasound scans at the 19 0/7 to 23 6/7 week of gestation (an estimated fetal weight of <3rd percentile or estimated fetal weight between the 3rd and 10th percentiles with a uterine artery pulsatility index of >95th percentile); and (5) 2021 International Society for the Study of Hypertension in Pregnancy maternal-fetal factor plus placental growth factor (with abnormal placental growth factor defined as an estimated fetal weight of <5th percentile for gestational age). The detection rates for outcomes of interest (ie, severe maternal hypertension, major maternal morbidity, perinatal mortality or major neonatal morbidity, neonatal intensive care unit admission ≥48 hours, and birthweight of <3rd percentile) ascertained by health record review were compared using the chi-square test. A P value of <.05 was considered statistically significant.Results: Among 40,241 singleton pregnancies, preeclampsia incidence varied by definition, from lows of 2.6% (traditional) and 3.0% (American College of Obstetricians and Gynecologists) to a high of 3.8% (International Society for the Study of Hypertension in Pregnancy maternal-fetal factor plus placental growth factor). The International Society for the Study of Hypertension in Pregnancy maternal-fetal factor plus placental growth factor definition (vs the traditional) best identified women who developed adverse outcomes: severe hypertension (detection rate: 70.6% vs 52.8%; P<.001), major maternal morbidity (detection rate: 100% vs 87.5%; P=.027), perinatal mortality or major morbidity (detection rate: 84.6% vs 69.5%; P=.004), neonatal intensive care unit admission ≥48 hours (detection rate: 76.6% vs 63.2%;, P=.0002), and birthweight of <3rd percentile (detection rate: 81.3% vs 61.9%; P<.0001]. The detection rates improved, going from the American College of Obstetricians and Gynecologists definition to the International Society for the Study of Hypertension in Pregnancy maternal-fetal factor plus placental growth factor definition, for severe hypertension (11.4%; P=.003), perinatal mortality or major morbidity (10.6%; P=.03), neonatal intensive care unit admission ≥48 hours (8.6%; P=.01), and birthweight of <3rd percentile (16.2%; P<.001). However, going from the International Society for the Study of Hypertension in Pregnancy maternal-fetal factor definition to the International Society for the Study of Hypertension in Pregnancy maternal-fetal factor plus placental growth factor definition, the detection of fetuses with a birthweight of <3rd percentile improved by 7.0% (P=.01), but no other improvement was seen for severe hypertension (1.7%; P=.33), major maternal morbidity (0%), perinatal mortality or major morbidity (4.0%; P=.20), and neonatal intensive care unit admission ≥48 hours (3.2%; P=.17).Conclusion: The criteria for uteroplacental dysfunction (including placental growth factor) from the 19- to 23-week assessment can be used in the assessment of women who are later suspected of having PE, to best identify pregnancies at risk of adverse outcomes. [ABSTRACT FROM AUTHOR]

Background: In the weeks preceding the clinical onset of preeclampsia, the maternal serum level of the angiogenic placental growth factor is decreased and that of the antiangiogenic factor soluble fms-like tyrosine kinase-1 is increased. Women presenting at specialist clinics with signs or symptoms of hypertensive disorders have been stratified according to concentrations of placental growth factor or the ratio of concentrations of soluble fms-like tyrosine kinase-1 and placental growth factor to determine clinical management for the subsequent 1-4 weeks. An alternative approach for the prediction of preeclampsia is use of the competing risks model, a Bayes' theorem based method, to derive patient-specific risk for preeclampsia by various combinations of maternal characteristics and medical history with multiples of the median values of biomarkers.Objective: The purpose of this study was to compare the performance of screening for delivery with preeclampsia at ≤2 and ≤4 weeks after assessment at 35+0-36+6 weeks gestation between the use of percentile cut-offs in placental growth factor alone or the soluble fms-like tyrosine kinase-1/placental growth factor ratio and the competing risks model.Study Design: This was a prospective observational study in women who attended a routine hospital visit at 35+0-36+6 weeks gestation in 2 maternity hospitals in England. The visits included the recording of maternal demographic characteristics and medical history and the measurement of serum placental growth factor and soluble fms-like tyrosine kinase-1 and mean arterial pressure. The areas under the receiver operating characteristics curves were used to compare the predictive performance for preeclampsia with delivery at ≤2 and ≤4 weeks from assessment of screening by placental growth factor alone and the soluble fms-like tyrosine kinase-1/placental growth factor ratio with that of a previously developed competing risks model with a combination of maternal factors, placental growth factor, soluble fms-like tyrosine kinase-1, and mean arterial pressure (triple test).Results: First, the study population of 15,247 pregnancies included 326 pregnancies (2.1%) that subsequently experienced preeclampsia. Second, in the screening for delivery with preeclampsia at ≤2 and ≤4 weeks from assessment, the performance of the triple test was superior to that of placental growth factor alone or the soluble fms-like tyrosine kinase-1/placental growth factor ratio. The area under the receiver operating characteristics curves for preeclampsia at ≤2 weeks in screening by the triple test (0.975; 95% confidence interval, 0.964-0.985) was higher than that of placental growth factor alone (0.900; 95% confidence interval, 0.866-0.935; P<.0001) and the soluble fms-like tyrosine kinase-1/placental growth factor ratio (0.932; 95% confidence interval, 0.904-0.960; P=.0001). Similarly, the areas under the receiver operating characteristics curves for preeclampsia at ≤4 weeks in screening by the triple test (0.907; 95% confidence interval, 0.886-0.928) was higher than that of placental growth factor alone (0.827; 95% confidence interval, 0.800-0.854; P<.0001) or the soluble fms-like tyrosine kinase-1/placental growth factor ratio (0.857; 95% confidence interval, 0.830-0.883; P<.0001). Third, at most, screen-positive rates of 2-30% the detection rate of delivery with preeclampsia at ≤2 and ≤4 weeks that was achieved by the triple test was approximately 10% higher than that of the soluble fms-like tyrosine kinase-1/placental growth factor ratio and 20% higher than that of placental growth factor alone; the negative predictive value was similar for the 3 tests.Conclusion: At 35+0-36+6 weeks gestation, the performance of screening for imminent delivery with preeclampsia by the competing risks model is superior to that of placental growth factor alone or the soluble fms-like tyrosine kinase-1/placental growth factor ratio. [ABSTRACT FROM AUTHOR]

Objectives: To examine the association between race and pre-eclampsia and gestational hypertension after adjustment for factors in maternal characteristics and medical history in a screening study from the Fetal Medicine Foundation (FMF) in England, and to perform a systematic review and meta-analysis of studies on pre-eclampsia., Design: Prospective observational study and systematic review with meta-analysis., Setting: Two UK maternity hospitals., Population: A total of 168 966 women with singleton pregnancies attending for routine ultrasound examination at 11-13 weeks of gestation without major abnormalities delivering at 24 weeks or more of gestation., Methods: Regression analysis examined the association between race and pre-eclampsia or gestational hypertension in the FMF data. Literature search to December 2021 was carried out to identify peer-reviewed publications on race and pre-eclampsia., Main Outcome Measure: Relative risk of pre-eclampsia and gestational hypertension in women of black, South Asian and East Asian race by comparison to white women., Results: In black women, the respective risks of total-pre-eclampsia and preterm-pre-eclampsia were 2-fold and 2.5-fold higher, respectively, and risk of gestational hypertension was 25% higher; in South Asian women there was a 1.5-fold higher risk of preterm pre-eclampsia but not of total-pre-eclampsia and in East Asian women there was no statistically significant difference in risk of hypertensive disorders. The literature search identified 19 studies that provided data on several million pregnancies, but 17 were at moderate or high-risk of bias and only three provided risks adjusted for some maternal characteristics; consequently, these studies did not provide accurate contributions on different racial groups to the prediction of pre-eclampsia., Conclusion: In women of black and South Asian origin the risk of pre-eclampsia, after adjustment for confounders, is higher than in white women., (© 2022 John Wiley & Sons Ltd.)

Objective: A survival-time regression model for gestational age at delivery with pre-eclampsia (PE) in singleton pregnancy, using maternal demographic characteristics and medical history, was reported previously. The objective of this study was to extend this model to dichorionic (DC) and monochorionic (MC) twin pregnancy., Methods: The study population included 1789 DC and 430 MC twin pregnancies and 93 297 singleton pregnancies. A survival-time model for gestational age at delivery with PE was developed from variables of maternal characteristics and medical history. The risk of PE with delivery < 37 weeks and < 42 weeks in twin pregnancies was determined and compared with that in singleton pregnancies., Results: In singleton pregnancies comprising women of Caucasian racial origin, mean weight of 69 kg at 12 weeks' gestation, mean height of 164 cm, nulliparous, with spontaneous conception, no family history of PE and no history of diabetes mellitus, systemic lupus erythematosus or antiphospholipid syndrome, the mean of the Gaussian distribution of gestational age at delivery with PE was 55 weeks. In DC twins with PE, mean gestational age at delivery was shifted to the left by 8.2 (95% CI, 7.2-9.1) weeks and in MC twins it was shifted to the left by 10.0 (95% CI, 8.5-11.4) weeks. The risk of delivery with PE occurring at, or before, a specified gestational age is given by the area under the fitted distribution curve. For a reference population with the above characteristics, the estimated risk of PE < 37 weeks' gestation, assuming no other cause of delivery, was 0.6% for singletons, 9.0% for DC twins and 14.2% for MC twins; the respective values for PE < 42 weeks were 3.6%, 27.0% and 36.5%., Conclusions: A model based on maternal characteristics and medical history has been developed for estimation of patient-specific risks for PE in DC and MC twin pregnancy. Such estimation of the a-priori risk for PE is an essential first step in the use of Bayes' theorem to combine maternal factors with biomarkers for the continuing development of more effective methods of screening for the disease. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: To examine the association between maternal racial origin 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 their first routine hospital visit at 11 + 0 to 13 + 6 weeks of gestation. Data on maternal characteristics, and medical and obstetric history were collected and pregnancy outcomes ascertained. Regression analysis was performed to examine the association between racial origin and adverse pregnancy outcomes including pre-eclampsia (PE), gestational hypertension (GH), gestational diabetes mellitus (GDM), preterm delivery (PTD), small-for-gestational age (SGA), large-for-gestational age (LGA), miscarriage, stillbirth and elective and emergency Cesarean section (CS)., Results: The study population included 76 158 singleton pregnancies with a live fetus at 11 + 0 to 13 + 6 weeks. In addition to maternal characteristics and obstetric history, Afro-Caribbean racial origin was associated with increased risk for miscarriage, stillbirth, PE, GH, spontaneous PTD, GDM, SGA and CS. In women of South Asian racial origin there was increased risk for PE, GDM, SGA and CS, and East Asian race contributed to the prediction of GDM and SGA., Conclusion: Maternal racial origin should be combined with other maternal characteristics and obstetric history when calculating an individualized adjusted risk for adverse pregnancy outcome., (Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.)

Objective: To examine the effect of method of conception on adverse pregnancy outcome after the 11-13 weeks scan., Methods: Prospective screening study for adverse obstetric outcomes in women with singleton pregnancies and live fetus with no obvious defects at 11(+0)-13(+6) weeks. The method of conception was recorded as spontaneous, in vitro fertilization (IVF) and assisted by ovulation induction (OI) drugs without IVF. Regression analysis was performed to examine the association between the method of conception and pregnancy outcome after adjustment for maternal characteristics., Results: In the study population of 41,577 pregnancies, conception was spontaneous in 40,261 (96.9%), by IVF in 634 (1.5%) and by OI in 682 (1.6%). In the pregnancies conceived by assisted reproductive technology, compared to spontaneous conceptions, there was a higher risk of stillbirth, pre-eclampsia, gestational hypertension, gestational diabetes mellitus, delivery of small for gestational age neonates and caesarean section. However, multiple regression analysis showed that after taking into account maternal characteristics, the only significant contributions of IVF were for pre-eclampsia and elective caesarean section and the contributions of OI were for miscarriage, spontaneous early preterm delivery and small for gestational age., Conclusions: Conception by IVF and OI is associated with increased risk for adverse pregnancy outcome., (Copyright © 2011 S. Karger AG, Basel.)