Background— Hypertensive disorders of pregnancy are a major contributor to death and disability for pregnant women and their infants. The diagnosis of preeclampsia by using blood pressure and proteinuria is of limited use because they are tertiary, downstream features of the disease. Placental growth factor (PlGF) is an angiogenic factor, a secondary marker of associated placental dysfunction in preeclampsia, with known low plasma concentrations in the disease. Methods and Results— In a prospective multicenter study, we studied the diagnostic accuracy of low plasma PlGF concentration (<5th centile for gestation, Alere Triage assay) in women presenting with suspected preeclampsia between 20 and 35 weeks’ gestation (and up to 41 weeks’ gestation as a secondary analysis). The outcome was delivery for confirmed preeclampsia within 14 days. Of 625 women, 346 (55%) developed confirmed preeclampsia. In 287 women enrolled before 35 weeks’ gestation, PlGF <5th centile had high sensitivity (0.96; 95% confidence interval, 0.89–0.99) and negative predictive value (0.98; 0.93–0.995) for preeclampsia within 14 days; specificity was lower (0.55; 0.48–0.61). Area under the receiver operating characteristic curve for low PlGF (0.87, standard error 0.03) for predicting preeclampsia within 14 days was greater than all other commonly used tests, singly or in combination (range, 0.58–0.76), in women presenting with suspected preeclampsia ( P <0.001 for all comparisons). Conclusions— In women presenting before 35 weeks’ gestation with suspected preeclampsia, low PlGF has high sensitivity and negative predictive value for preeclampsia within 14 days, is better than other currently used tests, and presents an innovative adjunct to management of such women.

More than half of all cases of preeclampsia occur in healthy first-time pregnant women. Our aim was to develop a method to predict those at risk by combining clinical factors and measurements of biomarkers in women recruited to the Screening for Pregnancy Endpoints (SCOPE) study of low-risk nulliparous women. Forty-seven biomarkers identified on the basis of (1) association with preeclampsia, (2) a biological role in placentation, or (3) a role in cellular mechanisms involved in the pathogenesis of preeclampsia were measured in plasma sampled at 14 to 16 weeks’ gestation from 5623 women. The cohort was randomly divided into training (n=3747) and validation (n=1876) cohorts. Preeclampsia developed in 278 (4.9%) women, of whom 28 (0.5%) developed early-onset preeclampsia. The final model for the prediction of preeclampsia included placental growth factor, mean arterial pressure, and body mass index at 14 to 16 weeks’ gestation, the consumption of ≥3 pieces of fruit per day, and mean uterine artery resistance index. The area under the receiver operator curve (95% confidence interval) for this model in training and validation cohorts was 0.73 (0.70–0.77) and 0.68 (0.63–0.74), respectively. A predictive model of early-onset preeclampsia included angiogenin/placental growth factor as a ratio, mean arterial pressure, any pregnancy loss <10 weeks, and mean uterine artery resistance index (area under the receiver operator curve [95% confidence interval] in training and validation cohorts, 0.89 [0.78–1.0] and 0.78 [0.58–0.99], respectively). Neither model included pregnancy-associated plasma protein A, previously reported to predict preeclampsia in populations of mixed parity and risk. In nulliparous women, combining multiple biomarkers and clinical data provided modest prediction of preeclampsia.

Background: Our aim was to identify and compare modifiable risk factors associated with adverse pregnancy outcomes in women with type 1 and type 2 diabetes and to identify effective maternity clinics. Methods:We included 17,375 pregnancies in 15,290 women with diabetes in a populationbased cohort study across 172 maternity clinics in England, Wales and the Isle of Man.Obstetric complications (preterm delivery, large birthweight) and adverse pregnancy outcomes (congenital anomaly, stillbirth, neonatal death) were obtained for pregnancies completed between 01 January 2014 and 31 December 2018. We assessed associations between modifiable (glycaemia, obesity, clinic) and non-modifiable risk factors (age, deprivation, ethnicity) with pregnancy outcomes.Results: Of 17,375 pregnancies, 8,690 (50.0%) were in women with type 1 and 8,685 (50.0%) in women with type 2 diabetes. The rates of preterm delivery (42.5% type 1, 23.4% type 2), and large birthweight (52.2% type 1, 26.2% type 2) were higher in type 1 diabetes (p<0.001).The prevalence of congenital anomaly (44.8/1000 type 1, 40.5/1000 type 2; p=0.175), and stillbirth (10.4/1000 type 1, 13.5/1000 type 2; p=0.072) did not differ but neonatal death rates (7.4/1000 type 1, 11.2/1000 type 2; p=0.013) were higher in type 2 diabetes. Independent risk factors for perinatal death were third trimester HbA1c > 48mmol/mol (OR 3.06, 95% CI 2.16 to 4.33), living in the highest deprivation quintile (OR 2.29 95% CI 1.16 to 4.52) and having type 2 diabetes (OR 1.65 95% CI 1.18 to 2.31). Variations in glycaemia and large birthweight were associated with maternal characteristics (diabetes duration, deprivation, BMI) without substantial differences between clinics.Interpretation: Our data highlight persistent adverse pregnancy outcomes in type 1 and type 2 diabetes. Maternal glycaemia and obesity are the key modifiable risk factors. No clinics were achieving appreciably better outcomes, suggesting that healthcare system changes are needed