Objective: The aim of this study was to assess the added value of the soluble fms‐like tyrosine kinase‐1 (sFlt‐1) and placental growth factor (PlGF) ratio for adjusting the periodicity of ultrasound examinations in early‐onset fetal growth restriction (FGR) and small for gestational age (SGA).Design: A prospective, observational study.Setting: Tertiary referral hospital.Population: One hundred and thirty‐four single pregnancies with ultrasonographic estimated fetal weight (EFW) below the 10th centile between 20⁺⁰ and 31⁺⁶ weeks of gestation with antegrade umbilical artery flow.Methods: The time from Doppler and sFlt‐1/PlGF assessment to delivery was recorded and classified into four ranges: <1, <2, <3 and 85 required an elective delivery before 1 week.Conclusions: sFlt‐1/PlGF values in early‐onset SGA and FGR are predictive of the time to delivery and could be used for planning fetal surveillance, by reducing the frequency of ultrasound in cases with sFlt‐1/PlGF < 38 and by providing closer follow‐up in cases with sFlt‐1/PlGF >85.Tweetable sFlt‐1/PlGF values in early‐onset SGA/FGR could be used in addition to Doppler for planning fetal surveillance.

Objectives: To compare the ability of first‐trimester combined screening for pre‐eclampsia (PE) to predict early‐onset and preterm PE when pregnancy‐associated plasma protein‐A (PAPP‐A) and placental growth factor (PlGF) were assessed before vs after 11 weeks' gestation.Methods: This was a secondary analysis of a prospective cohort study of singleton pregnancies undergoing routine first‐trimester screening conducted at Vall d'Hebron University Hospital, Barcelona, Spain, between October 2015 and September 2017. Demographic characteristics, obstetric history, maternal history and biophysical markers (mean uterine artery pulsatility index and mean arterial blood pressure (MAP)) were recorded at the first‐trimester scan (at 11 + 0 to 13 + 6 weeks' gestation). Maternal serum concentrations of PAPP‐A and PlGF were assessed from the routine first‐trimester blood test (at 8 + 0 to 13 + 6 weeks). Women were classified into two groups depending on whether serum biomarkers were assessed at 8 + 0 to 10 + 6 weeks or at 11 + 0 to 13 + 6 weeks. Probability scores for early‐onset and preterm PE were calculated by using two different algorithms: the multivariate Gaussian‐distribution model and The Fetal Medicine Foundation (FMF) competing‐risks model. Receiver‐operating‐characteristics (ROC) curves were produced and detection rates at fixed 5% and 10% false‐positive rates were computed to compare the performance of these algorithms when PAPP‐A and PlGF were assessed before vs after 11 weeks.Results: Of the 2641 women included, serum biomarkers were assessed before 11 weeks in 1675 (63.4%) and at or after 11 weeks in 966 (36.6%). Of these, 90 (3.4%) women developed PE, including 11 (0.4%) cases of early‐onset PE and 30 (1.1%) of preterm PE. Five (45.5%) cases of early‐onset and 16 (53.3%) of preterm PE were identified in the group in which serum biomarkers were assessed at 8 + 0 to 10 + 6 weeks and six (54.5%) cases of early‐onset and 14 (46.7%) of preterm PE in the group in which serum biomarkers were assessed at 11 + 0 to 13 + 6 weeks. In the prediction of early‐onset and preterm PE using the Gaussian algorithm, no differences were observed between the areas under the ROC curves (AUCs) when PAPP‐A and PlGF were measured before or after 11 weeks. In the prediction of early‐onset and preterm PE using the FMF algorithm, no differences were observed between AUCs for any of the combinations used for risk calculation when the serum biomarkers were obtained before vs after 11 weeks, except for the combination of PAPP‐A and MAP, which showed a greater AUC for the prediction of early‐onset PE when PAPP‐A was measured at or after 11 weeks.Conclusions: The prediction of early‐onset and preterm PE is similar when serum biomarkers are measured before or after 11 weeks. This allows the use of a two‐step approach for PE risk assessment that permits immediate risk calculation at the time of the first‐trimester scan. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Objective This study aimed to analyze the effect of pravastatin on angiogenic factors, feto–maternal Doppler findings and pregnancy outcomes in women with early-onset fetal growth restriction (FGR) treated with pravastatin compared with nontreated controls. Study Design This was a pilot study conducted between March 2016 and September 2017. Women with single pregnancies and FGR diagnosed at ≤ 28 weeks of gestation were offered 40 mg of pravastatin daily. Doppler progression, soluble fms-like tyrosine kinase 1 (sFlt-1)/placental growth factor (PlGF) values, and pregnancy outcomes were assessed and compared with consecutive historical controls. Controls were matched to treated women for gestational age, maternal characteristics, maternal and obstetric history, Doppler severity classification, and angiogenic factors at diagnosis. The sFlt-1/PlGF was measured in maternal serum at two different times: before pravastatin was started (ratio M0) and during pravastatin treatment (ratio M1). Doppler severity was classified into four categories: normal, mild, moderate, and severe. Results A total of 38 women were enrolled in this study. No differences were observed in baseline characteristics between groups. However, when compared with the ratio M0, M1 was increased by a median (interquartile range) of 67.0 (−34.8 to 197.3) in the control group but decreased by a median (interquartile range) of −10.1 (−53.1 to −0.07) in the pravastatin treated group (p < 0.001). No significant differences were observed in Doppler progression throughout pregnancy. Median interval from diagnosis to delivery was extended by 16.5 days, the median newborn birthweight was increased from 1,040 to 1,300 g, and the number of women with preeclampsia decreased from 9 (47.4%) to 6 (31.6%) in treated women; however, these trends were not statistically significant. Conclusion In women with early-onset FGR, treatment with pravastatin 40 mg daily was associated with significant improvement in the angiogenic profile. Additionally, median pregnancy duration and median birthweight increased and the incidence of PE was reduced in treated women. Nevertheless, since this pilot study was underpowered, none of these differences were statistically significant. Key Points ^* These authors contributed equally to this work.