Prediction of pre-eclampsia in twin pregnancy by maternal factors and biomarkers at 11-13 weeks' gestation: data from EVENTS trial.

OBJECTIVES: First, to validate a previously developed model for screening for pre-eclampsia (PE) by maternal characteristics and medical history in twin pregnancies; second, to compare the distributions 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) in twin pregnancies that delivered with PE to those in singleton pregnancies and to develop new models based on these results; and, third, to examine the predictive performance of these models in screening for PE with delivery at < 32 and < 37 weeks' gestation. METHODS: Two datasets of prospective non-intervention multicenter screening studies for PE in twin pregnancies at 11 + 0 to 13 + 6 weeks' gestation were used. The first dataset was from the EVENTS (Early vaginal progesterone for the preVention of spontaneous prEterm birth iN TwinS) trial and the second was from a previously reported study that examined the distributions of biomarkers in twin pregnancies. Maternal demographic characteristics and medical history from the EVENTS-trial dataset were used to assess the validity of risks from our previously developed model. The combined data from the first and second datasets were used to compare the distributional properties of log10 multiples of the median (MoM) values of UtA-PI, MAP, PlGF and PAPP-A in twin pregnancies that delivered with PE to those in singleton pregnancies and develop new models based on these results. The competing-risks model was used to estimate the individual patient-specific risks of delivery with PE at < 32 and < 37 weeks' gestation. Screening performance was measured by detection rates (DR) and areas under the receiver-operating-characteristics curve. RESULTS: The EVENTS-trial dataset comprised 1798 pregnancies, including 168 (9.3%) that developed PE. In the validation of the prior model based on maternal characteristics and medical history, calibration plots demonstrated very good agreement between the predicted risks and the observed incidence of PE (calibration slope and intercept for PE < 32 weeks were 0.827 and 0.009, respectively, and for PE < 37 weeks they were 0.942 and -0.207, respectively). In the combined data, there were 3938 pregnancies, including 339 (8.6%) that developed PE and 253 (6.4%) that delivered with PE at < 37 weeks' gestation. In twin pregnancies that delivered with PE, MAP, UtA-PI and PlGF were, at earlier gestational ages, more discriminative than in singleton pregnancies and at later gestational ages they were less so. For PAPP-A, there was little difference between PE and unaffected pregnancies. The best performance of screening for PE was achieved by a combination of maternal factors, MAP, UtA-PI and PlGF. In screening by maternal factors alone, the DR, at a 10% false-positive rate, was 30.6% for delivery with PE at < 32 weeks' gestation and this increased to 86.4% when screening by the combined test; the respective values for PE < 37 weeks were 24.9% and 41.1%. CONCLUSIONS: In the assessment of risk for PE in twin pregnancy, we can use the same prior model based on maternal characteristics and medical history as reported previously, but in the calculation of posterior risks it is necessary to use the new distributions of log10 MoM values of UtA-PI, MAP and PlGF according to gestational age at delivery with PE. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Comparison of different methods of measuring angle of progression in prediction of labor outcome.

OBJECTIVES: First, to compare the manual sagittal and parasagittal and automated parasagittal methods of measuring the angle of progression (AoP) by transperineal ultrasound during labor, and, second, to develop models for the prediction of time to delivery and need for Cesarean section (CS) for failure to progress (FTP) in a population of patients undergoing induction of labor. METHODS: This was a prospective observational study of transperineal ultrasound in a cohort of 512 women with a singleton pregnancy undergoing induction of labor. A random selection of 50 stored images was assessed for inter- and intraobserver reliability of AoP measurements using the manual sagittal and parasagittal and automated parasagittal methods. In cases of vaginal delivery, univariate linear, multiple linear and quantile regression analyses were performed to predict time to delivery. Univariate and multivariate binomial logistic regression analyses were performed to predict CS for FTP in the first stage of labor. RESULTS: The intraclass correlation coefficient (ICC) for the manual parasagittal method for a single observer was 0.97 (95% CI, 0.95-0.98) and for two observers it was 0.96 (95% CI, 0.93-0.98), indicating good reliability. The ICC for the sagittal method for a single observer was 0.93 (95% CI, 0.88-0.96) and for two observers it was 0.74 (95% CI, 0.58-0.84), indicating moderate reliability for a single observer and poor reliability between two observers. Bland-Altman analysis demonstrated narrower limits of agreement for the manual parasagittal approach than for the sagittal approach for both a single and two observers. The automated parasagittal method failed to capture an image in 19% of cases. The mean difference in AoP measurements between the sagittal and manual parasagittal methods was 11°. In pregnancies resulting in vaginal delivery, 54% of the variation in time to delivery was explained in a model combining parity, epidural and syntocinon use during labor and the sonographic findings of fetal head position and AoP. In the prediction of CS for FTP in the first stage of labor, a model which combined maternal factors with the sonographic measurements of AoP and estimated fetal weight was superior to one utilizing maternal factors alone (area under the receiver-operating-characteristics curve, 0.80 vs 0.76). CONCLUSIONS: First, the method of measuring AoP with the greatest reliability is the manual parasagittal technique and future research should focus on this technique. Second, over half of the variation in time to vaginal delivery can be explained by a model that combines maternal factors, pregnancy characteristics and ultrasound findings. Third, the ability of AoP to provide clinically useful prediction of CS for FTP in the first stage of labor is limited. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.