Revised competing‐risks model in screening for pre‐eclampsia in twin pregnancy by maternal characteristics and medical history

Abstract

Background We have proposed previously that the competing‐risks model for prediction of pre‐eclampsia (PE) based on maternal characteristics and medical history (prior model), developed in singleton pregnancies, can be extended to risk assessment for twins; in dichorionic (DC) and monochorionic (MC) twin pregnancies with the same characteristics as in singleton pregnancies, the distribution of gestational age at delivery with PE was shifted to the left by 8 and 10 weeks, respectively. However, in a subsequent validation study, we found that, in both the training and validation datasets, the observed incidence of PE was lower than the predicted one and such overestimation of risk was particularly marked for early PE. Objectives First, to develop a new extension of the competing‐risks prior model in screening for PE by maternal demographic characteristics and medical history in twin pregnancies in a training dataset. Second, to examine the predictive performance of this model in screening for PE with delivery < 34 weeks (early PE), < 37 weeks (preterm PE) and at any gestational age (all PE) in twins in a validation dataset. Third, to demonstrate the application of screening in a mixed population of singleton and twin pregnancies. Methods The data for this study were obtained from two prospective non‐intervention multicenter screening studies for PE in twin pregnancies at 11 + 0 to 13 + 6 weeks' gestation. The training and validation datasets consisted of 2219 and 2999 women, respectively. We used the training dataset to fit a model in which the effect of twins on shifting the distribution of gestational age at delivery with PE in singletons to the left should not be the same for all gestational ages but the shift should depend on the singleton prior mean; the effect increases with increasing prior mean. We examined the predictive performance of the model in the training and validation datasets using the area under the receiver–operating characteristics curve (AUC) and calibration plots. Data on 16 747 singleton pregnancies obtained from the Screening ProgRamme for prE‐Eclampsia (SPREE) study were included to examine the performance of screening in a mixed population of singleton and twin pregnancies. Results Calibration plots and calibration intercept and slope demonstrate superior predictive performance of the new model in the validation dataset. Although the AUC for twin pregnancies is lower than in singleton pregnancies, performance of screening in a mixed population of singleton and twin pregnancies is superior to that in singletons (AUC of 0.790 in a mixed population comprising 2% twins and 98% singletons compared to 0.775 in singletons). For the risk cut‐offs likely to be used in practice, all twin pregnancies screen positive using maternal characteristics and medical history. Conclusions A new competing‐risks model in screening for PE by maternal risk factors in twin pregnancy has been developed and, using this model, the predicted risks for early PE, preterm PE and all PE are in relatively good agr...

Impact of new definitions of pre‐eclampsia on incidence and performance of first‐trimester screening

“…In previous studies investigating the value of screening for PE by a combination of maternal demographic characteristics and medical history with biomarkers in the first, second and third trimesters in singleton and twin pregnancies, the outcome measure was PE as defined originally by the ISSHP 1,[4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] . In the first trimester, screening has been achieved successfully by a combination of maternal demographic characteristics and medical history, uterine artery pulsatility index (UtA-PI), mean arterial pressure (MAP) and serum placental growth factor (PlGF) through application of the competing-risks approach [4][5][6][7][8] .…”

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

“…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 10 , but in the calculation of posterior risks it is necessary to use the new distributions of log 10 MoM values of UtA-PI, MAP and PlGF according to gestational age at delivery with PE.…”

“…We used the dataset from the EVENTS trial 12 to validate the previously reported prior model for prediction of PE by maternal characteristics and medical history 10 . Calibration was assessed visually by plotting the observed incidence against that predicted for delivery with PE at < 32 and < 37 weeks' gestation.…”

“…The EVENTS trial was a multicenter study in which unselected twin pregnancies were randomized to vaginal progesterone (600 mg per day from 11–14 until 34 weeks' gestation), as compared with placebo; progesterone did not reduce the incidence of early spontaneous preterm birth 12 . The objectives of the current study were, first, to examine the predictive performance of the new model in screening for PE by maternal factors in twin pregnancies 10 in a validation dataset; second, to combine the data of biomarkers with those from our previous study 11 , compare the distributions 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 3 ; and, third, to examine the predictive performance of this model in screening for PE with delivery at < 32 weeks' gestation and at < 37 weeks.…”

“…However, in a subsequent validation study, we found that the observed incidence of PE was lower than the predicted one and such overestimation of risk was particularly marked for early PE 9 . Consequently, we developed a new model in which the effect of twins in shifting the distribution of gestational age at delivery with PE in singletons to the left was not the same for all gestational ages but rather the shift depended on the singleton prior mean; the shift to the left was greater if the prior mean was high and less if the prior mean was low 10 . In another screening study at 11–13 weeks' gestation in twin pregnancies, we measured UtA‐PI, MAP, PlGF and PAPP‐A and found that, in the PE group, compared to those that remained normotensive, MAP and UtA‐PI were increased and serum PlGF was decreased, whereas serum PAPP‐A was not significantly different 11 .…”