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

Abstract

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 as...

Cell‐free DNA testing of maternal blood in screening for trisomies in twin pregnancy: updated cohort study at 10–14 weeks and meta‐analysis

“…If cfDNA testing is adopted as a first-line method of screening for trisomy in twin pregnancy, it is still imperative that women should be offered an 11-14-week scan for, first, accurate dating of pregnancy from the crown-rump length of the largest twin, second, diagnosis of chorionicity, which is the main determinant of a wide range of adverse outcomes 34 , third, measurement of fetal nuchal translucency thickness and assessment of intertwin discordance in crown-rump length, which have a strong influence on adverse pregnancy outcome 35,36 , fourth, diagnosis of a vanishing twin, because this would preclude the use of cfDNA testing for at least 16 weeks after the estimated time of fetal demise 37,38 , fifth, early diagnosis of major fetal abnormalities 39 , sixth, to determine the presence of major defects, such as holoprosencephaly or exomphalos, in which case an invasive test with microarray rather than cfDNA testing would be the appropriate pregnancy management 40 , seventh, early screening for preterm pre-eclampsia, which is 8-9-times more common in twins than in singleton pregnancies 41,42 , and, eighth, measurement of cervical length, because, if this is short, prophylactic use of vaginal progesterone could substantially reduce the risk of preterm birth 43 .…”

Key messages for obstetricians and fetal medicine specialists from the confidential enquiry into stillbirth and neonatal death in twins

“…For pre-eclampsia <37 weeks, the DR was 25% for a 10% FPR. 26 The combination of maternal risk factors, uterine artery Doppler, mean arterial pressure and maternal serum placental growth factor increased the DR to 86% for a 10% FPR for delivery with early-onset preeclampsia <32 weeks' gestation.…”

“…For preeclampsia <37 weeks, the DR was 41% for a 10% FPR. 26 The evidence from the ASPRE trial on the effectiveness of low-dose aspirin (150mg/day) in the prevention of preeclampsia relates to singleton pregnancies only, as the trial excluded multiple pregnancies.…”

“…In a recent multicenter study in twin pregnancies, maternal risk factors alone had a detection rate (DR) of 31% at a 10% false‐positive rate (FPR) for delivery with early‐onset pre‐eclampsia < 32 weeks' gestation. For pre‐eclampsia < 37 weeks, the DR was 25% at a 10% FPR 26 . The combination of maternal risk factors, uterine artery Doppler, mean arterial pressure and maternal serum placental growth factor increased the DR to 86% at a 10% FPR for delivery with early‐onset pre‐eclampsia < 32 weeks' gestation.…”

First-Trimester Screening for Gestational Diabetes Mellitus in Twin Pregnancies

“…Twin pregnancies, compared to singletons, are at increased risk of pregnancy complications, including miscarriage, stillbirth, preterm birth, fetal growth restriction, and preeclampsia [10][11][12]. There is contradictory evidence concerning the incidence of GDM in twin pregnancies, with some studies reporting that this is higher than in singletons [13][14][15][16][17][18], while others found that the rates are similar [17,18].…”