Early vaginal progesterone versus placebo in twin pregnancies for the prevention of spontaneous preterm birth: a randomized, double-blind trial

Abstract

word count: 677, Main text word count: 3604. CONDENSATIONIn women with twin pregnancies universal treatment with vaginal progesterone did not reduce the incidence of spontaneous birth between 24 +0 and 33 +6 weeks' gestation. Short version of article title:Vaginal progesterone in unselected twin pregnancies. AJOG AT A GLANCE• Randomized controlled trial testing the hypothesis that in women with twin pregnancies, vaginal progesterone at a dose of 600 mg per day from 11-14 until 34 weeks' gestation, as compared with placebo, would result in a significant reduction in the incidence of spontaneous preterm birth between 24 +0 and 33 +6 weeks.• In women with twin pregnancies universal treatment with vaginal progesterone did not reduce the incidence of spontaneous birth between 24+0 and 33+6 weeks' gestation. Post hoc time to event analysis led to the suggestion that progesterone may reduce the risk of spontaneous birth <32 weeks in women with cervical length <30 mm and it may increase the risk for those with cervical length ≥30 mm.• In women with twin pregnancies universal treatment with vaginal progesterone does not reduce the incidence of early spontaneous birth.

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

“…In the first dataset, from the EVENTS trial 12 , data on maternal characteristics, MAP, UtA‐PI and PAPP‐A were available for 1798 pregnancies but serum PlGF was measured in only 1319 of the cases. In the second dataset 11 , data on maternal characteristics were available for 2140 pregnancies, but measurements of biomarkers were carried out for only some of the patients (UtA‐PI, n = 1704; MAP, n = 1227; PlGF, n = 1316; PAPP‐A, n = 1926).…”

“…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.…”

“…Two datasets of twin pregnancies were used for this study. The first dataset was from the EVENTS study, which was conducted at 22 maternity hospitals in England, Spain, Bulgaria, Italy, Belgium and France between May 2017 and April 2019 12 . All women found at a routine visit at 11 + 0 to 13 + 6 weeks' gestation to have a dichorionic or monochorionic diamniotic twin pregnancy with two live fetuses and no major fetal abnormality were invited to participate in a screening study on the prediction of adverse pregnancy outcome, irrespective of their decision to participate in the progesterone trial or not.…”

“…The mean log 10 MoM values for first-trimester biomarkers in twin pregnancies that developed PE and the common standard deviations and correlations are shown in Table 2. The fitted regression relationships between gestational Table 1 Maternal and pregnancy characteristics of twin pregnancies in study population of EVENTS trial 12 and in combined dataset of EVENTS trial and previous study 11…”

“…In this study, we used data of twin pregnancies from the EVENTS (Early vaginal progesterone for the preVention of spontaneous prEterm birth iN TwinS) trial 12 . 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.…”