Methods
fetal malformation, PTB, cholestasis, sPTB
VAGINAL BLEEDING, CONTRACTIONS, LIVER DISEASE, PREGNANCY COMPLICATIONS, CHOLESTASIS, PLACENTA PREVIA, THROMBOEMBOLISM, REGRESSION, DILATION, PRETERM BIRTH

We performed an ancillary analysis using a cohort strategy analysis of all twin pregnancies included in the P5 Trial (Pessary Plus Progesterone to Prevent Preterm Birth Study – Trial registration RBR-3t8prz, approved by the Brazilian National Review Board/CONEP – number 1.055.555) to describe Brazilian populational curves.
The P5 Trial was a multicenter, randomized, controlled trial involving 17 institutions (nine states in three regions: South, Southeast, and Northeast of Brazil) that compared the effectiveness of vaginal progesterone alone versus progesterone plus cervical pessary in women with short cervix. The study was coordinated by the University of Campinas from July 2015 to March 2019. A TVU screening program using a GE Logiq C5 (GE HealthCare. Chicago, IL, EUA) equipment or similar with a 5 to 9MHz transvaginal probe was offered as part of standard care for all women attending the ultrasound department during routine second trimester ultrasonographic examinations between 18 0/7 and 22 6/7 weeks. Women received information about the TVU technique and P5 study and all provided written informed consent. Sociodemographic characteristics, obstetric history, and current pregnancy information were previously collected.Exclusion criteria for CL measurement were related to symptoms or pregnancy complications: painful contractions, vaginal bleeding, cerclage during current pregnancy before the screening, ruptured membranes diagnosed before screening, severe liver disease, cholestasis during this pregnancy, previous or current thromboembolism, placenta previa, cervical dilation greater than 1 cm, monoamniotic twin pregnancy, higher order multiple pregnancies (triplets or higher), major fetal malformation in at least one fetus, and stillbirth. For this analysis, we also excluded singleton gestations. The information on pregnancies was accessed using an online database from the screening phase of the P5 trial. Considering P5 trial interventions, 80 women had CL ≤ 30mm and 71 accepted to participate in the RCT, where 71 of the patients received progesterone and 43 also received a cervical pessary.All participating sonographers received previous training in CL measurement according to the Fetal Medicine Foundation program, as well as additional training regarding the volume measurement developed by the University of Campinas's ultrasound department.Describing the TVU technique briefly, after emptying the bladder, the woman was placed in the dorsal lithotomy position. The TVU probe was introduced until the anterior fornix region, avoiding extra pressure on the cervix, which can artificially increase the CL. A sagittal view of the cervix, showing the endocervical mucosa, was used to properly identify the internal and external ostium (os). Sludge and funneling were also evaluated and described, if present.
Descriptive statistical analysis was performed for demographic characteristics, expressed as means and percentages. Logistic regression was used to estimate odds ratio (OR) for baseline characteristics, gestational age, and CL measurements. Mean, median, and percentiles of CL (P5, P10, P25, P50, P75, P90, and P95) were obtained for the descriptive analysis. The receiver operating characteristics (ROC) curve analysis was performed to identify the most effective cutoff point to predict a sPTB (< 37 weeks). We also used the ROC curve analysis to identify the most effective cutoff points to predict overall PTB (< 37) and sPTB at different gestational ages (< 37 and > 34 weeks – later PTB; < 34–PTB; and < 28 weeks – extreme PTB). We calculated sensitivity, specificity, negative (NPV) and positive predictive values (PPV), and likelihood ratios (LR). The Kaplan-Meyer survival curves were used to analyze time to delivery, considering CL intervals (≤ 10 mm, 10–15 mm, 15–20 mm, 20–25 mm, 25–30 mm, 30–35 mm, 35–40 mm, and > 40 mm). A
