Methods
PTB, sPTB
REGRESSION, SECONDARY, PRETERM BIRTH, VAGINA
This is a prospective multicenter cohort study involving singleton pregnant women screened during a multicenter randomized controlled trial entitled “Pessary plus Progesterone for Preventing Preterm Birth” (P5 trial; Registration no. RBR-3t8prz, approved by the Brazilian National Review Board/CONEP—number 1.055.555) [The standard technique followed the P5 study protocol and the Fetal Medicine Foundation orientation for CL measurement. Briefly, with the woman in dorsal lithotomy position and empty bladder, a TVU probe was introduced inside the vagina until the anterior fornix avoiding pressure. A sagittal view of the cervix, including the edge, identified the internal and external ostium. Calipers were used to measure the linear distance (in mm) between the external and internal ostium. Funneling and Sludge were described. All data from the screening phase were included in the online database Gsdoctor. Every participating center stored their ultrasound images with the CL measurements to confirm that all centers were correctly applying the TVU technique.All women with a CL ≤ 30 mm who did not have exclusion criteria and who accepted to participate in the trial were randomized into two groups: 200 mg/day vaginal progesterone or 200 mg/day vaginal progesterone + cervical pessary. Randomized women have delivery information in the P5 database. Women with CL > 30 mm had their childbirth and postnatal information collected from hospital medical registers and added to the P5 database.The sample for this analysis considered all women with CL ≤ 30 mm receiving only progesterone and a random selection of women with CL > 30 mm, keeping the populational distribution of cervical length. Women using cervical pessary were excluded since we did not have clear information of how it could influence the gestational age at birth and this treatment is not routine for preventing PTB. Considering that progesterone is an established evidence-based treatment for preventing PTB and women are encouraged to use it if they have a short CL identified in the mid-trimester, we included the P5 trial progesterone group in our cohort sample. The P5 trial total sample screened 13.7% women with CL ≤ 30 mm and 86.3% of CL > 30 mm. To maintain the same CL distribution, we projected the progesterone group to correspond to 13.7% of CL ≤ 30 mm for our analysis. To complete our final sample and reach the complementary 86.3% of CL > 30 mm, we selected singleton women with CL > 30 mm using a random model. We excluded women who had received a cervical pessary, multiple gestations and those with incomplete gestational outcome data. We kept very similar baseline characteristics percentages found in the total of singleton pregnant that participated in the P5 trial screening, maintaining homogeneity and avoiding any possible selection bias (Additional file Descriptive statistical analysis was performed for demographic characteristics, expressed as means and percentages. Logistic regression was used to estimate odds ratios for baseline characteristics, gestational age and CL at measurement. A multivariate logistic regression analysis was performed to estimate adjusted odds ratio for different gestational ages.For our primary outcome, receiver operating characteristic (ROC) curve analysis was performed to identify the most effective cutoff point to predict a PTB (< 37 weeks). Our secondary outcomes were ROC curve analysis to identify the most effective cutoff points to predict sPTB at different gestational ages (< 37, < 34, < 32 and < 28 weeks). 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). We calculated the number needed to screen (NNS) to detect one true positive sPTB < 34 in women with CL ≤ 25 mm. Considering a recent individual patient data (IPD)-metanalysis that included randomized clinical trials involving women with CL ≤ 25 mm treated with vaginal progesterone, the number needed to treat (NNT) with vaginal progesterone to prevent one sPTB < 34 weeks is 18 [