This was an observational study comparing two consecutive cohorts of pregnant women submitted to IoL with CRB associated with oral misoprostol, starting either concurrently at catether insertion or sequentially after its removal.
Patients were followed at the Obstetrics and Gynecology University Department of Mauriziano Umberto I Hospital in Turin: a retrospective cohort of women admitted from January 2021 to September 2023, and treated with CRB followed sequentially by oral misoprostol, was compared to a prospective cohort of patients undergoing concurrent use of the two methods, with data collected collected from October 2023 to May 2024 following the change in the Department’s protocol for IoL according to the most recent recommendations [10–13, 22].
The inclusion criteria were: women with singleton pregnancy at term, with cephalic presentation of the fetus, unfavourable cervix (Bishop’s score ≤ 4) and unruptured membranes at admission, submitted to IoL by CRB and oral misoprostol either concurrently or sequentially.
The exclusion criteria were: previous hysterotomy and other contraindications to the use of prostaglandins, fetal malpresentation, estimated fetal weight > 4500 g, intrauterine fetal death, abnormal placental insertion, spontaneous pre-labour rupture of membranes (PROM) at admission.
Data were retrieved through a review of hospital medical records.
According to the protocol used in our Unit, based on national guidelines [23], all women underwent at admission a 30 minutes cardiotocographic non-stress test (NST), digital examination with Bishop’s score (BS) assessment [24] and office transabdominal ultrasound for evaluation of fetal presentation and amniotic fluid.
Patients included in the study presented with an unfavourable cervix at obstetric examination, with a BS ≤ 4, requiring cervical ripening; this procedure was carried out with Cook® double-balloon catether (Cook Cervical Ripening Balloon; Cook Medical, Bloomington, Indiana, USA), inflated with 80 ml saline for both the uterine and the vaginal balloon. The catether was placed in the evening and left in place for 12–18 hours; removal was anticipated in case of active labour or cervical dilation causing spontaneous expulsion of the device, rupture of membranes, uterine hyperstimulation or antepartum vaginal bleeding.
In the retrospective cohort, IoL was continued with oral misoprostol (in galenic formulation) given at the dose of 50 mcg at 5 hours intervals, for a maximum of 4 administrations, starting sequentially after CRB removal. In the prospective cohort, oral misoprostol was administrated concurrently with CRB, starting with a first 25 mcg dose at insertion, followed after 3 hours by further 50 mcg doses for a maximum of 3 administration at 5 hours intervals [22].
When obstetric examination was favourable (BS ≥ 7 with adequate fetal head station) after CRB removal, IoL was continued by means of rupture of membranes (RoM) followed by intravenous oxytocin infusion if adequate uterine contractile activity did not start within 2 hours. Oxytocin was administered at infusion speed starting from 2.5 mIU/min and increasing by 2.5-5 mIU/min each 30 minutes, with a maximum velocity of 30 mIU/min, and continued until the onset of active labour. If those procedures were not possible after the completion of misoprostol administration, IoL was continued with vaginal dinoprostone gel (Prepidil®, Pfizer, New York, USA) given at the dose of 1–2 mg, at 6 hours intervals, for a maximum of 2 administrations.
Active labour was defined by regular uterine contractile activity (2–4 contractions every 10 minutes) with cervical effacement and dilation ≥ 5 cm. Failure of induction, requiring CS, was defined when active labour was not achieved despite the completion of prostaglandin administration followed by RoM and intravenous oxytocin admnistered for at least 15 hours [23].
The study population encompassed two cohort of patients (CRB associated with concurrent versus sequential oral misoprostol administration), for whom we compared data from clinical records and partographs regarding anamnestic and obstetric features and the course of IoL and labour.
The primary endpoint was the rate of VD. Secondary endpoints were: rates of achievement of active labour, VD within 24 hours after the start of IoL, operative vaginal delivery (OVD); intervals of time between start of IoL, active labour and delivery, duration of labour stages; rates of adverse events including obstetric intervention by CS or OVD for suspected intrapartum fetal distress, uterine tachysystole (defined as more than 5 contractions in 10 minutes), meconium-stained amniotic fluid, intrapartum fever or intra-amniotic infection (IAI), post-partum hemorrhage (PPH, defined as blood loss > 500 ml in VD and > 1000 ml in CS), uterine rupture, 3rd or 4th degree perineal tears, maternal severe morbidity causing intensive care unit admission or death; duration of hospitalization; neonatal outcomes including APGAR scores at 1 and 5 minutes after delivery, birth weight, and a composite outcome for overall perinatal complications (including APGAR score < 7 at 5 minutes, shoulder dystocia, respiratory distress syndrome, skin lacerations, meconium aspiration syndrome, neonatal intensive care unit admission, death).
Statistical analysis
Continuous variables were expressed as mean +/- standard deviation; categorical variables were expressed as n (%). Univariate analysis was performed for continuous variables with a two-tailed t-test for independent samples with unequal variances, and categorical variables with a Fisher’s test in case of binary outcome, or chi-squared test for multiple outcomes. A difference was considered statistically significant when it was associated with a two-tailed P < 0.05. Sample size was calculated for detecting a reduction in 25% for the CS rate, corresponding to the difference between the proportion in women with unfavourable cervix undergoing IoL in our Center [25, 26], and the ones reported in Literature for concurrent CRB and oral misoprostol admnistration [16–18, 21]; considering a power of 80%, an overall number of about 65 patients was deemed as necessary.
Statistical analyses were performed using SPSS 22.0 (Statistical Package for the Social Sciences) software (IBM Corp. Released 2013. IBM SPSS Statistics for Windows, Version 22.0. Armonk, NY: IBM Corp).