Balloon catheters versus vaginal prostaglandins for labour induction (CPI Collaborative): an individual participant data meta-analysis of randomised controlled trials.

BACKGROUND: Induction of labour is one of the most common obstetric interventions globally. Balloon catheters and vaginal prostaglandins are widely used to ripen the cervix in labour induction. We aimed to compare the effectiveness and safety profiles of these two induction methods. METHODS: We did an individual participant data meta-analysis comparing balloon catheters and vaginal prostaglandins for cervical ripening before labour induction. We systematically identified published and unpublished randomised controlled trials that completed data collection between March 19, 2019, and May 1, 2021, by searching the Cochrane Library, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, and PubMed. Further trials done before March 19, 2019, were identified through a recent Cochrane review. Data relating to the combined use of the two methods were not included, only data from women with a viable, singleton pregnancy were analysed, and no exclusion was made based on parity or membrane status. We contacted authors of individuals trials and participant-level data were harmonised and recoded according to predefined definitions of variables. Risk of bias was assessed with the ROB2 tool. The primary outcomes were caesarean delivery, indication for caesarean delivery, a composite adverse perinatal outcome, and a composite adverse maternal outcome. We followed the intention-to-treat principle for the main analysis. The primary meta-analysis used two-stage random-effects models and the sensitivity analysis used one-stage mixed models. All models were adjusted for maternal age and parity. This meta-analysis is registered with PROSPERO (CRD42020179924). FINDINGS: Individual participant data were available from 12 studies with a total of 5460 participants. Balloon catheters, compared with vaginal prostaglandins, did not lead to a significantly different rate of caesarean delivery (12 trials, 5414 women; crude incidence 27·0%; adjusted OR [aOR] 1·09, 95% CI 0·95-1·24; I2=0%), caesarean delivery for failure to progress (11 trials, 4601 women; aOR 1·20, 95% CI 0·91-1·58; I2=39%), or caesarean delivery for fetal distress (10 trials, 4441 women; aOR 0·86, 95% CI 0·71-1·04; I2=0%). The composite adverse perinatal outcome was lower in women who were allocated to balloon catheters than in those allocated to vaginal prostaglandins (ten trials, 4452 neonates, crude incidence 13·6%; aOR 0·80, 95% CI 0·70-0·92; I2=0%). There was no significant difference in the composite adverse maternal outcome (ten trials, 4326 women, crude incidence 22·7%; aOR 1·02, 95% CI 0·89-1·18; I2=0%). INTERPRETATION: In induction of labour, balloon catheters and vaginal prostaglandins have comparable caesarean delivery rates and maternal safety profiles, but balloon catheters lead to fewer adverse perinatal events. FUNDING: Australian National Health and Medical Research Council and Monash Health Emerging Researcher Fellowship.

Embedding a COVID-19 group sequential clinical trial within an ongoing trial: lessons from an unusual experience.

The Cape-Covid trial is an embedded clinical trial within the ongoing Cape-Cod trial. The Covid-19 pandemic appeared while we were conducting a randomized trial assessing the effectiveness of corticosteroids in severe community-acquired pneumonia. We took advantage of this ongoing trial to embed a sub-trial assessing hydrocortisone in SARS-CoV-2 infected patients. In this manuscript, we wish to share our experience when we needed to make fast and robust methodological decisions during the Covid-19 pandemic in a two weeks period of time.

First trimester uterine artery Doppler, sFlt-1 and PlGF to predict preeclampsia in a high-risk population.

OBJECTIVE: The study aims to evaluate the accuracy of combining uterine artery Doppler (UAD), PlGF and sFlt-1 in the first trimester for preeclampsia screening. METHODS: Prospectively enrolled women at high risk of preeclampsia were included. Transabdominal UAD measurements and serum biomarkers were collected between 11 and 13 weeks of gestation in three university hospitals and in one general hospital. The main outcome was preeclampsia. UAD parameters and biomarker levels among women with preeclampsia were compared with those of women in the unaffected group in univariate and multivariate analyses. RESULTS: Out of 226 women included from May 2007 to January 2011, 27 (11.9%) women developed preeclampsia. Among women affected by preeclampsia, the lowest pulsatility index was higher (p = 0.02), bilateral notching was more frequent (p = 0.01), and PlGF was lower (p < 0.001). No significant differences were observed for other indicators. The multivariate model, adjusted for laboratory and sonographic indicators, had an area under the curve (AUC) estimated at 0.76, which was not significantly different from the AUC of the univariate model adjusted only for PlGF (p = 0.7). CONCLUSION: In a high-risk population, PlGF in the first trimester is useful for predicting preeclampsia, but neither sFlt-1 nor any UAD indices improved the prediction of preeclampsia.