Journal Club Papers
Head-to-head: balloon catheters vs vaginal prostaglandins for induction of labour
Balloon catheters versus vaginal prostaglandins for labour induction (CPI Collaborative): an individual participant data meta-analysis of randomised controlled trials. Jones et al. Lancet, November 12 2022. doi: 10.1016/S0140-6736(22)01845-1
Induction of labour is common, with balloon catheters and vaginal prostaglandins often used to ripen the cervix as part of the induction process. Until now, research comparing these two methods has been of low to moderate quality. To overcome this the authors undertook a meta-analysis using individual participant data (as opposed to relying on aggregate data published in each paper) to provide a robust, reliable cohort to compare clinical outcomes of balloon catheters versus vaginal prostaglandins.
- Published and unpublished randomised controlled trials that compared methods of induction of labour were included. 56 trials met the inclusion criteria, and of these, 12 trials provided individual level participant data for 5,460 participants.
- Included participants had viable, singleton pregnancies and underwent induction of labour with a single or double balloon catheter or vaginal prostaglandins (PGE2 or low dose PGE1).
- The primary outcomes were:
1) delivery by caesarean section, including further analyses of likelihood of caesarean for fetal distress and failure to progress,
2) a composite of adverse perinatal outcomes (Apgar score <7 at 5 minutes, arterial umbilical cord pH <7.1, admission to NICU, severe respiratory compromise, neonatal infection, neonatal death, stillbirth)
3) a composite of adverse maternal outcomes (admission to ICU, maternal infection, severe postpartum haemorrhage >1000mL, maternal death).
- For caesarean section there was no difference in rates between balloon catheters and vaginal prostaglandins including for fetal distress (adjusted odd ratio (aOR) 0·86, 95% CI 0·71–1·04) and for failure to progress (aOR aOR 1·20, 95% CI 0·91–1·58)
- The use of a balloon catheter was associated with a 20% reduction in the likelihood of adverse perinatal outcomes when compared with prostaglandins (aOR 0.80, 95% CI: 0.70-0.92). This reduction was primarily driven by a reduction in neonatal acidosis (measured by arterial umbilical cord pH <7.1, aOR 0.72, 95% CI 0.53-0.98), and neonatal infection (aOR 0.63, 95% CI: 0.45-0.89).
- For maternal outcomes, there were no significant differences between balloon catheters and vaginal prostaglandins (aOR 1·02, 95% CI 0·89–1·18)
- There were lower rates of instrumental deliveries performed due to fetal distress among the balloon catheter group compared with the prostaglandin group (aOR 0.66, 95% CI: 0.49-0.88). This was a secondary outcome.
The main strength of this meta-analysis is the use of individual participant data, enabling a direct comparison of outcomes. Data were however unavailable for 44 of the eligible trials, though many of these excluded trials were small and from more than 10 years ago.
While the choice of induction of labour method should be individualised, this research has established that balloon catheters confer lower rates of neonatal adverse outcomes compared with vaginal prostaglandins.
Tighter or less tight glycaemic targets for women with gestational diabetes mellitus for reducing maternal and perinatal morbidity: A stepped-wedge, cluster-randomised trial. Crowther et al. PLOS MED, September 8 2022. doi: 10.1371/journal.pmed.1004087
Concerns about adverse growth and neurodevelopmental dose-related side effects of antenatal steroids have given rise to the concept that the current dose used clinically may be too high. And it may be possible that a lower dose could still provide short-term neonatal benefits, but lessen the risk of longer-term childhood problems. This study sought to investigate whether a half dose of betamethasone is non-inferior to the full dose for preventing respiratory distress syndrome (RDS).
This was a randomised, multicentre, double-blind, placebo-controlled, non-inferiority trial across 37 level three referral perinatal centres in France.
- Women were eligible for inclusion if they were pregnant with a singleton fetus at risk of preterm delivery and had already received a first injection of antenatal betamethasone before 32 weeks’ gestation (ie first dose of celestone, 11.4 grams).
- Between January 2017 – October 2019, 3,244 women were randomly assigned to receive either a half dose (saline placebo) or second full dose of betamethasone (5.4mg/mL betamethasone acetate plus 6.0mg/mL betamethasone sodium phosphate) 24 hours after their first dose. Randomisation was stratified by gestational age (<28 weeks or ≥28 weeks).
- The primary outcome was the need for exogenous intratracheal surfactant within 48 hours after birth.
Primary outcome: Exogenous intratracheal surfactant was required in 20.0% of infants in the half-dose group and 17.5% of infants in the full-dose group (risk difference 2.4% [95% CI 0.3-5.2]); non-inferiority was not shown (take note of the double negative!).
- The findings were similar in intention-to-treat and per-protocol analysis groups.
- There were no differences in secondary outcomes between the groups including rates of neonatal death, any respiratory distress syndrome; grade 3-4 intraventricular haemorrhage, stage ≥2 necrotising enterocolitis, severe retinopathy of prematurity, or bronchopulmonary dysplasia.
The interpretation is that a half-dose betamethasone regimen was associated with a 2.4% absolute increase in the need for exogenous intratracheal surfactant within the first 48 hours of life. There was also a trend towards more severe RDS (needing mechanical ventilation) with the half-dose regimen. However, it was not associated with a higher incidence of neonatal mortality or major prematurity-related complications, although it likely lacked the power needed to study these outcomes (i.e. needed to be a bigger study).
This study does not support a single dose of betamethasone for preterm infants at risk of preterm birth.
The authors also highlight the importance of weighing these results against potential childhood outcomes. they point towards their planned follow-up analysis at five years of age.
It will be interesting to see whether the dose reduction has any impact on childhood outcomes because most of these findings were short-term neonatal outcomes. The risk/benefit equation could shift if childhood developmental outcomes are better in the single dose arm (which could be the case, given the findings of the first paper in this JCOTR edition).
Monofilament suture versus braided suture thread to improve pregnancy outcomes after vaginal cervical cerclage (C-STICH): A pragmatic, randomised, controlled, phase 3, superiority trial. Hodgetts Morton et al. Lancet, October 22 2022. doi: 10.1016/S0140-6736(22)01808-6
This study sought to investigate the effectiveness of suture type (monofilament vs. braided) in preventing pregnancy loss. Previously, observational data has suggested that monofilament sutures may be more effective in preventing pregnancy loss. Braided sutures may also be associated with a greater risk of infection. Conversely, there are concerns about monofilament sutures becoming embedded and difficult to remove.
- This study recruited women at high risk of preterm birth who were offered a cervical cerclage. The study population thus included women with singleton pregnancies and a history of mid-trimester pregnancy loss, preterm birth, or previous cerclage or a shortened cervix on ultrasound. Women were recruited from 75 obstetric centres throughout the UK.
- Women were randomised to receive either monofilament suture (N=1,025) or braided suture (N=1,024). The type of cerclage placed (Shirodkar or McDonald) was at clinician discretion.
- The primary outcome was pregnancy loss (defined as miscarriage, stillbirth, or neonatal death in the first week of life).
Monofilament suture did not reduce the rate of pregnancy loss when compared with braided suture.
- Pregnancy loss occurred in 8.0% of the monofilament group vs 7.6% of the braided suture group (RR 1.05, 95% CI 0.79-1.40).
- No differences were found in any of the neonatal outcomes assessed. However, the trial was not powered to examine these outcomes.
Monofilament suture was associated with a significantly lower risk of maternal sepsis (42% reduction) and chorioamnionitis (55% reduction).
- Maternal sepsis occurred in 3.9% of the monofilament group vs 6.8% of the braided suture group (RR 0.58, 95% CI 0.40-0.82).
- The increased risk of maternal sepsis did not confer an increased risk of sepsis to the neonate (11.2% in monofilament group, vs 12.5% in braided suture group).
- Chorioamnionitis occurred in 2.7% of the monofilament group vs 6.0% of the braided suture group (RR 0.45, 95% CI 0.29-0.71).
- Longer-term neonatal outcomes were not assessed.
Monofilament was, however, associated with an increased risk of removal complications.
- Complications occurred in 56.5% of the monofilament group vs 42.2% of the braided suture group (RR 1.25, 95% CI 1.15-1.36). Removal complications included cervical tears (2.3% vs <1.0%), need for anaesthetic (40.9% vs 31.8%), or difficulty removing the suture (31.2% vs 14.6%).
- The high rate of complications in both groups may be explained by fact that cerclages were generally placed by experienced clinicians but not necessarily removed by clinicians with extensive experience.
The authors suggest that braided sutures remains a viable alternative when performing cerclage, given that the increased risk of maternal sepsis did not lead to an increased risk of neonatal sepsis.
The issue of infection risk merits further reflection. Compared with monofilament, braided suture was associated with a doubled risk of maternal sepsis and chorioamnionitis (but not neonatal sepsis). While these are secondary outcomes, the findings are biologically plausible. Conversely, the downsides to monofilament suture seem limited to difficulties in its removal, leading to regional anaesthesia so it could be properly removed. The JCOTR team will let you decide for yourselves which to ask for, as part of your next MacDonalds/Shirodkar adventure (but we know which one we will be reaching for…).