J Matern Fetal Neonatal Med. 2026 Dec;39(1):2708471. doi: 10.1080/14767058.2026.2708471. Epub 2026 Jul 29.
ABSTRACT
OBJECTIVE: To generate the evidence base, using national cohort data, to design a clinical trial evaluating whether cesarean section (CS) or vaginal birth (VB) offers better outcomes for very preterm infants.
BACKGROUND: Severe intraventricular hemorrhage (IVH) remains a major cause of death and brain injury amongst very preterm infants. Observational studies have suggested CS may reduce the risk, but it is not known which infants might benefit and whether a randomized trial, to generate robust evidence to guide clinical decisions, would be feasible.
METHODS: We examined births in England and Wales between 22 + 0 and 31 + 6 weeks' gestation (2012-2022; n = 74,423) and identified the infants that could take part in a trial. Three emulated target trials (ETTs) were constructed examining intended mode of birth (iVB vs iCS), across different populations, with confounding controlled by inverse probability weighting.
RESULTS: One in four(25.2%) very preterm infants could be considered for participation in a future trial. Infants born by CS had lower rates of severe IVH or death than those born by VB (4,319 (9.6%) vs 5,542 (18.7%)) (p < 0.001), although in the adjusted analyses using intended mode of birth the difference did not persist (e.g. ETT#1: 13.3% vs 13.0%, p = 0.609); except for non‑cephalic (breech) infants. Infants in a non-cephalic presentation in the iCS group had a significantly lower chance of death or sIVH in all three emulated trials (ETT#1, OR 0.73 (0.64-0.83); ETT#2, OR 0.65 (0.56-0.76); ETT#3, OR 0.81 (0.70-0.94).
CONCLUSIONS: Only a minority of very preterm births are realistically randomisable in a future trial, particularly babies in breech presentation who may benefit from a CS. An international multi-centre trial is needed to examine this question.
PMID:42527150 | DOI:10.1080/14767058.2026.2708471