Mode of birth and risk of death or severe intraventricular hemorrhage in very preterm infants: a national cohort and emulated target trial (the PRECIOUS (PREterm caesarean/vaginal birth and IVH/OUtcomeS) study)

Reeve, Nicola, Barnett, Jane, Cutter, Judith, Daniel, Rhian ORCID: https://orcid.org/0000-0001-5649-9320, Gale, Chris, Siassakos, Dimitrios and Odd, David ORCID: https://orcid.org/0000-0002-6416-4966 2026. Mode of birth and risk of death or severe intraventricular hemorrhage in very preterm infants: a national cohort and emulated target trial (the PRECIOUS (PREterm caesarean/vaginal birth and IVH/OUtcomeS) study). The Journal of Maternal-Fetal & Neonatal Medicine 39 (1) , 2708471. 10.1080/14767058.2026.2708471

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Schools > Medicine
Publisher:	Taylor and Francis Group
ISSN:	1476-7058
Date of First Compliant Deposit:	6 August 2026
Date of Acceptance:	20 July 2026
Last Modified:	06 Aug 2026 09:00
URI:	https://orca.cardiff.ac.uk/id/eprint/188752

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