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).

Authors

Nicola Reeve, Jane Barnett, Judith Cutter, Rhian Daniel, Chris Gale, Dimitrios Siassakos, David Odd

Published in

The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians. Volume 39. Issue 1. Pages 2708471. Epub Jul 29, 2026.

Abstract

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.
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.
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.
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).
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
Bibliographic data and abstract were imported from PubMed on 30 Jul 2026.

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