Landmark Series
PREMOD2: cord milking vs delayed clamping
A trial stopped early for a safety signal, and what it found in extremely preterm and older preterm infants.
Source: Katheria A, et al. JAMA. 2019;322(19):1877–1886 · Pediatrics. 2023;152(6):e2023063113.
The question
Is umbilical cord milking at least as safe as delayed cord clamping for preterm infants, judged by death or severe intraventricular hemorrhage (IVH)?
The study
- Planned as a noninferiority randomized trial in preterm infants (ClinicalTrials.gov NCT03019367).
- First report (JAMA 2019): infants born at 23–31 weeks in 9 centers across 4 countries. Enrollment was stopped at the first interim analysis after an imbalance in severe IVH between the groups. 474 infants were analyzed post hoc.
- Second report (Pediatrics 2023): the trial continued in older preterm infants. 1,019 infants born at 28–32 weeks at 19 centers in 4 countries, with a 1% noninferiority margin.
What they found
22% vs 6%Severe IVH at 23–27 weeks, milking vs delayed clamping
1.4% vs 1.4%Severe IVH or death at 28–32 weeks
- 2019, 23–31 weeks: death or severe IVH occurred in 12% with cord milking vs 8% with delayed clamping, a difference that was not statistically significant. But severe IVH alone was higher with cord milking (8% vs 3%).
- The signal came from the youngest babies. At 23–27 weeks, severe IVH occurred in 22% with cord milking vs 6% with delayed clamping.
- 2023, 28–32 weeks: severe IVH or death occurred in 7 of 511 (1.4%) with cord milking and 7 of 508 (1.4%) with delayed clamping.
Where the evidence stops
- The 2019 results come from a post hoc analysis of a trial that was stopped early. The authors say this precludes definitive conclusions.
- At 28–32 weeks, the rates were identical, but noninferiority could not be formally shown at the 1% margin. The authors estimate about 3,000 infants would be needed.
- Two-year neurodevelopmental outcomes were planned as a follow-up. The reports above cover the initial hospitalization.
References
- Katheria A, Reister F, Essers J, et al. Association of Umbilical Cord Milking vs Delayed Umbilical Cord Clamping With Death or Severe Intraventricular Hemorrhage Among Preterm Infants. JAMA. 2019;322(19):1877–1886. doi:10.1001/jama.2019.16004 · PubMed 31742630
- Katheria A, Szychowski J, Carlo WA, et al. Umbilical Cord Milking Versus Delayed Cord Clamping in Infants 28 to 32 Weeks: A Randomized Trial. Pediatrics. 2023;152(6):e2023063113. doi:10.1542/peds.2023-063113 · PubMed 37941523
Independent educational content, not medical advice. Not affiliated with or endorsed by the AAP. Summaries reflect the published papers; read the originals before changing practice.
