JOURNAL CLUB · LANDMARK TRIAL
Umbilical cord milking vs delayed cord clamping in preterm infants (PREMOD2)
Katheria A, Reister F, Essers J, et al. JAMA. 2019;322(19):1877-1886. A multicentre, non-inferiority randomised controlled trial, stopped early.
SEVERE IVH -
STOPPED EARLY
No difference in the composite
Death or severe IVH did not differ significantly (UCM 12% vs DCC 8%; risk difference 0.04, 95% CI -0.02 to 0.09, p=0.16).
More severe IVH with milking
UCM had a higher rate of severe IVH (8% vs 3%; risk difference 0.05, 95% CI 0.01 to 0.09, p=0.02).
Worst in the most preterm
The excess severe IVH was seen mostly in infants born at 23 to 27 weeks.
Stopped early for harm
Powered for 1500 but terminated at 474 on the DSMB’s advice for the IVH signal; the planned non-inferiority analysis could not be done, so results are post hoc.
WHY THIS MATTERS
- Placental transfusion - extra blood from the cord - benefits preterm infants
- Cord milking was adopted as a faster alternative when resuscitation is urgent
- But milking delivers a rapid bolus, which could raise cerebral blood flow and IVH risk
- It entered practice before being properly tested for safety
- Severe IVH is a major cause of harm in the very preterm, so safety matters
STRENGTHS
- A dedicated head-to-head RCT of two placental-transfusion methods
- Multicentre and international
- Outcome assessment was blinded, even though the intervention was not
- Resuscitation was standardised with videotaped review
- A safety signal important enough to change guidance
LIMITATIONS
- Stopped early for harm - early termination can exaggerate effects and precludes firm conclusions
- The planned non-inferiority analysis could not be done; results are post hoc
- Unmasked intervention (performance bias), though assessors were blinded
- A large number of post-randomisation exclusions (66 of 540)
- Underpowered against its 1500 target
Practice implications
Placental transfusion helps preterm babies, and delayed cord clamping is the established way to give it. Cord milking was adopted as a quicker alternative, but PREMOD2 found more severe IVH with milking than with delayed clamping, especially below 28 weeks - enough for the trial to be stopped early. The primary composite (death or severe IVH) was not significantly different and the findings are post hoc, but the safety signal was strong enough that ACOG now recommends against cord milking below 28 weeks. Prefer delayed cord clamping for placental transfusion in the very preterm; reserve milking, if used at all, for more mature babies and per your local guideline. For the non-vigorous baby who needs immediate resuscitation, prioritise effective ventilation.
When would you choose delayed cord clamping versus cord milking, and at what gestation?
How much should a post-hoc analysis of an early-terminated trial change your practice?
What is the plausible mechanism linking cord milking to IVH?
How do you provide placental transfusion when a very preterm baby needs immediate resuscitation?
JAMA 2019 ATTENDING A BIRTH
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Take-home message: PREMOD2 compared two ways of giving preterm babies placental blood - umbilical cord milking vs delayed cord clamping - and was stopped early because milking was linked to more severe IVH (8% vs 3%), especially below 28 weeks. The primary composite of death or severe IVH was not significantly different and the analysis is post hoc, so it is a safety signal rather than proof of harm - but a strong enough one that guidance now advises against cord milking in the very preterm. Delayed cord clamping remains the preferred method.
For educational purposes only. Journal club appraisal - figures paraphrased from the published trial and later reviews; read the full article for complete data. Always align practice to your local guidelines.