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PREMOD2 trial (cord milking against delayed clamping)

A trial in babies born at 23 to 31 weeks that compared milking the cord toward the baby with waiting before clamping. It was stopped early because severe bleeding in the brain was more common with cord milking.

  • Study
  • In this atlas

Overview

Design
Multicentre randomised parallel-group trial at nine university and private medical centres, planned as a noninferiority trial; the registry lists triple masking. Infants born at 23 to 31 weeks were assigned to umbilical cord milking or delayed cord clamping. Enrolment ran from June 2017 to September 2018, with final follow-up in December 2018 (abstract).
Phase
Not applicable
Enrolled
  • 1,201 participants (ClinicalTrials.gov gives no unit for the count) (enrolled count) (Premature Infants Receiving Milking or Delayed Cord Clamping: PREMOD2, retrieved )
  • 540 infants (randomized count) (Association of Umbilical Cord Milking vs Delayed Umbilical Cord Clamping With Death or Severe Intraventricular Hemorrhage Among Preterm Infants, retrieved )
  • 474 infants (enrolled and completed the trial) (enrolled count) (Association of Umbilical Cord Milking vs Delayed Umbilical Cord Clamping With Death or Severe Intraventricular Hemorrhage Among Preterm Infants, retrieved )
Sponsor
Not recorded
Funder
Not recorded
Registry
  • NCT NCT03019367
Started
(actual) (Premature Infants Receiving Milking or Delayed Cord Clamping: PREMOD2, retrieved )
Primary completion
(actual) (Premature Infants Receiving Milking or Delayed Cord Clamping: PREMOD2, retrieved )
Completion
(actual) (Premature Infants Receiving Milking or Delayed Cord Clamping: PREMOD2, retrieved )
Countries
Canada, Germany, Ireland, United States (Premature Infants Receiving Milking or Delayed Cord Clamping: PREMOD2, retrieved )
Care setting
Nine university and private medical centres in four countries. (Association of Umbilical Cord Milking vs Delayed Umbilical Cord Clamping With Death or Severe Intraventricular Hemorrhage Among Preterm Infants, retrieved )
Registry status
  • “COMPLETED” (U.S. National Library of Medicine (ClinicalTrials.gov), retrieved )
Stopped early
Enrollment stopped early, date not reported. A safety signal, an imbalance in the number of severe intraventricular haemorrhage events between the groups, was seen at the first interim analysis, and the data and safety monitoring board recommended stopping enrolment. The registry lists the study as completed. (Association of Umbilical Cord Milking vs Delayed Umbilical Cord Clamping With Death or Severe Intraventricular Hemorrhage Among Preterm Infants, retrieved )

Technical summary

Noninferiority randomised trial reported in JAMA 2019 (ClinicalTrials.gov NCT03019367): 540 infants randomised, 474 enrolled and completed (236 cord milking, 238 delayed clamping), against a plan of 750 per group. A safety signal at the first interim analysis stopped enrolment, so the planned noninferiority analysis could not be done and a post hoc comparison was made. The registry record lists the status as completed and an actual enrolment of 1201; this record keeps the registry figures beside the paper's without reconciling them. The harm signal belongs to cord milking, not to delayed clamping.

Arms

  • Umbilical cord milking

    Intervention None named

    Umbilical cord milking. 236 infants were in this group.

  • Delayed cord clamping

    Intervention Delayed umbilical cord clamping

    Delayed umbilical cord clamping. 238 infants were in this group.

Findings

No findings are published for this study.

Claims and evidence

Context Infants born at 23 to 31 weeks of gestation (PREMOD2 trial)

Recipient
Newborn
Population
Preterm infants born at 23 to 31 weeks of gestation. 540 infants were randomised and 474 (88%) were enrolled and completed the trial (236 cord milking, 238 delayed clamping). Enrolment stopped early, short of the planned 750 per group.
Care setting
Nine university and private medical centres.
Geography
Four countries; the abstract does not name them. ClinicalTrials.gov lists the United States, Canada, Germany and Ireland.
Life stage
Preterm infants born at 23 to 31 weeks of gestation
Gestational age
23 weeks 0 days (161 days) to 31 weeks 6 days (223 days), measured at birth
Postnatal age
Not reported
Follow-up
Death or severe intraventricular haemorrhage; final follow-up December 2018.
Eligibility: 1 inclusion criterion; exclusion criteria not stated
Included
  • Preterm infants born at 23 to 31 weeks of gestation
Excluded
None stated

  • Safety Interventional Certainty not assessed

    In PREMOD2, babies born at 23 to 31 weeks who received umbilical cord milking had more severe intraventricular haemorrhage (bleeding in the brain) than babies who had delayed cord clamping: 8% (20 of 236) against 3% (8 of 238), a risk difference of 5% (95% CI 1% to 9%; P = .02). At 23 to 27 weeks it was 22% (20 of 93) against 6% (5 of 89). Enrolment was stopped early because of this signal. The combined outcome of death or severe haemorrhage was 12% (29 of 236) against 8% (20 of 238), a difference that was not statistically significant. The signal belongs to cord milking; delayed clamping was the comparison group.

    Applies to Newborn
    • Preterm infants born at 23 to 31 weeks of gestation. 540 infants were randomised and 474 (88%) were enrolled and completed the trial (236 cord milking, 238 delayed clamping). Enrolment stopped early, short of the planned 750 per group.
    • Nine university and private medical centres.
    • Four countries; the abstract does not name them. ClinicalTrials.gov lists the United States, Canada, Germany and Ireland.
    • Preterm infants born at 23 to 31 weeks of gestation
    • Gestational age 23 weeks 0 days to 31 weeks 6 days, measured at birth
    • Postnatal age Not reported
    Follow-up Death or severe intraventricular haemorrhage; final follow-up December 2018.
    Certainty method
    Not assessed
    Limitations
    The trial stopped early, so the planned noninferiority analysis could not be done and the reported comparison is post hoc. The authors state that the early stop and the post hoc nature of the analyses preclude definitive conclusions. The subgroup interaction by gestational age was reported for severe haemorrhage only. 474 of 540 randomised infants were enrolled and completed the trial. Only the abstract was read.
    Last checked
    Not recorded
    Next evidence check due
    Not scheduled
    Sources and citations (4)

    1. Supports Association of Umbilical Cord Milking vs Delayed Umbilical Cord Clamping With Death or Severe Intraventricular Hemorrhage Among Preterm Infants

      Publication · JAMA · Edition PubMed record (abstract and bibliographic data) from NCBI E-utilities. The full text and the version of record were not fetched. · Published 2019-11-19 · DOI: 10.1001/jama.2019.16004 · PMID: 31742630 · PMCID: PMC6865839

      Locator
      Abstract, RESULTS, sentences 2 to 4
      How it applies
      Death or haemorrhage, severe haemorrhage and the 23 to 27 week subgroup.
      Retrieved
      Source effective date
      Not reported
      Source state
      Current
      Snapshot hash
      e5152bcbf3053fc59c8c97bca2f0878f9bd691a61d3c7d0ded773352b17efe07
      Reuse basis
      PubMed record fetched through NCBI E-utilities. Only the hash of the bytes is kept, because publisher copyright may apply to the abstract (https://pubmed.ncbi.nlm.nih.gov/disclaimer/). Short factual quotations under 25 words, with the citation.

    2. Supports Association of Umbilical Cord Milking vs Delayed Umbilical Cord Clamping With Death or Severe Intraventricular Hemorrhage Among Preterm Infants

      Publication · JAMA · Edition PubMed record (abstract and bibliographic data) from NCBI E-utilities. The full text and the version of record were not fetched. · Published 2019-11-19 · DOI: 10.1001/jama.2019.16004 · PMID: 31742630 · PMCID: PMC6865839

      Locator
      Abstract, DESIGN, SETTING, AND PARTICIPANTS, sentences 3 to 4
      How it applies
      The safety signal that stopped enrolment.
      Retrieved
      Source effective date
      Not reported
      Source state
      Current
      Snapshot hash
      e5152bcbf3053fc59c8c97bca2f0878f9bd691a61d3c7d0ded773352b17efe07
      Reuse basis
      PubMed record fetched through NCBI E-utilities. Only the hash of the bytes is kept, because publisher copyright may apply to the abstract (https://pubmed.ncbi.nlm.nih.gov/disclaimer/). Short factual quotations under 25 words, with the citation.

    3. Background Association of Umbilical Cord Milking vs Delayed Umbilical Cord Clamping With Death or Severe Intraventricular Hemorrhage Among Preterm Infants

      Publication · JAMA · Edition PubMed record (abstract and bibliographic data) from NCBI E-utilities. The full text and the version of record were not fetched. · Published 2019-11-19 · DOI: 10.1001/jama.2019.16004 · PMID: 31742630 · PMCID: PMC6865839

      Locator
      Abstract, INTERVENTIONS and RESULTS sentence 1
      How it applies
      Group sizes.
      Retrieved
      Source effective date
      Not reported
      Source state
      Current
      Snapshot hash
      e5152bcbf3053fc59c8c97bca2f0878f9bd691a61d3c7d0ded773352b17efe07
      Reuse basis
      PubMed record fetched through NCBI E-utilities. Only the hash of the bytes is kept, because publisher copyright may apply to the abstract (https://pubmed.ncbi.nlm.nih.gov/disclaimer/). Short factual quotations under 25 words, with the citation.

    4. Background Association of Umbilical Cord Milking vs Delayed Umbilical Cord Clamping With Death or Severe Intraventricular Hemorrhage Among Preterm Infants

      Publication · JAMA · Edition PubMed record (abstract and bibliographic data) from NCBI E-utilities. The full text and the version of record were not fetched. · Published 2019-11-19 · DOI: 10.1001/jama.2019.16004 · PMID: 31742630 · PMCID: PMC6865839

      Locator
      Abstract, CONCLUSIONS AND RELEVANCE
      How it applies
      The authors' own limits on the finding.
      Retrieved
      Source effective date
      Not reported
      Source state
      Current
      Snapshot hash
      e5152bcbf3053fc59c8c97bca2f0878f9bd691a61d3c7d0ded773352b17efe07
      Reuse basis
      PubMed record fetched through NCBI E-utilities. Only the hash of the bytes is kept, because publisher copyright may apply to the abstract (https://pubmed.ncbi.nlm.nih.gov/disclaimer/). Short factual quotations under 25 words, with the citation.

Record details

Record id
maternal:premod2-trial
Content hash
cf5e3c0a19ba02bb6fc701b9ca6a888dcf25c7bbb3261d5a7d03d7a6d45697fa