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Deferred cord clamping, cord milking, and immediate cord clamping at preterm birth : a systematic review and individual participant data meta-analysis

Seidler, Anna Lene ; Aberoumand, Mason ; Hunter, Kylie E. ; Barba, Angie ; Libesman, Sol ; Williams, Jonathan G. ; Shrestha, Nipun ; Aagerup, Jannik ; Sotiropoulos, James X. and Montgomery, Alan A. , et al. (2023) In The Lancet 402(10418). p.2209-2222
Abstract

Background: Umbilical cord clamping strategies at preterm birth have the potential to affect important health outcomes. The aim of this study was to compare the effectiveness of deferred cord clamping, umbilical cord milking, and immediate cord clamping in reducing neonatal mortality and morbidity at preterm birth. Methods: We conducted a systematic review and individual participant data meta-analysis. We searched medical databases and trial registries (from database inception until Feb 24, 2022; updated June 6, 2023) for randomised controlled trials comparing deferred (also known as delayed) cord clamping, cord milking, and immediate cord clamping for preterm births (<37 weeks' gestation). Quasi-randomised or cluster-randomised... (More)

Background: Umbilical cord clamping strategies at preterm birth have the potential to affect important health outcomes. The aim of this study was to compare the effectiveness of deferred cord clamping, umbilical cord milking, and immediate cord clamping in reducing neonatal mortality and morbidity at preterm birth. Methods: We conducted a systematic review and individual participant data meta-analysis. We searched medical databases and trial registries (from database inception until Feb 24, 2022; updated June 6, 2023) for randomised controlled trials comparing deferred (also known as delayed) cord clamping, cord milking, and immediate cord clamping for preterm births (<37 weeks' gestation). Quasi-randomised or cluster-randomised trials were excluded. Authors of eligible studies were invited to join the iCOMP collaboration and share individual participant data. All data were checked, harmonised, re-coded, and assessed for risk of bias following prespecified criteria. The primary outcome was death before hospital discharge. We performed intention-to-treat one-stage individual participant data meta-analyses accounting for heterogeneity to examine treatment effects overall and in prespecified subgroup analyses. Certainty of evidence was assessed with Grading of Recommendations Assessment, Development, and Evaluation. This study is registered with PROSPERO, CRD42019136640. Findings: We identified 2369 records, of which 48 randomised trials provided individual participant data and were eligible for our primary analysis. We included individual participant data on 6367 infants (3303 [55%] male, 2667 [45%] female, two intersex, and 395 missing data). Deferred cord clamping, compared with immediate cord clamping, reduced death before discharge (odds ratio [OR] 0·68 [95% CI 0·51–0·91], high-certainty evidence, 20 studies, n=3260, 232 deaths). For umbilical cord milking compared with immediate cord clamping, no clear evidence was found of a difference in death before discharge (OR 0·73 [0·44–1·20], low certainty, 18 studies, n=1561, 74 deaths). Similarly, for umbilical cord milking compared with deferred cord clamping, no clear evidence was found of a difference in death before discharge (0·95 [0·59–1·53], low certainty, 12 studies, n=1303, 93 deaths). We found no evidence of subgroup differences for the primary outcome, including by gestational age, type of delivery, multiple birth, study year, and perinatal mortality. Interpretation: This study provides high-certainty evidence that deferred cord clamping, compared with immediate cord clamping, reduces death before discharge in preterm infants. This effect appears to be consistent across several participant-level and trial-level subgroups. These results will inform international treatment recommendations. Funding: Australian National Health and Medical Research Council.

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author collaboration
organization
publishing date
type
Contribution to journal
publication status
published
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in
The Lancet
volume
402
issue
10418
pages
2209 - 2222
publisher
Elsevier
external identifiers
  • pmid:37977169
  • scopus:85176959671
ISSN
0140-6736
DOI
10.1016/S0140-6736(23)02468-6
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2023 Elsevier Ltd
id
4d4f7699-7db0-461a-b78f-05db197f2a8d
date added to LUP
2023-12-14 14:32:07
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2024-04-27 09:45:06
@article{4d4f7699-7db0-461a-b78f-05db197f2a8d,
  abstract     = {{<p>Background: Umbilical cord clamping strategies at preterm birth have the potential to affect important health outcomes. The aim of this study was to compare the effectiveness of deferred cord clamping, umbilical cord milking, and immediate cord clamping in reducing neonatal mortality and morbidity at preterm birth. Methods: We conducted a systematic review and individual participant data meta-analysis. We searched medical databases and trial registries (from database inception until Feb 24, 2022; updated June 6, 2023) for randomised controlled trials comparing deferred (also known as delayed) cord clamping, cord milking, and immediate cord clamping for preterm births (&lt;37 weeks' gestation). Quasi-randomised or cluster-randomised trials were excluded. Authors of eligible studies were invited to join the iCOMP collaboration and share individual participant data. All data were checked, harmonised, re-coded, and assessed for risk of bias following prespecified criteria. The primary outcome was death before hospital discharge. We performed intention-to-treat one-stage individual participant data meta-analyses accounting for heterogeneity to examine treatment effects overall and in prespecified subgroup analyses. Certainty of evidence was assessed with Grading of Recommendations Assessment, Development, and Evaluation. This study is registered with PROSPERO, CRD42019136640. Findings: We identified 2369 records, of which 48 randomised trials provided individual participant data and were eligible for our primary analysis. We included individual participant data on 6367 infants (3303 [55%] male, 2667 [45%] female, two intersex, and 395 missing data). Deferred cord clamping, compared with immediate cord clamping, reduced death before discharge (odds ratio [OR] 0·68 [95% CI 0·51–0·91], high-certainty evidence, 20 studies, n=3260, 232 deaths). For umbilical cord milking compared with immediate cord clamping, no clear evidence was found of a difference in death before discharge (OR 0·73 [0·44–1·20], low certainty, 18 studies, n=1561, 74 deaths). Similarly, for umbilical cord milking compared with deferred cord clamping, no clear evidence was found of a difference in death before discharge (0·95 [0·59–1·53], low certainty, 12 studies, n=1303, 93 deaths). We found no evidence of subgroup differences for the primary outcome, including by gestational age, type of delivery, multiple birth, study year, and perinatal mortality. Interpretation: This study provides high-certainty evidence that deferred cord clamping, compared with immediate cord clamping, reduces death before discharge in preterm infants. This effect appears to be consistent across several participant-level and trial-level subgroups. These results will inform international treatment recommendations. Funding: Australian National Health and Medical Research Council.</p>}},
  author       = {{Seidler, Anna Lene and Aberoumand, Mason and Hunter, Kylie E. and Barba, Angie and Libesman, Sol and Williams, Jonathan G. and Shrestha, Nipun and Aagerup, Jannik and Sotiropoulos, James X. and Montgomery, Alan A. and Gyte, Gillian M.L. and Duley, Lelia and Askie, Lisa M.}},
  issn         = {{0140-6736}},
  language     = {{eng}},
  number       = {{10418}},
  pages        = {{2209--2222}},
  publisher    = {{Elsevier}},
  series       = {{The Lancet}},
  title        = {{Deferred cord clamping, cord milking, and immediate cord clamping at preterm birth : a systematic review and individual participant data meta-analysis}},
  url          = {{http://dx.doi.org/10.1016/S0140-6736(23)02468-6}},
  doi          = {{10.1016/S0140-6736(23)02468-6}},
  volume       = {{402}},
  year         = {{2023}},
}