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. 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. 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. 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. Australian National Health and Medical Research Council.

中文翻译：

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早产时延迟脐带结扎、脐带挤奶和立即结扎脐带：系统评价和个体参与者数据荟萃分析

早产时的脐带夹紧策略可能会影响重要的健康结果。本研究的目的是比较延迟脐带结扎、脐带挤奶和立即结扎脐带在降低新生儿死亡率和早产发病率方面的效果。我们进行了系统回顾和个体参与者数据荟萃分析。我们检索了医学数据库和试验注册中心（从数据库建立到 2022 年 2 月 24 日；更新于 2023 年 6 月 6 日），寻找比较延迟（也称为延迟）脐带结扎、脐带挤奶和立即脐带结扎治疗早产的随机对照试验（<怀孕37周）。半随机或整群随机试验被排除在外。合格研究的作者被邀请加入 iCOMP 合作并共享个人参与者数据。所有数据均按照预先指定的标准进行检查、协调、重新编码并评估偏倚风险。主要结局是出院前死亡。我们进行了意向治疗的一阶段个体参与者数据荟萃分析，考虑了异质性，以检查整体治疗效果和预先指定的亚组分析。通过建议评估、制定和评估分级来评估证据的确定性。本研究已在 PROSPERO 注册，CRD42019136640。我们确定了 2369 条记录，其中 48 项随机试验提供了个体参与者数据，并且符合我们的初步分析条件。我们纳入了 6367 名婴儿的个人参与者数据（3303 名 [55%] 男性，2667 名 [45%] 女性，两名双性人，以及 395 名缺失数据）。与立即断脐相比，延迟断脐可减少出院前的死亡（比值比 [OR] 0·68 [95% CI 0·51–0·91]，高质量证据，20 项研究，n=3260，232 例死亡） ）。对于脐带挤奶与立即夹脐相比，没有发现明确的证据表明出院前死亡存在差异（OR 0·73 [0·44–1·20]，低确定性，18 项研究，n=1561，74 例死亡） 。同样，对于脐带挤奶与延迟脐带结扎相比，没有发现明确的证据表明出院前死亡存在差异（0·95 [0·59–1·53]，低确定性，12 项研究，n=1303，93 例死亡）。我们没有发现主要结局存在亚组差异的证据，包括孕龄、分娩类型、多胞胎、研究年份和围产期死亡率。这项研究提供了高质量的证据，表明与立即钳夹脐带相比，延迟脐带钳夹可以减少早产儿出院前的死亡。这种效应在多个参与者级别和试验级别亚组中似乎是一致的。这些结果将为国际治疗建议提供参考。澳大利亚国家健康和医学研究委员会。