Background

Delayed cord clamping and umbilical cord milking provide placental transfusion to vigorous newborns. Delayed cord clamping in nonvigorous newborns may not be provided owing to a perceived need for immediate resuscitation. Umbilical cord milking is an alternative, as it can be performed more quickly than delayed cord clamping and may confer similar benefits.

Objective

We hypothesized that umbilical cord milking would reduce admission to the neonatal intensive care unit compared with early cord clamping in nonvigorous newborns born between 35 and 42 weeks’ gestation.

Study Design

This was a pragmatic cluster-randomized crossover trial of infants born at 35 to 42 weeks’ gestation in 10 medical centers in 3 countries between January 2019 and May 2021. The centers were randomized to umbilical cord milking or early cord clamping for approximately 1 year and then crossed over for an additional year or until the required number of consented subjects was reached. Waiver of consent as obtained in all centers to implement the intervention. Infants were eligible if nonvigorous at birth (poor tone, pale color, or lack of breathing in the first 15 seconds after birth) and were assigned to umbilical cord milking or early cord clamping according to their birth hospital randomization assignment. The baseline characteristics and outcomes were collected following deferred informed consent. The primary outcome was admission to the neonatal intensive care unit for predefined criteria. The main safety outcome was hypoxic-ischemic encephalopathy. Data were analyzed by the intention-to-treat concept.

Results

Among 16,234 screened newborns, 1780 were eligible (905 umbilical cord milking, 875 early cord clamping), and 1730 had primary outcome data for analysis (97% of eligible; 872 umbilical cord milking, 858 early cord clamping) either via informed consent (606 umbilical cord milking, 601 early cord clamping) or waiver of informed consent (266 umbilical cord milking, 257 early cord clamping). The difference in the frequency of neonatal intensive care unit admission using predefined criteria between the umbilical cord milking (23%) and early cord clamping (28%) groups did not reach statistical significance (modeled odds ratio, 0.69; 95% confidence interval, 0.41–1.14). Umbilical cord milking was associated with predefined secondary outcomes, including higher hemoglobin (modeled mean difference between umbilical cord milking and early cord clamping groups 0.68 g/dL, 95% confidence interval, 0.31–1.05), lower odds of abnormal 1-minute Apgar scores (Apgar ≤3, 30% vs 34%, crude odds ratio, 0.72; 95% confidence interval, 0.56–0.92); cardiorespiratory support at delivery (61% vs 71%, modeled odds ratio, 0.57; 95% confidence interval, 0.33–0.99), and therapeutic hypothermia (3% vs 4%, crude odds ratio, 0.57; 95% confidence interval, 0.33–0.99). Moderate-to-severe hypoxic-ischemic encephalopathy was significantly less common with umbilical cord milking (1% vs 3%, crude odds ratio, 0.48; 95% confidence interval, 0.24–0.96). No significant differences were observed for normal saline bolus, phototherapy, abnormal 5-minute Apgar scores (Apgar ≤6, 15.7% vs 18.8%, crude odds ratio, 0.81; 95% confidence interval, 0.62–1.06), or a serious adverse event composite of death before discharge.

Conclusion

Among nonvigorous infants born at 35 to 42 weeks’ gestation, umbilical cord milking did not reduce neonatal intensive care unit admission for predefined criteria. However, infants in the umbilical cord milking arm had higher hemoglobin, received less delivery room cardiorespiratory support, had a lower incidence of moderate-to-severe hypoxic-ischemic encephalopathy, and received less therapeutic hypothermia. These data may provide the first randomized controlled trial evidence that umbilical cord milking in nonvigorous infants is feasible, safe and, superior to early cord clamping.

中文翻译：

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无活力婴儿的脐带挤奶：整群随机交叉试验

 背景

延迟脐带结扎和脐带挤奶为精力旺盛的新生儿提供胎盘输血。由于认为需要立即复苏，因此可能不会对活力不足的新生儿进行延迟脐带结扎。脐带挤奶是一种替代方法，因为它比延迟断脐更快，并且可能带来类似的好处。

 客观的

我们假设，对于妊娠 35 至 42 周之间出生的无活力新生儿，与早期脐带结扎相比，脐带挤奶会减少进入新生儿重症监护室的人数。

 研究设计

这是一项实用的整群随机交叉试验，研究对象为 2019 年 1 月至 2021 年 5 月期间在 3 个国家的 10 个医疗中心出生的妊娠 35 至 42 周的婴儿。这些中心被随机分配进行脐带挤奶或早期脐带结扎，为期约 1 年，然后再交叉一年或直到达到所需的同意受试者数量。在所有中心获得实施干预措施的同意的放弃。如果婴儿出生时缺乏活力（语气差、颜色苍白或出生后 15 秒内呼吸困难），则符合资格，并根据出生医院随机分配进行脐带挤奶或早期脐带结扎。在延迟知情同意后收集基线特征和结果。主要结局是按照预定标准入住新生儿重症监护病房。主要安全性结局是缺氧缺血性脑病。通过意向治疗概念分析数据。

 结果

在 16,234 名接受筛查的新生儿中，1780 名符合资格（905 名脐带挤奶，875 名早期脐带夹闭），1730 名通过知情同意获得了用于分析的主要结果数据（97% 符合资格；872 名脐带挤奶，858 名早期脐带夹闭）（606脐带挤奶，601 早期脐带夹闭）或放弃知情同意（266 脐带挤奶，257 早期脐带夹闭）。使用预定义标准，脐带挤奶组 (23%) 和早期脐带结扎组 (28%) 入院新生儿重症监护病房的频率差异未达到统计显着性（模型比值比，0.69；95% 置信区间，0.41） –1.14）。脐带挤奶与预先确定的次要结果相关，包括较高的血红蛋白（脐带挤奶组和早期脐带夹闭组之间的建模平均差为 0.68 g/dL，95% 置信区间，0.31–1.05）、异常 1 分钟 Apgar 评分的几率较低（Apgar ≤3，30% vs 34%，粗比值比，0.72；95% 置信区间，0.56–0.92）；分娩时的心肺支持（61% vs 71%，模拟比值比，0.57；95% 置信区间，0.33–0.99）和治疗性低温（3% vs 4%，粗比值比，0.57；95% 置信区间，0.33– 0.99）。脐带挤奶中中度至重度缺氧缺血性脑病的发生率显着降低（1% vs 3%，粗比值比，0.48；95% 置信区间，0.24–0.96）。生理盐水推注、光疗、异常 5 分钟 Apgar 评分（Apgar ≤6，15.7% vs 18.8%，粗比值比，0.81；95% 置信区间，0.62–1.06）或严重不良事件没有观察到显着差异出院前死亡的复合情况。

 结论

在妊娠 35 至 42 周出生的无活力婴儿中，脐带挤奶并没有减少按照预定标准入住新生儿重症监护病房的情况。然而，脐带挤奶组的婴儿血红蛋白较高，接受的产房心肺支持较少，中重度缺氧缺血性脑病的发生率较低，接受的治疗性低温也较少。这些数据可能提供第一个随机对照试验证据，证明对无活力婴儿进行脐带挤奶是可行、安全的，并且优于早期脐带结扎。