Umbilical Cord Milking in Nonvigorous Infants: A Cluster-Randomized Crossover Trial

Approximately 6 million infants each year require resuscitation at birth. Requiring this intervention is associated with higher risk of hypoxic-ischemic encephalopathy (HIE), cerebral palsy, attention-deficit or hyperactive disorder, autism, neonatal stroke, and death. In infants needing resuscitation, optimal cord management is essential to enhance placental transfusion. Delayed cord clamping (DCC) is used to enable placental transfusion in vigorous infants, but in nonvigorous infants—those who are limp, pale, or have minimal or no breathing—early cord clamping (ECC) is recommended. Another intervention for nonvigorous infants requiring resuscitation is umbilical cord milking (UCM). UCM can improve heart rate, blood pressure, urine output, cerebral oxygenation, and hemoglobin levels, and prevent anemia. In addition, it can achieve placental transfusion without delaying resuscitation as with DCC and can be completed as quickly as ECC. No harm has been observed in studies involving UCM. Despite these benefits, studies are lacking on optimal cord management strategies in nonvigorous infants requiring resuscitation. The aim of this study was to examine whether UCM reduces admission to the neonatal intensive care unit (NICU) versus ECC in nonvigorous newborns. This was a pragmatic, cluster-randomized, crossover trial conducted at 10 hospitals in the United States, Canada, and Poland. Included were viable infants delivered between January 2019 and May 2021 who were between 35 and 42 weeks of gestation and nonvigorous at birth. Nonvigorous was defined as poor tone, pallor, or lack of breathing in the first 15 seconds after birth. Excluded were infants with major congenital or chromosomal anomalies, cardiac defects except small ventricular septal defects, complete placental abruption or cutting through the placenta at delivery, monochorionic multiples, cord anomalies, and the presence of nonreducible nuchal cord. Hospitals were randomized 1:1 to UCM or ECC in period 1 from January 2019 to January 2020, then crossed over to the other intervention during period 2 from February 2020 to May 2021. The primary outcome was NICU admission related to the intervention in the first 24 hours of life. The safety outcome was HIE. A total of 1730 infants were included in the analysis with 872 in the UCM group and 858 in the ECC group. The difference in the frequency of NICU admission was not statistically significant, with 23% in the UCM group and 28% in the ECC group (odds ratio [OR], 0.69; 95% confidence interval [CI], 0.41–1.14). In comparison to the ECC group, UCM was associated with lower odds of abnormal 1-minute Apgar scores (Apgar ≤3, 30% vs 34%; crude OR, 0.72; 95% CI, 0.56–0.92), receipt of cardiorespiratory support in the delivery room (61% vs 71%; modeled OR, 0.57; 95% CI, 0.33–0.99), and therapeutic hypothermia (3% vs 4%; crude OR, 0.58; 95% CI, 0.33–0.99). In addition, there was no significant difference in any grade of HIE, although moderate-to-severe HIE was less common in the UCM group (1% vs 3%; crude OR, 0.48; 95% CI, 0.24–0.96). The UCM group also had increased hemoglobin (modeled mean difference, 0.68 g/dL; 95% CI, 0.31–1.05) and peak serum bilirubin (modeled mean difference, 1.4 mg/dL; 95% CI, 0.5–2.2). In nonvigorous newborns needing resuscitation, UCM was not associated with a reduction in NICU admissions compared with ECC. UCM was associated with a decrease in cardiorespiratory support in the delivery room, fewer cases of moderate-to-severe HIE, lower use of therapeutic hypothermia, and higher hemoglobin.