O1035: Umbilical Cord Milking in Non-vigorous Infants: A Pragmatic Cluster-randomized Crossover Trial

Background: Current standard of care in non-vigorous newborns is early cord clamping (ECC). Umbilical cord milking (UCM) may be superior to ECC in late preterm and term newborns who are not vigorous at birth. We tested whether UCM, compared to ECC, reduces NICU admission risk based on predefined criteria.

Methods: A pragmatic cluster-randomized crossover trial of infants born at 35-42 weeks gestation from 10 medical centers in 3 countries delivered between January 2019 and April 2021. Infants were eligible if non-vigorous at birth (poor tone, pale color, or lack of breathing in the first 15 seconds after birth) and were assigned to UCM or ECC according to the randomization assignment of their birth hospital. A waiver of consent was obtained from all sites to implement the intervention and collect NICU admission and death before discharge data. Baseline characteristics and outcomes were collected following informed consent. The primary outcome was admission to the NICU for predefined criteria. The main safety outcome was hypoxic-ischemic encephalopathy (HIE). Serious adverse events monitored included death before discharge, polycythemia, hyperbilirubinemia requiring an exchange transfusion, severe intraventricular hemorrhage (IVH), and pulmonary hemorrhage. Data were analyzed by intention to treat.

Results: Among 16,234 screened newborns, 1780 were eligible, 1730 had primary outcome data for analysis (97% of eligible; 872 UCM, 858 ECC) via informed or waived consent. NICU admissions did not differ significantly between UCM (23%) and ECC (28%) groups (OR 0.69, 95% CI 0.41-1.14). Modeled least-squares mean differences were modestly but significantly higher in the UCM group compared with the ECC group for 1- and 5-minute Apgar scores (0.50 95% CI 0.04-0.95, 0.19 95% CI 0.02-0.35, respectively). Therapeutic hypothermia (2.5 vs. 4.3% OR 0.57, 95% CI 0.33-0.99) and moderate-severe HIE (3 vs 1.5 %, OR 0.48, 95% CI 0.24-0.96) occurred less often in the UCM group. Among a subset of neonates, modeled least-squares mean differences were significantly higher in the UCM group compared with the ECC group for hemoglobin and peak serum bilirubin (0.68 95% CI 0.31-1.05, 1.35 95% CI 0.48-2.22, respectively). No differences were observed for mean blood pressure or length of hospitalization. No safety (death, intraventricular hemorrhage, or exchange transfusion) difference was observed (0.1% UCM, 0.7% ECC).

Conclusion: Among non-vigorous infants born at 35-42 weeks gestation, UCM did not reduce NICU admission for predefined criteria compared to ECC. Infants in the UCM arm had higher 1 and 5-minute Apgar scores, a lower need for respiratory support in the delivery room, less moderate to severe HIE, and a lower need for therapeutic hypothermia. UCM should be considered for non-vigorous infants born at 35-42 weeks.