Umbilical Cord Milking vs Delayed Cord Clamping and Associations with In-Hospital Outcomes among Extremely Premature Infants

Abstract

Objective: To compare in-hospital outcomes after umbilical cord milking vs delayed cord clamping among infants <29 weeks of gestation.

Study design: Multicenter retrospective study of infants born <29 weeks of gestation from 2016 to 2018 without congenital anomalies who received active treatment at delivery and were exposed to umbilical cord milking or delayed cord clamping. The primary outcome was mortality or severe (grade III or IV) intraventricular hemorrhage (IVH) by 36 weeks of postmenstrual age (PMA). Secondary outcomes assessed at 36 weeks of PMA were mortality, severe IVH, any IVH or mortality, and a composite of mortality or major morbidity. Outcomes were assessed using multivariable regression, incorporating mortality risk factors identified a priori, confounders, and center. A prespecified, exploratory analysis evaluated severe IVH in 2 gestational age strata, 22-24^6/7 and 25-28^6/7 weeks.

Results: Among 1834 infants, 23.6% were exposed to umbilical cord milking and 76.4% to delayed cord clamping. The primary outcome, mortality or severe IVH, occurred in 21.1% of infants: 28.3% exposed to umbilical cord milking and 19.1% exposed to delayed cord clamping, with an aOR that was similar between groups (aOR 1.45, 95% CI 0.93, 2.26). Infants exposed to umbilical cord milking had higher odds of severe IVH (19.8% umbilical cord milking vs 11.8% delayed cord clamping, aOR 1.70 95% CI 1.20, 2.43), as did the 25-28^6/7 week stratum (14.8% umbilical cord milking vs 7.4% delayed cord clamping, aOR 1.89 95% CI 1.22, 2.95). Other secondary outcomes were similar between groups.

Conclusions: This analysis of extremely preterm infants suggests that delayed cord clamping is the preferred practice for placental transfusion, as umbilical cord milking exposure was associated with an increase in the adverse outcome of severe IVH.

Trial registration: ClinicalTrials.gov: NCT00063063.

Keywords: Neonatal Research Network; intraventricular hemorrhage; placental transfusion.

Figure 1. Study Flow Diagram

Figure 2. Number of Infants Exposed to DCC or UCM per year (2016-2018) by Center

The y-axis shows percentage of preterm infants exposed to DCC (blue) or UCM (orange) and the x-axis shows the NRN centers. The years are differentiated by the shading which gets darker with each subsequent year (e.g., light blue represents the number of DCC exposed infants in 2016 and the darkest blue the number of DCC exposed infants in 2018). Centers A, B, C, D were no longer a part of the NRN centers in 2017 and 2018.

Figure 3. Raw and Adjusted Odds Ratio for Mortality or Severe Morbidity by Gestational Age.

Variables in the model include sex, antenatal steroids, positive pressure ventilation, intubation, resuscitation (PPV, intubation, chest compressions and/or epinephrine), race, 1-minute Apgar < = 4, antenatal hemorrhage, cesarean delivery, the interaction of GA and exposure to DCC or UCM, and center as a random effect. Only infants ≥24 weeks gestation were included in the model as there were no 22-week infants exposed to UCM and 100% of 23-week infants exposed to UCM experienced mortality or major morbidity. The four sites (A-D in Figure 1) that did not have exposed infants all three years were excluded from the model.