Extrauterine Placental Perfusion and Oxygenation in Infants With Very Low Birth Weight: A Randomized Clinical Trial

Abstract

Importance: An extrauterine placental perfusion (EPP) approach for physiological-based cord clamping (PBCC) may support infants with very low birth weight (VLBW) during transition without delaying measures of support.

Objective: To test whether EPP in resuscitation of infants with VLBW results in higher hematocrit levels, better oxygenation, or improved infant outcomes compared with delayed cord clamping (DCC).

Design, setting, and participants: This nonblinded, single-center randomized clinical trial was conducted at a tertiary care neonatal intensive care unit. Infants with a gestational age greater than 23 weeks and birth weight less than 1500 g born by cesarean delivery between May 2019 and June 2021 were included. Data were analyzed from October through December 2021.

Intervention: Prior to cesarean delivery, participants were allocated to receive EPP or DCC. In the EPP group, infant and placenta, connected by an intact umbilical cord, were detached from the uterus and transferred to the resuscitation unit. Respiratory support was initiated while holding the placenta over the infant. The umbilical cord was clamped when infants showed regular spontaneous breathing, stable heart rates greater than 100 beats/min, and adequate oxygen saturations. In the DCC group, cords were clamped 30 to 60 seconds after birth before infants were transferred to the resuscitation unit, where respiratory support was started.

Main outcomes and measure: The primary outcome was the mean hematocrit level in the first 24 hours after birth. Secondary prespecified outcome parameters comprised oxygenation during transition and short-term neonatal outcome.

Results: Among 60 infants randomized and included, 1 infant was excluded after randomization; there were 29 infants in the EPP group (mean [SD] gestational age, 27 weeks 6 days [15.0 days]; 14 females [48.3%]) and 30 infants in the DCC group (mean [SD] gestational age, 28 weeks 1 day [17.1 days]; 17 females [56.7%]). The mean (SD) birth weight was 982.8 (276.6) g and 970.2 (323.0) g in the EPP and DCC group, respectively. Intention-to-treat analysis revealed no significant difference in mean hematocrit level (mean difference [MD], 2.1 percentage points; [95% CI, -2.2 to 6.4 percentage points]). During transition, infants in the EPP group had significantly higher peripheral oxygen saturation as measured by pulse oximetry (adjusted MD at 5 minutes, 15.3 percentage points [95% CI, 2.0 to 28.6 percentage points]) and regional cerebral oxygen saturation (adjusted MD at 5 minutes, 11.3 percentage points [95% CI, 2.0 to 20.6 percentage points]). Neonatal outcome parameters were similar in the 2 groups.

Conclusions and relevance: This study found that EPP resulted in similar hematocrit levels as DCC, with improved cerebral and peripheral oxygenation during transition. These findings suggest that EPP may be an alternative procedure for PBCC in infants with VLBW.

Trial registration: ClinicalTrials.gov Identifier: NCT03916159.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Kribs reported receiving honoraria from Chiesi outside the submitted work. No other disclosures were reported.

Figures

Figure 1.. Study Flowchart

DCC indicates delayed cord clamping; EPP, extrauterine placental perfusion.

Figure 2.. Subgroup Analyses for Gestational Age, Sex, and Mode of Pregnancy

DCC indicates delayed cord clamping; EPP, extrauterine placental perfusion.

Figure 3.. Secondary Outcomes During Neonatal Transition

Values were picked at the precise time indicated from data of continuous monitoring and are presented as means and 95% CIs (whiskers). A mixed model for repeated measures with fixed effects for group, time, interaction group × time, and a first-order autoregressive–structured covariance matrix over time was fitted. Comparisons between groups at specific times were based on pairwise contrasts of marginal means, with 95% CIs and P values. DCC indicates delayed cord clamping; EPP, extrauterine placental perfusion; Fio2, fraction of inspired oxygen; Spo2, oxygen saturation as measured by pulse oximetry; rcSo2, regional cerebral oxygen saturation.