Physiological-based cord clamping in very preterm infants: the Aeration, Breathing, Clamping 3 (ABC3) trial-study protocol for a multicentre randomised controlled trial

Ronny Knol, Emma Brouwer, Thomas van den Akker, Philip L J DeKoninck, Enrico Lopriore, Wes Onland, Marijn J Vermeulen, M Elske van den Akker-van Marle, Leti van Bodegom-Vos, Willem P de Boode, Anton H van Kaam, Irwin K M Reiss, Graeme R Polglase, G Jeroen Hutten, Sandra A Prins, Estelle E M Mulder, Christian V Hulzebos, Sam J van Sambeeck, Mayke E van der Putten, Inge A Zonnenberg, Stuart B Hooper, Arjan B Te Pas, Ronny Knol, Emma Brouwer, Thomas van den Akker, Philip L J DeKoninck, Enrico Lopriore, Wes Onland, Marijn J Vermeulen, M Elske van den Akker-van Marle, Leti van Bodegom-Vos, Willem P de Boode, Anton H van Kaam, Irwin K M Reiss, Graeme R Polglase, G Jeroen Hutten, Sandra A Prins, Estelle E M Mulder, Christian V Hulzebos, Sam J van Sambeeck, Mayke E van der Putten, Inge A Zonnenberg, Stuart B Hooper, Arjan B Te Pas

Abstract

Background: International guidelines recommend delayed umbilical cord clamping (DCC) up to 1 min in preterm infants, unless the condition of the infant requires immediate resuscitation. However, clamping the cord prior to lung aeration may severely limit circulatory adaptation resulting in a reduction in cardiac output and hypoxia. Delaying cord clamping until lung aeration and ventilation have been established (physiological-based cord clamping, PBCC) allows for an adequately established pulmonary circulation and results in a more stable circulatory transition. The decline in cardiac output following time-based delayed cord clamping (TBCC) may thus be avoided. We hypothesise that PBCC, compared to TBCC, results in a more stable transition in very preterm infants, leading to improved clinical outcomes. The primary objective is to compare the effect of PBCC on intact survival with TBCC.

Methods: The Aeriation, Breathing, Clamping 3 (ABC3) trial is a multicentre randomised controlled clinical trial. In the interventional PBCC group, the umbilical cord is clamped after the infant is stabilised, defined as reaching heart rate > 100 bpm and SpO2 > 85% while using supplemental oxygen < 40%. In the control TBCC group, cord clamping is time based at 30-60 s. The primary outcome is survival without major cerebral and/or intestinal injury. Preterm infants born before 30 weeks of gestation are included after prenatal parental informed consent. The required sample size is 660 infants.

Discussion: The findings of this trial will provide evidence for future clinical guidelines on optimal cord clamping management in very preterm infants at birth.

Trial registration: ClinicalTrials.gov NCT03808051. First registered on January 17, 2019.

Keywords: Cord clamping; Physiological-based cord clamping; Preterm infants; Randomised clinical trial; Study protocol.

Conflict of interest statement

The authors declare that they have no competing interests. The Concords used in this trial were either designed and built by LUMC (for 3 participating centres) or purchased from Concord Neonatal B.V. (Leiden, The Netherlands; for 6 participating centres). ABtP, SBH and AHvK are members of the Scientific Advisory Board of Concord Neonatal B.V., but have no financial relationship or support. The company has no role in the design of the study; in the collection, analysis or interpretation of the data; or in the writing of the manuscript.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
The Concord, a purpose-built resuscitation trolley developed at Leiden University Medical Centre (LUMC)
Fig. 2
Fig. 2
The physiological-based cord clamping procedure using the Concord, applied in the intervention group. Stabilisation of the infant is performed while the cord is intact and the cord is clamped only after the infant is stabilised
Fig. 3
Fig. 3
The standard time-based cord clamping procedure, applied in the control group. Cord clamping is performed immediately or delayed for 30–60 s and stabilisation of the infant is performed after the cord is clamped using a standard resuscitation table
Fig. 4
Fig. 4
Timeline schedule of eligibility screening, consent, enrolment, allocation, intervention and assessments at all time points. CA corrected age
Fig. 5
Fig. 5
Flow chart illustrating the randomisation plan showing expected numbers needed to include 330 participants in each arm

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