Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Trials
Published in: Trials 1/2022

Open Access 01-12-2022 | Study protocol

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

Authors: 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

Published in: Trials | Issue 1/2022

Login to get access

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.
Appendix
Available only for authorised users
Literature
1.
Blencowe H, Cousens S, Chou D, Oestergaard M, Say L, Moller AB, et al. Born too soon: the global epidemiology of 15 million preterm births. Reprod Health. 2013;10(Suppl 1):S2.PubMedPubMedCentralCrossRef
2.
Harrison MS, Goldenberg RL. Global burden of prematurity. Semin Fetal Neonatal Med. 2016;21(2):74–9.PubMedCrossRef
3.
Stoll BJ, Hansen NI, Bell EF, Walsh MC, Carlo WA, Shankaran S, et al. Trends in care practices, morbidity, and mortality of extremely preterm neonates, 1993–2012. JAMA. 2015;314(10):1039–51.PubMedPubMedCentralCrossRef
4.
DeMauro SB, Roberts RS, Davis P, Alvaro R, Bairam A, Schmidt B, et al. Impact of delivery room resuscitation on outcomes up to 18 months in very low birth weight infants. J Pediatr. 2011;159(4):546–50.PubMedCrossRef
5.
Mian Q, Cheung PY, O’Reilly M, Barton SK, Polglase GR, Schmolzer GM. Impact of delivered tidal volume on the occurrence of intraventricular haemorrhage in preterm infants during positive pressure ventilation in the delivery room. Arch Dis Child Fetal Neonatal Ed. 2019;104(1):F57–62.PubMedCrossRef
6.
Oei JL, Finer NN, Saugstad OD, Wright IM, Rabi Y, Tarnow-Mordi W, et al. Outcomes of oxygen saturation targeting during delivery room stabilisation of preterm infants. Arch Dis Child Fetal Neonatal Ed. 2018;103(5):F446–54.PubMedCrossRef
7.
Polglase GR, Miller SL, Barton SK, Kluckow M, Gill AW, Hooper SB, et al. Respiratory support for premature neonates in the delivery room: effects on cardiovascular function and the development of brain injury. Pediatr Res. 2014;75(6):682–8.PubMedCrossRef
8.
Schmolzer GM, Te Pas AB, Davis PG, Morley CJ. Reducing lung injury during neonatal resuscitation of preterm infants. J Pediatr. 2008;153(6):741–5.PubMedCrossRef
9.
Tarnow-Mordi W, Morris J, Kirby A, Robledo K, Askie L, Brown R, et al. Delayed versus immediate cord clamping in preterm infants. N Engl J Med. 2017;377(25):2445–55.PubMedCrossRef
10.
Madar J, Roehr CC, Ainsworth S, Ersdal H, Morley C, Rudiger M, et al. European Resuscitation Council Guidelines 2021: newborn resuscitation and support of transition of infants at birth. Resuscitation. 2021;161:291–326.PubMedCrossRef
11.
Sweet DG, Carnielli V, Greisen G, Hallman M, Ozek E, Te Pas A, et al. European Consensus Guidelines on the Management of Respiratory Distress Syndrome - 2019 update. Neonatology. 2019;115(4):432–50.PubMedCrossRef
12.
Bhatt S, Alison BJ, Wallace EM, Crossley KJ, Gill AW, Kluckow M, et al. Delaying cord clamping until ventilation onset improves cardiovascular function at birth in preterm lambs. J Physiol. 2013;591(8):2113–26.PubMedPubMedCentralCrossRef
13.
Goos TG, Rook D, van der Eijk AC, Kroon AA, Pichler G, Urlesberger B, et al. Observing the resuscitation of very preterm infants: are we able to follow the oxygen saturation targets? Resuscitation. 2013;84(8):1108–13.PubMedCrossRef
14.
Phillipos E, Solevag AL, Aziz K, van Os S, Pichler G, O’Reilly M, et al. Oxygen saturation and heart rate ranges in very preterm infants requiring respiratory support at birth. J Pediatr. 2017;182:41–6.PubMedCrossRef
15.
Polglase GR, Dawson JA, Kluckow M, Gill AW, Davis PG, Te Pas AB, et al. Ventilation onset prior to umbilical cord clamping (physiological-based cord clamping) improves systemic and cerebral oxygenation in preterm lambs. PLoS ONE. 2015;10(2):e0117504.PubMedPubMedCentralCrossRef
16.
White LN, Thio M, Owen LS, Kamlin CO, Sloss S, Hooper SB, et al. Achievement of saturation targets in preterm infants <32 weeks’ gestational age in the delivery room. Arch Dis Child Fetal Neonatal Ed. 2017;102(5):F423–7.PubMedCrossRef
17.
Fogarty M, Osborn DA, Askie L, Seidler AL, Hunter K, Lui K, et al. Delayed vs early umbilical cord clamping for preterm infants: a systematic review and meta-analysis. Am J Obstet Gynecol. 2018;218(1):1–18.PubMedCrossRef
18.
Rabe H, Gyte GM, Diaz-Rossello JL, Duley L. Effect of timing of umbilical cord clamping and other strategies to influence placental transfusion at preterm birth on maternal and infant outcomes. Cochrane Database Syst Rev. 2019;9:CD003248.PubMed
19.
Yao AC, Moinian M, Lind J. Distribution of blood between infant and placenta after birth. Lancet. 1969;2(7626):871–3.PubMedCrossRef
20.
Bhatt S, Polglase GR, Wallace EM, Te Pas AB, Hooper SB. Ventilation before umbilical cord clamping improves the physiological transition at birth. Front Pediatr. 2014;2:113.PubMedPubMedCentralCrossRef
21.
Dawson JA, Kamlin CO, Vento M, Wong C, Cole TJ, Donath SM, et al. Defining the reference range for oxygen saturation for infants after birth. Pediatrics. 2010;125(6):e1340–7.PubMedCrossRef
22.
Dawson JA, Kamlin CO, Wong C, te Pas AB, O’Donnell CP, Donath SM, et al. Oxygen saturation and heart rate during delivery room resuscitation of infants <30 weeks’ gestation with air or 100% oxygen. Arch Dis Child Fetal Neonatal Ed. 2009;94(2):F87-91.PubMedCrossRef
23.
Christensen RD, Baer VL, Del Vecchio A, Henry E. Unique risks of red blood cell transfusions in very-low-birth-weight neonates: associations between early transfusion and intraventricular hemorrhage and between late transfusion and necrotizing enterocolitis. J Matern Fetal Neonatal Med. 2013;26(Suppl 2):60–3.PubMedCrossRef
24.
Patel RM, Knezevic A, Shenvi N, Hinkes M, Keene S, Roback JD, et al. Association of red blood cell transfusion, anemia, and necrotizing enterocolitis in very low-birth-weight infants. JAMA. 2016;315(9):889–97.PubMedPubMedCentralCrossRef
25.
Samuels N, van de Graaf RA, de Jonge RCJ, Reiss IKM, Vermeulen MJ. Risk factors for necrotizing enterocolitis in neonates: a systematic review of prognostic studies. BMC Pediatr. 2017;17(1):105.PubMedPubMedCentralCrossRef
26.
27.
Duley L, Dorling J, Pushpa-Rajah A, Oddie SJ, Yoxall CW, Schoonakker B, et al. Randomised trial of cord clamping and initial stabilisation at very preterm birth. Arch Dis Child Fetal Neonatal Ed. 2018;103(1):F6–14.PubMedCrossRef
28.
Katheria A, Poeltler D, Durham J, Steen J, Rich W, Arnell K, et al. Neonatal resuscitation with an intact cord: a randomized clinical trial. J Pediatr. 2016;178:75–80.PubMedPubMedCentralCrossRef
29.
Pratesi S, Montano S, Ghirardello S, Mosca F, Boni L, Tofani L, et al. Placental Circulation Intact Trial (PCI-T)-resuscitation with the placental circulation intact vs. cord milking for very preterm infants: a feasibility study. Front Pediatr. 2018;6:364.PubMedPubMedCentralCrossRef
30.
Winter J, Kattwinkel J, Chisholm C, Blackman A, Wilson S, Fairchild K. Ventilation of preterm infants during delayed cord clamping (VentFirst): a pilot study of feasibility and safety. Am J Perinatol. 2017;34(2):111–6.PubMedCrossRef
31.
Blank DA, Badurdeen S, Omar FKC, Jacobs SE, Thio M, Dawson JA, et al. Baby-directed umbilical cord clamping: a feasibility study. Resuscitation. 2018;131:1–7.PubMedCrossRef
32.
Hooper SB, Polglase GR, te Pas AB. A physiological approach to the timing of umbilical cord clamping at birth. Arch Dis Child Fetal Neonatal Ed. 2015;100(4):F355–60.PubMedCrossRef
33.
Brouwer E, Knol R, Vernooij ASN, van den Akker T, Vlasman PE, Klumper F, et al. Physiological-based cord clamping in preterm infants using a new purpose-built resuscitation table: a feasibility study. Arch Dis Child Fetal Neonatal Ed. 2019;104:F396–402.PubMed
34.
Knol R, Brouwer E, Klumper F, van den Akker T, DeKoninck P, Hutten GJ, et al. Effectiveness of stabilization of preterm infants with intact umbilical cord using a purpose-built resuscitation table-study protocol for a randomized controlled trial. Front Pediatr. 2019;7:134.PubMedPubMedCentralCrossRef
35.
de Vries LS, Eken P, Dubowitz LM. The spectrum of leukomalacia using cranial ultrasound. Behav Brain Res. 1992;49(1):1–6.PubMedCrossRef
36.
Volpe JJ. Intraventricular hemorrhage in the premature infant–current concepts. Part II Ann Neurol. 1989;25(2):109–16.PubMedCrossRef
37.
Bell MJ, Ternberg JL, Feigin RD, Keating JP, Marshall R, Barton L, et al. Neonatal necrotizing enterocolitis. Therapeutic decisions based upon clinical staging. Ann Surg. 1978;187(1):1–7.PubMedPubMedCentralCrossRef
38.
39.
Pumberger W, Mayr M, Kohlhauser C, Weninger M. Spontaneous localized intestinal perforation in very-low-birth-weight infants: a distinct clinical entity different from necrotizing enterocolitis. J Am Coll Surg. 2002;195(6):796–803.PubMedCrossRef
40.
Samuels N, van de Graaf R, Been JV, de Jonge RC, Hanff LM, Wijnen RM, et al. Necrotising enterocolitis and mortality in preterm infants after introduction of probiotics: a quasi-experimental study. Sci Rep. 2016;6:31643.PubMedPubMedCentralCrossRef
41.
Walsh MC, Wilson-Costello D, Zadell A, Newman N, Fanaroff A. Safety, reliability, and validity of a physiologic definition of bronchopulmonary dysplasia. J Perinatol. 2003;23(6):451–6.PubMedCrossRef
42.
43.
Chan AW, Tetzlaff JM, Gotzsche PC, Altman DG, Mann H, Berlin JA, et al. SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials. BMJ. 2013;346:e7586.PubMedPubMedCentralCrossRef
44.
Kanters TA, Bouwmans CAM, van der Linden N, Tan SS, Hakkaart-van RL. Update of the Dutch manual for costing studies in health care. PLoS ONE. 2017;12(11):e0187477.PubMedPubMedCentralCrossRef
45.
Begley CM, Gyte GM, Devane D, McGuire W, Weeks A, Biesty LM. Active versus expectant management for women in the third stage of labour. Cochrane Database Syst Rev. 2019;2:CD007412.PubMed
46.
McDonald SJ, Middleton P, Dowswell T, Morris PS. Effect of timing of umbilical cord clamping of term infants on maternal and neonatal outcomes. Cochrane Database Syst Rev. 2013;7:CD004074.
47.
Katheria AC, Sorkhi SR, Hassen K, Faksh A, Ghorishi Z, Poeltler D. Acceptability of bedside resuscitation with intact umbilical cord to clinicians and patients’ families in the United States. Front Pediatr. 2018;6:100.PubMedPubMedCentralCrossRef
48.
Sawyer A, Ayers S, Bertullies S, Thomas M, Weeks AD, Yoxall CW, et al. Providing immediate neonatal care and resuscitation at birth beside the mother: parents’ views, a qualitative study. BMJ Open. 2015;5(9):e008495.PubMedPubMedCentralCrossRef
Metadata
Title
Physiological-based cord clamping in very preterm infants: the Aeration, Breathing, Clamping 3 (ABC3) trial—study protocol for a multicentre randomised controlled trial
Authors
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
Publication date
01-12-2022
Publisher
BioMed Central
Published in
Trials / Issue 1/2022
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/s13063-022-06789-6

Other articles of this Issue 1/2022

Trials 1/2022 Go to the issue

Publisher Correction

Correction: Sterile water injections for relief of labour pain (the SATURN trial): study protocol for a randomised controlled trial

Research

A cost-effectiveness and value of information analysis to inform future research of tranexamic acid for older adults experiencing mild traumatic brain injury

Study protocol

An interactive mobile application versus an educational booklet to promote job retention in women undergoing adjuvant chemotherapy for breast cancer: a randomized controlled trial

Study protocol

The effect of virtual specialist conferences between endocrinologists and general practitioners about type 2 diabetes: study protocol for a pragmatic randomized superiority trial

Study protocol

The effects of polyunsaturated fatty acid (PUFA) administration on the microbiome-gut-brain axis in adolescents with anorexia nervosa (the MiGBAN study): study protocol for a longitudinal, double-blind, randomized, placebo-controlled trial

Study protocol

Efficacy of thunder-fire moxibustion in treating ankylosing spondylitis of kidney deficiency and governor meridian cold and its influence on TNF-α and RANKL: study protocol for a prospective, nonblinded, single-center, randomized controlled trial