Download PDF
Am J Perinatol 2023; 40(06): 630-637
DOI: 10.1055/s-0041-1730362
Original Article

Differential Alveolar and Systemic Oxygenation during Preterm Resuscitation with 100% Oxygen during Delayed Cord Clamping

Satyan Lakshminrusimha 
1   Department of Pediatrics, University of California Davis, Sacramento, California
,
Payam Vali 
1   Department of Pediatrics, University of California Davis, Sacramento, California
,
Praveen Chandrasekharan
2   Department of Pediatrics, University at Buffalo, Buffalo, New York
,
Wade Rich
3   Neonatal Research Institute, Sharp Mary Birch Hospital for Women and Newborns, San Diego, California
,
Anup Katheria
3   Neonatal Research Institute, Sharp Mary Birch Hospital for Women and Newborns, San Diego, California
› Author Affiliations Funding This study received financial support from Children's Miracle Network (PV) (grant numbers: HD072929 [S.L.], K12 HL138052 [P.C.], and R03HD096510 [P.C.]).
› Further Information
    Permissions and Reprints

Abstract

Objective Delayed cord clamping (DCC) and 21 to 30% O2 resuscitation is recommended for preterm infants but is commonly associated with low pulmonary blood flow (Qp) and hypoxia. 100% O2 supplementation during DCC for 60 seconds followed by 30% O2 may increase Qp and oxygen saturation (SpO2).

Study Design Preterm lambs (125–127 days of gestation) were resuscitated with 100% O2 with immediate cord clamping (ICC, n = 7) or ICC + 30% O2, and titrated to target SpO2 (n = 7) or DCC + 100% O2 for 60 seconds, which followed by cord clamping and 30% O2 titration (n = 7). Seven preterm (23–27 weeks of gestation) human infants received continuous positive airway pressure (CPAP) + 100% O2 for 60 seconds during DCC, cord clamping, and 30% O2 supplementation after cord clamping.

Results Preterm lambs in the ICC + 100% O2 group resulted in PaO2 (77 ± 25 mm Hg), SpO2 (77 ± 11%), and Qp (27 ± 9 mL/kg/min) at 60 seconds. ICC + 30% O2 led to low Qp (14 ± 3 mL/kg/min), low SpO2 (43 ± 26%), and PaO2 (19 ± 7 mm Hg). DCC + 100% O2 led to similar Qp (28 ± 6 mL/kg/min) as ICC + 100% O2 with lower PaO2. In human infants, DCC + CPAP with 100% O2 for 60 seconds, which followed by weaning to 30% resulted in SpO2 of 92 ± 11% with all infants >80% at 5 minutes with 100% survival without severe intraventricular hemorrhage.

Conclusion DCC + 100% O2 for 60 seconds increased Qp probably due to transient alveolar hyperoxia with systemic normoxia due to “dilution” by umbilical venous return. Larger translational and clinical studies are warranted to confirm these findings.

Key Points

  • Transient alveolar hyperoxia during delayed cord clamping can enhance pulmonary vasodilation.

  • Placental transfusion buffers systemic oxygen tension and limits hyperoxia.

  • Use of 100% oxygen for 60 seconds during DCC was associated with SpO2 ≥80% by 5 minutes.

Keywords

neonatology - delayed cord clamping - oxygen - resuscitaiton

Note

The clinical part of the study was approved by Sharp Mary Birch hospital IRB and consents were obtained from parents. Dr. Satyan Lakshminrusimha is a member of the Neonatal Resuscitation Program Steering Committee of the American Academy of Pediatrics (AAP). The opinions expressed in this manuscript are the author's own and does not reflect the official position of the AAP.


Authors' Contributions

S.L., A.K., P.V., P.K., and W.R. provided substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data, and also supported in final approval of the version to be published. S.L., A.K., P.V., and P.K. supported in drafting the article or revising it critically for important intellectual content.




Publication History

Received: 30 March 2021

Accepted: 11 April 2021

Article published online:
01 June 2021

© 2021. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 

  • References

  • 1 Lakshminrusimha S, Steinhorn RH. Pulmonary vascular biology during neonatal transition. Clin Perinatol 1999; 26 (03) 601-619
    CrossrefPubMedGoogle Scholar
  • 2 Chandrasekharan P, Rawat M, Lakshminrusimha S. How do we monitor oxygenation during the management of PPHN? Alveolar, arterial, mixed venous oxygen tension or peripheral saturation?. Children (Basel) 2020; 7 (10) E180
    PubMedGoogle Scholar
  • 3 Moudgil R, Michelakis ED, Archer SL. Hypoxic pulmonary vasoconstriction. J Appl Physiol (1985) 2005; 98 (01) 390-403
    CrossrefPubMedGoogle Scholar
  • 4 Nair J, Lakshminrusimha S. Update on PPHN: mechanisms and treatment. Semin Perinatol 2014; 38 (02) 78-91
    CrossrefPubMedGoogle Scholar
  • 5 Wyckoff MH, Wyllie J, Aziz K. et al; Neonatal Life Support Collaborators. Neonatal life support: 2020 international consensus on cardiopulmonary resuscitation and emergency cardiovascular care science with treatment recommendations. Circulation 2020; 142 (16_suppl_1, suppl_1): S185-S221
    CrossrefPubMedGoogle Scholar
  • 6 Welsford M, Nishiyama C, Shortt C. et al; International Liaison Committee on Resuscitation Neonatal Life Support Task Force. Initial oxygen use for preterm newborn resuscitation: a systematic review with meta-analysis. Pediatrics 2019; 143 (01) e20181828
    CrossrefPubMedGoogle Scholar
  • 7 Saugstad OD, Lakshminrusimha S, Vento M. Optimizing oxygenation of the extremely premature infant during the first few minutes of life: start low or high?. J Pediatr 2020; 227: 295-299
    CrossrefPubMedGoogle Scholar
  • 8 Perlman JM, Wyllie J, Kattwinkel J. et al; Neonatal Resuscitation Chapter Collaborators. Part 7: Neonatal resuscitation: 2015 international consensus on cardiopulmonary resuscitation and emergency cardiovascular care science with treatment recommendations. Circulation 2015; 132 (16, Suppl 1): S204-S241
    CrossrefPubMedGoogle Scholar
  • 9 Vento M, Aguar M, Escobar J. et al. Antenatal steroids and antioxidant enzyme activity in preterm infants: influence of gender and timing. Antioxid Redox Signal 2009; 11 (12) 2945-2955
    CrossrefPubMedGoogle Scholar
  • 10 Oei JL, Finer NN, Saugstad OD. et al. Outcomes of oxygen saturation targeting during delivery room stabilisation of preterm infants. Arch Dis Child Fetal Neonatal Ed 2018; 103 (05) F446-F454
    CrossrefPubMedGoogle Scholar
  • 11 Oei JL, Vento M, Rabi Y. et al. Higher or lower oxygen for delivery room resuscitation of preterm infants below 28 completed weeks gestation: a meta-analysis. Arch Dis Child Fetal Neonatal Ed 2017; 102 (01) F24-F30
    CrossrefPubMedGoogle Scholar
  • 12 Rabi Y, Singhal N, Nettel-Aguirre A. Room-air versus oxygen administration for resuscitation of preterm infants: the ROAR study. Pediatrics 2011; 128 (02) e374-e381
    CrossrefPubMedGoogle Scholar
  • 13 Oei JL, Saugstad OD, Lui K. et al. Targeted oxygen in the resuscitation of preterm infants, a randomized clinical trial. Pediatrics 2017; 139 (01) e20161452
    CrossrefPubMedGoogle Scholar
  • 14 Chandrasekharan P, Rawat M, Gugino SF. et al. Effect of various inspired oxygen concentrations on pulmonary and systemic hemodynamics and oxygenation during resuscitation in a transitioning preterm model. Pediatr Res 2018; 84 (05) 743-750
    CrossrefPubMedGoogle Scholar
  • 15 Dekker J, Martherus T, Lopriore E. et al. The effect of initial high vs. low FiO2 on breathing effort in preterm infants at birth: a randomized controlled trial. Front Pediatr 2019; 7 (504) 504-504
    CrossrefPubMedGoogle Scholar
  • 16 International Liaison Committee on Resuscitation. The International Liaison Committee on Resuscitation (ILCOR) consensus on science with treatment recommendations for pediatric and neonatal patients: neonatal resuscitation. Pediatrics 2006; 117 (05) e978-e988
    CrossrefPubMedGoogle Scholar
  • 17 Vali P, Lesneski A, Hardie M. et al. Continuous chest compressions with asynchronous ventilations increase carotid blood flow in the perinatal asphyxiated lamb model. Pediatr Res 2021
    PubMedGoogle Scholar
  • 18 Rawat M, Chandrasekharan P, Gugino SF. et al. Optimal oxygen targets in term lambs with meconium aspiration syndrome and pulmonary hypertension. Am J Respir Cell Mol Biol 2020; 63 (04) 510-518
    CrossrefPubMedGoogle Scholar
  • 19 Dupont WD, Plummer Jr WD. Power and sample size calculations for studies involving linear regression. Control Clin Trials 1998; 19 (06) 589-601
    CrossrefPubMedGoogle Scholar
  • 20 Rabe H, Wacker A, Hulskamp G, Homig-Franz I, Jorch G. Late cord clamping benefits extrauterine adaptation. Pediatr Res 1998; 44: 454 DOI: 10.1203/00006450-199809000-00244.
    CrossrefPubMedGoogle Scholar
  • 21 Rabe H, Jewison A, Fernandez Alvarez R. et al; Brighton Perinatal Study Group. Milking compared with delayed cord clamping to increase placental transfusion in preterm neonates: a randomized controlled trial. Obstet Gynecol 2011; 117 (2 Pt 1): 205-211
    CrossrefPubMedGoogle Scholar
  • 22 Mercer JS, McGrath MM, Hensman A, Silver H, Oh W. Immediate and delayed cord clamping in infants born between 24 and 32 weeks: a pilot randomized controlled trial. J Perinatol 2003; 23 (06) 466-472
    CrossrefPubMedGoogle Scholar
  • 23 Nelle M, Fischer S, Conze S. et al. Effects of later cord clamping on circulation in prematures. (Abstract) Pediatr Res 1998; 44: 420 DOI: 10.1203/00006450-199809000-00245.
    CrossrefPubMedGoogle Scholar
  • 24 Narenda A, Beckett CAT, Kyle E. et al. Is it possible to promote placental transfusion at preterm delivery?. Pediatr Res 1998; 44: 453
    PubMedGoogle Scholar
  • 25 Kinmond S, Aitchison TC, Holland BM, Jones JG, Turner TL, Wardrop CA. Umbilical cord clamping and preterm infants: a randomised trial. BMJ 1993; 306 (6871): 172-175
    CrossrefPubMedGoogle Scholar
  • 26 Ibrahim HM, Krouskop RW, Lewis DF, Dhanireddy R. Placental transfusion: umbilical cord clamping and preterm infants. J Perinatol 2000; 20 (06) 351-354
    CrossrefPubMedGoogle Scholar
  • 27 Mercer JS, Vohr BR, McGrath MM, Padbury JF, Wallach M, Oh W. Delayed cord clamping in very preterm infants reduces the incidence of intraventricular hemorrhage and late-onset sepsis: a randomized, controlled trial. Pediatrics 2006; 117 (04) 1235-1242
    Google Scholar
  • 28 Hofmeyr GJ, Bolton KD, Bowen DC, Govan JJ. Periventricular/intraventricular haemorrhage and umbilical cord clamping. Findings and hypothesis. S Afr Med J 1988; 73 (02) 104-106
    PubMedGoogle Scholar
  • 29 Hofmeyr GJ, Gobetz L, Bex PJ. et al. Periventricular/intraventricular hemorrhage following early and delayed umbilical cord clamping. A randomized controlled trial. Online J Curr Clin Trials 1993;Doc No 110:[2002 words; 2026 paragraphs]
    PubMedGoogle Scholar
  • 30 Rabe H, Reynolds G, Diaz-Rossello J. Early versus delayed umbilical cord clamping in preterm infants. Cochrane Database Syst Rev 2004; (04) CD003248
    PubMedGoogle Scholar
  • 31 Fogarty M, Osborn DA, Askie L. et al. Delayed vs early umbilical cord clamping for preterm infants: a systematic review and meta-analysis. Am J Obstet Gynecol 2018; 218 (01) 1-18
    Google Scholar
  • 32 Committee Opinion No. 684: Delayed umbilical cord clamping after birth. Obstet Gynecol 2017; 129 (01) e5-e10
    CrossrefPubMedGoogle Scholar
  • 33 Guidelines WHO. Approved by the Guidelines Review Committee. In Guidelines on Basic Newborn Resuscitation. Geneva: World Health Organization; 2012
    Google Scholar
  • 34 Wyllie J, Perlman JM, Kattwinkel J. et al; Neonatal Resuscitation Chapter Collaborators. Part 7: Neonatal resuscitation: 2015 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science with Treatment Recommendations. Resuscitation 2015; 95: e169-e201
    CrossrefPubMedGoogle Scholar
  • 35 Padilla-Sánchez C, Baixauli-Alacreu S, Cañada-Martínez AJ, Solaz-García Á, Alemany-Anchel MJ, Vento M. Delayed versus immediate cord clamping changes oxygen saturation and heart rate patterns in the first minutes after birth. J Pediatr 2020; 227: 149-156.e1
    CrossrefPubMedGoogle Scholar
  • 36 Dawson JA, Kamlin CO, Vento M. et al. Defining the reference range for oxygen saturation for infants after birth. Pediatrics 2010; 125 (06) e1340-e1347
    CrossrefPubMedGoogle Scholar
  • 37 Andersson O, Rana N, Ewald U. et al. Intact cord resuscitation versus early cord clamping in the treatment of depressed newborn infants during the first 10 minutes of birth (Nepcord III) - a randomized clinical trial. Matern Health Neonatol Perinatol 2019; 5: 15
    CrossrefPubMedGoogle Scholar
  • 38 Bhatt S, Alison BJ, Wallace EM. et al. Delaying cord clamping until ventilation onset improves cardiovascular function at birth in preterm lambs. J Physiol 2013; 591 (08) 2113-2126
    CrossrefPubMedGoogle Scholar
  • 39 Saini BS, Darby JRT, Portnoy S. et al. Normal human and sheep fetal vessel oxygen saturations by T2 magnetic resonance imaging. J Physiol 2020; 598 (15) 3259-3281
    CrossrefPubMedGoogle Scholar
  • 40 Polglase GR, Dawson JA, Kluckow M. 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 (02) e0117504
    CrossrefPubMedGoogle Scholar
  • 41 Hooper SB, Te Pas AB, Lang J. et al. Cardiovascular transition at birth: a physiological sequence. Pediatr Res 2015; 77 (05) 608-614
    CrossrefPubMedGoogle Scholar
  • 42 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
    CrossrefPubMedGoogle Scholar
  • 43 Stenning FJ, Hooper SB, Kluckow M. et al. Transfusion or timing: the role of blood volume in delayed cord clamping during the cardiovascular transition at birth. Front Pediatr 2019; 7 (405) 405
    CrossrefPubMedGoogle Scholar
  • 44 Katheria A, Reister F, Essers J. et al. Association of umbilical cord milking vs delayed umbilical cord clamping with death or severe intraventricular hemorrhage among preterm infants. JAMA 2019; 322 (19) 1877-1886
    Google Scholar
  • 45 Katheria AC, Szychowski JM, Essers J. et al. Early cardiac and cerebral hemodynamics with umbilical cord milking compared with delayed cord clamping in infants born preterm. J Pediatr 2020; 223: 51-56.e1
    CrossrefPubMedGoogle Scholar
  • 46 Katheria AC, Hassen K, Rich W, Poeltler D, Finer N. Resuscitation outcomes of infants that do not achieve a 5 min target SpO2 saturation. J Perinatol 2019; 39 (12) 1635-1639
    CrossrefPubMedGoogle Scholar
  • 47 Katheria A, Poeltler D, Durham J. et al. Neonatal resuscitation with an intact cord: a randomized clinical trial. J Pediatr 2016; 178: 75-80.e3
    Google Scholar
  • 48 Katheria AC, Brown MK, Faksh A. et al. Delayed cord clamping in newborns born at term at risk for resuscitation: a feasibility randomized clinical trial. J Pediatr 2017; 187: 313-317.e1
    CrossrefPubMedGoogle Scholar
  • 49 Duley L, Dorling J, Pushpa-Rajah A. et al; Cord Pilot Trial Collaborative Group. Randomised trial of cord clamping and initial stabilisation at very preterm birth. Arch Dis Child Fetal Neonatal Ed 2018; 103 (01) F6-F14
    CrossrefPubMedGoogle Scholar
  • 50 Vento M, Moro M, Escrig R. et al. Preterm resuscitation with low oxygen causes less oxidative stress, inflammation, and chronic lung disease. Pediatrics 2009; 124 (03) e439-e449
    CrossrefPubMedGoogle Scholar
  • 51 Vento M, Asensi M, Sastre J, García-Sala F, Pallardó FV, Viña J. Resuscitation with room air instead of 100% oxygen prevents oxidative stress in moderately asphyxiated term neonates. Pediatrics 2001; 107 (04) 642-647
    CrossrefPubMedGoogle Scholar
  • 52 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 (02) 111-116
    Article in Thieme ConnectPubMedGoogle Scholar
  • 53 Knol R, Brouwer E, Klumper FJCM. 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) 134
    CrossrefPubMedGoogle Scholar
  • 54 Pratesi S, Montano S, Ghirardello S. et al. Placental circulation intact trial (PCI-T)-resuscitation with the placental circulation intact versus cord milking for very preterm infants: a feasibility study. Front Pediatr 2018; 6: 364-364
    CrossrefPubMedGoogle Scholar
  • 55 van Leuteren RW, Scholten AWJ, Dekker J. et al. The effect of initial oxygen exposure on diaphragm activity in preterm infants at birth. Front Pediatr 2021; 9: 640491
    CrossrefPubMedGoogle Scholar
  • 56 Crawshaw JR, Kitchen MJ, Binder-Heschl C. et al. Laryngeal closure impedes non-invasive ventilation at birth. Arch Dis Child Fetal Neonatal Ed 2018; 103 (02) F112-F119
    CrossrefPubMedGoogle Scholar
  • 57 Kuypers K, Martherus T, Lamberska T, Dekker J, Hooper SB, Te Pas AB. Reflexes that impact spontaneous breathing of preterm infants at birth: a narrative review. Arch Dis Child Fetal Neonatal Ed 2020; 105 (06) 675-679
    CrossrefPubMedGoogle Scholar
  • 58 Kashyap AJ, Hodges RJ, Thio M. et al. Physiologically based cord clamping improves cardiopulmonary haemodynamics in lambs with a diaphragmatic hernia. Arch Dis Child Fetal Neonatal Ed 2020; 105 (01) 18-25
    CrossrefPubMedGoogle Scholar
  • 59 Brouwer E, Te Pas AB, Polglase GR. et al. Effect of spontaneous breathing on umbilical venous blood flow and during delayed cord clamping in preterm lambs. Arch Dis Child Fetal Neonatal Ed 2020; 105 (01) 26-32
    CrossrefPubMedGoogle Scholar
  • 60 Blank DA, Polglase GR, Kluckow M. et al. Haemodynamic effects of umbilical cord milking in premature sheep during the neonatal transition. Arch Dis Child Fetal Neonatal Ed 2018; 103 (06) F539-F546
    CrossrefPubMedGoogle Scholar