Expanding neonatal ECMO criteria: When is the premature neonate too premature

  • K. Taylor Wild
    Corresponding author. Division of Neonatology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
    Division of Neonatology, Department of Pediatrics, Children's Hospital of Philadelphia and University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
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  • Carmen Mesas Burgos
    Department of Pediatric Surgery, Karolinska University Hospital, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden
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  • Natalie E. Rintoul
    Division of Neonatology, Department of Pediatrics, Children's Hospital of Philadelphia and University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
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Published:November 17, 2022DOI:


      Extracorporeal membrane oxygenation (ECMO) is a universally accepted and life-saving therapy for neonates with respiratory or cardiac failure that is refractory to maximal medical management. Early studies found unacceptable risks of mortality and morbidities such as intracranial hemorrhage among premature and low birthweight neonates, leading to widely accepted ECMO inclusion criteria of gestational age ≥34 weeks and birthweight >2 kg. Although contemporary data is lacking, the most recent literature demonstrates increased survival and decreased rates of intracranial hemorrhage in premature neonates who are supported with ECMO. As such, it seems like the right time to push the boundaries of ECMO on a case-by-case basis beginning with neonates 32–34 weeks GA in large volume centers with careful neurodevelopmental follow-up to better inform practices changes on this select population.


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        • Cilley R.E.
        • Zwischenberger J.B.
        • Andrews A.F.
        • Bowerman R.A.
        • Roloff D.W.
        • Bartlett R.H.
        Intracranial hemorrhage during extracorporeal membrane oxygenation in neonates.
        Pediatrics. 1986; 78: 699-704
        • Bartlett R.H.
        • Gazzaniga A.B.
        • Jefferies M.R.
        • Huxtable R.F.
        • Haiduc N.J.
        • Fong S.W.
        Extracorporeal membrane oxygenation (ECMO) cardiopulmonary support in infancy.
        Trans Am Soc Artif Intern Organs. 1976; 22: 80-93
        • Bartlett R.H.
        • Gazzaniga A.B.
        • Toomasian J.
        • Corwin A.G.
        • Roloff D.
        • Rucker R.
        Extracorporeal membrane oxygenation (ECMO) in neonatal respiratory failure. 100 cases.
        Ann Surg. 1986; 204: 236-245
        • Gray B.W.
        • Shaffer A.W.
        • Mychaliska G.B.
        Advances in neonatal extracorporeal support: the role of extracorporeal membrane oxygenation and the artificial placenta.
        Clin Perinatol. 2012; 39: 311-329
      1. Extracorporeal life support organization (ELSO) registry report.
        Int. Summary. 2021; (October)
        • Leech R.W.
        • Kohnen P.
        Subependymal and intraventricular hemorrhages in the newborn.
        Am J Pathol. 1974; 77: 465-475
        • Hardart G.E.
        • Hardart M.K.
        • Arnold J.H.
        Intracranial hemorrhage in premature neonates treated with extracorporeal membrane oxygenation correlates with conceptional age.
        J Pediatr. 2004; 145: 184-189
        • Revenis M.E.
        • Glass P.
        • Short B.L.
        Mortality and morbidity rates among lower birth weight infants (2000 to 2500 grams) treated with extracorporeal membrane oxygenation.
        J Pediatr. 1992; 121: 452-458
        • Hirschl R.B.
        • Schumacher R.E.
        • Snedecor S.N.
        • Bui K.C.
        • Bartlett R.H.
        The efficacy of extracorporeal life support in premature and low birth weight newborns.
        J Pediatr Surg. 1993; 28: 1336-1340
        • Bartlett R.H.
        Esperanza: the first neonatal ECMO patient.
        Am Soc Artif Intern Organs J. 2017; 63: 832-843
        • Rozmiarek A.J.
        • Qureshi F.G.
        • Cassidy L.
        • et al.
        How low can you go? Effectiveness and safety of extracorporeal membrane oxygenation in low-birth-weight neonates.
        J Pediatr Surg. 2004; 39 ([*]): 845-847
        • Church J.T.
        • Kim A.C.
        • Erickson K.M.
        • et al.
        Pushing the boundaries of ECLS: outcomes in <34 week EGA neonates.
        J Pediatr Surg. 2017; 52: 1810-1815
        • Ramachandrappa A.
        • Rosenberg E.S.
        • Wagoner S.
        • Jain L.
        Morbidity and mortality in late preterm infants with severe hypoxic respiratory failure on extra-corporeal membrane oxygenation.
        J Pediatr. 2011; 159 (e3): 192-198
        • Schueller M.
        • Greenberg R.G.
        • Smith P.B.
        • Laughon M.M.
        • Clark R.H.
        • Hornik C.P.
        In-hospital outcomes following extracorporeal membrane oxygenation in a retrospective cohort of infants.
        Am J Perinatol. 2017; 34: 1347-1353
        • Smith K.M.
        • McMullan D.M.
        • Bratton S.L.
        • Rycus P.
        • Kinsella J.P.
        • Brogan T.V.
        Is age at initiation of extracorporeal life support associated with mortality and intraventricular hemorrhage in neonates with respiratory failure?.
        J Perinatol. 2014; 34: 386-391
        • Burgos C.M.
        • Frenckner B.
        • Broman L.M.
        Premature and extracorporeal life support: is it time? A systematic review.
        Am Soc Artif Intern Organs J. 2022; 68: 633-645
        • Bahrami K.R.
        • Van Meurs K.P.
        ECMO for neonatal respiratory failure.
        Semin Perinatol. 2005; 29: 15-23
        • Deprest J.A.
        • Nicolaides K.H.
        • Benachi A.
        • et al.
        Randomized trial of fetal surgery for severe left diaphragmatic hernia.
        NEJM. 2021; 385: 107-118
        • Delaplain P.T.
        • Zhang L.
        • Chen Y.
        • et al.
        Cannulating the contraindicated: effect of low birth weight on mortality in neonates with congenital diaphragmatic hernia on extracorporeal membrane oxygenation.
        J Pediatr Surg. 2017; 52: 2018-2025
        • Cuevas Guamán M.
        • Akinkuotu A.C.
        • Cruz S.M.
        • et al.
        Extracorporeal membrane oxygenation in premature infants with congenital diaphragmatic hernia.
        Am Soc Artif Intern Organs J. 2018; 64: e126-e129
        • Stevens T.P.
        • Chess P.R.
        • McConnochie K.M.
        • et al.
        Survival in early- and late-term infants with congenital diaphragmatic hernia treated with extracorporeal membrane oxygenation.
        Pediatrics. 2002; 110: 590-596
        • Tsao K.
        • Allison N.D.
        • Harting M.T.
        • Lally P.A.
        • Lally K.P.
        Congenital diaphragmatic hernia in the preterm infant.
        Surgery. 2010; 148: 404-410
        • Ali K.
        • Grigoratos D.
        • Cornelius V.
        • Davenport M.
        • Nicolaides K.
        • Greenough A.
        Outcome of CDH infants following fetoscopic tracheal occlusion - influence of premature delivery.
        J Pediatr Surg. 2013; 48: 1831-1836
        • Danzer E.
        • Hoffman C.
        • D'agostino J.A.
        • et al.
        Neurodevelopmental outcomes at 5 years of age in congenital diaphragmatic hernia.
        J Pediatr Surg. 2017; 52: 437-443
        • Bagdure D.
        • Torres N.
        • Walker L.
        • Waddell J.
        • Bhutta A.
        • Custer J.W.
        Extracorporeal membrane oxygenation for neonates with congenital renal and urological anomalies and pulmonary hypoplasia: a case report and review of the extracorporeal life support organization registry.
        J Pediatr Intensive Care. 2017; (06(03)): 188-193
        • O'Hare E.M.
        • Jelin A.C.
        • Miller J.L.
        • et al.
        Amnioinfusions to treat early onset anhydramnios caused by renal anomalies: background and rationale for renal anhydramnios fetal therapy trial.
        Fetal Diagn Ther. 2019; 45: 365-372
        • Hibbs A.
        • Evans J.R.
        • Gerdes M.
        • Hunter J.V.
        • Cullen J.A.
        Outcome of infants with bronchopulmonary dysplasia who receive extracorporeal membrane oxygenation therapy.
        J Pediatr Surg. 2001; 36: 1479-1484
        • Pena Hernandez A.
        • Carr N.R.
        • McCurnin D.
        • Armijo-Garcia V.
        Extracorporeal life support in pediatric patients with bronchopulmonary dysplasia and associated pulmonary hypertension.
        Am Soc Artif Intern Organs J. 2020; 66: 1063-1067
        • Kornhauser M.S.
        • Baumgart S.
        • Desai S.A.
        • et al.
        Adverse neurodevelopmental outcome after extracorporeal membrane oxygenation among neonates with bronchopulmonary dysplasia.
        J Pediatr. 1998; 132: 307-311
        • Ford M.A.
        • Gauvreau K.
        • McMullan D.M.
        • et al.
        Factors associated with mortality in neonates requiring extracorporeal membrane oxygenation for cardiac indications: analysis of the Extracorporeal Life Support Organization Registry Data.
        Pediatr Crit Care Med. 2016; 17: 860-870
        • Alarcon Manchego P.
        • Cheung M.
        • Zannino D.
        • Nunn R.
        • D'Udekem Y.
        • Brizard C.
        Audit of cardiac surgery outcomes for low birth weight and premature infants.
        Semin Thorac Cardiovasc Surg. 2018; 30: 71-78
        • Kim M.
        • Okunowo O.
        • Ades A.M.
        • Fuller S.
        • Rintoul N.E.
        • Naim M.Y.
        Single-center comparison of outcomes following cardiac surgery in low birth weight and standard birth weight neonates.
        J Pediatr. 2021; 238: 161-167.e1
        • Chu P.Y.
        • Li J.S.
        • Kosinski A.S.
        • Hornik C.P.
        • Hill K.D.
        Congenital heart disease in premature infants 25-32 weeks' gestational age.
        J Pediatr. 2017; 181: 37-41.e1
        • Steurer M.A.
        • Baer R.J.
        • Chambers C.D.
        • et al.
        Mortality and major neonatal morbidity in preterm infants with serious congenital heart disease.
        J Pediatr. 2021; 239: 110-116.e3
        • Hansen T.
        • Henriksen T.B.
        • Bach C.C.
        • Matthiesen N.B.
        Congenital heart defects and measures of prenatal brain growth: a systematic review.
        Pediatr Neurol. 2017; 72: 7-18.e1
        • Costello J.M.
        • Polito A.
        • Brown D.W.
        • et al.
        Birth before 39 weeks' gestation is associated with worse outcomes in neonates with heart disease.
        Pediatrics. 2010; 126: 277-284
        • Cnota J.F.
        • Gupta R.
        • Michelfelder E.C.
        • Ittenbach R.F.
        Congenital heart disease infant death rates decrease as gestational age advances from 34 to 40 weeks.
        J Pediatr. 2011; 159: 761-765
        • Wild K.T.
        • Rintoul N.
        • Kattan J.
        • Gray B.
        Extracorporeal life support organization (ELSO): guidelines for neonatal respiratory failure.
        Am Soc Artif Intern Organs J. 2020; 66: 463-470
        • Nelson K.E.
        • Rosella L.C.
        • Mahant S.
        • Guttmann A.
        Survival and surgical interventions for children with trisomy 13 and 18.
        JAMA. 2016; 316: 420
        • Meyer R.E.
        • Liu G.
        • Gilboa S.M.
        • et al.
        Survival of children with trisomy 13 and trisomy 18: a multi-state population-based study.
        Am J Med Genet. 2016; 170: 825-837
        • Cleary J.P.
        • Janvier A.
        • Farlow B.
        • Weaver M.
        • Hammel J.
        • Lantos J.
        Cardiac interventions for patients with trisomy 13 and trisomy 18: experience, ethical issues, communication, and the case for individualized family-centered care.
        World J Pediatr Congenit Heart Surg. 2022; 13: 72-76
        • Guner Y.S.
        • Khemani R.G.
        • Qureshi F.G.
        • et al.
        Outcome analysis of neonates with congenital diaphragmatic hernia treated with venovenous vs. venoarterial extracorporeal membrane oxygenation.
        J Pediatr Surg. 2009; 44: 1691-1701
        • McNally H.
        • Bennett C.C.
        • Elbourne D.
        • Field D.J.
        United Kingdom collaborative randomized trial of neonatal extracorporeal membrane oxygenation: follow-up to age 7 years.
        Pediatrics. 2006; 117: e845-e854
        • Madderom M.J.
        • Reuser J.J.
        • Utens E.M.
        • et al.
        Neurodevelopmental, educational and behavioral outcome at 8 years after neonatal ECMO: a nationwide multicenter study.
        Intensive Care Med. 2013; 3915841593
        • Partridge E.A.
        • Davey M.G.
        • Hornick M.A.
        • Flake A.W.
        An EXTrauterine environment for neonatal development: EXTENDING fetal physiology beyond the womb.
        Semin Fetal Neonatal Med. 2017; 22: 404-409
        • Church J.T.
        • Coughlin M.A.
        • Perkins E.M.
        • et al.
        The artificial placenta: continued lung development during extracorporeal support in a preterm lamb model.
        J Pediatr Surg. 2018; 53: 1896-1903
        • Partridge E.A.
        • Davey M.G.
        • Hornick M.
        • et al.
        Pumpless arteriovenous extracorporeal membrane oxygenation: a novel mode of respiratory support in a lamb model of congenital diaphragmatic hernia.
        J Pediatr Surg. 2018; 53: 1453-1460
        • Karamlou T.
        • Vafaeezadeh M.
        • Parrish A.M.
        • et al.
        Increased extracorporeal membrane oxygenation center case volume is associated with improved extracorporeal membrane oxygenation survival among pediatric patients.
        J Thorac Cardiovasc Surg. 2013; 145: 470-475
        • Guner Y.S.
        • Harting M.T.
        • Jancelewicz T.
        • Yu P.T.
        • Nardo M.D.
        • Nguyen D.V.
        Variation across centers in standardized mortality ratios for congenital diaphragmatic hernia receiving extracorporeal life support.
        J Pediatr Surg. 2022; (S0022-3468(22)00087-2)