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Pediatric Newborn Medicine Canon Classic Articles

Established by John Zupancic, MD, MS, ScD

Updated 6/15/15 by Saima Aftab, MD, Helen Christou, MD, Katherine Bell, MD and Christopher McPherson, PharmD.

Canon Classic Articles

Respiratory, Resuscitation and Extracorporeal Membrane Oxygenation (ECMO)


  • Fujiwara T, Chida S, Watabe Y, Maeta H, Morita T, and Abe T. Artificial Surfactant Therapy in Hyaline Membrane Disease. The Lancet. 1980 Jan 12;315(8159):55-9.
  • Merritt TA, Hallman M, Bloom BT, Berry C, Benirschke K, Sahn D, et al. Prophylactic treatment of very premature infants with human surfactant. N Engl J Med. 1986 Sep 25;315(13):785-90.
  • Kattwinkel J, Bloom BT, Delmore P, Davis C, et al. Prophylactic Administration of Calf Lung Surfactant Extract is More Effective Than Early Treatment of Respiratory Distress Syndrome in Neonates of 29 Through 32 Weeks’ Gestation. Pediatrics. 1993 Jul 1;92(1):90-8.
    • META-ANALYSIS: Cochrane review showed that with the advent of routine early CPAP and maternal steroid use, prophylactic surfactant administration no longer has benefit compared to selectively intubating infants with clinical signs of RDS: Rojas-Reyes MX, Morley CJ, Soll R. Prophylactic versus selective use of surfactant in preventing morbidity and mortality in preterm infants. Cochrane Database Syst Rev. 2012;3:CD000510
  • Verder H, Albertsen P, Ebbesen F, Greisen G, Robertson B, Bertelsen A, Agertoft L, Djernes B, Nathan E, Reinholdt J: Nasal continuous positive airway pressure and early surfactant therapy for respiratory distress syndrome in newborns of less than 30 weeks’ gestation. Pediatrics 1999; 103:E24.
    • Finer NN, Carlo WA, Walsh MC, Rich W, Gantz MG, Laptook AR, et al (SUPPORT Study Group). Early CPAP vs surfactant in extremely preterm infants. N Engl J Med. 2010 Jun 10;362(23):2235

Oxygen Saturation Targets

  • Vaucher Y, Peralta-Carcelan M, Finer NN, Carlo WA, Gantz M, et al (SUPPORT Study Group). Neurodevelopmental Outcomes in the Early CPAP and Pulse Oximetry Trial. N Engl J Med. 2012 Dec 27;367(26):2495-504.
  • Stenson B, Tarnow-Mordi WO, Darlow B, Simes J, Juszczak E, et al (BOOST II United Kingdom, Australia, and New Zealand Collaborative Groups). Oxygen Saturation and Outcomes in Preterm Infants. N Engl J Med. 2013 May 30; 368(22):2094-104.
  • Schmidt B, Whyte R, Asztalos E, Moddemann D, Poets C, et al (COT Group). Effects of Targeting Higher vs Lower Arterial Oxygen Saturations on Death or Disability in Extremely Preterm Infants. JAMA. 2013;309(20):2111-20.

BPD Prevention

  • Van Marter LJ, Leviton A, Allred EN, Pagano M, Kuban KC. Hydration during the first days of life and the risk of bronchopulmonary dysplasia in low birth weight infants. J Pediatr. 1990 Jun;116(6):942-9.
  • Cole CH, Colton T, Shah BL, Abbasi S, MacKinnon BL, Demissie S, et al. Early inhaled glucocorticoid therapy to prevent bronchopulmonary dysplasia. N Engl J Med. 1999 Apr 1;340(13):1005-10.
  • Johnson AH, Peacock JL, Greenough A, Marlow N, Limb ES, Marston L, et al. High-frequency oscillatory ventilation for the prevention of chronic lung disease of prematurity. N Engl J Med. 2002 Aug 29;347(9):633-42.
  • Courtney SE, Durand DJ, Asselin JM, Hudak ML, Aschner JL, Shoemaker CT. High-frequency oscillatory ventilation versus conventional mechanical ventilation for very-low-birth-weight infants. N Engl J Med. 2002 Aug 29;347(9):643-52.
  • Morley CJ, Davis PG, Doyle LW, Brion LP, Hascoet JM, Carlin JB (COIN trial). Nasal CPAP or intubation at birth for very preterm infants. N Engl J Med. 2008 Feb 14;358(7):700-8.
  • Schmidt B, Roberts RS, Davis P, Doyle LW, Barrington KJ, Ohlsson A, et al. Long-term effects of caffeine therapy for apnea of prematurity. N Engl J Med. 2007 Nov 8;357(19):1893-902.
    • Long term follow-up: Schmidt B, Anderson P, Doyle L, Dewey D, et al. Survival without disability to age 5 years after neonatal caffeine therapy for apnea of prematurity. JAMA. 2012;307(3):275-282
    • Long term follow-up: Doyle L, Schmidt B, Anderson J, Davis P, Moddemann D, et al. Reduction in Developmental Coordination Disorder with Neonatal Caffeine Therapy. J Pediatr. 2014 Aug;165(2):365-9.
  • Watterberg KL, Gerdes JS, Cole CH, Aucott SW, Thilo EH, Mammel MC, et al. Prophylaxis of early adrenal insufficiency to prevent bronchopulmonary dysplasia: a multicenter trial. Pediatrics. 2004 Dec;114(6):1649-57.
  • Cummings JJ, D'Eugenio DB, Gross SJ. A controlled trial of dexamethasone in preterm infants at high risk for bronchopulmonary dysplasia. N Engl J Med. 1989 Jun 8;320(23):1505-10.
  • Papile L, Tyson J, Stoll B, Wright L, Donovan E, et al. A Multicenter Trial of Two Dexamethasone Regimens in Ventilator-Dependent Premature Infants. N Engl J Med. 1998;338:1112-9.
  • Doyle L, Davis P, Morley C, McPhee A, and Carlin J (DART Study Investigators). Low-Dose Dexamethasone Facilitates Extubation Among Chronically Ventilator-Dependent Infants: A Multicenter, International, Randomized, Controlled Trial. Pediatrics. 2006;117(1):75-83.
  • O'Shea TM, Kothadia JM, Klinepeter KL, Goldstein DJ, Jackson BG, Weaver RG 3rd, Dillard RG: Randomized placebo-controlled trial of a 42-day tapering course of dexamethasone to reduce the duration of ventilator dependency in very low birth weight infants: outcome of study participants at 1-year adjusted age. Pediatrics 1999; 104:15-21
    • Long term follow-up: O’Shea TM, Washburn L, Nixon P, and Goldstein D. Ventilator Dependency in Very Low Birth Weight Infants: Neurodevelopmental Outcomes at 4 to 11 Years of Age. Pediatrics. 2007;120(3):594-602.
    • META-ANALYSIS: Meta-analysis of 20 RCT’s shows infants at higher risk of BPD have higher rates of survival free from cerebral palsy after systemic corticosteroids: Doyle L, Halliday H, Ehrenkranz R, Davis P, and Sinclair J. An Update on the Impact of Postnatal Systemic Corticosteroids on Mortality and Cerebral Palsy in Preterm Infants: Effect Modification by Risk of Bronchopulmonary Dysplasia. J Pediatr. 2014;165(6):1258-60.
  • Vitamin A supplementation for extremely-low-birth-weight infants. National Institute of Child Health and Human Development Neonatal Research Network. N Engl J Med. 1999 Jun 24;340(25):1962-8.

Non-invasive Modes of Ventilation

  • Manley B, Owen L, Doyle L, Andersen C, et al. High-Flow Nasal Cannulae in Very Preterm Infants after Extubation. N Engl J Med. 2013;369:1425-33.
  • Kirpalani H, Millar D, Lemyre B, Yoder B, et al. A Trial Comparing Noninvasive Ventilation Strategies in Preterm Infants. N Engl J Med. 2013 Aug 15;369:611-20.

ECMO and Inhaled Nitric Oxide

  • The collaborative UK ECMO (Extracorporeal Membrane Oxygenation) trial: follow-up to 1 year of age. Pediatrics. 1998 Apr;101(4):E1.
  • The Neonatal Inhaled Nitric Oxide Study Group. Inhaled nitric oxide in full-term and nearly full-term infants with hypoxic respiratory failure. New Engl J Med, 1997;336(9):597-604.
    • Long-term follow up: Inhaled nitric oxide in term and near-term infants: Neurodevelopmental follow-up of The Neonatal Inhaled Nitric Oxide Study Group (NINOS). J Pediatr. 2000;136(5):611-7.
  • Clark RH, Kueser TJ, Walker MW, Southgate WM, Huckaby JL, Perez JA, et al. Low-dose nitric oxide therapy for persistent pulmonary hypertension of the newborn. Clinical Inhaled Nitric Oxide Research Group. N Engl J Med. 2000 Feb 17;342(7):469-74.
  • Mercier JC, Hummler J, Durrmeyer X, Sanchez-Luna M, Carnielli V, et al. Inhaled nitric oxide for prevention of bronchopulmonary dysplasia in premature babies (EUNO): a randomised controlled trial. Lancet. 2010 Jul 31;376(9738):346-54.
  • Ballard RA, Truog W, Cnaan A, Martin R, Ballard P, et al. Inhaled Nitric Oxide in Preterm Infants Undergoing Mechanical Ventilation. N Engl J Med. 2006 Jul 27;355:343-53.
  • NIH Consensus Guidelines for iNO in Premature Infants


  • Saugstad OD, Ramji S, Irani SF, El-Meneza S, Hernandez EA, Vento M, et al. Resuscitation of newborn infants with 21% or 100% oxygen: follow-up at 18 to 24 months. Pediatrics. 2003 Aug;112(2):296-300.
  • Wiswell TE, Gannon CM, Jacob J, Goldsmith L, Szyld E, Weiss K, et al. Delivery room management of the apparently vigorous meconium-stained neonate: results of the multicenter, international collaborative trial. Pediatrics. 2000 Jan;105(1):1-7.

Apnea Monitoring

  • Ramanathan R, Corwin M, Hunt C, Lister G, Tinsley R, et al (CHIME Study Group). Comparison of Healthy Infants With Those at Increased Risk for SIDS. JAMA. 2001;285(17):2199-207.
Infectious Diseases
  • Boyer KM, Gotoff SP. Prevention of early-onset neonatal group B streptococcal disease with selective intrapartum chemoprophylaxis. N Engl J Med. 1986 Jun 26;314(26):1665-9.
  • Stoll BJ, Hansen NI, Sanches PJ, Faix RG, Poindexter BB, Van Meurs KP, et al. Early Onset Neonatal Sepsis: The Burden of Group B Streptococcal and E. coli Disease Continues. Pediatrics. 2011;127(5):817-26.
  • Clark R, Bloom B, Spitzer A, and Gerstmann D. Empiric Use of Ampicillin and Cefotaxime, Compared With Ampicillin and Gentamicin, for Neonates at Risk for Sepsis Is Associated With an Increased Risk of Neonatal Death. Pediatrics. 2006;117:67-74.
  • Brocklehurst P, et al (INIS Collaborative Group). Treatment of Neonatal Sepsis with Intravenous Immune Globulin. N Engl J Med. 2011;365:1201-11.
  • Kimberlin DW, Lin C, Sanchez P, Demmler G, et al. Effect of ganciclovir therapy on hearing in symptomatic congenital cytomegalovirus disease involving the central nervous system: A randomized, controlled trial. J Pediatr. 2003 Jul;143:16-25.
  • Kimberlin DW, et al. Valganciclovir for Symptomatic Congenital Cytomegalovirus Disease. N Engl J Med. 2015 Mar 5;372:933-43.
  • Kimberlin DW, Lin C, Jacobs R, Powell D, et al. Safety and Efficacy of High-Dose Intravenous Acyclovir in the Management of Neonatal Herpes Simplex Virus Infections. Pediatrics. 2001;108(2):230-8.
  • Kimberlin DW, Whitley R, Wan W, Powell D, et al. Oral Acyclovir Suppression and Neurodevelopment after Neonatal Herpes. N Engl J Med. 2011 Oct 6;365:1284-92.
  • Connor EM, Sperling RS, Gelber R, Kiselev P, Scott G, O'Sullivan MJ, et al. Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment. Pediatric AIDS Clinical Trials Group Protocol 076 Study Group. N Engl J Med. 1994 Nov 3;331(18):1173-80.
  • Benjamin DK, Hudak ML, Duara S, Randolph DA, Bidegain M, et al. Effect of Fluconazole Prophylaxis on Candidiasis and Mortality in Premature Infants. JAMA. 2014;311(17):1742-9.
  • Palivizumab, a humanized respiratory syncytial virus monoclonal antibody, reduces hospitalization from respiratory syncytial virus infection in high-risk infants. The IMpact-RSV Study Group. Pediatrics. 1998 Sep;102:531-7.
  • Updated AAP Synagis Guidelines from 2014
Neurology and Pain
  • Anand KJ, Sippell WG, and Aynsley-Green A. Randomised trial of fentanyl anaesthesia in preterm babies undergoing surgery: effects on the stress response. Lancet. 1987 Jan 31;329(8527):243-8.
  • Anand KJ, McIntosh N, Lagercrantz H, Young T, et al. Analgesia and Sedation in Preterm Neonates Who Require Ventilatory Support. (NOPAIN Trial). Arch Pediatr Adolesc Med. 1999;153:331-8.
    • Anand KJ, Hall RW, Desai N, Shephard B, Bergqvist LL, Young TE, et al. Effects of morphine analgesia in ventilated preterm neonates: primary outcomes from the NEOPAIN randomised trial. Lancet. 2004 May 22;363(9422):1673-82.
  • Simons S, van Dijk M, van Lingen RA, Roofthooft D, et al. Routine Morphine Infusion in Preterm Newborns Who Received Ventilatory Support. JAMA. 2003 Nov 12;290(18):2419-27.
    • Long-term follow up: de Graaf J, van Lingen RA, Simons SH, Anand KJ, et al. Long-term effects of routine morphine infusion in mechanically ventilated neonates on children’s functioning: Five-year follow-up of a randomized controlled trial. Pain. 2011;152:1391-7.
    • Long-term follow up: de Graaf J, van Lingen RA, Valkenburg AJ, Weisglas-Kuperus N, et al. Does neonatal morphine use affect neuropsychological outcomes a 8 to 9 years of age? Pain. 2013;154:449-58.
  • Azzopardi DV, Strohm B, Edwards AD, Dyet L, Halliday HL, Juszczak E, et al. Moderate hypothermia to treat perinatal asphyxial encephalopathy. N Engl J Med. 2009 Oct 1;361(14):1349-58.
  • Shankaran S, Laptook AR, Ehrenkranz RA, Tyson JE, McDonald SA, Donovan EF, et al. Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N Engl J Med. 2005 Oct 13;353(15):1574-84.
  • Azzopardi D, Strohm B, Marlow N, Brocklehurst P, Deierl A, Eddama O, et al. Effects of Hypothermia for Perinatal Asphyxia on Childhood Outcomes. N Engl J Med 2014; 371:140-149.
  • Shankaran S, Laptook A, Pappas A, McDonald S, Das A, Tyson J, et al. Effect of depth and duration of cooling on deaths in the NICU among neonates with hypoxic ischemic encephalopathy. JAMA 2014;312(24):2629-2639.
  • Schmidt B, Davis P, Moddemann D, Ohlsson A, Roberts RS, Saigal S, Solimano A, et al (TIPP Trial). Long-term effects of indomethacin prophylaxis in extremely-low-birth-weight infants. N Engl J Med 2001;344(26):1966-1972.
    • Long term follow-up: Schmidt B, Roberts R, Fanaroff A, Davis P, Kirpalani H, et al (TIPPInvestigators). Indomethacin prophylaxis, patent ductus arteriosus, and the risk of Bronchopulmonary dysplasia: further analyses from the trial of indomethacin prophylaxis in preterms. J Pediatr. 2006;148(6):730-4.
  • Vohr BR, Allan WC, Westerveld M, Schneider KC, Katz KH, et al. School-Age Outcomes of Very Low Birth Weight Infants in the Indomethacin Intraventricular Hemorrhage Prevention Trial. Pediatrics 2003;111(4):e340-6.
  • Painter MJ, Scher MS, Stein AD, Armatti S, Wang Z, Gardiner JC, et al. Phenobarbital compared with phenytoin for the treatment of neonatal seizures. N Engl J Med. 1999 Aug 12;341(7):485-9.
  • Adzick NS, Thom EA, Spong CY, Brock JW, Burrows PK, Johnson MP, Howell LJ, et al (MOMS Investigators). A Randomized Trial of Prenatal versus Postnatal Repair of Myelomeningocele. New Engl J Med. 2011;364, 993-1004.
  • Bell EF, Warburton D, Stonestreet BS, Oh W. Effect of fluid administration on the development of symptomatic patent ductus arteriosus and congestive heart failure in premature infants. N Engl J Med. 1980 Mar 13;302(11):598-604.
  • Van Overmeire B, Smets K, Lecoutere D, Van de Broek H, Weyler J, Degroote K, et al. A comparison of ibuprofen and indomethacin for closure of patent ductus arteriosus. N Engl J Med. 2000 Sep 7;343(10):674-81.
  • Van Overmeiere B, Allegaert K, Casaer A, Debauche C, et al. Prophylactic ibuprofen in premature infants: a multicentre, randomised, double-blind, placebo-controlled trial. Lancet. 2004;364:1945-49.
  • Valverde E, Pellicer A, Madero R, Elorza D, et al. Dopamine Versus Epinephrine for Cardiovascular Support in Low Birth Weight Infants: Analysis of Systemic Effects and Neonatal Clinical Outcomes. Pediatrics. 2006;117(6):e1213-22.
  • Osborn DA, Evans N, Kluckow M, Bowen J, and Rieger I. Low Superior Vena Cava Flow and Effect of Inotropes on Neurodevelopment to 3 Years in Preterm Infants. Pediatrics. 2007;120(2):372-80.
  • Paradisis M, Evans N, Kluckow M, and Osborn D. Randomized Trial of Milrinone Versus Placebo for Prevention of Low Systemic Blood Flow in Very Preterm Infants. J Pediatr. 2009;154:189-95.
  • Kirpalani H, Whyte RK, Andersen C, Asztalos EV, Heddle N, Blajchman MA, et al. The Premature Infants in Need of Transfusion (PINT) study: a randomized, controlled trial of a restrictive (low) versus liberal (high) transfusion threshold for extremely low birth weight infants. J Pediatr. 2006 Sep;149(3):301-7.
  • Ohls RK, Ehrenkranz RA, Wright LL, Lemons JA, Korones SB, Stoll BJ, et al. Effects of early erythropoietin therapy on the transfusion requirements of preterm infants below 1250 grams birth weight: a multicenter, randomized, controlled trial. Pediatrics. 2001 Oct;108(4):934-42.
Maternal-Fetal Medicine
  • Liggins GC and Howie RN. A controlled trial of antepartum glucocorticoid treatment for prevention of the respiratory distress syndrome. Pediatrics. 1972;50(4):515-25.
  • Meis PJ, Klebanoff M, Thom E, Dombrowski MP, Sibai B, Moawad AH, et al. Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate. N Engl J Med. 2003 Jun 12;348(24):2379-85.
  • Crowther CA, Hiller JE, Doyle LW, Haslam RR. Effect of magnesium sulfate given for neuroprotection before preterm birth: a randomized controlled trial. Australasian Collaborative Trial of Magnesium Sulphate (ACTOMgSO4) Collaborative Group. JAMA 2003;290:2669–76
    • Long term follow-up: Doyle LW, Anderson PJ, Haslam R, Lee K, Crowther C, et al (ACTOMgSO4 Group). School-age Outcomes of Very Preterm Infants After Antenatal Treatment With Magnesium Sulfate vs Placebo. JAMA. 2014 Sep 17;312(11):1105-13.
  • Thornton, JG, Hornbuckle, J, Vail, A, Spiegelhalter, DJ, Levene, M (GRIT study group). Infant wellbeing at 2 years of age in the Growth Restriction Intervention Trial (GRIT): multicentred randomised controlled trial. Lancet 2004;364:513-20.
    • Long term follow-up: Walker, DM, Marlow, N, Upstone, L, Gross, H, Hornbuckle, J, Vail, A, et al. The growth restriction intervention trial (GRIT): Long-term outcomes in a randomized trial of timing of delivery in fetal growth restriction. American Journal of Obstetrics and Gynecology 2011;204(1):34.e1-34.e
  • Ibrahim HM, Krouskop RW, Lewis DF, Dhanireddy R. Placental transfusion: umbilical cord clamping and preterm infants. J Perinatol. 2000;20(6):351-4.
    • META-ANALYSIS: Rabe H, Diaz-Rossello JL, Duley L, Dowswell T. 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. 2012;8(8):CD003248
  • Morris BH, Oh W, Tyson JE, Stevenson DK, Phelps DL, O'Shea TM, et al. Aggressive vs. conservative phototherapy for infants with extremely low birth weight. N Engl J Med. 2008 Oct 30;359(18):1885-96.
  • Moss RL, Dimmitt RA, Barnhart DC, Sylvester KG, Brown RL, Powell DM, et al. Laparotomy versus peritoneal drainage for necrotizing enterocolitis and perforation. N Engl J Med. 2006 May 25;354(21):2225-34.
  • Orenstein S, Hassal E, Furmaga-Jablonska W, Atkinson S, and Raanan M. Multicenter, Double-Blind, Randomized, Placebo-Controlled Trial Assessing the Efficacy and Safety of Proton Pump Inhibitor Lansoprazole in Infants with Symptoms of Gastroesophageal Reflux Disease. J Pediatr 2009;154;514-20.


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