title: Neurodevelopmental outcomes of extremely low birthweight infants randomised to different PCO2targets: the PHELBI follow-up study.
abstract: BACKGROUND
  Tolerating higher partial pressures of carbon dioxide (PCO2) in mechanically ventilated extremely low birthweight infants to reduce ventilator-induced lung injury may have long-term neurodevelopmental side effects. This study analyses the results of neurodevelopmental follow-up of infants enrolled in a randomised multicentre trial.
  
  
  METHODS
  Infants (n=359) between 400 and 1000 g birth weight and 23 0/7-28 6/7 weeks gestational age who required endotracheal intubation and mechanical ventilation within 24 hours of birth were randomly assigned to high PCO2or to a control group with mildly elevated PCO2targets. Neurodevelopmental follow-up examinations were available for 85% of enrolled infants using the Bayley Scales of Infant Development II, the Gross Motor Function Classification System (GMFCS) and the Child Development Inventory (CDI).
  
  
  RESULTS
  There were no differences in body weight, length and head circumference between the two PCO2target groups. Median Mental Developmental Index (MDI) values were 82 (60-96, high target) and 84 (58-96, p=0.79). Psychomotor Developmental Index (PDI) values were 84 (57-100) and 84 (65-96, p=0.73), respectively. Moreover, there was no difference in the number of infants with MDI or PDI <70 or <85 and the number of infants with a combined outcome of death or MDI<70 and death or PDI<70. No differences were found between results for GMFCS and CDI. The risk factors for MDI<70 or PDI<70 were intracranial haemorrhage, bronchopulmonary dysplasia, periventricular leukomalacia, necrotising enterocolitis and hydrocortisone treatment.
  
  
  CONCLUSIONS
  A higher PCO2target did not influence neurodevelopmental outcomes in mechanically ventilated extremely preterm infants. Adjusting PCO2targets to optimise short-term outcomes is a safe option.
  
  
  BACKGROUND
  ISRCTN56143743.
authors.affiliation: Division of Neonatology, University Hospital for Children and Adolescents, University of Leipzig, Leipzig, Germany.
authors.forename: Ulrich H
authors.initials: UH
authors.lastname: Thome
authors.affiliation: Division of Neonatology, IS Dr. von Hauner University Children's Hospital, Ludwig Maximilian University of Munich, München, Germany.
authors.forename: Orsolya
authors.initials: O
authors.lastname: Genzel-Boroviczeny
authors.affiliation: Division of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany.
authors.forename: Bettina
authors.initials: B
authors.lastname: Bohnhorst
authors.affiliation: Division of Neonatology and Pediatric Critical Care, University Hospital for Children and Adolescents, University of Ulm, Ulm, Baden-Württemberg, Germany.
authors.forename: Manuel
authors.initials: M
authors.lastname: Schmid
authors.affiliation: Division of Neonatology and Pediatric Critical Care, University Hospital for Children and Adolescents, Albert Ludwigs University Freiburg, Freiburg, Germany.
authors.forename: Hans
authors.initials: H
authors.lastname: Fuchs
authors.affiliation: Division of Neonatology and Pediatric Critical Care, Elisabeth Children's Hospital, Klinikum Oldenburg, Medical Campus, Carl von Ossietzky University of Oldenburg, Oldenburg, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Rohde
authors.affiliation: Hospital for General Pediatrics and Neonatology, Otto von Guericke University Magdeburg, Magdeburg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Avenarius
authors.affiliation: Division of Neonatology, University Hospital for Children and Adolescents, Friedrich-Alexander University Erlangen, Erlangen, Germany.
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Topf
authors.affiliation: Mutter-Kind-Zentrum, Klinikum rechts der Isar, Technical University of Munich, München, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Zimmermann
authors.affiliation: University Hospital for General Pediatrics and Neonatology, Justus Liebig University Giessen, Giessen, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Faas
authors.affiliation: Division of Neonatology, Hospital for Children and Adolescents, Vivantes-Hospital Neukölln, Berlin, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Timme
authors.affiliation: Hospital for Children and Adolescents, Children's Hospital of the Third Order, Munich, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Kleinlein
authors.affiliation: Division of Neonatology, University Hospital for Children and Adolescents of the J.W. Goethe University Frankfurt/Main, Frankfurt am Main, Germany.
authors.forename: Horst
authors.initials: H
authors.lastname: Buxmann
authors.affiliation: Hospital for Children and Adolescents, Central Hospital Augsburg, Augsburg, Germany.
authors.forename: Wilfried
authors.initials: W
authors.lastname: Schenk
authors.affiliation: St. Hedwig Hospital, University of Regensburg (H.S.), Regensburg, Germany.
authors.forename: Hugo
authors.initials: H
authors.lastname: Segerer
authors.affiliation: Department of Neonatology and Pediatric Intensive Care, Katholisches Klinikum, Ruhr University Bochum, Bochum, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Teig
authors.affiliation: Division of Neonatology, University Hospital for Children and Adolescents, University of Leipzig, Leipzig, Germany.
authors.forename: Annett
authors.initials: A
authors.lastname: Bläser
authors.affiliation: Division of Neonatology and Pediatric Critical Care, University Hospital for Children and Adolescents, Albert Ludwigs University Freiburg, Freiburg, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Hentschel
authors.affiliation: Division of Neonatology and Pediatric Critical Care, University Hospital for Children and Adolescents, Ernst Moritz Arndt University Greifswald, Greifswald, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Heckmann
authors.affiliation: Division of Neonatology, University Hospital for Children and Adolescents of the J.W. Goethe University Frankfurt/Main, Frankfurt am Main, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Schlösser
authors.affiliation: Hospital for Children and Adolescents, Children's Hospital of the Third Order, Munich, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Peters
authors.affiliation: Division of Neonatology, Hospital for Children and Adolescents, Vivantes-Hospital Neukölln, Berlin, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Rossi
authors.affiliation: Division of Neonatology, University Hospital for Children and Adolescents, Friedrich-Alexander University Erlangen, Erlangen, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Rascher
authors.affiliation: Hospital for General Pediatrics and Neonatology, Otto von Guericke University Magdeburg, Magdeburg, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Böttger
authors.affiliation: Division of Neonatology and Pediatric Critical Care, Elisabeth Children's Hospital, Klinikum Oldenburg, Medical Campus, Carl von Ossietzky University of Oldenburg, Oldenburg, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Seidenberg
authors.affiliation: Division of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany.
authors.forename: Gesine
authors.initials: G
authors.lastname: Hansen
authors.affiliation: Division of Neonatology and Pediatric Critical Care, University Hospital for Children and Adolescents, University of Ulm, Ulm, Baden-Württemberg, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Zernickel
authors.affiliation: Division of Neuropediatrics, University Hospital for Children and Adolescents, University of Ulm, Ulm, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Bode
authors.affiliation: Institute of Epidemiology and Medical Biometry, University of Ulm, Ulm, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Dreyhaupt
authors.affiliation: Institute of Epidemiology and Medical Biometry, University of Ulm, Ulm, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Muche
authors.affiliation: Division of Neonatology and Pediatric Critical Care, University Hospital for Children and Adolescents, University of Ulm, Ulm, Baden-Württemberg, Germany.
authors.forename: Helmut D
authors.initials: HD
authors.lastname: Hummler
mesh_terms: D000893:Anti-Inflammatory Agents / Q000009:adverse effects; D001997:Bronchopulmonary Dysplasia / Q000453:epidemiology; D002245:Carbon Dioxide / Q000097:blood*; D002547:Cerebral Palsy / Q000453:epidemiology; D002657:Child Development; D020345:Enterocolitis, Necrotizing / Q000453:epidemiology; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000009:adverse effects; D007223:Infant; D052577:Infant, Extremely Low Birth Weight; D062071:Infant, Extremely Premature; D007231:Infant, Newborn; D020300:Intracranial Hemorrhages / Q000453:epidemiology; D007442:Intubation, Intratracheal; D007969:Leukomalacia, Periventricular / Q000453:epidemiology; D008297:Male; D009483:Neuropsychological Tests; D012121:Respiration, Artificial
chemical_list: D000893:Anti-Inflammatory Agents; D002245:Carbon Dioxide; D006854:Hydrocortisone
keywords: Bayley scales; bronchopulmonary dysplasia; intraventricular haemorrhage; neurodevelopmental outcome; permissive hypercapnia