Neurodevelopmental outcomes of extremely low birthweight infants randomised to different PCO2 targets: the PHELBI follow-up study

Arch Dis Child Fetal Neonatal Ed. 2017 Sep;102(5):F376-F382. doi: 10.1136/archdischild-2016-311581. Epub 2017 Jan 13.

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 PCO2 or to a control group with mildly elevated PCO2 targets. 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 PCO2 target 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 PCO2 target did not influence neurodevelopmental outcomes in mechanically ventilated extremely preterm infants. Adjusting PCO2 targets to optimise short-term outcomes is a safe option.

Trial registration number: ISRCTN56143743.

Keywords: Bayley scales; bronchopulmonary dysplasia; intraventricular haemorrhage; neurodevelopmental outcome; permissive hypercapnia.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Anti-Inflammatory Agents / adverse effects
  • Bronchopulmonary Dysplasia / epidemiology
  • Carbon Dioxide / blood*
  • Cerebral Palsy / epidemiology
  • Child Development*
  • Enterocolitis, Necrotizing / epidemiology
  • Female
  • Humans
  • Hydrocortisone / adverse effects
  • Infant
  • Infant, Extremely Low Birth Weight*
  • Infant, Extremely Premature*
  • Infant, Newborn
  • Intracranial Hemorrhages / epidemiology
  • Intubation, Intratracheal
  • Leukomalacia, Periventricular / epidemiology
  • Male
  • Neuropsychological Tests
  • Respiration, Artificial*

Substances

  • Anti-Inflammatory Agents
  • Carbon Dioxide
  • Hydrocortisone