Neonatologist SickKids, University of Toronto and CHU de Québec, Université Laval Toronto, Ontario, Canada
Background: Very preterm neonates exposed to prolonged mechanical ventilation are at higher risk of brain injury and neurodevelopmental impairment early in life. However, the association of mechanical ventilation with neurodevelopment at school-age in very preterm children remains largely unknown.
Objective: To determine the relationship between exposure to mechanical ventilation and neurodevelopmental outcomes at age 8 years in very preterm children, accounting for neonatal brain injury.
Design/Methods: A prospective cohort of 105 very preterm children (mean GA 27 weeks, 60 [57%] male) completed preterm brain MRI (mean 32 weeks corrected age), and neurodevelopmental assessment at age 8 years. Severity of brain injury was determined by manually segmenting and quantifying volumes of white matter injury (WMI) and cerebellar hemorrhage and by the presence of grade 3 or 4 IVH. Cognition, visuomotor integration and motor function were assessed with WASI-II full-scale IQ, Beery-VMI 6th Ed and the MABC-2, respectively. Multivariable regressions adjusting for GA at birth, sex, maternal education, neonatal illness, and severity of brain injury were used to examine the association between duration of mechanical ventilation (i.e., invasive ventilation involving endotracheal intubation) and 8-year outcomes.
Results: Duration of mechanical ventilation in the neonatal period (median 13 days) was independently associated with lower visuomotor integration performance (ß=-0.38, p=0.001) and motor scores (ß=-0.46, p=0.002) at age 8 years. Duration of mechanical ventilation also predicted lower cognitive scores in females (ß=-0.37, p<0.001), but not males. No sex-specific association of mechanical ventilation for visuomotor integration or motor scores was found. In addition, the association between mechanical ventilation and poorer cognition was potentiated by neonatal WMI. The association between mechanical ventilation and adverse outcomes remained unchanged when accounting for neonatal infections, NEC stage ≥2 and significant hypotension. Conclusion(s): Mechanical ventilation in the neonatal period is associated with long-term adverse outcomes, beyond that accounted for brain injury evident on MRI. Female children and those with WMI are specifically vulnerable to the adverse relationship between mechanical ventilation and cognition, suggesting the need for targeted intervention strategies. Further research is needed to better understand the brain changes underlying the long-lasting effects of mechanical ventilation.
Table 1 Association between neonatal exposure to mechanical ventilation and adverse neurodevelopmental outcomes at 8 years of age in children born very preterm
Figure 1 Neonatal exposure to mechanical ventilation is associated with lower FSIQ at age 8 years in females born very preterm
Figure 2 Neonatal exposure to mechanical ventilation and WMI volume interact to predict FSIQ score at age 8 years
Authors/Institutions: Mireille Guillot, Hospital for Sick Children, Toronto, Ontario, Canada; Ting Guo, The Hospital for Sick Children, Toronto, Ontario, Canada; Anne Synnes, BC Women's Hospital, Vancouver, British Columbia, Canada; Jarred Garfinkle, McGill University, Westmount, Quebec, Canada; Vann Chau, University of Toronto, Toronto, Ontario, Canada; Ruth E. Grunau, University of British Columbia, Vancouver, British Columbia, Canada; Steven P. Miller, Hospital for Sick Children, Toronto, Ontario, Canada