Apnea is Associated with Neurodevelopmental Impairment in Very Low Birth Weight Infants

Objective: To determine whether apnea in preterm infants is associated with abnormal neurodevelopmental outcome.

Methods: We determined the number of days that apnea and bradycardia spells were noted by the nursing staff, during the initial hospitalization of 175 preterm infants of less than <1250 g birth weight or <32 weeks gestation who had been enrolled in the follow-up program of the Royal Victoria Hospital. Multiple logistic and multiple linear regression models were constructed to determine the relationships between apnea days and neurodevelopmental impairment at 3 years of age, after correcting for gestation, sex, intrauterine growth restriction, intraventricular hemorrhage, periventricular leukomalacia, pre- and postnatal steroids, and maternal education.

Results: A total of 41 infants had neurodevelopmental impairment (Bayley MDI or PDI <70, cerebral palsy or blindness). By multiple logistic regression, an increasing number of days on which at least one apnea occurred, "total apnea days", and male sex were significantly associated with increasing probability of neurodevelopmental impairment, p<0.01, the sum of days of assisted ventilation and apnea days occurring after extubation was also associated with impairment in a separate regression model, p<0.001. Lower MDI at 3 years was significantly associated with postnatal steroid use, p=0.004. Lower PDI was associated with increasing apnea days, male sex, and postnatal steroid use, p<0.001. Functional impairment (a score on any one of the four dimensions of the Vineland scale <70), found in 17% of the infants, was associated with increasing apnea days, p<0.05. Caffeine treatment was not independently associated with any outcome.

Conclusion: An increasing number of days that apnea was recorded during hospitalization was associated with a worse outcome. Among the potential explanations for this finding is the possibility that multiple recurrent hypoxic and bradycardic spells may cause brain injury.