Neonatal Sleep-Wake Analyses Predict 18-month Neurodevelopmental Outcomes

Abstract

Objectives: The neurological examination of critically ill neonates is largely limited to reflexive behavior. The exam often ignores sleep-wake physiology that may reflect brain integrity and influence long-term outcomes. We assessed whether polysomnography and concurrent cerebral near-infrared spectroscopy (NIRS) might improve prediction of 18-month neurodevelopmental outcomes.

Methods: Term newborns with suspected seizures underwent standardized neurologic examinations to generate Thompson scores and had 12-hour bedside polysomnography with concurrent cerebral NIRS. For each infant, the distribution of sleep-wake stages and electroencephalogram delta power were computed. NIRS-derived fractional tissue oxygen extraction (FTOE) was calculated across sleep-wake stages. At age 18-22 months, surviving participants were evaluated with Bayley Scales of Infant Development (Bayley-III), 3rd edition.

Results: Twenty-nine participants completed Bayley-III. Increased newborn time in quiet sleep predicted worse 18-month cognitive and motor scores (robust regression models, adjusted r2 = 0.22, p = .007, and 0.27, .004, respectively). Decreased 0.5-2 Hz electroencephalograph (EEG) power during quiet sleep predicted worse 18-month language and motor scores (adjusted r2 = 0.25, p = .0005, and 0.33, .001, respectively). Predictive values remained significant after adjustment for neonatal Thompson scores or exposure to phenobarbital. Similarly, an attenuated difference in FTOE, between neonatal wakefulness and quiet sleep, predicted worse 18-month cognitive, language, and motor scores in adjusted analyses (each p < .05).

Conclusions: These prospective, longitudinal data suggest that inefficient neonatal sleep-as quantified by increased time in quiet sleep, lower electroencephalogram delta power during that stage, and muted differences in FTOE between quiet sleep and wakefulness-may improve prediction of adverse long-term outcomes for newborns with neurological dysfunction.

Keywords: Neonatal polysomnography; near-infrared spectroscopy; neonatal intensive care; neurodevelopmental outcomes.

Figure 1

Neurodevelopmental outcome scores were associated with neonatal neurological examination scores and neonatal sleep parameters. (A) Lower (more normal) neonatal Thompson scores were associated with higher 18-month Bayley Scales of Infant Development, 3rd edition, cognitive scores; however, there were three outliers who received cognitive scores of 55. (B) The percent time spent in neonatal quiet sleep was associated with Bayley Scales of Infant Development, 3rd edition, cognitive scale scores; however, there were three outliers who received cognitive scores of 55, with a range of percent quiet sleep.

Figure 2

Neonatal EEG delta power was associated with neurodevelopmental outcome. EEG power (0.5–2 Hz) varied across sleep–wake stages for a full term newborn with HIE who had normal Bayley Scales of Infant Development, 3rd edition, scores across all domains at 18 months (A). The proportion of quiet sleep was higher and the overall delta power was lower for another term newborn with HIE who had Bayley Scales of Infant Development, 3rd edition, scores <60 in all domains at 18 months (B).

Figure 3

Changes in brain oxygen metabolism across sleep–wake stages were associated with neurodevelopmental outcome. Cerebral rSO₂ cycled across sleep–wake stages for a full term newborn with HIE who had normal Bayley Scales of Infant Development, 3rd edition, scores across all domains at 18 months (A). The changes across sleep–wake stages was muted for another term newborn with HIE who had quadriparetic cerebral palsy, no expressive language, and treatment-resistant epilepsy when she died at age 15 months (B).