Early Development of Sleep-wake Cycles in Premature Infants and Its Impact on Neurodevelopmental Outcome

General description - Aim of the study

Due to development of intensive care the number of surviving premature infants increased significantly.Delayed emergence of sleep-wake-cycling in newborns can be the first sign of brain injury. Clearly defined sleep-states can be identified from 32 weeks of gestation onwards. Few studies show, that extremely premature infants (<26 weeks of gestation) may already show early sleep-states. In our project we are aiming to study the emergence of sleep-wake-cycling in extremely premature infants, prospectively collecting electroencephalographic (EEG) data. Premature infants <29 weeks of gestation will be included and measured for a 3 hour period every second week with conventional and amplitude-integrated EEG. New analytical methods (automatic neonatal EEG algorithm) will be used and compared to conventional visual analysis. In an international and interdisciplinary cooperation between physicians, electrophysiologist and mathematicians we will be able to deduct conclusions providing important prognostic information for patient, parents and physicians.

State of the art and scientific challenge Increasingly data show, that a delayed emergence of sleep-wake cycling in newborns can be the first sign of brain injury and is associated to later adverse neurodevelopmental outcome. Due to increasing survival rates among the very premature population the prevention from later neurological deficit currently becomes even more important. Rates of cerebral palsy and ouvert cerebral lesions (cystic periventricular leukomalacia and peri/intraventricular haemorrhage) are decreasing, but the incidence of neurodevelopmental impairment remains high in preterm infants. This is explained by the understanding of different mechanisms in brain injury (for example inflammation, oxidative stress, impaired connectivity) and results in mainly cognitive impairment (1). Therefore greater attention needs to be directed toward preterm neonatal populations to better understand brain adaptation both with and without medical complications. Neurophysiologic surveillance is necessary in these infants to adequately asses cerebral function and is difficult within this population by clinical aspects only. Conventional EEG is today´s gold standard for neurophysiologic diagnosis. Nevertheless it is not suitable for continuous recording since it is producing large data volumes which cannot be assessed directly at the bedside. In an effort to solve this problem, various methods of reducing and compressing the EEG signal have been developed, the amplitude-integrated EEG (aEEG), being one of them.

Emergence of sleep-wake-cycling The concept of state during early brain ontogenesis of the preterm infant is controversial. It is generally accepted that patterns representing sleep in preterm infants are highly variable and less organized than patterns described for full-term infants. Well organized sleep states do not appear before 31 weeks of gestation and are not well established until 36 weeks postconceptional age. However several researchers have questioned this assumption based on studies of sleep in preterm infants (4-7). They support that rudimentary state differentation might be present as early as 26 weeks of gestation. In our study from 2001 we observed cyclical variations of EEG background activity resembling early sleep-wake cycles as early as at 24/25 weeks of gestation (2).

Neurophysiological methods - amplitude-integrated EEG For early identification of infants at high risk and to optimize treatment, it is mandatory to have access to a reliable validated diagnostic method with excellent predictive value for later neurodevelopmental outcome. The aEEG is a readily available, informative and reliable technique for continuous non-invasive monitoring of brain activity even in extremely premature infants. Our research group has more than ten years of experience using of the amplitude-integrated EEG and it is a simple method for continuous bedside monitoring in the neonatal intensive care unit setting. Our group has recently shown aEEG has a predictive value for later outcome in preterm infants and can therefore be used as an early prognostic tool for neurodevelopmental outcome (3).