Establishing a standardised approach for the measurement of neonatal noxious-evoked brain activity

Electroencephalography (EEG) can be used in neonates to measure brain activity changes that are evoked by noxious events, such as clinically-required immunisations, cannulation and heel lancing. EEG provides an alternative approach to infer pain experience in infants compared with more commonly used behavioural and physiological pain assessments. Establishing the generalisability and validity of these measures will help corroborate the use of brain-derived outcomes to evaluate the efficacy of new or existing drugs to treat neonatal pain. This study aims to test whether an EEG template of noxious-evoked brain activity, that was originally derived in a sample of term-aged infants at the Oxford John Radcliffe Hospital in 2017, can reliably distinguish noxious from non-noxious events in two independent datasets retrospectively collected at University College London Hospital and prospectively collected at Royal Devon & Exeter Hospital. We aim to reproduce three published results that use the EEG template to quantify noxious-evoked changes in brain activity. We will test (i) whether a significantly larger noxious-evoked template magnitude is recorded in response to a clinical heel lance compared to a non-noxious control heel lance procedure; (ii) whether the scale of the template magnitude evoked by a noxious heel lance is equivalent in independent cohorts of infants; and (iii) whether the magnitude of the noxious-evoked brain activity increases with age in premature infants up to 37 weeks postmenstrual age. Positive replication of these studies will build confidence in the use of brain-derived signals as valid and reliable pain-related outcomes which could be used to evaluate analgesic efficacy in neonates.