Explore electrophysiological markers to reflect brain maturity and the risk of neurodevelopmental disorders in preterm born children

Abstract

The survival rates have significantly increased for PTB children in recent years, but preterm-born (PTB) children remain at a high risk of having cognitive and neurodevelopmental problems. This thesis aims to investigate the long-term developmental outcomes of PTB children and the neuro-cognitive basis of their cognitive deficits and neurobehavioral impairment. In Chapter 2, we investigated the risk of attention deficit hyperactivity disorder (ADHD) in PTB children compared to children born full-term (FT), through a population-based cohort study. We retrieved medical records in children born between 2004 to 2014 in Hong Kong and followed them up until 2020. We have found an increased risk of ADHD in all subcategories of PTB children compared to children delivered at term. The effect of preterm birth on ADHD could be partially mediated by preterm postnatal complications including retinopathy of prematurity, intraventricular haemorrhage and early respiratory infections. In Chapter 3, we quantitively synthesized previous electroencephalogram (EEG) research that compared PTB and FT children at the age of 2 to 17 years. 20 EEG studies including resting-state EEG studies using quantitative spectral power analysis, and auditory event-related potentials (AERP) and visual evoked potentials (VEP) studies were included in the meta-analysis. Only excessive resting-state delta band power and attenuated visual evoked P1 were consistently reported to have significant differences between PTB and FT children. The results indicated that PTB children’s visual-spatial deficits could be related to their attenuated cortical sensory responses. However, a significant level of heterogeneity exists in the literature. In Chapter 4, in a resting-state EEG study comparing preschool PTB children and the age-matched control subjects FT children, we used an advanced EEG analysis protocol to separate the periodic and aperiodic components of the EEG power spectrum. We found that PTB children exhibited significantly elevated aperiodic offset and exponent as well as delta and theta band power compared to FT children. The traditional band power had a significant proportion of aperiodic components, and the abnormal aperiodic components were found to be significantly different in PTB children than in children FT children, which might be related to delayed brain maturation in PTB children. In conclusion, this thesis demonstrated that PTB children are at higher risk of neurobehavioral impairments such as attention-deficit hyperactivity disorders and cognitive deficits in early childhood compared to their full-term-born peers. PTB children should have enhanced developmental surveillance and long-term follow-up of their neurodevelopment and cognitive function during childhood. The developmental problems and cognitive deficits of PTB children might be related to disrupted cortical development at the end of the second trimester and during the third trimester. Early preterm postnatal complications can also contribute to the increased risk in childhood of neurodevelopmental disorders. The brain immaturity of PTB children could be demonstrated through the brain electrophysiological responses recorded in EEG, and some EEG parameters have the potential to become an electrophysiological marker to assist early screening and diagnosis of neurodevelopmental or cognitive problems in preschool children.