Early identification and intervention for infants at high risk of neurodevelopmental disorders

Developmental disability is a broad term encompassing many different diagnoses. These conditions, predominantly associated with the functioning of the neurological system and brain, manifest during infancy or childhood and usually last throughout a person’s lifetime. These are marked by delayed development or functional limitations in cognition, language, communication, behavior socialization or motor function, and are defined as ‘neurodevelopmental disorders’. Most neurodevelopmental disorders are caused by a complex mix of factors, that may affect neurological function. This might be due to genetics, due to conditions occurring during pregnancy, such as malnutrition, infection or parental behavior (i.e. smoking, drugs and/or drinking alcohol during pregnancy,…) or due to perinatal and neonatal complications. Neurodevelopmental problems due to injury that has occurred during the perinatal period can mainly be subdivided in 3 groups: - Infants with congenital malformations, including syndromes, chromosomal and genetic defects and inborn errors of metabolism - Infants that are born preterm and/or with low birthweight - Infants with a hypoxic-ischemic insult and/or perinatal stroke This doctoral thesis focused on preterm birth and perinatal stroke, two main perinatal causes of neurodevelopmental disorders and improved our insight about the neurodevelopmental outcome, early diagnosis and early intervention of those high-risk infants. PART I of this dissertation focused on very preterm (VPT)/very-low-birthweight (VLBW) infants. The care for preterm infants has improved considerably in the last decades, however, they continue to face complex medical and neurodevelopmental problems. In the last few decades preterm births increased and the survival of VPT/VLBW have improved, however this is not accompanied by increased morbidity. Although most preterm born infants do not develop major impairments, they are at higher risk to develop cerebral palsy (CP), motor and/or cognitive impairments and the risk increases with decreasing gestational age (GA) and birthweight (BW). Recent actual mortality, morbidity and neurodevelopmental outcome rates among VPT/VLBW infants is essential for family counseling and evaluation of innovative approaches to enhance outcomes. The first part of this dissertation comprises two chapters, providing an overview of the current prevalences of neurodevelopmental impairment, globally as well as for our local population. In chapter 1, existing literature regarding the overall neurodevelopmental outcome at two years corrected age in VLB/VLBW infants born over the last decade was reviewed and reported in a meta-analytic review. In chapter 2, the neonatal mortality and neurodevelopmental outcome in a national population-based cohort was investigated. PART II of this dissertation focused on infants with perinatal stroke. Perinatal stroke might not be as common as preterm birth, it is still an important group of infants because it is know that more than quart of the children with perinatal results in neurological deficits, however the exact number varies considerably between studies. Early detection and referral of infants at risk for intervention, rather than referral children with known CP has been called for. Nonetheless, this requires careful monitoring in the first months of development and appropriate early diagnostic tools. The literature on established and experimental approaches for the treatment of upper limb function unilateral spastic CP (USCP) in older children is comprehensive, however, in young infants this remain practically unexplored, despite evidence of a critical time limit for activity-dependent plasticity to influence the corticospinal tract development during the first years of life. Given the shortage of early intervention studies, very little is known about the feasibility of such intervention programs in very young infants. Part II is composed of two chapters, describing two original research articles. In chapter 3, the neurological outcome was for each specific type of stroke lesion reported in infants with perinatal stroke as well as the predictability of two motor evaluation tools (‘General movement assessment [GMA]’ and the ‘Hand assessment for infants [HAI]’) for early detection of USCP. Lastly, in chapter 4, a study was undertaken in infants with perinatal stroke at high risk of USCP to investigate the feasibility of a parent-delivered home-based early intervention program, comparing two therapy approaches, namely ‘Constraint-induced movement therapy (baby-CIMT)’ and ‘hand–arm bimanual training (baby-HABIT)’ and to address potential obstacles for further implementation. In conclusion, this dissertation provided some useful insight on the outcome of those high-risk infants as well as some newfound knowledge about early predictions tools and early intervention for infants with perinatal stroke. However, more research is needed in order to fully understand the impact of very preterm birth and perinatal stroke on the longer term and how early diagnosis and early intervention can be improved in high-risk infants.