Premature Mortality, Risk Factors, and Causes of Death Following Childhood-Onset Neurological Impairments: A Systematic Review

Abstract

Background: Neurological impairment (NI) and disability are associated with reduced life expectancy, but the risk and magnitude of premature mortality in children vary considerably across study settings. We conducted a systematic review to estimate the magnitude of premature mortality following childhood-onset NI worldwide and to summarize known risk factors and causes of death.Methods: We searched various databases for published studies from their inception up to 31st October 2020. We included all cohort studies that assessed the overall risk of mortality in individuals with childhood-onset epilepsy, intellectual disability (ID), and deficits in hearing, vision and motor functions. Comparative measures of mortality such as the standardized mortality ratio (SMR), risk factors and causes were synthesized quantitatively under each domain of impairment. This review is registered on the PROSPERO database (registration number CRD42019119239).Results: The search identified 2,159 studies, of which 24 studies were included in the final synthesis. Twenty-two (91.7%) studies originated from high-income countries (HICs). The median SMR was higher for epilepsy compared with ID (7.1 [range 3.1–22.4] vs. 2.9 [range 2.0–11.6]). In epilepsy, mortality was highest among younger age groups, comorbid neurological disorders, generalized seizures (at univariable levels), untreatable epilepsy, soon after diagnosis and among cases with structural/metabolic types, but there were no differences by sex. Most deaths (87.5%) were caused by non-epilepsy-related causes. For ID, mortality was highest in younger age groups and girls had a higher risk compared to the general population. Important risk factors for premature mortality were severe-to-profound severity, congenital disorders e.g., Down Syndrome, comorbid neurological disorders and adverse pregnancy and perinatal events. Respiratory infections and comorbid neurological disorders were the leading causes of death in ID. Mortality is infrequently examined in impairments of vision, hearing and motor functions.Summary: The risk of premature mortality is elevated in individuals with childhood-onset NI, particularly in epilepsy and lower in ID, with a need for more studies for vision, hearing, and motor impairments. Survival in NI could be improved through interventions targeting modifiable risk factors and underlying causes.

Cerebral palsy and developmental intellectual disability in children younger than 5 years: Findings from the GBD-WHO Rehabilitation Database 2019

“…Reports also suggest that less than half of children are clinically diagnosed by 24 months of age compared to the practice in HICs ( 9 ). Moreover, many children with CP die before their second birthday, thus remain undiagnosed and many may not be counted at all ( 31 ). There is a growing international recognition of the technological advances to make early detection and intervention for CP before the age of 2 years feasible even in countries where clinical diagnosis may typically be delayed until age 4 years ( 11 , 32 ).…”

“…Consequently, children with these conditions in LMICs are more likely to experience a lower quality of life compared to their peers in HICs ( 40 ). These children are also at greater risk of premature mortality ( 31 ). While primary prevention should be prioritized, the substantial unmet rehabilitation needs of these children and others with developmental disabilities in LMICs as highlighted by a recent WHO report require urgent and priority attention for these children and their families ( 39 ).…”

The burden of neurological impairments and disability in older children measured in disability-adjusted life-years in rural Kenya

“…The relative YLL-burden (44.7/1000) was much higher than YLD-burden (8.4/1000), with the former contributing a substantial 83% of the total DALYs, of which 35% were caused by epilepsy. This is not surprising because mortality is highest among children with untreated epilepsy which might present with comorbid neurological and behavioural disorders [ 8 ]. Many studies of NI in the literature did not conduct follow-up for mortality leading to a lack of data for comparison.…”

“…Besides, the epidemiology of NI may be changing with a decline in under-five mortality [ 4 ], whereby improved child survival due to better control of infections [ 5 ], has increased the burden of neurodisability among older children [ 6 ]. Children with NI not only have an increased risk for other medical and psychiatric comorbidities [ 7 ] but also have a higher risk of premature mortality compared with their peers in the general population [ 8 ].…”

Accelerating progress on early childhood development for children under 5 years with disabilities by 2030

“…The gap between mortality and disability might be larger still, as our disability estimates are limited to the six conditions published in GBD 2016 (epilepsy, developmental intellectual disability, hearing loss, vision loss, autism spectrum disorder, and attention-deficit hyperactivity disorder), and do not include, for instance, the highly prevalent cerebral palsy without comorbid intellectual disability. 11 Available evidence also suggests that children with developmental disabilities have increased risk of premature mortality or reduced life expectancy, 14 thus underscoring the potential societal costs of failing to provide and support intervention services for the affected children and their families when it matters most. In our opinion, these data clearly suggest that any global efforts at curtailing child mortality must be complemented by appropriate support for children with developmental disabilities as they have a greater risk of poor or suboptimal physical, language, cognitive, or psychosocial development than do children without developmental disabilities.…”