Determinants of health-related quality of life among adolescents with cerebral palsy in Bangladesh CURRENT STATUS:

Background: The health-related quality of life (HRQoL) of adolescents with cerebral palsy (CP) in low and middle-income countries is often poor, as is the case in Bangladesh. This study examined what modifiable factors are predictors of HRQoL among adolescents with CP in rural Bangladesh, a typical low- and middle-income country (LMIC). Methods: Adolescents with CP (10 to 18y) were identified using the Bangladesh Cerebral Palsy Register. HRQoL was assessed with the Cerebral Palsy Quality of Life-Teens questionnaire (CPQoL-Teens). Bivariate analysis and hierarchical multiple linear regression models related adolescent clinical characteristics and mental health, caregiver mental health and proxies of socioeconomic status to HRQoL outcomes. Results: 154 adolescents with CP (mean age 15y 1mo SD 1y 8mo, female n =31.2%) participated in this study. Numerous characteristics correlated to HRQoL; strongest correlation was between ‘feelings about functioning’ and motor impairment ( r =0.545). Nine factors were predictive of CPQoL-Teens dimensions; adolescent sex, school attendance, severity of motor impairment, hearing and speech impairment, mother’s education, primary caregiver depression and stress, and having a sanitary latrine at home resulting in score changes of between 0.79 (95% CI 0.24 to 1.35) to 35.1 (95% CI 6.03 to 64.22). Conclusions: Many of the factors predicting the HRQoL of adolescents with CP are amenable to intervention, and have the potential to improve adolescent wellbeing. Several determinants are priorities of the sustainable development goals (SDGs); these findings should inform resource prioritization to improve the wellbeing of adolescents with CP in Bangladesh and other LMICs. We extracted demographic and clinical information about adolescents from the BCPR database including age, sex, type of CP, severity of motor impairment using the gross motor function classification system (GMFCS), other associated impairments, school attendance and proxies of socioeconomic status such as monthly family income, household crowding, access to running water and sanitation. Impairments were categorized as yes/ no based on existing diagnosis or presence of impairment during BCPR assessment. GMFCS is a five level classification system; children classified at GMFCS level 1 are independently ambulant whereas children at Level V require wheeled mobility (23). BMI was calculated as weight divided by height and considered underweight if <18.5. Type of housing was defined as Kutcha (houses made from mud, thatch or other organic materials, considered impermanent); semi-pucca housing (made with a combination of materials, considered semi-permanent); and pucca (made from brick, stone, timber or cement, considered permanent). Number of household members was divided by number of rooms to provide persons per room rate of crowding. Non-sanitary latrine was defined as a latrine that discharges into open space.

Teens dimensions; adolescent sex, school attendance, severity of motor impairment, hearing and speech impairment, mother's education, primary caregiver depression and stress, and having a sanitary latrine at home resulting in score changes of between 0.79 (95% CI 0.24 to 1.35) to 35.1 (95% CI 6.03 to 64.22). Conclusions: Many of the factors predicting the HRQoL of adolescents with CP are amenable to intervention, and have the potential to improve adolescent wellbeing. Several determinants are priorities of the sustainable development goals (SDGs); these findings should inform resource prioritization to improve the wellbeing of adolescents with CP in Bangladesh and other LMICs.

Background
Health-related quality of life (HRQoL), a subjective multidimensional concept for measuring the interaction between health status and physical, psychological, and social aspects of wellbeing, is an emerging focus in low and middle-income countries (LMICs) such as Bangladesh (1). Particularly relevant to adolescents with cerebral palsy (CP), understanding of HRQoL can be used as an indicator of intervention outcomes and provide understanding of burden of disease (2). Moreover, understanding of HRQoL in LMICs flips the switch on poverty, allowing for focus on what people have, rather than what they do not (3).
CP is the major cause of childhood physical disability worldwide although the majority of cases are in LMICs (4). Estimated prevalence of CP in Bangladesh is 3.4 per 1,000 children and is likely to be associated with more severe physical, cognitive and communication impairments (5). Recent studies have determined that adolescents with CP in Bangladesh (6), and from other LMICs (7) have significantly poorer HRQoL outcomes than peers without disability, although little is known about determinants of HRQoL in these settings.
To date, the majority of HRQoL research has been conducted in high-income countries (HICs) and findings suggest it is predicted by a range of personal and environmental factors (8). For example, a European study of 551 adolescents with CP found psychological problems and parenting stress predicted HRQoL whereas socio-demographic and impairment severity characteristics did not (9). Other studies set in HICs have reported that impairment, in particular motor functioning, is predictive of physical wellbeing dimensions of HRQoL (10,11). These are important findings to inform HRQoL research in LMIC settings, however patterns of HRQoL appear to be different between HIC and LMIC (7,8). It is therefore reasonable to suggest that determinants of HRQoL will also differ between HIC and LMIC, requiring specific exploration.
Only a handful of studies from LMICs have examined determinants of HRQoL among children and adolescents with CP, of which only one has examined predictive relationships (7). The Turkish study of 40 children with CP found that, among other factors, motor function was predictive of 'physical wellbeing' using the Paediatric Quality of Life Inventory (12); other studies have confirmed an association between motor function and HRQoL (12)(13)(14)(15)(16). Studies from LMICs have also indicated a relationship between HRQoL dimensions and factors such as child age (13), child sex (13), child education (17), family income (13), speech impairment (18), cognitive impairment (14,18), visual impairment (14), epilepsy/ seizure disorder (14,15,18), caregiver age (16), and mother's education (13) (20) and is included as a potential determinant in our analysis. We also explore proxies of socio-economic status related to housing infrastructure due to their potential impact on adolescent wellbeing in the study context.  We extracted demographic and clinical information about adolescents from the BCPR database including age, sex, type of CP, severity of motor impairment using the gross motor function classification system (GMFCS), other associated impairments, school attendance and proxies of socio-economic status such as monthly family income, household crowding, access to running water and sanitation. Impairments were categorized as yes/ no based on existing diagnosis or presence of impairment during BCPR assessment. GMFCS is a five level classification system; children classified at GMFCS level 1 are independently ambulant whereas children at Level V require wheeled mobility (23).

Statistical methods
Descriptive statistics were used to summarise the cohort. Data was assessed for normality using Shapiro Wilk and visual inspection of residual plots. Bivariate analysis using Spearman's correlation was conducted to determine the relationship between HRQoL and adolescent and caregiver characteristics and proxies of socio-economic status; correlation were considered small (≤0.49), medium (0.50 to 0.79), and large (≥0.80) (28).
Hierarchical multiple linear regression was used to determine predictors of HRQoL.
Included predictor variables were selected on the basis of statistical (i.e. significant association to HRQoL, p<0.050) and theoretical concerns. Assumptions of linearity, homoscedasticity and normality were assessed through examination of residual plots; independence of observations assessed with Durbin-Watson statistic, and Multicollinearity assessed through correlation, tolerance and variance inflation factor (VIF) coefficients. No adjustment was made for multiple testing due to the investigative nature of the study. All statistical analysis was conducted using SPSS version 24 (IBM Armonk, NY, USA). A p value of <0.050 was considered significant.

Participant characteristics
192 adolescents with CP aged 10 to 18 years were enrolled in BCPR at the time of the present study. 154 (mean age 15y 1mo) agreed to participate of which 48 (31.2%) were female. Participation rate was 80.2%.
Characteristics of adolescents with CP and caregivers are provided in Table 1. Majority of adolescents had spastic type CP, of which quadriplegia and monoplegia/hemiplegia were most common; required wheeled mobility (i.e. GMFCS level III and above); and were underweight. More than half had cognitive impairment and more than two thirds had speech impairment. Majority had never received any rehabilitation or attended school, lived in kutcha housing (impermanent) and had limited infrastructure in the home such as lack of running tap water; approximately one third had either a non-sanitary latrine or no toilet facility.

Relationships of HRQoL outcomes to characteristics
Bivariate analysis Results of correlation analysis are shown in Table 2. Significant correlations were observed for all CPQoL-Teens sub-dimensions with small to moderate effect (r = 0.164 to 0.545), with exception of 'school wellbeing' which did not report any significant correlations (p>0.05).
'General wellbeing and participation' significantly correlated to 8 characteristics; school attendance, GMFCS, cognitive impairment, speech impairment, mother education, family income, housing permanence and sanitation; 'Communication and physical health' to 5 characteristics; school attendance, GMFCS, cognitive impairment, speech impairment and caregiver depression; 'Social wellbeing' to 6 characteristics; school attendance, cognitive impairment, speech impairment, mother age, mother education and housing permanence; 'Feelings about functioning' to 5 characteristics; school attendance, GMFCS, cognitive impairment, speech impairment and sanitation; 'Access to services' to 4 characteristics; being male, caregiver depression, anxiety and stress; and 'Family health' to 10 characteristics; school attendance, GMFCS, hearing impairment, mental health, mother age, mother education, caregiver depression, anxiety and stress, family income.

Hierarchical multiple linear regression
Hierarchical multiple linear regression was conducted to determine predictors of CPQoL-Teens. Assumptions of linearity, homoscedasticity and normality were met for all dimensions. Anxiety and stress were removed from the model for 'access to services', depression and anxiety from 'family health' and sanitation from 'general wellbeing and participation' due to multicollinearity. Assumptions of multicollinearity were met when these items were removed, and for all other dimensions.
The final models for each dimension, see Table 3, explained 14.3% to 24.4% of variation in scores. Nine variables independently predicted the CPQoL-Teens sub-dimensions; GMFCS Level 5, adolescent education and mother education predicted 'general wellbeing and participation'. Adolescent education and caregiver depression predicted 'communication and physical health'. Adolescent education, speech impairment and access to a toilet in the home were predictive of 'feelings about functioning'. Adolescent sex and caregiver depression predicted 'access to services'. Hearing impairment, adolescent education and caregiver stress predicted family health. No variables were found to be predictive of social wellbeing.

Discussion
This study examined what factors predict proxy-reported HRQoL of adolescents with CP in rural Bangladesh. We assessed adolescent impairment characteristics and mental health, caregiver mental health, and proxies of socio-economic status. Our findings identified numerous factors correlated to HRQoL of which nine were predictive. Majority of the identified factors are amenable to intervention and are priorities of the sustainable development goals such as 'gender equality', 'quality education' and 'clean water and sanitation'.
Our study examined the relationship between HRQoL and adolescent sex. We found that sex was predictive of 'access to services' with a higher proportion of males reporting better outcomes in this dimension. This finding is unique, although caution is recommended in interpretation due to the high proportion of male participants in our sample. Other studies from LMICs have reported a non-significant relationship between HRQoL dimensions and participant sex (12,15,17,29), with exception of a study of children with CP in India (14) which reported males to have poorer overall HRQoL. The apparent sex-bias in the present study may be understood by considering the broader socio-cultural context in Bangladesh. Prioritisation of males for health care and family resources is culturally prevalent, and is more marked for those living below the poverty line (30).
School attendance was a significant predictor of four CPQoL-Teens dimensions. Children with disability in Bangladesh have the right to attend school enshrined in legislation (31) however a range of issues often prevent participation, such as non-acceptance from the school, parent refusal and transport issues; moreover non-school attendance among adolescents with CP in rural Bangladesh is associated with severity of motor impairment, cognitive and/or speech impairment (6). Over half of adolescents with CP in our study had mild to moderate CP (59.7% with GMFCS I-III) however only 25.3% of participants attended school. Our findings of poorer wellbeing among non-school attenders supports that of a Brazilian study into children with CP (17).
We examined the relationship between adolescent impairments and HRQoL. Adolescent motor impairment (GMFCS L5), hearing and speech impairment were predictive of one CPQoL-Teens dimension each. Previous studies from LMICs have indicated a relationship between motor function and physical wellbeing dimensions of HRQoL, although no relationship has been consistently reported regarding other associated impairments (7).
Whilst the impairments themselves may not typically be modifiable, address of social stigma in the case of hearing impairment (32), and provision of hearing aids or implementation of non-verbal communication methods (33) may assist to improve outcomes in these dimensions. Cognitive impairment was associated with reduced scores on numerous CPQoL-Teens dimensions, however this was not predictive.
Caregiver characteristics correlated to, or were predictive of CPQoL-Teens dimensions, notably mother's age and education. Interestingly, the relationships of these factors were not significant for fathers. These findings have important implications for future intervention design; in Bangladesh mothers typically undertake the majority of caregiving and due to an absence of services and support they may hold the primary responsibility for their children's rehabilitation/ physical therapy (34). Investing in mother's education and provision of targeted interventions through mothers has the potential to increase understanding of effective mechanisms for improving the HRQoL of adolescent with CP.
Moreover, the present study confirmed previous reports that caregiver mental health is an important predictor of adolescent HRQoL (9, 35) although effect in the present study was small.
We examined the relationship of several proxies of socio-economic status and HRQoL.
Notably family income, living in permanent housing and having a sanitary latrine correlated to, or were predictive of CPQoL-Teens dimensions. Personal hygiene is likely to be a challenge for adolescents with motor impairments in the absence of assistive devices. Over one third of adolescents lived in housing without a sanitary latrine, indicating a daily struggle, forcing dependence on caregivers for essential daily tasks, and potentially increasing vulnerability to neglect and abuse.
There are a number of strengths and limitations to the present study. To the best of our knowledge this is the first study using a population-based sample to examine predictors of HRQoL among adolescents with CP in an LMIC. Moreover, we examined numerous variables that are likely to have a unique effect on HRQoL in LMICs. Our sample was homogenous in terms of socio-economic status, a possible limitation to our findings, and we examined determinants of proxy-reported HRQoL only. Due to the subjective nature of HRQoL, selfreported HRQoL data is ideal and has been reported elsewhere (6)

Consent for publication
Not applicable

Availability of data and materials
The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Competing interests
The authors declare that they have no competing interests.

Funding
This study has been supported by the Cerebral Palsy Alliance Research Institute Australia Project Grant (PG3615). RP and TK are supported by Cerebral Palsy Alliance Research Institute Australia Career Development Grants (CDG6416 and CDG04617, respectively).
The study sponsor played no role in study design; collection, analysis, and interpretation of data; writing of the report; and in the decision to submit the paper for publication.
Author's contribution