Study Design
We conducted a cross-sectional study of children aged six to twelve years with a past admission history of NNJ or HIE at Kilifi County Hospital (KCH).
Study Site
All study procedures and assessments were conducted at the Centre for Geographical Medicine Research-Coast (CGMRC) Neuro-assessment unit situated at the Kenyan Coast. We utilised the Kilifi Health Demographic Surveillance system (KHDSS) [32] to recruit a well-defined cohort who were admitted with severe NNJ or HIE.
Study Participants
Children who took part in this study were admitted to KCH in their neonatal period with a diagnosis of either NNJ or HIE. The diagnosis of NNJ was based on clinical laboratory measurement of total serum bilirubin (TSB) as well as medical history and examination during the first 28 days of life. NNJ was defined as a TSB level of > 85 µ/mols/l recorded in the clinical notes. HIE diagnosis was based on the clinical diagnosis recorded by a clinician. HIE diagnosis was given if a child; had convulsions, was unable to breastfeed, had apnoea, and or poor motor tone [33]. The comparison group were identified through the KHDSS and were included in the study if they did not have any history of hospital admission. The children were accompanied to the assessment with their primary caregivers (mostly their mothers). The study reports findings from 375 participants; 134 who survived NNJ, 107 survived HIE, and 134 participants in the comparison group (Fig. 1). The median age of the participants was 9 (interquartile range 7 to 11) years. Of the 375 participants included in this study, 57.3% were males. Thirteen cases had preterm birth (8 survivors of NNJ and 5 survivors of HIE). Most of the caregivers (84%) were married. More than half of the caregivers (69.3%) were Christians, 9.1% were Muslims, while the rest had a traditional religious affiliation. About half of the caregivers (52.5%) had primary education, 34.9% did not have a formal education, while the rest had college or university education. Thirty-nine per cent of the caregivers were farmers, 34.4% were traders, 14.7% were casual labourers, 5.3% were professionals, while the rest had other occupations.
Study Sample
G-power 3.1 software calculations gave an estimation of 127 participants in the NNJ group [34] and 90 participants in the HIE group [35] to provide a power of 0.95 (p = 0.05) to detect medium effect sizes between the affected groups and the comparison group. The number of participants in the comparison group was calculated using frequency matching, where 20 participants were required in each age band (6–12 years).
Assessments
Child-Level Data
Child Behavior Checklist (CBCL/6-18)
The CBCL/6-18 [36] was used to collect parent reports about child problem behaviour. The CBCL section on the child’s EBPs contains 118 questions to be answered with: 0 = not applicable, 1 = somewhat or sometimes applicable, and 2 = very much or very often applicable. Item scores are summed into eight syndrome scales, including Anxious/Depressed, Withdrawn/Depressed, Somatic Complaints, Social Problems, Thought Problems, Attention Problems, Rule-breaking Behaviour, and Aggressive Behaviour. These scales can further be combined into an Internalizing (Withdrawn, Somatic Complaints, Anxious/Depressed) and Externalizing (Rule-breaking Behaviour, Aggressive Behaviour) broadband scales, and a Total Problem score can be computed by summing all item scores. The latter three variables were used to compare the mental health outcomes between the affected and the unaffected children and to determine the underlying factors associated with poor mental health outcomes in NNJ or HIE. The Kiswahili version of the CBCL/6-18 has been used in Kenya and provided good psychometric properties with an internal consistency ranging from Cronbach alphas 0.58 to 0.95 depending on the syndrome scale and age group [18]. In this study, the CBCL also had good to excellent internal consistency for the two broadband and Total Problem scales (Cronbach alphas 0.66 to 0.87).
Pediatric Quality of Life Inventory (PedsQL)
The PedsQL [37] is a 23-item questionnaire for measuring health-related QoL (HRQL) in children and adolescents ages 2–18 years. In this study, the parent version was completed by the caregiver of the child (6 to 12 years).
The PedsQL has four main scales: physical functioning, emotional functioning, social functioning, and school functioning. Each negatively keyed item is measured with a five-point Likert scale that ranges from “1 = never” to “5 = almost always”. After reverse scoring of the item scores, the scale scores are computed as the sum of the item scores in each scale. These scores are transformed to a 0–100 scale such that higher scores indicate better HRQL.
In this study, a Physical Health Summary Score was computed by summing the reversed individual item scores of the physical functioning scale, and a Psychosocial Health Summary score by computing sum of the items over the number of items answered in the emotional, social, and school functioning scales. A Total Scale Score was computed as the sum of all the items over the number of items answered on all the four scales [38]. The PedsQL 4.0 had already been translated into Kiswahili and used in the Kenyan population, and it had demonstrated a fair to good internal consistency across scales (Cronbach alphas 0.58–0.85) [39].
Clinical and Anthropometrical Examinations
A trained clinician conducted a physical examination to determine the motor and sensory neuron responses of the children using a detailed neurological proforma adapted for this study, from a proforma that has been extensively used within the study setting [40].
We did anthropometric assessments and measured the children’s weight, height, middle-upper-arm measurements in centimetres as per the recommendations of the World Health Organization (WHO) [41]. The calculation of height-for-age (HAZ) and weight-for-age (WAZ) was done using the WHO Anthro plus for personal computers version 3.2.2 [42].
Medical History
A clinician conducted structured interviews with the caregivers to document the biomedical risk factors. Potential biomedical risk factors included in this study were abnormal pregnancy (defined as post-dated pregnancy, bleeding during pregnancy, pre-eclampsia, or any other health problems during pregnancy), place of birth (home versus hospital), abnormal delivery (defined as postpartum hemorrhage, emergency caesarean section, prolonged labor, obstructed labor, and maternal and fetal distress), delayed crying at birth, breathing problems at birth, hospital admission, presence of febrile seizures, and presence of any other medical problem after discharge from hospital.
Demographic Information
Caregivers’ demographic variables that were assessed include sex, age, level of education, marital status, and religion. We also captured information about the child’s sex, age, and number of years of schooling.
Caregiver-Level Data
The Patient Health Questionnaire (PHQ-9) [43] was administered to assess caregivers mental health in the past two weeks. The PHQ-9 is a 9-item self-report measure with possible scores ranging from 0 to 27. The participant responds to questions ranging from 0 to 3, depending on how well the statement best describes their situation. The PHQ-9 had excellent internal consistencies in this study (Cronbach's alpha = 0.82).
Household-Level Data
The Family Environment Questionnaire (FEQ) [44] was administered to measure the individual’s perception of their family life. The scale has items that measure the cohesion, expressiveness and conflicts experienced in the relationships in the family; an individual’s personal growth such as independence, moral-religious emphasis; and system maintenance. The items are summed up to obtain a total score. The FES had a relatively low internal consistency in this study (Cronbach’s alpha = 0.50).
The Kilifi Asset Index [45] was used to capture the family assets. The tool has items that accounts for different assets owned by the family, including electronic devices, livestock, house and land ownership. The participant is expected to indicate how many assets they own. A total score of assets owned was then computed.
Statistical Analysis
We compared the demographic characteristics of participants among the three groups (HIE, NNJ, and the comparison group) using analysis of variance (ANOVA) or Chi-square test.
Multivariate analysis of covariance (MANCOVA) was conducted to study group differences on the mental health and QoL measures while adjusting for age, sex, years of education, stunted growth, religion, family asset, maternal education level, marital status, and preterm birth. We conducted univariate regression analysis to identify factors that are associated with the mental health and QOL outcomes. Factors that yielded an association with the p-value level ≤ 0.25 were entered in the multiple regression analysis to investigate correlates of the mental health and QoL in NNJ or HIE [46]. We did a stepwise regression analysis with four models adjusting for age, sex, and years of education. In the first model, child characteristics (age, sex, stunted growth, and years of education were entered. In the second model, caregiver and family factors (family asset, maternal lack of education, marital status, family environment, and maternal mental health) were entered. In the third model, obstetric factors (abnormal pregnancy, place of birth, abnormal delivery, hospital admission, crying problems, and feeding problems) were entered, and in the fourth model, medical problems and neurological problems were added.