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Abstract
Introduction Children who are born to women living with HIV are at a greater risk of suboptimal neurodevelopment; however, evidence from sub-Saharan Africa is limited and functional developmental outcomes are rarely assessed in this vulnerable population. The School Readiness among HIV-Exposed Children (SRHEC) cohort study aims to assess the school readiness of preschool aged children born to women living with HIV and to identify the biological, environmental and social factors that contribute to school readiness in this population.
Methods and analysis The SRHEC cohort is an observational follow-up study of children born to HIV-infected pregnant women who were previously enrolled in a maternal vitamin D supplementation randomised, placebo-controlled trial in Dar es Salaam, Tanzania. This parent trial enrolled 2300 pregnant women and followed mothers and infants up to 1-year postpartum. Mother/caregiver and child pairs will be eligible for the SRHEC follow-up study if the child is between 3 and 6.5 years of age at assessment, and the mother/caregiver provides informed consent. The International Development and Early Learning Assessment tool will be used to assess children’s school readiness, including their early literacy, early numeracy, motor, socialemotional, and executive function skills. Data on maternal and child health and nutritional status (eg, anthropometry, blood pressure and diet) will be collected using standardised instruments and survey-based questionnaires. Data on maternal/caregiver depression and anxiety, maternal exposure to intimate partner violence, and HIV-related stigma will also be collected. Generalised linear and logistic regressions will be used to assess the relationship between child school readiness and biological, social, environmental factors.
Ethics and dissemination This study received ethical clearance from the Tanzanian National Institute of Medical Research, the Muhimbili University of Health and Allied Sciences, and the Harvard T.H. Chan School of Public Health. We will disseminate our results in the form of scientific conference presentations and peer-reviewed publications.
- HIV
- Epidemiology
- Growth
Data availability statement
Data cannot be shared publicly because of requirement for ethical approval and data transfer agreement. Deidentified data generated through this research may be made available after study completion, following a submitted request to SRHEC study team and completion of ethical approval and data transfer agreement from the Tanzania National Institute of Medical Research.
This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
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WHAT IS ALREADY KNOWN ON THIS TOPIC
With increasing availability of antiretroviral therapy for HIV-infected pregnant women in low-resource settings, the number of children who are HIV-exposed but uninfected (HEU) is increasing.
HEU children are at a greater risk of suboptimal growth and development; however, evidence to date has been primarily from high-income settings.
Furthermore, functional developmental outcomes, such as school readiness, are rarely assessed in HIV-affected paediatric populations.
WHAT THIS STUDY HOPES TO ADD
This prospective cohort study aims to assess the school readiness of preschool aged children born to women living with HIV in Dar es Salaam, Tanzania.
The study also aims to identify the biological, environmental and social factors that contribute to school readiness in this population.
Study findings will provide robust data for designing interventions to support school readiness and optimal growth and developmental outcomes among HIV-affected children.
Introduction
In 2015, the WHO released guidelines, known colloquially as ‘option B+’, which recommended that all pregnant and breastfeeding women with HIV should initiate lifelong antiretroviral therapy (ART), regardless of HIV disease stage, to prevent mother-to-child transmission and sexual transmission of HIV, and to improve maternal clinical outcomes.1 With global efforts continuing to increase the availability of and access to ART for women living with HIV in low-resource settings, the number of children who are HIV exposed but uninfected (HEU) is increasing. Globally, 14.8 million children aged 0–14 years are estimated to be HEU, 13.2 million of whom reside in sub-Saharan Africa.2 The number of HEU children has increased between 100% and 800% in the highest burden countries in sub-Saharan Africa since 2000.3
Evidence primarily from in high-income settings suggests that children who are born to women living with HIV are at a greater risk for suboptimal cognitive, motor, behavioural and socioemotional development as compared with their HIV-unexposed peers.4–6 Biological risk factors, such as exposure to HIV and ART in utero, increased risk of maternal illness, poor nutrition during pregnancy and increased risk of being born low birth weight or preterm, have been associated with higher risk of poor development among young children.7 8 Numerous social, economic and environmental factors related to living in an HIV-affected household, such as parental mental health and depression, stigma, reduced parental attention, and reduced availability of resources and income, are also likely to influence children’s development.4 5 However, the relative contribution of the biological and social, socioeconomic and environmental risk factors on the risk of suboptimal developmental outcomes of HIV-affected children in the context of sub-Saharan Africa remains unclear. In addition, few studies have examined the functional outcomes related to early development, such as school readiness, which comprises of a range of both academic and non-academic early learning and developmental skills that support successful engagement in schools, among HIV-affected children.
The Sustainable Development Goal (SDG) Target 4.2 calls for all girls and boys to have access to quality early childhood development, care and preprimary education to ensure that they are ready for primary education.9 Given the known developmental inequities faced by young HIV-affected children, there is an urgent need to understand what factors influence school readiness among HIV-affected children and to develop and implement interventions to support school readiness in this vulnerable population. To this end, the School Readiness among HIV-Exposed Children (SRHEC) cohort study aims to assess the development and school readiness of preschool aged children born to women living with HIV in Dar es Salaam, Tanzania, and to identify the biological, social, and environmental risk and protective factors that contribute to the school readiness in this population. The findings from this study will provide a unique opportunity to disentangle the multi-faceted relationships that influence child school readiness in HIV-affected paediatric populations, and to identify points of intervention to support child development.
Methods
Parent trial and cohort study design
The SRHEC cohort study is a cross-sectional follow-up of children born in an individually randomised double-blind, placebo-controlled trial of maternal vitamin D3 (cholecalciferol) supplementation conducted among pregnant women living with HIV in Dar es Salaam, Tanzania (ClinicalTrials.gov: NCT02305927). The detailed protocol of the trial, which was conducted between 2015 and 2019, has been published elsewhere.10 11 Briefly, the parent trial enrolled 2300 pregnant women living with HIV, who were ≥18 years of age, between 12 and 27 weeks gestational age, and receiving ART, to investigate whether daily vitamin D supplementation (3000 IU/day) could provide a low-cost adjunct intervention to improve maternal and child health outcomes. Women were enrolled in the trial from five public antenatal care clinics that provided antenatal care for pregnant women living with HIV. During the trial, Tanzania used the option B+ approach, where all pregnant women living with HIV were initiated on lifelong triple-drug ART, irrespective of CD4 T-cell counts or HIV disease stage. The first line of ART during the trial was tenofovir/lamivudine/efavirenz, which was used by 99% of women in the trial during pregnancy and the first year postpartum. Participants were followed at monthly visits during the prenatal period, at delivery, at 6, 10 and 14 weeks postpartum, and monthly thereafter up to 12 months postpartum. Detailed information on maternal sociodemographic characteristics, clinical outcomes (including HIV disease stage), nutrition status and depressive symptoms was collected during the prenatal period. In the postpartum period, mothers’ follow-up assessments included clinical examination, HIV disease stage assessment and anthropometric measurement. Child follow-up assessments included detailed clinical examination, infant feeding practices and anthropometry, as well as child development assessed by the Caregiver-Reported Early Development Index12 at the last visit. The primary outcomes of the trial were maternal HIV progression or death from any cause, small-for-gestational age births and infant stunting (length-for-age z-score ≤2 SD from the median of the reference population) at 12 months of age. Vitamin D supplementation had no effect on the primary trial outcomes.11
Participant eligibility for follow-up
All mother–child pairs who previously participated in the trial of maternal vitamin D supplementation will be eligible for inclusion in the SRHEC follow-up study if: (1) child age is between 3 and 6.5 years at the time of assessment and (2) the mother/caregiver provides informed consent. For a child whose mother was enrolled in the trial of vitamin D supplementation but was not available for the follow-up study (eg, due to death), we will ask the child’s current primary caregiver for consent to participate. We will use information collected during the parent trial to invite women previously enrolled in the parent trial for the follow-up study. Mother/caregiver and child pairs will be invited to the study clinics to learn more about the follow-up study and for study assessments if they agree to participate. Women who previously withdrew from the parent trial or who were lost to follow-up during the trial period, which was until 1-year postpartum, will not be contacted. Written informed consent will be obtained from all participants in the local language of Kiswahili.
Study procedures and assessments
Eligible mother/caregiver and child pairs who consent to participate in the follow-up study will be assessed in quiet rooms at study clinics in tertiary hospitals in Dar es Salaam, Tanzania. For each mother/caregiver and child pair, we will collect detailed information on various domains, including sociodemographic factors, nutritional status, mental health status and child development and school readiness (table 1). Tools and procedures used to measure each of these domains are described below.
Types of assessment planned for mother/caregiver and child pairs.
Child development and school readiness
We will use the International Development and Early Learning Assessment (IDELA) tool developed by Save the Children to assess school readiness in young children aged 3–6.5 years in low-resource settings.13 Briefly, the IDELA is a tool with 22 subtasks that is easily-administered, holistic, rigorous, culturally adaptable and open-source, used to assess four core domains: (1) motor development, (2) emergent literacy, (3) emergent numeracy, and (4) socialemotional development, plus an optional module on (5) executive functioning (ie, short-term memory, inhibitory control, sustained attention). The IDELA is designed to capture broadly cross-culturally relevant skills that support children’s transition into formal learning environments in school. It is administered on a one-on-one basis, does not require specific disciplinary trainings, and is administered using a minimal set of materials: a pencil, blank paper, small items for counting (such as beans or buttons), nine picture cards and a storybook. The IDELA is scored by calculating the average percentage of correct responses for each task within the four core domains (emergent numeracy, emergent literacy, motor and socialemotional), and the overall IDELA score, ranging from 0% to 100%, is calculated as the average percentage for the four domain scores.13 The IDELA tool has been previously adapted for and used in Tanzania.14 We will assess inter-rater reliability for 5% of IDELA assessments selected at random.
As a secondary measure of development, we will implement the Early Child Development Index 2030 (ECDI2030), which is commonly used in population-based surveys to assess whether a child is meeting expected developmental milestones in motor, language, math, literacy, executive functioning and socioemotional domains.15 The ECDI2030 is used to evaluate progress towards SDG target 4.2 and is administered as 20 close-ended questions to the mother or primary caregiver, where they indicate whether their child has exhibited the behaviour in each question. The ECDI2020 indicator is defined as the proportion of children 24–59 months of age who have achieved the minimum number of milestones expected for their age according to age-specific cut-off scores compared with all children aged 24–59 months of age. We will also use the Strengths and Difficulties Questionnaire (SDQ), which has previously been implemented in Tanzania, to assess children’s overall mental health status as indexed by internalising and externalising behaviours.16 Like the ECDI2030, the SDQ is a mother/caregiver-reported instrument; it includes 25 items rated on a Likert-like scale assessing frequency of emotional problems, conduct problems, hyperactivity, peer-problems and prosocial behaviour.17 The total difficulties score is generated by summing the scores from all scales except the prosocial scale. All child development and school readiness tools will be administered by nurses, who will be trained using the standard training procedures for each tool. Although primary school in Tanzania begins at age 7 and attendance in preschool educational programmes is rare in this population, we will also collect data on whether children enrolled in the study attend primary school and whether they had previously attendend or currently attend preschool education programmes.
Maternal and child health and nutrition
We will use standardised procedures to measure anthropometry. Maternal and child weight will be measured using electronic floor scale (ADE M320600, Germany) with 50 g precision up to 50 kg and 100 g precision thereafter. Participants will be requested to remove shoes and wear light clothing at the time of weight measurement. Maternal and child standing height will be measured using a stadiometer (ADE Mechanical Height MZ10017, Germany) with 1 mm precision and mid-upper arm circumference will be measured using a circumference tap measure (ADE MZ10021, Germany) with 1 mm precision. Child head circumference will be measured using a Schorr tape with 1 mm precision. All child anthropometric measures will be taken in triplicate and maternal measures will be recorded in duplicate. In addition to anthropometry, we will measure maternal blood pressure in duplicate, using a digital blood pressure machine (OMRON BP7200) with free-size cuff, with participant in a seated position after 5 min of rest. Anthropometric equipment will be calibrated daily, and the blood pressure monitor will be calibrated every month using a manual mercury sphygmomanometer. Minimum dietary diversity for women of reproductive age will be assessed using the Food and Agriculture Organisation guidelines, summing the total number of different food groups consumed.18 Child diet will be assessed using a modified 24-hour recall for infant and young child feeding practices (removing any items relevant to children <2 years of age only) where mothers/caregivers are asked about the types of foods consumed by the child in the last 24 hours to record the food groups.19 We will also assess child’s current health status as measured by episodes of morbidity, such as diarrhoea and fever, in the 2-week period prior to the assessment.
Maternal/caregiver mental health and social support
Maternal depression will be assessed using the Hopkins Symptom Checklist-25, which is composed of 15 items on depressive symptoms and 10 items on anxiousness symptoms, with each item having a possible score of 1–4 (1=not at all; to 4=extremely); it has previously been validated for use in Tanzania among pregnant women living with HIV.20 We will also measure the mother’s perception of social support using an adapted Duke University–University of North Carolina Functional Social Support Questionnaire, consisting of eight questions graded on a four-point Likert scale to measure constructs of support from confidants and affective support.21 The tool has been previously adapted for use in Tanzania and can be used to distinguish between two underlying constructs of instrumental and emotional support.22 We will also measure depression and perception of social support for primary caregivers, should the mother be unavailable.
Maternal HIV-related stigma and intimate partner violence
We will measure mothers’ reports of HIV-related stigma using an abbreviated version of the Berger scale,23 which has been previously used in Tanzania,24 25 and consists of seven questions graded on a five-point Likert scale to capture internalised stigma (shame, guilt) and externalised stigma as experienced by treatment from other people who are aware of the respondent’s HIV status. We will also assess prevalence of intimate partner violence (IPV), which in this context is most commonly directed towards women by male partners. IPV has been described to manifest in a range of behaviours, including but not limited to: physical, sexual, emotional or psychological, and controlling behaviours that include restricting financial or economic independence.26 Physical and sexual aspects of IPV will be assessed using an abbreviated mother-reported IPV module found in the Tanzania Demographic and Health Survey and has been previously used in other studies.27 28 Emotional and economic aspects of IPV will be assessed using abbreviated questions that were previously used in Tanzania.29 We will not assess HIV-related stigma or IPV for caregivers.
Caregiving practices and resources for learning
Caregiving practices, including disciplinary practices, such as corporal punishment, and responsive caregiving and stimulation practices (eg, reading, counting, playing), will be measured using the mother/caregiver-reported Family Care Indicators (FCI) taken from the Multiple Indicator Cluster Surveys.30 31 The FCI score will be a summative score based on responses (yes/no) for each individual item. We will also collect data on resources available for learning, such as books and toys, to assess children’s learning environment at home.
Maternal HIV variables at time of assessment
We will seek consent to retrieve mother’s medical information from the HIV treatment clinic and to link HIV treatment information, including information on HIV disease stage based on the WHO classification, history of ART regimens, viral load and laboratory results.
Data collected during pregnancy and first year postpartum
We will link the maternal/caregiver and child data collected in this study with existing data from parent vitamin D supplementation trial to assess long-term associations of maternal and child perinatal health with child development and school readiness in the preschool years.
Safety procedures and referrals
All research staff will be trained in a 2-week training workshop where they will learn about and familiarise themselves with all study procedures, including the planned referral scheme and supports that will be made available to participants and their children. Study staff members will also be trained in referring study mothers/caregivers for mental healthcare if they report IPV or depression. If signs of suicidality are reported, mothers/caregivers will be kept under observation until they are seen by a clinical psychiatrist and referred for mental health services. Mothers/caregivers and their children will be referred to clinical and nutritional services at the hospital if undernutrition and malnutrition are detected. We will follow strict safety precautions and procedures (eg, masks, hand sanitisers) to prevent the transmission of COVID-19 among the study staff and participants.
Sample size
All mother and infant pairs who were discharged from the parent trial at 12 months postpartum (n=2053) will be eligible for the SRHEC follow-up study and will be invited to participate in the study.
Quality assurance and data management
Standardisation sessions will be held every 3 months to ensure the data collectors are following the recommended techniques, to monitor reliability (precision and accuracy), and to take corrective measures if required. Data queries will be regularly generated and checked by study field staff as part of quality assurance/quality control measures to detect outliers and possible erroneous values.
Statistical analysis
We will generate summary statistics, overall and by age strata, of child outcome domains as described in the standard methodology for the IDELA, ECDI2030 and SDQ measures including both domain level and overall scores where appropriate. Subscale scores for caregiving practices, resources for learning, maternal depression and anxiety, will be similarly derived using internationally validated standards and cutoffs when available, and summative scores or z-scores as relevant. Child growth will be assessed using standardised indices and indicators of anthropometric measures using the WHO Child Growth Standards.32 33 Scores for child development and school readiness will be converted to overall z-scores based on study sample distribution with a mean of 0 and an SD of 1 for analysis. Using these standardised scores, we will assess the relationship between early child development assessed in the parent trial, at approximately 12 months of age and school readiness. We will also estimate differences in child health, nutrition, development and school readiness outcome scores across different exposures of interest using generalised linear regression models. Child age will be included as a confounder or effect modifier in all regression analysis, as appropriate. Relationships with categorial indicators of suboptimal child development will be estimated using modified Poisson regression with robust standard errors. All regression models will be adjusted for potential sociodemographic confounders, such as child sex, maternal/caregiver age, household wealth quintile and number of children in the household, among others.
Ethics and dissemination
This study received ethical clearance from the Tanzanian National Institute of Medical Research, the Muhimbili University of Health and Allied Sciences, and the Harvard TH Chan School of Public Health. Permission to conduct the study was granted by the President’s Office, Regional Administration and Local Government and the Regional Medical Officer (RMO) of Dar es Salaam. We will disseminate our results in the form of scientific conference presentations, presentations to the RMO and as peer-reviewed publications.
Data availability statement
Data cannot be shared publicly because of requirement for ethical approval and data transfer agreement. Deidentified data generated through this research may be made available after study completion, following a submitted request to SRHEC study team and completion of ethical approval and data transfer agreement from the Tanzania National Institute of Medical Research.
Ethics statements
Patient consent for publication
Ethics approval
This study received ethical clearance from the Tanzanian National Institute of Medical Research, the Muhimbili University Health and Allied Sciences, and the Harvard TH Chan School of Public Health. Permission to conduct the study was granted by the President’s Office, Regional Administration and Local Government (PORALG) and the Regional Medical Officer (RMO) of Dar es Salaam. Participants gave informed consent to participate in the study before taking part.
Acknowledgments
The authors thank the mothers/caregivers and children for their participation in the study and the nurses and nurse supervisors involved in data collection.
References
Footnotes
CRS and KPM are joint senior authors.
Contributors NP, AS, DM, JS, CRS, KPM contributed to the study conceptualisation, and all authors contributed to the study design and data collection. NP drafted the initial manuscript and revised the paper. All authors contributed to revising the manuscript for important intellectual content and have read and approved the final manuscript.
Funding The parent trial was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) under Award Number R01 HD83113. The follow-up data collection was supported by Harvard University Center for African Studies (no grant number), the Thrasher Research Fund Early Career Award (no grant number) and the National Institutes of Health Fogarty International Center and the National Institute of Child Health & Human Development (NICHD) under Award Number D43 TW010543. NP was further supported by the Canadian Institutes of Health Research Fellowship Award.
Disclaimer The content is solely the responsibility of the authors and does not necessarily represent the official views of the funders.
Competing interests None.
Patient and public involvement Patients and/or the public were not involved in the design of the study, but are involved in the conduct of and in the dissemination plans of this research.
Provenance and peer review Not commissioned; externally peer reviewed.