Rationale and Approach to Evaluating Interventions to Promote Child Health in LMICs

The age at which children enter school represents a transitional period between early childhood and adolescence that involves increasing autonomy, interaction with peers, and exposure to environments outside the home. Although mortality is generally much lower in the 5 to 9 age group compared with infancy and early childhood, there are many preventable causes of mortality, morbidity, and disability that emerge in this age group, including injuries, noncommunicable diseases, and vaccine-preventable and highly treatable infections.¹  Partly because of relatively low mortality rates and less frequent contacts with the health system, school-age children and younger adolescents ages 5 to 14 have been referred to as the “missing middle,” in that there is a dearth of robust data on key health indicators, morbidity burden, and cause-specific mortality in this group.²  Many health issues that have a high burden in early childhood can persist in older children, especially in low- and middle-income countries (LMIC), resource-constrained settings, and marginalized communities worldwide. Undernutrition and infections occurring in the context of poverty remain leading causes of morbidity and mortality in school-age children living in LMIC,³  whereas those children in higher-income settings are more likely to die due to injuries or noncommunicable disease (NCD). In addition, the prevalence of overweight and obesity in children and adolescents has increased steadily over the last few decades,⁴  though the rate of these increases varies widely among countries.⁵ 

New risk factors relating to diet, lifestyle, mental health, injuries, and NCDs also become more prominent as children approach and enter adolescence, many of which can contribute to the development of chronic NCDs over the life course. Within this period, school-age children begin to establish healthy lifestyle habits (eg, diet, physical activity, avoidance of substance use), and are learning about sexual and reproductive health and rights, as well as the measures they can take to protect themselves and others. This represents a window of opportunity for educational interventions to support good health, optimal development, and well-being. A growing body of evidence suggests that school-based and digital platforms and delivery strategies are promising tools that aid in the delivery of health interventions to older children.

The methodology and reviews described herein contributed to the portion of the upcoming 2022 Lancet Optimizing Child and Adolescent Health and Development Series⁶  related to school-age child and adolescent health interventions. This Lancet Series is the product of an ongoing academic collaboration involving global child health researchers worldwide, including many who are authors on articles within this supplement. The aim of the specific Lancet Series article citing this supplement is to provide a comprehensive overview of systematic reviews describing the most recent evidence for effective interventions to support maternal, newborn, child, and adolescent health and development from preconception through to 20 years of age.

Figure 1 provides an overview of the key child health domains, and a breakdown of the intervention review topics addressing key risk factors covered by the articles included in this journal supplement. On the basis of work done in previous comprehensive overviews of interventions for child and adolescent health (eg, Disease Control Priorities, 3rd edition⁷ ; Lancet Adolescent Health Commission⁸ ), we identified a comprehensive set of key child health domains that represented priority areas for interventions to address modifiable risks for the major causes of child mortality and morbidity. The factors that informed which domains were covered in this supplement included: conditions with a high global burden of disease, conditions with disproportionate impacts on vulnerable and marginalized populations, potential to support improved human capital development across the life course, and pragmatic considerations including whether the topic had recently been covered elsewhere. In cases where the child health domain was deemed too broad in scope for a single review (eg, infectious diseases), the subtopics for individual reviews were also chosen on the basis of these factors. The age group of specific interest for these reviews was older school-age children (ages 5–9.9), though the period of early adolescence (ages 10–14.9) was also recognized as an important area of overlap and transition. The general outcomes of interest aligned with those chosen through consensus by the Lancet Series working group. These included, but were not limited to, mortality, severe morbidity, disability, growth and development, knowledge and behavior, and indicators of improved human capital development such as academic achievement.

The methodological approaches taken, and child health domains covered in this supplement of reviews, was informed by a broad initial literature-scoping and evidence-mapping process to identify key health interventions and associated evidence for their effectiveness in the form of systematic reviews. This was done across all domains, from preconception and pregnancy to ages 0 to 20 to inform the 2022 Lancet Optimizing Child and Adolescent Health and Development Series.⁶  This involved leveraging existing large-scale intervention overviews (eg, Disease Control Priorities 3rd edition, Lancet Series) that had already highlighted existing effective interventions and the most recent systematic reviews detailing the evidence for their effectiveness. Additional targeted searches for newer interventions and systematic reviews in each domain were also conducted. Through this evidence-mapping process, we explored coverage and extent of LMIC-specific evidence across all child health domains to identify areas where school-age evidence was lacking and determined that there were significant gaps in existing evidence for intervention effectiveness in school-age children.

We funneled the reviews identified during this initial scoping process that contained studies covering school-age children and adolescents into the individual reviews for each domain of child health covered in this supplement. We elected to conduct targeted overviews of systematic reviews if there was deemed to be a large body of existing evidence syntheses. In cases where there was a lack of evidence syntheses of intervention effectiveness for a given domain of school-age child health, conventional systematic reviews of primary literature (ie, experimental studies) were conducted. The general methodology for these 2 approaches are described below. See Table 1 and Fig 1 for a summary of the review methods used for each child health domain, and Fig 2 for a breakdown of the main methodology followed in each type of review.

For those child health domains that encompassed a variety of intervention types addressing a wide range of risk factors and health conditions, and for which the initial scoping process identified a variety of existing systematic reviews of intervention effectiveness, an overview of systematic reviews was undertaken. This approach was taken to ensure comprehensiveness, reduce duplication of review efforts, and make the review process feasible.

In addition to incorporating those relevant reviews previously identified in the initial literature-scoping and evidence-mapping exercise, tailored searches were executed in several databases (eg, Medline, Cochrane Database of Systematic Reviews, Campbell Library) to identify literature published up until the end of 2020. Evidence derived from Cochrane reviews and other high-quality systematic reviews that synthesized evidence from randomized controlled trials and quasi-experimental studies examining the effectiveness of interventions was prioritized for inclusion. A first pass of title and abstract screening for relevance was conducted, followed by a full text screening that was done by at least 2 reviewers against inclusion criteria. Two reviewers independently filled a standardized data abstraction form to capture review characteristics, the characteristics of included studies and interventions (eg, age coverage, country representation, delivery platform), and pooled-effect estimates (eg, risk ratios, odds ratios, mean differences, 95% confidence intervals) derived from meta-analyses where they were reported. The main outcomes of interest across the reviews included measures of child morbidity, mortality, development, academic achievement, and mental and physical well-being. The extracted data were then matched among reviewers to check for errors and ensure consistency, and then consolidated into a single table for inclusion in the article. The AMSTAR 2 tool¹²  was used for review quality assessment, and was also conducted in duplicate, with any disagreements in ratings resolved by consensus or the involvement of a third reviewer.

If for a given domain the initial evidence-mapping exercise revealed that the existing evidence-synthesis literature was lacking for the school-age group, we proceeded with a conventional systematic review of primary literature. All systematic reviews were reported in accordance with the reporting guidance provided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria.¹³ 

Search strategies were developed using the population, intervention, control, and outcomes methodology, relevant medical subject headings terms, and keywords derived from the scoping search. The search terms were adapted for use in other bibliographic databases in combination with database-specific filters for controlled trials, where these were available. Searches for the individual, domain-specific reviews were conducted in a variety of databases, including but not limited to: PubMed, Embase, Medline, PsycINFO, Ovid SP, The Cochrane Library, Cochrane Central Register of Controlled Trials, Cochrane Methodology Register, and the World Health Organization regional databases. Evidence derived from LMIC was prioritized for synthesis, though evidence from high-income countries (HIC) settings was leveraged to highlight whether effective interventions exist in cases where LMIC evidence was sparse. Gray literature searches and additional hand searching were conducted in Google Scholar and reference lists of relevant articles, book chapters, and reviews.

After removal of duplicate studies, a multistage screening process was performed to select studies that met the eligibility criteria. Each title and abstract was assessed by at least 1 reviewer, who excluded those that were deemed irrelevant. At the full-text review stage, at least 2 reviewers assessed all full texts. Any disagreements in inclusion decisions were resolved by discussion and, where necessary, by consulting a third reviewer. At this stage, reasons for exclusion were documented. The methods section of each individual review in this supplement describes their selection and eligibility criteria, which differed depending on the child health domain being assessed. Data from included studies were independently extracted and coded by 2 review authors using standardized, previously piloted data extraction forms, which sought general study characteristics, details of the population, intervention, comparison groups, and quantitative outcome data. Data extraction forms were matched and checked, and if necessary, a third review author was consulted in the event of any disagreements to establish consensus.

Assessment of risk of bias for included studies was conducted according to criteria and tools outlined in the Cochrane Effective Practice and Organization of Care guidelines¹⁴  for randomized trials, nonrandomized trials, controlled before–after, interrupted time series, and the Cochrane Handbook for Systematic Reviews of Interventions.¹⁵  Assessments were conducted independently by 2 review authors; scores were compared, and a final risk of bias judgement was reported for the included studies of each systematic review. Randomized trials were assessed using the Cochrane Risk of Bias tool¹⁵  across the following domains: randomization process, deviations from the intended interventions (blinding of personnel, participants, and outcome assessment), missing outcome data, outcome measurement, the selection of the reported result, disclosure of funding, and conflicts of interest. Studies were assigned an overall risk of bias judgement accordingly (low risk, high risk, or some concerns/medium risk). Quasi-experimental study designs were assessed using the Risk of Bias Tool for Nonrandomized Studies of Interventions (ROBINS-I) tool.^15,16  Studies were assessed according to the following domains: bias because of confounding, bias in selection of study participants, bias in classification of interventions, bias because of deviations from intended interventions, bias because of missing data, bias in measurement of outcomes, and bias in selection of the reported result. Each study was assigned an overall risk of bias judgement (low, moderate, serious, and critical risk).

Meta-analyses were conducted where possible using Review Manager 5.4 software.¹⁷  Randomized controlled trials and cluster-randomized controlled trials were analyzed separately from quasi-experimental study designs. To mitigate heterogeneity within included studies, a random-effects meta-analysis was used for pooled outcomes. For those situations where meta-analysis was not possible, data on the effect of interventions from individual studies was tabulated and reported, and a narrative synthesis was conducted for each key intervention domain.

Where there were a sufficient quantity of comparable studies (in both interventions and outcome), a summary of the intervention effect and a measure of quality for key outcomes were produced using the Grading of Recommendations Assessment, Development and Evaluation approach.¹⁸  The Grading of Recommendations Assessment, Development and Evaluation approach considers 5 domains (study limitations, consistency of effect, imprecision, indirectness, and publication bias) to assess the quality of the body of evidence for each outcome. The evidence was downgraded from “high quality” by 1 level for serious (or by 2 levels for very serious) limitations, depending on assessments for risk of bias, indirectness of evidence, serious inconsistency, imprecision of effect estimates, or potential publication bias.

The aim of the authors of this supplement of reviews is to comprehensively assess the available evidence for the effectiveness of interventions to improve health and well-being in school-age children and adolescents. The initial literature-scoping and evidence-mapping process, followed by the different review approaches taken, has helped to maximize the scope covered across this set of reviews, and has allowed us to provide the most comprehensive assessment of the state of the published literature covering interventions for school-age children and adolescents. The individual reviews in this supplement have also highlighted child health domain-specific gaps in the evidence for both primary literature in the school-age group, and gaps in existing evidence syntheses.

It is important to note that, for the reviews within this supplement, the descriptions of intervention effects are meant to provide an overview of what is currently known in terms of evidence for effectiveness, and do not imply that other interventions were ineffective simply because there was an evidence gap. Given the limited space and large scope, it was only possible to provide the highlights of specific comparisons and outcomes in each of the results sections. Comprehensive tables of study characteristics, outcomes, and effect estimates are provided in both the main articles and appendices.

Although we were specifically interested in focusing on LMIC research, this was only feasible for a few review topics (eg, sexual and reproductive health and rights, neglected tropical diseases) because of a dearth of literature. Instead of being used to attempt to generalize their effectiveness to LMIC settings, evidence from intervention effectiveness in HIC settings are included and described to establish that effective interventions do indeed exist and may differ in their impact between settings. This approach has previously been used in the context of adolescent health interventions.¹⁹  This evidence from HIC could act as a starting point for future research and implementation in various LMIC settings, with program components tailored to local contexts.

In the case of those reviews taking the overview of systematic reviews approach, we were limited to including only those primary studies already included in systematic reviews and could not cover each subdomain in depth. Thus, we were unable to identify and include those primary studies that may not have been included in systematic reviews because of studies not being identified in review authors’ database searches, not meeting their inclusion criteria, or falling out of the time frame of the review. Furthermore, some systematic reviews of primary literature were unable to perform meta-analyses because of high heterogeneity or a lack of high-quality evidence from randomized trials, which makes synthesizing the existing evidence more difficult.

• Interventions for High- Burden Infectious Diseases in Children and Adolescents: A Meta-analysis²⁰ 

• Interventions to Improve Immunization Coverage Among Children and Adolescents: A Meta-analysis²¹ 

• Interventions for Neglected Tropical Diseases Among Children and Adolescents: A Meta-analysis²² 

• Prevention and Management of High-Burden Noncommunicable Diseases in School-Aged Children: A Systematic Review²³ 

• Mental Health and Positive Development Prevention Interventions: Overview of Systematic Reviews²⁴ 

• Digital Interventions for Universal Health Promotion in Children and Adolescents: A Systematic Review²⁵ 

• Interventions to Promote Physical Activity and Healthy Digital Media Use in Children and Adolescents: A Systematic Review²⁶ 

• Preventing Unintentional Injuries in School-Age Children: A Systematic Review²⁷ 

• Interventions Promoting Child Sexual and Reproductive Health and Rights In LMICs: A Systematic Review²⁸  and

• Delivery Strategies Supporting School-Age Child Health: A Systematic Review²⁹ 

HIC

high-income countries

LMIC

low- and middle-income countries

NCD

noncommunicable disease