Prevention and Management of High-Burden Noncommunicable Diseases in School-Age Children: A Systematic Review

A systematic search for literature published from January 1, 2000 to March 28, 2021 was conducted in Medline, Embase, Cochrane Database for Systematic Reviews, and the Campbell library using medical subject heading terms and keywords. An individualized search was run for each condition of interest using condition-specific terms, such as “asthma,” “anti-asthmatic agents,” and “bronchial hyperactivity;” and population related words, such as “children,” “adolescents,” and “school-age;” and intervention related words such as “program, education,” “treatment,” “therapeutics,” etc. The complete search syntax used for the Medline database is included in Supplemental Information. This systematic review has been designed in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols and registered within the International Prospective Register of Systematic Reviews (PROSPERO # CRD42020219910).¹⁶ 

Systematic reviews that met the eligibility criteria were those reporting pooled effect estimates on interventions delivered to children aged 5 to 14.9 years in high-income (HIC) and low- and middle-income countries (LMIC) for the following chronic disorders: asthma, epilepsy, rheumatic fever and rheumatic heart disease, sickle cell disease, type 1 diabetes, and childhood cancers. The primary setting of interest was LMICs, though we recognized that data are limited in these settings. As such, we sought to include relevant evidence from HICs. This approach is consistent with prior reviews of evidence in emerging areas, such as adolescent health. Interventions targeted at reducing exposure to environmental toxins that addressed one of following: indoor air pollution, outdoor air pollution, or other environmental contaminants targeted at care givers and parents were also included. Eligible interventions targeted either (1) health promotion, (2) prevention, (3) chronic care, (4) curative treatment and key outcomes of interest that were related to child development, morbidity, and mortality. While our primary focus is on late childhood and school age (5–9.9 years) and early adolescence (10–14.9 years), we included reviews that reported on interventions delivered to children and adolescents between the ages 5 and 19 if most of the sample fell within our target age range. Included systematic reviews used comparison arms that were either standard arm or usual care, placebo, or no intervention controls. Reviews of drug trials comparing the efficacy of, and/or side effects of 2 different but similar class of drugs for the purpose of promoting 1 medication over the other were excluded.

All identified indexed records were downloaded into EndNote software and duplicates were removed. Titles and abstracts were screened for relevance by a single reviewer, and all full text of potentially relevant publications were then screened in duplicate with reasons for exclusion noted at this stage. Data and information from publications that met the inclusion criteria were extracted in duplicate into a standardized form. Key variables regarding authors, publication year, setting, target population, study design, intervention descriptions, and pooled estimates (eg, risk ratios [RR], odds ratios [OR], and mean differences [MD]) from meta-analyses were extracted by 2 reviewers. The extracted data were compared, and any inconsistencies were resolved through discussion or by a third reviewer if needed. The quality of the systematic reviews was evaluated with a tool for the assessment of multiple systematic reviews (AMSTAR 2).¹⁷ 

The initial electronic search yielded 19 015 citations from indexed databases, with most being excluded after title and abstract screening as they did not meet the eligibility criteria outlined in the PRISMA flow diagram (Supplemental Information). Of the 865 potentially relevant full texts assessed, 50 were identified as eligible for this review.^18–65  Two of the systematic reviews included duplicate data (ie, analysis from the same set of studies that 2 other systematic reviews included).²⁹  Since these reviews met our inclusion criteria, we considered them as part of our total count of included reviews, however since the data are already presented from the formerly extracted reviews, we did not present the duplicated data. The characteristics of all included systematic reviews are summarized in Table 3.

Though we did not limit our results by geographical location, our focus was on collating evidence from LMIC settings, however only 12.5% (n = 6) of included reviews reported on evidence exclusively from LMIC. Most reviews, 69% (n = 33), reported on evidence from studies mainly conducted in HIC settings, and 19% (n = 9) of reviews did not report the geographical location of included studies.

Interventions were categorized into the following 3 groups: (1) health promotion, which included programs targeted at improving indoor and outdoor air pollution and reducing exposure to environmental contaminants; (2) prevention, which included treatment of acute pharyngitis to prevent rheumatic fever and rheumatic heart disease, educational programs for self-management of asthma to reduce exacerbations, and hospitalizations; and (3) chronic care, which is the management of asthma, epilepsy, RHD, sickle cell, and type 1 diabetes.

We broadly categorized interventions into those delivered through community-based, school-based, home-based, and hospital-based and outpatient- based platforms. Overall, a significant portion of reviews did not report the delivery platform, of those that reported, 27% (n = 16) reported outpatient settings, 13% (n = 8) home-based, 15% (n = 9) hospital-based, 13% (n = 8) community-based, and 8% (n = 5) in school-based platforms.

Asthma is a chronic respiratory condition characterized by bronchoconstriction, inflammation, and hypersecretion causing limitations in airflow and is one of the most common chronic conditions among children. Managing asthma includes adequate self-management, education regarding treatment and triggers to avoid, and how to manage symptoms.³⁴  We included 19 systemic reviews of asthma interventions.

Interventions included education that addressed self-management, relaxation therapy, and massage therapy; the reported outcomes were pulmonary function (Supplemental Information), frequency of emergency department visits, and hospitalizations.

A recent systematic review looked at comprehensive community-based interventions with 2 or more components for improving asthma outcomes in children. A wide variety of interventions were included in this review, such as community involvement (eg, awareness campaigns, neighborhood support, etc), asthma self-management education, and home environmental assessment (ie, home visits for trigger assessments with or without remediation supplies). All of the studies included were conducted in the United States, aside from 1 in Australia. The authors found that multicomponent asthma programs were associated with significant reductions in asthma-related emergency department visits (OR, 0.26, 95% confidence interval [CI], 0.20 to 0.35), and hospitalizations (OR 0.24, 95% CI, 0.15 to 0.38) (Table 2).¹⁸  Another targeted systematic review on school-based self-management interventions for asthma showed improvement in outcomes, such as frequency of hospitalizations with a standard mean difference (SMD) and 95% CI of −0.19, (−0.35 to −0.04), and a reduction in the frequency of emergency department visits (OR 0.70, 95% CI, 0.53 to 0.92).³⁰ 

One review found significant improvements in the mean change from baseline in forced expiratory volume peak (FEV1) when comparing placebo with once-a-day long-acting anticholinergic tiotropium bromide bronchodilator; mean difference of 102 mL (95% CI, 66 to137 mL).²¹  Another systematic review reported significant reductions in hospital admissions in children treated with inhaled anticholinergic agents (RR 0.73, 95% CI, 0.63 to 0.85).³⁶  A review looking at probiotics supplementation in children with asthma indicated significantly fewer episodes of asthma in the probiotics group compared with control (RR 1.3, 95% CI, 1.06 to 1.59).³¹  The pooled results also demonstrated that there was no significant difference between the 2 arms on the number of symptom-free days (MD 8.47, 95% CI, −4.8 to 21.75). Two reviews looked at vitamin D supplementation.^19,35  The first found there was a reduced risk of asthma exacerbations in children receiving vitamin D (RR, 0.41, 95% CI, 0.27 to 0.63). A review investigated the adjunctive use of macrolides reported no significant change in FEV1 from baseline.

Approximately 50 million people suffer from epilepsy globally, with nearly 80% living in LMICs.⁶⁷  With the appropriate use of antiepileptic medications, seizures can be controlled. Although low-cost treatments are available, nearly three-quarters of individuals living in LMICs will not receive the treatment they need.

Three reviews examining the effects of Ketogenic “type” diets on seizures in children with epilepsy were identified, with variable evidence.^56–58  Another review examined the efficacy of cannabidiol in reducing seizures among children with drug resistant epilepsy; the authors reported a statistically significant reduction in the median frequency of monthly seizures with cannabidiol compared with placebo, and an increase in the number of participants with at least a 50% reduction in seizures.⁵⁵  A meta-analysis from another review suggested that adjunctive treatment with levetiracetam was more effective than placebo; RR (95% CI) for the 50% responder rate and seizure freedom rate were 1.98 (1.49 to 2.63) and 5.12 (2.09 to 12.51), respectively.⁵⁴ 

Nearly 12 million people are affected by rheumatic fever and rheumatic heart disease, taking more than 200 000 lives annually.⁶⁸  Primary antibiotic prophylaxis is not only cost-effective, but it can successfully be implemented in resource-poor settings and is essential in limiting the progression of rheumatic fever to rheumatic heart disease.^68–70  Programs focused on early detection and treatment are essential in improving outcomes for these preventable conditions.

We identified 2 reviews examining primary prevention of rheumatic fever. One review examined rheumatic fever prevention by treating streptococcal pharyngitis with penicillin in school- and/or community-based programs. The results of this meta-analysis reported (RR 0.41, 95% CI 0.23 to 0.70) favoring treatment.⁶⁰  The second review looked at the comparable efficacy of new short-duration antibiotics (Azithromycin, Clarithromycin, and Cefuroxime) compared with the standard duration of 10-day oral penicillin in treating children with acute group A β-hemolytic streptococcal (GABHS) pharyngitis. The authors reported that 3 to 6 days of oral antibiotics had comparable efficacy to the gold standard 10-day penicillin regimen in areas with a high prevalence of rheumatic heart disease. These results should be interpreted with caution given the long-term risks of rheumatic fever and progressive heart disease without adequate treatment of GABHS. However, in countries with low rates of rheumatic fever, it appears safe and efficacious to treat children with acute GABHS pharyngitis with short duration antibiotics.⁵⁹ 

Sickle cell disease is a genetic condition in which individuals experience acute complications and progressive organ damage. Disease management and prevention programs are key in reducing the health burden and complications. We included 5 reviews examining sickle cell disease (SCD).

A Cochrane review examined interventions for patients and caregivers aiming to improve their knowledge and understanding of sickle cell disease and recognition of signs and symptoms of disease-related morbidity. Interventions were described as cognitive-based therapy or psychoeducation aimed to change knowledge, attitudes or skills, improve psychosocial aspects of the disease, as well as treatment adherence and health care utilization. Evidence showed that the educational programs improved patient’s knowledge (SMD 1.12 points, 95% CI, 0.72 to 1.52).⁶¹  A single trial reported on caregivers’ knowledge, which also showed an improvement (SMD 0.52 points, 95% CI, 0.03 to 1.00). A second Cochrane review examined the effects of prophylactic antibiotic regimens for preventing pneumococcal infection in children with sickle cell disease, with results favoring penicillin initiation (OR, 0.37, 95% CI, 0.16 to 0.86).⁶⁴ 

One review reported moderate quality evidence that long-term red cell transfusions may reduce the risk of stroke in children at higher risk of stroke who have not had previous long-term transfusions.⁶²  The use of malaria chemoprophylaxis (Chloroquine, Mefloquine, Mefloquine artesunate, Proguanil, Pyrimethamine, Sulfadoxine-pyrimethamine, or Sulfadoxine-pyrimethamine amodiaquine) in children with SCD was evaluated by 1 review. The authors reported that antimalarial chemoprophylaxis generally provided protection against parasitemia and clinical malaria episodes in children with SCD. However, no difference between intervention and placebo group was noted for the risk of hospitalization, blood transfusion, vaso-occlusive crisis, and mortality.⁶³  The efficacy of pharmacological analgesics used for the improvement of pain intensity and relief for acute pain crisis in pediatric patients with SCD was reported in 1 review, and showed no statistically significant differences and a lack of amelioration provided by pharmaceutical analgesics in the treatment group.⁶⁵ 

Type 1 diabetes (insulin-dependent diabetes mellitus), also commonly referred to as juvenile diabetes, is an autoimmune disease that can occur at any age but tends to develop during childhood. Poor metabolic control can cause acute complications, hypoglycemia, ketoacidosis, and chronic microvascular and macrovascular complications, which continue to be a major cause of morbidity and mortality.^71–74  Adequate management includes self-care tools, self-management education, and access to insulin. However, in many countries and for disadvantaged families, access is limited.⁷⁵ 

Seven systematic reviews examining interventions aimed at care for type 1 diabetes were included.^39–45  One review examined psychological interventions, which included supportive or counseling therapy, cognitive behavior therapy, psychoanalytically informed therapies, and family systems therapy. The authors reported the mean percentage of glycated hemoglobin was significantly reduced in children and adolescents who had received a psychological intervention compared with those in the control group with a pooled absolute reduction in glycated hemoglobin (HbA1c) of 0.48% (95% CI, 0.05 to 0.91; Supplemental Information). A systematic review of physical activity and sedentary behavior intervention studies reported significant reduction of HbA1c, indicating an improvement in glycemic control (MD −0.85%, 95% CI, −1.45 to −0.25). A review examining the effectiveness of adding metformin to insulin in children with type 1 diabetes mellitus for improving metabolic outcomes found metformin resulted in a modest decrease in the total daily dose of insulin, reduced body mass index (BMI) (kg/m²), and BMI z-score but was not superior to placebo in reducing HbA1c, lipid profile, and diabetic ketoacidosis events. A review of the effectiveness of family-directed interventions showed a pooled effect of −0.6 (−1.2 to −0.1) on HbA1c. One review found a statistically significant but a modest reduction in HbA1c with real-time continuous glucose monitoring interventions.

Cancer affects nearly 400 000 children and adolescents annually.⁷⁶  The most common types of cancers include leukemia, brain and central nervous system tumors, and lymphomas.⁷⁷  In HICs the survival rate is nearly 80%, while in LMICs it may be less than 30%. The lack of diagnosis, delayed diagnosis, obstacles to accessing care, and treatment abandonment all contribute to the avoidable deaths from cancer in LMICs.⁷⁸  While treatment of cancers can include a variety of regimens, medications, surgery, and radiotherapy, timely diagnosis is simply the most crucial factor and the foundation for developing a treatment and management plan. We found it most appropriate to focus this section on reviews that examined interventions aimed at improving detection.

A recent systematic review examined interventions aimed at improving early detection of childhood cancers in LMICs. The review included 12 studies and interventions ranged from training programs for health care providers to national awareness campaigns and education on early warning signs and symptoms. Five studies reported statistically significant results postintervention in key clinical outcomes, such as decrease in extraocular spread of retinoblastoma, and decrease in refusal and abandonment rates of treatment and an increase in knowledge and awareness. Because of the heterogeneity of outcomes, meta-analysis was not possible, and the current quality of evidence is low.³⁸  A 2016 Cochrane systematic review attempted to examine the effects of interventions for promoting participation in shared decision-making for children aged 4 to 18 with cancer, however no studies met the inclusion criteria.³⁷ 

No country is unaffected by pollution and shifts in globalization and rapid urbanization contribute to the rise of NCDs in LMICs as more people are exposed to indoor and outdoor pollution in densely packed cities.^79,80  Environmental factors are a main preventable cause of NCDs. Ambient (outdoor) and household air pollution cause deaths from cardiovascular diseases, chronic respiratory diseases, and lung cancer.⁸¹  Women and children are disproportionately affected and are more often exposed to harmful smoke caused by cooking, heating, and lighting with unclean fuels and inefficient technologies.⁸²  Sector policies and interventions that effectively address environmental causes of disease, eg, energy, housing, transport, and agriculture, and in settings such as cities, workplaces, and homes not only improve health outcomes, but have a positive impact on the climate and economy.^80,83,84 

Much overlap was seen among the records identified from the respective searches on outdoor pollution, indoor pollution, and environmental contaminants. Overall, we identified 2 reviews examining the levels of nicotine concentration in ambient air and parental cessation programs,^50,51  2 reviews focused on improved cook tops and stoves,^52,53  2 reviews on preventing domestic lead exposure,^48,49  1 review on interventions to reduce ambient particulate matter air pollution,⁴⁶  and 1 review on environmental awareness interventions.⁴⁷ 

One review reported that stand-alone targeted educational interventions showed no statistically significant reductions in children's blood lead levels when compared with general educational interventions. However, stand-alone environmental interventions appeared more effective in reducing blood lead levels. The authors suggest combining environmental and educational interventions and targeting multiple settings, which may have a greater effect in reducing blood lead levels, as suggested by 1 uncontrolled before-after study. A second review similarly found educational interventions were not effective at reducing blood lead levels in children, (MD −0.03, 95%CI, −0.13 to 0.07).

A systematic review on parental smoking cessation reported quit rates averaged 23.1% in the intervention group and 18.4% in the control group. Overall, while modest, the RR (95% CI) showed statistically significant improvement in quit rates in the intervention group compared with the control group, 1.34 (95% CI, 1.05 to 1.71). One review evaluated air pollution in homes as assessed by nicotine or particulate matter (PM), with a range of interventions; including self-help materials, counseling, phone support, nicotine replacement therapy (NRT), biochemical feedback, air cleaner, and tobacco smoke air pollution feedback. Although interventions showed reduced tobacco smoke pollution (as assessed by air nicotine or PM) in homes, contamination still remained.

Two reviews examined household air pollution reductions with cook stove interventions. One review reported that at the household level there were improvements in daily personal average concentrations of particulate matter (SMD 1.18, 95% CI, 1.05 to 1.32) and carbon monoxide concentrations in kitchens (SMD 0.83, 95% CI, 0.68 to 1.00). Significant improvement in personal particulate matter was observed among children (SMD 1.26, 95% CI, 0.91 to 1.75). A second review examining the effect of improved biomass cook stoves on acute respiratory infections and severe pneumonia in children showed no demonstrable impact.

A Cochrane review assessing the effectiveness of interventions to reduce ambient air pollution and improve associated health outcomes reported 38 unique interventions with heterogeneity across interventions, outcomes, and methods. The interventions were implemented in countries across the world, but the majority (79%) were implemented in HICs. Included studies showed varying effects of the interventions on health outcomes. Given the heterogeneity, it was difficult to generate any overall conclusions regarding the effectiveness of interventions in improving air quality or health. A systematic review examining the effectiveness of environmental awareness interventions reported short-term improvements in awareness and knowledge in 13 out of 14 studies. The results suggest that a number of health promotion interventions can aid in increasing short-term public awareness and environmental health risks, specifically, ultraviolet radiation and environmental tobacco smoke.

Although many NCDs are caused by preventable factors, including poor diet, tobacco use, harmful use of alcohol, and physical inactivity, many NCDs are not caused by modifiable factors, particularly those affecting children. Cardiovascular diseases, chronic respiratory diseases, cancer, and diabetes are all leading causes of global mortality. The importance of addressing these and other NCDs is acknowledged in the Sustainable Development Goals, which call for measures to reduce mortality from NCDs by 2030. We conducted a comprehensive review of systematic reviews of interventions addressing high burden, neglected NCDs, providing an overview of existing evidence-based interventions. Much of the evidence for the effectiveness of interventions among school-aged children was conducted in high income settings and may not be easily extrapolated to LMICs. However, several intervention programs are not only feasible but also cost-effective in LMICs. An economic study from India estimated that public financing for both first- and second-line therapy and other medical costs alleviates the financial burden from epilepsy and is cost-effective across wealth quintiles.⁸⁵  Primary antibiotic prophylaxis is not only cost-effective, but it can successfully be implemented in resource-poor settings. Investing in prevention and management of NCDs offers countries a higher return and contributes to economic growth for countries at all income levels.⁵ 

While evidence exists and we have identified several reviews highlighting interventions for school-aged children that improve outcomes, the bulk of these reviews only include evidence from a small number of studies with moderate to low quality evidence and a high level of heterogeneity with regards to participants, reported outcomes, and intervention characteristics. Most of the current literature on NCDs reports on mixed populations that includes both children and adults. A previous systematic review of systematic reviews on the state of evidence on acute asthma management in children included a total of 23 reviews; 8 included only children, and 15 included children and adults.

LMICs have long been burdened with malnutrition and infectious diseases. However, today LMICs are experiencing an increase in NCD burden.^86,87  Air pollution was the second largest risk factor causing NCDs globally in 2016, just after tobacco smoking, and caused 5 million deaths from NCDs. NCDs caused by air pollution include heart disease, stroke, chronic obstructive pulmonary disease, and lung cancer.^81,82  Nearly 92% of pollution-related deaths occur in LMICs, and in countries at every income level, the diseases caused by pollution are most prevalent among minorities and marginalized groups.⁸⁰  Three billion people, mainly living in LMICs, rely on polluting fuels for inefficient cooking, heating, and lighting technology, resulting in exposure to harmful smoke in their homes. Children are extremely vulnerable to even low-dose exposure to pollutants, especially during critical times of development in utero and in early infancy, which can result in disease and disability across the life course. Interventions to reduce exposure to air pollution and improve air quality have great potential to protect individuals’ health and contribute to reducing the burden of NCDs.⁸⁸  Ecuador’s national efficient cooking program aims to reduce greenhouse gas emissions by replacing liquefied petroleum gas with renewable energy sources like hydroelectricity. The impact of the national efficient cooking program implementation estimates a reduction of 2.9 million tons carbon dioxide equivalent (CO2eq) per year and total accumulative reduction of approximately 49 million tons CO2eq from 2012 to 2030.^89,90 

The current evidence does not enable determination of which interventions are the most effective and whether these interventions can be effectively delivered in LMIC settings. Targeting gaps in the literature could enhance the understanding of effectiveness of interventions, modes of delivery, and readiness for scale-up of these programs. Multicomponent and multisectoral approaches for addressing health and wellbeing are often the most effective. Approaches and efforts to confront NCDs should be embedded in public health programs, and primary care services should be made more readily accessible in schools or the community.

Our analysis has a number of potential limitations. We undertook a comprehensive literature search for published reviews to identify high-level evidence in peer-reviewed journals, and thus did not include unpublished reviews. A major limitation of the literature assessed is the high proportion of publications that do not report key information, such as the platforms involved in intervention delivery. We initially aimed to synthesize data in 2 separate age ranges: late childhood and school age (5–9.9 years) and early adolescence (10–14.9 years). However, it was not possible to disaggregate the findings by age group as most reviews reported on wide age ranges, which mostly combined these age bands. However, in the same respect, we came across reviews that included many studies with child and adolescent populations, however their meta-analyses also included populations with adults, and were therefore excluded. While our focus was on LMIC’s, the majority of reviews, 69% (33 reviews), included studies and data from high-income countries.

Our aim was to summarize the current base of systematic reviews focused on delivering NCD interventions to children and adolescents aged 5 to 19. However, our results had major limitations as we found significant gaps in the literature. Conditions like asthma and type 1 diabetes, which are well-studied and have well known standard of care regimens, are not necessarily represented in our results. Our results are not a reflection of the entirety of pharmacologic interventions that exist, nor representative of the effectiveness of all available medications used to manage the conditions included in this review. Our results are only a reflection of the reviews that exist, and more importantly, the significant gaps that do exist in the literature for so many well-studied conditions individually.

Although NCDs have their major impact on global mortality and morbidity in adulthood, they represent a considerable burden among children and adolescents, specifically mortality related to asthma, type 1 diabetes, leukemia, and rheumatic heart disease.⁹¹  Efforts to reduce their burden among children, adolescents, and into adulthood are essential. While some NCDs can be prevented through preventive measures, and lifestyle and behavioral modifications, conditions like congenital heart disease and type 1 diabetes cannot be prevented. Our review highlights the major gaps in the literature and our understanding of NCD prevention and management in LMICs, despite LMICs having the highest burden of NCDs and limited resources to manage them. While disparities in regard to access and quality of health care exist among HICs and LMICs, inequalities within countries and communities also determine the level and quality of care that children and adolescents receive. The limited quantity and quality of the evidence measuring effectiveness and associated health outcomes points to an urgent need for more robust evaluation of intervention effectiveness, as well as intervention delivery effectiveness, to improve the evidence base.

We thank Omar Irfan.

HIC

high-income countries

LMIC

low- and middle-income countries

NCDs

noncommunicable diseases