Calcium channel blockers for preventing cardiomyopathy due to iron overload in people with transfusion-dependent beta thalassaemia.

BACKGROUND: Beta-thalassaemia is an inherited blood disorder that reduces the production of haemoglobin. The most severe form requires recurrent blood transfusions, which can lead to iron overload. Cardiovascular dysfunction caused by iron overload is the leading cause of morbidity and mortality in people with transfusion-dependent beta-thalassaemia. Iron chelation therapy has reduced the severity of systemic iron overload, but removal of iron from the myocardium requires a very proactive preventive strategy. There is evidence that calcium channel blockers may reduce myocardial iron deposition. This is an update of a Cochrane Review first published in 2018. OBJECTIVES: To assess the effects of calcium channel blockers plus standard iron chelation therapy, compared with standard iron chelation therapy (alone or with a placebo), on cardiomyopathy due to iron overload in people with transfusion-dependent beta thalassaemia. SEARCH METHODS: We searched the Cochrane Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books, to 13 January 2022. We also searched ongoing trials databases and the reference lists of relevant articles and reviews. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of calcium channel blockers combined with standard chelation therapy versus standard chelation therapy alone or combined with placebo in people with transfusion-dependent beta thalassaemia. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. We used GRADE to assess certainty of evidence. MAIN RESULTS: We included six RCTs (five parallel-group trials and one cross-over trial) with 253 participants; there were 126 participants in the amlodipine arms and 127 in the control arms. The certainty of the evidence was low for most outcomes at 12 months; the evidence for liver iron concentration was of moderate certainty, and the evidence for adverse events was of very low certainty. Amlodipine plus standard iron chelation compared with standard iron chelation (alone or with placebo) may have little or no effect on cardiac T2* values at 12 months (mean difference (MD) 1.30 ms, 95% confidence interval (CI) -0.53 to 3.14; 4 trials, 191 participants; low-certainty evidence) and left ventricular ejection fraction (LVEF) at 12 months (MD 0.81%, 95% CI -0.92% to 2.54%; 3 trials, 136 participants; low-certainty evidence). Amlodipine plus standard iron chelation compared with standard iron chelation (alone or with placebo) may reduce myocardial iron concentration (MIC) after 12 months (MD -0.27 mg/g, 95% CI -0.46 to -0.08; 3 trials, 138 participants; low-certainty evidence). The results of our analysis suggest that amlodipine has little or no effect on heart T2*, MIC, or LVEF after six months, but the evidence is very uncertain. Amlodipine plus standard iron chelation compared with standard iron chelation (alone or with placebo) may increase liver T2* values after 12 months (MD 1.48 ms, 95% CI 0.27 to 2.69; 3 trials, 127 participants; low-certainty evidence), but may have little or no effect on serum ferritin at 12 months (MD 0.07 µg/mL, 95% CI -0.20 to 0.35; 4 trials, 187 participants; low-certainty evidence), and probably has little or no effect on liver iron concentration (LIC) after 12 months (MD -0.86 mg/g, 95% CI -4.39 to 2.66; 2 trials, 123 participants; moderate-certainty evidence). The results of our analysis suggest that amlodipine has little or no effect on serum ferritin, liver T2* values, or LIC after six months, but the evidence is very uncertain. The included trials did not report any serious adverse events at six or 12 months of intervention. The studies did report mild adverse effects such as oedema, dizziness, mild cutaneous allergy, joint swelling, and mild gastrointestinal symptoms. Amlodipine may be associated with a higher risk of oedema (risk ratio (RR) 5.54, 95% CI 1.24 to 24.76; 4 trials, 167 participants; very low-certainty evidence). We found no difference between the groups in the occurrence of other adverse events, but the evidence was very uncertain. No trials reported mortality, cardiac function assessments other than echocardiographic estimation of LVEF, electrocardiographic abnormalities, quality of life, compliance with treatment, or cost of interventions. AUTHORS' CONCLUSIONS: The available evidence suggests that calcium channel blockers may reduce MIC and may increase liver T2* values in people with transfusion-dependent beta thalassaemia. Longer-term multicentre RCTs are needed to assess the efficacy and safety of calcium channel blockers for myocardial iron overload, especially in younger children. Future trials should also investigate the role of baseline MIC in the response to calcium channel blockers, and include a cost-effectiveness analysis.

Effectiveness of Dietary Management for Moderate Wasting among Children > 6 Months of Age-A Systematic Review and Meta-Analysis Exploring Different Types, Quantities, and Durations.

Currently, no World Health Organization guidelines exist for the management of approximately 31.8 million moderately wasted children globally. The objective of this review was to synthesise evidence on the optimal type, quantity, and duration of dietary treatment for moderate wasting. Ten electronic databases were searched until the 23rd of August 2021. Experimental studies comparing interventions for the dietary management of moderate wasting were included. Meta-analyses were conducted and results were presented as risk ratios or mean differences with 95% confidence intervals. Seventeen studies comparing specially formulated foods were included involving 23,005 participants. Findings suggest little or no difference in recovery between Fortified Blended Foods (FBFs) with improved micronutrient and/or milk content (enhanced FBFs) and lipid-based nutrient supplements (LNS), whereas children treated with non-enhanced FBFs (locally produced FBFs or standard corn-soy blend) may have lower recovery rates than those treated with LNS. There was no difference in recovery when ready-to-use therapeutic and ready-to-use supplementary food were compared. Other outcomes mostly aligned with results for recovery. In conclusion, LNSs improve recovery compared to non-enhanced FBFs, but are comparable to enhanced FBFs. Programmatic choice of supplement should consider factors such as cost, cost-effectiveness, and acceptability. Further research is required to determine optimal dosing and duration of supplementation.

Interventions for High-Burden Infectious Diseases in Children and Adolescents: A Meta-analysis.

BACKGROUND: Approximately 2.2 million deaths were reported among school-age children and young people in 2019, and infectious diseases remain the leading causes of morbidity and mortality, especially in low and middle-income countries. We aim to synthesize evidence on interventions for high-burden infectious diseases among children and adolescents aged 5 to 19 years. METHODS: We conducted a comprehensive literature search until December 31, 2020. Two review authors independently screened studies for relevance, extracted data, and assessed risk of bias. RESULTS: We included a total of 31 studies, including 81 596 participants. Sixteen studies focused on diarrhea; 6 on tuberculosis; 2 on human immunodeficiency virus; 2 on measles; 1 study each on acute respiratory infections, malaria, and urinary tract infections; and 2 studies targeted multiple diseases. We did not find any study on other high burden infectious diseases among this age group. We could not perform meta-analysis for most outcomes because of variances in interventions and outcomes. Findings suggests that for diarrhea, water treatment, water filtration, and zinc supplementation have some protective effect. For tuberculosis, peer counseling, contingency contract, and training of health care workers led to improvements in tuberculosis detection and treatment completion. Continuation of cotrimoxazole therapy reduced the risk of tuberculosis and hospitalizations among human immunodeficiency virus-infected children and reduced measles complications and pneumonia cases among measles-infected children. Zinc supplementation led to a faster recovery in urinary tract infections with a positive effect in reducing symptoms. CONCLUSIONS: There is scarcity of data on the effectiveness of interventions for high-burden infectious diseases among school-aged children and adolescents.

Interventions for Neglected Tropical Diseases Among Children and Adolescents: A Meta-analysis.

BACKGROUND: Neglected tropical diseases (NTDs) are a group of communicable diseases affecting the poorest populations around the world. OBJECTIVE: To assess the effectiveness of interventions, including mass drug administration (MDA), water, sanitation, and hygiene (WASH), vector control, health education, and micronutrients supplementation, for NTDs among children and adolescents. METHODS: We conducted a literature search on the Cochrane Controlled Trials Register, Medline, and other databases until December 2020. We included randomized controlled trials and quasi-experimental studies conducted among children and adolescents. Two authors independently screened studies for relevance. Two authors independently extracted data, assessed the risk of bias, performed metaanalysis, and rated the quality of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation. RESULTS: We included 155 studies (231 articles) involving 262 299 participants. For soil-transmitted helminthiasis, MDA may reduce the prevalence of Ascaris, Trichuris, and hookworm by 58%, 36%, and 57%, respectively. We are uncertain of the effect of health education, WASH, and iron supplementation on soil-transmitted helminthiasis prevalence. For Schistosomiasis, health education probably reduces the intensity and prevalence of S. mansoni, whereas micronutrient supplementation may reduce anemia prevalence and the infection intensity of S. hematobium compared with no supplementation. We are uncertain of the effect of MDA and vector control on Schistosomiasis outcomes. For trachoma, health education probably reduces the prevalence of active Trachoma, whereas we are uncertain of the effect of MDA, WASH, and vector control on Trachoma outcomes. There is limited data on the effectiveness of interventions for NTDs targeting children and adolescents. CONCLUSION: Future studies are needed to evaluate the relative effectiveness and cost-effectiveness of various interventions specifically targeting children and adolescents.

Tackling Protein-Calorie Malnutrition during World Crises.

Undernutrition is still highly prevalent in developing countries and leads to a multitude of problems as it weakens the immune system, which leads to increased risk of infections and diet-related diseases. COVID-19 has worsened the existing situation and has resulted in unprecedented health, social, and economic disruptions across the world. Before COVID-19, about 54% children under 5 years were moderately or seriously malnourished, and after the COVID-19 pandemic, early estimates suggest that an additional 2.6 million children were stunted; 9.3 million were wasted, with an addition of 2.1 million maternal anemia cases; 168,000 child deaths; and USD 29.7 billion in productivity losses. This review is mainly focused on the health and nutrition sectors and highlights the impact of COVID-19 on malnutrition, food system and industry, and it also discusses the various measures implemented across the world to cater the burden of maternal and child malnutrition. Movement restrictions and lockdowns within and across the countries/borders have imposed an unprecedented stress and shock on the food supply chain, affecting harvest, food processing, supply, logistics, food demand, shortages, and cost. Many countries have implemented interventions such as cash transfers, food ration distribution, insurance plans, utility subsidy, and tax exemptions to assist the population to cope with the financial and health issues caused due to the outbreak. Other than these measures, evidence recommends some essential direct and indirect interventions which could help in reducing malnutrition during COVID-19. The COVID-19 pandemic has re-demonstrated the connection between food systems, nutrition, health, and prosperity and the need for a more holistic approach.

Optimal iron content in ready-to-use therapeutic foods for the treatment of severe acute malnutrition in the community settings: a protocol for the systematic review and meta-analysis.

INTRODUCTION: The current standard of care for children with severe acute malnutrition (SAM) involves using ready-to-use therapeutic food (RUTF) to promote growth; however, the precise formulation to achieve optimal recovery remains unclear. Emerging research suggests that alternative RUTF formulations may be more effective in correcting SAM-related complications such as anaemia and iron deficiency. This systematic review commissioned by the WHO aims to synthesise the most recent research on the iron content in RUTF and related products in the community-based treatment of uncomplicated severe malnutrition in children aged 6 months and older. METHODS AND ANALYSIS: We will search multiple electronic databases. We will include randomised controlled trials and non-randomised studies with a control arm. The intervention group will be infants who received RUTF treatments other than the current recommended guidelines set forth by the WHO. The comparison group is children receiving RUTF containing iron at the current WHO-recommended level of 1.9 mg/100 kcal (10-14 mg/100 g). The primary outcomes of interest include blood haemoglobin concentration, any anaemia, severe anaemia, iron-deficiency anaemia, recovery from SAM and any adverse outcomes. We will use meta-analysis to pool findings if sufficient homogeneity exists among included studies. The risk of bias in studies will be evaluated using the Cochrane risk of bias-2. We will use the Grading of Recommendations Assessment, Development, and Evaluation(GRADE) approach to examine the overall certainty of evidence. ETHICS AND DISSEMINATION: This is a systematic review and will not involve direct contact with human subjects. The findings of this review will be published in a peer-reviewed journal and will guide the WHO's recommendation on the optimal iron content in RUTFs for the treatment of SAM in children aged 6-59 months.

Vitamin C supplementation for prevention and treatment of pneumonia.

BACKGROUND: According to the Global Burden of Disease Study 2015, lower respiratory tract infection is the leading cause of infectious disease death, and the fifth most common cause of death overall. Vitamin C has a role in modulating resistance to infectious agents, therefore vitamin C supplementation may be important in preventing and treating pneumonia. OBJECTIVES: To assess the impact of vitamin C supplementation to prevent and treat pneumonia in children and adults. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, PubMed, CINAHL, LILACS, Web of Science, and two trials registers to 4 March 2020. We also checked references to identify additional studies. We did not apply any publication status or language filters. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs (studies using allocation methods that are not random, e.g. date of birth, medical record number) assessing the role of vitamin C supplementation in the prevention and treatment of pneumonia in children and adults compared to control or placebo. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included five studies in the review and identified two ongoing studies. The five included studies involved a total of 2655 participants; two studies were RCTs and three were quasi-RCTs. The included studies were conducted in one high-income country (USA) and three lower-middle-income countries (Bangladesh and Pakistan). Three studies were conducted in hospital inpatient settings, one in school, and one in a military training centre. Three studies included children under five years of age, one study included school-aged children, and one study included adult participants. Two studies assessed the effect of vitamin C supplementation for pneumonia prevention; and three studies assessed the effect of vitamin C supplementation as an adjunct to pneumonia treatment. For pneumonia prevention, the included studies provided supplementation in doses of 1 g daily for 14 weeks, 2 g daily for 8 weeks, and 2 g daily for 14 weeks. For pneumonia treatment, the included studies provided vitamin C supplementation in doses of 125 mg daily and 200 mg daily until the symptoms resolved or discharge, as an adjunct to the pneumonia treatment. Overall, the included studies were judged to be at either high or unclear risk of bias for random sequence generation, allocation concealment, and blinding; and the evidence certainty was very low. Two studies assessed the effect of vitamin C supplementation for pneumonia prevention; we judged the certainty of the evidence as very low. We are uncertain about the effect of vitamin C supplementation on pneumonia incidence and adverse events (urticaria). None of the included studies reported other primary outcomes (pneumonia prevalence and mortality) or any of the secondary outcomes. Three studies assessed the effect of vitamin C supplementation as an adjunct to pneumonia treatment; we judged the certainty of the evidence as very low. We are uncertain of the effect of vitamin C supplementation on duration of illness and hospitalisation. None of the included studies reported other primary or secondary outcomes. AUTHORS' CONCLUSIONS: Due to the small number of included studies and very low certainty of the existing evidence, we are uncertain of the effect of vitamin C supplementation for the prevention and treatment of pneumonia. Further good-quality studies are required to assess the role of vitamin C supplementation in the prevention and treatment of pneumonia.

Delivering nutrition interventions to women and children in conflict settings: a systematic review.

BACKGROUND: Low/middle-income countries (LMICs) face triple burden of malnutrition associated with infectious diseases, and non-communicable diseases. This review aims to synthesise the available data on the delivery, coverage, and effectiveness of the nutrition programmes for conflict affected women and children living in LMICs. METHODS: We searched MEDLINE, Embase, CINAHL, and PsycINFO databases and grey literature using terms related to conflict, population, and nutrition. We searched studies on women and children receiving nutrition-specific interventions during or within five years of a conflict in LMICs. We extracted information on population, intervention, and delivery characteristics, as well as delivery barriers and facilitators. Data on intervention coverage and effectiveness were tabulated, but no meta-analysis was conducted. RESULTS: Ninety-one pubblications met our inclusion criteria. Nearly half of the publications (n=43) included population of sub-Saharan Africa (n=31) followed by Middle East and North African region. Most publications (n=58) reported on interventions targeting children under 5 years of age, and pregnant and lactating women (n=27). General food distribution (n=34), micronutrient supplementation (n=27) and nutrition assessment (n=26) were the most frequently reported interventions, with most reporting on intervention delivery to refugee populations in camp settings (n=63) and using community-based approaches. Only eight studies reported on coverage and effectiveness of intervention. Key delivery facilitators included community advocacy and social mobilisation, effective monitoring and the integration of nutrition, and other sectoral interventions and services, and barriers included insufficient resources, nutritional commodity shortages, security concerns, poor reporting, limited cooperation, and difficulty accessing and following-up of beneficiaries. DISCUSSION: Despite the focus on nutrition in conflict settings, our review highlights important information gaps. Moreover, there is very little information on coverage or effectiveness of nutrition interventions; more rigorous evaluation of effectiveness and delivery approaches is needed, including outside of camps and for preventive as well as curative nutrition interventions. PROSPERO REGISTRATION NUMBER: CRD42019125221.

Effective interventions to address maternal and child malnutrition: an update of the evidence.

Malnutrition-consisting of undernutrition, overweight and obesity, and micronutrient deficiencies-continues to afflict millions of women and children, particularly in low-income and middle-income countries (LMICs). Since the 2013 Lancet Series on maternal and child nutrition, evidence on the ten recommended interventions has increased, along with evidence of newer interventions. Evidence on the effectiveness of antenatal multiple micronutrient supplementation in reducing the risk of stillbirths, low birthweight, and babies born small-for-gestational age has strengthened. Evidence continues to support the provision of supplementary food in food-insecure settings and community-based approaches with the use of locally produced supplementary and therapeutic food to manage children with acute malnutrition. Some emerging interventions, such as preventive small-quantity lipid-based nutrient supplements for children aged 6-23 months, have shown positive effects on child growth. For the prevention and management of childhood obesity, integrated interventions (eg, diet, exercise, and behavioural therapy) are most effective, although there is little evidence from LMICs. Lastly, indirect nutrition strategies, such as malaria prevention, preconception care, water, sanitation, and hygiene promotion, delivered inside and outside the health-care sector also provide important nutritional benefits. Looking forward, greater effort is required to improve intervention coverage, especially for the most vulnerable, and there is a crucial need to address the growing double burden of malnutrition (undernutrition, and overweight and obesity) in LMICs.

Large-scale food fortification has great potential to improve child health and nutrition.

PURPOSE OF REVIEW: Undernutrition, including micronutrient deficiencies, continues to plague children across the world, particularly in low and middle-income countries (LMICs). The situation has worsened alongside the SARS-CoV-2 pandemic because of major systemic disruptions to food supply, healthcare, and employment. Large-scale food fortification (LSFF) is a potential strategy for improving micronutrient intakes through the addition of vitamins and minerals to staple foods and improving the nutritional status of populations at large. RECENT FINDINGS: Current evidence unquestionably supports the use of LSFF to improve micronutrient status. Evidence syntheses have also demonstrated impact on some functional outcomes, including anemia, wasting, underweight, and neural tube defects, that underpin poor health and development. Importantly, many of these effects have also been reflected in effectiveness studies that examine LSFF in real-world situations as opposed to under-controlled environments. However, programmatic challenges must be addressed in LMICs in order for LSFF efforts to reach their full potential. SUMMARY: LSFF is an important strategy that has the potential to improve the health and nutrition of entire populations of vulnerable children. Now more than ever, existing programs should be strengthened and new programs implemented in areas with widespread undernutrition and micronutrient deficiencies.

Nutritional perspectives for the prevention and mitigation of COVID-19.

Worldwide, there is an array of clinical trials under way to evaluate treatment options against coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2. Concurrently, several nutritional therapies and alternative supportive treatments are also being used and tested to reduce the mortality associated with acute respiratory distress in patients with COVID-19. In the context of COVID-19, improved nutrition that includes micronutrient supplementation to augment the immune system has been recognized as a viable approach to both prevent and alleviate the severity of the infection. The potential role of micronutrients as immune-boosting agents is particularly relevant for low- and middle-income countries, which already have an existing high burden of undernutrition and micronutrient deficiencies. A systematic literature review was performed to identify nutritional interventions that might prevent or aid in the recovery from COVID-19. The PubMed, ScienceDirect, Cochrane, Scopus, Web of Science, and Google Scholar databases were searched electronically from February to April 2020. All abstracts and full-text articles were examined for their relevance to this review. The information gathered was collated under various categories. Deficiencies of micronutrients, especially vitamins A, B complex, C, and D, zinc, iron, and selenium, are common among vulnerable populations in general and among COVID-19 patients in particular and could plausibly increase the risk of mortality. Judicious use of need-based micronutrient supplementation, alongside existing micronutrient fortification programs, is warranted in the current global pandemic, especially in low- and middle-income economies.

Effects of preconception care and periconception interventions on maternal nutritional status and birth outcomes in low- and middle-income countries: A systematic review.

Background: The preconception period is an ideal time to introduce interventions relating to nutrition and other lifestyle factors to ensure good pregnancy preparedness, and to promote health of mothers and babies. In adolescents, malnutrition and early pregnancy are the common challenges, particularly among those who live in low- and middle-income countries (LMIC) where 99% of all maternal and newborn deaths occur. These girls receive little or no attention until their first pregnancy and often the interventions after pregnancy are too late to revert any detrimental health risks that may have occurred due to malnutrition and early pregnancy. Objectives: To synthesise the evidence of the effectiveness of preconception care interventions relating to delayed age at first pregnancy, optimising inter-pregnancy intervals, periconception folic acid, and periconception iron-folic acid supplementation on maternal, pregnancy, birth and child outcomes. Search Methods: Numerous electronic databases (e.g., CINAHL, ERIC) and databases of selected development agencies or research firms were systematically searched for all available years up to July 2019. In addition, we searched the reference lists of relevant articles and reviews, and asked experts in the area about ongoing and unpublished studies. Selection Criteria: Primary studies, including large-scale programme evaluations that assessed the effectiveness of interventions using randomised controlled trials (RCTs) or quasi-experimental designs (natural experiments, controlled before-after studies, regression discontinuity designs, interrupted time series [ITS]), that targeted women of reproductive age (i.e., 10-49 years) during the pre- and periconceptional period in LMICs were included. Interventions were compared against no intervention, standard of care or placebo. Data Collection and Analysis: Two or more review authors independently reviewed searches, selected studies for inclusion or exclusion, extracted data and assessed risk of bias. We used random-effects model to conduct meta-analyses, given the diverse contexts, participants, and interventions, and separate meta-analyses for the same outcome was performed with different study designs (ITS, RCTs and controlled before after studies). For each comparison, the findings were descriptively summarised in text which included detailing the contextual factors (e.g., setting) to assess their impact on the implementation and effectiveness of each intervention. Main Results: We included a total of 43 studies; two of these were included in both delaying pregnancy and optimising interpregnancy intervals resulting in 26 studies for delaying the age at first pregnancy (14 RCTs, 12 quasi-experimental), four for optimising interpregnancy intervals (one RCT, three quasi-experimental), five on periconceptional folic acid supplementation (two RCTs, three quasi-experimental), and 10 on periconceptional iron-folic acid supplementation (nine RCTs, one quasi-experimental). Geographically, studies were predominantly conducted across Africa and Asia, with few studies from North and Central America and took place in a combination of settings including community, schools and clinical. The education on sexual health and contraception interventions to delay the age at first pregnancy may make little or no difference on risk of unintended pregnancy (risk ratio [RR], 0.42; 95% confidence internal [CI], 0.07-3.26; two studies, =490; random-effect; χ 2 p .009; I 2 = 85%; low certainty of evidence using GRADE assessment), however, it significantly improved the use of condom (ever) (RR, 1.54; 95% CI, 1.08-2.20; six studies, n = 1604; random-effect, heterogeneity: χ 2 p .004; I 2 = 71%). Education on sexual health and and provision of contraceptive along with involvement of male partneron optimising interpregnancy intervals probably makes little or no difference on the risk of unintended pregnancies when compared to education on sexual health only (RR, 0.32; 95% CI, 0.01-7.45; one study, n = 45; moderate certainty of evidence using GRADE assessments). However, education on sexual health and contraception intervention alone or with provision of contraceptive showed a significant improvement in the uptake of contraceptive method. We are uncertain whether periconceptional folic acid supplementation reduces the incidence of neural tube defects (NTDs) (RR, 0.53; 95% CI, 0.41-0.77; two studies, n = 248,056; random-effect; heterogeneity: χ 2 p .36; I 2 = 0%; very low certainty of evidence using GRADE assessment). We are uncertain whether preconception iron-folic acid supplementation reduces anaemia (RR, 0.66; 95% CI, 0.53-0.81; six studies; n = 3430, random-effect; heterogeneity: χ 2 p < .001; I 2 = 88%; very low certainty of evidence using GRADE assessment) even when supplemented weekly (RR, 0.70; 95% CI, 0.55-0.88; six studies; n = 2661; random-effect; heterogeneity: χ 2 p < .001; I 2 = 88%; very low certainty of evidence using GRADE assessments),and in school set-ups (RR, 0.66; 95% CI, 0.51-0.86; four studies; n = 3005; random-effect; heterogeneity: χ 2 p < .0001; I 2 = 87%; very low certainty of evidence using GRADE assessment). Data on adverse effects were reported on in five studies for iron-folic acid, with the main complaint relating to gastrointestinal side effects. The quality of evidence across the interventions of interest was variable (ranging from very low to moderate) which may be attributed to the different study designs included in this review. Concerning risk of bias, the most common concerns were related to blinding of participants and personnel (performance bias) and whether there were similar baseline characteristic across intervention and comparison groups. Authors' Conclusions: There is evidence that education on sexual health and contraception interventions can improve contraceptive use and knowledge related to sexual health, this review also provides further support for the use of folic acid in pregnancy to reduce NTDs, and notes that weekly regimes of IFA are most effective in reducing anaemia. However the certainty of the evidence was very low and therefore more robust trials and research is required, including ensuring consistency for reporting unplanned pregnancies, and further studies to determine which intervention settings (school, community, clinic) are most effective. Although this review demonstrates promising findings, more robust evidence from RCTs are required from LMICs to further support the evidence.

Food supplements to reduce stunting in Pakistan: a process evaluation of community dynamics shaping uptake.

BACKGROUND: There is an increasing interest in use of food supplements to prevent childhood stunting, however the evidence on the process indicators is scarce. We in this study explore the barriers to the effective implementation of food supplementation programs and the possible mitigation strategies which can guide the design of future programs. METHODS: We undertook a process evaluation of a stunting prevention food supplementation pilot program in rural Pakistan that distributed Wheat Soy Blend (WSB) to pregnant & lactating women, and Lipid-based Nutrient Supplement (LNS) and micronutrient powder (MNP) to < 5 years children. We used a mixed methods approach through a quantitative survey of 800 households and conducted 18 focused group discussion (FGDs) (with male and female caregivers), 4 FGDs (with Community Health Workers (CHWs)) and 22 key informant interviews (with district stakeholders) to evaluate the community side factors affecting uptake through five parameters: value, acceptability, receipt of supplement, usage and correct dosage. RESULTS: The findings show that proportionately few beneficiaries consumed the full dose of supplements, despite reasonable knowledge amongst caregivers. Sharing of supplements with other household member was common, and the full monthly stock was usually not received. Qualitative findings suggest that caregivers did not associate food supplements with stunting prevention. WSB was well accepted as an extra ration, LNS was popular due its chocolaty taste and texture, whereas MNP sprinkles were perceived to be of little value. The cultural food practices led to common sharing, whereas interaction with CHWs was minimal for nutrition counselling. Qualitative findings also indicate CHWs related programmatic constraints of low motivation, multi-tasking, inadequate counselling skills and weak supervision. CONCLUSION: We conclude that the community acceptability of food supplements does not translate into optimal consumption. Hence a greater emphasis is needed on context specific demand creation and focusing on the supply side constraints with improved logistical planning, enhanced motivation and supervision of community workers with involvement of multiple stakeholders. While, similar studies are needed in varying contexts to help frame universal guidelines. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02422953 . Registered on April 22, 2015.

Vitamin C supplementation for prevention and treatment of pneumonia.

BACKGROUND: According to the Global Burden of Disease Study 2015, lower respiratory tract infection is the leading cause of infectious disease death, and the fifth most common cause of death overall. Vitamin C has a role in modulating resistance to infectious agents, therefore vitamin C supplementation may be important in preventing and treating pneumonia. OBJECTIVES: To assess the impact of vitamin C supplementation to prevent and treat pneumonia in children and adults. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, PubMed, CINAHL, LILACS, Web of Science, and two trials registers to 4 March 2020. We also checked references to identify additional studies. We did not apply any publication status or language filters. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs (studies using allocation methods that are not random, e.g. date of birth, medical record number) assessing the role of vitamin C supplementation in the prevention and treatment of pneumonia in children and adults compared to control or placebo. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included seven studies in the review and identified two ongoing studies. The seven included studies involved a total of 2774 participants; five studies were RCTs and two were quasi-RCTs. The included studies were conducted in high-income countries (UK, USA and Chile) and lower-middle-income countries (Bangladesh and Pakistan). Four studies were conducted in hospital inpatient settings, two in schools, and one in a military training centre. Three studies included children under five years of age, two school-aged children, one adult participants, and one older participants aged 60 to 90 years. Two studies assessed the effect of vitamin C supplementation for pneumonia prevention; four studies assessed the effect of vitamin C supplementation as an adjunct to pneumonia treatment; and one study assessed the role of vitamin C for both prevention and treatment of pneumonia. For pneumonia prevention, the included studies provided supplementation in doses of 500 mg daily for 14 weeks, 2 g daily for 8 weeks, and 2 g daily for 12 weeks. For pneumonia treatment, the included studies provided vitamin C supplementation in doses of 125 mg daily (until discharge), 200 mg for 4 weeks, and 200 mg until discharge, as an adjunct to the pneumonia treatment. We assessed the included studies as at overall either high or unclear risk of bias for random sequence generation, allocation concealment, and blinding. We judged the quality of the evidence as very low. Three studies assessed the effect of vitamin C supplementation for pneumonia prevention; we judged the quality of the evidence as very low. We are uncertain about the effect of vitamin C supplementation on pneumonia incidence (risk ratio (RR) 0.46, 95% confidence interval (CI) 0.06 to 3.61; 2 studies, 736 participants; I² = 75%; very low-quality evidence) and adverse events (urticaria) (RR 3.11, 95% CI 0.13 to 76.03; 1 study, 674 participants; very low-quality evidence). No included studies reported our other primary outcomes (pneumonia prevalence and mortality) or any of our secondary outcomes. Five studies assessed the effect of vitamin C supplementation as an adjunct to pneumonia treatment; we judged the quality of the evidence as very low. One study reported a decrease in the duration of illness in the vitamin C supplementation group (3.4 days ± 2.54) compared to the control group (4.5 days ± 2.35), and one study reported a decrease in number of days required for improvement in oxygen saturation (1.03 days ± 0.16 versus 1.14 days ± 1.0) and respiratory rate (3.61 days ± 1.50 versus 4.04 days ± 1.62) in the vitamin C supplementation group compared to the control group. We are uncertain of the effect of vitamin C supplementation on mortality due to pneumonia (RR 0.21, 95% CI 0.03 to 1.66; 1 study, 57 participants; very low-quality evidence). One study reported that the mean duration of hospital stay was 6.75 days amongst children in the vitamin C supplementation group and 7.75 days in the control group; another study reported a lower mean duration of hospital stay in the vitamin C supplementation group compared to the control group (109.55 hours ± 27.89 versus 130.64 hours ± 41.76). AUTHORS' CONCLUSIONS: Due to the small number of included studies and very low quality of the existing evidence, we are uncertain of the effect of vitamin C supplementation for the prevention and treatment of pneumonia. Further good-quality studies are required to assess the role of vitamin C supplementation in the prevention and treatment of pneumonia.

Effects of Preconception Care and Periconception Interventions on Maternal Nutritional Status and Birth Outcomes in Low- and Middle-Income Countries: A Systematic Review.

Pregnancy in adolescence and malnutrition are common challenges in low- and middle-income countries (LMICs), and are associated with many complications and comorbidities. The preconception period is an ideal period for intervention as a preventative tactic for teenage pregnancy, and to increase micronutrient supplementation prior to conception. Over twenty databases and websites were searched and 45 randomized controlled trials (RCTs) or quasi-experimental interventions with intent to delay the age at first pregnancy (n = 26), to optimize inter-pregnancy intervals (n = 4), and supplementation of folic acid (n = 5) or a combination of iron and folic acid (n = 10) during the periconception period were included. The review found that educational interventions to delay the age at first pregnancy and optimizing inter-pregnancy intervals significantly improved the uptake of contraception use (RR = 1.71, 95% CI = 1.42-2.05; two studies, n = 911; I2 = 0%) and (RR = 2.25, 95% CI = 1.29-3.93; one study, n = 338), respectively. For periconceptional folic acid supplementation, the incidence of neural tube defects were reduced (RR = 0.53; 95% CI = 0.41-0.77; two studies, n = 248,056; I2 = 0%), and iron-folic acid supplementation improved the rates of anemia (RR = 0.66, 95% CI = 0.53-0.81; six studies; n = 3430, I2 = 88%), particularly when supplemented weekly and in a school setting. Notwithstanding the findings, more robust RCTs are required from LMICs to further support the evidence.

Impact of Dietary Interventions during Pregnancy on Maternal, Neonatal, and Child Outcomes in Low- and Middle-Income Countries.

Optimal nutrition plays a crucial role in pregnancy. Maternal malnutrition is a risk factor for maternal, fetal, and neonatal complications and is more prevalent in low and middle-income countries (LMICs). This review aims to study the effectiveness of antenatal macronutrient nutritional interventions on maternal, neonatal, and child outcomes. We searched the CENTRAL, PubMed, Embase, and other databases for randomized controlled trials and quasi-experimental designs on healthy pregnant women in LMICs. We also searched grey literature and reports from Google Scholar, Web of Science, and websites of different organizations. Title/abstract screening, full-text screening, and data extraction filtered 15 studies for inclusion. Balanced energy protein (BEP) supplementation (n = 8) studies showed a reduced incidence of perinatal mortality, stillbirths, low birth weight (LBW) infants, small for gestational age (SGA) babies and increased birth weight. Food distribution programs (FDPs) (n =5) witnessed reduced rates of SGA, stunting, wasting, and increased birth weight and birth length. Studies on intervention for obesity prevention (n = 2) showed reductions in birth weight. Other findings were statistically insignificant. Subgroup analyses were conducted to study the effectiveness of supplementation between regions, location, the timing of supplementation and nutritional status; however, there were a limited number of studies in each subgroup. Data from our review supports the antenatal supplementation of BEP and FDP for the prevention of adverse maternal, neonatal, and child outcomes that can be utilized for future policymaking. However, more research is required before recommending obesity prevention programs.

Effectiveness of Interventions for Managing Acute Malnutrition in Children under Five Years of Age in Low-Income and Middle-Income Countries: A Systematic Review and Meta-Analysis.

Childhood malnutrition is a major public health concern, as it is associated with significant short- and long-term morbidity and mortality. The objective of this review was to comprehensively review the evidence for the management of severe acute malnutrition (SAM) and moderate acute malnutrition (MAM) according to the current World Health Organization (WHO) protocol using facility- and community-based approaches, as well as the effectiveness of ready-to-use therapeutic food (RUTF), ready-to-use supplementary food (RUSF), prophylactic antibiotic use, and vitamin A supplementation. We searched relevant electronic databases until 11 February 2019, and performed a meta-analysis. This review summarizes findings from a total of 42 studies (48 papers), including 35,017 children. Limited data show some benefit of integrated community-based screening, identification, and management of SAM and MAM on improving recovery rate. Facility-based screening and management of uncomplicated SAM has no effect on recovery and mortality, while the effect of therapeutic milk F100 for SAM is comparable to RUTF for weight gain and mortality. Local food and whey RUSF are comparable to standard RUSF for recovery rate and weight gain in MAM, while standard RUSF has additional benefits to CSB. Prophylactic antibiotic administration in uncomplicated SAM improves recovery rate and probably improves weight gain and reduces mortality. Limited data suggest that high-dose vitamin A supplementation is comparable with low-dose vitamin A supplementation for weight gain and mortality among children with SAM.

Micronutrient Supplementation and Fortification Interventions on Health and Development Outcomes among Children Under-Five in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis.

Micronutrient deficiencies continue to be widespread among children under-five in low- and middle-income countries (LMICs), despite the fact that several effective strategies now exist to prevent them. This kind of malnutrition can have several immediate and long-term consequences, including stunted growth, a higher risk of acquiring infections, and poor development outcomes, all of which may lead to a child not achieving his or her full potential. This review systematically synthesizes the available evidence on the strategies used to prevent micronutrient malnutrition among children under-five in LMICs, including single and multiple micronutrient (MMN) supplementation, lipid-based nutrient supplementation (LNS), targeted and large-scale fortification, and point-of-use-fortification with micronutrient powders (MNPs). We searched relevant databases and grey literature, retrieving 35,924 papers. After application of eligibility criteria, we included 197 unique studies. Of note, we examined the efficacy and effectiveness of interventions. We found that certain outcomes, such as anemia, responded to several intervention types. The risk of anemia was reduced with iron alone, iron-folic acid, MMN supplementation, MNPs, targeted fortification, and large-scale fortification. Stunting and underweight, however, were improved only among children who were provided with LNS, though MMN supplementation also slightly increased length-for-age z-scores. Vitamin A supplementation likely reduced all-cause mortality, while zinc supplementation decreased the incidence of diarrhea. Importantly, many effects of LNS and MNPs held when pooling data from effectiveness studies. Taken together, this evidence further supports the importance of these strategies for reducing the burden of micronutrient malnutrition in children. Population and context should be considered when selecting one or more appropriate interventions for programming.

Effects of preventive nutrition interventions among adolescents on health and nutritional status in low- and middle-income countries: A systematic review.

Background: Malnutrition is one of the most common causes of morbidity and mortality among children and adolescents and is now considered to be one of the largest risk factors responsible for the global burden of diseases along with poor diet. Objectives: The objective of this review was to assess the impact of preventive nutrition interventions (including nutrition education and counselling; micronutrient supplementation/fortification and macronutrient supplementation) to improve the health and nutritional status of adolescents aged 10-19 years in low- and middle-income countries (LMICs). The secondary objective of the review was to assess various contextual factors based on the World Health Organisation (WHO) health system building blocks framework that might potentially impact the effectiveness of these interventions for this age group. Search Methods: The search was conducted on Cochrane Controlled Trials Register (CENTRAL), MEDLINE, EMBASE, CINAHL, PsycINFO, the WHO nutrition databases, CAB Global Health, Social Science Citation Index, Scopus, WHO Global Health Index, ADOLEC and EPPI until February 5, 2019. We searched Google Scholar along with key nutrition agencies database such as Nutrition International, the Global Alliance for Improved Nutrition, the World Food Programme and HarvestPlus to search for nonindexed, grey literature to locate relevant programme evaluations and any additional trials. All searches were performed without any restrictions on publication date, language or publication status. Selection Criteria: We included randomised controlled trials, quasiexperimental studies, controlled before-after studies and interrupted time series evaluating the effectiveness of preventive nutrition interventions among adolescents between 10 and 19 years of age from LMICs. Data Collection and Analysis: Two review authors independently assessed trials for inclusion, assessed risk of bias and extracted data from included studies. Meta-analysis was conducted separately for each outcome and intervention. For dichotomous data, we reported risk ratios (RR) with 95% confidence intervals (CI). For continuous data, we reported the mean difference (MD) or standard mean difference (SMD) with 95% CI. Main Results: This review summarises findings from a total of 10 studies from 15 papers including 10,802 participants. All the studies included in this review assessed the impact of micronutrient supplementation/fortification on health and nutritional status among adolescents in LMIC. We did not find any study assessing the impact of nutrition education and counselling or on macronutrient supplementation among adolescents. Micronutrient supplementation/fortification interventions included calcium/vitamin D supplementation/fortification, iron supplementation with or without folic acid, zinc supplementation and multiple micronutrient (MMN) fortification. The majority of the studies (eight out of 10 studies) included adolescent girls aged between 10 and 19 years of age. We did not find any large scale preventive nutrition intervention programmes targeting adolescents in LMICs. We are uncertain of the effect of iron supplementation with or without folic acid on anaemia (daily supplementation; RR: 1.04, 95% CI 0.88, 1.24; one study; 1,160 participants; low quality evidence. Weekly supplementation; RR: 1.07, 95% CI: 0.91, 1.26; one study; 1,247 participants; low quality evidence). We are uncertain of the effect of various micronutrient supplementation/fortification on body mass index (calcium/vitamin D supplementation; (MD: -0.01 kg/m2; 95% CI: -1.20, 1.17; two studies; 730 participants; I 2 94%; very low quality evidence, iron supplementation with or without folic acid; MD: 0.29 kg/m2; 95% CI: -0.25, 0.83; two studies; 652 participants; I 2 69%; very low quality evidence, zinc supplementation; MD: 0.35 kg/m2; 95% CI: -0.15, 0.85; one study; 382 participants; very low quality evidence) and MMN fortification; MD: 0.23 kg/m2, 95% CI: -0.11, 0.57; two studies; 943 participants; I 2 22%; very low quality evidence). None of the included studies reported any other primary outcomes including morbidity or adverse effects. Iron supplementation with or without folic acid may improve haemoglobin concentrations (MD: 0.42 g/dL, 95% CI: 0.13, 0.71; four studies; 1,020 participants; I 2 89%; low quality evidence). Calcium/vitamin D supplementation may improve serum 25(OH) D levels (standardised mean difference [SMD]: 2.85, 95% CI: 0.89, 4.82; two studies; 395 participants; I 2 99%; low quality evidence). We are uncertain of the effect of calcium only supplementation (MD: 0.02 g/cm2, 95% CI: -0.00, 0.04; one study; 233 participants; low quality outcome) and calcium + vitamin D supplementation (MD: 0.02 g/cm2, 95% CI: -0.00, 0.04; one study; 235 participants; low quality evidence) on total bone mineral density (BMD). We are uncertain of the effect of MMN fortification on haemoglobin concentrations (MD: -0.10 g/dL, 95% CI: -0.88, 0.68; two studies; 1102 participants; I 2 100%; very low quality evidence); calcium supplementation on total body bone mineral content (BMC); (MD: 30.20 g, 95% CI: -40.56, 100.96; one study; 233 participants; low quality evidence), calcium + vitamin D supplementation on total body BMC (MD: 21.60 g, 95% CI: -45.32, 88.52; one study; 235 participants; low quality evidence) and zinc supplementation on serum zinc levels (SMD: 6.94, 95% CI: -4.84, 18.71; two studies; 494 participants; very low quality evidence). One study reported the impact of iron supplementation with or without folic acid on cognition of adolescent girls suggesting improved cognition in most of the tests with daily or twice weekly supplementation compared to once weekly or no supplementation. None of the other secondary outcomes were reported including any other development outcomes and all-cause mortality. These findings warrant caution while interpreting due to very few studies and high heterogeneity. Authors' Conclusions: There is limited evidence of micronutrient supplementation/fortification among adolescents on health and nutritional status in LMICs, with lack of evidence on nutrition education and counselling and macronutrient supplementation. The findings are generaliseable for adolescent girls since all studies (except one) targeted female adolescents.