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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.

As the world counts down to the 2025 World Health Assembly nutrition targets and the 2030 Sustainable Development Goals, millions of women, children, and adolescents worldwide remain undernourished (underweight, stunted, and deficient in micronutrients), despite evidence on effective interventions and increasing political commitment to, and financial investment in, nutrition. The COVID-19 pandemic has crippled health systems, exacerbated household food insecurity, and reversed economic growth, which together could set back improvements in undernutrition across low-income and middle-income countries. This paper highlights how the evidence base for nutrition, health, food systems, social protection, and water, sanitation, and hygiene interventions has evolved since the 2013 Lancet Series on maternal and child nutrition and identifies the priority actions needed to regain and accelerate progress within the next decade. Policies and interventions targeting the first 1000 days of life, including some newly identified since 2013, require renewed commitment, implementation research, and increased funding from both domestic and global actors. A new body of evidence from national and state-level success stories in stunting reduction reinforces the crucial importance of multisectoral actions to address the underlying determinants of undernutrition and identifies key features of enabling political environments. To support these actions, well-resourced nutrition data and information systems are essential. The paper concludes with a call to action for the 2021 Nutrition for Growth Summit to unite global and national nutrition stakeholders around common priorities to tackle a large, unfinished undernutrition agenda—now amplified by the COVID-19 crisis.

Background Almost two billion people who are deficient in vitamins and minerals are women and children in low‐ and middle‐income countries (LMIC). These deficiencies are worsened during pregnancy due to increased energy and nutritional demands, causing adverse outcomes in mother and child. To reduce micronutrient deficiencies, several strategies have been implemented, including diet diversification, large‐scale and targeted fortification, staple crop bio‐fortification and micronutrient supplementation. Objectives To evaluate and summarize the available evidence on the effects of micronutrient supplementation during pregnancy in LMIC on maternal, fetal, child health and child development outcomes. This review will assess the impact of single micronutrient supplementation (calcium, vitamin A, iron, vitamin D, iodine, zinc, vitamin B12), iron‐folic acid (IFA) supplementation, multiple micronutrient (MMN) supplementation, and lipid‐based nutrient supplementation (LNS) during pregnancy. Search Methods We searched papers published from 1995 to 31 October 2019 (related programmes and good quality studies pre‐1995 were limited) in CAB s, CINAHL, Cochrane Central Register of Controlled Trials, Embase, International Initiative for Impact Evaluations, LILACS, Medline, POPLINE, Web of Science, WHOLIS, ProQuest Dissertations & Theses Global, R4D, WHO International Clinical Trials Registry Platform. Non‐indexed grey literature searches were conducted using Google, Google Scholar, and web pages of key international nutrition agencies. Selection Criteria We included randomized controlled trials (individual and cluster‐randomized) and quasi‐experimental studies that evaluated micronutrient supplementation in healthy, pregnant women of any age and parity living in a LMIC. LMIC were defined by the World Bank Group at the time of the search for this review. While the aim was to include healthy pregnant women, it is likely that these populations had one or more micronutrient deficiencies at baseline; women were not excluded on this basis. Data Collection and Analysis Two authors independently assessed studies for inclusion and risk of bias, and conducted data extraction. Data were matched to check for accuracy. Quality of evidence was assessed using the GRADE approach. Main Results A total of 314 papers across 72 studies (451,723 women) were eligible for inclusion, of which 64 studies (439,649 women) contributed to meta‐analyses. Seven studies assessed iron‐folic acid (IFA) supplementation versus folic acid; 34 studies assessed MMN vs. IFA; 4 studies assessed LNS vs. MMN; 13 evaluated iron; 13 assessed zinc; 9 evaluated vitamin A; 11 assessed vitamin D; and 6 assessed calcium. Several studies were eligible for inclusion in multiple types of supplementation. IFA compared to folic acid showed a large and significant (48%) reduction in the risk of maternal anaemia (average risk ratio (RR) 0.52, 95% CI 0.41 to 0.66; studies = 5; participants = 15,540; moderate‐quality evidence). As well, IFA supplementation demonstrated a smaller but significant, 12% reduction in risk of low birthweight (LBW) babies (average RR 0.88, 95% CI 0.78 to 0.99; studies = 4; participants = 17,257; high‐quality evidence). MMN supplementation was defined as any supplement that contained at least 3 micronutrients. Post‐hoc analyses were conducted, where possible, comparing the differences in effect of MMN with 4+ components and MMN with 3 or 4 components. When compared to iron with or without FA, MMN supplementation reduced the risk of LBW by 15% (average RR 0.85, 95% CI 0.77 to 0.93; studies = 28; participants = 79,972); this effect was greater in MMN with >4 micronutrients (average RR 0.79, 95% CI 0.71 to 0.88; studies = 19; participants = 68,138 versus average RR 1.01, 95% CI 0.92 to 1.11; studies = 9; participants = 11,834). There was a small and significant reduction in the risk of stillbirths (average RR 0.91; 95% CI 0.86 to 0.98; studies = 22; participants = 96,772) and a small and significant effect on the risk of small‐for‐gestational age (SGA) (average RR 0.93; 95% CI 0.88 to 0.98; studies = 19; participants = 52,965). For stillbirths and SGA, the effects were greater among those provided MMN with 4+ micronutrients. Children whose mothers had been supplemented with MMN, compared to IFA, demonstrated a 16% reduced risk of diarrhea (average RR 0.84; 95% CI 0.76 to 0.92; studies = 4; participants = 3,142). LNS supplementation, compared to MMN, made no difference to any outcome; however, the evidence is limited. Iron supplementation, when compared to no iron or placebo, showed a large and significant effect on maternal anaemia, a reduction of 47% (average RR 0.53, 95% CI 0.43 to 0.65; studies = 6; participants = 15,737; moderate‐quality evidence) and a small and significant effect on LBW (average RR 0.88, 95% CI 0.78 to 0.99; studies = 4; participants = 17,257; high‐quality evidence). Zinc and vitamin A supplementation, each both compared to placebo, had no impact on any outcome examined with the exception of potentially improving serum/plasma zinc (mean difference (MD) 0.43 umol/L; 95% CI −0.04 to 0.89; studies = 5; participants = 1,202) and serum/plasma retinol (MD 0.13 umol/L; 95% CI −0.03 to 0.30; studies = 6; participants = 1,654), respectively. When compared to placebo, vitamin D supplementation may have reduced the risk of preterm births (average RR 0.64; 95% CI 0.40 to 1.04; studies = 7; participants = 1,262), though the upper CI just crosses the line of no effect. Similarly, calcium supplementation versus placebo may have improved rates of pre‐eclampsia/eclampsia (average RR 0.45; 95% CI 0.19 to 1.06; studies = 4; participants = 9,616), though the upper CI just crosses 1. Authors' Conclusions The findings suggest that MMN and vitamin supplementation improve maternal and child health outcomes, including maternal anaemia, LBW, preterm birth, SGA, stillbirths, micronutrient deficiencies, and morbidities, including pre‐eclampsia/eclampsia and diarrhea among children. MMN supplementation demonstrated a beneficial impact on the most number of outcomes. In addition, MMN with >4 micronutrients appeared to be more impactful than MMN with only 3 or 4 micronutrients included in the tablet. Very few studies conducted longitudinal analysis on longer‐term health outcomes for the child, such as anthropometric measures and developmental outcomes; this may be an important area for future research. This review may provide some basis to guide continual discourse around replacing IFA supplementation with MMN along with the use of single micronutrient supplementation programs for specific outcomes.

Progress has been made globally in improving the coverage of key maternal, newborn, and early childhood interventions in low-income and middle-income countries, which has contributed to a decrease in child mortality and morbidity. However, inequities remain, and many children and adolescents are still not covered by life-saving and nurturing care interventions, despite their relatively low costs and high cost-effectiveness. This Series paper builds on a large body of work from the past two decades on evidence-based interventions and packages of care for survival, strategies for delivery, and platforms to reach the most vulnerable. We review the current evidence base on the effectiveness of a variety of essential and emerging interventions that can be delivered from before conception until age 20 years to help children and adolescents not only survive into adulthood, but also to grow and develop optimally, support their wellbeing, and help them reach their full developmental potential. Although scaling up evidence-based interventions in children younger than 5 years might have the greatest effect on reducing child mortality rates, we highlight interventions and evidence gaps for school-age children (5–9 years) and the transition from childhood to adolescence (10–19 years), including interventions to support mental health and positive development, and address unintentional injuries, neglected tropical diseases, and non-communicable diseases.

Almost two billion people are deficient in key vitamins and minerals, mostly women and children in low- and middle-income countries (LMICs). Deficiencies worsen during pregnancy due to increased energy and nutritional demands, causing adverse outcomes in mother and child, but could be mitigated by interventions like micronutrient supplementation. To our knowledge, this is the first systematic review that aimed to compile evidence from both efficacy and effectiveness trials, evaluating different supplementation interventions on maternal, birth, child health, and developmental outcomes. We evaluated randomized controlled trials and quasi-experimental studies published since 1995 in peer-reviewed and grey literature that assessed the effects of calcium, vitamin A, iron, vitamin D, and zinc supplementation compared to placebo/no treatment; iron-folic (IFA) supplementation compared to folic acid only; multiple micronutrient (MMN) supplementation compared to IFA; and lipid-based nutrient supplementation (LNS) compared to MMN supplementation. Seventy-two studies, which collectively involved 314 papers (451,723 women), were included. Meta-analyses showed improvement in several key birth outcomes, such as preterm birth, small-for-gestational age (SGA) and low birthweight with MMN supplementation, compared to IFA. MMN also improved child outcomes, including diarrhea incidence and retinol concentration, which are findings not previously reported. Across all comparisons, micronutrient supplementation had little to no effect on mortality (maternal, neonatal, perinatal, and infant) outcomes, which is consistent with other systematic reviews. IFA supplementation showed notable improvement in maternal anemia and the reduction in low birthweight, whereas LNS supplementation had no apparent effect on outcomes; further research that compares LNS and MMN supplementation could help understand differences with these commodities. For single micronutrient supplementation, improvements were noted in only a few outcomes, mainly pre-eclampsia/eclampsia (calcium), maternal anemia (iron), preterm births (vitamin D), and maternal serum zinc concentration (zinc). These findings highlight that micronutrient-specific supplementation should be tailored to specific groups or needs for maximum benefit. In addition, they further contribute to the ongoing discourse of choosing antenatal MMN over IFA as the standard of care in LMICs.

In many low- and middle-income countries (LMICs) the double burden of malnutrition is high among adolescent girls, leading to poor health outcomes for the adolescent herself and sustained intergenerational effects. This underpins the importance of adequate dietary intake during this period of rapid biological development. The aim of this systematic review was to summarize the current dietary intake and practices among adolescent girls (10–19 years) in LMICs. We searched relevant databases and grey literature using MeSH terms and keywords. After applying specified inclusion and exclusion criteria, 227 articles were selected for data extraction, synthesis, and quality assessment. Of the included studies, 59% were conducted in urban populations, 78% in school settings, and dietary measures and indicators were inconsistent. Mean energy intake was lower in rural settings (1621 ± 312 kcal/day) compared to urban settings (1906 ± 507 kcal/day). Self-reported daily consumption of nutritious foods was low; on average, 16% of girls consumed dairy, 46% consumed meats, 44% consumed fruits, and 37% consumed vegetables. In contrast, energy-dense and nutrient-poor foods, like sweet snacks, salty snacks, fast foods, and sugar-sweetened beverages, were consumed four to six times per week by an average of 63%, 78%, 23%, and 49% of adolescent girls, respectively. 40% of adolescent girls reported skipping breakfast. Along with highlighting the poor dietary habits of adolescent girls in LMIC, this review emphasizes the need for consistently measured and standardized indicators, and dietary intake data that are nationally representative.

IntroductionAfghanistan’s health system has faced considerable challenges since the Taliban takeover in 2021, leaving the population vulnerable to an increased risk of morbidity and mortality. Research to illuminate the current functioning of the health system and approaches for strengthening its key components is critically needed to address imminent and evolving health needs of the Afghan people.MethodsA health systems’ research agenda for Afghanistan that uses a systematic and evidence-based wisdom of the crowds’ approach has yet to be developed. Using the Child Health and Nutrition Research Initiative methodology, this study identifies the top 20 health systems’ research priorities among experienced Afghanistan health researchers. Priorities were also considered when disaggregating data by subgroups, such as Afghan versus non-Afghan respondents and those from low- and middle-income versus high-income settings.ResultsA total of 303 researchers were invited to score the research questions; 86 responded to the scoring survey and 55 completed it (60% were of Afghan origin). The highest priority questions were relatively diverse in terms of topic area, with questions spanning system-level factors, healthcare quality, community-based healthcare, improvements in the pharmaceutical sector, epidemiological trends, health management information systems and surveillance, access to care and approaches to improving service delivery in Afghanistan, among many others. ‘Delivery’-focused and ‘development’-focused questions were prioritised, demonstrating that participants assigned greater importance to more practical research questions that would explore features of and approaches to improving existing health system structures within the current Afghan context. Results were consistent across subgroups.ConclusionThis research prioritisation exercise fills a gap by generating consensus and establishing a research agenda for strengthening Afghanistan’s health system.

Long standing diabetes leads to structural and functional alterations in both the micro- and the macro-vasculature. Vascular endothelial cells (ECs) are the primary target of the hyperglycemia-induced adverse effects. Vascular stem cells that give rise to endothelial progenitor cells (EPCs) and mesenchymal progenitor cells (MPCs) represent an attractive target for cell therapy for diabetic patients. A number of studies have reported EPC dysfunction as a novel participant in the culmination of the diabetic complications. The controversy behind the identity of EPCs and the similarity between these progenitor cells to hematopoietic cells has led to conflicting results. MPCs, on the other hand, have not been examined for a potential role in the pathogenesis of the complications. These multipotent cells, however, do show a therapeutic role. In this article, we summarize the vascular changes that occur in diabetic complications highlighting some of the common features, the key findings that illustrate an important role of vascular stem cells (VSCs) in the pathogenesis of chronic diabetic complications, and provide mechanisms by which these cells can be used for therapy.

Suboptimal complementary feeding practices remain highly prevent. This review aims to comprehensively synthesize new emerging evidence on a set of topics related to the selection and consumption of complementary foods. We synthesized evidence related to five key topics focused on nutritional interventions that target the complementary feeding period, based on four systematic reviews that include updated evidence to February 2022. While there have been many studies examining interventions during the complementary feeding period, there is an overall lack of relevant information through which to draw conclusions on the ideal feeding schedule by food type. Similarly, few studies have examined the effects of animal milk versus infant formula for non-breastfed infants (6–11 months), though those that did found a greater risk of anemia among infants who were provided cow’s milk. This review highlights a number of interventions that are successful at improving micronutrient status and anthropometry during the complementary feeding period, including fortified blended foods, locally and commercially produced supplementary foods, and small-quantity lipid-based nutrient supplements. Complementary feeding education for caregivers can also be used to improve nutrition outcomes among infants in both food secure and insecure populations.