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Repercussions of inborn errors of immunity on growth.
Goudouris, ES, Segundo, GRS, Poli, C
Jornal de pediatria. 2019;:49-58
Abstract
OBJECTIVES This study aimed to review the literature on the repercussions of the different inborn errors of immunity on growth, drawing attention to the diagnosis of this group of diseases in patients with growth disorders, as well as to enable the identification of the different causes of growth disorders in patients with inborn errors of immunity, which can help in their treatment. DATA SOURCES Non-systematic review of the literature, searching articles since 2000 in PubMed with the terms "growth", "growth disorders", "failure to thrive", or "short stature" AND "immunologic deficiency syndromes", "immune deficiency disease", or "immune deficiency" NOT HIV. The Online Mendelian Inheritance in Man (OMIN) database was searched for immunodeficiencies and short stature or failure to thrive. DATA SUMMARY Inborn errors of immunity can affect growth in different ways, and some of them can change growth through multiple simultaneous mechanisms: genetic syndromes; disorders of the osteoarticular system; disorders of the endocrine system; reduction in caloric intake; catabolic processes; loss of nutrients; and inflammatory and/or infectious conditions. CONCLUSIONS The type of inborn errors of immunity allows anticipating what type of growth disorder can be expected. The type of growth disorder can help in the diagnosis of clinical conditions related to inborn errors of immunity. In many inborn errors of immunity, the causes of poor growth are mixed, involving more than one factor. In many cases, impaired growth can be adjusted with proper inborn errors of immunity treatment or proper approach to the mechanism of growth impairment.
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Study protocol to assess the impact of an integrated nutrition intervention on the growth and development of children under two in rural Bangladesh.
Ara, G, Sanin, KI, Khanam, M, Sarker, SA, Khan, SS, Rifat, M, Chowdhury, IA, Askari, S, Afsana, K, Ahmed, T
BMC public health. 2019;(1):1437
Abstract
BACKGROUND The period from birth to two years is the "critical window" for achieving optimal growth and development. An inadequate quality and quantities of complementary foods, poor child-feeding practices and infection negatively impact the growth of under-twos. Approximately one-third of under-fives in developing countries are stunted; many are also micronutrient deficient. An estimated 6% of mortalities among under-fives can be prevented by ensuring optimal complementary feeding. The objective of the study was to assess the ability of a 12-month integrated nutrition intervention to improve the nutritional status (length-for-age Z-score) of 6 to 12-month-old children in rural Bangladesh. METHODS In this community-based randomized controlled trial, the intervention group received a package of interventions that includes, food vouchers; to prepare egg-based nutritious snacks (suji firni for < 1-year-olds, suji halwa for > 1-year-olds), micronutrient powder to fortify children's food at home, child feeding counselling and water, sanitation and hygiene (WASH), behaviour change communication. The control group received routine health messages provided by the government. Baseline and endline surveys were conducted; Data collection was performed monthly on children's growth, food voucher utilization, child feeding and morbidity. In addition, we assessed the cognitive development of the children after 12 months of intervention. CONCLUSION This trial aims to explore whether an integrated nutrition intervention can mitigate childhood stunting during the critical window of opportunity in rural Bangladesh. The results may provide robust evidence to improve the linear growth of children in developing countries. TRIAL REGISTRATION The study was retrospectively registered on August 17, 2018 and is available online at ClinicalTrials.gov (ID: NCT02768181).
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Environmental enteric dysfunction and child stunting.
Budge, S, Parker, AH, Hutchings, PT, Garbutt, C
Nutrition reviews. 2019;(4):240-253
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Abstract
In 2017, an estimated 1 in every 4 (23%) children aged < 5 years were stunted worldwide. With slow progress in stunting reduction in many regions and the realization that a large proportion of stunting is not due to insufficient diet or diarrhea alone, it remains that other factors must explain continued growth faltering. Environmental enteric dysfunction (EED), a subclinical state of intestinal inflammation, can occur in infants across the developing world and is proposed as an immediate causal factor connecting poor sanitation and stunting. A result of chronic pathogen exposure, EED presents multiple causal pathways, and as such the scope and sensitivity of traditional water, sanitation, and hygiene (WASH) interventions have possibly been unsubstantial. Although the definite pathogenesis of EED and the mechanism by which stunting occurs are yet to be defined, this paper reviews the existing literature surrounding the proposed pathology and transmission of EED in infants and considerations for nutrition and WASH interventions to improve linear growth worldwide.
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Supplementation With Lactoferrin and Lysozyme Ameliorates Environmental Enteric Dysfunction: A Double-Blind, Randomized, Placebo-Controlled Trial.
Cheng, WD, Wold, KJ, Bollinger, LB, Ordiz, MI, Shulman, RJ, Maleta, KM, Manary, MJ, Trehan, I
The American journal of gastroenterology. 2019;(4):671-678
Abstract
INTRODUCTION Environmental enteric dysfunction (EED) predisposes children throughout the developing world to high rates of systemic exposure to enteric pathogens and stunting. Effective interventions that treat or prevent EED may help children achieve their full physical and cognitive potential. The objective of this study is to test whether 2 components of breast milk would improve a biomarker of EED and linear growth during the second year of life. METHODS A prospective, randomized, double-blind, placebo-controlled clinical trial among children aged 12-23 months was conducted in rural Malawi. The experimental group received a daily supplement of 1.5 g of lactoferrin and 0.2 g of lysozyme for 16 weeks. The primary outcome was an improvement in EED, as measured by the change in the percentage of ingested lactulose excreted into the urine (Δ%L). RESULTS Among 214 children who completed the study, there was a significant difference in Δ%L between the control and experimental groups over 8 weeks (an increase of 0.23% vs 0.14%, respectively; P = 0.04). However, this relative improvement was not as strongly sustained over the full 16 weeks of the study (an increase of 0.16% vs 0.11%, respectively; P = 0.17). No difference in linear growth over this short period was observed. The experimental intervention group had significantly lower rates of hospitalization and the development of acute malnutrition during the course of the study (2.5% vs 10.3%, relative risk 0.25; P < 0.02). DISCUSSION Supplementation with lactoferrin and lysozyme in a population of agrarian children during the second year of life has a beneficial effect on gut health. This intervention also protected against hospitalization and the development of acute malnutrition, a finding with a significant clinical and public health importance. This finding should be pursued in larger studies with longer follow-up and optimized dosing.
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Nutritional interventions for preventing stunting in children (birth to 59 months) living in urban slums in low- and middle-income countries (LMIC).
Goudet, SM, Bogin, BA, Madise, NJ, Griffiths, PL
The Cochrane database of systematic reviews. 2019;(6):CD011695
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Abstract
BACKGROUND Nutritional interventions to prevent stunting of infants and young children are most often applied in rural areas in low- and middle-income countries (LMIC). Few interventions are focused on urban slums. The literature needs a systematic assessment, as infants and children living in slums are at high risk of stunting. Urban slums are complex environments in terms of biological, social, and political variables and the outcomes of nutritional interventions need to be assessed in relation to these variables. For the purposes of this review, we followed the UN-Habitat 2004 definitions for low-income informal settlements or slums as lacking one or more indicators of basic services or infrastructure. OBJECTIVES To assess the impact of nutritional interventions to reduce stunting in infants and children under five years old in urban slums from LMIC and the effect of nutritional interventions on other nutritional (wasting and underweight) and non-nutritional outcomes (socioeconomic, health and developmental) in addition to stunting. SEARCH METHODS The review used a sensitive search strategy of electronic databases, bibliographies of articles, conference proceedings, websites, grey literature, and contact with experts and authors published from 1990. We searched 32 databases, in English and non-English languages (MEDLINE, CENTRAL, Web of Science, Ovid MEDLINE, etc). We performed the initial literature search from November 2015 to January 2016, and conducted top up searches in March 2017 and in August 2018. SELECTION CRITERIA Research designs included randomised (including cluster-randomised) trials, quasi-randomised trials, non-randomised controlled trials, controlled before-and-after studies, pre- and postintervention, interrupted time series (ITS), and historically controlled studies among infants and children from LMIC, from birth to 59 months, living in urban slums. The interventions included were nutrition-specific or maternal education. The primary outcomes were length or height expressed in cm or length-for-age (LFA)/height-for-age (HFA) z-scores, and birth weight in grams or presence/absence of low birth weight (LBW). DATA COLLECTION AND ANALYSIS We screened and then retrieved titles and abstracts as full text if potentially eligible for inclusion. Working independently, one review author screened all titles and abstracts and extracted data on the selected population, intervention, comparison, and outcome parameters and two other authors assessed half each. We calculated mean selection difference (MD) and 95% confidence intervals (CI). We performed intervention-level meta-analyses to estimate pooled measures of effect, or narrative synthesis when meta-analyses were not possible. We used P less than 0.05 to assess statistical significance and intervention outcomes were also considered for their biological/health importance. Where effect sizes were small and statistically insignificant, we concluded there was 'unclear effect'. MAIN RESULTS The systematic review included 15 studies, of which 14 were randomised controlled trials (RCTs). The interventions took place in recognised slums or poor urban or periurban areas. The study locations were mainly Bangladesh, India, and Peru. The participants included 9261 infants and children and 3664 pregnant women. There were no dietary intervention studies. All the studies identified were nutrient supplementation and educational interventions. The interventions included zinc supplementation in pregnant women (three studies), micronutrient or macronutrient supplementation in children (eight studies), nutrition education for pregnant women (two studies), and nutrition systems strengthening targeting children (two studies) intervention. Six interventions were adapted to the urban context and seven targeted household, community, or 'service delivery' via systems strengthening. The primary review outcomes were available from seven studies for LFA/HFA, four for LBW, and nine for length.The studies had overall high risk of bias for 11 studies and only four RCTs had moderate risk of bias. Overall, the evidence was complex to report, with a wide range of outcome measures reported. Consequently, only eight study findings were reported in meta-analyses and seven in a narrative form. The certainty of evidence was very low to moderate overall. None of the studies reported differential impacts of interventions relevant to equity issues.Zinc supplementation of pregnant women on LBW or length (versus supplementation without zinc or placebo) (three RCTs)There was no evidence of an effect on LBW (MD -36.13 g, 95% CI -83.61 to 11.35), with moderate-certainty evidence, or no evidence of an effect or unclear effect on length with low- to moderate-certainty evidence.Micronutrient or macronutrient supplementation in children (versus no intervention or placebo) (eight RCTs)There was no evidence of an effect or unclear effect of nutrient supplementation of children on HFA for studies in the meta-analysis with low-certainty evidence (MD -0.02, 95% CI -0.06 to 0.02), and inconclusive effect on length for studies reported in a narrative form with very low- to moderate-certainty evidence.Nutrition education for pregnant women (versus standard care or no intervention) (two RCTs)There was a positive impact on LBW of education interventions in pregnant women, with low-certainty evidence (MD 478.44g, 95% CI 423.55 to 533.32).Nutrition systems strengthening interventions targeting children (compared with no intervention, standard care) (one RCT and one controlled before-and-after study)There were inconclusive results on HFA, with very low- to low-certainty evidence, and a positive influence on length at 18 months, with low-certainty evidence. AUTHORS' CONCLUSIONS All the nutritional interventions reviewed had the potential to decrease stunting, based on evidence from outside of slum contexts; however, there was no evidence of an effect of the interventions included in this review (very low- to moderate-certainty evidence). Challenges linked to urban slum programming (high mobility, lack of social services, and high loss of follow-up) should be taken into account when nutrition-specific interventions are proposed to address LBW and stunting in such environments. More evidence is needed of the effects of multi-sectorial interventions, combining nutrition-specific and sensitive methods and programmes, as well as the effects of 'up-stream' practices and policies of governmental, non-governmental organisations, and the business sector on nutrition-related outcomes such as stunting.
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Stunting and Overweight among 12-24-Month-Old Children Receiving Vaccination in Ho Chi Minh City, Vietnam.
Giao, H, Le An, P, Truong Vien, N, Van Khanh, T, Quang Vinh, B
BioMed research international. 2019;:1547626
Abstract
INTRODUCTION Malnutrition and obesity are a double burden on children in developing countries and could induce higher risks of noncommunicable diseases in the long term. In the big cities of Vietnam, both issues are present and share the issue of nutrition problems; the prevalence of malnutrition in children is gradually decreasing while the prevalence of obesity is increasing rapidly. The paper aims to identify the prevalence of stunting and overweight/obesity in apparently healthy young children in Ho Chi Minh City (HCMC). METHODS A prospective cross-sectional study recruited 12-24-month-old children receiving national vaccination in community health centers in HCMC from February 2016 to July 2017. Sixteen healthcare centers were randomly selected among 8 districts of HCMC. Stunting and overweight were defined by height-for-age z-score <-2 SD and BMI z-score ≥+2 SD. RESULTS A total of 768 children had mean age of 16.8±4.2 months old, 51.7% boys. The prevalence of stunting and overweight/obesity was 8.2% and 10.7%, respectively. Stunting was associated with older age, boys, and low birth weight of children and occupation of mothers (P <0.05). No associated risk factor was observed for overweight/ obesity status. CONCLUSION The prevalence of overweight/obesity was higher than the prevalence of stunting in 12-24-month-old children in HCMC. Overweight/obesity would be a public health problem for children in big cities.
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Biomarkers of GH action in children and adults.
Schilbach, K, Olsson, DS, Boguszewski, MCS, Bidlingmaier, M, Johannsson, G, Jørgensen, JL
Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society. 2018;:1-8
Abstract
Growth hormone (GH) and IGF-I levels in serum are used as biomarkers in the diagnosis and management of GH-related disorders but have not been subject to structured validation. Auxological parameters in children and changes in body composition in adults, as well as metabolic parameters and patient related outcomes are used as clinical and surrogate endpoints. New treatment options, such as long acting GH and GH antagonists, require reevaluation of the currently used biochemical biomarkers. This article will review biomarkers, surrogate endpoints and clinical endpoints related to GH treatment in children and adults as well as in acromegaly.
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Study Protocol for a Randomized, Double-Blind, Community-Based Efficacy Trial of Various Doses of Zinc in Micronutrient Powders or Tablets in Young Bangladeshi Children.
Islam, MM, McDonald, CM, Krebs, NF, Westcott, J, Rahman, AE, El Arifeen, S, Ahmed, T, King, JC, Black, RE
Nutrients. 2018;(2)
Abstract
Zinc is essential to supporting growth in young children especially for tissues undergoing rapid cellular differentiation and turnover, such as those in the immune system and gastrointestinal tract. Therapeutic zinc supplementation has been initiated in low-income countries as part of diarrhea treatment programs to support these needs for young children, but the effects of preventive supplemental zinc as a tablet or as a multiple micronutrient powder (MNP) on child growth and diarrheal disease are mixed and pose programmatic uncertainties. Thus, a randomized, double-blind community-based efficacy trial of five different doses, forms, and frequencies of preventive zinc supplementation vs. a placebo was designed for a study in children aged 9⁻11 months in an urban community in Dhaka, Bangladesh. The primary outcomes of this 24-week study are incidence of diarrheal disease and linear growth. Study workers will conduct in-home morbidity checks twice weekly; anthropometry will be measured at baseline, 12 weeks and 24 weeks. Serum zinc and other related biomarkers will be measured in a subsample along with an estimate of the exchangeable zinc pool size using stable isotope techniques in a subgroup. Therapeutic zinc will be provided as part of diarrhea treatment, in accordance with Bangladesh's national policy. Therefore, the proposed study will determine the additional benefit of a preventive zinc supplementation intervention. The protocol has been approved by the Institutional Review Boards (IRBs) of icddr,b and Children's Hospital Oakland Research Institute (CHORI). The IRB review process is underway at the University of Colorado Denver as well.
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Geospatial inequalities and determinants of nutritional status among women and children in Afghanistan: an observational study.
Akseer, N, Bhatti, Z, Mashal, T, Soofi, S, Moineddin, R, Black, RE, Bhutta, ZA
The Lancet. Global health. 2018;(4):e447-e459
Abstract
BACKGROUND Undernutrition is a pervasive condition in Afghanistan, and prevalence is among the highest in the world. We aimed to comprehensively assess district-level geographical disparities and determinants of nutritional status (stunting, wasting, or underweight) among women and children in Afghanistan. METHODS The study used individualised data from the recent Afghanistan National Nutrition Survey 2013. Outcome variables were based on growth and weight anthropometry data, which we analysed linearly as Z scores and as dichotomous categories. We analysed data from a total of almost 14 000 index mother-child pairs using Bayesian spatial and generalised least squares regression models accounting for the complex survey design. FINDINGS We noted that childhood stunting, underweight, and combined stunting and wasting were consistently highest in districts in Farah, Nangarhar, Nuristan, Kunar, Paktia, and Badakhshan provinces. District prevalence ranged from 4% to 84% for childhood stunting and 5% to 66% for underweight. Child wasting exceeded 20% in central and high-conflict regions that bordered Pakistan including east, southeast, and south. Among mothers, dual burden of underweight and overweight or obesity existed in districts of north, northeast, central, and central highlands (prevalence of 15-20%). Linear growth and weight of children were independently associated with household wealth, maternal literacy, maternal anthropometry, child age, food security, geography, and improved hygiene and sanitation conditions. The mother's body-mass index was determined by many of the same factors, in addition to ethnolinguistic status and parity. Younger mothers (<20 years old) were more underweight and shorter than older mothers (aged 20-49 years). INTERPRETATION Afghanistan's rapidly changing political, socioeconomic, and insecurity landscape has both direct and indirect implications on population nutrition. Novel evidence from our study can be used to understand these multifactorial determinants and to identify granular disparities for local level tracking, planning, and implementation of nutritional interventions. FUNDING None.
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Nutritional status and dietary intakes of children amid the nutrition transition: the case of the Eastern Mediterranean Region.
Nasreddine, LM, Kassis, AN, Ayoub, JJ, Naja, FA, Hwalla, NC
Nutrition research (New York, N.Y.). 2018;:12-27
Abstract
The Eastern Mediterranean Region (EMR) is undergoing social and economic changes that may impact the nutritional status of children living in its countries. The objective of this review is to evaluate the nutritional status and dietary intakes of children (0-12 years) in selected EMR countries, namely, Jordan, Lebanon, Kingdom of Saudi Arabia (KSA), and the United Arab Emirates. MedLine, PubMed, Scopus, and Google Scholar were searched for relevant articles published between 1990 and 2016; international organizations and governmental websites were also searched. Stunting in the region was estimated at 7.3% to 9.3%, wasting at 1.1% to 11.8%, and underweight at 1.6% to 5.3%. In contrast, overweight and obesity affected 19% to 21% of school-aged children from Lebanon and KSA. Available biochemical data showed that pediatric anemia, vitamin A, and vitamin D deficiencies remain a challenge in the region. Dietary intake studies have identified inadequate intakes of iron, calcium, zinc, folic acid, vitamin A, and vitamin D, concurrently with high intakes of fat, saturated fat, and sugar. This review provides valuable insight into the nutrition situation of children in 2 major areas of the EMR, the Levant and the Gulf, and identified several gaps and challenges in existing nutritional assessment studies. Key issues include the triple burden of malnutrition in this age group (underweight, nutrient inadequacies, and overweight/obesity), while calling for integrated action to improve the nutritional status of children in countries of the region. Opportunities for future research include nationwide nutritional and dietary surveys in countries where the largest data gaps remain such as the United Arab Emirates and KSA.