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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.
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Stunting, wasting, and mid upper arm circumference status among children admitted to Nemazee Teaching Hospital.
Dehghani, SM, Javaherizadeh, H, Heidary, M, Honar, N, Ataollahi, M, Ilkanipour, H, Moravej, H
Nutricion hospitalaria. 2018;(1):33-37
Abstract
INTRODUCTION AND AIM The aim of this study was to evaluate nutritional status in children without prior hospital admission or evidence of chronic disease. SUBJECTS AND METHODS The current study is a cross-sectional and observational study which was conducted for assessing the nutritional status of children. In this study, consecutive sampling was used, with a sample size about 400 children aged 6 months to 18 years at first hospital admission. All subjects were hospitalized consecutively in the Pediatric Emergency Department of the Nemazee Teaching Hospital of Shiraz University of Medical Sciences (Shiraz, Islamic Republic of Iran). All children with evidence or history of chronic diseases such as liver cirrhosis, microcephaly, macrocephaly due to congenital infection or abnormal skull shape, patients with muscular or neurological problem, with prolonged steroid usage, nephrotic syndrome, cardiac problem, and protein loosing enteropathy were excluded from the study. The duration of the study was six months, starting from January 2016. RESULTS In the current study, 430 (225 boys and 175 girls) cases were included. Mean age was 5.39 (SEM 0.23) for boys and 5.78 (SEM 0.38) for girls. According to H/A criteria (current height/ideal height), 194 (48.5%) patients were stunted, 75 (18.8%) were mild, 49 (12.3%) were moderate and 70 (17.5%) were severe. According to W/A data (current weight/ideal weight), 188 (47%) of the patients studied were malnourished. Of these cases, 118 (29.5%) had mild malnutrition; 54 (13.5%), moderate; and 16 (4%), severe. According to body mass index (BMI), 40 (10%) patients were overweight, four (16%) were obese, and four (1%) were severe obese. In relation to middle upper arm circumference (MUAC), 56 (14%) patients were malnourished, 33 (8.3%) were at risk, 14 (3.5%) presented moderate malnutrition, and 9 (2.3%), severe malnutrition. CONCLUSION Prevalence of malnutrition among children without prior admission was 48.5% (according to H/A). According to W/A, 47% of children had different degrees of malnutrition.
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Genetic causes of proportionate short stature.
Argente, J, Pérez-Jurado, LA
Best practice & research. Clinical endocrinology & metabolism. 2018;(4):499-522
Abstract
Human growth is a very complex phenomenon influenced by genetic, hormonal, nutritional and environmental factors, from fetal life to puberty. Although the GH-IGF axis has a central role with specific actions on growth, numerous genes are involved in the control of stature. Genome-wide association studies have identified >600 variants associated with human height, still explaining only a small fraction of phenotypic variation. Since short stature in childhood is a common reason for referral, pediatric endocrinologists must be aware of the multifactorial and polygenic contributions to height. Multiple disorders characterized by growth failure of prenatal and/or postnatal onset due to single gene defects have been described. Their early diagnosis, facilitated by advances in genomic technologies, is of upmost importance for their clinical management and to provide genetic counseling. Here we review the current clinical and genetic information regarding different syndromes and hormone abnormalities with proportionate short stature as the main feature, and provide an update of the approach for diagnosis and management.
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Environmental enteric dysfunction and systemic inflammation predict reduced weight but not length gain in rural Bangladeshi children.
Campbell, RK, Schulze, KJ, Shaikh, S, Raqib, R, Wu, LSF, Ali, H, Mehra, S, West, KP, Christian, P
The British journal of nutrition. 2018;(4):407-414
Abstract
Environmental enteric dysfunction (EED) and systemic inflammation (SI) are common in developing countries and may cause stunting. In Bangladesh, >40 % of preschool children are stunted, but EED and SI contributions are unknown. We aimed to determine the impact of EED and SI (assessed with multiple indicators) on growth in children (n 539) enrolled in a community-based randomised food supplementation trial in rural Bangladesh. EED was defined with faecal myeloperoxidase, α-1 antitrypsin and neopterin and serum endotoxin core antibody and glucagon-like peptide-2, consolidated into gut inflammation (GI) and permeability (GP) scores, and urinary lactulose:mannitol α-1 acid glycoprotein (AGP) characterised SI. Biomarker associations with anthropometry (15-, 18- and 24-month length-for-age (LAZ), weight-for-length (WLZ) and weight-for-age (WAZ) z scores) were examined in pairwise correlations and adjusted mixed-effects regressions. Stunting, wasting and underweight prevalence at 18 months were 45, 15 and 37 %, respectively, with elevated EED and SI markers common. EED and SI were not associated with 15-24-month length trajectory. Elevated (worse) GI and GP scores predicted reduced 18-24-month WLZ change (β -0·01 (se 0·00) z score/month for both). Elevated GP was also associated with reduced 15-18-month WLZ change (β -0·03 (se 0·01) z score/month) and greater 15-month WLZ (β 0·16 (se 0·05)). Higher AGP was associated with reduced prior and increased subsequent WLZ change (β -0·04 (se 0·01) and β 0·02 (se 0·00) z score/month for 15-18 and 18-24 months). The hypothesised link from EED to stunting was not observed in this sample of Bangladeshi 18-month-olds, but the effects of EED on constrained weight gain may have consequences for later linear growth or for other health and development outcomes.
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The impact of rickets on growth and morbidity during recovery among children with complicated severe acute malnutrition in Kenya: A cohort study.
Ngari, MM, Thitiri, J, Mwalekwa, L, Timbwa, M, Iversen, PO, Fegan, GW, Berkley, JA
Maternal & child nutrition. 2018;(2):e12569
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Abstract
The effects of rickets on children recovery from severe acute malnutrition (SAM) are unknown. Rickets may affect both growth and susceptibility to infectious diseases. We investigated the associations of clinically diagnosed rickets with life-threatening events and anthropometric recovery during 1 year following inpatient treatment for complicated SAM. This was a secondary analysis of clinical trial data among non-human immunodeficiency virus-infected Kenyan children with complicated SAM (2-59 months) followed for 1 year posthospital discharge (ClinicalTrials.gov ID NCT00934492). The outcomes were mortality, hospital readmissions, and growth during 12 months. The main exposure was clinically diagnosed rickets at baseline. Of 1,778 children recruited, 230 (12.9%, 95% CI [11.4, 14 .6]) had clinical signs of rickets at baseline. Enrolment at an urban site, height-for-age and head circumference-for-age z scores were associated with rickets. Rickets at study enrolment was associated with increased mortality (adjusted Hazard Ratio [aHR] 1.61, 95% CI [1.14, 2.27]), any readmission (aHR 1.37, 95% CI [1.09, 1.72]), readmission for severe pneumonia (aHR 1.37, 95% CI [1.05, 1.79]), but not readmission with diarrhoea (aHR 1.05, 95% CI [0.73, 1.51]). Rickets was associated with increased height gain (centimetres), adjusted regression coefficient 0.19 (95% CI [0.10, 0.28]), but not changes in head circumference, mid-upper arm circumference, or weight. Rickets was common among children with SAM at urban sites and associated with increased risks of severe pneumonia and death. Increased height gain may have resulted from vitamin D and calcium treatment. Future work should explore possibility of other concurrent micronutrient deficiencies and optimal treatment of rickets in this high-risk population.
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Nutritional therapy complications in children with ultra-short bowel syndrome include growth deficiency but not cholestasis.
Olszewska, K, Ksiazyk, J, Kozlowski, D, Pajdowska, M, Janusz, M, Jaworski, M
Acta paediatrica (Oslo, Norway : 1992). 2018;(6):1088-1093
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AIM: Children with ultra-short bowel syndrome (USBS) have not been extensively studied to date because the condition is rare. The aim of the study was to assess the nutritional status of children with USBS receiving home parenteral nutrition, using citrulline serum concentration and cholestasis. METHODS We studied 17 patients with USBS, with a median age of 6.6 years and median duration of parenteral nutrition of 6.6 years. The study was carried out at The Children's Memorial Health Institute, Warsaw, from January 2014 to January 2015. RESULTS The median standard deviation score (SDS) was -1.2 for body mass according to chronological age, -1.72 according to height and -0.59 according to height for age. Patients requiring seven days per week parenteral nutrition had a citrulline concentration below 10 μmol/L. Decreased bone-mineral density was observed in 87% of the patients. Low values of 25-hydroxyvitamin D were found in 53% of the children. None of the patients had elevated conjugated bilirubin levels above 34.2 μmol/L. CONCLUSION Children with USBS were growth deficient according to their chronological age, with frequent abnormal bone mineralisation and vitamin D deficiency. Children requiring parenteral nutrition seven days a week had citrulline concentrations below 10 μmol/L. Cholestasis was not seen.
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Evidence-based approaches to childhood stunting in low and middle income countries: a systematic review.
Hossain, M, Choudhury, N, Adib Binte Abdullah, K, Mondal, P, Jackson, AA, Walson, J, Ahmed, T
Archives of disease in childhood. 2017;(10):903-909
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OBJECTIVE We systematically evaluated health and nutrition programmes to identify context-specific interventional packages that might help to prioritise the implementation of programmes for reducing stunting in low and middle income countries (LMICs). METHODS Electronic databases were used to systematically review the literature published between 1980 and 2015. Additional articles were identified from the reference lists and grey literature. Programmes were identified in which nutrition-specific and nutrition-sensitive interventions had been implemented for children under 5 years of age in LMICs. The primary outcome was a change in stunting prevalence, estimated as the average annual rate of reduction (AARR). A realist approach was applied to identify mechanisms underpinning programme success in particular contexts and settings. FINDINGS Fourteen programmes, which demonstrated reductions in stunting, were identified from 19 LMICs. The AARR varied from 0.6 to 8.4. The interventions most commonly implemented were nutrition education and counselling, growth monitoring and promotion, immunisation, water, sanitation and hygiene, and social safety nets. A programme was considered to have effectively reduced stunting when AARR≥3%. Successful interventions were characterised by a combination of political commitment, multi-sectoral collaboration, community engagement, community-based service delivery platform, and wider programme coverage and compliance. Even for similar interventions the outcome could be compromised if the context differed. INTERPRETATION For all settings, a combination of interventions was associated with success when they included health and nutrition outcomes and social safety nets. An effective programme for stunting reduction embraced country-level commitment together with community engagement and programme context, reflecting the complex nature of exposures of relevance. PROSPERO REGISTRATION NUMBER CRD42016043772.