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1.
Vitamin D for Growth and Rickets in Stunted Children: A Randomized Trial.
Crowe, FL, Mughal, MZ, Maroof, Z, Berry, J, Kaleem, M, Abburu, S, Walraven, G, Masher, MI, Chandramohan, D, Manaseki-Holland, S
Pediatrics. 2021;(1)
Abstract
BACKGROUND AND OBJECTIVES Vitamin D is essential for healthy development of bones, but little is known about the effects of supplementation in young stunted children. Our objective was to assess the effect of vitamin D supplementation on risk of rickets and linear growth among Afghan children. METHODS In this double-blind, placebo-controlled trial, 3046 children ages 1 to 11 months from inner-city Kabul were randomly assigned to receive oral vitamin D3 (100 000 IU) or placebo every 3 months for 18 months. Rickets Severity Score was calculated by using wrist and knee radiographs for 631 randomly selected infants at 18 months, and rickets was defined as a score >1.5. Weight and length were measured at baseline and 18 months by using standard techniques, and z scores were calculated. RESULTS Mean (95% confidence interval [CI]) serum 25-hydroxyvitamin D (seasonally corrected) and dietary calcium intake were insufficient at 37 (35-39) nmol/L and 372 (327-418) mg/day, respectively. Prevalence of rickets was 5.5% (placebo) and 5.3% (vitamin D): odds ratio 0.96 (95% CI: 0.48 to 1.92); P = .9. The mean difference in height-for-age z score was 0.05 (95% CI: -0.05 to 0.15), P = .3, although the effect of vitamin D was greater for those consuming >300 mg/day of dietary calcium (0.14 [95% CI: 0 to 0.29]; P = .05). There were no between-group differences in weight-for-age or weight-for-height z scores. CONCLUSIONS Except in those with higher calcium intake, vitamin D supplementation had no effect on rickets or growth.
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2.
The Clinical Spectrum of Resistance to Thyroid Hormone Alpha in Children and Adults.
Erbaş, İM, Demir, K
Journal of clinical research in pediatric endocrinology. 2021;(1):1-14
Abstract
Resistance to thyroid hormone alpha occurs due to pathogenic, heterozygous variants in THRA. The entity was first described in 2012 and to date only a small number of patients with varying severity have been reported. In this review, we summarize and interpret the heterogeneous clinical and laboratory features of all published cases, including ours. Many symptoms and findings are similar to those seen in primary hypothyroidism. However, thyroid-stimulating hormone levels are normal. Free triiodothyronine (T3) levels are in the upper half of normal range or frankly high and free thyroxine (T4) levels are low or in the lower half of normal range. Alterations in free T3 and free T4 may not be remarkable, particularly in adults, possibly contributing to underdiagnosis. In such patients, low reverse T3 levels, normo- or macrocytic anemia or, particularly in children, mildly elevated creatine kinase levels would warrant THRA sequencing. Treatment with L-thyroxine results in improvement of some clinical findings.
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IGF-I deficiency and enhanced insulin sensitivity due to a mutated growth hormone receptor gene in humans.
Guevara-Aguirre, J, Torres, C, Peña, G, Palacios, M, Bautista, C, Guevara, A, Gavilanes, AW
Molecular and cellular endocrinology. 2021;:111044
Abstract
Human size is achieved by the coordinated expression of many genes. From conception to adulthood, a given genomic endowment is modified by highly variable environmental circumstances. During each stage of a person's life, distinct nutritional and hormonal influences continuously shape growing physical features until mature characteristics are attained. Underlying processes depend on precise provision of substrates and energy extracted by insulin action from nutrients, which allows cell proliferation, differentiation, and survival, under the concerted actions of growth hormone and insulin-like growth factor-I (IGF-I). It should be noted that growth and metabolic signaling pathways are interdependent and superimposed at multiple levels. Attainment of a fully developed human phenotype should be considered as a harmonious increment in body size rather than a simple increase in height. From this perspective we herein analyze adult features of individuals with an inactive growth hormone receptor, who consequently have severely diminished concentrations of serum insulin and endocrine IGF-I.
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4.
Maternal Preconception Body Size and Early Childhood Growth during Prenatal and Postnatal Periods Are Positively Associated with Child-Attained Body Size at Age 6-7 Years: Results from a Follow-up of the PRECONCEPT Trial.
Nguyen, PH, Young, MF, Khuong, LQ, Tran, LM, Duong, TH, Nguyen, HC, Martorell, R, Ramakrishnan, U
The Journal of nutrition. 2021;(5):1302-1310
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Abstract
BACKGROUND Growth faltering is associated with adverse consequences during childhood and later life. However, questions remain on the relative importance of preconception maternal nutritional status (PMNS) and child growth during the first 1000 d of life. OBJECTIVES We examined associations between PMNS, gestational weight gain (GWG), and child growth during the first 1000 d with attained body size at age 6-7 y. METHODS We used data from a follow-up of a double-blinded randomized controlled trial of preconception micronutrient supplementation in Vietnam (n = 5011 women). The outcomes included offspring height-for-age z score (HAZ), BMI-for-age z score (BMIZ), and prevalence of stunting and overweight/obese at age 6-7 y (n = 1579). We used multivariable linear and Poisson regression models to evaluate the relative contributions of PMNS (height and BMI), GWG, and conditional growth in 4 periods: fetal, 0-6 mo, 6-12 mo, and 12-24 mo. RESULTS PMNS was positively associated with child-attained size at 6-7 y. For each 1-SD higher maternal height and BMI, offspring had 0.28-SD and 0.13-SD higher HAZ at 6-7 y, respectively. Higher maternal BMI and GWG were associated with larger child BMIZ (β: 0.29 and 0.10, respectively). Faster linear growth, especially from 6 to 24 mo, had the strongest association with child HAZ at 6-7 y (β: 0.39-0.42), whereas conditional weight measures in all periods were similarly associated with HAZ (β: 0.10-0.15). For BMIZ at 6-7 y, the magnitude of association was larger and increased with child age for conditional weight gain (β: 0.21-0.41) but smaller for conditional length gain. Faster growth in the first 2 y was associated with reduced risk of stunting and thinness but increased risk of overweight/obese at 6-7 y. CONCLUSIONS Interventions aimed at improving child growth while minimizing the risk of overweight during the school age years should target both women of reproductive age prior to conception through delivery and their offspring during the first 1000 d. The trial was registered at clinicaltrials.gov as NCT01665378.
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High Early Parenteral Lipid in Very Preterm Infants: A Randomized-Controlled Trial.
Alburaki, W, Yusuf, K, Dobry, J, Sheinfeld, R, Alshaikh, B
The Journal of pediatrics. 2021;:16-23.e1
Abstract
OBJECTIVE To determine whether high early parenteral soybean oil lipid intake in very low birth weight (VLBW) infants in the first week after birth decreases the proportion of weight loss and subsequently the incidence of extrauterine growth restriction (EUGR). STUDY DESIGN This was a randomized controlled trial of appropriate for gestational- ge VLBW infants. Lipid intake in the control group started at 0.5-1 g/kg per day and increased daily by 0.5-1 g/kg per day till reaching 3 g/kg per day. The intervention group was started on 2 g/kg per day that increased to 3 g/kg per day the following day. RESULTS Of the 176 infants assessed for eligibility, 83 were included in the trial. Infants in the intervention group were started on lipid sooner (13.8 ± 7.8 vs 17.5 ± 7.8 hour; P = .03) and had higher cumulative lipid intake in the first 7 days of age (13.5 ± 4.2 vs 10.9 ± 3.5 g/kg per day; P = .03). Infants in the intervention group had a lower percentage of weight loss (10.4 vs 12.7%; P = .02). The mean triglyceride level was higher in the intervention group (1.91 ± 0.79 vs 1.49 ± 0.54 mmol/L; P = .01), however, hypertriglyceridemia was similar between the 2 groups. The incidence of EUGR was lower in the intervention group (38.6% vs 67.6%; P = .01). Head circumference z score was higher in the intervention group (-1.09 ± 0.96 vs -1.59 ± 0.98; P = .04). CONCLUSIONS In VLBW infants, provision of a high early dose of parenteral lipid in the first week of age results in less weight loss and lower incidence of EUGR. TRIAL REGISTRATION Clinicaltrials.gov: NCT03594474.
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Ten years with biosimilar rhGH in clinical practice in Sweden - experience from the prospective PATRO children and adult studies.
Lundberg, E, Kriström, B, Zouater, H, Deleskog, A, Höybye, C
BMC endocrine disorders. 2020;(1):55
Abstract
BACKGROUND In 2007, Omnitrope® was the first biosimilar recombinant human growth hormone (rhGH) to be approved in Sweden for treatment in adults and children. Over 10 years' safety and effectiveness data for biosimilar rhGH can now be presented. METHODS PATRO Children and PATRO Adults are multicenter, longitudinal, observational, post-marketing surveillance studies. Eligible patients include children 0-18 years and adults receiving biosimilar rhGH treatment. Adverse events (AEs) are monitored for safety evaluation. Growth variables in children and metabolic data in adults are recorded for effectiveness evaluation. RESULTS As of January 2019, data from 136 children (48% male) were reported from Swedish centers. Mean age in rhGH treatment-naïve patients at study entry (n = 114) was 7.5 years, with mean 3.6 years treatment duration. No severe AEs of diabetes, impaired glucose tolerance, or malignancy were reported. The most frequently reported AE was nasopharyngitis (n = 16 patients). No clinically relevant anti-hGH or neutralizing antibodies were observed. The mean change from baseline in height standard deviation score (SDS) in naïve prepubertal GH deficiency patients was + 0.79 at 1 year, + 1.27 at 2 years, and + 1.55 at 3 years. Data from 293 adults (44% rhGH-naïve, 51% male) were included. Fatigue was the most frequently reported AE (n = 26 patients). The incidence of new neoplasms or existing neoplasm progression was 23.8 patients per 1000 patient-years. Type 2 diabetes mellitus was reported in four patients. At baseline in rhGH-naïve adults, mean (SD) body mass index (BMI) was 29.1 (5.6) kg/m2 and mean (SD) insulin-like growth factor (IGF)-I SDS was - 3.0 (1.4). Mean daily dose increased from 0.1 mg at baseline to 0.3 mg after 4 years. IGF-I SDS normalized during the first year of treatment. Mean BMI and glucose were unchanged over 4 years, while low-/high-density lipoprotein cholesterol ratio decreased. CONCLUSIONS For the first time, Swedish data from the PATRO Children and Adults studies are presented. The 10-year data suggest that biosimilar rhGH is well tolerated across pediatric and adult indications. Safety and effectiveness were similar to previous reports for other rhGH preparations. These results need to be confirmed in larger cohorts, highlighting the importance of long-term post-marketing studies.
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Stunting and Anemia in Children from Urban Poor Environments in 28 Low and Middle-income Countries: A Meta-analysis of Demographic and Health Survey Data.
Assaf, S, Juan, C
Nutrients. 2020;(11)
Abstract
Child malnutrition remains a global concern with implications not only for children's health and cognitive function, but also for countries' economic growth. Recent reports suggest that global nutrition targets will not be met by 2025. Large gaps are evident between and within countries. One of the largest disparities in child malnutrition within counties is between urban and rural children. Large disparities also exist in urban areas that have higher rates of child malnutrition in the urban poor areas or slums. This paper examines stunting and anemia related to an urban poverty measure in children under age 5 in 28 low and middle-income countries with Demographic and Health Survey data. We used the United Nations Human Settlements Programme (UN-HABITAT) definition to define urban poor areas as a proxy for slums. The results show that in several countries, children had a higher risk of stunting and anemia in urban poor areas compared to children in urban non-poor areas. In some countries, this risk was similar to the risk between the rural and urban non-poor. Tests of heterogeneity showed that these results were not homogeneous across countries. These results help to identify areas of greater disadvantage and the required interventions for stunting and anemia.
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Auxological and endocrinological features in internationally adopted children.
Stagi, S, Papacciuoli, V, Boiro, D, Maggioli, C, Ndambao, NN, Losi, S, Chiappini, E, Toni, S, Ndiaye, O
Italian journal of pediatrics. 2020;(1):82
Abstract
In internationally adopted children disorders of linear growth, puberty development, thyroid function, and bone metabolism are frequently reported. It is important that these children receive careful auxological and endocrinological evaluations and follow-up.Pediatricians and other healthcare providers should be aware that auxological and endocrinological problems are common in newly arrived international adoptees.
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Fecal dysbiosis in infants with cystic fibrosis is associated with early linear growth failure.
Hayden, HS, Eng, A, Pope, CE, Brittnacher, MJ, Vo, AT, Weiss, EJ, Hager, KR, Martin, BD, Leung, DH, Heltshe, SL, et al
Nature medicine. 2020;(2):215-221
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Abstract
Most infants with cystic fibrosis (CF) have pancreatic exocrine insufficiency that results in nutrient malabsorption and requires oral pancreatic enzyme replacement. Newborn screening for CF has enabled earlier diagnosis, nutritional intervention and enzyme replacement for these infants, allowing most infants with CF to achieve their weight goals by 12 months of age1. Nevertheless, most infants with CF continue to have poor linear growth during their first year of life1. Although this early linear growth failure is associated with worse long-term respiratory function and survival2,3, the determinants of body length in infants with CF have not been defined. Several characteristics of the CF gastrointestinal (GI) tract, including inflammation, maldigestion and malabsorption, may promote intestinal dysbiosis4,5. As GI microbiome activities are known to affect endocrine functions6,7, the intestinal microbiome of infants with CF may also impact growth. We identified an early, progressive fecal dysbiosis that distinguished infants with CF and low length from infants with CF and normal length. This dysbiosis included altered abundances of taxa that perform functions that are important for GI health, nutrient harvest and growth hormone signaling, including decreased abundance of Bacteroidetes and increased abundance of Proteobacteria. Thus, the GI microbiota represent a potential therapeutic target for the correction of low linear growth in infants with CF.
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WHO infant and young child feeding indicators in relation to anthropometric measurements.
Al-Taiar, A, Alqaoud, N, Hammoud, MS, Alanezi, F, Aldalmani, N, Subhakaran, M
Public health nutrition. 2020;(10):1665-1676
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Abstract
OBJECTIVE This study aimed to report the WHO infant and young child feeding (IYCF) indicators from Kuwait and to investigate the associations between these indicators and anthropometric measurements. DESIGN The Kuwait Nutritional Surveillance System uses observational cross-sectional approach to collects data by face-to-face interviews with mothers or child guardians using a structured questionnaire that was developed based on the WHO IYCF indicators. The weight and height of infants and young children were measured using digital scales in a standardised manner. SETTING Vaccination centres in all governorates (provinces) of Kuwait. PARTICIPANTS Infants and young Kuwaiti children aged 0-23 months (N 5839). RESULTS The prevalence of exclusive breastfeeding and age-appropriate breastfeeding were 8·0 and 7·4 %, respectively. The prevalence of stunting and wasting was 7·5 and 2·4 %, respectively, while the prevalence of overweight and obesity was 6·5 and 1·6 %, respectively. In the multivariable analysis, exclusive breastfeeding and age-appropriate breastfeeding were more common in children with stunted growth (AOR 1·71 (95 % CI 1·08, 2·70; P = 0·021) and 1·44 (95 % CI 1·01, 2·06; P = 0·046), respectively). The introduction of solid/semisolid or soft foods was inversely associated with stunting (AOR 0·52; 95 % CI 0·30, 0·90; P = 0·021). Only age-appropriate breastfeeding was inversely associated with overweight (AOR 0·62; 95 % CI 0·39, 0·98; P = 0·043). CONCLUSION Our findings showed that indicators of breastfeeding are low in Kuwait. Our findings suggest that the associations between different WHO IYCF indicators and stunting as well as overweight is complex, which highlights the need for a better understanding of WHO IYCF indicators in both low- and high-income countries.