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1.
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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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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3.
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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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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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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Oesophageal atresia: The growth gap.
Traini, I, Menzies, J, Hughes, J, Leach, ST, Krishnan, U
World journal of gastroenterology. 2020;(12):1262-1272
Abstract
Poor growth is an under-recognised yet significant long-term sequelae of oesophageal atresia (OA) repair. Few studies have specifically explored the reasons for growth impairment in this complex cohort. The association between poor growth with younger age and fundoplication appears to have the strongest supportive evidence, highlighting the need for early involvement of a dietitian and speech pathologist, and consideration of optimal medical reflux management prior to referring for anti-reflux surgery. However, it remains difficult to reach conclusions regarding other factors which may negatively influence growth, due to conflicting findings, inconsistent definitions and lack of validated tool utilisation. While swallowing and feeding difficulties are particularly frequent in younger children, their relationship with growth remains unclear. It is possible that these morbidities impact on the diet of children with OA, but detailed analysis of dietary composition and quality, and its relationship with these complications and growth, has not yet been conducted. Another potential area of research in OA is the role of the microbiota in growth and nutrition. While the microbiota has been linked to growth impairment in other paediatric conditions, it is yet to be investigated in OA. Further research is needed to identify the most important contributory factors to poor growth, the role of the intestinal microbiota, and effective interventions to maximise growth and nutritional outcomes in this cohort.
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Δ1 -Pyrroline-5-carboxylate synthetase deficiency: An emergent multifaceted urea cycle-related disorder.
Marco-Marín, C, Escamilla-Honrubia, JM, Llácer, JL, Seri, M, Panza, E, Rubio, V
Journal of inherited metabolic disease. 2020;(4):657-670
Abstract
The bifunctional homooligomeric enzyme Δ1 -pyrroline-5-carboxylate synthetase (P5CS) and its encoding gene ALDH18A1 were associated with disease in 1998. Two siblings who presented paradoxical hyperammonemia (alleviated by protein), mental disability, short stature, cataracts, cutis laxa, and joint laxity, were found to carry biallelic ALDH18A1 mutations. They showed biochemical indications of decreased ornithine/proline synthesis, agreeing with the role of P5CS in the biosynthesis of these amino acids. Of 32 patients reported with this neurocutaneous syndrome, 21 familial ones hosted homozygous or compound heterozygous ALDH18A1 mutations, while 11 sporadic ones carried de novo heterozygous ALDH18A1 mutations. In 2015 to 2016, an upper motor neuron syndrome (spastic paraparesis/paraplegia SPG9) complicated with some traits of the neurocutaneous syndrome, although without report of cutis laxa, joint laxity, or herniae, was associated with monoallelic or biallelic ALDH18A1 mutations with, respectively, dominant and recessive inheritance. Of 50 SPG9 patients reported, 14 and 36 (34/2 familial/sporadic) carried, respectively, biallelic and monoallelic mutations. Thus, two neurocutaneous syndromes (recessive and dominant cutis laxa 3, abbreviated ARCL3A and ADCL3, respectively) and two SPG9 syndromes (recessive SPG9B and dominant SPG9A) are caused by essentially different spectra of ALDH18A1 mutations. On the bases of the clinical data (including our own prior patients' reports), the ALDH18A1 mutations spectra, and our knowledge on the P5CS protein, we conclude that the four syndromes share the same pathogenic mechanisms based on decreased P5CS function. Thus, these syndromes represent a continuum of increasing severity (SPG9A < SPG9B < ADCL3 ≤ ARCL3A) of the same disease, P5CS deficiency, in which the dominant mutations cause loss-of-function by dominant-negative mechanisms.
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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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10.
Amino Acid Digestibility of Extruded Chickpea and Yellow Pea Protein is High and Comparable in Moderately Stunted South Indian Children with Use of a Dual Stable Isotope Tracer Method.
Devi, S, Varkey, A, Dharmar, M, Holt, RR, Allen, LH, Sheshshayee, MS, Preston, T, Keen, CL, Kurpad, AV
The Journal of nutrition. 2020;(5):1178-1185
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Abstract
BACKGROUND Legumes are an excellent plant source of the limiting indispensable amino acid (IAA) lysine in vegetarian, cereal-based diets. However, their digestibility is poor largely because of their antiprotease content. Extrusion can enhance digestibility by inactivating trypsin inhibitors and thus potentially improve the protein quality of legumes. OBJECTIVE We measured the digestibility of extruded chickpea and yellow pea protein with use of a dual stable isotope method in moderately stunted South Indian primary school children. METHODS Twenty-eight moderately stunted children (height-for-age z scores <-2.0 SD and >-3.0 SD) aged 6-11 y from low to middle socioeconomic status were randomly assigned to receive a test protein (extruded intrinsically [2H]-labeled chickpea or yellow pea) along with a standard of U-[13C]-spirulina protein to measure amino acid (AA) digestibility with use of a dual stable isotope method. Individual AA digestibility in the test protein was calculated by the ratios of AA enrichments in the test protein to the standard protein in the food and their appearance in blood plasma collected at 6 and 6.5 h during the experiment, representing a plateau state. RESULTS The mean AA digestibility of extruded chickpea and yellow pea protein in moderately stunted children (HAZ; -2.86 to -1.2) was high and similar in both extruded test proteins (89.0% and 88.0%, respectively, P = 0.83). However, lysine and proline digestibilities were higher in extruded chickpea than yellow pea (79.2% compared with 76.5% and 75.0% compared with 72.0%, respectively, P < 0.02). CONCLUSION Extruded chickpea and yellow pea protein had good IAA digestibility in moderately stunted children, which was 20% higher than an earlier report of their digestibility when pressure-cooked, measured by the same method in adults. Higher digestibility of lysine and proline highlights better retention of these AA in chickpea during extrusion-based processing. Extrusion might be useful for developing high-quality protein foods from legumes. This trial was registered at www.ctri.nic.in as CTRI/2018/03/012439.