Italian and North American dietary intake after ivacaftor treatment for Cystic Fibrosis Gating Mutations

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Bone Health in a Nonjaundiced Population of Children with Biliary Atresia

Objectives. To assess bone health in a cohort of nonjaundiced children with biliary atresia (BA) and the effect of growth and development on bone outcomes. Methods. Children ages one to eighteen years receiving care from Children's Hospital of Philadelphia were recruited. Each child was seen once and assessed for growth, pubertal development, concurrent medications, bilirubin, ALT, albumin, vitamin D status, bone mineral density (BMD), and bone mineral content (BMC) of the lumbar spine and whole body. Results. BMD declined significantly with age, and upon further analysis with a well-phenotyped control cohort, it was found that BMC was significantly decreased for both lumbar spine and whole body, even after adjustment for confounding variables. An age interaction was identified, with older subjects having a significantly greater impairment in BMC. Conclusions. These preliminary results demonstrate that children with BA, including those without jaundice, are likely to have compromised bone health even when accounting for height and puberty, which are common confounding factors in chronic disease. Further investigation is needed to identify the determinants of poor bone mineral status and to develop strategies to prevent osteoporosis later in life

Genetic factors are important determinants of impaired growth after infant cardiac surgery

ObjectivesWe sought to estimate the prevalence and identify the predictors of impaired growth after infant cardiac surgery.MethodsWe performed a secondary analysis of a prospective study of the role of apolipoprotein E gene polymorphisms on neurodevelopment in young children after infant cardiac surgery. Prevalence estimates for growth velocity were derived by using anthropometric measures (weight and head circumference) obtained at birth and at 4 years of age. Genetic evaluation was also performed. Growth measure z scores were calculated by using World Health Organization Child Growth Standards. Growth velocity was evaluated by using 2 different techniques: first by clustering the children into one of 3 growth velocity subgroups based on z scores (impaired growth, difference < −0.5 standard deviation; stable growth, difference of −0.5 to 0.5 standard deviation; and improving growth, difference > 0.5 SD) and second by using continuous difference scores. Statistical analyses were conducted with a combination of proportional odds models for the ordered categories and simple linear regression for the continuous outcomes.ResultsThree hundred nineteen full-term subjects had complete anthropometric measures for weight and head circumference at birth and 4 years. The cohort was 56% male. Genetic examinations were available for 97% (309/319) of the cohort (normal, 74%; definite or suspected genetic abnormality, 26%). Frequency counts for weight categories were as follows: impaired growth, 37%; stable growth, 31%; and improving growth, 32%. Frequency counts for head circumference categories were as follows: impaired growth, 39%; stable growth, 28%; and improving growth, 33%. The presence of a definite or suspected genetic syndrome (P = .04) was found to be a predictor of impaired growth for weight but not for head circumference. When growth z scores were used as continuous outcomes, the apolipoprotein E ε2 allele was found to be predictive of lower z scores for both weight (P = .02) and head circumference (P = .03).ConclusionsImpaired growth for both weight and head circumference is common (both >30%) in this cohort of children after infant cardiac surgery. Both the apolipoprotein E ε2 allele and the presence of a definite or suspected genetic syndrome were associated with impaired weight growth velocity. The apolipoprotein E ε2 allele was also associated with impaired growth velocity for head circumference. Persistent poor growth might have long-term implications for the health and development of children with congenital heart defects

Use of Compartmental Modeling and Retinol Isotope Dilution to Determine Vitamin A Stores in Young People with Sickle Cell Disease Before and After Vitamin A Supplementation

BACKGROUND: Suboptimal plasma retinol concentrations have been documented in US children with sickle cell disease (SCD) hemoglobin SS type (SCD-HbSS), but little is known about vitamin A kinetics and stores in SCD. OBJECTIVES: The objectives were to quantify vitamin A total body stores (TBS) and whole-body retinol kinetics in young people with SCD-HbSS and use retinol isotope dilution (RID) to predict TBS in SCD-HbSS and healthy peers as well as after vitamin A supplementation in SCD-HbSS subjects. METHODS: Composite plasma [ RESULTS: Model-predicted group mean TBS for subjects with SCD-HbSS was 428 μmol, equivalent to ∼11 mo of stored vitamin A; vitamin A disposal rate was 1.3 μmol/d. Model-predicted TBS was similar to that predicted by RID at 3 d postdosing (mean, 389 μmol; ∼0.3 μmol/g liver); TBS predictions at 3 compared with 28 d were not significantly different. Mean TBS in healthy peers was similar (406 μmol). RID-predicted TBS for subjects with SCD-HbSS was not significantly affected by vitamin A supplementation at either dose. CONCLUSIONS: Despite differences in plasma retinol concentrations, TBS was the same in subjects with SCD-HbSS compared with healthy peers. Because 56 d of vitamin A supplementation at levels 1.2 to 2.6 times the Recommended Dietary Allowance did not increase TBS in these subjects with SCD-HbSS, further work will be needed to understand the effects of SCD on retinol metabolism. This trial was registered as NCT03632876 at clinicaltrials.gov

Caloric compensation and eating in the absence of hunger in 5- to 12-y-old weight-discordant siblings

Background: An impaired ability to compensate for calories and increased eating in the absence of hunger (EAH) has been associated with increased energy intake and weight gain in unrelated children

Revised Pediatric Reference Data for the Lateral Distal Femur Measured by Hologic Discovery/Delphi Dual-Energy X-Ray Absorptiometry

BackgroundLateral distal femur (LDF) scans by dual energy x-ray absorptiometry (DXA) are often feasible in children for whom other sites are not measurable. Pediatric reference data for LDF are not available for more recent DXA technology.AimsTo assess older pediatric LDF reference data, construct new reference curves for LDF bone mineral density (BMD), and demonstrate the comparability of LDF BMD to other measures of BMD and strength assessed by DXA and by peripheral quantitative computed tomography (pQCT).MethodsLDF, spine and whole body scans of 821 healthy children, 5 to 18 years of age, recruited at a single center were obtained using a Hologic Delphi/Discovery system. Tibia trabecular and total BMD (3% site), cortical geometry (38% site) (cortical thickness, section modulus, strain strength index) were assessed by pQCT. Sex and race-specific reference curves were generated using LMS-ChartMaker and Z-scores calculated and compared by correlation analysis.ResultsZ-scores for LDF BMD based on published findings demonstrated overestimation or underestimation of the prevalence of low BMD-for-age depending on the region of interest considered. Revised LDF reference curves were generated. The new LDF Z-scores were strongly and significantly associated with weight, BMI, spine and whole body BMD Z-scores, and all pQCT Z-scores.ConclusionThese findings demonstrate the comparability of LDF measurements to other clinical and research bone density assessment modes, and enable assessment of BMD in children with disabilities, who are particularly prone to low trauma fractures of long bones, and for whom traditional DXA measurement sites are not feasible

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead