Changes In Linear Growth Research Articles

Adolescent and Young Adult Development in Transplant Recipients.

Solid organ transplantation (SOT) is the gold standard of therapy for individuals with end-organ dysfunction. Improved survival outcomes after SOT can help adolescent and young adult (AYA) recipients lead long and healthy life. However, successful SOT during adolescence and young adulthood is often complicated by the innate developmental challenges of this age group. The psychosocial tasks of adolescence include identity development, autonomous decision-making, establishing social networks, educational and vocational preparation, and navigating romantic relationships. These goals may be amplified or delayed for pediatric SOT recipients. Adolescence is also marked by rapid physical changes in linear growth and the development of secondary sexual characteristics. Yet AYA may experience physical and pubertal delays related to transplantation, as well as exaggerated body image dissatisfaction due to medication side effects. Strict adherence to medication and post-transplant regimens may interfere with adolescents' desire for normalcy and fitting in with peers. Healthcare providers should be aware that AYA value education and self-empowerment in transplant care. Transplant success needs to be defined by both medical and psychosocial outcomes, particularly when it relates to the vulnerable AYA population. Fortunately, investment from the patient, family, and care team can aid in transplant recovery and success. This article will identify the developmental challenges faced by AYA undergoing solid organ transplantation as well as strategies to engage positive outcomes.

Longitudinal analysis of cortisol changes during pubertal development in indigenous Qom girls.

Pubertal research has primarily focused on hypothalamic-pituitary-gonadal axis (HPG) regulation of puberty, though the hypothalamic-pituitary-adrenal axis (HPA) is increasingly considered critical. Heightened HPA function proxied by increasing cortisol levels may play a role in accelerated pubertal timing. However, the extent to which cortisol varies across ages and its relation to pubertal changes in linear growth are less well substantiated. We explored relationships between age, linear growth, adiposity, C-peptide (proxy for insulin), and cortisol across puberty, and we tested whether higher cortisol levels are associated with earlier ages at menarche and peak height velocity. We utilize longitudinal data (n = 777 urine samples) from Qom females ages 7-14 (n = 46) and test our pre-registered analysis using Bayesian longitudinal mixed effects models and joint modeling techniques. We find limited evidence supporting the overarching hypothesis that HPA upregulation is associated with pubertal maturation or timing. We find some evidence that HPA upregulation, as proxied by cortisol, may be more clearly related to differences in relative linear growth at early-mid puberty, as measured by height-for-age z-scores. Transdisciplinary perspectives on puberty, including the assumption that stressors acting via cortisol accelerate pubertal development, are discussed.

Linear growth beyond 24 months and child neurodevelopment in low- and middle-income countries: a systematic review and meta-analysis

AimTo synthesize available evidence on the association between change in linear growth (height for age z score, HAZ) beyond the first two years of life with later child neurodevelopment outcomes in Low- and middle-income countries (LMICs).MethodsWe searched PubMed, Web of Science, and EMBASE for cohort studies on the association between change in HAZ after age two and neurodevelopment outcomes in middle or late childhood. Data extraction was done independently by two reviewers.ResultsA total of 21 studies, that included 64,562 children from 13 LMICs were identified. Each unit increase in change in HAZ above two years is associated with a + 0.01 increase (N = 8 studies, 27,393 children) in the cognitive scores at 3.5 to 12 years of age and a + 0.05-standard deviation (SD) increase (95% CI 0.02 to 0.08, N = 3 studies, 17,830 children) in the language score at 5 to 15 years of age. No significant association of change in HAZ with motor (standardized mean difference (SMD) 0.04; 95% CI: -0.10, 0.18, N = 1 study, 966 children) or socio-emotional scores (SMD 0.00; 95% CI: -0.02, 0.01, N = 4 studies, 14,616 participants) was observed.ConclusionChanges in HAZ after the first two years of life appear to have a small or no association with child neurodevelopment outcomes in LMICs.

Hormonal Determinants of Growth and Weight Gain in the Human Fetus and Preterm Infant.

The factors controlling linear growth and weight gain in the human fetus and newborn infant are poorly understood. We review here the changes in linear growth, weight gain, lean body mass, and fat mass during mid- and late gestation and the early postnatal period in the context of changes in the secretion and action of maternal, placental, fetal, and neonatal hormones, growth factors, and adipocytokines. We assess the effects of hormonal determinants on placental nutrient delivery and the impact of preterm delivery on hormone expression and postnatal growth and metabolic function. We then discuss the effects of various maternal disorders and nutritional and pharmacologic interventions on fetal and perinatal hormone and growth factor production, growth, and fat deposition and consider important unresolved questions in the field.

When did the substantial loss of child linear growth occur?

Epidemiological studies show that the height-for-age Z-scores (HAZ) falter dramatically shortly after birth until the end of the first two years. Understanding these changes in linear growth in the first two years can help us understand the critical period of child linear growth and propose interventions. This study objectives were to describe the pattern of linear growth faltering and analyze the changes in length-for-age Z-scores (LAZs) throughout the first two years based on birthweight and length status. This study analyzed 408 children, participants in Longitudinal Study on Child Growth and Development in Bogor, Indonesia. The linear growth pattern was described based on birthweight and length status. Birthweight and length status was categorized into normal and Small for Gestational Age (SGA). Changes in LAZs (Δ LAZs) in 0-6 months, 6-12 months, and 12-23 months were calculated. General Linear Model Univariate analysis was conducted to analyze the difference of Δ LAZ between SGA and normal children. Though full-term SGA children have significantly higher linear growth velocity during the first 6 months of the infancy period, full-term SGA children could not catch up with the attained growth/height of normal children throughout the first two years. Thus, full-term SGA children ended up with a higher prevalence of stunted. Both in SGA and normal children, the substantial loss of LAZ occurred between 0-6 months. The finding in this study showed that the first 1000 days of life is still the best period in stunting prevention; however, the stunting prevention program should start earlier, focusing on the first 500 days of life, and potentially the prenatal period.

Different Doses, Forms, and Frequencies of Zinc Supplementation for the Prevention of Diarrhea and Promotion of Linear Growth among Young Bangladeshi Children: A Six-Arm, Randomized, Community-Based Efficacy Trial

BackgroundChildren in resource-limited settings remain vulnerable to zinc deficiency and its consequences. ObjectivesTo evaluate the effects of different doses, durations, and frequencies of zinc supplementation on the incidence of diarrhea and change in linear growth among young children. MethodsWe conducted a randomized, partially double-blind, controlled, 6-arm, community-based efficacy trial in Dhaka, Bangladesh. Children aged 9–11 mo were randomly assigned to receive 1 of the following interventions for 24 wk: 1) standard micronutrient powder (MNP) containing 4.1 mg zinc and 10 mg iron, daily; 2) high-zinc (10 mg), low-iron (6 mg) (HiZn LoFe) MNP, daily; 3) HiZn (10 mg) LoFe (6 mg)/HiZn (10 mg), no-iron MNPs on alternating days; 4) dispersible zinc tablet (10 mg), daily; 5) dispersible zinc tablet (10 mg), daily for 2 wk at enrollment and 12 wk; 6) placebo powder, daily. Primary outcomes were incidence of diarrhea and change in length-for-age z-score (LAZ) over the 24-wk intervention period. Home visits were conducted twice weekly to assess diarrhea and other morbidity. Incidence and prevalence outcomes were compared among groups with Poisson regression; continuous outcomes were compared using ANCOVA. ResultsA total of 2886 children were enrolled between February 2018 and July 2019. The mean incidence and prevalence of diarrhea among all participants was 1.21 episodes per 100 d and 3.76 d per 100 d, respectively. There were no differences in the incidence or prevalence of diarrhea across intervention groups. The decline in LAZ was slightly smaller among children in the daily HiZn LoFe MNP group compared with the placebo powder group (P < 0.05). ConclusionsThe dose of zinc in MNPs as well as the duration and frequency of supplementation evaluated in this trial were not effective in reducing diarrhea; however, the daily HiZn LoFe MNP formulation offered modest improvements in linear growth among young children. This trial was registered at clinicaltrials.gov as NCT03406793.

Intergenerational change in anthropometry of children and adolescents in the New Delhi Birth Cohort.

A comparison of the anthropometry of children and adolescents with that of their parents at the same age may provide a more precise measure of intergenerational changes in linear growth and body mass index (BMI). New Delhi Birth Cohort participants (F1), born between 1969 and 1972, were followed up for anthropometry at birth and at 6-monthly intervals until 21 years of age. At variable intervals 1447 children, aged 0-19 years (F2) and born to 818 F1 participants, were measured (weight and height), providing 2236 sets of anthropometries. Intergenerational changes (F2-F1) in height and BMI [absolute and standard deviation (SD) units] were computed by comparing children with their parents at corresponding ages. F2 children were taller (P < 0.001) than their parents at corresponding ages; the increase {mean [95% confidence interval (CI)] World Health Organization SD units} was 0.97 (0.83, 1.11), 1.21 (1.10, 1.32), 1.09 (0.98, 1.19), 1.10 (1.00, 1.21) and 0.75 (0.65, 0.85) for age categories of 0-5, 5-7.5, 7.5-10, 10-12.5 and >12.5 years, respectively. In absolute terms, this increase ranged from 3.5 cm (0-5-year-olds) to 7.5 cm (10-12.5-year-olds). The corresponding increases in BMI SD scores were 0.32 (0.18, 0.47), 0.60 (0.45, 0.75), 1.13 (0.99, 1.27), 1.30 (1.15, 1.45) and 1.00 (0.85, 1.15), respectively. The absolute BMI increase ranged from 1-3 kg/m2 at >5 years age to ∼3 kg/m2 at >10-years of age. The intergenerational increases were comparable in both sexes, but were greater in children born and measured later. A positive change in socioeconomic status was associated with an increase in height across the generations. Children and adolescents, throughout the ages 0-19 years, have become considerably taller and have a higher BMI than their parents at corresponding ages in an urban middle-class Indian population undergoing socioeconomic improvements.

Effect of iron and zinc supplementation on linear growth of stunted Egyptian children under 5 years of age.

Background: Linear growth is the best indicator of children’s well-being and provides an accurate marker of inequalities in human development. Aim: Study and compare the effect of micronutrients supplementation (Iron and zinc) on linear growth of infants and children less than 5 years of age suffering from stunted growth. Patients and Methods: A randomized study included 60 children less than 5 years of age came to the department of clinical nutrition in a university hospital for nutritional assessment. Cases randomly divided equally into two groups. Group A received iron supplementation only and group B received supplementation with iron and zinc. Follow up of length/height was done after 6 months of supplementation. Outcome Measures: Length/height for age and sex (birth to 5 years Z-scores, WHO, 2003). Results: On comparing the length/ height of the two groups before (p=0.472) and after supplementation (p=0.923) respectively, no statistically significant differences were found between supplementation with iron only and with iron plus zinc. Yet, upon calculation the rate of change in linear growth after 6 months, a significant difference (p=0.002) was evident on comparing group B who received zinc plus iron (mean=13.6 cm increase in height) vs. Group A who only received iron (mean=10.8 cm increase in height). Conclusion: Zinc supplementation in addition to iron led to significant acceleration of linear growth of stunted children compared to supplementation with iron alone.

How countries can reduce child stunting at scale: lessons from exemplar countries

ABSTRACTBackgroundChild stunting and linear growth faltering have declined over the past few decades and several countries have made exemplary progress.ObjectivesTo synthesize findings from mixed methods studies of exemplar countries to provide guidance on how to accelerate reduction in child stunting.MethodsWe did a qualitative and quantitative synthesis of findings from existing literature and 5 exemplar country studies (Nepal, Ethiopia, Peru, Kyrgyz Republic, Senegal). Methodology included 4 broad research activities: 1) a series of descriptive analyses of cross-sectional data from demographic and health surveys and multiple indicator cluster surveys; 2) multivariable analysis of quantitative drivers of change in linear growth; 3) interviews and focus groups with national experts and community stakeholders and mothers; and 4) a review of policy and program evolution related to nutrition.ResultsSeveral countries have dramatically reduced child stunting prevalence, with or without closing geographical, economic, and other population inequalities. Countries made progress through interventions from within and outside the health sector, and despite significant heterogeneity and differences in context, contributions were comparable from health and nutrition sectors (40% of change) and other sectors (50%), previously called nutrition-specific and -sensitive strategies. Improvements in maternal education, maternal nutrition, maternal and newborn care, and reductions in fertility/reduced interpregnancy intervals were strong contributors to change. A roadmap to reducing child stunting at scale includes several steps related to diagnostics, stakeholder consultations, and implementing direct and indirect nutrition interventions related to the health sector and nonhealth sector .ConclusionsOur results show that child stunting reduction is possible even in diverse and challenging contexts. We propose that our framework of organizing nutrition interventions as direct/indirect and inside/outside the health sector should be considered when mapping causal pathways of child stunting and planning interventions and strategies to accelerate stunting reduction to achieve the 2030 Sustainable Development Goals.

A double-blind placebo-controlled trial of azithromycin to reduce mortality and improve growth in high-risk young children with non-bloody diarrhoea in low resource settings: the Antibiotics for Children with Diarrhoea (ABCD) trial protocol

BackgroundAcute diarrhoea is a common cause of illness and death among children in low- to middle-income settings. World Health Organization guidelines for the clinical management of acute watery diarrhoea in children focus on oral rehydration, supplemental zinc and feeding advice. Routine use of antibiotics is not recommended except when diarrhoea is bloody or cholera is suspected. Young children who are undernourished or have a dehydrating diarrhoea are more susceptible to death at 90 days after onset of diarrhoea. Given the mortality risk associated with diarrhoea in children with malnutrition or dehydrating diarrhoea, expanding the use of antibiotics for this subset of children could be an important intervention to reduce diarrhoea-associated mortality and morbidity. We designed the Antibiotics for Childhood Diarrhoea (ABCD) trial to test this intervention.MethodsABCD is a double-blind, randomised trial recruiting 11,500 children aged 2–23 months presenting with acute non-bloody diarrhoea who are dehydrated and/or undernourished (i.e. have a high risk for mortality). Enrolled children in Bangladesh, India, Kenya, Malawi, Mali, Pakistan and Tanzania are randomised (1:1) to oral azithromycin 10 mg/kg or placebo once daily for 3 days and followed-up for 180 days. Primary efficacy endpoints are all-cause mortality during the 180 days post-enrolment and change in linear growth 90 days post-enrolment.DiscussionExpanding the treatment of acute watery diarrhoea in high-risk children to include an antibiotic may offer an opportunity to reduce deaths. These benefits may result from direct antimicrobial effects on pathogens or other incompletely understood mechanisms including improved nutrition, alterations in immune responsiveness or improved enteric function. The expansion of indications for antibiotic use raises concerns about the emergence of antimicrobial resistance both within treated children and the communities in which they live. ABCD will monitor antimicrobial resistance. The ABCD trial has important policy implications. If the trial shows significant benefits of azithromycin use, this may provide evidence to support reconsideration of antibiotic indications in the present World Health Organization diarrhoea management guidelines. Conversely, if there is no evidence of benefit, these results will support the current avoidance of antibiotics except in dysentery or cholera, thereby avoiding inappropriate use of antibiotics and reaffirming the current guidelines.Trial registrationClinicaltrials.gov, NCT03130114. Registered on April 26 2017.

Pathobiome driven gut inflammation in Pakistani children with Environmental Enteric Dysfunction.

Environmental Enteric Dysfunction (EED) is an acquired small intestinal inflammatory condition underlying high rates of stunting in children <5 years of age in low- and middle-income countries. Children with EED are known to have repeated exposures to enteropathogens and environmental toxins that leads to malabsorptive syndrome. We aimed to characterize association of linear growth faltering with enteropathogen burden and subsequent changes in EED biomarkers. In a longitudinal birth cohort (n = 272), monthly anthropometric measurements (Length for Age Z score- LAZ) of asymptomatic children were obtained up to 18 months. Biological samples were collected at 6 and 9 months for the assessment of biomarkers. A customized TaqMan array card was used to target 40 enteropathogens in fecal samples. Linear regression was applied to study the effect of specific enteropathogen infection on change in linear growth (ΔLAZ). Presence of any pathogen in fecal sample correlated with serum flagellin IgA (6 mo, r = 0.19, p = 0.002), fecal Reg 1b (6 mo, r = 0.16, p = 0.01; 9mo, r = 0.16, p = 0.008) and serum Reg 1b (6 mo, r = 0.26, p<0.0001; 9 mo, r = 0.15, p = 0.008). At 6 months, presence of Campylobacter [β (SE) 7751.2 (2608.5), p = 0.003] and ETEC LT [β (SE) 7089.2 (3015.04), p = 0.019] was associated with increase in MPO. Giardia was associated with increase in Reg1b [β (SE) 72.189 (26.394), p = 0.006] and anti-flic IgA[β (SE) 0.054 (0.021), p = 0.0091]. Multiple enteropathogen infections in early life negatively correlated with ΔLAZ, and simultaneous changes in gut inflammatory and permeability markers. A combination vaccine targeting enteropathogens in early life could help in the prevention of future stunting.

Effectiveness of provision of animal-source foods for supporting optimal growth and development in children 6 to 59 months of age.

Effectiveness of provision of animal-source foods for supporting optimal growth and development in children 6 to 59 months of age.

Overgrowth of costochondral graft in temporomandibular joint ankylosis reconstruction: A retrospective study.

Temporomandibular joint (TMJ) ankylosis is a situation in which the mandibular condyle is fused to the glenoid fossa by bone or fibrous tissue. The management of TMJ ankylosis has a complicated chore, and it is challenging for the maxillofacial surgeon because of technical hitches and high rate of reankylosis. Costochondral graft (CCG) is a common treatment modality for TMJ ankylosis. One of disadvantages of CCG is unpredictability of growth pattern and risk of overgrowth. This report illustrates the fate of CCG used in the TMJ reconstruction and also the management of patients with CCG overgrowth. A retrospective evaluation of 14 patients presented with unilateral TMJ ankylosis reconstructed using CCG treated in our hospital from 2000 to 2013 was done. Only patients with unilateral ankylosis treated by CCG with at least 2-year follow-up and complete case records with clinical and radiographic details were included in the study. Patients with bilateral ankylosis, reankylosis, missing details, and the patients with <2-year follow-up were excluded from the study. The patients were selected based on the specified inclusion/exclusion criteria. All the patients were analyzed clinically and radiographically. Facial appearance, jaw motion, occlusion, contour, and linear growth changes were documented preoperatively, immediately postoperatively, and long term (>2 years). Totally 14 unilateral temporomandibular ankylosis cases were reconstructed using CCG from the period of 2000-2013. The mean age of the patients is 5.2 years with the standard deviation of 1.48 ranging from 3 to 9 years. Follow-up of the patients ranges from 2 to 6 years with mean follow-up of 3 years. Out of 14 patients, 2 patients had normal growth of CCG after the mean follow-up of 3 years, whereas 5 patients presented with moderate growth, 4 patients with CCG overgrowth, and 3 patients presented with no growth of CCG following surgery. Overgrown CCG was treated with condylar shaving, and orthodontic elastic was maintained to stabilize the occlusion. Moderately grown and nongrowing CCG was treated by internal distractor for the management of facial symmetry. Facial asymmetry and malocclusion were successfully corrected in all patients with altered growth pattern. The growth pattern of the CCG is extremely unpredictable, which can be in the form of no growth at all or excessive growth, and mandibular overgrowth on the grafted site can actually be more troublesome than the lack of growth. Care should also be taken to ensure proper postoperative functional therapy and to examine the role of cartilage thickness on future growth in young patients.

The magnitude of changes in linear growth within Taiwanese families: intrinsic sex-associated biology, socially mediated behaviors, or both?

This study evaluates competing hypotheses about implications of greater female growth canalization for differences in male and female growth as developmental settings improve. Intergenerational declines in gender bias and rapid economic growth in Taiwan permit assessment of the two hypotheses using anthropometric and background information from 107 Taiwanese parents and their young adult offspring. Differences in parents' values were first evaluated across grandfathers' occupational status categories reflecting good to relatively poor early circumstances in the parental generation. The extent of intergenerational change in heights or knee heights within 56 father-son pairs were then compared with those in 51 statistically independent mother-daughter pairs across the same occupational categories using repeated measures analyses. Change in mean heights and knee heights across grandfathers' occupational categories were noticeably greater for fathers than mothers. Overall, intergenerational gains within families in height and knee height were statistically significant (p < 0.0005) in father-son (3.89 cm; 1.85 cm) and mother-daughter pairs (4.14 cm; 1.67 cm). However, among families where grandfather's occupations were "privileged," father-son pairs are similar in average height (Δ = -0.36 cm) and knee height (Δ = 0.53 cm) while mothers were significantly shorter (Δ = 3.88 cm) with shorter knee heights (Δ = 1.74 cm) than their daughters. The hypothesis that females are inherently less capable of responding to growth promoting characteristics of early environments is not supported. Intergenerational declines in male preference combined with rapid but equitable economic growth better account for intergenerational changes reported.

What's up with catch‐up? No evidence of population‐level catch‐up growth in children under 5 years of age when using height‐for‐age difference (HAD) instead of height‐for‐age z‐scores (HAZ)

Studies conducted in past decades showed little or no population‐level linear catch‐up growth (defined as reductions in absolute height deficit) in children after 2 y of age. Recent studies, however, have reported catch‐up growth in groups of children using height‐for‐age z‐scores (HAZ). We assessed whether population‐level catch‐up growth is found when height‐for‐age difference (HAD; child's height compared to standard in cm) is used instead of HAZ.Using data from Demographic and Health Surveys (DHS), Young Lives (YL), and the Consortium on Health‐Oriented Research in Transitional Societies (COHORTS), we compared changes in HAD and HAZ in populations of children between 2 and 5 y. We show that HAZ is inappropriate to measure changes in linear growth as populations of children age because they are constructed using SDs from cross‐sectional data, which increase with age. Using HAD, we find not only an absence of population‐level catch‐up growth, but a continued deterioration reflected in a decrease in mean HAD between 2 and 5 y; HAZ shows either no change (DHS) or an improvement in mean HAZ (YL, COHORT) as groups of children age.We show no evidence of population‐level catch‐up in children between 2 to 5 y when using HAD. The continued widening of the height deficit after 2 y does not challenge the current focus on the first 1,000 days, but raises questions regarding prevention of continued deterioration and the potential of children to benefit from nutrition interventions after 2 y of age.Funded by the CGIAR Research Program on Agriculture for Nutrition and Health (A4NH), led by IFPRI.

Maxillary growth and maturation during infancy and early childhood

To describe maxillary growth and maturation during infancy and early childhood. Serial cephalograms (N=210) of 30 subjects (15 females and 15 males) from the Bolton-Brush Growth Study were analyzed. Each subject had a series of six consecutive cephalograms taken between birth and 5 years of age, as well as one adult cephalogram. Twelve maxillary measurements (eight linear and four angular) and seven landmarks were used to characterize maxillary growth. Maturation of the linear measures was described as a percentage of adult status. Maxillary and anterior cranial base size increased in both sexes between 0.4 and 5 years of age. The linear anteroposterior (AP) measures (S-SE, SE-N, ANS-PNS) increased almost as much as the vertical measures (S-PNS, SE-PNS, N-A, N-ANS) over the first 5 years. After 5 years of age there was significantly more vertical than AP growth. The size and shape changes that occurred were greatest between 0.4 and 1 years; yearly velocities decelerated regularly thereafter. Overall linear growth changes that occurred between 0.5 and 5 years of age (a span of 4.5 years) were generally greater than the changes in maxillary growth that occurred between 5 and 16 years (a span of 11 years). The linear measures showed a gradient of maturation, with the AP measures being more mature than the vertical measures. Male maxillae were less mature than female maxillae at every age. The maxilla undergoes its greatest postnatal growth change during infancy and early childhood, when relative AP growth and maturation are emphasized.

656 Enhancement of Linear Growth and Weight Velocity by Cyproheptadine in Children with Idiopathic Growth Hormone Deficiency Receiving this Hormone

BackgroundThe current study examined the hypothesis that Cyproheptadine can enhance linear growth and increase weight velocity in children with idiopathic GH deficiency.Method10 children with idiopathic GH deficiency received Cyproheptadine 0.3mg/kg...

Pharmacodynamic responses of plasma and tissue C-type natriuretic peptide to GH: correlation with linear growth in GH-deficient rats

Studies from genetic modification and spontaneous mutations show that C-type natriuretic peptide (CNP) signalling plays an essential part in postnatal endochondral growth, but measurement of CNP proteins and changes in their abundance in tissues and plasma during normal growth has not been reported. Using rodent pups with GH deficiency, we now describe the pharmacodynamic response of CNP and rat amino-terminal proCNP (NTproCNP) in plasma and tissues, and relate these to changes in linear growth (nose-tail length, tibial length and tibial growth plate width) during the course of 1 week of GH or saline (control) administration. Compared with saline, significant increases in plasma and tissue CNP forms were observed after 24 h in GH-treated pups and before any detectable change in linear growth. Whereas CNP abundance was increased in most tissues (muscle, heart and liver) by GH, enrichment was the greatest in extracts from growth plates and kidney. Plasma and tissue concentrations in GH-treated pups were sustained or further increased at 1 week when strong positive associations were found between plasma NTproCNP and linear growth or tissue concentrations. High content of NTproCNP in kidney tissue strongly correlated with plasma concentrations, which is consistent with previous data showing renal extraction of the peptide. In showing a prompt and significant increase in CNP in tissues driving normal endochondral growth, these findings provide further rationale for CNP agonists in the treatment of growth disorders resistant to current therapies and support the use of CNP concentrations as biomarkers of linear growth.

Determinants of Changes in Linear Growth and Body Composition in Incident Pediatric Crohn's Disease

Pediatric Crohn's disease (CD) is associated with growth, lean mass (LM), and fat mass (FM) deficits. This study assessed and identified determinants of changes in height and body composition in children with CD following. Whole-body LM and FM were assessed using dual-energy x-ray absorptiometry in 78 CD subjects at diagnosis, 6, 12, and a median of 43 months (range, 24-63) later. Race- and sex-specific Z scores for lean mass (LM-ht-Z) and fat mass (FM-ht-Z) relative to height were derived using reference data in >900 controls. Serum cytokines and growth factors were measured, and quasi-least squares regression was used to identify determinants of changes in height and body composition. LM-ht-Z and FM-ht-Z (both P<.005) improved significantly after diagnosis; however, female patients had persistent LM deficits vs controls (-0.50+/-1.02, P<.05). Serum interleukin-6, tumor necrosis factor-alpha, and lipopolysaccharide binding protein decreased significantly (all P<.001). Greater increases in LM-ht-Z were associated with infliximab therapy (P<.05), increases in albumin (P<.001) and decreases in erythrocyte sedimentation rate (P<.05), interleukin-6 (P<.005), and lipopolysaccharide binding protein (P<.05). Greater increases in FM-ht-Z were associated with glucocorticoid, methotrexate, and infliximab therapy, and increases in albumin (P<.05) and growth hormone binding protein (P<.05). Overall, height-Z did not improve; however, greater increases in insulin-like growth factor-1 (P<.05) and decreases in tumor necrosis factor-alpha (P<.05), interleukin-6 (P<.05), and lipopolysaccharide binding protein (P<.05) levels were associated with increases in height-Z. Immune-mediated mechanisms contribute to growth and body composition deficits in CD. Therapies should target these deficits.

Does the secular increase in body mass in children contribute to the increasing incidence of type 1 diabetes?

The incidence of type 1 diabetes in children has increased in most developed countries after World War II, and simultaneously, normal children have experienced accelerated weight gain and growth. We set out to explore whether any relationship can be seen between the incidence of childhood type 1 diabetes and changes in linear growth and body mass in Finnish children over a 12-yr period. Incidence rates for type 1 diabetes in Finnish children under the age of 15 yr were obtained from the National Central Drug Registry. The rates were averaged for 3-yr intervals over the 15-yr period 1979-1993 and related to data on mean height, weight, and body mass index (BMI) in 15-yr-old children generated for the years 1980, 1983, 1986, 1989, and 1992 by the 'Cardiovascular Risk in Young Finns' study. There was a positive correlation between the incidence of childhood type 1 diabetes and mean heights (r = 0.84; p = 0.039), mean weights (r = 0.85; p = 0.036), and mean BMIs (r = 0.87; p = 0.028) in 15-yr-old children over the 12-yr study period. This observation suggests that accelerated linear growth and increasing body mass may contribute to the rising incidence of childhood type 1 diabetes seen in most developed countries since World War II. This effect might be mediated through increased beta-cell stress induced by hyperinsulinemia and decreased insulin sensitivity, associated with rapid linear growth and obesity.