Height Growth Velocity Research Articles

SUN-093 Prospective Clinical Assessment Study in Children with Achondroplasia: The PROPEL Trial

BACKGROUND: Achondroplasia (ACH) is the most common non-lethal form of skeletal dysplasia, affecting between 1 in 15,000 to 1 in 30,000 live births [Horton et al. 2007; Waller et al. 2008]. Children and adults with ACH have disproportionate short stature, with a final height of approximately 131 cm for males and 124 cm for females. They are prone to significant co-morbidities, including obstructive sleep apnea, chronic otitis media with conductive hearing loss, spinal stenosis and a propensity towards obesity. In some infants, narrowing of the foramen magnum may result in compression of the spinal cord with neurologic sequelae, requiring timely neurosurgical intervention. There are currently no approved therapies for the treatment of ACH in either the United States or the European Union, and management is generally supportive in nature. The PROPEL trial is a prospective, non-interventional study examining baseline growth parameters and health status in children with ACH being assessed for potential enrollment into interventional studies with infigratinib, an oral FGFR1-3 inhibitor in development for achondroplasia. Methods: Children with ACH between the ages of 2.5 and 10 years are eligible for enrollment in this prospective, non-interventional trial to evaluate growth parameters and determine clinical status. Participants will be assessed at baseline, month 3, month 6, and every 6 months thereafter. The primary endpoint is annualized height growth velocity. Secondary endpoints include change from baseline in other growth parameters (including body proportionality); analysis of bone biomarkers (e.g., bone alkaline phosphatase, collagen X fragment); and the occurrence of medical events and surgical procedures. Participants will be enrolled in the study for a minimum of 6 months up to a maximum of 2 years before being considered for enrollment in a QED-sponsored phase 2/3 interventional trial. Current status: The PROPEL study is underway with the first patient enrolled in August 2019. Planned total enrollment is 200 children with ACH.

Imaging Biomarkers of the Physis: Cartilage Volume on MRI vs. Tract Volume and Length on Diffusion Tensor Imaging.

Current methods to predict height and growth failure are imprecise. MRI measures of physeal cartilage are promising biomarkers for growth. In the physis, to assess how 3D MRI volume measurements, and diffusion tensor imaging (DTI) measurements (tract volume and length) correlate with growth parameters and detect differences in growth. We compared patients exposed to cis-retinoic acid, which causes physeal damage and growth failure, with normal subjects. Case-control. Twenty pediatric neuroblastoma survivors treated with cis-retinoic acid and 20 age- and sex-matched controls. 3T; DTI and 3D double-echo steady-state (DESS) sequences. On distal femoral MR studies, physeal 3D volume and DTI tract measurements were calculated and compared to height. We used partial Spearman correlation, analysis of covariance, logistic regression, Wald test, and the intraclass correlation coefficient (ICC). The height percentile correlated most strongly with DTI tract volumes (r = 0.74), followed by mean tract length (r = 0.53) and 3D volume (r = 0.40) (all P < 0.02). Only tract volumes and lengths correlated with annualized growth velocity. Relative to controls, patients showed smaller tract volumes (8.00 cc vs. 13.71 cc, P < 0.01), shorter tract lengths (5.92 mm vs 6.99 mm, P = 0.03), and smaller ratios of 3D cartilage volume to tract length; but no difference (4.51 cc vs 4.85 cc) in 3D MRI volumes. The 10 patients with the lowest height percentiles had smaller tract volumes (5.07 cc vs. 10.93 cc, P < 0.01), but not significantly different 3D MRI volumes. Tract volume is associated with abnormal growth, with an accuracy of 75%. DTI tract volume of the physis/metaphysis predicts abnormal growth better than physeal cartilage volumetric measurement and correlates best with height percentile and growth velocity. 2 TECHNICAL EFFICACY: Stage 2 J. Magn. Reson. Imaging 2020;52:544-551.

5-year mental health and eating pattern outcomes following bariatric surgery in adolescents: a prospective cohort study

Mental health problems are prevalent among adolescents with severe obesity, but long-term mental health outcomes after adolescent bariatric surgery are not well known. We aimed to assess mental health outcomes over 5 years of follow-up after Roux-en-Y gastric bypass surgery in adolescents who participated in the Adolescent Morbid Obesity Surgery (AMOS) study. This was a non-randomised matched-control study in adolescents aged 13-18 years who had a BMI of 40 kg/m2 or higher, or 35 kg/m2 or higher in addition to obesity-related comorbidity; who had previously undergone failed comprehensive conservative treatment; and were of pubertal Tanner stage III or higher, with height growth velocity beyond peak. A contemporary control group, matched for BMI, age, and sex, who underwent conventional obesity treatment, was obtained from the Swedish Childhood Obesity Treatment Register. Data on dispensed psychiatric drugs and specialist treatment for mental disorders were retrieved from national registers with complete coverage. In the surgical group only, questionnaires were used to assess self-esteem (Rosenberg Self-Esteem [RSE] score), mood (Mood Adjective Checklist [MACL]), and eating patterns (Binge Eating Scale [BES] and Three-Factor Eating Questionnaire-R21 [TFEQ]). This study is registered with ClinicalTrials.gov (NCT00289705). Between April 10, 2006, and May 20, 2009, 81 adolescents (53 [65%] female) underwent Roux-en-Y gastric bypass surgery, and 80 control participants received conventional treatment. The proportion of participants prescribed psychiatric drugs did not differ between groups in the years before study inclusion (pre-baseline; absolute risk difference 5% [95% CI -7 to 16], p=0·4263) or after intervention (10% [-6 to 24], p=0·2175). Treatment for mental and behavioural disorders did not differ between groups before baseline (2% [-10 to 14], p=0·7135); however, adolescents in the surgical group had more specialised psychiatric treatment in the 5 years after obesity treatment than did the control group (15% [1 to 28], p=0·0410). There were few patients who discontinued psychiatric treatment post-surgery (three [4%] receiving psychiatric drug treatment and six [7%] receiving specialised care for a mental disorder before surgery). In the surgical group, self-esteem (RSE score) was improved after 5 years (mixed model mean 21·6 [95% CI 19·9 to 23·4]) relative to baseline (18·9 [17·4 to 20·4], p=0·0059), but overall mood (MACL score) was not (2·8 [2·7 to 2·9] at 5 years vs 2·7 [2·6 to 2·8] at baseline, p=0·0737). Binge eating was improved at 5 years (9·3 [7·4 to 11·2]) relative to baseline (15·0 [13·5 to 16·5], p<0·0001). Relative changes in BMI were not associated with the presence or absence of binge eating at baseline. Mental health problems persist in adolescents 5 years after bariatric surgery despite substantial weight loss. Although bariatric surgery can improve many aspects of health, alleviation of mental health problems should not be expected, and a multidisciplinary bariatric team should offer long-term mental health support after surgery. Swedish Research Council, VINNOVA, Västra Götalandsregionen, ALF VG-region, Region Stockholm, Swedish Child Diabetes Foundation, Swedish Heart and Lung Foundation, Tore Nilsson's Foundation, SUS Foundations and Donations, Capio Research Foundation, and Mary von Sydow's Foundation.

Comparative Analyses of Height Growth Velocities of School Boys in South Korea and Japan in the Past 50 Years

The paper compares the height growth velocities of male schoolchildren in South Korea and Japan over the period 1961-2018. Growth in height was measured with the same birth cohorts, not by comparing mean height of ascending ages in the same year. Starting from a lower economic base and mean height in the 1960s, high school males aged 17 in South Korea became 3 cm taller in mean height than their Japanese peers in the mid-2000s versus 2 - 3 cm shorter in the 1960s through 1970s. Children in Japan ceased to grow taller by the end of the 1980s, not because they quit taking more animal-sourced foods, meat and milk, but because they had drastically steered away from fruit and vegetables in their diets since the end of the 1970s. Having largely converged economically with Japan, South Korean children ceased to grow any taller in the mid-2000s. More importantly, it was discovered in this study that successive cohorts in South Korea started to fall gradually but steadily in height growth velocity from 1st graders in middle school, aged 12 years to 3rd graders in high school, and aged 17 years, to be once again 3 cm below their Japanese peers in the early-2010s. Analysis of Korea Household Expenditure Surveys classified by age groups of household head, decomposed by the author, revealed that children under 20 years of age in South Korea began to steer away from fruit and, particularly, vegetables in their at-home consumption in the mid-1990s, to average only 15% of the level of older adults in their 50s in the mid-2010s. These results lend supports to the importance of fruit and vegetables as determinants in height and its growth velocities in two genetically similar nations over time and stages of economic growth.

Posture of adolescent volleyball players – a two-year study

Summary Study aim: The aim of this study was to assess and compare the posture of male and female adolescent volleyball players and non-training individuals over a 2-year period. Material and methods: The study group comprised 32 volleyball players and 30 non-athlete peers. Posture was assessed with a photogrammetric method based on the moiré phenomenon. Participants were examined 3 times at the ages of 14, 15 and 16 years. Training experience of the studied volleyball players at the time of the 1st measurement was less than 5 months. Results: In volleyball players greater asymmetry in the pelvis position was noted (rotation to the right). The right scapula was more outlying than the left, and the right shoulder was more elevated than the left. Volleyball training did not result in sagittal spinal curvatures. Male non-athlete participants exhibited a significant increase in thoracic kyphosis and a decrease in lumbar lordosis over a two-year period. Conclusion: Volleyball training affects the alignment of the pelvis, shoulder girdle and scapulae. The study revealed a number of differences in spinal curvatures between male volleyball players and non-athletes which could be associated with growth velocity and differences in body height.

ACCELERATED CHILDHOOD SKELETAL AGING IS PROTECTIVE OF DEVELOPMENT OF SARCOPENIA IN LATER LIFE

Sarcopenia is an age-related loss of muscle mass and strength that has a multitude of adverse sequelae. Similar to other aging-related phenomenon, sarcopenia is likely the product of inputs that begin in utero and continue throughout the lifespan. We hypothesized that patterns of childhood skeletal growth predict sarcopenia status later in life. Data are from N=202 lifelong participants of the Fels Longitudinal Study (median lifetime visits=33). At the sarcopenia measure visit, participants were aged 65.8 + 10.3 years, 54% female, with body mass index of 27.5 + 4.9. Sarcopenia was defined using published sex-specific cutpoints from dual energy x-ray absorptiometry quantified appendicular lean mass/height2. Childhood skeletal age was calculated from serial hand-wrist radiographs (FELS method). Residual skeletal aging (RSA) was calculated as skeletal age minus predicted chronological age at peak height growth velocity during adolescence. RSA variance was similar in both sexes, with a range of -2 (delayed skeletal aging) to +2 years (accelerated skeletal aging). In older age, 6% of males and 22% of females exhibited sarcopenia. In multivariate logistic regression models controlling for age, self-reported physical activity, and grip strength (all measured at sarcopenia visit), accelerated RSA was protective of sarcopenia (Adjusted OR=0.58; 95% CI: 0.35-0.94). This is the first study to link childhood skeletal maturation to sarcopenia later in life. Biological pathways that explain this association likely include physiological, environmental, and genetic factors that facilitate communication between bone and muscle, and span the life course. Determining their influence is the next important step in this work.

Impact of antiretroviral treatment on height evolution of HIV infected children

BackgroundAntiretroviral treatment (ART) has been shown to have a beneficial effect on the weight evolution but its effect on height remains unclear. We described patterns of height evolution and identified predictors of catch-up growth in HIV-infected children on ART.MethodsTo describe the height evolution from birth to adulthood, we developed a nonlinear mixed effect model using data from perinatally HIV-infected children who initiated ART from 1999 to 2013 in a prospective cohort study in Thailand. The main covariates of interest were: sex, ART regimen (dual nucleoside reverse-transcriptase inhibitor, non-nucleoside reverse transcriptase inhibitor (NNRTI)-, or protease inhibitor (PI)-based), baseline CD4 percentage, HIV-RNA load and CDC HIV Classification stage and occurrence of AIDS-defining events.ResultsA total 477 children (43% boys) contributed 18,596 height measurements over a median duration of 6.3 years on ART (interquartile range, 3.0 to 8.3). At ART initiation, median age was 6.2 years (1.8 to 9.6), 16% of children were underweight (weight-for-age z-score < − 2), 49% presented stunting (height-for-age z-score < − 2), and 7% wasting (weight-for-height z-score < − 2). The most frequent regimen at ART initiation was NNRTI-based (79%). A model with 4 components, birth length and 3 exponential functions of age accounting for the 3 growth phases was developed and show that the height-growth velocity was inversely associated with the age at ART initiation, the adult height was significantly lower in those who had experienced at least one AIDS-defining event while, as expected, the model found that adult height in females was lower than in males. Age at ART initiation, type of ART regimen, CDC stage, CD4 percentages, and HIV-RNA load were not associated with the final height.ConclusionsThe younger the children at ART initiation, the greater the effect on height-growth velocity, supporting the World Health Organization’s recommendation to start ART as early as possible. However, final adult height was not linked to the age at ART initiation.

Efficacy and safety of a biosimilar recombinant human growth hormone (r-hGH Cristalia) compared with reference r-hGH in children with growth hormone deficiency (CERES study): A randomized, multicentric, investigator-blind, phase 3 trial

ObjectiveThe CERES study was a randomized, multicenter, investigator-blind trial aimed to evaluate the efficacy and safety of a recombinant human growth hormone (r-hGH) developed by Cristalia, as a biosimilar product, with analytical, functional and pharmacokinetics similarities comparable to Genotropin™, in children with growth hormone deficiency (GHD). DesignA total of 135 naïve prepubertal children with GHD were recruited, of whom 97 were randomized in 14 Brazilian sites to received either r-hGH Cristalia (n = 49) or Genotropin™ (n = 48). Efficacy was evaluated considering the height standard deviation score (SDS) and growth velocity as auxological parameters, IGF-1 and IGFBP-3 were measured as pharmacodynamic parameters during 12 months treatment time. Safety was assessed by monitoring adverse events, immunogenicity, blood count with platelets, biochemical profile and hormonal levels particularly fasting glucose, insulin and HbA1C. ResultsThe auxological parameters and IGF-1 and IGFBP-3 levels were comparable between both groups of patients. At end of study or the 12th month treatment, the means growth velocity was 9.7 cm/year and 9.5 cm/year, for r-hGH Cristalia and Genotropin™, respectively. The ANCOVA mean difference between the groups was 0.16 cm/year to Cristalia group (CI 95% = −0.72 to 1.03 cm/year). There was no difference in adherence among the treatment groups. The safety profile was comparable between groups. ConclusionsThe clinical similarity between r-hGH and Genotropin™ was demonstrated within 12 month of treatment. On the basis of comparability of quality, safety, and efficacy to the reference product, r-hGH from Cristalia can be considered a cost-effective therapeutic option for patients with growth disorders.

Dietary intake from birth through adolescence in relation to risk of benign breast disease in young women.

Nutritional factors during different periods in life impact breast cancer risk. Because benign breast disease (BBD) is a well-established risk factor for breast cancer, we investigated childhood nutrition from birth through age 14year and subsequent BBD. A prospective cohort study of 9031 females, 9-15year at baseline, completed questionnaires (including heights, weights) annually from 1996 to 2001, in 2003, 2005, 2007, 2010, 2013 and 2014. In 1996, mothers reported infant feeding practices during their daughters first year of life. Beginning in 1996, participants completed annual food frequency questionnaires. In 2005, participants (18 year +) began reporting whether they had ever been diagnosed with biopsy-confirmed BBD (N = 173 cases). Multivariable logistic regression models estimated associations between childhood nutrition and BBD, adjusted for maternal breast disease and childhood body size factors. Although no infant nutrition factors were associated with biopsy-confirmed BBD, certain adolescent dietary factors were. A multivariable model simultaneously included the most important diet and body size factors from different age periods: higher BBD risk was associated with greater age 10year consumption of animal (non-dairy, energy-adjusted) fat (OR 2.27, p < .02, top vs. bottom quartiles) and with lower 14year consumption of nuts/peanut butter (OR 0.60, p = .033, top vs. bottom quartiles). Greater intake of animal (non-dairy) fat at 10year and lower intake of nuts/peanut butter at 14year were independently associated with higher BBD risk. These dietary factors appeared to operate on BBD risk independent of childhood growth (gestational weight gain, childhood BMI and height, adolescent height growth velocity), young adult height and BMI, and family history.

Height growth velocity during infancy and childhood in achondroplasia.

There is a lack of knowledge about longitudinal growth during childhood in achondroplasia. We report patterns of linear growth and height growth velocity references. The sample consisted of 84 children, 41 girls and 43 boys. Growth data was collected from birth until mid-childhood. The median (interquartile range) number of measurements per child was 13.5 (12, 15). Individual growth curves were estimated by fitting the Reed 1st model to each individual's height for age data. Height growth velocities references for age centiles were calculated by LMS method. Mean (SD) birth length was 46.14 cm (2.17) and 45.53 cm (2.16), for boys and girls respectively. Individual growth curves were analyzed. Shifts in growth channels were seen: out of 84 infants, 41 (48.8%) changed more than 1 SDS between birth to 5 years old. The numbers of infants shifting upward were similar (20/84) to the infants shifting downward (21/84). Height growth velocity curves show that after a period of fast decreasing growth velocity since birth, with a mean of 15.5 cm/year and 9.5 cm/year at 6 month and 1 year old, the growth velocity is stable in late preschool years, with a mean of 4.3 cm/year. Shifts in growth channels were seen between birth and 5 years old. Professionals who follow up them must consider this phenomenon during infancy. ACH children experienced a period of fast decreasing growth during infancy and the growth curve was similar in shape and lesser in magnitude than the general population.

Why Do Normal Children Have Acromegalic Levels of IGF-I During Puberty?

The rapid pubertal height growth is unique to humans, but why do we have it? Although the spurt contributes 13% to 15% to the final adult height, we hypothesized that the biological significance of the high acromegalic levels of GH and IGF-I, which are behind the pubertal growth spurt, might primarily occur to stimulate the reproductive organs. Animal data have demonstrated that adult Igf1 and Igf2 gene knockout mice that survive show a dramatic reduction in the size of the reproductive organs and are infertile. In humans, case reports of mutations in the genes affecting the GH-IGF axis and growth (GH, GHRH, GH-R, STAT5b, IGF-I, IGF-II, IGF-1R, PAPPA2) are also characterized by delayed pubertal onset and micropenis. Furthermore, GH treatment will tend to normalize the penile size in patients with GH deficiency. Thus, the endocrine effects of high IGF-I levels might be needed for the transition of the sexual organs, including the secondary sex characteristics, from the "dormant" stages of childhood into fully functioning reproductive systems. The peak IGF-I levels, on average, occur 2 years after the peak height growth velocity, suggesting reasons other than longitudinal growth for the high IGF-I levels, and remain high in the years after the height spurt, when the reproductive systems become fully functional. We suggest that the serum levels of IGF-I should be monitored in children with poor development of sexual organs, although it remains to be investigated whether GH should be added to sex steroids in the management of hypogonadism for some pubertal children (e.g., boys with micropenis).

Relation between changes in weight parameters and height parameters in prepubertal children: daily weight gain and BMIi changes in relation to linear growth during nutritional rehabilitation of underweight children.

Background: Early detection of abnormal weight loss or gain in childhood may be important for preventive purposes. Variable growth response to nutrition rehabilitation have been reported in children with failure to thrive (FTT) who do not have any chronic disease or systematic illness due to different clinical and nutritional approach in their management. Aim of the study: To analyze the association of different body mass index (BMI) and BMI- SDS, to linear growth (Ht-SDS) in different BMI categories of prepubertal children. In addition, we studied the effect of weight changes on linear growth in a randomly selected group of prepubertal underweight children who received nutritional rehabilitation (NR) for 9±2 months. Subjects and methods: 102 children, between 1 and 9 years, followed at the General Pediatric Clinic, between January 2017 to December 2017, because of abnormal weight gain (decreased or increased) which was not associated with any acute or chronic illness were included in the study. Anthropometric measurements included weigh, height, Ht-SDS, BMI, and BMI-SDS. Children BMI-SDS were categorized into 4 groups: Group 1: BMI-SDS <-2, group 2: BMI-SDS <-1 but >-2, group 3 BMI-SDS >-1 but <2, group 4 BMI-SDS >2. We also evaluated the effects of weight changes on linear growth in a randomly selected group of underweight children who received nutritional counselling and oral nutritional supplementation (n = 51) for 9±months. Results: HT-SDS in children of groups 1 and 2 (underweight and at risk of underweight children) was significantly lower than Ht-SDS of groups 3 and 4 (normal and overweight children). Ht-SDS in children of group 4 was significantly higher than the Ht-SDS of children in group 3. A significant linear correlation was found between BMI-SDS and Ht-SDS in these prepubertal children. Discussion: After nutritional rehabilitation for a year, 55% of underweight children increased their BMI-SDS and 43% increased their Ht-SDS. Children who had weight gain >7g/d, over the whole period of follow-up, (n =14) increased their BMI-SDS and Ht-SDS significantly after versus before NR. The BMI-SDS and Ht-SDS did not increase significantly in the group of children who had weight gain <7 g/day. 28 children out of 51 improved their BMI-SDS after nutritional rehabilitation (group A) and 23 did not have improvement in their BMI-SDS (Group B). Group A had higher weight gain per day versus group B. Height growth velocity was significantly higher in Group B (7.4±3.6 cm/yr) versus group A (5.7±2.8 cm/yr). Ht-SDS increased significantly in the group of patients who had lower Ht-SDS before NR. Children who had faster linear growth velocity, after nutritional rehabilitation, did not increase their BMI-SDS. Linear regression showed a significant correlation between BMI-SDS and Ht-SDS supporting the notion that proper nutrition and maintaining normal BMI-SDS is essential for adequate gain in height. Conclusion: It appears that calculating the weight gain per day, BMI-SDS and Ht-SDS are clinically useful parameters to detect the effect of weight gain on linear growth and to monitor the nutritional management. Daily weight gain was correlated significantly to height growth rate during nutritional rehabilitation. Based on our findings and literature reports, we suggest an algorithm for follow-up of underweight/ malnourished children based mainly on anthropometric assessment. (www.actabiomedica.it)

Linear growth of children with celiac disease after the first two years on gluten- free diet: a controlled study.

Background: Celiac disease (CD) is a lifelong disorder with gluten-induced manifestations in different organs especially growth. Gluten free diet (GFD) is required to achieve remission and prevent abnormal growth. Study reports on growth of children with celiac disease on long-term GFD are not consistent. Objective: We evaluated the effect of GFD on growth of children with the classical form of CD (diagnosed by serology and small intestine mucosal biopsy) on log-term GFD (>2 years). Methods: We studied growth parameters (weight gain/day, BMI and BMI-SDS, height growth velocity, Ht-SDS) and lab data in 30 prepubertal children, aged 7.4±2.6 years, with CD, who were on GFD since the age of 3.2±1.6 years of age (>2 years on GFD) for duration of 1 year. The anthropometric data of 30 randomly selected normal, age and sex matched, children were used as control. Lab investigations of CD children included complete blood count (CBC), renal and liver functions (aspartate transaminase - AST, alanine aminotransferase - ALT, and alkaline phosphatase- ALP, serum albumin, fasting blood glucose, vitamin D, and thyroid function and antibodies. Results: The weight gain per day was on average or above, for age and sex, in 27 children and below average in 3. Two out of those 3 children had slow linear growth (decreased Ht-SDS by -0.56 and -0.1, over one year). BMI-SDS was normal in 26/30 patients (>-1.5). BMI-SD changed from -0.36±1.1 to -0.33±1.1 during the year of treatment. BMI-SDS decreased in 9 children during the follow up period that was explained by their fast-linear growth (increased Ht-SDS) in seven of them. The Ht-SDS was <-2 in four out of 30 children at the beginning of the study (2 years after being on GFD) and in 2 children after a year of follow-up (catch-up growth). Ht-SDS remained normal or increased in 28/30 children during the year of treatment (-0.38 ±1.2 to -0.22±1.1), with a positive trend: 0.15±0.4 SDS. Only one patient crossed down 1 Ht-SDS during the year of follow up, with low weight gain/day and decreased BMI-SDS that can be explained by poor compliance with GFD. Ht-SDS and BMI-SDS increased significantly in the CD group versus controls during the year of follow-up. All patients had normal serum albumin, liver enzyme and hemoglobin levels. 33.3% of patients had low serum ferritin level and 33.3% had a vitamin D deficiency. Conclusions: Most of our children with CD grew normally both in height and weight during GFD. Significant catch-up growth occurred in some of them after 2 years of being on GFD. Those with low BMI-SDS and/or Ht-SDS needed further management, including reinforcement on the importance of GFD and investigations on factors affecting growth pattern. Measuring weight gain /day appears to be a sensitive indicator for monitoring growth in these children. Vitamin D and iron status should be monitored, and deficiencies corrected. (www.actabiomedica.it)

Association of Height Growth in Puberty with Lung Function. A Longitudinal Study.

Rationale: Puberty may influence lung function, but the precise role of pubertal height growth in lung development is unclear.Objectives: To examine associations of timing of puberty and peak velocity of pubertal height growth with lung function in adolescence and early adulthood.Methods: Longitudinal analyses of repeat height measurements from age 5 to 20 years for a British birth cohort with 4,772 males and 4,849 females were conducted to characterize height growth trajectories and to derive pubertal age and peak height velocity using the validated SITAR (SuperImposition by Translation and Rotation) model. Association of these estimates with prebronchodilator and post-bronchodilator spirometry measures: FEV1; FVC; FEV1/FVC; FEF25-75% at age 15 and 24 years were investigated using multivariable regression models adjusted for lung function at age 8 years, height and age at time of outcome measurements, and potential confounders.Measurements and Main Results: Later pubertal age and greater peak velocity were associated with higher FEV1 and FVC at 24 years in both sexes. A 1-year increase in pubertal age was associated with a 263-ml higher FVC (95% confidence interval [CI], 167-360 ml) for males (n = 567) and 100-ml (95% CI, 50-150 ml) higher FVC for females (n = 990). A 1-cm/yr increase in peak velocity was associated with 145-ml (95% CI, 56-234 ml) and 50-ml (95% CI, 2-99 ml) increases in FVC for males and females, respectively. No associations were found with FEV1/FVC.Conclusions: Later onset and greater peak velocity of height growth in puberty are associated with increased FEV1 and FVC in young adults but there was no evidence of dysanapsis of pubertal lung growth.

Comparison of effectiveness of growth hormone therapy according to disease-causing genes in children with Noonan syndrome.

PurposeTo analyze the growth response to growth hormone (GH) therapy in prepubertal patients with Noonan syndrome (NS) harboring different genetic mutations.MethodsTwenty-three patients with prepubertal NS treated at Pusan National University Children’s Hospital between March 2009 and July 2017 were enrolled. According to the disease-causing genes identified, the patients with NS were divided into 4 groups. Three groups were positive for mutations of the PTPN11, RAF1, and SOS1 genes. The five genes undetected (FGU) group was negative for PTPN11, RAF1, SOS1, KRAS, and BRAF gene mutations. The influence of genotype was retrospectively analyzed by comparing the growth parameters after GH therapy.ResultsThe mean chronological age at the start of GH treatment was 5.85±2.67 years. At the beginning of the GH treatment, the height standard deviation score (SDS), growth velocity (GV), and lower levels of insulin-like growth factor-1 (IGF)-1 levels were not statistically different among the groups. All the 23 NS patients had significantly increased height SDS and serum IGF-1 level during the 3 years of treatment. GV was highest during the first year of treatment. During the 3 years of GH therapy, the PTPN11, RAF1, and SOS1 groups showed less improvement in height SDS, IGF-1 SDS, and GV, and less increase in bone age-to-chronological age ratio than the FGU group.ConclusionThe 3-year GH therapy in the 23 prepubertal patients with NS was effective in improving height SDS, GV, and serum IGF-1 levels. The FGU group showed a better response to recombinant human GH therapy than the PTPN11, RAF1, and SOS1 groups.

Analysis of the influencing factors of recombinant human growth hormone effect in the children with Turner syndrome

Objective: To analyze the clinical data, karyotype, growth hormone receptor (GHR) exon 3 polymorphism, etc. in Turner syndrome before and after recombinant human growth hormone (rhGH) treatment, and thereby to understand the related factors influencing the rhGH curative effect in children with Turner syndrome. Methods: This was a retrospective study of 31 cases with Turner syndrome who were treated with growth hormone for more than 1 year in the pediatric outpatient department of Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology from January 2010 to January 2017. The GHR Exon3 polymorphism was detected by PCR assay, Turner syndrome children were divided according to GHR exon3 genotype for homozygous for the full-length GHR isoform (fl/fl-GHR)and carriers of one or two copies of the GHR exon3 allele(fl/d3-GHR;d3/d3-GHR).According to the karyotype, the children were divided into 45,X karyotype group and other karyotype group. The height standard deviation (Ht-SDS) and growth velocity (GV) as indicators to measure rhGH treatment efficacy, the data were analyzed by the SPSS12.0 software (t test, one-way ANOVA and multiple linear regression analysis). Results: (1) The mean age at diagnosis of 31 cases was (12.2±2.9) years, the bone age was (8.9±2.4) years, the height was (126.2±10.5) cm and the Ht-SDS was (-3.5±1.3) SDS. The karyotype was 45,X in 14 patients, 17 cases had other karyotypes. Thirteen cases were of (fl/fl-GHR) (42%), 14 cases of fl/d3-GHR (45%) and 4 cases of d3/d3-GHR(13%).Among the 31 cases, the main reason for 5 patients' hospitalization was no secondary sexual characteristics, another 26 cases had short stature (accounting for 81%).(2) After Growth hormone treatment, growth rate (cm/year)(7.3±1.4, 7.0±3.0, 7.0±1.3) and Ht-SDS (-2.8±1.2, -2.5±0.9, -2.2±0.8) were significantly higher than the pre-treatment levels (2.9±0.9, -3.5±1.3), the difference was statistically significant (F=54.12, 4.43, P<0.05) ; the third year Ht-SDS(-2.2±0.8)higher than the first year Ht-SDS(-2.8±1.2), the difference was statistically significant (t=-2.3, P<0.05) .(3)Before rhGH treatment, the height of 45,X karyotype group was significantly lower than that of other karyotypes ((122.1±9.1) cm vs. (129.9±10.3) cm, t=-2.2, P<0.05)). Before and after rhGH treatment, there was no significant difference in growth rate (cm/year) and Ht-SDS, between 45, X karyotype group and other karyotype group, but with the prolongation of treatment time, the Ht-SDS of other karyotype groups had an improvement trend compared with the 45,X karyotype groups. (4) After short-term and long-term treatment with rhGH, there were no significant differences in GV, Ht-SDS between patients with different genotypes (P>0.05). (5) Multivariate linear regression analysis showed that ΔHt-SDS was negatively correlated with the age at initial treatment(partial regression coefficient=-0.098, P <0.05), and positively correlated with GV before treatment(partial regression coefficient=0.202, P<0.05). Conclusions: In Turner's syndrome children, the earlier the rhGH treatment started, the faster the growth rate before treatment and the longer treatment duration, the better effect of rhGH treatment was obtained. Before rhGH treatment, the height of 45,X karyotype group was significantly lower than that of other karyotypes. Before and after rhGH treatment, there was no significant difference in growth rate (cm/year) and Ht-SDS, but with the prolongation of treatment time, the Ht-SDS of other karyotype groups had an improvement trend compared with the 45,X karyotype groups. GHR exon 3 polymorphism did not significantly affect the efficacy of rhGH in Turner syndrome children, but large-scale long-term studies are still needed.

Growth velocity of children and its affective factors in northwestern Iran: A longitudinal study using marginal models.

Background: Child growth is an important health indicator in human’s lifespan. Evaluating growth variations in infants and children is highly important. This study was conducted to evaluate the risk factors of child growth retardation and determine childhood growth velocity in Zanjan province, Iran. Methods: This longitudinal study was conducted on 7892 children aged 0 to 2 years in Zanjan province in 2013. The sampling method was multi-stage cluster sampling. To determine the growth velocity, 2- pointed model was used. We applied the marginal models of generalized equation estimators (GEE). The related curves were obtained using LOWESS method, and data were analyzed using R Version 2.14.1. Results: In this study, 3879 (49%) of the participants were female, and the mean age of mothers was 27.1±5.4 years. Growth velocity had a significant association with gender, mother’s residency, multiple pregnancies, gestational age, and exclusive breastfeeding (p<0.001). A significant association was observed between gender and weight growth velocity (p<0.001). Moreover, exclusive breastfeeding had a significant association with weight growth velocity (p<0.001). Conclusion: Growth velocity in girls was slightly higher than in boys, however, no considerable difference was found between height growth velocity of girls and boys. The findings of this study also indicated that each month increase in exclusive breastfeeding leads to less growth velocity in children. So, exclusive breastfeeding is strongly recommended to prevent childhood obesity.

Comparison of statural height growth velocity at different cervical vertebral maturation stages

Knowledge of a patient's stage of growth and development plays a vital role in diagnosis, treatment planning, results, and stability of the outcome. Cervical vertebral maturation (CVM) predicts the stage of growth and development, but its validity has only been investigated restrospectively, using historic samples. Our objective was to assess prospectively whether a correlation exists between CVM stage and statural height growth velocity. Participants were aged between 8 and 18years and of both sexes. Standing height was measured every 6weeks with participants barefoot and in natural head position. CVM stage was assessed from lateral cephalograms taken at the start of treatment. Intraobserver and interobserver reliability of CVM staging and statural height measurements were assessed using the Cohen weighted kappa, percentage of agreement, intraclass correlation coefficient, and Bland-Altman plots, respectively. Analysis of variance was used to test for statistically significant differences between growth velocities at the CVM stages. We analyzed 108 participants. The peak in statural height growth velocity occurred at CVM stage 3 (P=0.001). There was a statistically significant difference in the mean annualized growth velocity between all CVM stages except stages 2 and 4. Girls had their peak pubertal growth spurt an average of 1.2years earlier than did boys. This study suggests that there is a significant relationship between CVM stage and statural height velocity.

The effect of early growth patterns and lung function on the development of childhood asthma: a population based study

BackgroundInfant weight gain is associated with lower lung function and a higher risk of childhood asthma. Detailed individual childhood growth patterns might be better predictors of childhood respiratory morbidity than...

A degradation fragment of type X collagen is a real-time marker for bone growth velocity.

Despite its importance as a key parameter of child health and development, growth velocity is difficult to determine in real timebecause skeletal growth is slowand clinical tools to accurately detect very small increments of growth do not exist. We report discovery of a marker for skeletal growth in infants and children. The intact trimeric noncollagenous 1 (NC1) domain of type X collagen, the markerwe designated as CXMfor Collagen X Marker, is a degradation by-product of endochondral ossification that is released into the circulation in proportion to overall growth plate activity. Thismarker corresponds to the rate of linear bone growth at timeofmeasurement. Serumconcentrations of CXMplotted against age showa pattern similar to well-established height growth velocity curves and correlate with height growth velocity calculated from incremental height measurements in this study. The CXM marker is stable once collected and can be accurately assayed in serum, plasma, and dried blood spots. CXMtestingmay be useful for monitoring growth in the pediatric population, especially responses of infants and children with genetic and acquired growth disorders to interventions that target the underlying growth disturbances. The utility of CXM may potentially extend to managing other conditions such as fracture healing, scoliosis, arthritis, or cancer.