Height Z-score Research Articles

Fluoxetine and Sertraline Inhibit Height Growth and Growth Hormone Signaling During Puberty.

The aim of this study was to examine the effect of fluoxetine and sertraline on height growth and insulin-like growth factor-1 (IGF-1) during puberty. In this 6-month cohort study, electronic medical records were used to identify 8- to 15-year-old participants, within 1 month of starting fluoxetine (n = 39) or sertraline (n = 27), and sexual maturation stages 2 to 4 were confirmed. Conditions that interfere with height growth led to exclusion. Participants underwent anthropometric assessments and phlebotomy. Healthy, unmedicated children (n = 36) also provided anthropometric data. After the baseline height Z-score, sex, Tanner stage, daily selective serotonin reuptake inhibitor (SSRI) dose, and time were accounted for, the interaction effect of dose by time was inversely associated with height Z-score in SSRI-treated participants (β = -0.18; 95% confidence interval [CI]: -0.35, -0.02). Sertraline and fluoxetine did not differ in their effect on height growth. Compared with being unmedicated, SSRI treatment was associated with a smaller growth in height (time × dose 2-way interaction effect β = -1.30; 95% CI: -2.52, -0.09). The interaction effect of dose by time was significant for body mass index Z-score (β = 0.35; 95% CI: 0.06, 0.64) but not weight Z-score (β = 0.24; 95% CI: -0.01, 0.49). Body mass index Z-score increased more with sertraline compared with fluoxetine (time × dose × SSRI type 3-way interaction effect P < 0.05). SSRI dose was inversely associated with IGF-1 (β = -63.5; 95% CI: -112.2, -14.7) but not insulin growth factor binding protein-3 concentration (β = -207.3; 95% CI: -536.2, 121.5). Fluoxetine and sertraline reduce height gain and IGF-1 concentration, in a dose-dependent manner. Longer-term studies are necessary.

7795 Gender based differences in peripubertal growth patterns may offer insight into the twofold representation of boys compared to girls among children referred for growth hormone stimulation tests

Abstract Disclosure: Y. Dekel: None. L. Horowitz : None. R. Gendelman: None. M. Cohen: None. Background: Growth hormone (GH) stimulation tests are essential in the diagnostic assessment of pediatric GH deficiency (GHD). However, the tests bare multiple limitations, resulting from both intrinsic and child-related factors. Thus, referral decisions are key in making a correct diagnosis. Several studies demonstrated a gender bias in referral for short stature evaluation with a higher proportion of boys referred and diagnosed with GHD. Moreover, the boys had higher height z-scores upon referral. About 100 GH stimulation-tests are conducted annually at our pediatric endocrinology unit. We aimed to characterize the children that underwent GH stimulation-testing between 2017-2021, specifically focusing on differences based on: 1) gender 2) GH secretion status (deficient vs. sufficient). Methods: A retrospective review of charts of children aged 0-18 years that performed GH stimulation-tests at the Rambam pediatric endocrinology unit between the years 2017-2021 was conducted. Children followed at an outside clinic that had a first GH stimulation-test elsewhere, were excluded. Data was collected through the electronic database and by manually screening medical charts. The IBM SPSS statistics package 21 version was used for analysis. Results: Four-hundred children were included in the study, 266 boys (66.5%) and 134 girls (33.5%). Mean age 8.8±4.2 years, mean height z-score -2.3±0.7 and mean mid-parental height standard-deviation-scores (MPH-SDS) -0.6±0.7. The mean difference between MPH-SDS and child height-z-score was 1.7±0.8 SDS. Mean age was younger in girls compared with boys, 7.3±3.3 and 9.6±4.4 years respectively (p&amp;lt;0.001). Age distribution differed between genders, while refferals peaked between 3-4 years of age in both girls and boys, a second peak at 13-14 years of age was evident only in boys. Interestingly, there was no significant difference between boys and girls in height z-score, difference from MPH-SDS or rates of GHD. Overall, 93 (23.3%) children were diagnosed with GHD, 32 girls (24%) and 61 boys (23%). Children with GHD were younger and had higher BMI-SDSs compared to GH sufficient children, age 7.8±3.8, 9.2±4.3 years respectively (p=0.003), BMI z-score 0.17±1.38, -0.47±1.15 respectively (p&amp;lt;0.001). Conclusion: Twice as many boys than girls were referred for GH stimulation tests in our cohort. Based on differences in age distribution, the peripubertal physiologic growth deceleration that occurs later in boys, likely contributes to this finding. This male-to-female ratio is similar to ratios reported in the literature regarding short stature referrals; however, in contrast to the literature, in our cohort it could not be explained by an anthropometric bias in referral criteria. Presentation: 6/3/2024

7673 Genetic Analysis and Clinical Characterization of Patients with Congenital Hypopituitarism Due to Gene Defects

Abstract Disclosure: T.M. Sasson: None. I.J. Arnhold: None. B.B. Mendonca: None. L.R. Carvalho: None. Introduction: Congenital hypopituitarism is characterized by the deficiency of one or more hormones secreted by the anterior pituitary gland. The genetics of this pathology is complex, and the molecular diagnosis is established in approximately 13% of cases. Objectives: The aim of the present study is to characterize the phenotype harboring pathogenic variants causing congenital hypopituitarism. Methods: Among 393 subjects with congenital hypopituitarism followed up at a tertiary health center, 57 subjects (14,5%) were selected due to a confirmed molecular diagnosis by exome in 9 subjects or by gene panel or Sanger sequencing in 48 subjects. This was a retrospective study where data from medical records, clinical, laboratory and radiological characteristics were analyzed. Results: The most frequent variants identified by sequencing analyzes were in the following genes: PROP1 (29.8%), GH1 (22.8%), GHRHR (15.7%), followed by GLI2, OTX2, HESX1, POU1F1, TGIF1, GHRS, CDH2, SATB1, SOX3 e LZTR1. Consanguinity was reported in 50% of cases, and there was the presence of familial cases of short stature in 60%. The average age at the start of follow-up was 11.1 years (11 SD), 40% of them were male and 52.3% had physical stigmata typical of GH deficiency. Regarding hormonal deficiencies, 27 (47%) had isolated Growth Hormone Deficiency (DGHI) and the others, multiple deficiencies. MRI study of the pituitary gland showed some alteration in 66%, 54% of whom had adenohypophysis hypoplasia and 31% had an ectopic or non-visualized neurohypophysis. From 29 patients with IGF-1 levels available, 28 were below the reference range for sex and age. The serum GH peak after the stimulus test was on average 1.28 ng/mL (1.4SD), of these, only 4 cases had GH peak between 3.3 and 5.0 ng/mL and 1 patient with low IGF-1 and an ectopic neurohypophysis had GH peak of 6.0 ng/mL in a glucagon test. Regarding growth, the initial height in z-score was -4.8 and the average growth at the end of the first year of treatment was 10.7cm, with the average height after this period of Z-3.35. The average of final delta target height (final height Z-score minus the target height Z-score) of patients who underwent hormonal treatment was -0,53 (good response = delta &amp;lt;-1.5). Conclusion: In subjects with congenital hypopituitarism and an established molecular diagnosis, the most frequently affected genes were PROP1 and GH1, the great majority presented a stimulated GH peak &amp;lt; 3.3 ng/mL (only one patient had GH &amp;gt; 5), low basal serum IGF-1 and good increase in growth speed at the end of the first year of treatment with recovery of final height at the end of GH therapy. Presentation: 6/3/2024

8304 Growth trajectories of children born preterm and full-term with low birth weight to preschool ages; a nationwide study

Abstract Disclosure: E. Kang: None. J. Cha: None. J. Na: None. S. Ryu: None. Y. Choi: None. J. Kim: None. Context: Children born preterm (PT) and full-term with low birth weight (FT-LBW) are known to be at considerable risk of poor growth outcomes. Objective: To investigate the growth trajectories of children born PT and FT-LBW from birth to preschool ages. Methods: A total of 1,150,508 newborns were included in the study, comprising 41,454 children born PT and 38,250 children born FT-LBW, who participated in the first three rounds (4-6, 9-12, 18-24 months) of the National Health Screening Program for Infants and Children (NHSPIC). Growth measurements were obtained from the NHSPIC database and converted into the Z-scores. Growth data at two, four, and six years of age were measured as outcome variables. The impact of being born small on poor growth outcomes was investigated using a generalized estimating equation and Cox proportional hazards regression analysis. Results: The median birth weight of three groups was 2.3kg for PT, 2.4kg for FT-LBW, and 3.2kg for FT control group, respectively. The incidence of short stature defined as height Z-score &amp;lt; -2 standard deviation score (SDS) and failure to thrive (BMI Z-score &amp;lt; -2 SDS) was highest in FT-LBW group, followed by the PT group, and control group. At four years of age, the incidence rates were 6.0% vs. 5.2% vs. 1.9% for short stature and 4.6% vs. 3.9% vs. 1.7% in FTT. The β estimate of height outcome was lower in both the PT and FT-LBW groups with -0.326 SDS in PT and -0.456 SDS in FT-LBW group. Conclusion: The FT-LBW group was consistently shorter and lighter throughout the preschool period than the PT group. This highlights the significance of growth monitoring in high-risk populations. Presentation: 6/3/2024

6471 Adult Height in Male Survivors of Childhood Cancer Treated with Aromatase Inhibitors and Growth Hormone

Abstract Disclosure: N.I. Pollock: None. M. Song: None. A. Wolf: None. Y. Li: None. C. Hawkes: None. N. Motamedi: None. M.R. Denburg: None. S. Mostoufi-Moab: None. Title: Adult Height in Male Survivors of Childhood Cancer Treated with Aromatase Inhibitors and Growth Hormone Objectives: Aromatase inhibitor (AI) therapy in combination with growth hormone (GH), or as monotherapy, may have a role in improving height outcomes in male pediatric patients with GH deficiency (GHD). The effectiveness of AI therapy in the childhood cancer survivors is not known. In this retrospective study, we assess adult height (AH) in childhood cancer survivors treated with AI combined with GH therapy compared to those treated with GH alone. Methods: This was a single center retrospective cohort study of male survivors of childhood cancer treated with GH for diagnosis of GHD between 2007 and 2023. We compared AH outcomes in males treated with GH alone or in combination with off-label use of AI. Demographic and clinical characteristics, including anthropometric measurements, endocrinopathies, and cancer history, were obtained from the medical record. AH was noted as height documented at fusion of growth plates or following 18 years of age. Differences in demographic, clinical, and treatment characteristics were assessed using univariate tests of association. Multivariable regression with stepwise selection was used to examine risk factors associated with AH. All statistical analyses were performed using Stata 18.0. Results: Ninety-two patients were included; 70 were treated with GH monotherapy and 22 with combination AI/GH. Median age at AI initiation was 13.6 years (IQR 12.3-14.3) versus 11.2 years (IQR 8.6-12.9) for GH (unpaired t-test p-value &amp;lt;0.01; 95% CI -4.01, -1.91). A greater proportion of patients in the AI/GH group had been treated with stem cell transplantation, abdominal radiation, total body irradiation, and cis-retinoic acid (Fisher’s exact p-value &amp;lt;0.01). There was no statistically significant difference in AH or AH Z-score between treatment groups, with the median AH Z-score in the AI/GH group -1.95 (IQR -3.11, -0.75) versus -1.39 (IQR -2.65, 0.11) in the GH group. In multivariable linear regression, history of radiation to the spine (β= -5.9, 95% CI -11.2, -0.6), height Z-score (β= 0.3, 95% CI 0.11, 0.46), BMI Z-score (β= 3.2, 95% CI 0.95, 5.5), and advanced bone age at GH or AI treatment initiation (β= -10.1, 95% CI -17.3, -2.9) were significantly associated with AH. Conclusions: Adjunctive treatment with AI and GH was not associated with increased AH outcomes in male survivors of childhood cancer compared to GH monotherapy. Future work is needed to determine optimal adjunctive medical therapy to maximize FAH impacted by cancer therapy for this patient population. Presentation: 6/3/2024

6805 Impact of Feeding Types on Catch-Up Growth in Early Infancy Among Small-for-Gestational-Age Infants: A Nationwide Korean Study

Abstract Disclosure: J. Choi: None. Y. Choe: None. S. Yang: None. Purpose: The study aimed to compare growth patterns and catch-up growth (CUG) in small-for-gestational-age (SGA) infants up to age four, based on feeding type during the first 4-6 months, using nationwide data. Methods: A total of 42,295 children born SGA (21,917 boys, 52.%) who underwent the first (4-6 month), 2nd (9-12 month), 3rd (18-24 month) and 5th (42-48 month) National Health Screening Program for Infants and Children (NHSPIC) under the National Health Insurance Service from 2007 to 2014 were included. The study population was categorized into two groups based on the primary milk feeding type recorded in the self-reported questionnaire during the first round of NHSPIC: the ”Breastfed”group, and the "Formula-fed" group. Catch-up growth (CUG) was defined as a Height Standard Deviation Score (Ht SDS) of 3rd percentile or above at the 5th NHSPIC visits. We used propensity scores to 1:1 match breastfed and formula-fed group based on sex, birth weight, cesarean section, socioeconomic status, residance. Multivariate logistic regression analysis was performed to evaluate the effect of milk feeding type on CUG at 4 years of age. Results: 49.1% of infants (n = 20,774) were breastfed and 50.9% (n = 21,521) were formula-fed. The median birth weight was 2.7 kg (interquartile range: 2.5-2.9 kg), and 98.7% of the children (n = 41,752) achieved CUG by the 5th NHSPIC round. Following propensity score matching, both groups included 19,308 infants. At four years of age, the breastfed group showed a lower likelihood of achieving CUG compared to the formula-fed group (aOR 0.794, 95% CI 0.665-0.948). During the 1st NHSPIC round, the breastfed group had a significantly lower weight Z-score (mean: -0.05, range: -0.64 to 0.41) than the formula-fed group (mean: 0.14, range: -0.42 to 0.78, p &amp;lt; 0.001). This trend was more pronounced from the 1st to 2nd round, with greater decreases in both weight and height Z-scores for the breastfed group (weight difference: -0.36, range: -0.74 to 0.02; height difference: -0.21, range: -0.62 to 0.20) compared to the formula-fed group (weight difference: -0.17, range: -0.53 to 0.20; height difference: -0.13, range: -0.53 to 0.28, p &amp;lt; 0.001). However, from the 2nd round, the breastfed group demonstrated faster gains in both weight and height (p &amp;lt; 0.001). Conclusion : In a study of Korean SGA infants, those breastfed during the first 4-6 months post-birth had lower CUG rates at four years compared to formula-fed infants. The breastfed group exhibited less weight and height gain, especially between the 1st and 2nd NHSPIC rounds, aligning with the initial phase of solid food introduction. These findings may suggest the need for enhanced nutritional supplementation for breastfed SGA infants. Further research is necessary to explore other factors that may impact growth during this critical developmental period. Presentation: 6/3/2024

Potential effects of attention deficit hyperactivity disorder medication on body height and body weight in a longitudinal pediatric cohort study, the LIFE Child study.

Purpose: To investigate the potential impact of drugs for the treatment of attention deficit hyperactivity disorder (ADHD) on body weight and height in children and adolescents from the LIFE ('Leipzig Research Centre for Civilization Diseases', Leipzig, Germany) Child cohort. Methods: We included 2,115 participants aged ≥6 to <18.25 years who attended the LIFE study center between 2011 and 2020 in our analysis, of whom 48 used ADHD drugs. Anthropometric and medication data from baseline to the third follow-up visit were available for 659 participants. Body height and body weight measurements were subsequently converted to z-scores. A repeated measures analysis of variance (ANOVA) was performed on the z-scores of both ADHD drug users and non-users to determine potential trends in body weight and body height from baseline to the 3 rd annual follow-up. Results: At the last visit with ADHD drug use of the 48 ADHD drug users, 40% (19/48) of the children and adolescents were below the 25 th reference percentile for weight. Z-scores for body height declined from baseline to the 3rd annual follow-up in individuals who used ADHD drugs (n=10; Differencemeans =-0.310; p=0.002) compared to non-users (n=649; Differencemeans =0.102; p<0.001). Body weight also decreased from baseline to 3rd follow-up in the ADHD drug group (n=10; Differencemeans =-0.473; p<0.001) compared to the non-user group (n=649; Differencemeans =0.015; p=0.161). Conclusion: We observed a potential tendency towards lower Z-scores for body height and body weight in individuals taking ADHD medication for an extended period compared to the corresponding age- and sex-matched populations.

Effect of chorioamnionitis on postnatal growth in very preterm infants: a population-based study in Japan.

There is growing evidence that preterm infants born to mothers with chorioamnionitis (CAM) have increased risk of various neonatal morbidities and long-term neurological disorders; however, the effect of CAM on postnatal growth remains insufficiently investigated. This study evaluated the effect of histological CAM on postnatal growth trajectories in very preterm infants using a nationwide neonatal database in Japan. A multicenter retrospective study was conducted using clinical data of 4220 preterm neonates who weighed ≤ 1500g and were born at < 32weeks of gestation between 2003-2017 (CAM group: n = 2110; non-CAM group: n = 2110). Z-scores for height and weight were evaluated at birth and 3years of age. Univariable and multivariable analyses were conducted to evaluate the effect of histological CAM on ΔZ-scores of height and weight during the first three years with a stratification by infant sex and the stage of histological CAM. Multivariable analyses showed that histological CAM was associated with accelerated postnatal increase (ΔZ-score) in weight (β coefficient [95% confidence interval]; 0.10 [0.00 to 0.20]), but not in height among females (0.06 [- 0.04 to 0.15]) and not in height and weight among males (0.04 [- 0.04 to 0.12] and 0.02 [- 0.07 to 0.11], respectively). An interaction analysis demonstrated no significant difference in the effect of histological CAM on the ΔZ-scores of height and weight during the first three years between male and female infants (height, p = 0.81; weight p = 0.25). Intrauterine exposure to maternal CAM contributes to accelerated postnatal weight gain in female preterm infants during the first three years.

Moderate-to-vigorous physical activity modulates the association between serum 25-hydroxyvitamin D and bone stiffness in European children and adolescents

It remains unclear how serum 25-hydroxyvitamin D (25(OH)D) concentrations relate to childhood bone health. We hypothesized that 25(OH)D was inversely associated with bone turnover biomarkers and positively associated with bone stiffness. Cross-sectional analyses were performed using data from participants (2-15-year-old, 51% boys) from the IDEFICS/I.Family cohort, comprising 3,638 serum 25(OH)D measurements collected in 2007/2008 and 2012/2013 across eight European countries. A biomarker of bone formation (serum osteocalcin), a biomarker of bone resorption (serum C-terminal telopeptides of type I collagen [CTx]), and stiffness index measured using calcaneal quantitative ultrasound were considered outcomes. Linear mixed-effects models were used to adjust for confounders (i.e., age, sex, parental education, time spent in sports club, dairy products consumption, sedentary behavior, height and weight z-scores), the cluster effect of country and repeated measurements. Interactions of calcium intake, moderate-to-vigorous physical activity (MVPA) and weight status with 25(OH)D on outcomes were tested. Only 1 in 3 participants reached the sufficient 25(OH) D concentration of 20 ng/ml. Sufficient 25(OH)D was associated with higher stiffness index if participants had MVPA ≥ 60 min/day (β = 12.14, p < 0.05). Moreover, 25(OH)D was inversely associated with CTx (β = -7.09, p < 0.05); this association was positive but not statistically significant among primary school children living with overweight/obesity. No interaction was observed for calcium intake. In conclusion, serum 25(OH)D and CTx were inversely associated. MVPA interacted the positive association between 25(OH)D and bone stiffness, highlighting the importance of promoting MVPA guidelines in future vitamin D and bone health interventions.

357P Correlation between height, weight, and body mass index z-scores and clinical outcome assessments in young boys with Duchenne muscular dystrophy

357P Correlation between height, weight, and body mass index z-scores and clinical outcome assessments in young boys with Duchenne muscular dystrophy

Bone Accrual Trajectories in Children and Adolescents with Perinatal HIV Infection.

Low bone mineral density (BMD) has been reported in children and adolescents living with perinatally-acquired HIV (PHIV). Little is known about their bone accrual through puberty compared to an uninfected healthy cohort. To compare bone accrual in PHIV and healthy children. PHIV children aged 7-16 years had dual energy X-ray absorptiometry (DXA) at entry, 2 years, and then at least 2 years later. Bone accrual was compared to healthy children from the Bone Mineral Density in Childhood Study (BMDCS). United States academic clinical research centers. 172 PHIV; 1321 BMDCS. We calculated height-adjusted whole-body and spine BMD and bone mineral content (BMC) Z-scores in PHIV using BMDCS reference curves. We fit piecewise weighted linear mixed effects models with change points at 11 and 15 years, adjusted for age, sex, race, height Z-score, and Tanner stage, to compare BMD and BMC Z-scores across actual age by cohort.Main Outcome Measure: BMD/BMC Z-scores. Height-adjusted whole-body BMD and BMC Z-scores in PHIV were lower across age compared to BMDCS children. Spine BMD Z-score across age was higher in PHIV after height adjustment. Whole-body and spine bone area tended to be lower in PHIV. PHIV had slower accrual in whole-body and spine bone area before 14 years. After 15 years, bone area accruals were similar, as were height-adjusted spine BMC Z-scores, across age. PHIV had persistent deficits in all measures except height-adjusted spine BMD and BMC Z-scores. Data are needed on PHIV followed to adulthood.

Different growth patterns in two siblings with Schimke immuno-osseous-dysplasia.

Schimke immuno-osseous-dysplasia (SIOD) is an autosomal recessive systemic disease due to pathogenic variants in SMARCAL1. Manifestations include nephrotic syndrome (NS), kidney failure, T-cell dysfunction, vaso-occlusive disease, and disproportionate short stature, a general feature of this disease. Here, we present a markedly different growth pattern in two brothers with SIOD sharing the same homozygous R561C missense variant. The index patient presented at the age of 11years with NS and severely disproportionate short stature, followed by kidney failure at the age of 16, and severely reduced adult height (z-score - 8.0). In contrast, the younger brother showed normal growth until the age of 8years. Mild proteinuria was noted at the age of 4.5, followed by NS at 9.5years, kidney failure at 11years, progressive disproportionate stature, and reduced adult height (z-score - 4.5). Both brothers had comparable disproportion in adulthood (sitting height index z-score - 0.88 and - 1.44, respectively).

Impact of X-linked hypophosphatemic rickets/osteomalacia on health and quality of life: baseline data from the SUNFLOWER longitudinal, observational cohort study.

The SUNFLOWER study was initiated in Japan and South Korea to clarify the course of X-linked hypophosphatemic rickets/osteomalacia (XLH); delineate its physical, mental, and financial burdens; and collect information on treatment. Here, we report cross-sectional data at the time of patient enrollment to better understand the real-world management and complications in patients with XLH and examine the effect of XLH on quality of life (QOL). This is an ongoing, longitudinal, observational cohort study of patients with a diagnosis of XLH. Data from 147 patients (118 in Japan and 29 in South Korea) were evaluated. In total, 77 children (mean age, 9.7yr; 67.5% female) and 70 adults (mean age, 37.6yr; 65.7% female) were enrolled. PHEX gene mutations were confirmed in 46/77 (59.7%) children and 37/70 (52.9%) adults. Most patients in both age groups were receiving a combination of phosphate and active vitamin D at baseline. The mean height Z-score was -2.21 among adults (male: -2.34; female: -2.14). The mean Rickets Severity Score in children was 1.62. Whereas children appeared to have low pain levels (mean revised faces pain scale score, 1.3), adults reported mild-to-moderate pain (mean Brief Pain Inventory pain severity, 2.02). Mean QOL in children (assessed using the 10-item short-form health survey for children) was low, with a score below normative level for physical functioning. In adults, results from the Western Ontario and McMaster Universities osteoarthritis index indicated the presence of pain, stiffness, and decreased physical function. The respective mean total days/year of work/school non-attendance due to symptoms/complications and management of XLH were 0.7 and 3.0 among adults, and 6.4 and 6.1 among children. Our findings reconfirmed a relationship between disease and QOL in patients with XLH. We anticipate that these data will be important in enabling clinicians to understand the daily reality of patients with XLH.

Persistent growth-promoting effects of vosoritide in children with achondroplasia are accompanied by improvements in physical and social aspects of health-related quality of life

Purpose: Evaluate the impact of vosoritide on health-related quality of life in children with achondroplasia. MethodsParticipants received vosoritide (15 μg/kg/day) in an extension trial (NCT03424018) after having participated in a placebo-controlled trial (NCT03197766). ResultsThe population comprised 119 participants (mean [SD] age 9.7 [2.6] years). Mean treatment duration was 4 (0.78) years. At year 3, the largest mean (SD) changes were observed in the Quality of Life of Short Stature Youth physical score (5.99 [19.41], caregiver reported; 6.32 [20.15], self-reported) and social score (2.85 [8.29] and 6.76 [22.64], respectively). Changes were greatest in participants with ≥1 SD increase in height z-score (physical: 11.36 [19.51], caregiver-reported [n = 38]; 8.48 [21.83], self-reported [n = 28]) (social: 5.84 [15.45] and 9.79 [22.80], respectively). To determine how domain scores may change with age in untreated persons, models were produced using observational/untreated-person data. A 1-year increase in age was associated with a change of 0.16 (SE, 0.55) and 0.16 (0.50), for caregiver-reported physical and social domain scores, respectively. Self-reported scores changed by 1.45 (0.71) and 1.92 (0.77), respectively. ConclusionThese data suggest that after 3 years of treatment, vosoritide demonstrates a positive effect on physical and social functioning among children with achondroplasia, particularly in children with a more pronounced change in height z-score.

Clinical significance of sarcopenia in children with neuroblastic tumors

PurposeTo elucidate the clinical significance of sarcopenia in children with neuroblastic tumors (NTs).MethodsWe conducted a retrospective observational study and analyzed the z-scores for height, body weight, body mass index, and skeletal muscle index (HT-z, BW-z, BMI-z, and SMI-z) along with the clinical characteristics of 36 children with NTs. SMI-z was calculated from 138 computed tomography scans at diagnosis, during treatment, and at follow-up. The International Neuroblastoma Risk Group classification was used to identify high-risk groups. We analyzed the data at diagnosis for prognostic analysis and changes over time after diagnosis in the HT-z, BW-z, BMI-z, and SMI-z groups.ResultsAmong the four parameters at diagnosis, only SMI-z predicted overall survival (hazard ratio, 0.58; 95% confidence interval, 0.34–0.99). SMI-z, HT-z, and BW-z significantly decreased over time after diagnosis (P < 0.05), while BMI-z did not (P = 0.11). In surviving high-risk NT cases without disease, SMI-z, HT-z, and BW-z significantly decreased over time (P < 0.05), while BMI-z did not (P = 0.43).ConclusionIn children with NT, the SMI-z at diagnosis was a significant prognostic factor and decreased during treatment and follow-up along with HT-z and BW-z. Monitoring muscle mass is important because sarcopenia may be associated with growth impairment.

Nephrocalcinosis and kidney function in children and adults with X-linked hypophosphatemia: baseline results from a large longitudinal study.

In patients with X-linked hypophosphatemia (XLH), conventional therapy with oral phosphate salts and active vitamin D has been associated with nephrocalcinosis. However, the nature of the relationships among XLH, its treatment, nephrocalcinosis, and kidney function remain poorly understood. Renal ultrasounds were performed and glomerular filtration rates were estimated (eGFR) at baseline in burosumab-naïve patients with XLH who participated in burosumab clinical trials (NCT02181764, NCT02526160, NCT02537431, NCT02163577, NCT02750618, NCT02915705) or enrolled in the XLH Disease Monitoring Program (XLH-DMP; NCT03651505). In this cross-sectional analysis, patient, disease, and treatment characteristics were described among patients with and without nephrocalcinosis. The analysis included 196 children (mean [SD] age 7.6 [4.0] yr) and 318 adults (40.3 [13.1] yr). Mean (SD) height z-score was -1.9 (1.2) for children and -2.3 (1.7) for adults. Nearly all children (97%) and adults (94%) had previously received conventional therapy. Nephrocalcinosis was detected in 22% of children and 38% of adults. In children, reduced eGFR <90mL/min/1.73m2 was more prevalent in those with nephrocalcinosis (25%) than in those without (11%), a finding that was not observed in adults. Children with nephrocalcinosis had lower mean values of TmP/GFR (p<.05), serum 1,25(OH)2D (p<.05), and eGFR (p<.001) and higher mean serum calcium concentrations (p<.05) than did those without nephrocalcinosis. Adults with nephrocalcinosis had lower mean serum phosphorus (p<.01) and 1,25(OH)2D (p<.05) concentrations than those without. Exploratory logistic regression analyses revealed no significant associations between the presence of nephrocalcinosis and other described patient or disease characteristics. Nephrocalcinosis was observed in nearly one-quarter of children and more than one-third of adults with XLH. Further study is needed to better understand the predictors and long-term consequences of nephrocalcinosis, with surveillance for nephrocalcinosis remaining important in the management of XLH.

Macrophage-Stimulating 1 Polymorphism rs3197999 in Pediatric Patients with Inflammatory Bowel Disease.

Background and Objectives: Inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), often necessitates long-term treatment and hospitalizations and also may require surgery. The macrophage-stimulating 1 (MST1) rs3197999 polymorphism is strongly associated with the risk of IBD but its exact clinical correlates remain under investigation. We aimed to characterize the relationships between the MST1 rs3197999 genotype and the clinical characteristics in children and adolescents with IBD within a multi-center cross-sectional study. Materials and Methods: Clinical data included serum C-reactive protein (CRP), albumin, activity indices (PUCAI, PCDAI), anthropometric data, pharmacotherapy details, surgery, and disease severity. Genotyping for rs3197999 was carried out using TaqMan hydrolysis probes. Results: The study included 367 pediatric patients, 197 with Crohn's disease (CD) (40.6% female; a median age of 15.2 years [interquartile range 13.2-17.0]) and 170 with ulcerative colitis (UC) (45.8% female; a median age of 15.1 years [11.6-16.8]). No significant relationships were found between MST1 genotypes and age upon first biologic use, time from diagnosis to biological therapy introduction, PUCAI, PCDAI, or hospitalizations for IBD flares. However, in IBD, the height Z-score at the worst flare was negatively associated with the CC genotype (p = 0.016; CC: -0.4 [-1.2-0.4], CT: -0.1 [-0.7-0.8], TT: 0.0 [-1.2-0.7)]). The TT genotype was associated with higher C-reactive protein upon diagnosis (p = 0.023; CC: 4.3 mg/dL [0.7-21.8], CT 5.3 mg/dL [1.3-17.9], TT 12.2 mg/dL [3.0-32.9]). Conclusions: This study identified links between MST1 rs3197999 and the clinical characteristics of pediatric IBD: height Z-score and CRP. Further studies of the associations between genetics and the course of IBD are still warranted, with a focus on more extensive phenotyping.

Regional Disparities in Growth Patterns of Children with Cerebral Palsy: A Comparative Analysis of Saudi Arabian, UK, and US Data.

In order to understand the global variations in the growth trajectories of cerebral palsy patients, this study aimed to compare the growth patterns of cerebral palsy patients in Saudi Arabi with United States and United Kingdom counterparts. Anthropometric data from 107 participants with cerebral palsy in Saudi Arabia were collected, including age, gender, cerebral palsy type, Gross Motor Function Classification System level, birth weight, weight at assessment, height at assessment, body mass index, and head circumference at assessment. This study found discrepancies between the growth patterns of Saudi Arabian children with cerebral palsy and United Kingdom and the United States growth charts, particularly among those with severe cerebral palsy. Significant differences were observed in weight, height, and body mass index z-scores when comparing Saudi Arabian data with the United kingdom and United States reference data. These findings emphasize the importance of validating growth charts across different populations to ensure accurate monitoring and clinical management of children with cerebral palsy. Additionally, this study highlights the need for region-specific growth references to better address the diverse needs of individuals with cerebral palsy worldwide.

Burosumab Efficacy and Safety in Patients with X-Linked Hypophosphatemia: Systematic Review and Meta-analysis of Real-World Data.

To assess the efficacy and safety of burosumab in children and adults with X-linked hypophosphatemia based on real-world evidence. MEDLINE (via PubMed) and Cochrane Library were searched until 18 October 2023 for single-arm (before-after) studies. Registries including Clinicaltrials.gov, EU Clinical Trials, WHO International Clinical Trials Registry Platform, and conference abstracts. The outcomes were a change in serum phosphorus concentrations and change in RSS, a change in serum ALP, bone-specific ALP, a change in the ratio of Tubular maximum reabsorption of Phosphate to Glomerular Filtrate rate, a change in serum 1,25(OH)2D and 25(OH)2D concentrations, change in height Z-score, McMaster Universities Osteoarthritis Index (WOMAC) and safety outcomes. An inverse variance random-effects meta-analysis was applied for data synthesis. Fifteen studies (289 participants) were included. Burosumab treatment improved serum phosphate concentrations [mean difference 0.88mg/dl, 95% confidence interval 0.70 to 1.07, I2 = 92%), Rickets Severity score (mean difference -1.86, 95% confidence interval -2.5 to -1.21, I2 = 71%), serum alkaline phosphate concentrations (mean difference -1.86, 95% confidence interval -2.5 to -1.21, I2 = 71%), serum 1,25(OH)2D concentrations (mean difference 18.91pg/ml, 95% confidence interval 6.39 to 31.43, I2 = 96%) and renal phosphate reabsorption (mean difference 1.22 mg/dl, 95% confidence interval 0.70 to 1.74, I2 93%). Burosumab treatment improved overall clinical and laboratory findings in patients with X-linked hypophosphatemia.

The effect of Lactobacillus reuteri on pulmonary function test and growth of cystic fibrosis patients.

Cystic fibrosis (CF) patients frequently experience gut microbiota dysbiosis. Probiotic supplementation is a potential therapeutic approach to modify gut microbiota and improve CF management through the gut-lung axis. The aim of this study was to investigate the effect of Lactobacillus reuteri supplementation on pulmonary function test, respiratory symptoms and growth in CF patients. A randomized, placebo-controlled clinical trial was carried out on 40 children with CF aged from 6 to 20 years. Participants were designated to receive either L. reuteri or placebo daily for 4 months. Pulmonary function tests, weight, height and body mass index (BMI) z-scores were measured pre and post treatment. The median baseline BMI of the patients was 16.28 kg m-2. A significant change in the probiotic group's BMI z-score after the study period was observed (P = 0.034) but not for weight and height z-scores (P > 0.05). After treatment, Pseudomonas aeruginosa grew in sputum cultures of seven in the placebo and one patient in the intervention group (P = 0.03) while at baseline it grew in the sputum of four patients in each group. There was no significant difference in forced expiratory volume in the first second, forced expiratory flow at 25-75% or forced vital capacity change between the two groups after the treatment period (P > 0.05). Additionally, no significant differences were found in pulmonary exacerbations, hospitalization frequencies or COVID-19 infection between the two groups during the study (P > 0.05). The results suggest that L. reuteri supplementation may impact the growth of severely malnourished CF patients. Furthermore, it may be concluded that this strain might reduce P. aeruginosa in the sputum culture of CF patients. © 2024 Society of Chemical Industry.