Effect of Nutritional Supplementation on Growth in Short and Lean Prepubertal Children after 1 Year of Intervention.

OBJECTIVE: To determine the 1-year effectiveness and safety of nutritional supplementation with the study formula on linear growth and weight gain in short and lean prepubertal children and to validate the previously reported findings in those initially treated with placebo. STUDY DESIGN: Two-phase 1-year intervention (double-blind placebo-controlled [0-6 months] and open-labeled extension [6-12 months]) in which all participants were offered to continue the study using the study formula. Anthropometric measures and 3-day food diary were assessed at baseline and after 6 and 12 months of intervention. RESULTS: A total of 129 out of 150 children (86%) completed the open-labeled extension-phase. In "good" consumers of the formula (intake ≥50% of recommended dose) throughout the entire year height-SDS continued to improve in the extension phase, with a total gain of 0.19 ± 0.14 SD. In "good" consumers of the formula initially randomized to the placebo-group, the gain in height-SDS significantly improved (from 0.04 ± 0.13 to 0.12 ± 0.11; P = .001), replicating the results of the "good" consumers of the formula during the blinded-phase (0.12 ± 0.12). "Poor" consumers (intake <50% of recommended dose) did not improve their height-SDS. No significant changes in body mass index SDS were observed with the consumption of the formula. A dose-response was found between the amount of formula consumed/kg and the increment in height-SDS and weight-SDS (r = 0.36; P < .001 and r = 0.18; P = .041, respectively). No serious adverse events were reported. CONCLUSIONS: One year of a nutritional supplement was effective in promoting the linear growth of short and lean prepubertal children, with no change in body mass index status. TRIAL REGISTRATION: ClinicalTrials.gov:NCT01158352.

Thyroid Functions in Healthy Infants during the First Year of Life.

OBJECTIVE: To study the pattern of thyroid function testing in healthy newborns during the first year of life. STUDY DESIGN: We used the computerized database of a health management organization. Among the 18,507 infants insured by the Clalit Health Services born in the Sheba Medical Center between 2002 and 2007, 652 full-term healthy newborns with birth weight >2 kg and no significant perinatal morbidity underwent thyrotropin (TSH) determination as outpatients in their first year of life. The Clalit Health Services database provided demographic data, laboratory results, and dispensed medications for the newborns and their mothers. RESULTS: Initial serum TSH levels were within normal range (0.35-5.5 mIU/L) in 91.1%, elevated (> 5.5-≤ 10 mIU/L) in 8.3%, and highly elevated (>10 mIU/L) in 0.6% of the studied cohort. The 97.5 and 2.5 percentile values were 7.4 and 0.74 mIU/L, respectively. TSH measurements were repeated in 34.2%, 72.2%, and 100% of children with normal, elevated, and highly elevated initial levels, respectively; results were normal in 96%, 74%, and 50% of patients with initial normal, elevated, and highly elevated TSH, respectively; repeated TSH levels were > 97.5 percentile in 35% of patients with initial TSH > 97.5 percentile compared with 1% with first results < 97.5 percentile (P = .005). Only 4 (0.6%) of the 652 newborns included in the study received thyroxin treatment. CONCLUSION: The normal TSH levels found in most healthy infants with normal thyroid screening and the spontaneous normalization of TSH values below 7.4 mIU/liter, substantiate the reliability of the screening, reduce unnecessary work-up and unnecessary thyroxin treatment of neonates meeting these criteria.

Effect of a nutritional supplement on growth in short and lean prepubertal children: a prospective, randomized, double-blind, placebo-controlled study.

OBJECTIVE: To determine the effect of nutritional supplementation on height, weight, and body mass index (BMI) in short and lean prepubertal children. STUDY DESIGN: A prospective, randomized, double-blinded, placebo-controlled trial of nutritional supplementation at the endocrinology department of a tertiary pediatric medical center of healthy, lean, short, prepubertal children 3-9-years-old. Anthropometry measurements were measured at 6 months. RESULTS: Two hundred participants (149 boys) entered the study and 171 (85.5%) completed the intervention period. Baseline characteristics including age, sex, height-SDS, weight-SDS, BMI-SDS, and dietary caloric and protein intakes were similar in the formula and placebo groups. 'Good' consumers (intake of ≥50% of the recommended dose) in the formula group significantly improved height-SDS (P < .001) and weight-SDS (P = .005) with no change in BMI-SDS compared with 'poor' consumers and the placebo group. In the formula-treated group a positive correlation was found between the amount of formula consumed per body weight and the gain in height-SDS (r = 0.44, P < .001) and weight-SDS (r = 0.35, P = .002); no significant correlations were found in the placebo group. No serious adverse events were reported during the study. CONCLUSIONS: Nutritional intervention with the formula was found to be a feasible, effective, and safe approach for promoting the physical growth of short and lean prepubertal children.

Interrelationship of extent of precocious adrenarche in appropriate for gestational age girls with clinical outcome.

OBJECTIVE: To assess the interrelationship between extent of adrenarche at presentation in girls with precocious adrenarche (PA) born appropriate for gestational age and their growth pattern, pubertal course and adult height. STUDY DESIGN: We reviewed clinical and laboratory data from medical charts of 85 girls with PA aged 5.0 to 8.8 years at referral, stratified in 3 subgroups according to bone age (BA) minus chronological age (CA) ≤0 years; 0 1 year. RESULTS: Extent of pubarche and dehydroepiandrosterone-sulfate levels were greatest in the BA-CA >1 subgroup (P=.02, P=.008, respectively), who also were taller at diagnosis (P=.002) and during childhood (P=.01). In all subgroups, pubertal onset was within normal range; menarche occurred earlier than in control subjects (P<.02); all attained adult height within their mid-parental height range. Predicted adult height was overestimated in girls with BA ≤CA (P=.04) and underestimated with BA-CA >1 (P<.001). CONCLUSIONS: Although a more pronounced adrenarche and BA advancement at diagnosis in girls with PA born appropriate for gestational age had an impact on their pre-pubertal growth pattern, it was not associated with early and rapid progression of puberty or reduced adult height. This reassuring clinical course indicates that PA is a benign condition, irrespective of the extent of adrenarche at presentation. Adult height prediction is unreliable in PA.

Premature thelarche: age at presentation affects clinical course but not clinical characteristics or risk to progress to precocious puberty.

OBJECTIVES: To determine whether age at premature thelarche (PT) onset affects the clinical characteristics, course, and risk of progression to precocious puberty (PP). STUDY DESIGN: Data regarding course of growth and puberty were retrieved from the medical files of 139 girls with PT followed up from 1995 to 2005. Analysis was based on age at PT appearance (birth, 1-24 months, and 2-8 years); course was categorized as regressive, persistent, progressive, or cyclic. RESULTS: At diagnosis, height standard deviation score, bone age-chronological age ratio, and hormonal values were comparable in the 3 age groups. PT regressed in 50.8%, persisted in 36.3%, progressed in 3.2% and had a cyclic course in 9.7%. A progressive or cyclic course was significantly more prevalent among girls presenting after 2 years (52.6%) compared with girls presenting at birth (13.0%) or at 1 to 24 months (3.8%) (P < .001). PP occurred in 13% irrespective of age at PT presentation or clinical course. CONCLUSIONS: Clinical and anthropometric characteristics at admission and risk of PP were similar in all girls with PT, regardless of age at onset. There are currently no clinical or laboratory tests that can predict the risk of progression to PP at presentation.

Differentiated thyroid carcinoma in pediatric patients: comparison of presentation and course between pre-pubertal children and adolescents.

OBJECTIVE: To evaluate the clinical characteristics, course, and outcome of differentiated thyroid carcinoma (DTC) in pre-pubertal children compared with adolescents. STUDY DESIGN: The records of 10 pre-pubertal and 17 pubertal patients in whom DTC was diagnosed and who were observed in our tertiary pediatric endocrine clinic were reviewed. Extension of tumor at presentation, treatment modality, course, and outcome were analyzed. RESULTS: A positive family history of DTC was more prevalent in the pre-pubertal group (P = .037). At diagnosis, they had a greater degree of extrathyroid extension (P = .012), lymph node involvement (P = .009), and lung metastases (P = .009). The extent of surgery was similar in both groups, whereas the weight-adjusted radioiodine (I(131)) ablative dose was higher in the pre-pubertal group (P = .004). During the median follow-up of 5 years, the overall survival rate was 100% for both groups, with no significant difference in evidence of residual tumor after initial therapy or the recurrence rate. CONCLUSION: DTC has a more aggressive presentation in pre-pubertal children. Rigorous initial surgical and I(131) treatment, followed by thyrotropin suppression, was found to result in an outcome similar to that achieved in the pubertal group.