Salvatore Seminara

Catch-Up Growth in Short-at-Birth NICU Graduates

The statural catch-up growth, defined as reaching at least tenth length/height percentile (P10) for normal population standards (–1.28 SD score, SDS), was studied in 73 infants short at birth (length < P10 for gestational age) admitted to NICU. Mean gestational age at birth was 35.2 weeks (range 29–41) and mean birth length standard deviation score –2.31 (–4.52/–1.46). Infants were measured at birth, at 3, 6, 12, 18, and 24 months corrected age and then once a year until 6 years chronological age. Statural catch-up growth was studied, with reference both to normal population standards and to individual genetic target. With reference to normal population standards, 44% of infants had caught-up at 3 months of age, 51% at 3 years, 66% at 4 years and 73% at 6 years. In the case of individual genetic targets, a similar trend was present, but the absolute values were slightly higher from 4 to 6 years (73 vs. 66% and 78 vs. 73%, respectively). Statistically significant changes in mean standard deviations score for chronological age were present from birth to 3 months, 3 to 12 months, 3 to 4 years and 5 to 6 years (p < 0.05). No differences were found in this trend of recovery when considering ponderal index (PI) at birth (symmetrical vs. asymmetrical), sex (male vs. female) or gestational age (p > 0.05). In the majority of cases infants with short stature at birth admitted to a NICU had a statural catch-up growth within the first years of life. This is more evident when considered in relation to individual genetic target rather than to normal population standards.

Effect of long-term growth hormone treatment on carbohydrate metabolism in children with growth hormone deficiency

Growth hormone (GH) has well known effects on carbohydrate metabolism. We have evaluated the effects of long‐term growth hormone (GH) therapy on carbohydrate metabolism in children with classical GH deficiency (GHD) or GH neurosecretory dysfunction (GHND)

Normal energy intake range in children with chronic nonspecific diarrhea: association of relapses with the higher level.

An increase in energy intake often occurs at weaning. The increase may be due partly to prompting by the caregiver to accelerate the childs weight gain and partly motivated by the palatability of common weaning foods. Increased food intakes initiated during weaning and continued into the second year of life may be associated with chronic, nonspecific diarrhea in selected children. An educational project was designed to reduce intakes augmented by either cause. Reductions were achieved by the regulation of energy-dense foods in the childs diet and reliance on the childs appetite control to determine meal size. The educational intervention was applied prospectively under nonblinded, controlled conditions. Children, 1 to 2 years of age, with chronic nonspecific diarrhea were assigned randomly to either a treatment or control group. Compliance, food consumption, preprandial glycemia, and outdoor activities were reported by the childrens mothers in four 7-day diaries; symptoms related to the childrens clinical condition and anthropometric and biochemical indices of nutritional status were noted at the beginning and end of a 7-month period. Forty-four of 53 children in the experimental group maintained compliance, and 44 of 47 children in the control group completed the follow-up. Energy intake decreased significantly by almost one-third in the experimental group. Growth, skinfold thickness measurements, and outdoor activities were similar between experimental and control groups over the 7-month period. Diarrheal episodes occurred in 6, 1, and 2 children in the experimental group at 1.5, 3, and 7 months and in 22, 18, and 15 children in the control group, respectively (p < 0.002). Twenty of 32 parameter of clinical status were more advantageous in the experimental group compared to 9 of 32 in the control group in a comparison of the mean values in the two groups at the final examination (p < 0.05). Serum folate (p < 0.001) also was significantly higher in the experimental group. The described intervention appeared to achieve lower energy intakes in a safe and reproducible manner. It may be a useful tool to prevent overeating and control signs and symptoms associated with chronic, nonspecific diarrhea.

Determinants of Vitamin D Levels in Italian Children and Adolescents: A Longitudinal Evaluation of Cholecalciferol Supplementation versus the Improvement of Factors Influencing 25(OH)D Status.

Objective. This paper aims to assess 25(OH)D levels in Italian children and adolescents identifying risk factors for 25(OH)D deficiency and to evaluate whether a normal 25(OH)D value can be restored in 25(OH)D-deficient patients. Methods. We evaluated 25(OH)D levels in 679 Italian children and adolescents (≤10, 11–20, 21–30, and >30 ng/mL were defined as severe deficiency, deficiency, insufficiency, and sufficiency, resp.). Of these, 365 25(OH)D-deficient were followed up for 1 year; 205 were treated with cholecalciferol (Arm A: 400 I.U.) and 160 by improving the environmental variables influencing 25(OH)D levels (Arm B). Results. At cross-sectional evaluation, 11.3% showed sufficiency, 30.0% insufficiency, and 58.7% 25(OH)D deficiency. Mean 25(OH)D was 19.08 ± 8.44 ng/mL. At the enrollment time (T 0), no difference was found between Arms A and B with respect to distribution and 25(OH)D levels. At end time (T 1) 26.0% (29.7% in Arm A versus 20.6% in Arm B) showed sufficiency, 38.4% (42.0% versus 34.4%) insufficiency, and 35.6% (28.3% versus 45.0%) 25(OH)D deficiency. Mean 25(OH)D level was 23.71 ± 6.83 ng/mL. Conclusions. Neither changes of lifestyle nor 400 I.U. cholecalciferol supplementation alone appears to be sufficient to restore adequate 25(OH)D levels.

Determinants of vitamin d levels in children and adolescents with down syndrome.

Background. Poor studies have evaluated 25-hydroxycholecalciferol (25(OH)D) levels in Down syndrome (DS). Objective. To assess in DS subjects serum 25(OH)D value, to identify risk factors for vitamin D deficiency, and to evaluate whether a normal 25(OH)D value can be restored with a 400 I.U. daily supplement of cholecalciferol in respect to controls. Methods. We have longitudinally evaluated 31 DS patients (aged 4.5–18.9 years old) and 99 age- and sex-matched healthy controls. In these subjects, we analysed calcium, phosphate, parathyroid hormone (PTH), 25(OH)D concentrations, and calcium and 25(OH)D dietary intakes, and we quantified outdoor exposure. After 12.3 months (range 8.1–14.7 months) of 25(OH)D supplementation, we reevaluated these subjects. Results. DS subjects showed reduced 25(OH)D levels compared to controls (P < 0.0001), in particular DS subjects with obesity (P < 0.05) and autoimmune diseases history (P < 0.005). PTH levels were significantly higher in DS subjects than controls (P < 0.0001). After cholecalciferol supplementation, 25(OH)D levels were significantly ameliorated (P < 0.05), even if reduced compared to controls (P < 0.0001), in particular in DS subjects with obesity (P < 0.05) and autoimmune diseases (P < 0.001). Conclusions. Hypovitaminosis D is very frequent in DS subjects, in particular in presence of obesity and autoimmune diseases. In these subjects, there could be a need for higher cholecalciferol supplementation.

Williams-beuren syndrome is a genetic disorder associated with impaired glucose tolerance and diabetes in childhood and adolescence: new insights from a longitudinal study.

Background: In adults with Williams-Beuren syndrome (WBS), a common endocrine abnormality is type 2 diabetes mellitus (T2DM) or impaired glucose tolerance (IGT). However, few and sporadic data are available in children, adolescents, and young adults with WBS. Aim: To evaluate the frequency of IGT and T2DM in a cohort of children and young patients with WBS. Patients and Methods: We longitudinally evaluated 27 patients (9 males and 18 females, median age at study onset 13.6 years) with WBS. The median follow-up was 3.6 years. Variables of insulin resistance and β-cell function were evaluated in all subjects using an oral glucose tolerance test. The homeostasis model assessment (HOMA) of insulin resistance and the Matsuda index of insulin sensitivity were calculated. The study of the GCK and HNF1Α genes was performed in patients with glucose metabolism abnormalities. 45 age- and sex-matched healthy subjects and 51 age-, sex- and BMI-matched subjects were recruited as two control groups. Results: Considering nutritional status, 7 (25.9%) patients were obese, 9 (33.3%) overweight, and 11 (40.8%) normal-weight. One (3.1%) patient had acanthosis nigricans. IGT was diagnosed in 7 (25.9%) WBS patients and T2DM in 3 (11.1%). Considering all WBS patients, the median value of HOMA was 5.23 (range 2.93-14.89; insulin 24.73 ± 14.67 μU/ml; glucose 104.98 ± 16.06 mg/dl). Considering BMI values, HOMA was 11.00 (range 6.53-12.56), 5.64 (range 3.54-7.95), and 4.54 (range 3.21-5.43), and insulin was 34.53 ± 6.84, 22.76 ± 8.91, and 19.47 ± 6.01 μU/ml in obese, overweight, and normal-weight WBS patients, respectively. Comparing the results with the two control groups, WBS patients showed higher insulin values than healthy controls (p < 0.001), but similar values as the BMI-matched control group (p = n.s.). However, WBS patients showed significantly higher values of glycemia (healthy control group, p < 0.001; BMI-matched control group, p < 0.05) and HOMA (healthy control group, p < 0.001; BMI-matched control group, p < 0.05) than the two control groups. Finally, among WBS patients there was a higher number of subjects with IGT and T2DM than among healthy controls (p < 0.0001) and the BMI-matched control group (p = 0.0002). Conclusion: Our data strongly suggest that IGT and T2DM may be frequently discovered in children, adolescents, and young adults with WBS. WBS should be included among the genetic syndromes associated with T2DM. Further studies are necessary to evaluate the etiopathogenesis of this aspect.

Oral Clonidine Provocative Test in the Diagnosis of Growth Hormone Deficiency in Childhood: Should We Make the Timing Uniform?

Introduction: Oral clonidine is one of the most frequent drugs used for the diagnosis of growth hormone deficiency (GHD), but the duration of the test, depending on which European centres use it, is not uniform and can vary from 120 to 150 min or even 180 min. Subjects and Methods: To standardize this test, evaluating the possibility to shorten it to 90 min, we investigated the response of GH to the oral clonidine test in 291 children evaluated for short stature (height <–2 SD). Of these, 164 were diagnosed as idiopathic short stature (ISS) and 127 as GHD. In these patients, we calculated: (1) the frequency distribution of the GH peaks to clonidine in GHD and in ISS at various times; (2) the percentage of GH peaks to clonidine before and after 90 min in all and in ISS children; (3) the percentage of the first GH value ≧10 ng/ml before 90 min and after 90 min in ISS. Results: GH peak distribution varied between 30 and 180 min, even though the vast majority of peaks occurred between 30 and 60 min. There was no significant difference (p > 0.05) in the peak distribution between ISS and GHD children. The percentages of GH peaks within 90 min were 92.1% in all children and 95.7% in ISS. If considering the first value of GH ≧10 ng/ml this last percentage reaches 96.3%. Conclusion: Our study suggests that the oral clonidine test can be administered for only 90 min without significantly changing its validity. This test should be standardized at 90 min in European protocols just as in those currently used in the USA in order to reduce the discomfort of patients and the cost of this diagnostic procedure.

Dopamine Infusion and Anterior Pituitary Gland Function in Very Low Birth Weight Infants

Background: Previous studies demonstrated that dopamine infusion reduces plasma concentration of thyroxine (T4), thyroid stimulating hormone (TSH), prolactin (PRL), and growth hormone (GH) in adults, children, and infants. Objectives: The purpose of this prospective observational study was to evaluate the relationship between dopamine infusion and the dynamics of T4, TSH, PRL, and GH in preterm newborns weighing less than 1,500 g (very low birth weight infants, VLBW) admitted in a neonatal intensive care unit of a university hospital over a one year period. Methods: A total of 97 preterm newborns were enrolled and divided into two groups: group B included hypotensive infants treated with plasma expanders and dopamine infusion; group A was the control group including newborns who were never treated with dopamine. The newborns were studied dynamically through blood samples taken every day till 10 days. Newborns of group B were studied during dopamine infusion and after its withdrawal. Results: Among the VLBW newborns who were given dopamine, the four pituitary hormones had different dynamics: a reduction of T4, TSH, and PRL levels was noticed since the first day of treatment, and a rebound of their levels was evident since the first day after its interruption. On the contrary, the postprandial GH levels were roughly constant: GH plasma concentrations were in fact a little lower in newborns treated with dopamine, and a slight increase was observed after its withdrawal. However, observed differences were not statistically significant. Conclusions: The results suggest that dopamine infusion reduces T4, TSH, and PRL plasma levels in preterm VLBW infants and have no effect on postprandial GH rate. This hormonal suppression reverses rapidly after dopamine withdrawal. This observation suggests that the iatrogenic pituitary suppression probably cannot produce long-term injuries.

Parathyroid Hormone Levels in Healthy Children and Adolescents

Background: Parathyroid hormone (PTH) is important in the assessment of calcium metabolism disorders. However, there are few data regarding PTH levels in childhood and adolescence. Aim: The aim of this study was to determine PTH levels in a large group of healthy children and adolescents. Patients and Methods: We retrospectively evaluated PTH levels in 1,580 healthy Caucasian children and adolescents (849 females, 731 males, aged 2.0-17.2 years) with 25-hydroxyvitamin D [25(OH)D] levels ≥30 ng/ml. All subjects with genetic, endocrine, hepatic, renal, or other known diseases were excluded. Results: The serum intact PTH concentration (median and inter-quartile range) was 23.00 (15.00-31.60) pg/ml. In our population, the mean 25(OH)D value was 34.27 ± 4.12 ng/ml. The median PTH concentration in boys was 23.00 (15.00-32.00) pg/ml, whereas in girls it was 23.10 (15.00-31.10) pg/ml. However, in girls, PTH levels significantly increased in the age group of 8.1-10.0 years compared to the age group of 2.1-4.0 years (p < 0.0001), whereas in boys it significantly increased in the age groups of 10.1-12.0 years (p < 0.0001) and 12.1-14.0 years (p < 0.0001), leading to the hypothesis of a relationship between PTH level and pubertal and bone growth spurts. Conclusions: PTH levels in healthy children and adolescents covered a narrower range than the adult values. Obtaining reference values of PTH in childhood and adolescence could aid in the estimation of appropriate values of bone metabolites.

The ever-expanding conundrum of primary osteoporosis: aetiopathogenesis, diagnosis, and treatment

In recent years, as knowledge regarding the etiopathogenetic mechanisms of bone involvement characterizing many diseases has increased and diagnostic techniques evaluating bone health have progressively improved, the problem of low bone mass/quality in children and adolescents has attracted more and more attention, and the body evidence that there are groups of children who may be at risk of osteoporosis has grown. This interest is linked to an increased understanding that a higher peak bone mass (PBM) may be one of the most important determinants affecting the age of onset of osteoporosis in adulthood. This review provides an updated picture of bone pathophysiology and characteristics in children and adolescents with paediatric osteoporosis, taking into account the major causes of primary osteoporosis (PO) and evaluating the major aspects of bone densitometry in these patients. Finally, some options for the treatment of PO will be briefly discussed.