Increased risk of group B streptococcal sepsis and meningitis in HIV-exposed uninfected infants in a high-income country.

The purpose of this study is to compare group B Streptococcus (GBS) infection incidence in HIV-exposed uninfected (HEU) and HIV-unexposed (HU) infants in a Spanish cohort. We conducted a retrospective study in 5 hospitals in Madrid (Spain). Infants ≤ 90 days of life with a GBS infection were included from January 2008 to December 2017. Incidence of GBS infection in HEU and HU children was compared. HEU infants presented a sevenfold greater risk of GBS infection and a 29-fold greater risk of GBS meningitis compared to HU, with statistical significance. Early-onset infection was tenfold more frequent in HEU children, with statistical significance, and late-onset infection was almost fivefold more frequent in the HUE infants' group, without statistical significance. CONCLUSION: HEU infants presented an increased risk of GBS sepsis and meningitis. One in each 500 HEU infants of our cohort had a central nervous system infection and 1 in each 200, a GBS infection. Although etiological causes are not well understood, this should be taken into account by physicians when attending this population. WHAT IS KNOWN: • HIV-exposed uninfected infants are at higher risk of severe infections. • An increased susceptibility of these infants to group B Streptococcus infections has been described in low- and high-income countries, including a higher risk of meningitis in a South African cohort. WHAT IS NEW: • Group B Streptococcal meningitis is more frequent in HIV-exposed uninfected infants also in high-income countries. • Physicians should be aware of this increased risk when attending these infants.

Imported malaria in children in Madrid, Spain, 2007-2013.

BACKGROUND: The majority of malaria cases diagnosed in Europe in the last few years have occurred in people living in non-endemic areas travelling back to their home country to visit friends and relatives (VFRs). Children account for 15-20% of imported malaria, with known higher risk of severe disease. MATERIAL AND METHODS: A retrospective multicentre study was conducted in 24 hospitals in Madrid (Spain) including patients under 16 years diagnosed with malaria (2007-2013). RESULTS: A total of 149 episodes in 147 children were reported. Plasmodium falciparum was the species most commonly isolated. Twenty-five patients developed severe malaria and there was one death related to malaria. VFR accounted for 45.8% of our children. Only 17 VFRs had received prophylaxis, and 4 of them taken appropriately. They presented more frequently with fever (98% vs. 69%), a longer time with fever (55 vs. 26%), delay in diagnosis of more than three days (62 vs. 37%), and more thrombocytopenia (65 vs. 33%) than non-VFRs, and with significant differences (p<0.05). CONCLUSIONS: VFRs represent a large proportion of imported malaria cases in our study. They seldom took adequate prophylaxis, and delayed the visit to the physician, increasing the length of fever and subsequent delaying in diagnosis. Appropriate preventive measures, such as education and pre-travel advices should be taken in this population.

Pharmacogenomics of insulin-like growth factor-I generation during GH treatment in children with GH deficiency or Turner syndrome.

Individual responses to growth hormone (GH) treatment are variable. Short-term generation of insulin-like growth factor-I (IGF-I) is recognized as a potential marker of sensitivity to GH treatment. This prospective, phase IV study used an integrated genomic analysis to identify markers associated with 1-month change in IGF-I (ΔIGF-I) following initiation of recombinant human (r-h)GH therapy in treatment-naïve children with GH deficiency (GHD) (n=166) or Turner syndrome (TS) (n=147). In both GHD and TS, polymorphisms in the cell-cycle regulator CDK4 were associated with 1-month ΔIGF-I (P<0.05). Baseline gene expression was also correlated with 1-month ΔIGF-I in both GHD and TS (r=0.3; P<0.01). In patients with low IGF-I responses, carriage of specific CDK4 alleles was associated with MAPK and glucocorticoid receptor signaling in GHD, and with p53 and Wnt signaling pathways in TS. Understanding the relationship between genomic markers and early changes in IGF-I may allow development of strategies to rapidly individualize r-hGH dose.

Serum inhibin B levels before and after varicocelectomy in early adolescence.

BACKGROUND: Whereas no clear relationship has been observed between varicocelectomy and serum inhibin B levels in men, in adolescents comparison between inhibin B levels before and after varicocelectomy is lacking. AIM: To evaluate the effect of varicocele surgical treatment on inhibin B levels in adolescents at the beginning of puberty compared to a group of healthy adolescents. SUBJECTS AND METHODS: We studied 28 adolescents in Tanner 2 pubertal stage with a grade III left-sided varicocele (patients) compared to 13 age and pubertal stage-matched healthy adolescents (controls). All patients underwent blood tests to determine serum inhibin B levels before and 6 months after varicocelectomy by Palomo procedure. For comparison we investigated inhibin B levels in controls and repeated this test 6 months later. Testicular ultrasound was performed for patients only. RESULTS: Baseline inhibin B concentrations of patients and controls were 109.90 ± 40.26 and 109.33 ± 38.34 pg/ml, respectively. No significant changes were observed in patients' inhibin B concentrations after varicocelectomy (116.00 ± 42.65 pg/ml), or in controls during the 6 months' follow-up (99.12 ± 30.09 pg/ml). Doppler examination after treatment shows a complete resolution of varicocele in all the patients without alterations in testicular parenchyma. CONCLUSIONS: Varicocelectomy performed on adolescents at T2 pubertal stage might be useful to avoid alteration in inhibin B production and consequently in testicular function. Further studies are necessary to confirm the prognostic value of inhibin B levels and the benefit of early varicocelectomy in preserving the fertility of these adolescents.

Could the savory taste of snacks be a further risk factor for overweight in children?

INTRODUCTION: The quantity, type and composition of snack foods may play a role in the development and maintenance of obesity in children. A high consumption of energy-dense snacks may promote fat gain. AIMS: To assess the type and number of snacks consumed weekly by a large sample of 8- to 10-year-old children, as well as to assess its relationship with body size. RESULTS: The children consumed on average 4 snacks per day. There was no statistical difference in the number of servings per day between obese and nonobese children. However, the mean energy density of the foods consumed was significantly higher for obese and overweight children than for normal weight children [6.8 (0.3) kJ/g, 6.8 (0.16) kJ/g, and 6.3 (0.08) kJ/g, respectively; P < 0.05]. Logistic regression analysis showed that the energy density of the snacks (kJ/g), their savory taste (servings/week), television viewing (hours/day) and sports activity (hours/week) independently contributed to predict obesity in children. However, when the parents' body mass index was included among the independent variables of the regression, only salty foods and sports activity showed an independent association with childhood obesity. CONCLUSIONS: Parents' eating habits and lifestyle influence those of their children, as suggested by the association between parents' obesity and their children's energy-dense food intake at snacktime, the savory taste of snacks and sedentary behavior. However, regardless of parents' body mass index, the preference for savory snacks seems to be associated with overweight in prepubertal children.

A technique of mRNA extraction and labeling from circulating lymphocytes of children treated with growth hormone replacement therapy for microarray analysis.

GH replacement therapy exhibits a wide spectrum of response in terms of growth. Nevertheless, standardized doses are still given in clinical practice. In order to optimize the therapy, it is necessary to identify its markers of responsiveness. Given the presence of GH receptors in the circulating lymphocytes, accessible by means of a simple blood withdrawal, blood becomes the tissue of choice as a source of RNA for in vivo gene expression analysis. Hence, the purpose of the present paper is to develop a method of preparation of RNA from lymphocytes suitable for microarray analysis, focusing on the reduction of the blood volume withdrawal in order to perform the analysis on pediatric subjects. After lymphocyte isolation and total RNA extraction from 6 ml of blood, we carried out an amplification procedure preserving the relative abundance of each transcript. Thereafter, we hybridized the labeled amplified RNA on an oligo chip (Human 30K A, MWGBiotech), but the unsuccessful detection of a good signal to noise ratio indicates that labeled RNA is still insufficient. Therefore, we suggest performing pools of total RNA from different subjects with similar responsiveness to the therapy. It can be speculated that, upon comparison of the obtained data with those derived from pools of controls properly responding to the therapy, specific hallmarks of the condition of low responsiveness, devoid of inter-individual variability, will be evidenced.

[Late onset group B Streptococcus infection: 7 year experience in a tertiary hospital (2000-2006)]. / Infección tardía por estreptococo del grupo B: experiencia en un hospital de tercer nivel (2000-2006).

INTRODUCTION: Group B Streptococcus (GBS) is a major cause of neonatal infection. Two forms of the disease have been described according to the age of presentation: early, beginning in the first 6 days of life, and late, occurring from day 7 up to 3 months of age. OBJECTIVES: To analyze the epidemiology of the late onset form of GBS disease in a tertiary hospital after implementing preventive strategies aimed to reduce the rate of vertical transmission. METHODS: We retrospectively reviewed the medical records of children diagnosed with late GBS infection between January 2000 and December 2006. Diagnostic criteria included a positive blood culture and/or a positive cerebrospinal fluid (CSF) culture for GBS in any patient aged between 7 and 89 days. RESULTS: 24 patients were identified, most of them presenting after January 2005. Median age was 36.2 days (range 9 to 81). GBS isolates in blood were found in 20 patients, 1 in CSF and 3 in both. Most frequently children presented with fever (70.8 %) and irritability (54.1 %). Five patients (20.8 %) had a cellulitis-adenitis syndrome. Cefotaxime and ampicillin were the most often used antibiotic combination. No ampicillin resistances were found. CONCLUSIONS: The number of children with late GBS disease has increased in our center. Accordingly, the recent recommendations for the prevention of perinatal GBS vertical transmission were not effective for reducing late GBS infection. This may be due to horizontal infections from maternal sources, community or cross infections. It is important to maintain clinical suspicion of late GBS infection and start early antibiotic treatment.

[Attention deficit and hyperactivity disorder, a current problem]. / Trastorno por déficit de atención e hiperactividad: un problema actual.

INTRODUCTION: Attention deficit disorder and hyperactivity (ADDH), is a condition that affects the normal development of children. The symptoms include difficulty of controlling physical activity, inattention and learning disorders. The ADDH must be diagnosed in accordance with the clinical findings defined in the DSM IV. OBJECTIVE: To describe the epidemiology and clinical characteristics of children diagnosed with ADDH in our hospital. MATERIAL AND METHODS: Biannual observational study. Variables evaluated were: age, sex, personal and family medical history, symptoms, therapy and treatment response. RESULTS: There 83 participants (87 % Male and 13 % Female), of which 32.5 % were diagnosed during the study. Ages ranged from 3-8 years (84 %). There was a family history related to ADDH in 38 % of patients, and personal history of prematurity, acute foetal distress, small for gestational age, convulsions were reported. Association of hyperactivity and attention deficit was found in 65 % of participants. Other related symptoms were cognitive disorder (62 %), language disabilities (41 %) and motor disorders (35 %). Treatment was on-going in 65 % of the patients, 27.7 % of them having adverse effect. Evolution with therapy was favourable in 61 %. CONCLUSIONS: These findings suggest that ADDH is one of the most common childhood psychiatric disorders, mainly affecting boys. There is usually a family history. Failure in school was one of the principal conditions. Association between attention deficit and hyperactivity, mainly hyperactivity, is the most common presentation. Other disorders such as motor and language disabilities are also common in these patients. Methylphenidate showed favourable outcomes in 61 % of the patients studied.

Assisted infant toilet training: is it time for a critical revision?

Toilet training is an essential issue in child education, and its completion represents a developmental milestone. Although for the last 40 years the Western medical community has recommended to start toilet training after 18 months of age, today a growing number of parents are accepting assistant infant toilet training that can begin relatively soon after birth. As currently practiced, assisted infant toilet training emphasizes infant-caregiver communication for the gradual acquisition of bowel and bladder control. Signals emitted by the infant lead the caregiver during elimination assistance. This review will help the reader to understand this new phenomenon.

[Kingella kingae as a common cause of arthritis septic in children]. / Kingella kingae como agente causal frecuente de artritis séptica en Pediatría.

OBJECTIVE: Kingella kingae is a common colonizer of the oropharynx in children that may lead to invasive infection, mainly osteoarticular infections. Invasive infections occur almost exclusively in young children, fundamentally fewer than two years old. K. kingae infections in children are probably underdiagnosed due to the difficulty in growing in routine cultures and the absence of systematic realization of molecular techniques to identify it. It is the most common bacteria involved in childhood osteoarticular infections in recent series and increasingly being recognized in Spain. We report our experience on the epidemiological and clinical characteristics of osteoarticular infections in children in recent years. METHODS: Retrospective analysis of septic arthritis by K. kingae identified by PCR in joint fluid in children during 2010-2016. Epidemiological, clinical and laboratory characteristics are presented. RESULTS: Five arthritis by K. kingae were identified, all of them in ≤6 years old children. Median leukocytes, CRP and ESR were 12950 leukocytes/µL, 4.84 mg/dL and 58 mm/h respectively, and 61,322 leukocytes /µL in joint fluid. All patients evolved favorably. CONCLUSIONS: Osteoarticular infections by K. kingae in children usually present low increase of inflammatory markers despite being invasive infections. The development of PCR in sterile samples has greatly improved the diagnostic yield of K. kingae infections improving the management of osteoarthritis in children.

Lack of association between thyrotropin receptor gene polymorphisms and subclinical hypothyroidism in children.

Subclinical hypothyroidism is defined as a serum TSH level above the statistically set reference range, associated to normal free thyroid hormone concentrations. Genetic and environmental factors contribute to the inter- and intra-individual biological variations of TSH levels, sometimes leading to uncertainty of treatment in the clinical practice, especially when moderate elevations above the upper limit of the reference range are considered (5< TSH <10 mIU/l). In this view, the study of association between subclinical hypothyroidism and possible molecular effectors, such as polymorphisms in the TSH receptor (TSHR) gene, could be interesting. In this paper, we analyzed the TSHR gene polymorphisms in 103 hyperthyrotropinemic infants. A control group of 120 newborns of the same ethnic background was used to evaluate the frequencies of each polymorphism in the population. We found a statistically significant difference in the allelic frequency of the P52T polymorphism, being that the T variant was more represented in the control group (p=0.03). However, no significant results have been obtained in the analysis of the association between genotypes and serum TSH levels. In conclusion, we analyzed 7 polymorphic variants of TSHR gene in subclinical hypothyroidism. The only significant result refers to the allelic frequency of A in the P52T polymorphism, which is statistically reduced when compared with that of a control group.

Geometry and bone density.

Bone development is a key process in the growing child. It is, therefore, of paramount importance to survey this process, which is characterized by increasing length and size of the bone together with its progressive mineralization. The bone status can be evaluated by different techniques, each of them having its pros and cons. Furthermore, it should be underlined that the results of bone assessment depend not only from the employed technique but also from the auxological characteristics of the subjects. It is, therefore, the aim of this review to examine the characteristics of the various methods of bone evaluation, such as dual energy X-ray absorptiometry (DEXA), peripheral quantitative computed tomography (pQCT), ultrasound and metacarpal index and to explain how changes in bone structure and geometry may influence the results.

Nutrient oxidation during moderately intense exercise in obese prepubertal boys.

The aim of this study was to measure the nutrient oxidation rate during walking at different speeds and to identify the walking speed associated with the highest fat oxidation rate in a group of prepubertal boys with different levels of adiposity. Twenty-four prepubertal boys (age, 10 +/- 1 yr) with different levels of overweight (body mass index, 25.5 +/- 3.5 kg/m(2); sd score of body mass index, 3.4 +/- 1.1) performed a treadmill test. We measured by indirect calorimetry their respiratory exchange while they walked at speeds of 4, 5, and 6 km/h as well as their maximal oxygen uptake. The fat oxidation rate did not change significantly when the speed of walking was increased, whereas carbohydrate oxidation increased significantly (P < 0.001). A significant (P < 0.05) association was found between adiposity (percent fat mass) and the fat to carbohydrate oxidation ratio during walking at 4, 5, and 6 km/h (r = 0.37, r = 0.37, and r = 0.36, respectively), adjusting for exercise intensity (maximal oxygen uptake, percentage). The lowest fat to carbohydrate oxidation ratio, i.e. the highest fat oxidation/carbohydrate oxidation rate, was found at a walking speed of 4 km/h. Moderately intense exercise promoted the highest fat to carbohydrate oxidation ratio. Increasing the exercise intensity did not promote fat oxidation. Therefore, walking at a speed of 4 km/h is recommended as practicable exercise for obese boys and, consequently, for the treatment of childhood obesity.

Genetic analysis carried out on blood-spots of phenylalanine hydroxylase-deficient newborns detected by northeastern Italian neonatal screening.

The aim of this work was to perform genetic analysis on 18 different blood-spot samples collected from neonates detected as hyperphenylalaninemic by Northeastern Italian screening program. DNA was extracted from blood-spots. Exons/introns of PAH gene were amplified by polymerase chain reaction (PCR), and PCR products were purified and sequenced with both forward and reverse primers. The most frequent mutations were IVS12nt1g>a (16.7%) and R408W, P281L and L48S (all together 11.1%). As expected, compound heterozygosity was the usual finding; homozygosity was found only in two patients with R158Q and IVS2nt5g>c mutations. The V230I mutation was reported for the first time in Italy. We found six previously described polymorphisms (V245V, IVS4nt47c>t, IVS2nt19t>c, IVS3nt-22c>t, IVS5nt-54a>g, and E280>Q280). To our knowledge, four genotypes were not previously described: R158Q/V230I present in one patient with classical PKU; and L48S/R408Q, A403V/IVS2nt-13t>g, and G272X/V230I present in patients showing HPA phenotype. Most of the mutations were located in the exons 12 and 7 and in exon/intron 2 (83.3% detection of total mutations in PKU or HPA patients of Northeastern Italy). From a practical viewpoint, the genetic analysis of blood-spots collected on Guthrie cards for neonatal screening for PKU could be a simple method to establish the genotype of neonates. Consequently, the genotype/phenotype correlation could lead to a more accurate diagnosis and prognosis for families.

The risk of diabetes mellitus in children born small for gestational age and treated with recombinant growth hormone.

Children born small for gestational age (SGA) are known to be at risk for both short stature and type 2 diabetes mellitus in later life. To evaluate the influence of recombinant growth hormone (rhGH) therapy on insulin sensitivity, 24 children born SGA were treated with GH at traditional doses, from 0.23 mg/kg/week (group A) to 0.46 mg/kg/week (group B). We evaluated glycosylated haemoglobin, basal glucose and insulin levels before and 1 and 2 years after GH therapy. The homeostasis model assessment (HOMA) index was used to evaluate insulin sensitivity. After 2 years of GH therapy, glycosylated haemoglobin and basal glucose did not change significantly. Insulin sensitivity fell, but still remained within the normal range. In conclusion, 2-year GH therapy had beneficial effects in SGA children without changes in glucose homeostasis. Moreover, the insulin sensitivity reduction did not correlate to the GH dose used.

Intravenous neridronate in adults with osteogenesis imperfecta.

Osteogenesis imperfecta (OI) is a heritable disease of connective tissue, characterized by increased bone fragility. Bisphosphonates currently seems to be the most promising therapy, at least in children. We tested IV neridronate, an amino-bisphosphonate structurally similar to alendronate and pamidronate in adults with OI. Twenty-three men and 23 premenopausal women with OI were randomized to either iv neridronate (100 mg infused intravenously for 30 minutes every 3 months) or no treatment with a ratio of 2 to 1. Control patients were given the same bisphosphonate therapy at the end of the first year. Clinical evaluation included bone densitometry measurements using dual energy X-ray absorptiometry (DXA), fasting serum and urinary biochemistry every 6 months, and radiographs of the spine taken at baseline and after 12 and 24 months of follow-up. Spine and hip bone mineral density rose by 3.0 +/- 4.6% (SD) and by 4.3 +/- 3.9%, respectively, within the first 12 months of treatment, whereas small insignificant changes were observed in the control group. During the second year of follow-up, additional 3.91% and 1.49% increases were observed at the spine and hip, respectively. Markers of skeletal turnover significantly fell during neridronate treatment. Fracture incidence during neridronate treatment was significantly lower than before therapy and compared with controls. Neridronate iv infusions, administered quarterly, significantly increase bone mineral density and lowered the risk of clinical fracture in adults with OI. Bisphosphonate therapy seems to provide clinical benefits, not only to children with OI, but also to adult patients.

Fat oxidation and adiposity in prepubertal children: exogenous versus endogenous fat utilization.

Fat balance plays an important role in fat mass regulation. The mechanisms by which fat intake and fat oxidation are controlled are poorly understood. In particular, no data are available on the origin, i.e. exogenous (meal intake) or endogenous (adipose tissue lipolysis), of fat oxidized during the postprandial period in children and the proportion between these two components. In this study we tested the hypothesis that there is a relationship between adiposity and the oxidative fate of fat taken with a mixed meal in a group of 15 children with a wide range of fat mass (9-64%). The combination of stable isotope analysis ([13C] enriched fatty acids added to a mixed meal) and indirect calorimetry allowed us to differentiate between the exogenous and endogenous resting fat oxidation rate over the 9-h postprandial period. During the 9 hours of the postprandial period, the children oxidized an amount of fat comparable to that ingested with the meal [26.8 (+/-2.31) g vs. 26.4 (+/-2.3) g, respectively, P = ns]. On average, exogenous fat oxidation [2.99 (+/-3.0) g/9 h] represented 10.8% (+/-0.9) of total fat oxidation. Endogenous fat oxidation, calculated as the difference between total fat oxidation and exogenous fat oxidation, averaged 23.4 (+/-1.9) g/9 h and represented 88.2% (+/-0.9) of total fat oxidation. Endogenous fat oxidation as well as exogenous fat oxidation were highly correlated to total fat oxidation (r = 0.83, P < 0.001; r = 0.84, P < 0.001, respectively). Exogenous fat oxidation expressed as a proportion of total fat oxidation was directly related to fat mass (r = 0.56, P < 0.03), while endogenous fat oxidation expressed as a proportion of total fat oxidation was inversely related (r = -0.57, P < 0.03) to the degree of adiposity. The enhanced exogenous fat oxidation observed when adiposity increases in the dynamic phase of obesity may be viewed as a protective mechanism to prevent further increase in fat mass and hence to maintain fat oxidation at a sufficient rate when the body is exposed to a high amount of dietary fat, as typically encountered in obese children.

Early variations of plasma somatomedin activity in the newborn.

In neonates, plasma somatomedin as measured by the porcine cartilage assay was very low during the first day of life. A striking increase was observed on day 4 and 5, with a return to lower values at a later age. These findings indicate an early capacity to generate somatomedin activity in newborns.

Meal-induced thermogenesis and obesity: is a fat meal a risk factor for fat gain in children?

Diet composition, in particular fat intake, has been suggested to be a risk factor for obesity in humans. Several mechanisms may contribute to explain the impact of fat intake on fat gain. One factor may be the low thermogenesis induced by a mixed meal rich in fat. In a group of 11 girls (10.1 +/- 0.3 yr), 6 obese (body mass index, 25.6 +/- 0.6 kg/m(2)), and 5 nonobese (body mass index, 19 +/- 1.6 kg/m(2)), we tested the hypothesis that a mixed meal rich in fat can elicit energy saving compared with an isocaloric and isoproteic meal rich in carbohydrate. The postabsorptive resting energy expenditure and the thermic effect of a meal (TEM) after a low fat (LF; 20% fat, 68% carbohydrate, and 12% protein) or an isocaloric (2500 kJ or 600 Cal) and isoproteic high fat (HF; 48% fat, 40% carbohydrate, and 12% protein) meal were measured by indirect calorimetry. Each girl repeated the test with a different, randomly assigned menu (HF or LF) 1 week after the first test. TEM, expressed as a percentage of energy intake was significantly higher after a LF meal than after a HF meal (6.5 +/- 0.7% vs. 4.3 +/- 0.4%; P < 0.01). The postprandial respiratory quotient (RQ) was significantly higher after a LF meal than after a HF meal (0.86 +/- 0.013 vs. 0.83 +/- 0.014; P < 0.001). The HF low carbohydrate meal induced a significantly lower increase in carbohydrate oxidation than the LF meal (20.3 +/- 6.2 vs. 61.3 +/- 7.8 mg/min; P < 0.001). On the contrary, fat oxidation was significantly higher after a HF meal than after a LF meal (-1.3 +/- 2.4 vs. -15.1 +/- 3.6 mg/min; P < 0.01). However, the postprandial fat storage was 8-fold higher after a HF meal than after a LF meal (17.2 +/- 1.7 vs. 1.9 +/- 1.8 g; P < 0.001). These results suggest that a high fat meal is able to induce lower thermogenesis and a higher positive fat balance than an isocaloric and isoproteic low fat meal. Therefore, diet composition per se must be taken into account among the various risk factors that induce obesity in children.

Prevention of bone demineralization by calcium supplementation in precocious puberty during gonadotropin-releasing hormone agonist treatment.

We have previously demonstrated a negative impact on peak bone mass in girls with precocious puberty treated with GnRH agonist (GnRHa). Several studies have shown that a high calcium intake positively influences bone mass in prepubertal girls and leads to a higher peak bone mass. The aim of this study was to evaluate the effect of calcium supplementation in girls with precocious puberty during GnRHa treatment. Forty girls affected by true central precocious puberty and treated with the GnRHa triptorelin were studied for 2 yr. After diagnosis, the patients were randomly assigned to three groups: group A, treated only with GnRHa; group B, treated for 12 months solely with GnRHa and then supplemented with calcium gluconolactate/carbonate (1 g calcium/day in two doses) for 12 months; and group C, treated from the beginning with combined GnRHa and calcium. Bone mineral density (BMD) at the lumbar spine was measured by dual energy x-ray absorptiometry at the beginning of the study and after 12 and 24 months and was expressed as the calculated true volumetric density (BMDv) in milligrams per cm3. Group A showed a decrease in absolute BMDv levels, in SD score for chronological age (CA), and even more in SD score for bone age (BA). Group B showed the same behavior during the first year, but this trend was reversed in the second year, when calcium supplementation was added to GnRHa treatment. Group C showed an increase in absolute BMDv levels and in SD score for CA and BA. BMDv variations (expressed as absolute values, SD score for CA, and SD score for BA) became statistically significant at 24 months between groups C and A (P = 0.036, P = 0.032, and P = 0.025, respectively). The behavior of the lumbar spine BMDv in the three groups is consistent with a positive effect of calcium supplementation during GnRHa treatment. In calcium-supplemented patients, the normal process of bone mass accretion at puberty is preserved despite GnRHa treatment. Therefore, the reduction in BMD during GnRHa treatment in girls with precocious puberty is at least completely reversible and preventable if calcium supplementation is associated from the beginning.