Filter

Refine by Access

Refine by Date

—
  • Print
  • Save

Search Results

You are looking at 71 - 80 of 843 items for

  • Abstract: adolescen* x
  • Abstract: boy* x
  • Abstract: child* x
  • Abstract: girl* x
  • Abstract: neonat* x
  • Abstract: paediatric x
  • Refine by Access: Content accessible to me x
Clear All Modify Search
Free access

Acylated/unacylated ghrelin ratio in cord blood: correlation with anthropometric and metabolic parameters and pediatric lifespan comparison

S Bellone, F Prodam, S Savastio, D Avanzo, A Pagani, L Trovato, G E Walker, G Genoni, and G Bona

Context

Ghrelin is a peptide with multiple functions that circulates in acylated (AG) and unacylated (UAG) forms. However, the role of ghrelin in neonates (NN) remains to be clarified.

Objective

The aim of this study was to determine ghrelin concentrations of the two forms in NN to clarify their biological roles. As such, ghrelin levels at birth were compared with those in later life.

Setting and design

Tertiary Care Center. In this cross-sectional study, we evaluated AG, UAG, AG/UAG ratio, and insulin levels in venous cord blood from NN and in fasted normal weight (NW) and obese (OB) children, both prepubertal and pubertal.

Subjects

We studied 82 NN, 82 NW, and 58 OB children.

Results

AG levels were lower in NN than in NW and OB children (P<0.0001), more specifically the prepubertal NW and OB children (P<0.0001). UAG levels were higher in NN than in NW and OB children (P<0.0001). Therefore, the AG/UAG ratio was lower in NN than in NW and OB children (P<0.0001). NN showed insulin levels similar to NW and lower than OB children (P<0.0001). At birth UAG was positively correlated with AG (Pearson: 0.425; P<0.0001) and negatively with insulin (−0.253; P<0.02). In NW and OB, UAG and AG were positively correlated to each other and negatively correlated with insulin and body mass index (−0.566; P<0.0001).

Conclusions

NN compared with children, showed higher UAG and lower AG levels. The AG/UAG ratio showed a very different profile in NN, being lower than in NW and OB children, thus suggesting a different metabolic function for the two forms in NN. Further studies are needed to clarify the exact role of the different ghrelin forms in NN.

Free access

Children whose diet contained olive oil had a lower likelihood of increasing their body mass index Z-score over 1 year

J J Haro-Mora, E García-Escobar, N Porras, D Alcázar, J Gaztambide, A Ruíz-Órpez, S García-Serrano, E Rubio-Martín, E García-Fuentes, J P López-Siguero, F Soriguer, and G Rojo-Martínez

Objective

Changes in eating habits may be influential in the ever-increasing rate of childhood obesity. Our aim was to determine whether those children who consume olive oil have a lower risk of weight gain compared with children who consume other oils.

Design and methods

The study included 18 girls and 74 boys, all aged 13–166 months. A survey was completed for each subject about eating habits and physical activity. A sample of subcutaneous adipose tissue was also obtained for cellular study. Data were recorded on the mean size of the adipocytes, the number of preadipocytes, and the concentration of particular fatty acids. The weight and height of the children were measured 13 months later.

Results

The likelihood that after 1 year the children would have increased their body mass index (BMI) Z-score above the initial score was less in the children who consumed only olive oil (odds ratio (OR)=0.22; 95% confidence interval (CI): 0.08–0.63; P=0.005). These results remained after adjusting for age, physical activity and BMI (OR=0.19; 95% CI: 0.06–0.61; P=0.005) and after adjusting for age, physical activity and adipocyte volume (OR=0.15; 95% CI: 0.04–0.52; P=0.003).

Conclusions

Diets with mono unsaturated fatty acid (MUFA)-rich olive oil could reduce the risk of obesity in childhood.

Free access

Molecular and clinical analysis of a neonatal severe hyperparathyroidism case caused by a stop mutation in the calcium-sensing receptor extracellular domain representing in effect a human ‘knockout’

D T Ward, M Z Mughal, M Ranieri, M M Dvorak-Ewell, G Valenti, and D Riccardi

Objective

Loss-of-function calcium-sensing receptor (CAR) mutations cause elevated parathyroid hormone (PTH) secretion and hypercalcaemia. Although full Car deletion is possible in mice, most human CAR mutations result from a single amino acid substitution that maintains partial function. However, here, we report a case of neonatal severe hyperparathyroidism (NSHPT) in which the truncated CaR lacks any transmembrane domain (CaRR392X), in effect a full CAR ‘knockout’.

Case report

The infant (daughter of distant cousins) presented with hypercalcaemia (5.5–6 mmol/l corrected calcium (2.15–2.65)) and elevated PTH concentrations (650–950 pmol/l (12–81)) together with skeletal demineralisation. NSHPT was confirmed by CAR gene sequencing (homozygous c.1174C-to-T mutation) requiring total parathyroidectomy during which only two glands were located and removed, resulting in normalisation of her serum PTH/calcium levels.

Design and methods

The R392X stop codon was inserted into human CAR and the resulting mutant (CaRR392X) expressed transiently in HEK-293 cells.

Results

CaRR392X expressed as a 54 kDa dimeric glycoprotein that was undetectable in conditioned medium or in the patient's urine. The membrane localisation observed for wild-type CaR in parathyroid gland and transfected HEK-293 cells was absent from the proband's parathyroid gland and from CaRR392X-transfected cells. Expression of the mutant was localised to endoplasmic reticulum consistent with its lack of functional activity.

Conclusions

Intriguingly, the patient remained normocalcaemic throughout childhood (2.5 mM corrected calcium, 11 pg/ml PTH (10–71), age 8 years) but exhibited mild asymptomatic hypocalcaemia at age 10 years, now treated with 1-hydroxycholecalciferol and Ca2 + supplementation. Despite representing a virtual CAR knockout, the patient displays no obvious pathologies beyond her calcium homeostatic dysfunction.

Free access

Effect of weight reduction on insulin sensitivity, sex hormone-binding globulin, sex hormones and gonadotrophins in obese children

N H Birkebæk, A Lange, P Holland-Fischer, K Kristensen, S Rittig, H Vilstrup, A Handberg, and H Gronbaek

Objective

Obesity in men is associated with reduced insulin sensitivity and hypoandrogenism, while obesity in women is associated with reduced insulin sensitivity and hyperandrogenism. In children, the effect of obesity and weight reduction on the hypothalamo-pituitary–gonadal axis is rarely investigated. The aim of the present study was to investigate the effect of weight reduction in obese Caucasian children on insulin sensitivity, sex hormone-binding globulin (SHBG), DHEAS and the hypothalamo-pituitary–gonadal axis.

Methods

One hundred and sixteen (65 females) obese children with a median age of 12.3 (7–15) years were examined before and after a 10-week stay at a weight loss camp. Examination included anthropometry and fasting blood samples measuring plasma glucose, serum insulin, SHBG, DHEAS, testosterone, 17β-oestradiol, FSH and LH.

Results

Body mass index (BMI) decreased (P<0.01), insulin sensitivity and SHBG increased (P<0.01), independent of gender and puberty. The changes in insulin sensitivity and the changes in SHBG correlated significantly (P<0.01) independent of gender, puberty and the changes in BMI. Testosterone increased in boys (P<0.01) and tended to decrease in girls (P=0.05, in girls after menarche (P=0.03)). FSH increased in boys and girls. LH increased in boys and was unchanged in girls.

Conclusions

During weight loss, insulin sensitivity and SHBG increased significantly in obese children, and the changes in insulin sensitivity and the changes in SHBG correlated significantly independent of gender, puberty and the changes in BMI. There was sexual dimorphism in the changes of testosterone, with the changes in boys towards increased virilisation and the changes in girls towards less virilisation.

Free access

Newborn TSH concentration and its association with cognitive development in healthy boys

Carmen Freire, Rosa Ramos, Esperanza Amaya, Mariana F Fernández, Piedad Santiago-Fernández, Maria-Jose Lopez-Espinosa, Juan-Pedro Arrebola, and Nicolas Olea

Objective

An association between thyroid function during pregnancy or infancy and neurodevelopment in children has been demonstrated. We aimed to investigate whether newborn TSH concentrations are related to subsequent neurocognitive development.

Design

We conducted a longitudinal study on 178 children from a general population birth cohort in Granada (Spain) born in 2000–2002.

Methods

TSH concentrations were measured in umbilical cord blood, and cognitive functions were assessed at 4 years of age using the McCarthy's scales of children's abilities (MSCA). Organochlorine (OC) compound concentrations and the combined oestrogenicity (total effective xeno-oestrogenic burden (TEXB)) were also determined in the placentae.

Results

Mean newborn TSH was 3.55 mU/l (range=0.24–17 mU/l). In multivariate regression analyses, adjusting for maternal and child characteristics, higher newborn TSH concentrations showed a decrease of 3.51 and 3.15 points on the MSCA general cognitive and executive function scores respectively and were associated with a higher risk of scoring below the 20th percentile (P20) on the quantitative score (odds ratio (OR)=2.64). Children with TSH in the upper quartile (4.19–17.0 mU/l) were at higher risk of scoring <P20 on span memory (OR=5.73), whereas children with TSH in the second quartile (2.05–2.95 mU/l) were at lower risk of scoring <P20 on the verbal scale (OR=0.24). Neonatal TSH status was also associated with general cognitive and executive function outcomes when controlling for prenatal exposure to OCs or placental TEXB.

Conclusions

Newborn thyroid hormone status expressed by TSH in cord blood may adversely affect later cognitive function. A more thorough screening for neonatal thyroid deficiency is warranted.

Free access

Novel GLIS3 mutations demonstrate an extended multisystem phenotype

P Dimitri, J T Warner, J A L Minton, A M Patch, S Ellard, A T Hattersley, S Barr, D Hawkes, J K Wales, and J W Gregory

Introduction

Mutations in the GLI-similar 3 (GLIS3) gene encoding the transcription factor GLIS3 are a rare cause of neonatal diabetes and congenital hypothyroidism with six affected cases from three families reported to date. Additional features, described previously, include congenital glaucoma, hepatic fibrosis, polycystic kidneys, developmental delay and facial dysmorphism.

Subjects

We report two new cases from unrelated families with distinct novel homozygous partial GLIS3 deletions. Both patients presented with neonatal diabetes mellitus, severe resistant hypothyroidism in the presence of elevated thyroglobulin and normal thyroid anatomy, degenerative liver disease, cystic renal dysplasia, recurrent infections and facial dysmorphism. These novel mutations have also resulted in osteopenia, bilateral sensorineural deafness and pancreatic exocrine insufficiency, features that have not previously been associated with GLIS3 mutations. Gene dosage analysis showed that the parents were carriers of a deletion encompassing exons 1–2 (case 1) or exons 1–4 (case 2) of the 11 exon gene. Genome-wide SNP analysis did not reveal a common ancestral GLIS3 haplotype in patient 2.

Conclusions

Our results confirm partial gene deletions as the most common type of GLIS3 mutations, accounting for four of five families identified to date. We propose that mutations in GLIS3 lead to a wider clinical phenotype than previously recognised. We also report the first case of a recessive GLIS3 mutation causing neonatal diabetes and congenital hypothyroidism in a child from a non-consanguineous pedigree, highlighting the importance of molecular genetic testing in any patient with this phenotype.

Free access

Psychological and behavioural aspects in children and adolescents with congenital hypothyroidism diagnosed by neonatal screening: comparison between parents' and children's perceptions

Nicoletta Bisacchi, Milva Orquidea Bal, Laura Nardi, Ilaria Bettocchi, Graziana D'Addabbo, Veronica Conti, Sara Monti, Franco D'Alberton, Alessandro Cicognani, and Alessandra Cassio

Objective

To compare the psychological adjustment and behaviour of congenital hypothyroidism (CH) children and their parents with a control group.

Study design

A cross-sectional study was carried out with 84 CH subjects diagnosed by neonatal screening (range 2.7–18.6 years), subdivided into four age groups: group 1 (2–5 years); group 2 (6–10 years); group 3 (11–13 years); and group 4 (14–18 years) and was compared with an age-matched control group. Patients were assessed using two questionnaires: Child Behaviour Checklist for parents and Youth Self-Report for children over 11 years of age.

Results

In groups 1, 3 and 4, total score (TS), internalising score (IS=problems within the self) and externalising score (ES=conflicts with other people) as reported by parents were not significantly different in CH patients and in controls. In group 2, parents of CH children showed values of TS (P<0.05), IS (P<0.05), ES (P<0.05) and scores on other scales significantly higher than controls. In self-reports of groups 3 and 4, the behavioural scales were not significantly different in CH patients and in controls.

Conclusions

Paediatricians should be informed about the increased risk of the development of behavioural problems at primary school age in CH patients. At this age special attention should be paid to parental worries and anxiety. However, it can be reassuring for the patients and parents to know that the problems may be related to CH, and that they may spontaneously disappear.

Free access

Pregnancy in women heterozygous for MCT8 mutations: risk of maternal hypothyroxinemia and fetal care

Helton Estrela Ramos, Melina Morandini, Aurore Carré, Elodie Tron, Corinne Floch, Laurent Mandelbrot, Nathalie Neri, Benoit De Sarcus, Albane Simon, Jean Paul Bonnefont, Jeanne Amiel, Isabelle Desguerre, Vassili Valayannopoulos, Mireille Castanet, and Michel Polak

Context

Monocarboxylate transporter 8 (MCT8 or SLC16A2) mutations cause X-linked Allan–Herndon–Dudley syndrome. Heterozygous females are usually asymptomatic, but pregnancy may modify thyroid function and MCT8 is expressed in the placenta, suggesting that maternal and fetal abnormalities might develop even in the absence of MCT8 fetal mutation. Genetic counseling is so far based on X-linked transmission, and prenatal diagnosis is rarely performed.

Objective

To describe thyroid function and the prenatal diagnosis in pregnant mothers harboring heterozygous MCT8 mutations and management of the persistent maternal hypothyroxinemia.

Patients

Two women heterozygous for MCT8 mutations (c.1690G>A and c.1393-1G>C) were monitored throughout pregnancy.

Methods

Prenatal diagnosis included sex determination, direct MCT8 sequencing, and familial linkage analysis. Ultrasonography and hormonal assays for maternal thyroid function evaluation were performed serially during pregnancy. Neonatal thyroid hormonal status was assessed.

Results

None of the three fetuses (two males and one female) carried MCT8 mutations. One of the two heterozygous mothers revealed gestational hypothyroxinemia, prompting early levothyroxine (l-T4) therapy until delivery. The second heterozygous mother showed normal thyroid function but was preventively traited by l-T4 and all of the three neonates had normal thyroid hormone levels and thyroid gland at birth, suggesting advantages of prenatal care and/or compensatory mechanisms.

Conclusion

Heterozygous MCT8 women should be monitored for requirement of l-T4 therapy to prevent fetal and neonatal hypothyroidism and to avoid risk of potential cognitive delay due to gestational hypothyroxinemia. Moreover, when the disease-causing mutation is known and/or the first child is affected, prenatal diagnosis for male fetuses should be assessed early for MCT8 mutations by direct sequencing.

Free access

Association between thyroid function tests at baseline and the outcome of patients with sepsis or septic shock: a systematic review

Anna G Angelousi, Drosos E Karageorgopoulos, Anastasios M Kapaskelis, and Matthew E Falagas

Abstract

Introduction

The severity of critical illness is associated with various patterns of thyroid hormone abnormalities. We sought to evaluate whether the outcome of patients with, specifically, sepsis or septic shock is associated with the thyroid function tests evaluated at diagnosis or admission in the intensive care unit (ICU).

Methods

We performed a systematic review of relevant studies by searching PubMed.

Results

We included nine studies that all had a prospective cohort design. Seven involved children or neonates, and two involved adults. Mortality was the outcome evaluated in eight studies, while the length of ICU stay was evaluated in the remaining study. In univariate analysis, six of the nine included studies showed that either, free or total, triiodothyronine or thyroxine was lower in the group of patients with sepsis or septic shock who had unfavorable outcome than in those who had favorable outcome. Two other studies showed higher TSH values in the group of patients with unfavorable outcome. No significant relevant findings were observed in the remaining study. Regarding the correlation of sepsis prognostic scoring systems with thyroid function tests, the three studies that provided specific relevant data showed variable findings.

Discussion

Most of the relevant studies identified favor the concept that decreased thyroid function at baseline might be associated with a worse outcome of patients with sepsis or septic shock. Although these findings are not consistent, the role of thyroid function in affecting or merely predicting the outcome of sepsis or septic shock merits further investigation.

Free access

The pubertal transition in 179 healthy Danish children: associations between pubarche, adrenarche, gonadarche, and body composition

Annette Mouritsen, Lise Aksglaede, Kaspar Soerensen, Casper P Hagen, J H Petersen, Katharina M Main, and Anders Juul

Background

Pubertal onset is usually defined by breast development in girls and testicular growth in boys. Pubarche is defined as the attainment of pubic hair and is considered as a sign of pubertal transition. Pubarche is preceded by a gradual increase in production of adrenal androgens, DHEA and Δ4-androstenedione (Adione), a process termed adrenarche.

Objective

To study the natural course of pubertal transition and the associations with adrenarche, body fat, and linear growth.

Design and methods

A longitudinal study of 179 healthy children (89 girls) with higher socioeconomic background examined every 6 months for 5 years. Pubic hair stage, breast stage, genital stage, testicular volume (TV), height, weight, and four skinfolds were measured.

Results

In girls, median age (25th and 75th percentiles) at thelarche (B2+) was 10.1 years (9.3–10.9). In boys, median age at attaining a TV >3 ml was 11.5 years (10.9–12.0). Median age at pubarche (PH2+) was 10.9 years (10.3–11.4) in girls and 11.6 years (10.8–12.4) in boys. Only 6.8% (4/59) of the girls and 24.6% (15/61) of the boys developed pubic hair as the first isolated sign of puberty. Serum DHEAS and Adione increased with age, although the increase in Adione was most pronounced in girls. No associations between early age at thelarche/testicular growth and increased body fat (BMI and sum of four skinfolds) were observed.

Conclusion

Danish children rarely experience pubarche as the first sign of puberty. No associations between age at pubertal onset and body composition were found. Circulating levels of Adione, but not DHEAS, increased with the onset of puberty, although with large interindividual variability.