Laura Lucaccioni

Turner syndrome–issues to consider for transition to adulthood

BACKGROUND Turner syndrome (TS) is associated with a spectrum of health problems across the age span, which requires particular attention during the transition period in these adolescents. AREAS OF AGREEMENT The majority of girls with TS require oestrogen replacement from puberty onwards, which is important for adequate feminization, uterine development and maintenance of bone health. There is a lifetime increased risk from autoimmune conditions like hypothyroidism, coeliac disease, hearing loss and aortic dilatation with the potential to lead to aortic dissection. A systematic and holistic approach to provision of health care in TS is needed. AREAS OF CONTROVERSY Several unanswered questions remain, including the choice of hormone replacement therapy in the young person with TS and in adulthood; the optimal mode of cardiovascular assessment; the best management and assessment prior to and during pregnancy. AREAS TIMELY FOR DEVELOPING RESEARCH The optimal model of care and transition to adult services in TS requires attention. Further research is needed in relation to cardiovascular risk assessment, pregnancy management and hormone replacement therapy in TS.

The impact of the Italian guidelines on antibiotic prescription practices for acute otitis media in a paediatric emergency setting.

BackgroundAcute otitis media (AOM) is one of the most common childhood infectious diseases. The recent Italian Pediatric Guidelines for the treatment of AOM constitutes a step forward in the management of children with uncomplicated AOM. The aim of this study was to evaluate antibiotic prescription patterns for AOM in a Pediatric Emergency Department (PED) after those guidelines were introduced and to assess the relationship between implementation of the “watchful waiting” strategy and the incidence of acute mastoiditis in the PED.MethodsThis retrospective study was conducted between 1st January 2007 to 31st December 2013 at the PED of the University of Modena and Reggio Emilia in Modena (Italy). All children between 0 and 14 years who were examined because of symptoms and/or signs of AOM and acute mastoiditis were enrolled. Pearson’s chi-squared test was used to evaluate if introduction of the Italian Paediatric Guidelines was associated with a reduction in the antibiotic prescription pattern in children with AOM and/or with an increase in mastoiditis frequency.Results4,573 (89.4%) patients were included in our analysis, antibiotics were prescribed to 81% cases of the children diagnosed with AOM. The frequency of antibiotic prescribing continued to be stable after the Italian guidelines were introduced (82% versus 81%).Forty children were admitted to hospital with a diagnosis of acute mastoiditis. Our study did not find any association between the number of cases of acute mastoiditis and the percentage of patients treated with antibiotics; the annual incidence of mastoiditis before and after the new guidelines were published was, in fact, stable.ConclusionsDespite the diffusion of clinical guidelines recommending a “watchful waiting” approach for children with AOM, the antibiotic prescription rate continues to be high. It appears to be more difficult to impact the percentage of cases for which antibiotics are prescribed than the type of antibiotic that is utilized. In view of these findings, a close follow-up control by the primary care paediatrician or a scheduled follow-up appointment at the PED and incisive campaigns to promote parents’ awareness of proper antibiotic use appear to be warranted.

The ontogeny of fidgety movements from 4 to 20 weeks post-term age in healthy full-term infants

BACKGROUND Fidgety movements (FMs) are an early accurate marker for normal development. AIM The study assessed the ontogeny of normal FMs from 4 to 20weeks post-term age (PTA). STUDY DESIGN Longitudinal prospective study of healthy full-term infants video recorded every second week from birth to 20weeks PTA. SUBJECTS 21 full-term newborns were enrolled. OUTCOME MEASURES Temporal organization, amplitude, character, predominance in proximal and/or distal parts of the body and the presence of FMs in fingers and wrists were independently scored by three observers. RESULTS From 4 to 10weeks PTA, FMs were sporadic, becoming intermittent in 1-2weeks; they occurred in the proximal parts, with larger and jerkier movements in the following period. From 11 to 16weeks PTA FMs became smaller in amplitude and slower in speed, they were present in all body parts and were more continual than before. Rotational movements in wrists and ankles and finger movements with open hands appeared. From 17 to 20weeks PTA, FMs became more discontinuous and disappeared at 18-20weeks PTA. CONCLUSIONS Developmental course of FMs was seen between 4 and 20weeks PTA with changes in temporal organization, amplitude, speed and body parts involved. The best time for scoring FMs is between 12 and 16weeks PTA.

Precocious pubertal development: a challenge for pediatric endocrinologists

Precocious puberty is one of the most common conditions encountered in the pediatric endocrinology clinic and can be defined as the appearance of secondary sexual characteristics in girls under 8 years and boys under 9 years of age. The timing of pubertal onset has received increasing attention because of a reported gradual decline in age at menarche in most populations. Proposed mechanisms for these changes include: an improvement in socioeconomic conditions with consequent increased nutritional status and a rise in a number of environmental pollutants. The challenges for pediatric endocrinologists are increasing: what are the mechanisms of precocious puberty in modern society? Should our diagnostic criteria be changed? When to treat? What are the consequences of treatment? Little is known of the short and long term consequences of GnRH-analog treatment, especially in terms of psychological consequences for children and their families.

Central Precocious Puberty and Response to GnRHa Therapy in Children with Cerebral Palsy and Moderate to Severe Motor Impairment: Data from a Longitudinal, Case-Control, Multicentre, Italian Study

Background Children affected by neurodevelopmental disability could experience early pubertal changes at least 20 times more than the general population. Limited data about central precocious puberty (CPP) among children affected by cerebral palsy (CP) are available. Methods This is a longitudinal, observational, retrospective, case-control study involving 22 children affected by CPP and CP (group A), 22 paired with CP but without CPP (group B), and 22 children with CPP without CP. Auxological, biochemical, and instrumental data were collected at diagnosis of CPP and at 2 follow-up visits. Results No differences were detected between groups A (at baseline) and B. At diagnosis of CPP, height SDS adjusted for target height (H-TH SDS) was significantly reduced in A than in C (−0.63 ± 1.94 versus 1.56 ± 1.38), while basal LH and oestradiol levels were significantly elevated in A than in C. During follow-up, despite an effective treatment, growth impairment deteriorated in A than in C (Δ H-SDS from diagnosis of CPP to last follow-up: −0.49 ± 0.91 versus 0.21 ± 0.33, p = 0.023). Conclusions Diagnosis of CPP could be partially mislead in CP due to growth failure that got worse during follow-up despite therapy. CPP in CP seems to progress rapidly along time supporting the hypothesis of a more intense activation of hypothalamic-pituitary-gonadal-axis in these patients.

The measurement of urinary gonadotropins for assessment and management of pubertal disorder

OBJECTIVE: Measurement of urinary LH (uLH) and FSH (uFSH) may facilitate non-invasive pubertal assessment but there is a need for further validation by studying children and adolescents with disorders of puberty. DESIGN: 65 cases (Male: 25) with a median age of 12 years (2.9–18.1) supplied at least one non-timed urine sample for uLH and uFSH measurement by immunoassay and corrected for creatinine excretion. 25 cases were receiving GnRH-agonist (GnRH-a) at the time of sample collection. In 41 cases, urine samples were collected prior to a LHRH test and in 12 cases matched serum samples for basal LH (sLH) and FSH (sFSH) were also available. RESULTS: There was a significant correlation between sLH and uLH:uCr (r=0.82; p-value <0.001) and sFSH and uFSH:uCr (r=0.93; p-value <0.001). Based on receiver operator characteristics analysis, a uLH:uCr value of 0.05 IU/mmol as a cut-off would detect a LH peak >5U I/L with a sensitivity of 86% and a specificity of 72% with a positive predictive value of 93%. In pubertal boys (6) and girls (22) with a sLH peak >5UI/L, median uLH:uCr was 0.27 IU/mmol (0.27–0.28) and 0.17 IU/mmol (0.09–0.43), respectively. The median uFSH:uCr was 0.51 IU/mmol (0.41–0.60) for boys and 1.1 IU/mmol (0.21–2.44) for girls. In the 25 cases on GnRH-a, the median uLH:uCr for boys and girls was 0.02 IU/mmol (0.01–0.02) and 0.02 IU/mmol (0.004–0.07), respectively, and the median uFSH:uCr was 0.07 IU/mmol (0.05–0.09) and 0.27 IU/mmol (0.09–0.54), respectively. CONCLUSION: Urinary gonadotrophins reflect serum gonadotrophin concentration and may represent a reliable non-invasive method of assessing pubertal progress.

Thyroid function in Down syndrome

Down syndrome is the most commonly encountered human chromosomal disorder. Down syndrome is associated with thyroid dysfunction including: hypothyroidism, both congenital and acquired, and hyperthyroidism. A genetic predisposition and a propensity to acquire autoimmune disorders seem to be possible factors, though their causal relation remains unclear. The aim of the review is to describe what is currently known about the association between Down syndrome and thyroid dysfunction.

Central precocious puberty in a 3 year-old girl with Phenylketonuria: a rare association?

BackgroundCentral precocious puberty (CPP) and phenylketonuria (PKU) are two rare conditions, the latter being the rarer. To date, only one case featuring both these conditions has been reported, and hyperphenylalaninemia was assumed triggering CPP.Case presentationWe present a 3.2 years old girl referred with a 12 months history of breast and pubic hair development, and vaginal discharge. Hyperphenylalaninemia had been identified by newborn screening and PKU subsequently confirmed by plasma amino acid and genetic analysis. Early dietary control of plasma phenylalanine had been excellent afterwards, resulting in phenylalanine concentrations consistently within the recommended range. Clinical scenario, hormonal assessment and imaging were in keeping with true idiopathic central precocious puberty. Treatment with long lasting gonadotropin-releasing hormone analogue led to regression of secondary sexual characteristics.ConclusionWe describe for the first time CPP in a girl affected with PKU but with persistently well controlled blood phenylalanine concentrations. This finding is in contrast to a previous report which suggested persistently high phenylalaninemia levels as potential trigger for CPP in PKU patients. Our report, together with the lack of evidence in published cohort studies of children with PKU, strongly suggests this rare association is coincidental and independent of the presence of severe hyperphenylalaninemia.

Endpoints in paediatric oncology

PurposeThe purpose of this review is to address the issue of endpoints in paediatric oncology. Oncologists use this term to refer to an outcome they are trying to measure with a clinical trial, which may become accordingly the object of scientific articles. The outcome measured may concern both efficacy and safety, although from different perspectives.MethodsBased on both literature and experience developed in clinical trials, the different types of endpoints have been critically analysed in their power to provide the highest information of therapeutic interest (efficacy and safety) with the least risk and discomfort for the individual. Primary, secondary and surrogate endpoints have been distinguished. The most relevant differences have been discussed in comparison with adult oncology settings of endpoints.ResultsThe rarity of cancer in childhood and adolescence and the objective difficulty of enrolling statistically conceivable numbers of individuals have determined the utmost positive development of large scale, multinational clinical trials. The most interesting consequence is that the impact of multiplicity interferences, which is usually present in virtually all clinical trials developed for adults with cancer, is not a common event in paediatric oncology. Nevertheless, many of the questions concerning the different impact on outcome and survival of clinical trials developed in adult oncology remain unanswered due to the objective limitations still existing in terms of cure compared with paediatric oncology. The powerful consistency of cure rate, as the most relevant endpoint of clinical trials developed in paediatric oncology, addresses additional considerations to support the relevant differences existing between adult and paediatric oncology: both the development of clinical trials with different aims (confirmatory versus primary response) and the limited impact of multiplicity limitations may determine different implications regarding the meaning of endpoints in paediatric and adult oncology.ConclusionThe aim of cancer treatment is to improve survival (SUR) and quality of life (QoL), but some restraints on the conduct of clinical trials may make these goals unattainable. Clinical trial endpoints represent a measure method aimed to grant answers to questions addressed by the clinical trial itself. The effect of the new regulation is expected to stimulate high-quality research and provide robust information on paediatric drugs to increase the availability of such drugs to children.

Brain-derived neurotrophic factor and epilepsy: a systematic review

Several in vitro, ex vivo and in vivo studies imply brain-derived neurotrophic factor (BDNF) in the pathophysiology of epilepsy. Aim of our work is to report the most important findings regarding BDNF and its potential role in epilepsy. We targeted those publications addressing both in vitro and in vivo evidences of relationship between BDNF and epilepsy. Basic researches, randomized trials, cohort studies, and reviews were contemplated to give a breadth of clinical data. Medline, CENTRAL, and Science Direct were searched till August 2017 using keywords agreed by the authors. Together with a defined role in developmental and mature brain, BDNF has excitatory effects in neuronal cultures and animal brain slices. Furthermore, both BDNF and its conjugated receptor (i.e. Tropomyosin receptor kinase B or TrkB) are increased in animal models and humans with epilepsy, particularly in the temporal and hippocampal areas. Acute injection of BDNF in brain of mice induces seizures, which are almost or totally abolished blocking its transcription and pathway. Chronic infusion of BDNF is conversely associated with a decreased neuronal excitability, probably via several mechanism including an increase in central levels of neuropeptide Y (NPY), altered conductance of chloride, and downregulation of TrkB. While genetic studies are inconclusive, serum BDNF is more frequently higher in patients with epilepsy and appears to be correlated to severity of disease. Current evidences suggest that inhibiting BDNF-TrkB signaling and reinforcing the NPY system could represent a potential therapeutic strategy for epilepsy, especially for temporal lobe epilepsy.