Endocrine, auxological and metabolic profile in children and adolescents with Down syndrome: from infancy to the first steps into adult life.

Down syndrome (DS) is the most common chromosomal disorder worldwide. Along with intellectual disability, endocrine disorders represent a remarkable share of the morbidities experienced by children, adolescents and young adults with DS. Auxological parameters are plotted on syndrome-specific charts, as growth rates are reduced compared to healthy age- and gender-matched peers. Furthermore, children with DS are at increased risk for thyroid dysfunctions, diabetes mellitus, osteopenia and obesity compared to general population. Additionally, male individuals with DS often show infertility, while women tend to experience menopause at an overall younger age than healthy controls. Given the recent outstanding improvements in the care of severe DS-related comorbidities, infant mortality has dramatically decreased, with a current average life expectancy exceeding 60 years. Accordingly, the awareness of the specificities of DS in this field is pivotal to timely detect endocrine dysfunctions and to undertake a prompt dedicated treatment. Notably, best practices for the screening and monitoring of pediatric endocrine disorders in DS are still controversial. In addition, specific guidelines for the management of metabolic issues along the challenging period of transitioning from pediatric to adult health care are lacking. By performing a review of published literature, we highlighted the issues specifically involving children and adolescent with DS, aiming at providing clinicians with a detailed up-to-date overview of the endocrine, metabolic and auxological disorders in this selected population, with an additional focus on the management of patients in the critical phase of the transitioning from childhood to adult care.

Thyroid Function Tests in Children and Adolescents With Trisomy 21: Definition of Syndrome-Specific Reference Ranges.

CONTEXT: The lack of syndrome-specific reference ranges for thyroid function tests (TFT) among pediatric patients with Down syndrome (DS) results in an overestimation of the occurrence of hypothyroidism in this population. OBJECTIVE: To (a) outline the age-dependent distribution of TFT among pediatric patients with DS; (b) describe the intraindividual variability of TFT over time; and (c) assess the role of elevated thyrotropin (TSH) in predicting the future onset of overt hypothyroidism. METHODS: In this retrospective, monocentric, observational analysis, we included 548 patients with DS (0-18 years) longitudinally assessed between 1992 and 2022. Exclusion criteria were abnormal thyroid anatomy, treatments affecting TFT, and positive thyroid autoantibodies. RESULTS: We determined the age-dependent distribution of TSH, FT3, and FT4 and outlined the relative nomograms for children with DS. Compared with non-syndromic patients, median TSH levels were statistically greater at any age (P < .001). Median FT3 and FT4 levels were statistically lower than controls (P < .001) only in specific age classes (0-11 for FT3, 11-18 years for FT4). TSH levels showed a remarkable fluctuation over time, with a poor (23%-53%) agreement between the TSH centile classes at 2 sequential assessments. Finally, the 75th centile was the threshold above which TSH values predicted future evolution into overt hypothyroidism with the best statistical accuracy, with a satisfactory negative predictive value (0.91), but poor positive predictive value (0.15). CONCLUSION: By longitudinally assessing TFT in a wide pediatric DS population, we outlined the syndrome-specific reference nomograms for TSH, FT3, and FT4 and demonstrated a persistent upward shift of TSH compared to non-syndromic children.

The bronchiolitis epidemic in 2021-2022 during the SARS-CoV-2 pandemic: experience of a third level centre in Northern Italy.

BACKGROUND: The aim of this study is to compare the 2021-2022 bronchiolitis season to the four previous years (2017-2018, 2018-2019, 2019-2020, 2020-2021) to see if there was an anticipation of the peak, an overall increase of cases, and an increased need of intensive care. METHODS: A retrospective single-centre study in the San Gerardo Hospital Fondazione MBBM, Monza, Italy was performed. Emergency Departments (ED) visits of patients aged < 18 years and ≤ 12 months were analyzed: the incidence of bronchiolitis on total assessments, the urgency level at triage and the hospitalization rate were compared. Data of children admitted to the Pediatric Department due to bronchiolitis were analyzed in terms of need of intensive care, respiratory support (type and duration), length of hospital stay, main etiological agent, patient characteristics. RESULTS: During 2020-2021 (first pandemic period) an important reduction in the ED attendance for bronchiolitis was observed, while in 2021-2022 there was an increase in incidence of bronchiolitis (13% of visits in infants < 1 year) and in the rate of urgent accesses (p = 0.0002), but hospitalization rates did not differ compared to previous years. Furthermore, an anticipated peak in November 2021 was observed. In the 2021-2022 cohort of admitted children to the Pediatric Department, a statistically significative increased need of intensive care unit was detected (Odds Ratio 3.1, 95% CI 1.4-6.8 after adjustment for severity and clinical characteristics). Instead, respiratory support (type and duration) and length of hospital stay did not differ. RSV was the main etiological agent and RSV-bronchiolitis determined a more severe infection (type and duration of breathing support, intensive care need and length of hospital stay). CONCLUSIONS: During Sars-CoV-2 lockdowns (2020-2021), there was a dramatic decrease of bronchiolitis and others respiratory infections. In the following season, 2021-2022, an overall increase of cases with an anticipated peak was observed and data analysis confirmed that patients in 2021-2022 required more intensive care than children in the four previous seasons.

Evaluation of the Pattern of Use of a Pediatric Emergency Department in Italy.

OBJECTIVES: The aim of this study was to evaluate access to a pediatric emergency department (PED) in a large hospital, in particular to estimate the prevalence of potentially avoidable accesses and the characteristics of return visits. METHODS: Clinical health records from the PED of San Gerardo Hospital, Monza, Italy, were retrospectively reviewed. The study population was composed of subjects younger than 18 years who attended the PED during the period from October 1, 2017, to November 30, 2017.Accesses were defined nonurgent if characterized by white or green triage codes and patient's discharge as the outcome and were defined potentially avoidable if nonurgent and with no diagnostic/therapeutic procedures performed except a visit by the ED pediatrician.Return visits were defined as accesses that occurred within 72 hours of the first index visit. RESULTS: A total of 2064 children and adolescents younger than 18 years had at least 1 ED attendance between October and November 2017, for a total of 2364 accesses.The most frequent diagnoses were upper respiratory tract infections (29.5% of accesses), followed by gastroenteritis (7.0%) and abdominal pain (7.0%). In all, 1810 accesses (88%) were classified as "nonurgent," and 1228 (60%) potentially avoidable, 373 of which were probably avoidable because they occurred when the primary care physician was available.The number of return visits was 98 (5% of the accesses): 74 were nonurgent, 31 of which potentially avoidable. On 17 occasions, both index and return visits were potentially avoidable. CONCLUSIONS: We confirm that most of the accesses to a PED are nonurgent and potentially avoidable. Interventions are needed to improve the appropriateness of use of emergency services.

Complications and risk factors for severe outcome in children with measles.

OBJECTIVE AND DESIGN: Risk factors for severe measles are poorly investigated in high-income countries. The Italian Society for Paediatric Infectious Diseases conducted a retrospective study in children hospitalised for measles from January 2016 to August 2017 to investigate the risk factors for severe outcome defined by the presence of long-lasting sequelae, need of intensive care or death. RESULTS: Nineteen hospitals enrolled 249 children (median age 14.5 months): 207 (83%) children developed a complication and 3 (1%) died. Neutropaenia was more commonly reported in children with B3-genotype compared with other genotypes (29.5% vs 7.7%, p=0.01). Pancreatitis (adjusted OR [aOR] 9.19, p=0.01) and encephalitis (aOR 7.02, p=0.04) were related to severe outcome in multivariable analysis, as well as C reactive protein (CRP) (aOR 1.1, p=0.028), the increase of which predicted severe outcome (area under the receiver operating characteristic curve 0.67, 95% CI 0.52 to 0.82). CRP values >2 mg/dL were related to higher risk of complications (OR 2.0, 95% CI 1.15 to 3.7, p=0.01) or severe outcome (OR 4.13, 95% CI 1.43 to 11.8, p<0.01). CONCLUSION: The risk of severe outcome in measles is independent of age and underlying conditions, but is related to the development of organ complications and may be predicted by CRP value.

Hodgkin lymphoma in a patient with mosaic trisomy 18: First clinical observation.

We report the case of a 17-year-old boy with a mosaic trisomy 18, who was diagnosed with Hodgkin lymphoma. The patient showed only poor growth and two muscular ventricular septal defects; no facial dysmorphims were present. He was admitted to our hospital because of asthenia and weight loss; a mediastinal enlargement was found and an histological diagnosis of nodular sclerosis Hodgkin lymphoma on mediastinal biopsy was performed. Contextually, a chromosomal analysis on bone marrow aspirate and on peripheral blood revealed a mosaic trisomy 18. This result was confirmed also with cytogenetic analysis on skin fibroblasts. While there is a well-documented association between trisomy 18 and solid cell tumors, this is, to our knowledge, the first reported case of Hodgkin lymphoma in a patient with a mosaic trisomy 18, enlarging the spectrum of possible oncologic manifestations of the disease.

Double-blind, placebo-controlled trial comparing effects of supplementation of two micronutrient sprinkles on fatty acid status in Cambodian infants.

BACKGROUND: Infants in developing countries require early dietary interventions to prevent nutritional deficiencies, above all protein, energy, iron and zinc. To what extent these interventions may affect the fatty acid (FA) status is still unknown. OBJECTIVES: To examine and compare the effects of 2 micronutrient "sprinkles" supplementations (iron 12.5 mg + folic acid 150 microg, iron/folate and iron 12.5 mg + folic acid 150 microg + zinc 5 mg + vitamins A, C and D3, mineral/micronutrient [MMN]) versus placebo on the FA status of Cambodian infants. METHODS: A total of 204 infants age 6 mo and living in Kompong Chhnang Province, Cambodia, were randomly assigned to receive daily supplementation of MMN (n = 68) and iron/folate (n = 68) or placebo (n = 68) for a 12-mo period in powder form as sprinkles. At the end of the intervention period, FAs in the range of 16 to 24 C were determined in blood drops absorbed on a strip collected from 182 subjects, and values among the 3 intervention subgroups and those of 21 Italian 18-mo-old, normal-growing infants as the reference group were compared. RESULTS: At the end of the supplementation trial, higher levels of the 2 essential FAs (EFAs) (linoleic acid, 18:2n-6, and alpha-linolenic acid, 18:3n-3) were found in the MMN group. No differences occurred for the major longer chain derivatives of both EFAs arachidonic acid (20:4n-6) and docosahexaenoic acid (22:6n-3). In MMN supplemented Cambodians, blood levels of linoleic acid approached those of Italian infants, and in addition their alpha-linolenic acid levels were improved. Cambodian infants, mostly still breast-fed through the second year of life, showed significantly higher levels of long-chain derivatives of both the n-6 and the n-3 series compared with Italians. CONCLUSIONS: Supplementation with iron, folic acid, zinc and vitamins was associated with an increase of linoleic acid and alpha-linolenic acid levels in Cambodian infants versus placebo, without significant changes in the concentrations of their longer chain derivatives, resulting in a FA status closer to Italian counterparts for the essential polyunsaturated FA levels. The iron/folate-treated infants showed no differences compared with the other 2 groups. Studies are needed to differentiate the potential effects of the supplemented micronutrients on the FA status.

Double-blind, placebo-controlled trial comparing effects of supplementation with two different combinations of micronutrients delivered as sprinkles on growth, anemia, and iron deficiency in cambodian infants.

OBJECTIVES: To assess and compare efficacy of two micronutrient sprinkle supplementation on growth, anemia, and iron deficiency in Cambodian infants. METHODS: A total of 204 infants aged 6 months and living in Kompong Chhnang Province, Cambodia were randomly assigned to receive daily supplements of either iron (12.5 mg) plus folic acid (150 mug) plus zinc (5 mg) (MMN, n = 68), or iron (12.5 mg) plus folic acid (150 microg) alone (FFA, n = 68), or placebo (n = 68) for a 12 month period in powder form as sprinkles. Anthropometrics was evaluated bimonthly. Biochemical assessment was performed at baseline and at the end of intervention period. RESULTS: At baseline, the overall mean (SD) of hemoglobin concentration was 101 g/L. No difference among groups was found for growth pattern. Significant decline was observed for weight-for-age and height-for-age z-scores in any group (P < 0.0001). The rate of recovery from anemia was significant (P < 0.001) and comparable between MMN (54%) and FFA (53%) groups and higher than in the placebo group (22%, P < 0.0001). Through the study period, no significant change in the rate of iron deficiency was found in MMN and FFA groups, whereas it increased in the placebo group (31%, baseline vs. 52%, end of study; P < 0.0001). CONCLUSION: Both MMN and FFA supplements were effective for preventing or treating anemia in Cambodian infants and stabilizing plasma levels of ferritin. Use of micronutrients in a controlled home setting, as sprinkled daily supplements, may be promising in preventing and treating anemia in developing countries.