Italian Journal of Pediatrics

Gut microbiota plays a significant role in human health and energy balance, and provides protection against disease states. An altered balance between microbiota and its host (dysbiosis) would appear to contribute to the development of Inflammatory Bowel Disease (IBD), Crohn’s Disease (CD) and Ulcerative Colitis (UC). CD and UC are chronic inflammatory diseases of the gastrointestinal tes.

Acute cerebellar ataxia (ACA) is a relatively common neurological disease in children. Most common types of ACA are acute post-infectious (APCA) and acute disseminated encephalomyelitis (ADEM). Less common but important causes include opsoclonus-myoclonus syndrome (OMS) and acute cerebellitis. Cerebellar neoplasms and acute hydrocephalus are additional causes of paediatric ataxia. APCA is the most common cause of ACA in children, comprising about 30-50% of total cases. This is a report about an immunocompetent 4-yrs-old male affected by APCA, due to co-infection by human herpesvirus-6 (HHV-6) and adenovirus, with symptoms mimicking myositis.

A highly variable phenotype characterized by thyroid, respiratory and neurological defects has been reported in an already established group of disorders namely NKX2.1-related disorders. We describe here the case of an infant with a novel mutation of the NKX2.1 gene characterized by mild clinical presentation. Aim of the study was to elucidate the genotype-phenotype correlation in our patient. We performed genetic analysis of the NKX2.1 gene in an infant with no neonatal respiratory distress and near-normal results at neonatal screening test for congenital hypothyroidism, choreoathetosis, ataxia and delayed independent walking. A novel mutation of the NKX2.1 gene has been identified, that is responsible for a mild framework of congenital hypothyroidism and neurological symptoms. The frequency of congenital hypothyroidism cases associated with NKX2.1 mutations is expected to be higher in a subgroup of patients, selected according to the neurological presentation. In these patients the analysis of NKX2.1 mutational status is recommended.

Autism spectrum disorder is a complex condition with wide variation in type and severity that involves persistent challenges in social interaction, speech and nonverbal communication, restricted/repetitive behaviours and adaptive behaviours. In recent years, research has deepened the study of the predictive factors of optimal outcome, intended as indicators of positive trajectory in children with a previous diagnosis of autism who, after a therapeutic path, show a significant reduction in the “core” symptoms of autism and a positive evolution in social, adaptive, affective, and relational skills. The study included 40 children aged 21 to 66 months, enrolled between 2015 and 2016 for an autism spectrum disorder clinical suspicious. Children were re-evaluated after at least 2 years of therapy and they were divided into two groups: the ASD-ASD group included children with a confirmed diagnosis of ASD, and the ASD-OO comparison group included children who no longer met the criteria for an autism classification. The aim of this retrospective study was to investigate the presence of cognitive, emotional and relational predictors capable of predicting the presence of optimal outcome in with a diagnosis of autism; the predictors taken into consideration were the intelligence quotient, the play, the emotional contagion and the understanding of other’s intentions. In this way, it is possible to support clinicians in defining a more complete diagnostic framework of autism, using assessment tools that can be administered quickly and therefore suitable for short observation sessions in paediatric patients. The findings showed that 15 out of 40 children, after at least for 2 years, no longer fell into the diagnostic ASD category based on the ADOS-2, DSM-5 and clinical criteria. The children in the ASD-OO group initially had a higher IQ than those in the ASD-ASD group, lower severity of autistic symptoms, greater understanding of intentions, more emotional contagion, and better quality of play. The results suggest that the initial coexistence of skills in these areas at the time of the first diagnostic assessment may allow us to predict the possibility of achieving optimal outcome after 2 years of therapy. The data of this study highlight the importance of considering, during assessment, intelligence quotient, play, emotional contagion, and understanding of the intentions of others as potential prognostic predictors that can become useful tools for clinicians and paediatricians. This allows us to focus attention, in both the diagnostic and prognostic phases, on emotional-relational variables that can support the clinician in defining a more complete diagnostic framework and in planning a more personalized therapeutic path.

In children with congenital heart disease (CHD) respiratory syncytial virus (RSV) infection may have a severe course, with increased risk of morbidity and mortality, requiring hospital admission and intensive care. The aim of the present study was to evaluate the effect of prophylaxis with palivizumab in preventing RSV-associated hospitalization in infants with CHD. We carried out an observational, retrospective study in a paediatric cardiology division at a secondary-care centre in Italy, extracting from the database children with CHD who, from November 2004 to March 2022, matched the criteria for palivizumab prophylaxis, to evaluate the hospitalization rate in CHD patients with and without palivizumab prophylaxis and their RSV-related hospitalization characteristics compared with a group of children without CHD and no other underlying clinical conditions (control group, CG), hospitalized for RSV infection. One hundred twenty-eight children with CHD were enrolled in the study, mainly (71.9%) with increased pulmonary flow, and received palivizumab prophylaxis. Twenty-seven received hospital care for bronchiolitis. Almost all CHD patients hospitalized for bronchiolitis (26 out of 27) received partial prophylaxis (≤ 3 doses). CHD patients with bronchiolitis stay longer in the hospital than control (14.4 ± 21.7 days vs 6.2 ± 2.3 days) some of which require intensive care (n = 4). Our study provides evidence of the efficacy of palivizumab in protecting patients with hemodynamically significant CHD under the age of 2 years from RSV disease and its life-threatening complications. Reducing hospitalisation rate, morbidity, and mortality in this category of patients, passive immune prophylaxis with palivizumab may impact healthcare resource availability and utilisation.

Pseudohypoaldosteronism type 1 (PHA1) is a rare genetic disease due to the peripheral resistance to aldosterone. Its clinical spectrum includes neonatal salt loss syndrome with hyponatremia and hypochloraemia, hyperkalemia, metabolic acidosis and increased plasmatic levels of aldosterone. Two genetically distinct forms of disease, renal and systemic, have been described, showing a wide clinical expressivity. Mutations in the genes encoding for the subunits of the epithelial sodium channels (ENaC) are responsible for generalized PHA1. We hereby report on two Italian patients with generalized PHA1, coming from the same small town in the center of Sicily. The first patient is a male child, born from the first pregnancy of healthy consanguineous Sicilian parents. A novel SCNN1A (sodium channel epithelial subunit alpha) gene mutation, inherited from both heterozygous parents, was identified by next generation sequencing (NGS) in the homozygous child (and later, also in the heterozygous maternal aunt). A more detailed family history disclosed a possible related twenty-year-old girl, belonging to the same Sicilian small town, with referred neonatal salt loss syndrome associated to hyperkalemia, and subsequent normal growth and neurodevelopment. This second patient had a PHA1 clinical diagnosis when she was about 1 year old. The genetic investigation was, then, extended to her and to her family, revealing the same mutation in the homozygous girl and in the heterozygous parents. The neonatologist should consider PHA1 diagnosis in newborns showing hyponatremia, hyperkalemia and metabolic acidosis, after the exclusion of a salting-loss form of adrenogenital syndrome. The increased plasmatic levels of aldosterone and aldosterone/renin ratio, associated to a poor response to steroid administration, confirmed the diagnosis in the first present patient. An accurate family history may be decisive to identify the clinical picture. A multidisciplinary approach and close follow-up evaluations are requested, in view of optimal management, adequate growth and development of patients. Next generation sequencing (NGS) techniques allowed the identification of the SCNN1A gene mutation either in both patients or in other heterozygous family members, enabling also primary prevention of disease. Our report may broaden the knowledge of the genetic and molecular bases of PHA1, improving its clinical characterization and providing useful indications for the treatment of patients. Clinical approach must be personalized, also in relation to long-term survival and potential multiorgan complications.

Globalization caused a shift in trial locations towards low-middle income countries, raising ethical concerns. These include the risk that conditions primarily affecting children in these countries will be neglected in favor of those affecting developed countries. We analyzed 253 published and 69 ongoing pharmacological RCTs performed in Latin America between 2000 and 2015 involving exclusively children. While over 50% of the previously highly investigated diseases were no longer priorities, other diseases acquired greater attention in recent years. Brazil and Mexico resulted as the most active countries. A large gap remains between the real needs of children in these countries and scientific research.