No COVID-19 pandemic impact on incidence and clinical presentation of celiac disease in Italian children.

AIM: We aimed to evaluate the impact of Coronavirus Disease-19 (COVID-19) pandemic on the incidence and clinical presentation of celiac disease (CD) in children. METHODS: The diagnoses of CD were compared between the COVID-19 pandemic (from April 2020 to March 2022) and the pre-pandemic period (from April 2018 to March 2020) in three Italian Paediatric Gastroenterology centres (Varese, Como, Catanzaro). Electronic patient records were reviewed and additional information were collected through parental interview. The diagnosis of CD was made according to ESPGHAN criteria. SARS-CoV-2 infection was diagnosed based on pre-vaccination positive serum antibodies or nasopharyngeal swabs. Z test and chi-square were used for statistical analysis. RESULTS: The overall number of paediatric diagnosis of CD did not differ between the two years pre-pandemic and pandemic periods (177 and 172 cases) in the three Italian participating centres. Clinical presentation of CD was also similar throughout the study periods. SARS-CoV-2 infection has been documented in 10.6% of children but only in 5.8% of these occurred before CD diagnosis. CONCLUSION: Different to what reported for other autoimmune diseases, the incidence and presenting symptoms of CD in our paediatric population did not change during the COVID-19 pandemic compared to the previous 2 years.

Mobile Health technology in pediatric esophagogastroduodenoscopy quality indicators assessment: results from a national program of the Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition.

BACKGROUND AND AIMS: Upper endoscopy procedures (UEP, esophagogastroduodenoscopy [EGDS] and retrograde endoscopic retrograde cholangiography [ERCP]) are an established standard of care in pediatric gastroenterology. The Pediatric endoscopy quality improvement network (PEnQuIN) recently published its pediatric-specific endoscopy quality guidelines. This study, initiated by the Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition (SIGENP), aims to evaluate the adherence of Italian Pediatric Endoscopy Centers to these established quality standards. METHODS: Conducted between April 2019 and March 2021, this nationwide study utilized a smartphone app-based approach. Data encompassing pediatric endoscopy facilities, patient profiles, endoscopy indications, 17 procedure-related PEnQuIN indicators, and a GHAA-9m patient satisfaction questionnaire were systematically collected. RESULTS: A comprehensive analysis of 3582 procedures from 24 PECs revealed that 2654 (76%) were UEP. The majority of centers (75%) involved more than one operator, with 9 PEC incorporating adult endoscopists, responsible for 5% of UEPs. Overall, adherence to quality standards was good; however, areas of improvement include sub-optimal reporting of sedation details, adherence to disease-specific guidelines, and patient satisfaction questionnaire completeness (56%). The complication rate aligned with literature standards (1%), and patient satisfaction was generally high. A noteworthy observation was a 30% decrease monthly reporting rate and a shift in disease-specific patterns following the COVID-19 outbreak. CONCLUSIONS: Pediatric UEP practices in Italy adhere well to established quality standards. Emphasizing the adoption of disease-specific guidelines is crucial for optimizing resources, enhancing diagnostic accuracy, and minimizing unnecessary procedures. Prioritizing patient satisfaction is important for immediate enhancements in practice as well as for future research endeavors.

SMC1A epilepsy syndrome: clinical data from a large international cohort.

SMC1A epilepsy syndrome or developmental and epileptic encephalopathy-85 with or without midline brain defects (DEE85, OMIM #301044) is an X-linked neurologic disorder associated with mutations of the SMC1A gene, which is also responsible for about 5% of patients affected by Cornelia de Lange syndrome spectrum (CdLS). Only described in female patients, SMC1A epilepsy syndrome is characterized by the onset of severe refractory epileptic seizures in the first year of life, global developmental delay, a variable degree of intellectual disability, and dysmorphic facial features not typical of CdLS. This was a descriptive observational study for the largest international cohort with this specific disorder. The main goal of this study was to improve the knowledge of the natural history of this phenotype with particular attention to the psychomotor development and the epilepsy data. The analyzed cohort shows normal prenatal growth with the subsequent development of postnatal microcephaly. The incidence of neonatal problems (seizures and respiratory compromise) is considerable (51.4%). There is a significant prevalence of central nervous system (20%) and cardiovascular malformations (20%). Motor skills are generally delayed. The presence of drug-resistant epilepsy is confirmed; the therapeutic role of a ketogenic diet is still uncertain. The significant regression of previously acquired skills following the onset of seizures has been observed. Facial dysmorphisms are variable and no patient shows a classic CdLS phenotype. To sum up, SMC1A variants caused drug-resistant epilepsy in these patients, more than two-thirds of whom were shown to progress to developmental and epileptic encephalopathy. The SMC1A gene variants are all different from each other (apart from a couple of monozygotic twins), demonstrating the absence of a mutational hotspot in the SMC1A gene. Owing to the absence of phenotypic specificity, whole-exome sequencing is currently the diagnostic gold standard.

Celiac disease in autism spectrum disorder: data from an Italian child cohort.

BACKGROUND: In recent decades some studies described the frequent co-occurrence of celiac disease autoimmunity and overt celiac disease in patients with autism. Therefore, it was suggested that celiac disease could play a possible role in the etiopathogenesis of autism spectrum disorder. However, several other studies have not confirmed this association. The aim of the present study was to elucidate the potential association between autism spectrum disorder and celiac disease. METHODS: We prospectively collected data from an Italian cohort of 223 children at the time of their clinical diagnosis of autism spectrum disorder in the 2019-2020 period. A serological celiac disease screening was performed and data were available for 196 patients; male (M):female (F) ratio = 4.4:1; median age = 3.6 years; age range = 1.6-12.8 years. Full-blown celiac disease was established according to the diagnostic algorithm of the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) 2012 or 2019 guidelines. Fisher's exact test was used to compare the celiac disease seroprevalence and prevalence in our autism spectrum disorder cohort and in the Italian healthy pediatric population studied by Gatti et al. to highlight the possible differences between the two groups. RESULTS: A not statistically significant difference between the celiac disease seroprevalence in our autism spectrum disorder cohort (4.08%) and Gatti's Italian healthy group (2.22%) was found, p = 0.0810; OR = 1.871. A similar result emerged for overt celiac disease prevalences (2.24% versus 1.58%, respectively), p = 0.2862; OR = 1.431. CONCLUSIONS: Our data validates a weakness of association between autism spectrum disorder and celiac disease. On the basis of our results, a regular screening for CD in patients with ASD is not recommended to a greater extent than in the general population.

Celiac disease prevalence and predisposing-HLA in a cohort of 93 Williams-Beuren syndrome patients.

Williams-Beuren syndrome is considered to be at increased risk for celiac disease, as for recent literature data and celiac disease guidelines, despite pathogenic mechanisms are still unclear. Our study analyzed the prevalence of autoimmune disorders, HLA DQ2 and/or DQ8 haplotypes, of transglutaminase antibodies and of diagnosis of celiac disease in a cohort of 93 Williams-Beuren syndrome's patients (mean age 21.26 years). Our study showed an increased prevalence of celiac disease equal to 10.8% (10/93 patients). We did not find a significant different frequency of predisposing HLA in subjects with Williams-Beuren syndrome compared to literature data in the general population (49.5% vs. 42.9%, with p > .1), nor a susceptibility to autoimmunity. This suggests that the increased prevalence of celiac disease in Williams-Beuren syndrome cannot be ascribed to HLA haplotype and may be related to other factors that still need to be identified in these patients.

Hematemesis in Infants: The First Evidence-Based Score to Predict the Need for Timely Endoscopy.

OBJECTIVES: Infantile acute upper gastrointestinal bleeding involves a decision for therapeutic intervention that most pediatricians first coming into contact with the patient are, not unreasonably, unable to objectively provide. Therefore, some objective tools of individual risk assessment would seem to be crucial. The principal aim of the present study was to investigate the anamnestic and clinical parameters of infants with hematemesis, together with laboratory and instrumental findings, to create a scoring system that may help identify those infants requiring an appropriate and timely application of upper gastrointestinal (GI) endoscopy. METHODS: Clinical data of infants admitted for hematemesis to the participating centers over the study period were systematically collected. According to the outcome dealing with rebleeding, need for blood transfusion, mortality, finding of GI bleeding lesions, or need for surgical intervention, patients were blindly divided into a group with major clinical severity and a group with minor clinical severity. Univariate and multivariate logistic regressions were conducted to investigate significant prognostic factors for clinical severity. RESULTS: According to our findings, we drafted a practical diagnostic algorithm and a clinical score able to predict the need for timely upper GI endoscopy (BLOVO infant score). Our clinical scoring system was created by incorporating anamnestic factors, clinical parameters, and laboratory findings that emerged as predictors of a worst outcome. CONCLUSIONS: We provided the first objective tool of individual risk assessment for infants with hematemesis, which could be very useful for pediatricians first coming into contact with the patient in the emergency department.

Colon hypoganglionosis in Beckwith-Wiedemann syndrome: a new rare comorbidity?

We describe the case of a patient with a clinical and molecular diagnosis of Beckwith-Wiedemann Syndrome (BWS) and a clinical, radiologic and histologic diagnosis of colon isolated hypoganglionosis. BWS is a genetic multisystem disorder characterized by generalized and lateralized overgrowth, macroglossia, abdominal wall defects, neonatal hypoglycemia and predisposition to embryonal tumors (Brioude et al., Nat Rev Endocrinol 1998; 14:229-249). Hypoganglionosis of the colon is a condition that clinically resembles Hirschsprung's disease and it is part of a group of numerous and heterogeneous conditions that are defined 'Variants of Hirschsprung's disease' (Friedmacher and Puri, Pediatr Surg Int 2013; 29:855-872). To the best of our knowledge, the association of BWS with Hirschsprung's disease has been observed only in one patient, an infant with hypoglycemia (Shah et al., BMJ Case Rep 2020; 13:e235121). We suppose that dysganglionosis could be rare comorbidity of BWS. We suggest to put particular attention to patients affected by BWS who develop early severe constipation taking into account the possibility to study them at radiologic and histologic levels to show the possible evidence of Hirschsprung's disease variants.

Caregiver Social Status and Health-Related Quality of Life in Neurologically Impaired Children on Home Enteral Nutrition.

We aimed to investigate the association between caregiver social status and health-related quality of life (HRQoL) in children with neurological impairment (NI) on home enteral nutrition (HEN). This was an ancillary study of a multicenter, cross-sectional study which explored HRQoL in 75 NI children on HEN. All the caregivers from the original cohort were contacted, and data on education level, occupation and marital status were collected. The association between social status and HRQoL was investigated using a multiple Poisson Generalized Linear Model. In total, 93 caregivers were included, responsible for the care of 71 children. The caregivers of four children of the original cohort did not answer the questionnaire. Mothers with high-level education presented lower HRQoL in comparison to mothers with low-level (ß: -5.97; 95% CI -11.51, -0.10; p = 0.027) or medium-level education (ß: 4.85; 95% CI -9.87, 0.53; p = 0.044). The analysis of the subgroup of cases in which the main caregiver was represented by both parents gave similar findings, with education level of the father being negatively correlated with HRQoL. Our data showed that higher education level may negatively affect quality of life of caregivers of NI children. This could be helpful in identifying at-risk families and addressing supportive efforts.

Williams-Beuren Syndrome and celiac disease: A real association?

Celiac disease (CD) screening in patients with Williams-Beuren Syndrome (WBS) is suggested, although data described in literature are discordant regarding CD prevalence in WBS. We retrospectively collected data from 101 WBS Italian patients [mean age: 13.5 years], to clarify the CD prevalence in a large cohort. All patients underwent a CD biochemical screening: IgA and anti-transglutaminase reflex antibodies (tTGA). CD-specific HLA typing was available for 42 patients. Small intestinal biopsy was performed in patients according to ESPGHAN guidelines. In 7 WBS patients an overt celiac disease was diagnosed. In 3 patients CD was confirmed by symptoms, HLA-DQ heterodimers and CD specific antibodies title, whereas in 4 patients, it was confirmed by a small intestinal biopsy. CD prevalence in our cohort is 6.9% (7/101). In 42/101 patients the CD-specific HLA typing was available, detecting 29/42 (69%) patients genetically predisposed to CD. The CD prevalence and CD-specific HLA prevalence are both higher than in the general population (p < 0.001; p < 0.001). Our cohort is the most numerous described confirming that the CD risk in WBS patients is significantly greater than in general population. Moreover, our HLA typing results, as well as scientific literature, suggest that the higher CD prevalence in WBS patients might not be intrinsically related to the genetic disease itself but with the higher HLA prevalence. However, HLA typing should be performed in bigger WBS cohorts to confirm this hypothesis. Our data confirms that HLA typing is mandatory in WBS patients and that CD screening should be performed only if genetically predisposed.

Complex nutritional deficiencies in a large cohort of Italian patients with Cornelia de Lange syndrome spectrum.

Cornelia de Lange syndrome Spectrum (CdLSp) is characterized by intellectual disability, facial dysmorphisms, and growth impairment. Although eating difficulties are a well-known feature of the disease, there is no data regarding the nutritional deficiencies of these patients. The food intake was tracked using a dietary transcription provided by the family/caregivers, biochemical nutritional parameters were measured with laboratory tests and through an accurate clinical evaluation of the incidence of qualitative and quantitative imbalances in a cohort of 73 patients with CdLSp ware determined. Of these 73, 62 (85%) subjects provided a complete and detailed dietary transcription. In the studied population, a quantitative caloric imbalance in 47/62 (76%) subjects was observed. The caloric intake was low in 27/62 (43%) subjects whereas excessive in 20/62 (33%). Only 15/62 (24%) had an optimum caloric intake. Regarding micronutrients, a calcium intake deficiency in 32% of the patients (20/62) was observed. Blood tests revealed a low iron level in 22/73 (30%) of the patients and 25(OH)D deficiency in 49/73 (67%). Serum hypocalcemia was not evidenced. Qualitative and quantitative imbalances resulted in more frequent than expected in CdLSp patients. A qualitative imbalance was more prevalent in younger patients while in older patients prevailed mainly a quantitative disproportion. We found no statistically meaningful correlation between dietary imbalances, genetic, or clinical parameters. Our findings highlight the need for further studies to evaluate the basal metabolic rate of CdLSp patients and find a correlation with their growth impairment.

Nissen fundoplication in Cornelia de Lange syndrome spectrum: Who are the potential candidates?

Cornelia de Lange spectrum (CdLSp) is a rare genetic condition characterized by intellectual disability, facial dysmorphisms, major malformations, growth impairment, and development delay. Approximately 80% of CdLSp patients have gastroesophageal reflux disease (GERD) with a varied clinical presentation. The aim of this study is to define potential clinical/genetic risk factors based on the clinical phenotype description of CdLSp patients with severe GERD who underwent surgical treatment. We retrospectively collected data from 23 CdLSp patients, 13 females and 10 males. Mean age of the patients undergoing surgical treatment was of 4 years. 21/23 (91%) had a molecular characterization, of which 21/21 (100%) had a NIPBL gene mutation, while 2/23 (9%) did not have a genetical characterization, only a clinical diagnosis. Most of our patients presented a moderate-severe severity score (21/23, 91%) with limb malformations evidenced in 10/23 (44%) of our patients and a moderate-severe intellectual disability in 20/23 (87%). Therefore, CdLSp patients harboring NIPBL variants, upper limb malformations and severe psychomotor delay are more likely to suffer from severe GERD, not responsive to proton pump inhibitors treatment. These features should be considered as clinical markers for potentially severe GERD that might require surgical treatment.

Health-Related Quality of Life and Home Enteral Nutrition in Children with Neurological Impairment: Report from a Multicenter Survey.

We aimed to measure the health-related quality of life (HRQoL) of children with neurological impairment (NI) on home enteral nutrition (HEN). An original survey among the caregivers of NI children on HEN for ≥ 12 months followed in three Italian centers (Messina, Como and Varese) was carried out between January 2013 and September 2018. The questionnaire was made up of 12 issues focused on the frequency with which certain situations associated with HEN are perceived, and grouped into physical and psychological/social dimensions. The results were analyzed statistically according to the age of the children, underlying disease, and the HEN programs' duration. In total, 80 caregivers were approached, and 75 surveys were completed (an overall response rate of 93.7%). Nearly all the caregivers reported a satisfying HRQoL, ranging from acceptable (n = 6, 8%), to good (n = 22, 29.3%), to excellent (n = 47, 62.7%). A significant correlation was found between HRQoL and underlying NI-associated disease (p = 0.001). Our data showed that HEN positively affects the QoL of NI children and their caregivers. This should encourage healthcare providers to consider this nutritional intervention early in the approach to this group of patients, in order to prevent or reduce QoL impairment.

Paediatric Home Artificial Nutrition in Italy: Report from 2016 Survey on Behalf of Artificial Nutrition Network of Italian Society for Gastroenterology, Hepatology and Nutrition (SIGENP).

Home Artificial Nutrition (HAN) is a safe and efficacious technique that insures children's reintegration into the family, society and school. Epidemiological data on paediatric HAN in Italy are not available. AIM: to detect the prevalence and incidence of Home Parenteral Nutrition (HPN) and Home Enteral Nutrition (HEN), either via tube or mouth, in Italy in 2016. MATERIALS AND METHODS: a specific form was sent to all registered SIGENP members and investigators of local HAN centres, inviting them to provide the requested centre's data and demographics, underlying diseases and HAN characteristics of the patients. RESULTS: we recorded 3403 Italian patients on HAN aged 0 to 19 years from 22 centres: 2277 HEN, 950 Oral Nutritional Supplements (ONS) and 179 HPN programs. The prevalence of HEN (205 pts/million inhabitants) and HPN (16 pts/million inhabitants) has dramatically increased in Italy in the last 9 years. Neurodisabling conditions were the first indication for HEN by tube or mouth while HPN is mainly requested in digestive disorders. CONCLUSIONS: HAN is a widespread and rapidly growing treatment in Italy, as well as in other European countries. Awareness of its extent and characteristics helps improving HAN service and patients' quality of life.

Use of nutritional devices in Cornelia de Lange syndrome: Data from a large Italian cohort.

Cornelia de Lange syndrome (CdLS) is a genetic condition characterized by intellectual disability, peculiar facial dysmorphisms, multiorgan malformations, and growth problems. Majority cases of CdLS are caused by mutations in genes of Cohesin pathway. Although feeding problems are a well-known feature, no specific data have been published about the use of nutritional devices. We analyzed use, type, time of introduction, and duration of nutritional devices in 73 CdLS patients. In total, 29/73 (40%) used a device; nasogastric tube (NGT) in 28/73 (38%) and percutaneous endoscopic gastrostomy (PEG) in 7/73 (10%). NGT was placed during the first days/weeks of life. 19/28 (68%) maintained it for less than 3 months, 7/28 (25%) for a period between 3 and 12 months, while 2/28 (7%) for more than 1 year. PEG was placed within the first year in 4/7 (57%) and removed in two patients after 4 years These data have been matched with a wide number of genetic and clinical variables. Presence of upper limb malformations is positively correlated with the need of a device. From the opposite side, the use of a device positively correlates with a more severe prognosis as regard growth, intellectual development and disease severity. Our data show that nutritional devices are frequently used by CdLS patients, also if the majority of them (93.1%) succeed with time in achieving a normal oral nutrition. Finally, the need, the type of device used and the duration of NGT or/plus PEG can be considered a further sign of worse prognosis of the disease itself.

Bulb biopsies for the diagnosis of celiac disease in pediatric patients.

BACKGROUND: Celiac disease (CD) is a gluten-dependent enteropathy. The current standard for diagnosing CD involves obtaining 4 biopsy samples from the descending duodenum. It has been suggested that duodenal bulb biopsies may also be useful. OBJECTIVE: To assess the utility of bulbar biopsies for the diagnosis of CD in pediatric patients. DESIGN: Prospective study. SETTING: Single center. PATIENTS: Forty-seven consecutively enrolled pediatric patients with celiac serologies and a clinical suspicion of CD. INTERVENTIONS: All patients underwent EGD, and 4 biopsy samples were obtained from the duodenal bulb and 4 from the descending duodenum of each child. MAIN OUTCOME MEASUREMENTS: The pathologist blindly reported the Marsh histological grade for the diagnosis of CD of the bulb and descending duodenum. RESULTS: The diagnosis of CD was histologically confirmed in 89.4% (42/47) of the cases of biopsy samples obtained from the descending duodenum and in all 47 obtained from the bulb. In 35 patients (74.5%), histology was the same in the bulb and duodenum; in 11 (23.4%) cases, the grade of atrophy was higher in the bulb than in the descending duodenum, and 5 (10.6%) had bulb histology positive for CD but negative duodenal findings. One child (2.1%) had a higher histological grade in the duodenum than in the bulb. The diagnostic gain with bulbar biopsies was 10.6%. LIMITATIONS: Small sample and absence of a comparison group (asymptomatic children with normal CD antibodies). CONCLUSIONS: We suggest examining 4 biopsy samples from the duodenal bulb and 4 from the descending duodenum to improve diagnostic accuracy of CD.

IgA anti-actin antibodies in children with celiac disease: comparison of immunofluorescence with Elisa assay in predicting severe intestinal damage.

BACKGROUND: Previous studies have demonstrated that the presence of serum IgA antibodies against actin filaments (AAA) in patients with celiac disease (CD) is strongly associated with mucosal damage and severe degrees of villous atrophy.The aims of the present study were (1) to verify the effectiveness of IgA-AAA in newly diagnosed CD patients in a clinical setting (2) to compare the immunofluorescence assay with ELISA assay; (3) to compare the correlation of our IgA anti-tissue transglutaminase antibodies (tTG-Ab) class with mucosal intestinal lesions. METHODS: 90 patients underwent endoscopy and multiple biopsies for suspected CD on the basis of symptoms, in presence of positive tTG-Ab tests. Twenty biopsied and 25 not-biopsied subjects with negative tTG-Ab were tested as control groups. IgA-AAA assays were performed by indirect immunofluorescence using rat epithelial intestinal cells, and by ELISA with a commercial kit. tTG-Ab assay was a radio-binding assay. Intestinal specimens were collected by upper endoscopy and the histological study was done according to the Marsh's classification modified by Oberhuber (M/O). Auto-antibodies assays and histological evaluation have been performed blindly by skilled operators. RESULTS: CD diagnosis was confirmed in 82 patients (type I M/O in 2 patients, IIIA in 18 patients, IIIB in 29 patients and IIIC in 33 patients). Two patients with type 1 lesion in presence of positive tTG-Ab and abdominal complaints, started a gluten free diet. The rate of IgA-AAA positivity (sensitivity) by IFI and ELISA in histologically proven celiac disease patients, were 5.5% and 25% patients in IIIA, 27.5% and 34.4% patients in IIIB, 78.8% and 75% in IIIC patients, respectively.Patients with normal or nearly normal mucosa, regardless of tTG-Ab status, presented negative IgA-AAA IFI assay. On the other hand, 1 patient with normal mucosa but positive tTG-Ab, also presented positive IgA-AAA ELISA. All healthy non biopsied controls had negative IgA-AAA. tTG-Ab serum concentration was significantly correlated with more severe intestinal lesion (IIIB, IIIC M/O). CONCLUSIONS: IgA-AAA may be undetectable in presence of severe mucosal damage. Histology is still necessary to diagnose celiac disease and IgA-AAA cannot be included in usual screening tests, because it has little to offer if compared to the well-established tTG-Ab.IgA-AAA could be an adjunctive, very useful tool to support the diagnosis of CD in case of suboptimal histology, when the biopsy is to be avoided for clinical reasons, or in case of negative parents' consensus.