Epidemiology of Paediatric Italian Food Allergy: Results of the EPIFA study.

Background: Updated epidemiologic data are important for defining effective public health strategies for pediatric food allergy (FA). Objective: The Epidemiology of Paediatric Italian Food Allergy (EPIFA) study was designed to investigate the epidemiology of pediatric FA in one of the most heavily populated Italian regions. Methods: A retrospective cohort study was performed in collaboration with family pediatricians aimed at investigating the epidemiology of Italian pediatric FA during 2009 to 2021. Family pediatricians in the Campania region were invited to use the Google Forms platform for online compilation of data forms. Data forms were reviewed by experienced pediatric allergists at the coordinating center. Results: A total population of 105,151 subjects (aged 0-14 years) was screened during the study period. Data from 752 FA patients were evaluated. A progressive increase in FA incidence and prevalence was observed from 2009 to 2021, with a relative increase up to 34% and 113.6%, respectively, at the end of study period. The relative increase in FA prevalence was higher in the 0-3-year-old age group in the same study period (+120.8%). The most frequent allergens were cow's milk, hen's egg, and nuts. Conclusion: The results of the EPIFA study showed an increase in pediatric FA incidence and prevalence from 2009 to 2021 in Italy. These results underline the necessity of new effective strategies for preventing and managing these conditions.

COVID-19 vaccine hesitancy: a survey in a population highly compliant to common vaccinations.

Vaccination is a key protective factor against COVID-19. Some vaccines have already received emergency authorization from Health Agencies, but growing skepticism and vaccine hesitancy will probably affect COVID-19 vaccination campaigns. In the attempt to shed light on this issue, we conducted an online survey in a population of parents referring to 4 pediatric practices in Naples, Italy in whom we evaluated potential vaccine acceptability in relation to socio-demographic characteristics, perception of personal health and of the impact of COVID-19, and attitudes toward general vaccination practices. Vaccination rates were analyzed also in the corresponding pediatric population.Almost 27% of participants declared they were in favor of vaccinations, and in fact real life vaccination rates in children exceeded the national mean. Only 26.5% of respondents declared they would receive COVID-19 vaccine. Vaccine refusal was attributed to safety concerns in 76% of parents. Specific vaccine attributes further reduced the acceptance rate. Female gender, younger age and lower education level were associated with non-adherence to vaccination. Among extrinsic factors of COVID-19 vaccination, only information from National Health Authorities was significantly associated to vaccine acceptance.The rate of potential COVID-19 vaccine acceptability was very poor in our population of parents. Vaccine hesitancy was mainly due to safety concerns. Demographic and educational factors were correlated to vaccine acceptability. Health education and communication strategies are needed to achieve large-scale vaccine acceptability and finally herd immunity.

Efficacy of ginger as antiemetic in children with acute gastroenteritis: a randomised controlled trial.

BACKGROUND: Ginger is a spice with a long history of use as a traditional remedy for nausea and vomiting. No data on the efficacy of ginger are presently available for children with vomiting associated with acute gastroenteritis (AGE). AIM: To test whether ginger can reduce vomiting in children with AGE. METHODS: Double-blind, randomised placebo-controlled trial in outpatients aged 1 to 10 years with AGE-associated vomiting randomised to ginger or placebo. The primary outcome was the occurrence of ≥1 episode of vomiting after the first dose of treatment. Severity of vomiting and safety were also assessed. RESULTS: Seventy-five children were randomised to the ginger arm and 75 to the placebo arm. Five children in the ginger arm and 4 in the placebo arm refused to participate in the study shortly after randomisation, leaving 70 children in the ginger arm and 71 in the placebo arm (N = 141). At intention-to-treat analysis (N = 150), assuming that all children lost to follow-up had reached the primary outcome, the incidence of the main outcome was 67% (95% CI 56 to 77) in the ginger group and 87% (95% CI 79 to 94) in the placebo group, corresponding to the absolute risk reduction for the ginger versus the placebo group of -20% (95% CI -33% to -7%, P = 0.003), with a number needed to treat of 5 (95% CI 3 to 15). CONCLUSION: Oral administration of ginger is effective and safe at improving vomiting in children with AGE. TRIAL REGISTRATION: The trial was registered on https://clinicaltrials.gov/ with the identifier NCT02701491.

Long-term multi-endpoint exposure of the microalga Raphidocelis subcapitata to lanthanum and cerium.

Significant release of rare earth elements (REEs) into the environment is mainly due to active or abandoned mining sites, but their presence is globally increasing due to their use in several industrial sectors. The effects on primary producers as Raphidocelis subcapitata are still limited. This research focused on La and Ce as the two most widespread REEs that can be currently found up to hundreds of µg/L in water and wastewater. Microalgae were exposed to La and Ce for 3 days (pH = 7.8) (short-term exposure) to derive the effective concentrations inhibiting the growth on 10% (EC10) of the exposed population. EC10 values (0.5 mg/L of La and 0.4 mg/L of Ce) were used for the 28 days long-term exposure (renewal test) to observe after 7, 14, 21, and 28 days on a multi-endpoint basis microalgae growth inhibition (GI), biomarkers of stress (reactive oxygen species (ROS), superoxide dismutase (SOD), and catalase (CAT)), and bioconcentration. Results evidenced that La and Ce EC10 increased GI (day 28) up to 38% and 28%, respectively. ROS, CAT, and SOD activities showed differential responses from day 7 to day 14, 21, and 28, suggesting, in most of the cases, that La and Ce effects were counteracted (i.e., being the values at day 28 not significantly different, p > 0.05, from the relative negative controls), except for La-related ROS activities. La and Ce significantly bioconcentrated in microalgae populations up to 2- and 5-fold (i.e., at day 28 compared to day 7), in that order. Bioconcentrated La and Ce were up to 3157 and 1232 µg/g dry weight (day 28), respectively. These results suggested that low La and Ce concentrations can be slightly toxic to R. subcapitata having the potential to be bioaccumulated and potentially transferred along the food web.

The therapeutic efficacy of Bifidobacterium animalis subsp. lactis BB-12® in infant colic: A randomised, double blind, placebo-controlled trial.

BACKGROUND: The pathogenesis of infant colic is poorly defined. Gut microbiota seems to be involved, supporting the potential therapeutic role of probiotics. AIMS: To assess the rate of infants with a reduction of ≥50% of mean daily crying duration after 28 days of intervention with the probiotic Bifidobacterium animalis subsp. lactis BB-12® (BB-12). Secondary outcomes were daily number of crying episodes, sleeping time, number of bowel movements and stool consistency. METHODS: Randomized controlled trial (RCT) on otherwise healthy exclusively breastfed infants with infant colic randomly allocated to receive BB-12 (1 × 109  CFU/day) or placebo for 28 days. Gut microbiota structure and butyrate, beta-defensin-2 (HBD-2), cathelicidin (LL-37), secretory IgA (sIgA) and faecal calprotectin levels were assessed. RESULTS: Eighty infants were randomised, 40/group. The rate of infants with reduction of ≥50% of mean daily crying duration was higher in infants treated with BB-12, starting from the end of 2nd week. No infant relapsed when treatment was stopped. The mean number of crying episodes decreased in both groups, but with a higher effect in BB-12 group (-4.7 ± 3.4 vs -2.3 ± 2.2, P < 0.05). Mean daily stool frequency decreased in both groups but the effect was significantly higher in the BB-12 group; stool consistency was similar between the two groups. An increase in Bifidobacterium abundance (with significant correlation with crying time reduction), butyrate and HBD-2, LL-37, sIgA levels associated with a decrease in faecal calprotectin level were observed in the BB-12 group. CONCLUSIONS: Supplementation with BB-12 is effective in managing infant colic. The effect could derive from immune and non-immune mechanisms associated with a modulation of gut microbiota structure and function.

Iodine deficiency among Italian children and adolescents assessed through 24-hour urinary iodine excretion.

BACKGROUND: Iodine is an essential micronutrient for intellectual development in children. Information on iodine intakes based on 24-h urinary iodine excretion (UIE) is scant, because iodine status is only assessed by the measurement of urinary iodine concentration (UIC) in spot urine samples. OBJECTIVES: The aim of our study was to evaluate the iodine intake of school-age children and adolescents, using UIE measurement in 24-h urine collections. METHODS: The study population included 1270 healthy subjects (677 boys, 593 girls) aged 6-18 y (mean age ± SD: 10.3 ± 2.9) from 10 Italian regions. Daily iodine intake was estimated as UIE/0.92, based on the notion that $\sim$92% of the dietary iodine intake is absorbed. The adequacy of intakes was assessed according to the Dietary Reference Values for iodine of the European Food Safety Authority (EFSA). Body mass index (BMI) and UIC were also measured for each subject. RESULTS: Based on the scientific opinion of EFSA, 600 of 1270 subjects (47.2%) had a lower than adequate iodine intake, with a higher prevalence among girls (54.6%) compared with boys (40.2%) (P < 0.001). Although UIE and 24-h urinary volumes increased with age (P < 0.001), a progressive decrease in the percentage of subjects with iodine excretion <100 µg/24 h (P < 0.001) was observed, without any significant difference in the percentage of subjects with UIC <100 µg/L. No significant association was detected between BMI z-score and UIE (P = 0.603) or UIC (P = 0.869). CONCLUSIONS: A sizable proportion of our population, especially girls, appeared to be at risk of iodine inadequacy. The simple measurement of UIC could lead to underestimation of the occurrence of iodine deficiency in younger children, because of the age-related smaller urine volumes producing spuriously higher iodine concentrations.

Preventive Effect of Cow's Milk Fermented with Lactobacillus paracasei CBA L74 on Common Infectious Diseases in Children: A Multicenter Randomized Controlled Trial.

Background: Fermented foods have been proposed to prevent common infectious diseases (CIDs) in children attending day care or preschool. OBJECTIVES: To investigate the efficacy of dietary supplementation with cow's skim milk fermented with the probiotic Lactobacillus paracasei CBA L74 in reducing CIDs in children attending day care or preschool. Methods: Multicenter, randomized, double-blind, placebo-controlled trial on healthy children (aged 12-48 months) consuming daily 7 grams of cow's skim milk fermented with L. paracasei CBA L74 (group A), or placebo (maltodextrins group B) attending day care or preschool during the winter season. The main outcome was the proportion of children who experienced ≥1 episode of CID during a 3-month follow-up. Fecal biomarkers of innate (α- and ß-defensins, cathelicidin) and acquired immunity (secretory IgA) were also monitored. Results: A total of 126 children (71 males, 56%) with a mean (SD) age of 33 (9) months completed the study, 66 in group A and 60 in group B. At intention to treat analysis, the proportion of children presenting ≥1 CID was 60% in group A vs. 83% in group B, corresponding to an absolute risk difference (ARD) of -23% (95% CI: -37% to -9%, p < 0.01). At per-protocol-analysis (PPA), the proportion of children presenting ≥1 CID was 18% in group A vs. 40% in group B, corresponding to an absolute risk difference (ARD) of -22% (95% CI: -37% to -6%, p < 0.01). PPA showed that the proportion of children presenting ≥1 acute gastroenteritis (AGE) was significantly lower in group A (18% vs. 40%, p < 0.05). The ARD for the occurrence of ≥1 AGE was -22% (95% CI: -37% to -6%, p < 0.01) in group A. Similar findings were obtained at PPA regarding the proportion of children presenting ≥1 upper respiratory tract infection (URTI), which was significantly lower in group A (51% vs. 74%, p < 0.05), corresponding to an ARD of -23% (95% CI: -40% to -7%, p < 0.01). Significant changes in innate and acquired immunity biomarkers were observed only in subjects in group A. Conclusions: Dietary supplementation with cow's skim milk fermented with L. paracasei CBA L74 is an efficient strategy in preventing CIDs in children.

Cow's milk and rice fermented with Lactobacillus paracasei CBA L74 prevent infectious diseases in children: A randomized controlled trial.

BACKGROUND & AIM: Fermented foods have been proposed for the prevention of infectious diseases. We evaluated the efficacy of fermented foods in reducing common infectious diseases (CIDs) in children attending daycare. METHODS: Prospective randomized, double-blind, placebo-controlled trial (registered under Clinical Trials.gov identifier NCT01909128) on healthy children (aged 12-48 months) consuming daily cow's milk (group A) or rice (group B) fermented with Lactobacillus paracasei CBA L74, or placebo (group C) for three months during the winter season. The main study outcome was the proportion of children who experienced at least one CID. All CIDs were diagnosed by family pediatricians. Fecal concentrations of innate (α- and ß-defensins and cathelicidin LL-37) and acquired immunity biomarkers (secretory IgA) were also evaluated. RESULTS: 377 children (193 males, 51%) with a mean (SD) age of 32 (10) months completed the study: 137 in group A, 118 in group B and 122 in group C. Intention-to-treat analysis showed that the proportion of children who experienced at least one CID was lower in group A (51.8%) and B (65.9%) compared to group C (80.3%). Per-protocol analysis showed that the proportion of children presenting upper respiratory tract infections was lower in group A (48.2%) and group B (58.5%) compared with group C (70.5%). The proportion of children presenting acute gastroenteritis was also lower in group A (13.1%) and group B (19.5%) compared with group C (31.1%). A net increase of all fecal biomarkers of innate and acquired immunity was observed for groups A and B compared to group C. Moreover, there was a negative association between fecal biomarkers and the occurrence of CID. CONCLUSION: Dietary supplementation with cow's milk or rice fermented with L. paracasei CBA L74 prevents CIDs in children attending daycare possibly by means of a stimulation of innate and acquired immunity.

Acceptability and efficacy of a gel hypotonic oral rehydration solution in children with acute gastroenteritis.

OBJECTIVE: Oral rehydration solution remains the mainstay of acute gastroenteritis therapy. The aim of this study was to investigate the acceptability of a new zinc-containing hypotonic super-oral rehydration solution (ORS) in a gel formulation and its efficacy in reducing the duration and severity of diarrhea in children. METHODS: This was a randomized-controlled trial of children (5-36 months of age) observed for diarrhea lasting less than 24 h. Children were randomized to receive standard hypotonic ORS (group 1) or a gel hypotonic super-ORS containing zinc (group 2). The main study outcome was ORS intake in the first 24 h. ORS intake at 4 h, rate of diarrhea resolution at 72 h of treatment, total duration and severity of diarrhea, hospitalization, and adverse effects were also evaluated. RESULTS: Eighty-three children were enrolled (group 1: 40; group 2: 43). The amount of ORS consumed at 24 h was significantly higher in group 2 than in group 1. A similar result was observed at 4 h. The number of children who refused ORS (<10 ml/kg/day) was lower in group 2 versus group 1 (P=0.001). The number of children presenting diarrhea after 72 h of treatment was lower in group 2 versus group 1 (P=0.028). Also, the mean duration of diarrhea was shorter in group 2 than in group 1 (P=0.001). The hypotonic super-ORS containing zinc in a gel formulation had a positive effect on the severity of diarrhea. No patient required hospitalization. No adverse events were observed in either of the two study groups. CONCLUSION: The new zinc-containing hypotonic super-ORS in a gel formulation is effective in the management of childhood acute gastroenteritis.

High sodium and low potassium intake among Italian children: relationship with age, body mass and blood pressure.

BACKGROUND: Hypertension is the leading cause of death in developed countries and reduction of salt intake is recommended as a key preventive measure. OBJECTIVE: To assess the dietary sodium and potassium intakes in a national sample of Italian children and adolescents and to examine their relationships with BMI and blood pressure (BP) in the framework of the MINISAL survey, a program supported by the Italian Ministry of Health. POPULATION AND METHODS: The study population included 1424 healthy subjects (766 boys, 658 girls) aged 6-18 years (mean age: 10.1±2.9) who were consecutively recruited in participating National Health Service centers in 10 Italian regions. Electrolyte intake was estimated from 24 hour urine collections tested for completeness by the concomitant measurement of creatinine content. Anthropometric indices and BP were measured with standardized procedures. RESULTS: The average estimated sodium intake was 129 mmol (7.4 g of salt) per day among boys and 117 mmol (6.7 g of salt) among girls. Ninety-three percent of the boys and 89% of the girls had a consumption higher than the recommended age-specific standard dietary target. The estimated average daily potassium intakes were 39 mmol (1.53 g) and 36 mmol (1.40 g), respectively, over 96% of the boys and 98% of the girls having a potassium intake lower than the recommended adequate intake. The mean sodium/potassium ratio was similar among boys and girls (3.5 and 3.4, respectively) and over 3-fold greater than the desirable level. Sodium intake was directly related to age, body mass and BP in the whole population. CONCLUSIONS: The Italian pediatric population is characterized by excessive sodium and deficient potassium intake. These data suggest that future campaigns should focus on children and adolescents as a major target in the framework of a population strategy of cardiovascular prevention.

Effect of different starting doses of levothyroxine on growth and intellectual outcome at four years of age in congenital hypothyroidism.

To evaluate the effect of different initial levothyroxine (LT4) replacement doses on growth and intellectual outcome in patients with congenital hypothyroidism (CH) detected by neonatal screening program, the longitudinal growth and intelligence quotient (IQ) were assessed and compared at 4 years of age in 83 patients with CH. The patients were divided into three groups according to the initial LT4 dose used: (1) group 1 (n = 42) received the previously recommended dose of 6.0-8.0 microg/kg per day; (2) group 2 (n = 21) received a dose of 8.1-10.0 microg/kg per day; (3) Group 3 (n = 20) a dose of 10.1-15.0 microg/kg per day. The IQ, evaluated by the Wechsler Preschool and Primary Scale of Intelligence test at 4 years of age, was significantly higher in group 3 (IQ 98 +/- 9) compared to group 1 (IQ 88 +/- 13; p < 0.05) but not compared to group 2 (IQ 94 +/- 13). However, the IQs were below the normal range (< 85) in six patients from group 2 (28%), but in none of the patients from group 3 (p = 0.03). Patients from group 3, with severe CH at diagnosis, had an IQ (97 +/- 9) at 4 years of age, which was not different from that of patients from the same group with moderate CH at diagnosis (IQ 99 +/- 9). Similar results were also observed in patients from group 2 however, mean IQ scores in these patients (93 +/- 12) were several points lower than those observed in patients from group 3 (95 +/- 15). After the first month of treatment, optimal serum levels of thyroxine (T4) and free thyroxine (FT4) were achieved in all groups, however, only patients from group 3 were able to normalize thyrotropin (TSH) (group 1, 16.0 +/- 12.0; group 2, 9.2 +/- 10.0; and group 3, 2.4 +/- 3.3 mU/L; p < 0.0001). Twelve patients from group 2 treated with an initial LT4 dose above 9 microg/kg per day were able to normalize TSH levels within the first 3 months of life and this resulted in a better IQ (97 +/- 16) compared to the remaining patients from the same group (IQ 90 +/- 9). In the whole group of 83 patients the IQ at 4 years of age was positively correlated to both initial LT4 dosage (r = 0.27, p < 0.02) and FT4 concentrations after the first month of treatment (r = 0.29, p < 0.02), and negatively correlated to TSH concentrations after the first month of treatment (r = -0.27, p < 0.02). No significant differences were observed in height, weight, head circumference, and bone age maturation among the three groups of patients. No clinical signs or symptoms of overtreatment were observed during follow-up in patients receiving the higher LT4 dosage. Our results indicate that high LT4 starting doses rapidly normalize serum TSH concentrations resulting in an improvement of the IQ at 4 years of age, even in patients with severe CH at diagnosis. Growth and bone age maturation are not affected by such a high dose.