Potential Micronutrient Deficiencies in the First 1000 Days of Life: The Pediatrician on the Side of the Weakest.

PURPOSE OF REVIEW: This study is to examine potential micronutrient deficiencies and any need for supplementation in children following specific diet plans in the first 1000 days of life. RECENT FINDINGS: Optimal nutrition in the first 1000 days of life has a lifelong positive impact on child development. Specific intrauterine and perinatal factors, pathological conditions, and dietary restrictions can represent potential risk factors for micronutrient deficiencies in the first 1000 days of life, which can have negative systemic consequences. Preterm and low-birth-weight infants are intrinsically at risk because of immature body systems. Children affected by cystic fibrosis are prone to malnutrition because of intestinal malabsorption. The risk of micronutrient deficiency can increase in various situations, including but not limited to children following selective dietary regimens (vegetarian and vegan diets and children affected by specific neuropsychiatric conditions) or specific dietary therapies (children affected by food allergies or specific metabolic disorders and children following restricted diet as a part of therapeutic approach, i.e., ketogenic diet for epilepsy). In light of this situation, the micronutrient status in these categories of children should be investigated in order to tailor strategies specific to the individual's metabolic needs, with a particular focus on deficiencies which can impair or delay the physical and cognitive development of children, namely, vitamin B12, vitamin D and folic acid, as well as oligo-elements such as iron, zinc, calcium, sodium, magnesium, and phosphorus, and essential fatty acids such as omega-3. Identification of micronutrient deficiency in the first 1000 days of life and timely supplementation proves essential to prevent their long-term consequences.

Vitamin D Supplementation in the Assessment of Cardiovascular Risk Factors in Overweight and Obese Children.

Background: Childhood obesity is associated with cardiovascular-disease (CVD) risk factors, an unfavorable lipid profile and reduced levels of 25(OH)D. The aim of our study is to evaluate whether vitamin D supplementation may play a role in the assessment of the CVD risk factors in overweight/obese children and adolescents. Methods: We performed a retrospective observational study involving children (9−15 years of age) with a known diagnosis of overweight or obesity (BMI > 25) and decreased levels of 25(OH)D (<25 ng/mL), who underwent oral vitamin D supplementation (100,000 UI, one vial/month) for six months. The anthropometric parameters, 25(OH)D, serum lipids and ALT levels were measured at the beginning (T0) and after 6 months (T1). Results: Of the 58 patients recruited, 45 had an increase in the serum 25(OH)D levels after supplementation. Vitamin D supplementation was associated with a decrease in the serum levels of the total cholesterol (p = 0.009), LDL-C (p = 0.005) and ALT (p = 0.005), and an increase in HDL-C (p = 0.03). These results were confirmed when the correction for the body mass index (BMI) was applied. Conclusions: The favorable effect of vitamin D supplementation on the total cholesterol, LDL-C, HDL-C and ALT could transform these values into modifiable risk factors starting in early childhood, with beneficial effects on long-term health.

Supportive treatment of vascular dysfunction in pediatric subjects with obesity: the OBELIX study.

INTRODUCTION: Overweight or obese children develop abnormal endothelial cell dysfunction and arterial intima-media thickening with increased vasomotor tone and inflammation. Curcumin, resveratrol, zinc, magnesium, selenium, and vitamin D have shown beneficial effects on endothelial function. We test, among overweight and obese pediatric subjects, the effects on the endothelium of a combination of curcumin, resveratrol, zinc, magnesium, selenium, and vitamin D. METHODS: Forty-eight subjects (6-17 years) were randomized into two groups (placebo vs treatment) attended three visits at 0, 3, and 6 months (±15 days). Endothelial function was assessed by means of a post-occlusive release hyperemic (PORH) test for estimation of delta flow (DF) and hyperemic AUC index, and a heat provocation test (HPT) to measure DF HPT (DFHPT). RESULTS: Significant DF difference was noted at 6 months in both groups (p < 0.001). Overall time trend was significantly different between baseline, 3 months, and 6 months both in placebo (p < 0.05) and treatment (p < 0.001) groups and their comparison (p < 0.001). No differences were noted in hyperemic AUC index (3 and 6 months), whilst there were significant differences in time trends of rreatment (p < 0.001) and placebo (p < 0.05) groups and their comparison (p < 0.001). DFHPT difference between groups was significant at 3 and 6 months (p < 0.05). The overall time trend was significant exclusively in Treatment group between 3 and 6 months (p < 0.05). Correlation with anthropometrics was found for DF and body mass index (r = 0.677 6 months, p < 0.05), as well as for hyperemic AUC index and males (r = 0.348, p < 0.05), while DFHPT showed no correlation. CONCLUSION: Curcumin, resveratrol, zinc, magnesium, selenium, and vitamin D appear to be promising in enhancing endothelial function by improvement of both DF in the PORH test and DF in the HPT, lowering the risk of developing cardiovascular diseases in overweight and obese pediatric subjects.

IgE-mediated fish allergy in children: is omega-3 supplementation useful?

The management of fish allergy relies on the elimination of all fish from the diet. Nevertheless, an exclusion diet can be problematic from a paediatric nutritional perspective. The issue of a substitute diet for children suffering from fish allergy seems to be not adequately addressed and the consequences of a fish exclusion diet in paediatric age are not known. Fish has an important nutritional value, it is rich in vitamins of group B, D and A, selenium, calcium and phosphorus, iron, zinc, magnesium, iodine and omega-3. While vitamins and iodine are normally present in the diet, omega-3 is present in few other foods, such as vegetable seed oils and nuts. Hence, the scientific research indicates a generic advice regarding a possible omega-3 supplementation in children with fish allergy. Given the knowledge about omega-3 supplementation having a potential good risk-benefit ratio and the absence of serious adverse events related to the omega-3 supplementation, this type of supplementation may seem advisable in children affected by fish allergy.

Prevention of recurrent respiratory infections : Inter-society Consensus.

Recurrent respiratory infections (RRIs) are a common clinical condition in children, in fact about 25% of children under 1 year and 6% of children during the first 6 years of life have RRIs. In most cases, infections occur with mild clinical manifestations and the frequency of episodes tends to decrease over time with a complete resolution by 12 years of age. However, RRIs significantly reduce child and family quality of life and lead to significant medical and social costs.Despite the importance of this condition, there is currently no agreed definition of the term RRIs in the literature, especially concerning the frequency and type of infectious episodes to be considered. The aim of this consensus document is to propose an updated definition and provide recommendations with the intent of guiding the physician in the complex process of diagnosis, management and prevention of RRIs.

Honey and children: only a grandma's panacea or a real useful tool?

Honey is a natural product that has been used as medication since the ancient times for its nutritive and therapeutic value. Despite these properties, honey use has been limited in evidence-based medicine due to the lack of evidence in clinical settings, particularly in paediatric population. An increasing interest has grown towards honey during the last years. The aim of this article is to examine the possible role of honey as a therapeutic tool in paediatrics. We performed a literature search to summarise the highest quality evidences, analysed articles regarding honey's nutritional properties and therapeutic value. The state of the art is represented by evidences related to beneficiary effects of honey on respiratory, gastroenterological and oncohaematologic diseases. Many other uses could promisingly come from in vitro studies or clinical trial based on adult samples. Honey shows an excellent risk-benefit profile and can be safely administrated in children older than 12 months. In conclusion, honey does not only represent a grandma's remedy, but is a real useful tool in different clinical settings, including paediatrics practice. However, there is a need for high-quality, large randomised controlled trials confirming effectiveness and practical application of honey in paediatric population.

Canned tuna tolerance in children with IgE-mediated fish allergy: an allergological and nutritional view.

Scientific research, diagnostic tools and clinical experience have shown that children suffering from IgE-mediated fish allergy do not need to follow a strict exclusion diet. In fact, they could tolerate some species of fish, which could be reintroduced in the diet by verifying their tolerance with an oral food challenge in a clinical setting. Consequently, it is possible to look a new insight on diagnosis and management of IgE-mediated fish allergy in children, considering the use of canned tuna in clinical settings. Authors performed a literature search through the Cochrane Library and Medline/PubMed databases. All quantitative and qualitative pediatric studies involving diagnosis and management of IgE-mediated fish allergy and the use of canned tuna in clinical settings were considered. Articles related to allergological and nutritional features of fish, and especially canned tuna, were selected. This research was conducted on May 2020. Canned tuna shows peculiar allergological and nutritional characteristics. Relating to allergy, canning process, characterized by cooking the fish under pressure for a time equal to about 7 hours, can lead a conformational change in parvalbumin, making it less allergenic. In terms of nutrition, canned tuna contains B, D and A vitamins and, above all, omega-3 fatty acids and shows a favourable and significantly sustainable nutritional profile. Lower allergenicity, adequate nutritional value and its rich availability in markets at reasonable costs, could make the use of canned tuna as a solution with an excellent risk/benefit ratio in the field of IgE-mediated fish allergy.

Appropriate and inappropriate vitamin supplementation in children.

The vitamin status of a child depends on many factors and most of the clinical studies do not take into account the different access to adequate nutrition of children coming from different countries and the consequent major differences in micronutrients or vitamin deficits between low-income and high-income countries. Vitamin supplements are included in the general field of dietary supplements. There is a large amount of not always factual material concerning vitamin supplements, and this may sometimes create confusion in clinicians and patients. Inadequate information may lead to the risk of attributing beneficial properties leading to their over-use or misuse in the paediatric field. Vitamin supplementation is indicated in all those conditions in which a vitamin deficiency is found, either because of a reduced intake due to reduced availability of certain foods, restrictive diets or inadequate absorption. The lack of guidelines in these fields may lead paediatricians to an improper use of vitamins, both in terms of excessive use or inadequate use. This is due to the fact that vitamin supplementation is often intended as a therapy of support rather than an essential therapeutic tool able to modify disease prognosis. In fact, various vitamins and their derivatives have therapeutic potential in the prevention and treatment of many diseases, especially in emerging conditions of paediatric age such as type 2 diabetes and the metabolic syndrome. The aim of the present article is to analyse the state of the art and consider new perspectives on the role of vitamin supplements in children.

Bone Marrow Foot Oedema in Adolescents: The Role of Vitamin D.

BACKGROUND: Bone marrow oedema (BMO) in children/adolescents is a rare clinical condition without an etiologic cause. It is associated with typical increased signal intensity on T2-weighted magnetic resonance images (MRI) and an increase in bone turnover in which vitamin D plays a pivotal role. No treatment guidelines for these young patients are to date available. METHODS: We performed a retrospective study in a pediatric setting of 13 patients with diagnosis of primary BMO of the foot on the basis of clinical and radiological findings. Data collection included sex, age, patient history, symptoms at presentation, clinical examination, laboratory bone turnover markers, vitamin D levels, MRI, treatment, and outcome. RESULTS: Vitamin D deficiency or insufficiency was found in 76.9% of cases. All patients were treated with adequate vitamin D daily intake, a short course of analgesic therapy, physical therapy, avoiding detrimental feet and ankle immobilization. All fully recovered in 3-month lag period. CONCLUSIONS: Our data highlight that environmental factors, such as underestimated articular or bone microtraumatisms, as well as joint hyper mobility, in a bone turnover milieu of vitamin D deficiency could be the cause of this clinical conditions. Adequate vitamin D supplementation, associated with physical and analgesic therapy, is crucial in the management of BMO.

Vitamin C: should daily administration keep the paediatrician away?

Vitamin C is an organic compound that is almost ubiquitous in the daily diet of individuals. There are clear indications of supplementation when secondary deficiency is detected related with reduced dietary intake or reduced absorption. On the other hand, indications for supplementation concerning an increased need are controversial. Several authors have studied the role of vitamin C as an adjuvant in the treatment of diseases that may affect children and adolescents. These diseases affect all organs and systems: specifically, vitamin C supplementation could play a role in respiratory, neurological, psychiatric, oncohematological, nephrological, ophthalmological and nutritional disorders. In paediatric age, a significant benefit of vitamin C supplementation has been observed in depressive pathology, iron-deficiency anaemia and chronic renal failure related to haemodialysis. No evidence was found with vitamin C supplementation on mortality, cognitive performance, quality of life, eye diseases, infections, cardiovascular diseases and tumours. This evidence may be related to the fact that in developed countries, vitamin C is almost ubiquitous in the daily diet of each individual. In conclusion, studies on non-industrialised populations in which there could be a real benefit from such supplementation, have yet to be conducted.

Vitamin D Daily versus Monthly Administration: Bone Turnover and Adipose Tissue Influences.

Vitamin D is involved in bone metabolism and in many various extra-skeletal diseases such as malabsorption syndromes, cardiovascular and metabolic diseases, cancer, and autoimmune and neurological diseases. However, data on the optimal route of administration are not consistent. The aims of our study were to analyze not only the influence of daily vs. monthly administration of vitamin D on bone metabolism and bone turnover, but also the effects of different routes of administration on fat mass in a cohort of adults with low levels of 25(OH) vitamin D3 at baseline. We analyzed 44 patients with hypovitaminosis at baseline and after six months of two different regimens of administration: seven drops (1750 IU)/day vs. 50,000 IU/month. We found that the two regimens were equivalent; 36 out of 44 patients reached the normal range of vitamin D after six months of treatment. Interestingly, the main determinant of vitamin D at baseline was the waist circumference. In addition, 22 patients treated by monthly regimen were evaluated after 18 months of treatment. At the end of follow-up, patients showed normal levels of vitamin D, with increased calcium levels and decreased bone turnover. Waist circumference also decreased. Our results support the efficacy of vitamin D3 given monthly both for correcting hypovitaminosis and for maintaining vitamin D levels. The relationship between serum 25(OH)vitamin D3 concentration and waist circumference supports vitamin D having a protective role in the current setting, since waist size is directly associated with the risk of cardiovascular and metabolic diseases.

Antioxidant supplementation and exhaled nitric oxide in children with asthma.

BACKGROUND: The effect of allergen avoidance on airway inflammation is similar to that observed with treatment with inhaled steroids, whereas inhaled steroids have no effect on oxidative stress-induced inflammation. OBJECTIVE: The aim of this study was to retrospectively evaluate the potential effect of an antioxidant dietary supplement on exhaled nitric oxide over a month in pediatric patients on stable antiasthma treatment. METHODS: Forty-seven children with moderate-to-severe asthma were retrospectively evaluated. All the patients were sensitive to Dermatophagoides pteronyssinus and Dermatophagoides farinae, and they were receiving the minimum inhaled corticosteroid dosage required to maintain adequate control. Within a few weeks of admission at Misurina Hospital in the Alps, the regular treatment was gradually reduced, then some children who were receiving a daily dose of inhaled corticosteroids, ≤200 mcg of fluticasone propionate, were prescribed a nutraceutical dietary supplement for at least 4 weeks. Lung function and fractional exhaled nitric oxide (FeNO) measurements were recorded at the beginning and after 1 month of the dietary supplementation. RESULTS: Baseline lung function and FeNO values did not differ between the two groups of patients. After 4 weeks of nutraceutical supplementation, FeNO values decreased, from 19.00 ppb (interquartile range, 14-31 ppb) to 11.00 ppb (interquartile range, 6-23 ppb) (p = 0.03). No significant reduction was observed in the group that did not receive the supplementation, and no significant difference between groups was observed, both at baseline and after 4 weeks of nutraceutical supplementation. CONCLUSION: Supplementation with a nutraceutical of antioxidants and anti-inflammatory compounds, such as curcumin, resveratrol, soy phospholipids, zinc, selenium, and vitamin D, may be associated with reduced airway inflammation, as documented by a fall in FeNO.

Is vitamin D deficiency correlated with childhood wheezing and asthma?

There is increasing evidence that vitamin D regulates immune responses. There is also epidemiological evidence of a relationship between vitamin D deficiency and development of asthma. In addition, several epidemiological studies suggest that low levels of vitamin D during pregnancy and early life are inversely associated with the risk of developing respiratory infections and wheezing in childhood. Vitamin D also seems to reduce asthma exacerbation and increase the response to glucocorticoids. These findings have led to considering a possible link between the occurrence of allergic respiratory diseases and low levels of vitamin D. However, the precise role of vitamin D in the pathogenesis of asthma still remains unclear, emphasizing the need for well-designed trials on vitamin D supplementation to decipher its role in preventing and/or managing the disease. This review examines the relationship that exists between vitamin D deficiency and childhood wheezing and asthma.

Colostrum-derived B and T cells as an extra-lymphoid compartment of effector cell populations in humans.

Colostrum contains cellular components that convey immunological protection to offspring. In the present study the main subsets of lymphocytes present in colostrum and in peripheral blood of healthy screened mothers were compared through the evaluation of >15 different flow cytometry markers. Colostrum and peripheral blood samples were collected within 3 days after full-term delivery. Flow cytometry assays and laboratory tests were performed soon after collection. Among B cells, percentages of CD19(+)CD5(+) cells, pertaining to natural immunity system, were significantly higher in colostrum than in peripheral blood (33 vs. 5%, p = 0.047). CD4(+) T cells, effector cells (CD45RA(+)/CD27(-)) and effector memory cells (CD45RA(-)/CD27(-)) were significantly higher in colostrum (p < 0.001) than in peripheral blood, as well as activated CD4(+) T cells (HLA(-)DR(+)) (36% vs. 6% p = 0.0022) and CD4(+) terminally differentiated effector T cells (CD57(+)) (p < 0.001). With regards to CD8(+) T cells, a comparable significant increase in effector (p < 0.02) and effector memory cells (p < 0.001) was also observed. Moreover, an increased surface expression of HLA-DR and CD57 (p < 0.001) on CD8(+) T cells in colostrum was detected. Colostrum contains a different distribution of lymphocyte subsets with respect to peripheral blood from mothers, confirming the observation that lymphocytes probably migrate in milk in a selective way. Colostrum T and B lymphocytes appear to be enriched with subsets possessing effector functions or belonging to the innate immune system, what could transfer a prompt line of defence to offspring.

Analysis of urinary parameters as risk factors for nephrolithiasis in children with celiac disease.

PURPOSE: Intestinal malabsorption can cause urinary stone disease via enteric hyperoxaluria. It has been shown that celiac disease, a common malabsorption disorder, is associated with an increased risk of calcium oxalate kidney stones in adults. Since no published data are available in the pediatric population, we analyzed urinary excretion of electrolytes in children with celiac disease to assess the risk of nephrolithiasis. MATERIALS AND METHODS: The study population consisted of 115 children 1 to 16 years old (mean 5 years) with positive serological tests for celiac disease (anti-endomysium and anti-tissue transglutaminase antibodies) referred to us for jejunal biopsy to confirm the diagnosis. Assessment was requested because patients presented with poor growth, anemia, gastrointestinal disorders or a family history of celiac disease. After obtaining informed consent we performed urine tests to measure urinary variables and blood tests to exclude metabolic disorders and evaluate renal function. RESULTS: All patients had a biopsy confirmed diagnosis of celiac disease. Oxaluria was normal in all children studied. However, levels of urinary calcium were decreased in patients with celiac disease and were inversely associated with disease severity (p = 0.0004). CONCLUSIONS: In contrast to adults, increased urinary excretion of oxalate was not detectable in children presenting with celiac disease. Therefore, the risk of nephrolithiasis appears not to be increased compared to healthy children. The observed hypocalciuria probably further decreases the tendency to form kidney stones.

Immune regulatory cytokines in the milk of lactating women from farming and urban environments.

Children living on farms have fewer allergies. It is unclear whether breastfeeding in different environments contributes to preventing allergies by exposing offspring to different cytokines that can modulate immune responses. The aim of this study was to quantify and compare levels of Transforming Growth Factor-beta1 (TGF-beta1) and Interleukin-10 (IL-10) in the colostrum and mature milk of mothers living in towns at sea level (references) and mothers on farms. Milk samples were collected within 3 days postpartum (colostrum) and at the first month of the baby's life (mature milk). Sixty-nine reference mothers and 45 farm mothers participated in the study. TGF-beta1 concentrations were significantly higher both in the colostrum (p < 0.05) and in mature milk (p < 0.05) of farm mothers. In the reference mothers, a significant decrease in TGF-beta1 concentrations was observed between colostrum (650, range 0-8000 pg/ml) and mature milk (250, range 0-8000 pg/ml) (p < 0.05). In farm mothers, TGF-beta1 concentrations were 1102 pg/ml (range 0-14,500) in colostrum and remained high in mature milk (821 pg/ml, range 0-14,650). IL-10 concentrations were higher in the mature milk of farm mothers (p < 0.05). No significant differences in IL-10 were observed between colostrum and mature milk in the control group (15 pg/ml, range 0-1800, and 0 pg/ml, range 0-230) or in farm mothers (9.5 pg/ml, range 0-1775, and 14.2 pg/ml, range 0-930), respectively. Exposure to a farm environment is associated with higher concentrations of TGF-beta1 and IL-10 in breast milk when compared to exposure to an urban environment. Higher cytokine concentrations in breast milk may influence early modulation of the development of an immune response, leading to a reduced prevalence of allergy-related diseases in farm children.