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 and Osteogenesis Imperfecta in Pediatrics.

Osteogenesis Imperfecta (OI) is a heterogeneous group of inherited skeletal dysplasias characterized by bone fragility. The study of bone metabolism, in these disease, is problematic in terms of clinical and genetic variability. The aims of our study were to evaluate the importance of Vitamin D levels in OI bone metabolism, reviewing studies performed on this topic and providing advice reflecting our experience using vitamin D supplementation. A comprehensive review on all English-language articles was conducted in order to analyze the influence of vitamin D in OI bone metabolism in pediatric patients. Reviewing the studies, contradictory data were found on the relationship between 25OH vitamin D levels and bone parameters in OI, and in several studies the baseline levels of 25OH D were below the threshold value of 75 nmol/L. In conclusion, according to the literature and to our experience, we highlight the importance of adequate vitamin D supplementation in children with OI.

Effects of micronutrient and phytochemical supplementation on cardiovascular health in obese and overweight children: a narrative review.

PURPOSE OF REVIEW: Cardiovascular damage could begin early in life. Our aim was to examine the current state of the art related to micronutrient supplementation on vascular health in obese and overweight children. We considered only the studies performed over the past few years. RECENT FINDINGS: Vitamin D supplementation in the obese pediatric population with vitamin D deficiency could improve the vascular health of these subjects. The evidence is less clear on supplementation with other micronutrients. Zinc supplementation is currently the most supported by the literature. SUMMARY: As of today, we can only speculate that supplementation with other micronutrients could improve the vascular health of obese and overweight children. Strong limitations are the different instrumental methods used to assess vascular health in obese children and adolescents under micronutrients supplementation. Actually, indirect indicators more reliable to evaluate vascular health seem to be lipid profile and insulin sensitivity. Furthermore, there is a particular lack of studies in this area in recent years, especially in the pediatric population. Additional studies performed in this population should be pursued to clarify significant relationships between micronutrients and vascular health.

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.

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.

Micronutrients and Brain Development.

PURPOSE OF REVIEW: This review summarizes the most recent evidence regarding the effects of micronutrients on brain development. RECENT FINDINGS: Emerging evidence indicates that nutrition in the early life can profoundly influence neurodevelopment, affecting later life health outcomes, neurocognitive performances, and disease risks. Inadequate early life nutrition has been associated with some neuropsychiatric disorders. Epigenetic mechanisms could play a crucial role, imprinting the genomes in early life making the individual more susceptible to develop diseases later in life. Children adequately nourished are more likely to reach their developmental potential in cognitive, motor, and socioemotional abilities, with positive societal repercussions. Data from further clinical trials are needed before more definitive conclusions can be drawn regarding the efficacy of dietary interventions for improving neurocognitive and social outcomes and preventing some neuropsychiatric illnesses. Nevertheless, it is reasonable to make recommendations to our patients to adopt certain dietary habits to optimize early life nutritional status in order to avoid long-term adverse consequences. Strategies of prevention should focus on ensuring more quality food to preconceptional, pregnant, lactating women and to children in their early life, not only in those areas where malnutrition is common but also in developed countries.

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.

Behind human milk and breastfeeding: not only food.

After birth, breastfeeding should not be considered only a normal and physiological event; in fact, it encloses both physical and the psychological aspects. Human milk cannot be compared to any formula milk. Specifically, human milk has immunological and nutritional properties and it is considered the best available option which guarantees an adequate growth and an optimal development of a child. Differences in term of mediators and hormones have been shown between infants who were breastfed and ones who were not. A key point is represented by unmeasurable environmental and psycho-affective factors. So, it may be simplistic to consider human milk only as a nutrient; since it encompasses much more. The aim of our commentary is to review clinical studies about breastfeeding, analysing its consequences on the neuro-developmental achievement, growth and risk of obesity within a holistic view.

Nutrition in the First 1000 Days: Ten Practices to Minimize Obesity Emerging from Published Science.

The prevalence of childhood overweight and obesity has increased in most countries the last decades. Considering this in a simplistic way, we can say that obesity is the result of an imbalance between energy intake and energy expenditure. Moreover, the environment from conception to childhood could influence the child's future health. The first 1000 days of life start with woman's pregnancy, and offer a unique window of opportunity to contribute to obesity prevention. In light of the actual literature, the aim of our article is to discuss a proposal of 10 good practices to minimize obesity in the first 1000 days emerging from published science. (1) Both the mother's and the father's behaviors are important. A balanced diet with appropriate fat and protein intake, and favoring fruits and vegetables, is recommended for both parents during the conception period and pregnancy. Furthermore, overweight/obese women who are planning to become pregnant should reduce their weight before conception. (2) During pregnancy, at birth, and during early life, body composition measurements are crucial to monitor the baby's growth. (3) Exclusive breastfeeding is recommended at the beginning of life until six months of age. (4) Four to six months of age is the optimal window to introduce complementary feeding. Until one year of age, breast milk or follow-on/commercial formula is the main recommended feeding source, and cow's milk should be avoided until one year of age. (5) Fruit and vegetable introduction should begin early. Daily variety, diversity in a meal, and repeated exposure to the food, up to eight times, are efficient strategies to increase acceptance of food not well accepted at first. There is no need to add sugar, salt, or sugary fluids to the diet. (6) Respect the child's appetite and avoid coercive "clean your plate" feeding practices. Adapt the portion of food and don't use food as reward for good behavior. (7) Limit animal protein intake in early life to reduce the risk of an early adiposity rebound. Growing-up milk for children between one and three years of age should be preferred to cow's milk, in order to limit intake and meet essential fatty acid and iron needs. (8) The intake of adequate fat containing essential fatty acids should be promoted. (9) Parents should be role models when feeding, with TV and other screens turned-off during meals. (10) Preventive interventions consisting of promoting physical activity and sufficient time dedicated to sleep should be employed. In fact, short sleep duration may be associated with increased risk of developing obesity. Based on literature reviews, and given the suggestions described in this manuscript, concerted public health efforts are needed to achieve the healthy objectives for obesity and nutrition, and to fight the childhood obesity epidemic.

High-protein goat's milk diet identified through newborn screening: clinical warning of a potentially dangerous dietetic practice.

OBJECTIVE: Breast-feeding is an unequalled way of providing optimal food for infants' healthy growth and development and the WHO recommends that infants should be exclusively breast-fed for the first 6 months of life. For mothers who are unable to breast-feed or who decide not to, infant formulas are the safest alternative. Despite recommendations, it is possible that parents make potentially harmful nutritional choices for their children because of cultural beliefs or misinformation on infant nutrition. We describe a possible health risk of not breast-feeding, highlighting a potentially dangerous dietetic practice. Design/Setting/Subjects We report the case of a newborn who was fed with undiluted goat's milk because her mother could not breast-feed and was not aware of infant formulas. RESULTS: The dietary mistake was detected because of a positive expanded newborn screening result, characterized by severe hypertyrosinaemia with high methionine and phenylalanine levels, a pattern suggestive of severe liver impairment. The pattern of plasma amino acids was related to a goat's milk diet, because of its very different composition compared with human milk and infant formula. CONCLUSIONS: Our experience demonstrates that, when breast-feeding is not possible or is not exclusive, infants may be at risk of dangerous nutritional practices, including diets with very high protein content, such as a goat's milk diet. Families of not breast-fed infants may need appropriate advice on safe alternatives for infant nutrition to avoid the risks of inappropriate diets.

Epigenetic mechanisms elicited by nutrition in early life.

A growing number of studies focusing on the developmental origin of health and disease hypothesis have identified links among early nutrition, epigenetic processes and diseases also in later life. Different epigenetic mechanisms are elicited by dietary factors in early critical developmental ages that are able to affect the susceptibility to several diseases in adulthood. The studies here reviewed suggest that maternal and neonatal diet may have long-lasting effects in the development of non-communicable chronic adulthood diseases, in particular the components of the so-called metabolic syndrome, such as insulin resistance, type 2 diabetes, obesity, dyslipidaemia, hypertension, and CVD. Both maternal under- and over-nutrition may regulate the expression of genes involved in lipid and carbohydrate metabolism. Early postnatal nutrition may also represent a vital determinant of adult health by making an impact on the development and function of gut microbiota. An inadequate gut microbiota composition and function in early life seems to account for the deviant programming of later immunity and overall health status. In this regard probiotics, which have the potential to restore the intestinal microbiota balance, may be effective in preventing the development of chronic immune-mediated diseases. More recently, the epigenetic mechanisms elicited by probiotics through the production of SCFA are hypothesised to be the key to understand how they mediate their numerous health-promoting effects from the gut to the peripheral tissues.

Bone mass at final height in precocious puberty after gonadotropin-releasing hormone agonist with and without calcium supplementation.

The aim of our longitudinal study was to evaluate bone mass in girls affected by central precocious puberty (CPP) that have reached final height, treated with GnRH agonist triptorelin (GnRHa), with or without calcium supplementation. We studied 48 Caucasian females affected by CPP (age at diagnosis, 7.19 +/- 0.96 yr), randomly assigned to two groups: group A (n = 21) treated with GnRHa and group B (n = 27) treated with GnRHa plus calcium gluconolactate and carbonate (1 g calcium/day in two doses) for at least 2 yr. Auxological parameters (standing height, weight, body mass index) and bone mineral density (BMD) at the lumbar spine [L2-L4, anteroposterior (AP)-BMD; lateral BMD; volumetric (v)BMD)] by dual-energy x-ray absorptiometry were evaluated at the beginning [chronological age (CA), 7.29 +/- 0.91 yr; bone age (BA), 8.80 +/- 1.24 yr] and end of treatment (CA, 11.27 +/- 0.97 yr; BA, 12.35 +/- 0.43 yr) and at final height (CA, 16.17 +/- 1.9 yr; BA, 16.93 +/- 0.98 yr, in each case >15 yr). Total bone mineral content, total BMD, and fat percentage were evaluated at the end of the study period using dual-energy x-ray absorptiometry. Final height was significantly higher than predicted height at diagnosis (159.9 +/- 6.3 cm vs. 152.9 +/- 9.6 cm; P < 0.05). Body mass index and fat percentage were not statistically different from control values. Densitometric values at final evaluation in groups A and B together were lower than in controls, but the differences were not statistically significant. The vBMD was significantly higher in group B than in group A at the end of treatment period (0.213 +/- 0.022 g/cm(3) vs. 0.192 +/- 0.021 g/cm(3); P < 0.01) and at final evaluation (0.246 +/- 0.023 g/cm(3) vs. 0.227 +/- 0.024 g/cm(3); P < 0.05). The percentage change (Delta%) between the start and end of treatment period in AP-BMD and vBMD was significantly higher in group B than in group A (Delta% AP-BMD: 20.36% +/- 1.10% vs. 16.16% +/- 1.90%, P < 0.01; Delta% vBMD: 19.08% +/- 3.52% vs. 9.26% +/- 5.15%; P < 0.01) and also between the start of treatment and final evaluation (Delta% AP-BMD: 61.23% +/- 1.61% vs. 56.97% +/- 1.45%, P < 0.01; Delta% vBMD: 36.69% +/- 5.01% vs. 28.01% +/- 5.76%, P < 0.01). In all our females with CPP treated with GnRHa, bone densitometric parameters were in the normal range for age and sex. However, bone mass achievement seemed to be better preserved in the group of patients supplemented with calcium.