Lower risk of atopic dermatitis among infants born extremely preterm compared with higher gestational age.

BACKGROUND: It is not yet known whether the risk of developing atopic dermatitis (AD) is influenced by preterm birth. Moreover, AD risk has not been assessed in a large sample of extremely preterm infants (< 29 weeks' gestation). OBJECTIVES: To determine whether the risk of AD is influenced by preterm birth. METHODS: We investigated the relationship between gestational age (GA) and AD using data from two independent population-based cohorts, including a total of 2329 preterm infants, of whom 479 were born extremely preterm. RESULTS: There was a lower percentage of children with AD in the extremely preterm group compared with those born at a greater GA (Epipage cohort, 2-year outcome: 13·3% for 24-28 weeks, 17·6% for 29-32 weeks, 21·8% for 33-34 weeks, P = 0·02; LIFT cohort, 5-year outcome: 11% for 24-28 weeks, 21·5% for 29-32 weeks, 19·6% for 33-34 weeks, P = 0·11). After adjusting for confounding variables, a lower GA (< 29 weeks) was significantly associated with decreased risk of AD in the Epipage cohort [adjusted odds ratio (aOR) 0·57, 95% confidence interval (CI) 0·37-0·87; P = 0·009] and the LIFT cohort (aOR 0·41, 95% CI 0·18-0·90; P = 0·03). CONCLUSIONS: Very low GA (< 29 weeks) was associated with a lower risk of AD compared with higher GA (29-34 weeks) and full-term birth.

Dietary treatment of cows' milk protein allergy in childhood: a commentary by the Committee on Nutrition of the French Society of Paediatrics.

The diagnosis of cows' milk protein allergy (CMPA) requires first the suspicion of diagnosis based on symptoms described in the medical history, and, second, the elimination of cows' milk proteins (CMP) from the infant's diet. Without such rigorous analysis, the elimination of CMP is unjustified, and sometimes harmful. The elimination diet should be strictly followed, at least until 9-12 months of age. If the child is not breast fed or the mother cannot or no longer wishes to breast feed, the first choice is an extensively hydrolysed formula (eHF) of CMP, the efficacy of which has been demonstrated by scientifically sound studies. If it is not tolerated, an amino acid-based formula is warranted. A rice protein-based eHF can be an alternative to a CMP-based eHF. Soya protein-based infant formulae are also a suitable alternative for infants >6 months, after establishing tolerance to soya protein by clinical challenge. CMPA usually resolves during the first 2-3 years. However, the age of recovery varies depending on the child and the type of CMPA, especially whether it is IgE-mediated or not, with the former being more persistent. Once the child reaches the age of 9-12 months, an oral food challenge is carried out in the hospital ward to assess the development of tolerance and, if possible, to allow for the continued reintroduction of CMP at home. Some children with CMPA will tolerate only a limited daily amount of CMP. The current therapeutic options are designed to accelerate the acquisition of tolerance thereof, which seems to be facilitated by repeated exposure to CMP.

The role of nutrition in non-alcoholic fatty liver disease treatment in obese children.

Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent chronic liver disease that occurs mostly in the context of insulin resistance and obesity. It has rapidly evolved into the most common cause of liver disease among children. The incidence is high in obese children and a greater risk of disease progression is associated with severe obesity, highlighting the role of nutrition. To date, there is no consensus on NAFLD management. This is a narrative review of clinical studies on the potential benefit of nutritional interventions, including lifestyle modifications, vitamins, docosahexaenoic acid, and probiotics in children with NAFLD. The Comité de nutrition de la Société Française de Pédiatrie (CN-SFP) emphasizes the effect of limiting added sugar intake, i.e., fructose or sucrose-containing beverages, and promoting physical activity in the care of NAFLD.

"Baby-led weaning" - Progress in infant feeding or risky trend?

Baby-led weaning (BLW), proposed as a new form of complementary feeding, has emerged as a real trend phenomenon in the media. Infants are seated at the family table from the age of 6 months, facing the foods they grab and bring to their mouth: they decide which foods they want to eat and what amount. The consumption of mashed foods and the use of a spoon are totally discouraged. BLW is increasingly used in nurseries and centers of young children. A bibliographic search carried out between 2000 and 2021 found 423 articles, of which 38 were selected. The clinical studies selected are 11 cross-sectional observational studies and two randomized controlled studies. BLW promotes breastfeeding, the early introduction of morsels, the respect of the child's appetite, the use of unprocessed foods, and the choice of "homemade" and friendliness. These benefits can nonetheless be reached with usual complementary feeding (SCF), according to current recommendations. Other benefits are claimed without scientific evidence such as easier achievement of dietary complementary feeding and an optimal growth with prevention of excess weight gain. BLW has some obvious downsides. The infant may not get enough energy, iron, zinc, vitamins, and other nutrients, or too much protein, saturated fat, salt, or sugar. The risk of choking, which must be distinguished from the physiological gagging reflex, has not been ruled out by scientific studies. Currently, the Nutrition Committee of the French Pediatric Society considers that the data published to date in terms of benefits and risks of BLW do not lend themselves to advice for this practice in preference over SCF carried out according to current recommendations.

Enteral nutrient supply for preterm infants: commentary from the European Society of Paediatric Gastroenterology, Hepatology and Nutrition Committee on Nutrition.

The number of surviving children born prematurely has increased substantially during the last 2 decades. The major goal of enteral nutrient supply to these infants is to achieve growth similar to foetal growth coupled with satisfactory functional development. The accumulation of knowledge since the previous guideline on nutrition of preterm infants from the Committee on Nutrition of the European Society of Paediatric Gastroenterology and Nutrition in 1987 has made a new guideline necessary. Thus, an ad hoc expert panel was convened by the Committee on Nutrition of the European Society of Paediatric Gastroenterology, Hepatology, and Nutrition in 2007 to make appropriate recommendations. The present guideline, of which the major recommendations are summarised here (for the full report, see http://links.lww.com/A1480), is consistent with, but not identical to, recent guidelines from the Life Sciences Research Office of the American Society for Nutritional Sciences published in 2002 and recommendations from the handbook Nutrition of the Preterm Infant. Scientific Basis and Practical Guidelines, 2nd ed, edited by Tsang et al, and published in 2005. The preferred food for premature infants is fortified human milk from the infant's own mother, or, alternatively, formula designed for premature infants. This guideline aims to provide proposed advisable ranges for nutrient intakes for stable-growing preterm infants up to a weight of approximately 1800 g, because most data are available for these infants. These recommendations are based on a considered review of available scientific reports on the subject, and on expert consensus for which the available scientific data are considered inadequate.

Efficacy and safety of hydrolyzed rice-protein formulas for the treatment of cow's milk protein allergy.

Foods for special medical purposes (FSMPs) with a protein fraction made of hydrolyzed rice protein (HRPs) have been on the market in Europe since the 2000s for the treatment of cow's milk protein allergy (CMPA). HRP formulas (HRPFs) are proposed as a plant-based alternative to cow's milk protein-based extensively hydrolyzed formulas (CMP-eHF) beside the soy protein formulas whose use in CMPA is controversial. HRPFs do not contain phytoestrogens and are derived from non-genetically modified rice. HRPFs are strictly plant-based apart from the addition of vitamin D3 (cholecalciferol). As the amino acid content of rice proteins differs from that of human milk proteins, the protein quality of these formulas is improved by supplementation with free lysine, threonine, and tryptophan. The consumption of HRPFs has risen: for example, in France HRPFs account for 4.9% in volume of all formulas for children aged 0-3 years. Several studies have shown the adequacy of HRPFs in treating CMPA. They ensure satisfactory growth from the 1st weeks of life for infants and toddlers, both in healthy children and in those with CMPA. HRPFs can be used to treat children with CMPA either straightaway or in second intention in cases of poor tolerance to CMP-eHF for organoleptic reasons or for lack of efficacy. In France, the cost of HRPFs is close to that of regular infant or follow-on formulas.

Nutritional risks of ARFID (avoidant restrictive food intake disorders) and related behavior.

Avoidant/restrictive food intake disorder (ARFID) has recently been added to the DSM V (Diagnostic and Statistical Manual of Mental Disorders, 5th edition) as a new class of eating disorders (EDs). ARFID is characterized by a lack of interest in eating or avoiding specific types of foods because of their sensory characteristics. This avoidance results in decreased nutritional intake, eventually causing nutritional deficiencies. In severe cases, ARFID can lead to dependence on oral nutritional supplements, which interferes with psychosocial functioning. The prevalence of ARFID can be as high as 3% in the general population, and it is often associated with gastrointestinal symptoms and mainly appears in children with anxiety disorders. Given the high prevalence of ARFID, a rapid and systematic nutrition survey should be conducted during every pediatric consultation. Its treatment should also be adapted depending on the severity of the nutritional problem and may involve hospitalization with multidisciplinary care (pediatrician, nutritional therapist, dietitian, psychologists, and speech therapists).

[Feeding during the first months of life and prevention of allergy]. / Alimentation des premiers mois de vie et prévention de l'allergie.

Allergy consists in the different manifestations resulting from immune reactions triggered by food or respiratory allergens. Both its frequency and severity are increasing. The easiest intervention process for allergy prevention is the reduction of the allergenic load which, for a major allergen such as peanuts, has to begin in utero. The primary prevention strategy relies first on the detection of at risk newborns, i.e. with allergic first degree relatives. In this targeted population, as well as for the general population, exclusive breastfeeding is recommended until the age of 6 months. The elimination from the mother's diet of major food allergens potentially transmitted via breast milk may be indicated on an individual basis, except for peanut, which is systematically retrieved. In the absence of breastfeeding, prevention consists in feeding at-risk newborns until the age of 6 months with a hypoallergenic formula, provided that its efficiency has been demonstrated by well-designed clinical trials. Soy based formulae are not recommended for allergy prevention. Complementary feeding should not be started before the age of 6 months. Introduction of egg and fish into the diet can be made after 6 months but the introduction of potent food allergens (kiwi, celery, crustaceans, seafood, nuts, especially tree nuts and peanuts) should be delayed after 1 year. This preventive policy seems partially efficacious on early manifestations of allergy but does not restrain the allergic march, especially in its respiratory manifestations. Probiotics, prebiotics as well as n-3 fatty polyunsaturated acids have not yet demonstrated any definitive protective effect.

[Folic acid and prevention of neural tube closure defects: the question is not solved yet]. / Prévention par l'acide folique des défauts de fermeture du tube neural: la question n'est toujours pas réglée.

Between 1981 and 1996, several interventional studies proved the efficacy of periconceptional folic acid supplementation in the prevention of neural tube closure defects (NTCD), first in women at risk (with a previous case of NTCD) and also in women of the general population in age to become pregnant. The poor observance of this supplementation led several countries (USA, Canada, Chile...) to decide mandatory folic acid fortification of cereals, which permitted a 30% (USA) to 46% (Canada) reduction in the incidence of NTCD. Moreover, this benefit was accompanied by a diminished incidence of several other malformations and of stroke and coronary accidents in elderly people. However, several papers drew attention to an increased risk of colorectal and breast cancer in relation with high blood folate levels and the use of folic acid supplements. A controlled interventional study showed a higher rate of recurrence of colic adenomas and a higher percentage of advanced adenomas in subjects receiving 1mg/day of folic acid. A recent study demonstrated an abrupt reversal of the downward trend in colorectal cancer 1 year after the beginning of cereal folic acid fortification in the USA and Canada. Two studies also reported impaired cognitive functions in elder persons with defective vitamin B(12) status. Taken in aggregate, these studies question the wisdom of a nationwide, mandatory, folic acid fortification of cereals. As of today, despite their limited preventive efficacy, a safe approach is to keep our current French recommendations and to increase the awareness of all caregivers, so as to improve the observance of these recommendations.

Nutritional management of cow's milk allergy in children: An update.

Cow's milk is one of the most common foods responsible for allergic reactions in children. Cow's milk allergy (CMA) involves immunoglobulin E (IgE)- and non-IgE-mediated reactions, the latter being both variable and nonspecific. Guidelines thus emphasize the need for physicians to recognize the specific syndromes of CMA and to respect strict diagnostic modalities. Whatever the clinical pattern of CMA, the mainstay of treatment is the elimination from the diet of cow's milk proteins. The challenge is that both the disease and the elimination diet may result in insufficient height and weight gain and bone mineralization. If, during CMA, the mother is not able or willing to breastfeed, the child must be fed a formula adapted to CMA dietary management, during infancy and later, if the disease persists. This type of formula must be adequate in terms of allergic efficacy and nutritional safety. In older children, when CMA persists, the use of cow's milk baked or heated at a sufficient temperature, frequently tolerated by children with CMA, may help alleviate the stringency of the elimination diet. Guidance on the implementation of the elimination diet by qualified healthcare professionals is always necessary. This guidance should also include advice to ensure adequate bone growth, especially relating to calcium intake. Specific attention should be given to children presenting with several risk factors for weak bone mineral density, i.e., multiple food allergies, vitamin D deficiency, poor sun exposure, steroid use, or severe eczema. When CMA is outgrown, a prolonged elimination diet may negatively impact the quality of the diet over the long term.

Parenteral nutrition for preterm infants: Issues and strategy.

Due to transient gut immaturity, most very preterm infants receive parenteral nutrition (PN) in the first few weeks of life. Yet providing enough protein and energy to sustain optimal growth in such infants remains a challenge. Extrauterine growth restriction is frequently observed in very preterm infants at the time of discharge from hospital, and has been found to be associated with later impaired neurodevelopment. A few recent randomized trials suggest that intensified PN can improve early growth; whether or not such early PN improves long-term neurological outcome is still unclear. Several other questions regarding what is optimal PN for very preterm infants remain unanswered. Amino acid mixtures designed for infants contain large amounts of branched-chain amino acids and taurine, but there is no consensus on the need for some nonessential amino acids such as glutamine, arginine, and cysteine. Whether excess growth in the first few weeks of life, at a time when very preterm infants receive PN, has an imprinting effect, increasing the risk of metabolic or vascular disease at adulthood continues to be debated. Even though uncertainty remains regarding the long-term effect of early PN, it appears reasonable to propose intensified initial PN. The aim of the current position paper is to review the evidence supporting such a strategy with regards to the early phase of nutrition, which is mainly covered by parenteral nutrition. More randomized trials are, however, needed to further support this type of approach and to demonstrate that this strategy improves short- and long-term outcome.

Calcium and protein kinetics in prepubertal boys. Positive effects of testosterone.

We investigated the effects of 4-6-wk administration of testosterone on calcium and protein metabolism in six healthy prepubertal short boys (mean age +/- SE = 12.9 +/- 0.6 yr). At baseline, subjects received a 4-h infusion of L-[1-13C]leucine and L-[2-15N]glutamine, and were given 42Ca intravenously, and 44Ca PO. Testosterone enanthate (approximately 3 mg/kg) was given I.M. 2 wk apart (two doses n = 5, three doses n = 1), and the study was repeated 4-5 d after the last injection. After testosterone therapy, there were significant increases in serum testosterone and mean peak and total growth hormone concentrations. Net calcium absorption (Va) and retention (Vbal) also increased (Va 13.3 +/- 2.3 vs 21.5 +/- 2.3; mg.kg-1.d-1, Vbal 8.0 +/- 2.1 vs 16.6 +/- 2.5, mg.kg-1.d-1, P < .05 both), as well as Ca's net forward flow into bone and total exchangeable pool (16 and 20%, respectively). The rate of appearance of leucine (an indicator of proteolysis) increased by 17.6 +/- 5.9%, P = 0.036. Leucine oxidation decreased by 48.6 +/- 8.0%, P = 0.004; thus, nonoxidative leucine disappearance, which estimates protein synthesis, increased significantly by 34.4 +/- 7.7%, P = 0.009. Glutamine's rate of appearance also increased (+32%), mostly through enhanced glutamine de novo synthesis (+42%). In conclusion, short term testosterone administration significantly increases calcium's retention and net forward flow into bone in prepubertal humans, as well as whole body estimates of protein and calcium anabolism. These effects may represent a pure androgen effect, an amplification of growth hormone's action or some combination of these factors.

Vitamin A in pediatrics: An update from the Nutrition Committee of the French Society of Pediatrics.

Vitamin A (retinol) fulfills multiple functions in vision, cell growth and differentiation, embryogenesis, the maintenance of epithelial barriers and immunity. A large number of enzymes, binding proteins and receptors facilitate its intestinal absorption, hepatic storage, secretion, and distribution to target cells. In addition to the preformed retinol of animal origin, some fruits and vegetables are rich in carotenoids with provitamin A precursors such as ß-carotene: 6µg of ß-carotene corresponds to 1µg retinol equivalent (RE). Carotenoids never cause hypervitaminosis A. Determination of liver retinol concentration, the most reliable marker of vitamin A status, cannot be used in practice. Despite its lack of sensitivity and specificity, the concentration of retinol in blood is used to assess vitamin A status. A blood vitamin A concentration below 0.70µmol/L (200µg/L) indicates insufficient intake. Levels above 1.05µmol/L (300µg/L) indicate an adequate vitamin A status. The recommended dietary intake increases from 250µg RE/day between 7 and 36 months of age to 750µg RE/day between 15 and 17 years of age, which is usually adequate in industrialized countries. However, intakes often exceed the recommended intake, or even the upper limit (600µg/day), in some non-breastfed infants. The new European regulation on infant and follow-on formulas (2015) will likely limit this excessive intake. In some developing countries, vitamin A deficiency is one of the main causes of blindness and remains a major public health problem. The impact of vitamin A deficiency on mortality was not confirmed by the most recent studies. Periodic supplementation with high doses of vitamin A is currently questioned and food diversification, fortification or low-dose regular supplementation seem preferable.

Role of glutamine as a glucose precursor in fasting humans.

Recently, significant incorporation of labeled carbon into plasma glucose was documented during infusion of 14C-labeled glutamine in postabsorptive humans. Such labeling of plasma glucose can occur as a result of two different processes: either 1) through incorporation of glutamine carbon into glucose via glutamine entering Krebs cycle at alpha-ketoglutarate or 2) through simple fixation of labeled CO2 resulting from oxidation of labeled glutamine. Therefore, these studies were designed to determine 1) whether glutamine contributes carbon to gluconeogenesis other than through mere CO2 fixation, and, if so, 2) whether the apparent transfer of carbon from glutamine to glucose increases with fasting. Eight healthy adults were studied on two consecutive days: once after an overnight (18-h) fast and again on the second day of fasting (42-h fast). On each study day, subjects received a simultaneous 5-h infusion of D-[6,6-2H2lglucose, L-[3,4-13C2lglutamine, and L-[1-14C]leucine. Apparent rates of incorporation of glutamine carbon into glucose were estimated from the appearance of 13C into plasma glucose; glucose and glutamine production rates (appearance rate [Ra]) were determined from plasma [2H2]glucose and [13C2]glutamine enrichments, respectively. The appearance of 14C into plasma glucose was used to correct the measured rates of carbon transfer from glutamine to glucose as a result of CO2 fixation. We observed that of the apparent contribution of labeled glutamine to gluconeogenesis, only 4% occurred as a result of fixation of labeled CO2, while 96% seemed to occur through other routes. We also observed that between 18 and 42 h of fasting, 1) the relative contribution of protein breakdown to glutamine production was enhanced, while that of de novo synthesis declined; 2) the apparent contribution of glutamine to glucose production rose from 8 +/- 1 to 16 +/- 3% of overall glucose Ra; and 3) the relative apparent contribution of glutamine to gluconeogenesis remained constant. From the current data, it cannot be ascertained to what extent the apparent carbon transfer from glutamine to glucose represents a true contribution of glutamine to gluconeogenesis or mere carbon exchange between the trichloroacetic acid cycle and the gluconeogenic pathway. These findings are nevertheless compatible with a role of glutamine as a significant precursor of glucose in fasting humans.

Corticosteroid-binding globulin modulates cortisol concentration responses to a given production rate.

In most clinical situations, the ability of the adrenal to produce cortisol is studied with measurements of cortisol concentration. The validity of this assumes the existence of a predictable relationship between cortisol production and plasma cortisol concentration. This assumption was tested by determining if production rates, as simulated by constant cortisol infusions, were predictive of the resultant plasma and urine cortisol concentrations in dexamethasone-suppressed subjects. Additional attempts to predict simulated cortisol production rates were made with infusions of [9,12,12-2H3]cortisol. Thirty-six 8-h cortisol infusions were performed in 24 subjects. Although there was a tendency to achieve a higher plasma cortisol concentration response at a higher cortisol infusion rate (P < 0.04), the known cortisol infusion rate was a poor predictor of plasma cortisol responses (r2 = 0.12). Addition of corticosteroid-binding globulin concentration (CBG) as a covariate greatly improved the predictability of plasma cortisol responses (r2 = 0.52). Urine free cortisol, normalized to inulin excretion, had a predictable relationship to cortisol infusion rate (r2 = 0.82). Isotope-enrichment data from a group of 6 subjects receiving multiple cortisol infusions during administration of [9,12,12-2H3]cortisol gave the most accurate predictions of the known cortisol infusion rates (r2 = 0.93). It is concluded that: 1) cortisol infusion (production) rate and plasma cortisol concentration are poorly correlated; 2) CBG is an important modulator of concentration responses to a given production rate; and 3) short (8-h) infusions of [9,12,12-2H3]cortisol may be used to determine cortisol production rates in humans. The mechanisms by which CBG modulates cortisol concentration responses are elaborated in a companion report.

Oral nutrition in patients receiving home cyclic parenteral nutrition: pattern of substrate utilization.

Patients receiving cyclic home parenteral nutrition (PN) often have a significant oral caloric intake. This study describes the metabolic use of fuels, as assessed by indirect calorimetry, in eight stable, ambulatory, noncancerous, adult patients receiving glucose-based PN with (PN + oral) or without (PN only) a self-selected oral intake. Patients' weight was 91 +/- 2% (mean +/- SE) of ideal body weight, and fat mass was 22 +/- 5 and 31 +/- 2% of actual body weight in males and females, respectively. Under the PN-only regimen, providing 104 +/- 5% of predicted basal energy expenditure (BEE), patients were in equilibrium for energy and nitrogen balances. Oral supplementation (absorbed oral intake 80 +/- 5% of BEE) was associated with positive energy and nitrogen balances but also with nearly continuous net fat synthesis. We conclude that the glucose-based PN + mixed oral regimen enables the patients to face the increased energy requirements of everyday ambulatory life but is not associated with an optimal body composition in long-term PN patients.

Determination of glutamine in muscle protein facilitates accurate assessment of proteolysis and de novo synthesis-derived endogenous glutamine production.

BACKGROUND: Results of tracer studies indicate that skeletal muscle contributes to approximately 70% of overall glutamine production in healthy adults; the contribution of de novo synthesis being estimated at approximately 60%. However, measurement of the de novo synthesis rate in muscle tissue requires knowledge of the appearance rate of glutamine in plasma and the quantity of glutamine derived from intracellular proteolysis. Thus, the content of glutamine in muscle protein is a prerequisite for an accurate calculation. OBJECTIVE: The objective of the study was to measure glutamine in muscle protein. DESIGN: Muscle specimens (open biopsies) were obtained from humans (10 men and 4 women), rats (n = 4), cows (n = 4), and pigs (n = 4). Glutamine was assessed via prehydrolysis derivatization, rapid microwave-enhanced acid hydrolysis, and 5-dimethylaminonaphthalene-1-sulfonyl chloride (dansyl chloride) reversed-phase HPLC, and expressed per mg alkali-soluble protein (ASP) and DNA. RESULTS: Glutamine concentrations in muscle cell protein of various species ranged from 41 to 49 microg/mg ASP; the differences were not species related. The combined means (+/-SDs) for the 4 species were 43.6 +/- 4.9 microg/mg ASP and 11.9 +/- 2.0 mg/mg DNA, respectively. In humans, there was no apparent influence of age, sex, or BMI. CONCLUSIONS: Direct and specific measurements of glutamine in intact muscle protein were 50% lower than assumed previously. We used data compiled from earlier studies to recalculate the contributions of proteolysis and de novo synthesis to the endogenous production of glutamine in selected age groups of healthy humans; these contributions remained remarkably constant at approximately 13% and approximately 87%, respectively.