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.

Survey of prick test, total and specific age during food allergy in children.

AIM: To analyze the results of a systematic survey of biological tests in a symptomatic pediatric population consulting for the exploration of a possible food allergy. PATIENTS AND METHODS: 406 children included in this study, mean age 3.3+3.2 years (2 months-16 years), 159 girls and 247 boys, had cutaneous tests (Stallergènes, Paris, France), assaying of total and specific IgE, and RAST Fx5 (Pharmacia & Upjohn Diagnostics AB, Uppsala, Sweden). Those children suffering from eczema (34.9%), digestive disorders (26.1%), ORL and pulmonary (8.3%), anaphylactic choc (3.4%) or mixed symptoms (27.3%). RESULTS: The overall positivity of cutaneous tests, all confused age periods, was 34.1% with the following order: egg white (52%, p < 0.05 vs. other food), peanut (46%), egg yolk (42%), fish (34%), wheat (33%), soy (32%), cow's milk (24%) and rice (17%). It decreased significantly with age only for the egg white, 61% (0-1 year) and 68% (1-2 years) vs 31% (> 6 years), p < 0.05. The positivity of cutaneous tests for egg and peanut was more frequent with eczema than with digestive manifestations (64% vs. 44%, 57.6% vs. 34% and 56% vs. 38.7%, p < 0.05). The title of total IgE increased with age, r 0.5 p 0.001. The positivity of specific food IgE was more frequent at 4-6 years (68%) than at 0-1 year (36%), p < 0.05. It revealed, all confused age periods, the following order: egg white (74%) and peanut (64%), p < 0.05 vs. other food, cow's milk (59%), wheat (55%), soy (45%) and fish (24%). The number of high specific food IgE titers was significantly higher than the number of positive cutaneous tests by order of frequency; egg white, peanut, cow's milk, wheat and soy, p < 0.05; the reverse was observed for fish, p < 0.05. Percentage of subjects combining a high title of specific food IgE and a positive cutaneous test for egg white (39.4%) was significantly higher than the percentage of those combining a high RAST Fx5 title and a positive cutaneous test for at least one of 6 corresponding foods (25.2%), p < 0.05. CONCLUSION: The positivity of different food cutaneous tests, the rate of total and specific IgE titers and the agreement of the results varied according to age, food and symptoms.

Natural course of sensitization to hen's egg in children not previously exposed to egg ingestion.

BACKGROUND: Clinical adverse reactions to egg may occur in infants or children who have never eaten egg. They may be sensitized or even react at first egg ingestion. Few studies are available concerning the reality of egg white allergy in such sensitized children, the natural evolution of this condition and the appropriate decisions to make. OBJECTIVES: To analyze the actuality and natural course of egg allergy in children sensitized without previous of hen's egg ingestion. METHODS: We set up a clinical decision tree based on clinical history and specific egg white IgE to manage patients who had never ingested egg but were sensitized as demonstrated by a positive SPT and report a cohort of 30 such children RESULTS: The mean level of egg white specific IgE at first analysis, i.e. before 12 months, was high, 28.3 KU(A) /L, with a large range, from 0.6 to >100 KU(A) /L, below 6 KU(A) /L in only 8 patients. In 6 children ("no challenge" group), IgE values remained >8 KU(A) /L by the end of the survey and the oral challenge with egg was always denied. Their mean + SD IgE level was at 51.7 + 38 KU(A) /L at 1 year and 19.7 + 13 KU(A) /L at a mean age of 34 + 5 months. All had an associated anaphylactic reaction with milk and 5 were still allergic to milk by the end of the survey. In the remaining 24 infants, egg was given for the first time at a mean age of 30 + 9 months, by error in 4 cases, all exhibiting an immediate reaction, and in a hospital setting in 20, among whom 14 reacted. Among those 18, with a specific IgE level at 9.1 + 10 KU(A) /L at 28 + 9 months, 4 became tolerant between 3 and 4 years, with specific IgE levels below 1.3 KU(A) /L and a 5th one with specific IgE >100 KU(A) /L at 6 months tolerated scrambled eggs at age 7 year, with specific IgE at 2.6 KU(A) /L. In the 6 others, labeled "non allergic", egg white specific IgE levels were significantly lower, whatever the age, than in the "no challenge" group. The age at challenge was 35 + 8 months, with a mean specific IgE level at 1.0 + 0.9 KU(A) /L. CONCLUSION: In children sensitized to egg without previous ingestion of that food, egg tolerance appears probably in some by the age of 3 but may reveal much more prolonged in a limited number.

Circulating leptin in normal children and during the dynamic phase of juvenile obesity: relation to body fatness, energy metabolism, caloric intake, and sexual dimorphism.

In 112 obese compared with 42 lean children, we found that serum leptin is elevated early in the evolution of childhood-onset obesity (28.4 +/- 1.4 vs. 4.5 +/- 0.4 ng/ml in lean children, P < 0.0001) and correlates with adiposity. Obese children also had higher serum leptin normalized to fat mass. Despite high serum leptin, obese children ingested 2-3 times more calories than did lean control subjects (P < 0.0001) and gained weight rapidly (10.2 +/- 0.3 vs. 2.9 +/- 0.1 kg/year in control subjects, P < 0.0001). Girls had higher leptin levels than did boys, in obese as well as in nonobese children, and showed a closer correlation between adiposity and serum leptin. Elevation of serum leptin was comparable before and after puberty in obese boys, but puberty further increased leptin levels in obese girls (36 +/- 3 ng/ml), resulting in a clear sexual dimorphism with pubertal obese boys (22 +/- 5 ng/ml, P < 0.005). In conclusion, increased serum leptin reflects but does not halt fat deposition in childhood obesity. After normalization to body adiposity, leptin was found to be increased independently by obesity status, female sex, and female sexual maturation.

[Food allergy in the child: an exploratory study on the impact of the elimination diet on food neophobia]. / Impact du régime d'éviction sur la néophobie dans le cadre d'une allergie alimentaire chez l'enfant : étude exploratoire.

OBJECTIVES: This study was designed to analyse the impact of an elimination diet in children with food allergy, and its perception by their parents on the later reticence of children to test unknown foods, food neophobia. METHODS: The degree of food neophobia of children having outgrown their allergy (mean age, 7 years 2 months) was compared to that of a sibling (9 years 5 months) using a standardized scale and a questionnaire of food friendliness. Parents were also asked to fill in a questionnaire on the disease and its burden on the family. RESULTS: Children having outgrown their allergy are more reluctant to test new foods than their non-allergic brother or sister, as shown by their scoring on the food neophobia scale and the number of unknown foods following the cure of the disease. Two factors increase the level of food neophobia, the distressing effect and the duration of the period elapsed until the diagnosis was made, as well as the distressing effect and the lack of variety in the meal preparation. CONCLUSION: Food neophobia, a normal phase between 2 and 10 years, is worsened by the elimination diet required by food allergy, especially in case of late diagnosis and when the time elapsed before diagnosis and the preparation of meals were perceived as difficult to bear.

[Do breast-feeding and "diet" milks have any preventive or curative effect in the management of atopic dermatitis in children?]. / L'allaitement et les laits "de régime" ont-ils un intérêt préventif ou curatif dans la prise en charge de la dermatite atopique de l'enfant?

A) The preventive interest of infants' food in the onset of atopic dermatitis. Measures of prevention of atopic dermatitis concern predisposed children. Most studies agree on the protective effect of breast feeding for at least 3 to 4 months, compared with industrial milk products, on the onset of atopic dermatitis. Partial breast feeding is not protective. There is no preventive effect of breast feeding on the onset of atopic dermatitis in the absence of a family history of atopy. However, a few studies have raised the question of the aggravation of eczema during prolonged breast feeding. The "breast fed" group is probably not a homogenous group. Mothers' milk contains IgA, TGFb-type cytokines and long-chain polyinsaturated fatty acids that may play an important part in the acquisition of tolerance to food and the prevention of atopic dermatitis. The administration of a protein hydrolysate is preferable in terms of prevention of an allergy to a formula based on cow's milk, but does not provide any benefit compared with breast feeding. The preventive effect on atopic dermatitis of a casein hydrolysate is greater than that of a partial hydrolysate, which itself is greater than a formula based on cow's milk. In conclusion, the first preventive measure is breast feeding for 3 to 4 months, associated with intensive protein hydrolysate in the case of mixed feeding. In the absence of breast feeding, intensive hydrolysate is recommended in children at high risk. B) The curative interest of infants' food in the management of atopic dermatitis. The curative interest implies the responsibility of food in the triggering-off or maintenance of atopic dermatitis. This concerns non-diversified infants exhibiting severe or moderate eczema concomitant to digestive disorders. In such cases, the diagnosis of food allergy should be evoked. If the infant is fed on industrial milk, a test diet should be proposed with a hydrolysate or based on amino acids, followed by the re-introduction of the formula used previously. If the infant is exclusively breast fed, diagnosis of an allergy to one of the foodstuffs ingested by the mother should be searched for and treated. Early diagnosis of food allergy in infants, before diversification, is the optimal factor of prognosis.

Effect of BN 50727 on pathological findings and tissue platelet activating factor levels during ileal ischemia in newborn piglets.

The role of platelet activating factor (PAF), a potent ulcerogen mediator in the digestive tract, is thought to be important in the genesis of necrotizing enterocolitis. The aim of this study was to evaluate the role of PAF in the perpetuation and aggravation of gastrointestinal damage resulting from limited ischemia in the 2-day-old piglet using a natural PAF antagonist (BN 50727). Animals were separated into six groups: U4, controls; S, sham operated animals undergoing laparotomy; I4 and I9, ligation of the mesenteric vessels in the last ileal loop; IT4 and IT9, same procedure together with treatment with BN 50727 (50 mg/kg) orally before and after surgery and intraperitoneally during surgery. Animals were killed at day 4 in groups U4, S, I4 and IT4 and at day 9 in groups I9 and IT9, with histological studies and mediator measurements taken. Macroscopic and histological lesions of intestinal wall in groups I4, I9, IT4 and IT9 were similar to those of human neonatal necrotizing enterocolitis and did not vary according to the absence or the presence of BN 50727 treatment (P = .7, I4 v IT4 and P = .9, I9 v IT9). Peritoneal bands were significantly reduced in treated groups IT4 and IT9 as compared with untreated ones I4 and I9 (P = .003). Mucosal PAF levels in the terminal ileum were higher in group I4 than in groups U4 or I9. In the upper loop, mucosal PAF levels were comparable in all groups. An increase in stool PAF levels was observed only in group I9 (26.4 ng/g v 4.7 ng/g, I9 v U4 + S, P < .05), whereas values comparable to those observed in controls were detected in other groups (I4, 7.2 ng/g; IT4, 4.5 ng/g; IT9, 6.8 ng/g). Tumor necrosis factor alpha (TNF alpha) measurements did not exhibit any difference between groups. Using a PAF antagonist, the role of PAF in the aggravation of intestinal damage after ischemia was not remarkable because treatment did not induce any modifications of parietal intestinal lesions. PAF antagonists appeared to reduce significantly the local peritoneal consequences of local inflammation.

Conservative intestinal surgery to avoid short-bowel syndrome in multiple intestinal atresias and necrotizing enterocolitis: 6 cases treated by multiple anastomoses and Santulli-type enterostomy.

Neonates with multiple sites of intestinal atresia (MIA) may be predisposed to short-gut syndrome. Anastomoses of the intervening segments may prevent this complication. 5 neonates with MIA, one of them with a gastroschisis, were operated on: a proximal enterostomy was constructed, a side-to-end anastomosis as described by Santulli and several end-to-end anastomoses between the intervening intestinal segments (n = 3 to 7) were performed. An additional infant, initially operated on for a necrotizing enterocolitis (NEC) was managed with the same surgical procedure. Without use of this technique, the remaining length of small intestine would have been 28, 27, 40, 58, 70 and 7 cm. This technique enabled an intestinal length of 49, 54, 96, 107, 92 and 93 cm respectively to be achieved. Ileocecal valve was present in all 5 cases with MIA, but resected in the case with NEC. The enterostomy was reversed 7 weeks later. The initial outcome (delay of enteral feeding, duration of parenteral nutrition) was good: the babies were weaned from parenteral nutrition (PN) after a mean time of 90 days (48 to 163 days). The prognosis (mean follow-up: 31 months, range 14 to 57) was good with regards to growth and development and length of time required before adaptation to normal enteral feedings and stools. This surgical method allows complete decompression of the proximal jejunum so that nutriment can pass into the distal bowel allowing it to enlarge. In cases of MIA, a long tapering proximal enteroplasty is a better procedure than resecting more than 5-10 cm of the proximal distended and hypertrophied bowel. We prefer to perform an enterostomy in association with multiple anastomoses between intervening intestinal segments. The enterostomy is preserved for long enough waiting period to enable the reversion of the histochemical and morphological changes that may have taken place in the bowel.

[Patch tests in the diagnosis of food allergies in the nursing infant]. / Les patch-tests dans le diagnostic de l'allergie alimentaire chez le nourrisson.

The atopy patch-test has been shown to be useful in diagnosis of delayed reactions in infants with atopic dermatitis or digestive symptoms. The combination of skin prick testing and patch testing can significantly enhance the accuracy in diagnosis of specific food allergy in infants with atopic dermatitis or digestive symptoms.

[Peanut allergy]. / Allergie à l'arachide.

Clinical manifestations of peanut allergy are miscellanous extending from simple itching to anaphylactic shock. They may appear early in life. The diagnosis relies upon history, prick tests, specific IgE dosage, and if necessary oral challenge test. Most often peanut allergy is longstanding requiring a complete exclusion of peanut from the food. In addition peanut oil being a frequent hidden allergen, it is recommended that any patient with recognized peanut allergy carries a first aid kit to be used in case of allergic accident.

[Allergy to protein hydrolysates. Report of 30 cases]. / Allergie aux hydrolysats de protéines. A propos de 30 cas.

AIM OF THE STUDY: To describe the population of children allergic to cow's milk protein and their usual substitutes made of protein hydrolysates, and who are efficiently taken care of by using Neocate, an amino acid based formula. PATIENTS AND METHODS: Allergy to protein hydrolysates was diagnosed in 30 infants, aged from 15 d to 13 months (median = 3 months), who remained symptomatic while receiving a protein hydrolysate for 15 d to 12 months (median = 1.8 months). After a complete clinical and biological evaluation, an amino acid based diet using Neocate was attempted, followed after one month by an oral challenge test with the protein hydrolysate. RESULTS: Symptoms occurred mainly in the digestive tract (25 cases) in the form of regurgitations (18 cases), diarrhea (17 cases) and colicky pain (10 cases); failure to thrive was seen in ten cases. Neocate improved the clinical condition rapidly (within 3-10 d), and allowed the children to gain weight (27.5 +/- 10.8 g/d). Skin prick tests with cow's milk hydrolysates were positive in 13 out of 26 children; total IgE was raised in cases of cutaneous symptoms (six cases), and associated with increased specific IgE for cow's milk. During the intestinal permeability test, the lactitol/mannitol ratio which initially increased, decreased following Neocate (6.58 +/- 2.92% vs. 3.47 +/- 1.58%, P = 0.0004). Multiple food allergies were present in 22 cases. During challenge with a hydrolysate, the clinical reaction was immediate in 13 cases, partially delayed in 13 cases and delayed in four cases. CONCLUSION: Allergy to cow's milk hydrolysates may occur and has to be considered in the presence of anaphylaxis and also chronic digestive symptoms such as regurgitations, diarrhea and colicky pain, when these symptoms persist during cow's milk free diet.

[Treatment of severe cow's milk protein allergy using Neocate]. / Traitement des allergies aux protéines du lait de vache séverès, par Néocate.

A hydrolysate of proteins is considered to be adapted to treatment of allergy to cow's milk proteins when it is tolerated by 90% of allergic children. This suggestion implies that 10% of the children who are allergic to cow's milk proteins do not tolerate the preparations based on hydrolysates of proteins and presupposes the case of intolerance or allergy henceforth widely reported. The diagnosis must mention before the existence or the persistence in an infant fed with a hydrolysate of proteins of non-specific clinical signs often attached to more frequent pathologies, such as gastro-oesophageal reflux or colic. Substitution of a hydrolysate by another is one alternative, but the level of residual peptides of protein hydrolysates explains only the cases of severe allergy, the child may show reactions to these residual epitopes. The alternative is use of a formulation based on amino-acids, which allows diagnosis by an elimination-provocation test of protein hydrolysate. An elementary formulation based on amino-acids may permit to await the period of acquisition of tolerance.

[Infant food allergy: digestive manifestations]. / L'allergie alimentaire du nourrisson: manifestations digestives.

Food allergies are frequent in infants where digestive signs predominate. The symptoms are extremely variable and most often non-specific. The signs may be immediate or delayed. The pathology of eosinophilia seems to be frequent and may occur in all parts of the intestine. Diagnosis will be orientated to skin tests, prick and/or patch, measurement of IgE and search for eosinophils in digestive biopsies. Exclusion diet of the suspect food, followed by reintroduction of the food will give certainty to the diagnosis.