HLA ANTIGENS IN INTESTINAL COW'S MILK ALLERGY

ABSTRACT. The histocompatibility antigens of one hundred patients with a severe form of cow's milk allergy were studied. HLA-A and B locus antigens were identified in all patients, C locus antigens in 62 patients and DR locus antigens in 41 patients. The A, B and C locus antigen frequencies were compared with those of healthy blood donors, and DR locus antigen frequencies with those of healthy unrelated volunteers and cadaver kidney donors. The series included six patients with concomitant coeliac disease, who were treated as a separate group. No statistically significant differences between the patients and controls were observed, but suggestive differences became apparent when the patient group was divided into subgroups according to the presence or absence of certain co-existing conditions, and the severity of the initially observed intestinal lesion. It is concluded that several factors contribute to the pathogenesis of intestinal cow's milk allergy, and that in some cases genes linked to the HLA region may play a role.     

THE SPECTRUM OF COW'S MILK ALLERGY IN CHILDHOOD Clinical, Gastroenterological and Immunological Studies

Abstract. Seventeen of 52 children suspected of having cow's milk allergy had this diagnosis confirmed after milk challenge in hospital. A broad spectrum of reactions was observed including skin eruptions, respiratory symptoms and gastrointestinal disturbance. Not all patients with gastrointestinal symptoms showed small bowel mucosal damage. Only patients with skin reactions had positive skin tests. IgA deficiency and IgE elevation were common. Four patients had symptoms within 3 days of birth. Twelve children tolerated cow's milk by three years of age. Cow's milk allergy can cause a variety of symptoms. Challenge with milk for several days may be required before allergic manifestations can be demonstrated.     

RESPONSE OF THE JEJUNAL MUCOSA TO COW'S MILK IN THE MALABSORPTION SYNDROME WITH COW'S MILK INTOLERANCE A Light- and Electron-Microscopic Study

Three infants, in whom the malabsorption syndrome, small intestinal. mucosal damage and clinical cow's milk intolerance were found, were challenged with cow's milk after initial treatment with breast milk. The small intestinal mucosa was investigated with light and electron microscopy both before and after provocation. Clinically one patient reacted rapidly in a few hours and showed round cell infiltration in the surface epithelium and lamina propria 20 hours after a single challenge. Electron microscopy showed short microvilli, abnormal nuclei and thickened basement lamina in the surface epithelium. Two patients reacted slowly. One of them showed similar changes 4 days after commencement of the provocations, but the changes were much more evident 38 days later, when symptoms were also apparent. At this time large accumulations of lysosomes in the apical part of the surface epithelial cell and marked thickening of the basal lamina with accumulations of whirly collagen fibres were detected. The third patient reacted in a milder way, both clinically and morphologically. This study indicates that cow's milk, apparently through its protein fraction, may damage the surface epithelium of the small intestinal mucosa. These alterations during provocation periods resemble those found in coe-liac disease during gluten provocation.     

A PROSPECTIVE STUDY OF COW'S MILK PROTEIN INTOLERANCE IN SWEDISH INFANTS

Abstract. 1079 of 1548 newborn infants were followed during their first year. 328 were prospectively contacted once a month. 751 were followed up at child welfare clinics. Altogether 20 were diagnosed as being cow's milk protein intolerant (1.9%). Symptoms from the gastrointestinal tract and the skin predominated. Only 2 had respiratory symptoms. Ten had their symtpoms within one week after the introduction of cow's milk, 3 of them at their first cow's milk-containing meal. A further 4 already had symptoms when fed only human milk. The others (6 infants) showed symptoms after more than one week on a cow's milk containing diet. Before 2 years of age, 13 had recovered. Twelve of the cow's milk protein intolerant infants also showed adverse reactions to other foods, soy-protein intolerance being the most common (7 infants). A family history of allergy was found in 35% (116) of the 328 infants and in 70% (14) of those with cow's milk protein intolerance.     

THE SIGNIFICANCE OF COPROANTIBODIES TO COW'S MILK PROTEINS

An attempt has been made to delineate further the significance of milk coproantibodies. The presence of precipitating and of high levels of hemagglutinating antibodies in feces was found only in patients with milk sensitivity or celiac disease. These cases showed also high levels of serum antibodies to milk. In mongolism and dysautonomia no abnormal titers of coproantibodies were found, in spite of strong reactions in the sera. Antibodies to milk were found by radio-im-munoelectrophoresis to consist mainly of immunoglobulin A in feces and immunoglobulin G in serum. Serum milk antibodies of the IgA type were found only in patients with milk sensitivity or celiac disease.     

A FOLLOW-UP STUDY OF INFANTS WITH ADVERSE REACTIONS TO COW'S MILK I. Serum IgE, Skin Test Reactions and RAST in Relation to Clinical Course

Abstract. 47 infants with cow's milk sensitivity were followed for a period varying between 6 months to 4 years (mean 28 months). The age at onset of symptoms varied between 14 days to 20 months. The clinical course was studied in relation to reaginic allergy by use of serum IgE, skin prick test and RAST. Infants with an immediate onset of symptoms from the gastrointestinal tract and the skin after cow's milk intake were discerned as a distinct entity having a high frequency of atopy in the family, positive skin tests and positive RASTs to milk (71%). Cases with delayed reactions to cow's milk seldom had a positive RAST or skin test. Most infants of both groups showed an increasing tolerance to milk. In RAST positive infants the RAST-titers increased significantly after onset of symptoms. After having reached a peak the titers subclined in several cases. The titers did not reflect the degree of milk sensitivity during the follow-up period. However, infants who developed high titers seemed to develop tolerance more slowly than infants with low titers.     

CHANGING PATTERN OF COW'S MILK INTOLERANCE: An Analysis of the Occurrence and Clinical Course in the 60s and mid-70s

ABSTRACT. Verkasalo, M., Kuitunen, P., Savilahti, E. and Tiilikainen, A. (Children's Hospital, University of Helsinki, Finland). Changing pattern of cow's milk intolerance. Acta Paediatr Scand, 70: 289, 1981.–The rapid changeover to commercial adapted infant formulae which took place in Finland between 1973 and 1975 was studied as a factor in the occurrence of severe intestinal cow's milk intolerance (CMI). Of infants treated for CMI in 1962-73, ninety-three percent (25/27) were on homemade or unadapted formulae. The admission rate for CMI in these years was 0.22/1 000 liveborn infants breast fed less than six months. During 1974-77 the corresponding figure was 0.56, with 85 % of the patients (18/26) on adapted cow's milk formulae. The patients treated before 1974 had a longer symptomatic period before admission, greater growth retardation and more severe intestinal damage than those seen during and after 1974. This is believed to reflect mainly the increasing awareness of CMI on the part of both laymen and the medical profession. In the history of 2/3 of the patients at least one of the following conditions was noted: non-breast feeding, infectious gastroenteritis, praematurity, 21-trisomy, prior intra-abdominal surgery, Hirschsprung's disease, and atopic disease in family members. The long follow-up averaging over four years revealed four patients with coeliac disease. In one of these the proximal jejunal mucosa was normal after two years on gluten-containing diet, but he showed a mucosal relapse as late as between 2 to 4 years on normal diet.     

BREAST MILK THYROXINE AND NOT COW'S MILK MAY MITIGATE AND DELAY THE CLINICAL PICTURE OF NEONATAL HYPOTHYROIDISM

Abstract. Sack, J., Frucht, H., Amado, O., Brish, M. and Lunenfeld, B. (Institute of Endocrinology, the Chaim Sheba Medical Center, Tel Hashomer, Israel). Breast milk thyroxine and not cow's milk may mitigate and delay the clinical picture of neonatal hypothyroidism. Acta Paediatr Scand, Suppl. 277: 54, 1979.-Thyroxine concentration was measured in human milk and Cow's milk products by a specific radioimmunoassay. The mean (± S.E.M.) milk T4 concentration during the first 5 days postpartum was 0.7±0.3 µg/dl (n=11). The mean T4 concentration between 6–49 days postpartum rose to 3.1±0.2 µg/dl (n=108), falling after 50 days to a mean of 1.4±0.2 µg/dl (n=39). The mean (± S.E.M.) T3 concentration in breast milk in the first 50 days postpartum was 386±17 ng/dl (n=56). T4 concentration in cow's milk products was less than 0.3 µg/dl. Thyroxine concentration in 24 hours breast milk collection ranged from 0.7 to 7.7 µg/dl and the total T4 in this milk ranged from 0.7 to 28 µg/day. These data suggest that milk of human but not bovine origin may provide a significant exogenous source of T4 to the premature infant. This amount of exogenous T4 which is insufficient in preventing the proceeding of neonatal hypothyroidism, may delay the clinical recognition of this disorder. This once again emphasizes the importance of early screening for neonatal hypothyroidism.     

PROSPECTIVE STUDIES OF THE EFFECT OF BREAST FEEDING ON INCIDENCE OF INFECTION AND ALLERGY

ABSTRACT. Chandra, R. K. (Department of Pediatrics, Memorial University of Newfoundland, St. John's, Newfoundland, Canada). Prospective studies of the effect of breast feeding on incidence of infection and allergy. Acta Paediatr Scand 68: 691, 1979.—The effect of exclusive breast feeding in the first few weeks after birth on infant morbidity due to infectious and allergic disorders was investigated in three separate prospective studies. In a rural community in India, breast-fed infants had a significantly lower incidence of respiratory infection, otitis, diarrhoea, dehydration and pneumonia. In an urban population in Canada, breast feeding was associated with a marked decrease in the occurrence of otitis and respiratory disease and to a lesser extent of diarrhoea and dehydration. In newborn siblings of children with atopic disease exclusively breast-fed for a minimum of six weeks, the incidence of eczema, recurrent wheezing, elevated serum IgE, IgE-antibodies to cow's milk, complement activation in vivo after milk challenge and hemagglutinating antibodies to β-lactoglobulin was significantly lower compared with formula-fed matched group. These observations provide clinical data attesting the immunologic advantages of human milk.     

METABOLIC AND ENDOCRINE RESPONSES TO A MILK FEED IN SIX-DAY-OLD TERM INFANTS: DIFFERENCES BETWEEN BREAST AND COW'S MILK FORMULA FEEDING

ABSTRACT. Lucas, A., Boyes, S., Aynsley-Green, A. (Department of Paediatrics, John Radcliffe Hospital, Oxford) and Bloom, S. R. (Hammersmith Hospital, London, England). Metabolic and endocrine responses to a milk feed in six-day-old term infants: JMfferences between breast and cow's milk formula feeding. Acta Paediatr Scand, 70:195, 1981. – There is little information on the metabolic and endocrine responses to milk feeding in the neonatal period particularly in relation to the mode of nutrition and composition of the milk. Plasma concentrations of insulin, glucagon and gastric inhibitory polypeptide (GIP) together with blood levels of glucose, ketone bodies, pyruvate, lactate and glycerol were measured pre- and post-prandially in 79 healthy six-day-old term infants who had been either breast fed or fed on a modified cow's milk formula (Cow and Gate Premium) from birth. Formula fed infants had a greater insulin and GIP response to feeding and their basal and postprandial blood ketones were considerably lower than in breast fed infants. In addition a significantly greater post feed rise in both lactate and pyruvate concentrations was observed with formula feeding. These results may have significant implications regarding infant feeding and postnatal metabolism.     

THE METABOLIC CONSEQUENCES OF HUMAN MILK AND FORMULA FEEDING IN PREMATURE INFANTS

Abstract. Schultz, K., Soltész, G. and Mestyán, J. (Department of Paediatrics, University Medical School, Pécs, Hungary). The metabolic consequences of human milk and formula feeding in premature infants. Acta Paediatr Scand, 69: 647, 1980.—Twenty premature low-birthweight infants were divided into two groups and assigned randomly to either a pooled human milk or to a cow's milk based infant formula feeding regimen. The protein intake was 2.0 g/kg/day in the human milk fed group and 4.4 g/kg/day in the formula fed group of infants. The concentrations of different metabolites were estimated at weekly intervals, and plasma amino acid analysis was performed biweekly on blood samples in the two groups of infants during the four-week study period. Formula milk fed infants had significantly lower fasting blood glucose levels and developed azotaemia, hyperaminoacidemia and metabolic acidosis in the early weeks of postnatal life. Blood lactate and plasma free fatty acid concentrations did not change significantly in the two groups during the study. No significant differences were found in the rate of weight gain between the two groups of infants, although formula fed infants regained their birthweight more slowly than human milk fed infants. High protein formula feeding causes potentially unfavorable metabolic and amino acid imbalances in preterm infants in the early postnatal life.     

Influences of neonatal serum IgE concentration,family history and diet on the incidence of cow's milk allergy

Serum IgE concentration was measured on the 5th day of life in 943 infants. All infants were included in a 3 month follow-up study. The frequency of cow's milk allergy was studied according to either family history, IgE level, or both. Feeding (mother's milk or formula feeding) was taken into account. Manifestations suggestive of food allergy were hardly observed in breast-fed babies. In the formula-fed group a positive family history correlated with a 40% incidence of allergic manifestations, compared to a 13% incidence (P<0.001) in the group with negative family history. A high IgE level (IgE>1.3 U/ml) indicated a 43% risk of developing allergic manifestations in formula-fed babies as compared to 15% (P<0.001) in the group with normal results of a screening test. Frequency of allergic manifestations in a subgroup with a negative family history and a high IgE level (38%) was equal to the frequency in the subgroup with a positive family history and negative screening test results (IgE<1.3 U/ml) (36%). The incidence in the subgroup with both positive screening test results and a positive family history was 49%. None of these differences were significant. The frequency in the subgroup with both parameters negative was 8% (P<0.001 to 3 other subgroups). Our results indicate that the family history seems to correlate as well with the incidence of allergic manifestations as the neonatal serum IgE concentration. Serum IgE concentration as a neonatal screening test for allergy provides significant information about the risk of developing allergy compared to the family history only in formula-fed babies with a negative family history. This could be an important factor in improving the cost/benefit ratio of screening programs for allergy.     

IMMUNOLOGICAL SPECIFICITY AND CORRELATION OF DIAGNOSTIC TESTS FOR BRONCHIAL ALLERGY TO CLADOSPORIUM HERBARUM

Abstract. A total of 104 children with allergic bronchial asthma were included in studies comparing the results of RAST and skin testing with each other and with the results of bronchial challenges using different concentrations of extracts of Cladosporium herbarum. Prick tests predicted bronchial allergy to the mould in 83–96% of the cases compared to 74–83% for RAST predicting such bronchial allergy. Bronchial reactions to top concentrations of the extracts were considered immunologically non-specific and probably due to contents of irritants in most instances.     

IRON ABSORPTION FROM INFANT MILK FORMULA AND THE OPTIMAL LEVEL OF IRON SUPPLEMENTATION

Abstract. Thirty healthy infants, aged 11–13 months, were studied with regard to the iron absorption from proprietary milk formula. The infants were divided into three groups (I-III) depending on the concentration of iron in the formula: 0.8 (I), 6.8 (II), and 12.8 (III) mg/1, respectively. The calculated amount of iron absorbed per test dose of SO ml of milk averaged 5 μg (I), 32 μg (II), and 43 μg (III). Group I differed significantly from groups II and III. No correlation was found between iron absorption and hemoglobin, MCV, serum transferrin saturation or serum ferritin within the range of normal values. Our findings suggest that at least 7 mg of iron as ferrous sulphate per litre of formula is required to prevent iron deficiency.     

LONGITUDINAL CHANGES IN SELENIUM CONTENT OF BREAST MILK

ABSTRACT. The selenium (Se) contents of human milk, serum and hair obtained from 22 lactating mothers were measured by fluorometric analysis. The Se contents in 41 milk samples from different stages of lactation were obtained longitudinally from 10 mothers. They showed a large variance of individual samples at any stage of studies. The highest Se level was found in colostrum (median 80 ng/ml); subsequently, Se content declined significantly during the first month of lactation and then came to a plateau level (median 17–18 ng/ml). No positive correlation of Se content was found between the serum and the milk samples at three months of lactation. No positive correlation of Se content was found between the hair and the milk samples obtained from lactating mothers.     

Characteristics of infants admitted to hospital for persistent colic, and comparison with healthy infants

AIM: To describe clinical characteristics of infants with colic admitted to hospital because of ongoing excessive crying (colic). METHODS: Characteristics of 104 infants admitted to hospital because of severe excessive crying (cases) were compared to those of 100 healthy thriving controls randomly selected from records of well baby clinics. RESULTS: Half of the cases were reported to cry excessively from the day of birth, and feeding changes had been recommended in 77%. A medical cause of excessive crying was identified in none of the cases. Almost all infants showed a rapid transition to normal crying behaviour during admission; none cried for >3 h per day. Mean gestational age and mean Apgar scores were slightly lower in cases than in controls. There was a trend of positive family history of atopy being more common in controls (45%) than in cases (38%, p = 0.14). Feeding problems were more common in cases (71%) than in controls (36%, 95% CI for difference 21.6%-46.9%). Pregnancy or birth complications were much more common in cases (85%) than in controls (37%; 95% CI 35%-58%). CONCLUSIONS: Infants with severe excessive crying show normalization of crying behaviour during hospital admission, and are unlikely to have medical causes for their colic. The most important risk factor for excessive crying was a complicated pregnancy or birth, suggesting that this might predispose parents to regard normal crying behaviour as excessive.     

LACTOSE AND PROTEIN ABSORPTION FROM BREAST MILK AND COW'S MILK PREPARATIONS AND ITS INFLUENCE ON THE INTESTINAL FLORA Investigations on two Infants with an Artificial Anus

Abstract. Lactose and protein absorption from breast milk and a cow's milk preparation enriched up to 7% of lactose were studied in two infants with an artificial anus applied in the ascending colon region. The concentrations of protein, lactose, glucose and galactose were measured in the fistula stools. In addition, the stools were analysed microbiologically. There were relatively high concentrations of lactose and its decomposition products and low concentrations of protein and aminonitrogen in the fistula stools when breast milk was fed. When the cow's milk formula was applied, only traces of lactose but high amounts of protein were measured. The microbiological findings are in agreement with the hypothesis that the bacterial flora of the large intestine is influenced by the lactose and protein concentrations in the intestinal content which reach the large intestine.     

LIPOLYTIC ACTIVITY IN MILK FROM MOTHERS OF UNJAUNDICED INFANTS

ABSTRACT. Lipoprotein lipase activity and free fatty acid concentrations are measured in samples of milk collected from 50 mothers of infants without prolonged neonatal jaundice; in many samples the values are in the same high range as observed in all samples collected from nine mothers of jaundiced infants. These findings are discussed with relevance to the problems of breast-milk jaundice and factors controlling the milk secretion.     

INCREASING INCIDENCE OF NEONATAL SEPTICEMIA: CAUSATIVE ORGANISM AND PREDISPOSING RISK FACTORS

ABSTRACT. Bennet, R., Eriksson, M. and Zetterstrom, R. (Department of Paediatrics, Karolinska Institute, St. Göran's Children's Hospital, Stockholm, Sweden). Increasing incidence of neonatal septicemia: Causative organism and predisposing risk factors. Acta Paediatr Scand, 70:207, 1981. –The incidence of neonatal septicemia in the referral area of St. Göran's Children's Hospital in Stockholm has been studied during a ten-year period (1969–1978). An increase was noticed during the period 1974–1978 in comparison with the preceding five-year period. The incidence per 1000 live births was 1.4 and 3.1, respectively. The incidence of osteoarthritis increased from 0.21 to 0.41 per 1000. Mortality rate from neonatal septicemia remained unchanged. Gram-negative organisms as an etiologic factor seemed to be decreasing while staphylococcal infections have increased. Group B streptococcal infection occurred with the same frequency during the whole period. The low incidence of enteric organisms might be related to the common practice of feeding the babies with milk from their own mothers. Perinatal risk factors were equally common in both five-year periods. The observed increase of the prevalence of neonatal septicemia caused by Staphylococcus aureus may be explained by a higher rate of survival of highly susceptible low-birthweight infants and other sick neonates treated in the neonatal intensive care unit.     

MILK AND MINERAL INTAKES OF BREASTFED INFANTS

ABSTRACT. Picciano, M. F., Calkins, E. J., Garrick, J. R. and Dcering, R. H. Foods and Nutrition Department, University of Illinois, Urbana, Illinois and Christie Clinic, Champaign, Illinois). Milk and mineral intakes of breastfed infants. Acta Paediatr Scand, 70:189, 1981.–Milk and mineral intakes of twenty-six full term infants receiving human milk as their sole milk source were determined by "test weighing" and direct analyses of milk samples at months 1, 2 and 3 of lactation. Data indicate that volume of milk ingested ranged from 295 to 996 ml/day and mean intakes (606, 601, 626 ml/day at months 1, 2 and 3, respectively) are less than the often quoted 850 ml/day. Taking into account Swedish and Scottish data and that from the present investigation, it appears that typical human milk intakes are 500 to 800 ml/day. No relationship was observed between volume of intake and growth of infants. Ranges of intake for copper, iron, zinc, calcium, phosphorus, magnesium, sodium, potassium and chloride are comparable to values reported for these mineral intakes by both early and modern investigators even though different data collection techniques and analytical methods were employed.