Serum and saliva Ig-levels in infants of non-atopic mothers fed breast milk or cow's milk-based formulas

Of twenty-five healthy, full term infants without a family history of atopic diseases, 13 were exclusively breast-fed from birth for a minimum of 31/2 months (median 41/2 months), whereas the remaining 12 infants were fed with cow's milk-based formulas from birth for a minimum of 4 months. In the latter group of children a significant increase in serum IgE as well as in salivary IgA was found. In infants exclusively breast-fed, no increase in serum IgE was seen until 6 months of age; at nine months of age, salivary IgA was still significantly lower than in the infants fed cow's milk-based formulas. No children developed obvious allergic diseases during the first three years of life. Thus, cow's milk proteins given to newborn children of non-atopic mothers did not seem to increase the risk of IgE-mediated diseases, maybe due to the development of "blocking" IgA-antibodies in the alimentary tract.     

Plasma Antibodies to Cow's Milk Are Increased by Early Weaning and Consumption of Unmodified Milk, but Production of Plasma IgA and IgM Cow's Milk Antibodies Is Stimulated Even during Exclusive Breast-Feeding

ABSTRACT. We measured levels of cow's milk-specific (CM) antibodies of immunoglobulin classes G, A and M by enzyme-linked immunosorbent assay in plasma of 198 healthy infants; a variable number of samples taken at birth and at ages of 2, 4, 6, 9, 12 and 28 months were available (altogether 765 samples). The rise in the level of IgG CM antibodies was highest and most rapid in infants exposed to CM formula before the age of 1 month. The level fell by 9 months, but rose again by 12 months. This second rise was attributed to the introduction of dairy milk. Partially breast-fed and fully weaned infants had similar levels of IgG CM antibodies. The levels of IgG CM antibodies were unaffected by the infants' own atopy, their heredity for atopy, and the umbilical serum level of IgG CM antibodies. IgA and IgM CM antibodies were absent at birth. Their levels increased similarly in exclusively breast-fed infants and infants fed CM formula. We conclude that plasma IgG antibodies to cow's milk are increased by early weaning and by consumption of unmodified cow's milk. Production of plasma IgA and IgM antibodies to cow's milk is stimulated even during exclusive breast-feeding.     

Iron, zinc, copper and selenium status of breast-fed infants and infants fed trace element fortified milk-based infant formula

Infants were fed cow's milk-based formulas containing 4 mg of iron/I from 1.5 to 6 months of age and their hematological status was compared to infants receiving the same formula but with 7 mg of iron/l and with breast-fed infants. One formula with 4 mg of iron/l contained iron as ferrous sulfate, in another, part of the iron was provided as bovine lactoferrin. We also studied the effect of selenium (10 μg/l) and copper (0.4 mg/l) supplementation on selenium and copper status. There were no significant differences in hematological indices among the groups at 6 months of age; all infants had satisfactory iron status. Serum transferrin receptor levels, a potential novel indicator of iron status, were highest in breast-fed infants, suggesting a cellular need for iron, and lowest in infants receiving formula with 7 mg of iron/l. Selenium status, as assessed by serum glutathione peroxidase activity, was similar at 6 months of age in breast-fed infants and infants fed formula fortified with selenium but lower in infants fed unfortified formula. The lowest levels of glutathione peroxidase activity were found in infants fed the highest concentration of iron (7 mg/l). Serum copper concentrations were similar in all groups, but the lowest levels were found in infants fed the highest concentration of iron. These results suggest that 4 mg of iron/l is adequate for infants up to 6 months of age and that higher levels may have some negative effects.     

Prolonged exclusive breast-feeding results in low serum concentrations of immunoglobulin G, A and M

Serum levels of IgG, IgA and IgM were measured in 198 infants at ages 2, 4, 6, 9 and 12 months. By age 9 months 30 infants were still exclusively breast-fed; their IgG and IgM levels were significantly lower than those of infants weaned early to formula (before age 3.5 months). By 12 months 6 infants were still exclusively breast-fed; their IgA levels were by then also similarly lower. There was no significant difference in the number of infections experienced by these groups of infants. After 2 months on formula feeding, the IgG and IgM levels of the infants who were exclusively breast-fed for 9 months had caught up with the levels of the infants weaned early to formula. Only at 12 months of age prealbumin levels of the exclusively breast-fed infants showed a positive correlation to IgG and IgA levels; no correlation was found between immunoglobulin levels and levels of serum iron and zinc.     

Prolonged Exclusive Breast-Feeding Results in Low Serum Concentrations of Immunoglobulin G, A and M

ABSTRACT. Serum levels of IgG, IgA and IgM were measured in 198 infants at ages 2, 4, 6, 9 and 12 months. By age 9 months 30 infants were still exclusively breast-fed; their IgG and IgM levels were significantly lower than those of infants weaned early to formula (before age 3.5 months). By 12 months 6 infants were still exclusively breast-fed; their IgA levels were by then also similarly lower. There was no significant difference in the number of infections experienced by these groups of infants. After 2 months on formula feeding, the IgG and IgM levels of the infants who were exclusively breast-fed for 9 months had caught up with the levels of the infants weaned early to formula. Only at 12 months of age prealbumin levels of the exclusively breast-fed infants showed a positive correlation to IgG and IgA levels; no correlation was found between immunoglobulin levels and levels of serum iron and zinc.     

Posthospitalization growth and bone mineral status of normal preterm infants. Feeding with mother's milk or standard formula

The growth and bone mineralization were studied in ten preterm infants fed human milk and 14 preterm infants fed cow's milk-based formula. After discharge from the hospital, at 42, 48, and 56 weeks' postmenstrual age, anthropometric measures of weight, length, occipital frontal circumference, mid-upper arm circumference, triceps, and subscapular skin folds were obtained. Blood was drawn for determinations of serum calcium, phosphorus, 25-hydroxyvitamin D, alkaline phosphatase, and albumin levels. Bone mineral analyses were performed by photon absorptiometry. Mean (+/- SD) gestational ages in nursing and formula-fed infants were similar (32.0 +/- 2.5 vs 31.5 +/- 1.5 weeks), as were their mean (+/- SD) birth weights (1.76 +/- 0.42 vs 1.52 +/- 0.30 kg). After hospitalization, both groups had similar rates of growth in weight, length, head circumference, mid-upper arm circumference, triceps, and subscapular skinfold thickness. The formula-fed group had higher serum phosphorus levels at 42 weeks, higher serum calcium levels at 48 weeks, and higher serum albumin concentrations at 56 weeks than the breast-fed group. By 56 weeks' postmenstrual age, the bone mineral content was higher in the formula-fed group. Our data suggest that after hospitalization, preterm infants fed their own mother's milk have similar growth patterns but a different bone mineralization rate compared with preterm infants fed a standard cow's milk-based formula.     

Mucosal IgA, mucosal cow's milk antibodies, serum cow's milk antibodies and gastrointestinal permeability in infants

We have studied development of the levels of IgA cow's milk (CM) antibodies in the saliva, faeces and serum of 20 term and 20 preterm infants from birth to 8 months. All infants already had IgA in their saliva during the first week of life. The levels peaked at the age of one month, thereafter decreasing in both groups; from the age of three months levels remained stable. Term infants had higher levels than preterm infants, but no differences were found between breastfed and CM-fed infants. Breastfed infants had higher levels of IgA in their faeces than did CM-fed infants; the IgA levels were similar in breast-fed term and preterm infants, being highest at birth, and decreasing thereafter. We also showed rising titers of serum IgA CM antibodies, with higher levels in infants regularly exposed to CM than in breast-fed infants. We sought associations between the magnitude of intestinal permeability to human a-lactalbumin (ALA) measured at the ages of 4-7 days and one month and the levels of IgG antibodies to CM, but no such relation was found.;     

A comparison of secretory antibodies in breast-fed and formula-fed infants over the first six months of life

In the present study salivary IgA, anti-Escherichia coli, anti-beta-lactoglobulin and anti-poliovirus type 1 IgA and IgM in serum and saliva were evaluated longitudinally in 13 breast-fed and 14 formula-fed infants over the first six months of life. Salivary IgA was quantified by electroimmunodiffusion; specific IgA and IgM antibodies were determined in serum and saliva by ELISA. Salivary IgA was significantly lower at age one month in breast-fed compared with formula-fed infants but in breast-fed infants salivary IgA increased with age and was significantly higher at six months than at one month. In both groups of infants, at the age of six months, salivary IgA levels were significantly lower than in adult controls. No significant differences in secretory anti-E. coli were observed between the two groups of infants. Salivary anti-poliovirus IgA and IgM antibodies increased transiently only to disappear in most babies at age six months, while anti-beta lactoglobulin IgA and IgM, present in saliva at all ages, showed a wide scatter. No important differences in specific serum IgA or IgM antibodies were observed either between the groups or at different times within the groups.     

The development of atopic sensitization in Estonian infants

In a prospective study, 251 infants were followed from birth up to 12 months of age, recording manifestations of allergy by questionnaires at 3, 6, 9 and 12 months and by clinical examinations at 6 and/or 12 months. Blood samples were obtained at birth and at 6 and 12 months and analysed for serum lgE levels. The children were skin-prick tested with foods at 6 and 12 months of age and with inhalant allergens at 12 months. Blood samples from SPT-positive individuals and controls were analysed for the presence of IgE antibodies to common inhalant allergens and their cord sera for the presence of IgE antibodies to cow's milk and egg. Twelve infants (7%) were sensitized against foods [3 to cow's milk (CM) and 9 to egg white (EW)] at 6 months and 11 (5%) (2 to CM and 9 to EW) at 12 months. Seventeen infants (7%) had IgE antibodies against inhalant allergens at 6 and/or 12 months, as determined by either SPT and/or the demonstration of circulating IgE antibodies. Out of 30 children with positive SPT and/or circulating IgE antibodies against foods and inhalant allergens at any age, 6 had atopic dermatitis, 4 gastrointestinal food allergy, 1 urticaria and 4 probable allergy, while 15 had no clinical manifestation of allergy. Immunoglobulin E antibodies against Ascaris were detected in 17% of the infants with S-IgE levels >20kU/l. The study indicates that the incidence of sensitization and manifestations of allergic disease is similar among Estonian and Scandinavian infants during the first year of life. Given earlier findings indicating a significantly higher prevalence of atopic disease in Scandinavian school-children relative to their counterparts in Eastern Europe, the present study suggests that the key events which determine disease expression do not occur exclusively during the first year of life.     

Folate nutrition is optimal in exclusively breast-fed infants but inadequate in some of their mothers and in formula-fed infants

Plasma concentrations of folate were studied in a group of exclusively breast-fed infants and their mothers (their numbers gradually decreased from 200 at birth to 7 at 12 months) and in infants completely weaned to a cow's milk formula (containing 35 micrograms of folate/L) and solid foods. The exclusively breast-fed infants were in no danger of folate deficiency; their plasma levels were elevated after the age of 2 months and, on average, were 2.0-3.3-fold higher than maternal levels throughout the study. None of these infants had an inadequate plasma concentration, whereas up to 5% of the mothers had values less than or equal to 3 micrograms/L, despite supplementation during lactation with 0.1 mg folate/day. In the formula-fed infants, 69-94% of the plasma folate concentrations lay below the lowest concentration for the breast-fed infants. Although no infant had signs of anemia or macrocytosis in red cell indices, the infants weaned earliest had the lowest hemoglobin concentrations (p = 0.09) and the highest mean corpuscular volume (MCV) values (p = 0.06) at 9 months of age. Thus, an infant fed a formula containing the recommended amount of folate runs a risk of folate deficiency.     

Compliance with a Dietary Manipulation Programme in Families with Infants Prone to Atopy

ABSTRACT. The success of familial compliance with a dietary manipulation programme was studied prospectively in 91 newborn babies from atopic families for up to 12 months. The control group consisted of 72 infants from non-atopic families. The percentages of infants breast-fed at the age of six months were 58% and 38% in the study group and control group, respectively. The introduction of cow's milk based formulas was postponed until the age of three months in 63% of the infants in the study group and 47% of the infants in the control group. Solid food was avoided during the first three months in 76% and 45% of the infants in the study group and control group, respectively. Maternal age, smoking and low social class were associated with poor compliance. The existence of atopic dermatitis in any member of the family was associated with good compliance. The main advantages of our programme were the increased number of children breast-fed until the age of six months, and the reduced number of infants introduced to cow's milk based formulas or solid food before three months of age.     

Development of immunoglobulin G and immunoglobulin E antibodies to cow's milk proteins and ovalbumin after a temporary neonatal exposure to hydrolyzed and whole cow's milk proteins

The ingestion of food antigens usually results in the induction of oral tolerance, but the clinical and immunologic consequences of brief exposure to cow's milk proteins during the neonatal period are not well‐documented. The aim of this work was to study immunoglobulin (Ig)E and IgG responses to cow's milk proteins and ovalbumin after exposure during the first three days of life in infants who were otherwise exclusively breast‐fed. A group of 129 infants was randomly assigned at birth to one of three feeding regimens: human milk (HM), cow's milk formula (CMF), or a casein hydrolysate formula (CHF), during the first three days of life. They were then all exclusively breast‐fed for a varying period of time and followed for two years. Serum IgG and IgE antibodies to cow's milk proteins and ovalbumin (OVA) were analyzed in blood samples obtained at birth, at 4 days and at 2, 4, 8, 12 and 24 months of age. The levels of IgG antibodies to β‐lactoglobulin (IgG‐BLG) and bovine serum albumin (IgG‐BSA) were higher in the CMF and the HM groups than in the CHF group for up to two years. This was particularly obvious for IgG‐BLG in infants who started weaning before two months. The levels of IgG antibodies to casein (IgG‐CAS) were higher in the CMF goup, as compared with the CHF group at 8 and 12 months. The levels of IgG antibodies to OVA were similar in all three feeding groups. The levels of IgE antibodies to CAS or OVA were similar in the three feeding groups. Exposure to cow's milk during the first three days of life stimulated IgG antibody production to cow's milk proteins and this was still obvious at 2 years of age, while feeding with a casein hydrolysate during the first three days of life was associated with low levels of IgG antibodies to cow's milk proteins.     

Compliance with a dietary manipulation programme in families with infants prone to atopy

The success of familial compliance with a dietary manipulation programme was studied prospectively in 91 newborn babies from atopic families for up to 12 months. The control group consisted of 72 infants from non-atopic families. The percentages of infants breast-fed at the age of six months were 58% and 38% in the study group and control group, respectively. The introduction of cow's milk based formulas was postponed until the age of three months in 63% of the infants in the study group and 47% of the infants in the control group. Solid food was avoided during the first three months in 76% and 45% of the infants in the study group and control group, respectively. Maternal age, smoking and low social class were associated with poor compliance. The existence of atopic dermatitis in any member of the family was associated with good compliance. The main advantages of our programme were the increased number of children breast-fed until the age of six months, and the reduced number of infants introduced to cow's milk based formulas or solid food before three months of age.     

Serum zinc concentration in exclusively breast-fed infants and in infants fed an adapted formula

Serum zinc concentrations have been determined in 28 healthy full-term Italian infants of both sexes at birth, as well as at 3 and at 5 months of age. Fourteen exclusively breast-fed infants who served as a control group were compared with 14 infants fed a cow's milk based adapted infant formula. No significant differences in serum zinc concentration between the breast-fed and the bottle-fed group became apparent during the study. The results of this study suggest a similar zinc nutriture in both groups. The availability of zinc from the adapted infant formula was not significatly different from that of human milk. These findings may be explained by the composition of the adapted formula tested, e.g. by a protein composition fairly close to that of human milk, by the presence of zinc derived from the natural ingredients only, by the low Fe/Zn ratio and by the elevated citrate content.     

Breast feeding modifies production of SIgA cow's milk-antibodies in infants

One hundred and fifty-eight healthy mature newborns were divided into 3 groups according to their risk of allergy: Group A, no risk (n = 62), group B, low risk (n = 30) and Group C, high risk (n = 66). Saliva was collected at birth and after 3 and 6 months. SIgA anti-casein and anti-beta-lactoglobulin were determined by a direct ELISA technique. The highest concentrations of secretory antibodies were measured after birth. After 3 months, breast fed infants had lower salivary SIgA anti-casein concentrations than the group receiving cow's milk (p less than 0.01). The effect of breast-feeding was seen even after a nursing period of only 3 weeks. Infants without risk of allergy fed cow's milk exclusively had higher SIgA anti-casein (p less than 0.03) and anti-beta-lactoglobulin concentrations than low risk infants at the age of 6 months. These data show a modifying effect of breast feeding on salivary SIgA production against cow's milk protein.     

Breast Feeding Modifies Production of SlgA Cow's Milk-Antibodies in Infants

ABSTRACT. One hundred and fifty-eight healthy mature newborns were divided into 3 groups according to their risk of allergy: Group A, no risk ( n =62), group B, low risk ( n = 30) and Group C, high risk ( n = 66). Saliva was collected at birth and after 3 and 6 months. SIgA anti-casein and anti-β-lactoglobulin were determined by direct ELISA technique. The highest concentrations of secretory antibodies were measured after birth. After 3 months, breast fed infants had lower salivary SIgA anti-casein concentrations than the group receiving cow's milk ( p ≤0.01). The effect of breast-feeding was seen even after nursing period of only 3 weeks. Infants without risk of allergy fed cow's milk exclusively had higher SIgA anti-casein ( p < 0.03) and anti-β-lactoglobulin concentrations than low risk infants at the age of 6 months. These data show modifying effect of breast feeding on salivary SIgA production against cow's milk protein.     

Early feeding of preterm infants and allergic symptoms during childhood

A follow-up study of 69 premature infants showed that at a mean age of 11.4 years they had a cumulative incidence of allergic symptoms similar to that reported in unselected series. The 38 premature infants fed exclusively with human milk to the age of four months had more allergic symptoms than the 31 premature infants fed with adapted cow's milk formula from birth (mean number of symptoms 1.6 versus 0.6, p = 0.0025). The excess of symptoms was mostly cutaneous, and often associated with a specific food. In logistic regression models, the only variable with a statistically significant association (standardized odds ratio 3.15, 95% confidence interval 1.12–8.8, p = 0.03) with symptomatic allergy was the type of feed. The frequency of positive skin prick tests and the mean levels of serum IgE and antibodies to cow's milk were similar in the two groups. We infer that food allergy was more common in the group fed with human milk.     

Bioavailability of iron in soy-based formula and its effect on iron nutriture in infancy

Soy products have been reported to inhibit absorption of nonheme food iron and fortification iron. Iron bioavailability from a soy formula (Prosobee-PP 710) (iron added as ferrous sulfate: 12 mg/L; ascorbic acid: 54 mg/L) was examined in 16 adult women using the extrinsic radioactive tag method. The geometric mean absorption from the soy formula was only 1.7%. The effect of this formula on iron nutrition in infants was studied in 47 healthy term infants weaned spontaneously before 2 months of age and who received the formula ad libitum until 9 months of age. For control, 45 infants received a cow's milk formula fortified with ferrous sulfate (iron: 15 mg/L; ascorbic acid: 100 mg/L), which has been shown to be effective in preventing iron deficiency, and 49 additional breast-fed infants were also followed. All babies received solid foods (vegetables and meat) starting at 4 months of age. Iron nutritional status was determined at 9 months. Infants fed soy formula and iron-fortified cow's milk had similar mean values of hemoglobin, mean corpuscular volume, transferrin saturation, free erythrocyte protoporphyrin, and serum ferritin; both formula groups differed significantly (P less than .05) from the breast-fed group in all measurements except free erythrocyte protoporphyrin. Anemia (hemoglobin less than 11 g/dL) was present in only 4.3% and 2.2% of infants receiving the soy and the fortified formulas, respectively, v 27.3% in the breast-fed group. These results indicate that soy formula, in spite of the lower iron bioavailability when measured in adults, is essentially as effective as iron-fortified cow's milk in preventing iron deficiency in infants.     

Growth of newborn, term infants fed soy formulas for 1 year.

Few studies have measured long-term growth in infants fed soy protein-based formulas. The effect of nucleotide (NT) supplementation of soy protein-based infant formulas on growth is unknown. Growth was therefore evaluated in healthy term infants fed a soy protein-based formula (SOY; n = 73), SOY with added NT (72 mg added NT/L) at human milk (HM) levels (SOYN, n = 73), or mixed feeding (MF, n = 67) in a randomized, masked, parallel 1-year feeding study. The MF group (a nonrandomized reference group) was fed HM exclusively from birth to 2 months of age followed by HM and/or a standard milk-based formula (Similac with Iron with no supplemental NTs) to 1 year of age. Results indicated that growth (weight, length, and head circumference) was normal and comparable among the three groups. All three groups had similar plasma albumin (at 2 months of age) and hemoglobin levels (at 12 months of age). Thus, this study demonstrated similar growth in the first year of life among infants fed MF feeding or soy formula with or without supplemental NTs.     

Food Intake and Growth of Infants between Six and Twenty-six Weeks of Age on Breast Milk, Cow's Milk Formula, or Soy Formula

ABSTRACT. In 59 normal infants attending well-baby clinics, food consumption was registered until 26 and growth until 52 weeks of age. They were either breast-fed or formula-fed with a cow's milk product or a soy protein product. The average consumption of breastmilk was 746, 796, 722 and 689 g/day at 6, 14, 22 and 26 weeks respectively. Bottle-fed infants received larger volumes, and at 6 and 14 weeks were the calculated total energy intakes significantly higher than in breast-fed infants. No differences were seen between the feeding groups with respect to length and the sum of four skin folds. The soy formula-fed children, who happened to be 200 g heavier at birth, had lower weight gains during the first 6 weeks than the other two groups. Thereafter, the average weights of the soy formula group did not differ from the other groups. At 3 months, the soy formula-fed children displayed a slower mineralisation and maturation of bone, but the difference was no longer significant when re-examined at 6 months. Formulas based on soy protein isolates seem to be acceptable as substitutes for cow's milk formulas in feeding normal infants.