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.     

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.     

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.     

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.     

Exclusively breast-fed healthy infants grow slower than reference infants

We have studied the nutritional adequacy of exclusive breast-feeding by following prospectively the growth and protein nutrition of healthy infants during the 1st yr of life. The number of exclusively breast-fed infants was 116 at the age of 6 months and 36 at 9 months. These infants had slower length velocity after age 3 months than a comparison group of 32 infants who were weaned early and given formula plus solids. As a group, the exclusively breast-fed infants lagged slightly, but progressively, behind in relative length. By 9 months, 45% of them versus 18% of the comparison group showed a greater than 1 SD decrease in relative length. No such decrease was found in relative weight. Skinfolds and weight for length index showed that they were heavier for their length than the comparison infants. At 6 and 9 months the calculated protein intake (0.9 g/kg/day) was much less than the recommended amount (2.0 g/kg/day). Serum prealbumin concentration was lower than in the comparison group but this was noted as early as 4 months. No relation was found between the parameters of growth and protein nutrition either individually or in general. Whether the slower growth of the exclusively breast-fed infants represents appropriate physiological growth or whether it indicates nutritional deficiency is not known but we did not find any evidence of protein deficiency. Six infants did, however, show subsequent catch-up growth which could indicate previous malnutrition.     

Serum and Saliva Ig-levels in Infants of Non-Atopic Mothers Fed Breast Milk or Cow's Milk-based Formulas

ABSTRACT. 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 3½ months (median 4½ 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.     

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.     

Effects of feeding regimen on blood glucose levels and plasma concentrations of pancreatic hormones and gut regulatory peptides at 9 months of age: comparison between infants fed with milk formula and infants exclusively breast-fed from birth

Little is known about the development of gut endocrine responses to food intake in infants after the first postnatal month. To examine this question and to ascertain whether the mode of feeding from birth affects postprandial endocrine changes, blood glucose levels and the plasma concentrations of 11 regulatory peptides were measured at 9 months of age before and after a breast feeding in 13 exclusively breast-fed infants and before and after a formula feeding in 7 infants weaned during the first 3 months of life. In the prefeeding concentrations of these substances, no significant differences were found between the two groups, with the possible exception of the plasma concentration of pancreatic polypeptide (p = 0.06). Postprandially, the responses were significantly smaller in the breast-fed infants, whose plasma concentrations of insulin, gastric inhibitory polypeptide, pancreatic polypeptide, and cholecystokinin were lower than in the formula-fed infants. In addition, the overall level of the insulin-glucagon ratio was lower (p = 0.03) in the breast-fed infants. A difference in the opposite direction was observed for plasma gastrin levels. No significant differences appeared between the groups for blood glucose, or plasma glucagon, vasoactive intestinal polypeptide, motilin, enteroglucagon, secretin, or neurotensin concentrations after feeding. It is concluded that at 9 months of age, the gut regulatory responses to milk feeding are of lower magnitude than during the neonatal period, but even at this age the response patterns still depend on the mode of feeding.     

Role of prolonged breast feeding in infant growth

The growth of 238 healthy full-term infants was followed under a carefully monitored nutritional protocol during the first year of life. The infants were weaned at different ages either to a proprietary infant milk formula or to a home-prepared cow's milk formula. Solid foods were introduced at 3.5 months of age. The 56 infants who were breast-fed for a period of at least 6 months were compared to infants weaned prior to one month of age to one of the two milk regimens. In the breast-fed infants, the weight, weight-for-height-age, and skinfold thickness were similar to values in the proprietary formula-fed infants but were lower than the corresponding values in the cow's milk-fed infants at 6 months of age and subsequently. By using weight-for-height-age as a criterion, no obesity was found among any of the 238 infants, and only 1.7% were considered to be overweight. The results indicate that present recommendations for infant feeding in Finland--including prolonged breast feeding, the use of proprietary milk formulas after weaning, and later introduction of solid foods--prevent overnutrition.     

Serum immunoglobulins in the first year of life

Serum IgG, IgM, and IgA were measured in 316 infants younger than 12 months of age. Information including the child's race, sex, age, and past history of infections or atopy was collected. Birth records were also reviewed to ascertain the child's birthweight and gestational age. Serum IgG levels were higher in black infants than in white infants after the age of 4 months. Serum IgM levels were higher in black females than in black males for infants older than 1 month. For infants younger than 4 months of age, those weighing less than 2500 g at birth had lower IgG levels than those weighing more than 2500 g. Infants younger than 1 month whose gestational age had been less than 36 weeks had lower IgG levels than those greater than 36 weeks. Infants aged 1 to 4 months whose gestational age had been less than 36 weeks had lower IgG levels than did those 40 or more weeks. Infants with a positive history for atopy had lower IgG levels than similarly aged infants with a negative history.     

ROLE OF PROLONGED BREAST FEEDING IN INFANT GROWTH

Abstract. The growth of 238 healthy full-term infants was followed under a carefully monitored nutritional protocol during the first year of life. The infants were weaned at different ages either to a proprietary infant milk formula or to a home-prepared cow's milk formula. Solid foods were introduced at 3.5 months of age. The 56 infants who were breast-fed for a period of at least 6 months were compared to infants weaned prior to one month of age to one of the two milk regimens. In the breast-fed infants, the weight, weight-for-height-age, and skinfold thickness were similar to values in the proprietary formula-fed infants but were lower than the corresponding values in the cow's milk-fed infants at 6 months of age and subsequently. By using weight-for-height-age as a criterion, no obesity was found among any of the 238 infants, and only 1.7% were considered to be overweight. The results indicate that present recommendations for infant feeding in Finland—including prolonged breast feeding, the use of proprietary milk formulas after weaning, and later introduction of solid foods—prevent over-nutrition.     

反复肺炎婴幼儿血清β-防御素-1和免疫球蛋白A、G、M水平的研究

目的：通过检测反复肺炎婴幼儿和健康婴幼儿血清中β-防御素-1（hBD-1）和免疫球蛋白A（IgA）、免疫球蛋白G（IgG）、免疫球蛋白M（IgM）浓度,探讨hBD-1和IgA、IgG、IgM在反复肺炎发病中的可能作用。方法：收集35例2~24月龄反复肺炎和35例健康婴幼儿的血清,处理后应用酶联免疫吸附法（ELISA）检测血清中hBD-1浓度,应用免疫比浊法测定血清IgA、IgG、IgM浓度,并分析血清hBD-1与IgA、IgG、IgM之间的相关性。结果：反复肺炎组血清hBD-1浓度为14±11 μg/mL,显著低于健康对照组（18±11 μg/mL）,差异有统计学意义（P0.05）。结论：反复肺炎婴幼儿存在血清hBD-1、IgA、IgG水平低下的现象,提示呼吸道免疫防御功能存在障碍,这可能是婴幼儿反复肺炎的免疫因素之一;对反复肺炎婴幼儿同时检测 hBD-1、IgA、IgG、IgM具有重要的临床意义。     

Response to RIT 4237 Oral Rotavirus Vaccine in Human Milk, Adapted- and Soy-Formula Fed Infants

ABSTRACT. During the first month of life 28 full-term newborns were breast-fed (18 males and 11 females). Thereafter 8 infants continued breast-feeding while the remainder were randomly fed on either an adapted milk formula ( n =13) or a soy-formula ( n =7). At five months, after an oral dose of RIT 4237 rotavirus vaccine of bovine origin was given, growth and IgM/IgG type antibodies against rotavirus were measured. Weight gain was similar in all infants. There were 2 IgM and 1 IgG responders out of 7 soy fed infants, compared with 4 out of 8 human milk fed (both IgM and IgG) and 7 out of 13 IgM and 6/12 IgG formula fed infants responding to vaccination. This observation confirms previous results obtained with polio, diphtheria tetanus and pertussis vaccines indicating that soy-protein formulas may interfere with immunization processes.     

Serum immunoglobulin levels in normal Sudanese children

Immunoglobulin levels were estimated in 138 infants, of whom 33 were normal newborn and 105 were healthy infants one to 24 months of age. Most of the newborn were delivered after a normal pregnancy. In all the infants relatively high levels of cord IgM were found. Similarly, relatively high levels of IgA were found in cord blood in 72% of the subjects studied. Physiological hypogammaglobulinaemia was not found in the early months of life. Adult levels of IgM were developed by six months of age while 36% of the adult levels of IgA and 57% of the adult levels of IgG were reached by two years of age.     

Antibody Responses to Parenteral and Oral Vaccines Are Impaired by Conventional and Low Protein Formulas as Compared to Breast-feeding

ABSTRACT. The vaccine response to poliovirus, diphtheria and tetanus toxoids in relation to protein intake was studied in infants, either breast-fed or given low (1.1 g/100 ml) or conventional (1.5 g/100 ml) protein formula. Serum, salivá and faeces antibodies were measured by the enzyme-linked immunosorbent assay. Neutralizing poliovirus antibodies were determined. The serum, saliva and faeces antibody responses in the two formula-fed groups of infants did not differ significantly, but for the low protein formula group which had significantly higher serum neutralizing titres to poliovirus after the second vaccine dose than the conventional formula group. However, the breast-fed group had significantly higher antibody levels than the two formula-fed groups together: serum IgG to diphtheria toxoid (p<0.01) and serum neutralization of poliovirus (p<0.001) at 21-40 months of age, saliva secretory IgA to tetanus (p<0.01), diphtheria toxoid (p<0.01) and poliovirus (p<0.05), as well as faecal IgM to tetanus toxoid (p<0.05) and poliovirus (p <0.01 and p <0.05) at 3 and 4 months of age. Breast-fed infants thus showed better serum and secretory responses to peroral and parenteral vaccines than the formula-fed, whether with a conventional or low protein content.     

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.;     

Immunologic response to early and routine DTP immunization in infants

The effect of early immunization, prior to discharge from the newborn nursery, on subsequent immunity as determined by enzyme-linked immunosorbent assay (ELISA) immunoglobulin (Ig) M and IgG antibody titers to filamentous hemagglutinin and lymphocytosis-promoting toxin (LPT) of Bordetella pertussis and by standard pertussis agglutinin titers was investigated. Eighteen infants received routine diphtheria-tetanus-pertussis (DTP) immunization at 2, 4, and 6 months of age; 17 other infants received routine immunization and an additional DTP immunization in the newborn nursery. Antibody was determined on samples of cord blood and whole blood obtained at 4, 6, and 9 months of age. IgM anti-filamentus hemagglutinin was significantly higher at 4 and 6 months of age in the group that received early immunization (P less than .05). There was no significant difference in IgM anti-LPT, IgG anti-filamentus hemagglutinin, IgG anti-LPT, or pertussis agglutinin antibodies. Six control infants had high cord IgG anti-LPT titers. These six infants had significantly lower antibody titers to LPT at 6 and 9 months of age when compared with control with control infants with lower cord titers. Thirteen infants in the early immunization group with lower cord IgG anti-LPT titers achieved significantly lower titers at 9 months of age than the 12 comparable infants in the control group.     

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.     

Response to RIT 4237 oral rotavirus vaccine in human milk, adapted-and soy-formula fed infants

During the first month of life 28 full-term newborns were breast-fed (18 males and 11 females). Thereafter 8 infants continued breast-feeding while the remainder were randomly fed on either an adapted milk formula (n=13) or a soy-formula (n=7). At five months, after an oral dose of RIT 4237 rotavirus vaccine of bovine origin was given, growth and IgM/IgG type antibodies against rotavirus were measured. Weight gain was similar in all infants. There were 2 IgM and 1 IgG responders out of 7 soy fed infants, compared with 4 out of 8 human milk fed (both IgM and IgG) and 7 out of 13 IgM and 6/12 IgG formula fed infants responding to vaccination. This observation confirms previous results obtained with polio, diphtheria tetanus and pertussis vaccines indicating that soy-protein formulas may interfere with immunization processes.     

Development of secretory immunity in breast fed and bottle fed infants.

Samples of saliva and nasal secretions were collected sequentially from 15 breast fed and 15 bottle fed infants on five occasions between 6 days and 9 months of age. Total immunoglobulin concentrations of G, M, and A classes, and class specific antibodies to tetanus toxoid and a pool of commensal strains of Escherichia coli were measured by solid phase radioimmunoassay and expressed per milligram of total protein. There were significant differences between feeding groups, which changed with age. Total IgM and IgA concentrations and IgA antibodies to E. coli were higher in the saliva and nasal secretions of breast fed infants at 6 days. There followed a rapid increase in IgM and IgA concentrations in secretions from all infants, and between 6 weeks and 9 months concentrations were higher in the saliva (but not in the nasal secretions) of the bottle fed group. There were no significant differences between the feeding groups for total IgG, specific G, M, and A antibodies to tetanus toxoid, and G and M antibodies to E. coli. These results suggest that breast feeding enhances secretory immunity in the early neonatal period only. By 6 weeks, local antigens are the main source of stimulation for production of immunoglobulin in the respiratory mucosa and thus may be obscuring any additional stimulation by growth factors in breast milk.