Antibacterial characteristics in the feces of breast-fed and formula-fed infants during the first year of life

BACKGROUND: Human milk is known to protect infants from a number of infectious diseases. Much less is known about the bioactivity of milk-derived factors in the intestine. In this study, potentially protective characteristics in the feces of breast-fed and formula-fed infants were compared. METHODS: The feces of 26 breast-fed and 18 formula-fed infants were collected during the first year of life. In each sample, the concentrations of total protein, immunoglobulin A, and sialic acid were measured. In addition, the effect of the fecal samples was measured on the adhesion of enteropathogenic Escherichia coli (EPEC) to Caco-2 cells and on transepithelial electrical resistance (TER) during an infection. RESULTS: In the first month, sialic acid and immunoglobulin A were found in the feces of breast-fed infants in substantially higher concentrations than in the feces of formula fed infants (sialic acid, 1197 +/- 370 microg/ mL versus 31 +/- 19 microg/ mL; immunoglobulin A, 0.11 +/- 7 mg/mL versus 0.3 +/- 1 mg/mL) and thereafter decreased to similar levels in half a year. Adhesion of EPEC to Caco-2 cells was inhibited between 65% and 85% by stools from both groups. The decrease of TER during EPEC infection was unaffected by fecal samples of any origin or age. CONCLUSION: Potentially protective factors are present in higher concentrations in the stools of breast-fed infants than in stools of formula-fed infants. Interestingly, feces from breast-fed and formula-fed infants inhibited bacterial adhesion to a similar level, but neither was able to preserve epithelial barrier function.     

Plasma concentrations of vitamin D metabolites in unsupplemented breast-fed infants

Plasma concentrations of the vitamin D metabolites 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, 24,25-dihydroxyvitamin D and 25,26-dihydroxyvitamin D were determined in 12 solely breast-fed infants 4 days and 6 weeks after birth. They were not exposed to sunlight, but the mothers received an average of 600 IU vitamin D2 per day during the study period. The mothers' 25-hydroxyvitamin D levels did not change significantly (medians 42 and 58 nmol/l), but the median level dropped from 26 to 15 nmol/l in the infants (P less than 0.001). There was a close correlation between maternal and infant levels at 4 days (r = 0.95). The babies with the highest initial levels showed the most marked decrease by 6 weeks. The median concentrations of 24,25-dihydroxyvitamin D and 25,26-dihydroxyvitamin D decreased similarly from 1.7 to 0.8 and 0.63 to 0.35 nmol/l respectively, (P less than 0.001). The 1,25-dihydroxyvitamin D levels were within normal limits as were plasma calcium, phosphorus, and alkaline phosphatase. The data suggest that fetal stores of vitamin D may be rapidly depleted, and that breast milk may be inadequate as the only source of vitamin D, even for breast-fed infants of vitamin D-supplemented mothers.     

Plasma concentrations of vitamin K1 and PIVKA-II in bottle-fed and breast-fed infants with and without vitamin K prophylaxis at birth

Plasma vitamin K₁ and proteins induced by vitamin K absence (PIVKA) were assayed simultaneously 1–4 days and 29–35 days after delivery in three groups of infants: breast-fed not receiving vitamin K at birth (n=12), bottle-fed without vitamin K administration at birth (n=7) and breast-fed receiving 1 mg vitamin K₁ administered by intramuscular injection at birth (n=13). The bottle-fed infants had a significantly higher vitamin K₁ plasma level than breast-fed infants who did not receive vitamin K₁ at birth. Extremely high levels of vitamin K were obtained 1–4 days after intramuscular administration. At the age of 1 month, breast-fed infants had the same plasma vitamin K₁ concentration whether or not they had received vitamin K₁ supplements. Decarboxy prothrombin (PIVKA-II) a reliable indicator of biochemical vitamin K deficiency, was found in 5 out of 12 breast-fed and in 2 out of 6 bottle-fed infants who had not received supplemental vitamin K₁ after birth. In a separate study, we followed up to 90 days after birth a larger group if infants. PIVKA-II was found with significantly greater frequency in breast-fed infants receiving no vitamin K than in breast-fed infants receiving 1 mg vitamin K intramuscularly at birth, or in bottle-fed infants without extra vitamin K₁. These data form a strong argument for routine vitamin K prophylaxis after birth for all breast-fed infants. The optimum dose and manner of administration require further study.Abbreviations PIVKA proteins induced by vitamin K absence - PIVKA-II decarboxy prothrombin - AU arbitrary units     

Failure to thrive and psychomotor regression revealing vitamin B12 deficiency in 3 infants]

The newborn's vitamin B12 storage exclusively comes from placenta transfer, later from animal food.We relate 3 observations of infants (3-11-13 months) with failure to thrive, anorexia, vomiting and for the two olders refusal of weaning, associated with psychomotricity regression and hypotony. Blood cell count showed a macrocytosis without anemia (case 2-3) and a severe microcytic anemia for the first case caused by a mild alpha-thalassemia, with megaloblastic bone marrow. Vitamin B12 levels were very low associated with increased methylmalonic acid and homocysteine serum levels which confirm the diagnostic . Cerebral imaging showed diffuse cortical atrophy. Cobalamin deficiency was caused by strict vegetarian diets mothers of breastfed infants (cases 2-3) and for younger by mother's unrecognized pernicious anemia. 3 mothers had no anemia and normal B12 's levels at diagnosis. Vitamin B12 supply lead to a rapid clinical and hematologic improvement. In two cases, neurologic recovery was incomplete. About one hundred case of B12 deficiency 's infant are reported, 2/3 are breast-fed by vegetarian mothers, and 1/4 have mothers with pernicious anemia. The failure to thrive is due to anorexia, refusal of weaning and partial villous atrophy. Neurologic manifestations are secondary to cerebral disorders, sometimes revealed by an exposure to anesthetic nitrous oxyd. The macrocytic anemia is inconstant. The etiologic research of developmental delay in an infant may include vitamin B12's deficiency, even if there is no haematologic signs, especially if breast-fedding 's mothers is vegetarian.     

Vitamin K1 (phylloquinone) and vitamin K2 (menaquinone) status in newborns during the first week of life

Since 1961 the Committee on Nutrition of the American Academy of Pediatrics has recommended that prophylactic vitamin K be administered parenterally to all newborn infants, although the exact requirement for vitamin K in the newborn infant is unknown. There is little information about the vitamin K1 (phylloquinone, present in green vegetables) and vitamin K2 (menaquinones, synthesized by intestinal flora) status of newborn infants. In this study during the first week of life vitamin K status was assessed by measuring serum concentrations of phylloquinone in 23 mother-infant pairs at the time of birth. Maternal phylloquinone concentration (1.7 +/- 1.0 ng/mL, mean +/- SD) was significantly higher (P less than .02) than cord serum concentration (1.1 +/- 0.6 ng/mL). All infants were then given a standard 1-mg injection of vitamin K1. Ten infants were fed formula (containing 58 ng/mL of vitamin K1) and 13 were exclusively breast-fed. On day 5 of life, serum concentrations of vitamin K1 did not differ between breast-fed (21.0 +/- 12.4 ng/mL) and formula-fed (27.5 +/- 9.7 ng/mL) infants, reflecting the large amounts of parenteral vitamin K1 at birth. During the first week of life, formula-fed infants had much higher fecal concentrations of vitamin K1 (due to large oral intake) and more significant quantities (greater than or equal to 200 pmol/g of dry weight) of fecal menaquinones (reflecting differences in bacterial flora) than did breast-fed infants.(ABSTRACT TRUNCATED AT 250 WORDS)     

Relationship of milk intake and vitamin K supplementation to vitamin K status in newborns

Vitamin K status was evaluated by measuring blood acarboxyprothrombin (PIVKA-II) levels on the fifth day of life. The incidence of PIVKA-II-positive infants was higher in breast-fed babies than in those given supplementary (mixed) feeding. The median of total amount of milk intake during the first 3 days was significantly lower in PIVKA-II-positive infants than in PIVKA-II-negative infants among infants given both types of feedings. In addition, there was a significant negative correlation between a positive PIVKA-II proportion and the amount of milk intake in the breast-fed babies. The minimum dose of vitamin K2 necessary to prevent a positive PIVKA-II reading was 15 micrograms among babies with a normal absorption potential.     

Vitamin B12 absorption in cystic fibrosis

Vitamin B12 absorption was measured in 30 patients with cystic fibrosis by means of the urinary excretion method and found to be impaired, i.e. less than 10%, in 25. The mean urinary excretion amounted to 4.7 +/- 0.8%. In all patients vitamin B12 absorption improved by the addition of trypsin (18.9 +/- 2.1%). Addition of the vitamin B12 analogue cobinamide, which prevents vitamin B12-binding by R-binders, raised the vitamin B12 absorption to 15.0 +/- 2.2%. A further improvement was obtained by the simultaneous addition of cobinamide and trypsin, 18.2 +/- 2.6%, the same value as with trypsin alone. Assuming that cobinamide addition was effective in suppressing all R-binder activity, the additional effect of trypsin suggests a second, stimulatory function of trypsin on vitamin B12 absorption, separate from R-binder-inactivation. In 5 patients only marginal improvement of vitamin B12 absorption was gained by the addition of either trypsin or cobinamide. The deficient serum vitamin B12 (110 pmol/l) in one of them indicates that the normal pancreas-substitution therapy not always implies sufficient restoration of vitamin B12 absorption.     

Vitamin B12 Absorption in Cystic Fibrosis

Vitamin B12 absorption was measured in 30 patients with cystic fibrosis by means of the urinary excretion method and found to be impaired, i.e. less than 10%, in 25. The mean urinary excretion amounted to 4.7 ± 0.8 %. In all patients vitamin B12 absorption improved by the addition of trypsin (18.9 ± 2.1 %). Addition of the vitamin B12 analogue cobinamide, which prevents vitamin B12-binding by R-binders, raised the vitamin B12 absorption to 15.0 ± 2.2 %. A further improvement was obtained by the simultaneous addition of cobinamide and trypsin, 18.2 ± 2.6 %, the same value as with trypsin alone. Assuming that cobinamide addition was effective in suppressing all R-binder activity, the additional effect of trypsin suggests a second, stimulatory function of trypsin on vitamin B12 absorption, separate from R-binder-inactivation. In 5 patients only marginal improvement of vitamin B12 absorption was gained by the addition of either trypsin or cobinamide. The deficient serum vitamin B12 (110 pmol/I) in one of them indicates that the normal pancreas-substitution therapy not always implies sufficient restoration of vitamin B12 absorption.     

Neurological consequences of vitamin B12 deficiency and its treatment

In developed countries, the vitamin B12 deficiency usually occurs in children exclusively breast-fed, whose mothers are vegetarians, causing low stores of vitamin B12. Symptoms of vitamin B12 deficiency appear during the second trimester of life and include failure to thrive, lethargy, hypotonia, and arrest or regression of developmental skills. A megaloblastic anemia can be present. One half of the infants exhibit abnormal movements before the start of treatment with intramuscular cobalamin, which disappear 1 or 2 days after. More rarely, movement disorders appear a few days after treatment, whereas neurological symptoms are improving. These abnormal movements can last for 2 to 6 weeks. If not treated, vitamin B12 deficiency can cause lasting neurodisability. Therefore, efforts should be directed to preventing deficiency in pregnant and breast-feeding women on vegan diets and their infants by giving them vitamin B12 supplements. When preventive supplementation has failed, one should recognize and treat quickly an infant presenting with failure to thrive and delayed development.     

Crying, fussing and colic behaviour in breast- and bottle-fed infants

Persistent infant crying and "colic" have been linked in some studies to feeding, but this association has not been tested in a planned longitudinal study comparing breast- with formula fed babies. We used validated maternal diaries of infant behaviours, kept for three days at both two and six weeks of infant age, in a comparative study of 97 breast- or formula fed babies. The total duration of overall crying rose significantly between 2 and 6 weeks in breast-fed infants and fell in those fed formula. At 6 weeks, breast-fed infants cried an average of almost 40 minutes more per day than formula fed infants; and 31% cried for more than three hours per day, compared with only 12% of the formula fed group. At six weeks, breast-fed infants also slept almost 80 minutes less per day than the formula fed babies. While six weeks is the established peak age for infant crying, those fed formula peaked much earlier and at 2 weeks intense crying/colic behaviour occurred in 43% of formula fed babies and just 16% of those fed by breast. These findings link the timing of the infant crying peak to the mode of feeding. Our data indicate that any regimen designed to reduce crying should commence in the neonatal period in formula fed infants.     

Brain atrophy caused by vitamin B12-deficient anemia in an infant

Vitamin B12 deficiency in infants often presents with nonspecific hematological, gastrointestinal, and neurological manifestations. It is usually caused by inadequate intake, abnormal absorption, or congenital disorders of vitamin B12 metabolism, including transport disorders. We describe a vitamin B12-deficient infant with severe anemia who was breastfed. His mother had undiagnosed vitamin B12 deficiency having undergone total gastrectomy 18 years earlier. The infant developed normally after taking vitamin B12. It is important to suspect vitamin B12 deficiency in mothers who have undergone gastrectomy. Early diagnosis and treatment of vitamin B12 deficiency in infants is important and will help improve long-term prognosis.     

Elevated Serum Vitamin B12 in Cystic Fibrosis

ABSTRACT. In 62 patients with cystic fibrosis the serum vitamin B12 concentration ranged from 160–2 600 pmol/l with a mean of 1105 pmol/l. Both vitamin B12-binding proteins in the serum, transcobalamin II and R-binders, carried increased amounts of vitamin B12, but showed relatively normal levels of unsaturated vitamin B12-binding capacity. This combination is rather typical for hepatic dysfunction, although the recurrent pulmonary infections might exert an upward effect on plasma R-binder concentration through increased turnover of myeloid cells. A significant positive correlation between transcobalamin II-vitamin B12 and serum alkaline phosphatase suggests that transcobalamin H-bound vitamin B12 might be an early indicator of focal biliary cirrhosis, which is known to occur in these patients.     

THE EFFECT OF DIGESTIVE ENZYMES ON THE BINDING AND BACTERIOSTATIC PROPERTIES OF LACTOFERRIN AND VITAMIN B12 BINDER IN HUMAN MILK

Abstract. Samson, R. R., Mirtle, C. and McClelland, D. B. L. (University Department of Therapeutics and Clinical Pharmacology, The Royal Infirmary, Edinburgh, Scotland). The effect of digestive enzymes on the binding and bacteriostatic properties of lactoferrin and vitamin B12 binder in human milk. Acta Paediatr Scand, 69:517, 1980.—Human milk contains unsaturated lactoferrin and vitamin B12 binding protein. It has been suggested that these proteins may exert antibacterial effects in the intestine of the breast fed infant, but the effect of the intestinal environment on the antibacterial effect of these proteins has not been described. In this study human milk was treated with pepsin and trypsin and the influence of digestion on iron and vitamin B12 binding capacity, bacterial uptake of iron and vitamin B12 from milk and bacteriostatic effect was studied. Pepsin digestion had no effect on vitamin B12 binding capacity, or the ability of bacteria to take up vitamin B12, or the growth inhibitory effect on a vitamin B12 dependant strain. In contrast, pepsin digestion (or low pH alone) released iron from milk and abolished its bacteriostatic effect. Trypsin digestion slightly reduced the molecular size of the vitamin B12 binding protein without releasing free vitamin B12; the bacteriostatic effect on a vitamin B12 dependant organism was, however, abolished. In contrast, trypsin digestion did not affect iron binding or bacteriostatic effects attributable to lactoferrin. The findings support an in vivo bacteriostatic role for lactoferrin in the breast fed neonate's intestine but do not support a similar role for the vitamin B12 binding protein.     

Vitamin K deficiency in breast-fed infants at one month of age

PIVKA-II (protein induced by vitamin K absence or antagonist-II) was measured, as an indicator of vitamin K deficiency, in breast-fed infants of approximately 1 month of age. The infants consisted of three different groups: untreated (group 1); those given 5 mg vitamin K once at birth (group 2); and those given 5 mg twice, at birth and at 14 days after birth (group 3). At 1 month of age, the rate of PIVKA-II-positive infants and their PIVKA-II levels were significantly reduced in group 3 as compared with the levels of the other two groups, whereas these parameters were similar between groups 1 and 2. This observation suggested that vitamin K administration once at birth may be unsafe by 1 month of age. An additional administration of vitamin K seemed to be necessary for complete prevention of vitamin K deficiency, causing severe bleeding in breast-fed infants of approximately 1 month of age.     

Sugar absorption in healthy preterm and full-term infants

We have studied carbohydrate absorption in 40 healthy term infants and 10 preterm neonates (31-35 weeks gestation) by respiratory H2, fecal pH, and chromatographic analysis of stools. Sequential studies of H2 excretion (24-h collection) in response to breast feeding were carried out in premature infants during the first 8 weeks of life. Five expired H2 during the first 2 weeks, and two continued to do so in the 3rd to 4th weeks. Breath H2 excretion fell below 10 ppm by 8 weeks and was not related to feeding or sleep. In term neonates, the frequency of incomplete carbohydrate absorption (4-h test) at the end of the first week was 36% for 14 breast-fed, 42% for 12 formula-fed, and 64% for 14 mixed-fed neonates (not significant differences). There were no significant differences between the absorbing and malabsorbing subjects in fecal pH. Chromatographic analysis showed only small quantities of sugars. In summary, incomplete carbohydrate absorption occurred in a high percentage of the newborns studied; the 24-h test evaluated better than the 4-h test; and negative breath H2 excretion indicated development of the capacity of the small intestine to hydrolyze carbohydrates. In the majority of the preterm malabsorbing babies, completely functional lactase occurs within the first month of life. The growth modulators in human milk may increase the rate of maturing of the small intestine.     

EFFECT OF SEASON AND VITAMIN D SUPPLEMENTATION ON PLASMA CONCENTRATIONS OF 25-HYDROXYVITAMIN D IN NORWEGIAN INFANTS

ABSTRACT. Plasma concentrations of 25-hydroxyvitamin D (250HD) were determined in 81 vitamin D supplemented or unsupplemented infants at the end of winter. The values were compared with maternal levels and with concentrations found in 22 unsupplemented infants at the end of summer. The 250HD levels of the neonates were lower, but closely related to maternal values ( r =0.95, p <0.0005). Unsupplemented breast-fed infants had lower 250HD levels at 6 weeks than at 4 days (16±7 vs. 32±15 nmol/l, mean ±1 SD, p <0.0005). The mean 250HD level of vitamin D supplemented 6-12 months old infants was intermediate between those of the unsupplemented nursed groups and the unsupplemented children studied during summer (53±28 vs. 85±28 nmol/l, p <0.0005). Six weeks old infants who had received a milk formula containing 400 IU vitamin D₃ per liter had levels similar to the latter group (92±21 nmol/l). The data suggest that the vitamin D stores acquired during fetal life, or from ultraviolet light exposure during the summer, may be inadequate to maintain safe levels of 250HD throughout the winter, but that a daily supplement of 400 IU is adequate to establish concentrations in the summer range.     

Effect of season and vitamin D supplementation on plasma concentrations of 25-hydroxyvitamin D in Norwegian infants

Plasma concentrations of 25-hydroxyvitamin D (25OHD) were determined in 81 vitamin D supplemented or unsupplemented infants at the end of winter. The values were compared with maternal levels and with concentrations found in 22 unsupplemented infants at the end of summer. The 25OHD levels of the neonates were lower, but closely related to maternal values (r = 0.95, p less than 0.0005). Unsupplemented breast-fed infants had lower 25OHD levels at 6 weeks than at 4 days (16 +/- 7 vs. 32 +/- 15 nmol/l, mean +/- 1 SD, p less than 0.0005). The mean 25OHD level of vitamin D supplemented 6-12 months old infants was intermediate between those of the unsupplemented nursed groups and the unsupplemented children studied during summer (53 +/- 28 vs. 85 +/- 28 nmol/l, p less than 0.0005). Six weeks old infants who had received a milk formula containing 400 IU vitamin D3 per liter had levels similar to the latter group (92 +/- 21 nmol/l). The data suggest that the vitamin D stores acquired during fetal life, or from ultraviolet light exposure during the summer, may be inadequate to maintain safe levels of 25OHD throughout the winter, but that a daily supplement of 400 IU is adequate to establish concentrations in the summer range.     

Does breast feeding influence liver biochemistry?

OBJECTIVE: It is assumed that early feeding can affect liver biochemistry because breast-fed infants have a higher risk of hyperbilirubinemia than formula-fed infants. The authors sought to determine how feeding mode affected liver biochemistry in healthy term infants. METHODS: Healthy term infants were followed up during infancy with a monthly questionnaire about feeding mode. Blood samples were obtained at 2, 6, and 9 months. Liver biochemistry (serum albumin, alkaline phosphatase, lactic dehydrogenase, aspartate aminotransferase [AST], and bilirubin), total insulin-like growth factor 1 (IGF-I), and insulin growth factor binding protein 3 (IGFBP-3) were determined at all ages. RESULTS: Mean AST and bilirubin were significantly higher in breast-fed infants at 2 and 6 months. In addition, mean albumin levels were higher in breast-fed infants at 2 months. Alkaline phosphatase, IGF-I, IGFBP-3, and lactic dehydrogenase levels did not differ between the feeding groups. AST levels did not correlate significantly with bilirubin, albumin, alkaline phosphatase, or lactic dehydrogenase values. There was a strong positive association between AST and IGF-I at 2 months (r = 0.47, P = 0.004). CONCLUSION: Cytomegalovirus infection, vitamin K deficiency, and macromolecular forms of AST could be an explanation for a higher AST level among breast-fed infants. However, no other clinical or paraclinical sign of liver disease was seen, all infants were given oral vitamin K, and the AST did not rise to levels comparable to those seen in individuals with macromolecular AST. The authors speculate the most likely explanation of the elevated AST is induction of hepatocytes by factors in human milk. This is supported by the higher albumin levels in breast-fed infants and the positive association between AST and IGF-I.     

Visual acuity and cognitive outcomes at 4 years of age in a double-blind, randomized trial of long-chain polyunsaturated fatty acid-supplemented infant formula

BACKGROUND: While there is a large body of data on the effects of long-chain polyunsaturated fatty acid supplementation of infant formula on visual and cognitive maturation during infancy, longterm visual and cognitive outcome data from randomized trials are scarce. AIM: To evaluate docosahexaenoic acid (DHA) and arachidonic acid (ARA)-supplementation of infant formula on visual and cognitive outcomes at 4 years of age. METHODS: Fifty-two of 79 healthy term infants who were enrolled in a single-center, double-blind, randomized clinical trial of DHA and ARA supplementation of infant formula were available for follow-up at 4 years of age. In addition, 32 breast-fed infants served as a "gold standard". Outcome measures were visual acuity and the Wechsler Preschool and Primary Scale of Intelligence--Revised. RESULTS: At 4 years, the control formula group had poorer visual acuity than the breast-fed group; the DHA- and DHA+ARA-supplemented groups did not differ significantly from the breast-fed group. The control formula and DHA-supplemented groups had Verbal IQ scores poorer than the breast-fed group. CONCLUSION: DHA and ARA-supplementation of infant formula supports visual acuity and IQ maturation similar to that of breast-fed infants.     

Macromolecular absorption in infants with infantile colic

Intestinal absorption of macromolecules, using human alpha-lactalbumin (alpha-LA) as a marker, was studied in breast-fed and formula-fed infants with infantile colic. Serum samples taken at 30 and 60 min after an intake of human milk were analyzed for alpha-LA by a competitive radioimmunoassay technique. Breast-fed infants with infantile colic had significantly higher s-alpha-LA levels compared with age-matched breast-fed control infants 0-1 month of age: median value 926 micrograms alpha-LA/l serum/l human milk/kg bodyweight (n = 11) versus 150 (n = 34); 1-2 months of age: 173 (n = 22) versus 31 (n = 16); 2-3 months of age: 132 (n = 8) versus 11 (n = 16). Similarly, formula-fed colicky infants had significantly higher s-alpha-LA levels than age-matched formula-fed control infants 1-2 months of age: median value 126 (n = 12) versus less than 10 (n = 14); 2-3 months of age: 156 (n = 11) versus less than 10 (n = 10). The increased absorption of the macromolecule human alpha-lactalbumin in infantile colic suggests that the gut mucosa is affected in infants with infantile colic.