Effect of human breast milk on biological metabolism in infants

The metabolic changes that occur during the postnatal weaning period appear to be particularly important for future health, and human breast milk is considered to provide the optimal source of nutrition for infants. Our previous studies examined the effect of feeding type on antioxidative properties, glucose and insulin metabolism, the lipid profile, metabolomics, and prostaglandin (PG) metabolism in term and preterm infants. A urinary marker of oxidative DNA damage (8‐hydroxy‐2′‐deoxyguanosine) was significantly lower in breast‐fed term and preterm infants than in formula‐fed infants. Markers of insulin sensitivity were significantly lower and atherosclerotic indices were significantly higher in breast‐fed preterm infants than in mixed‐fed infants at discharge. On urinary metabolomics analysis, choline, choline metabolites, and lactic acid were significantly lower in breast‐fed term infants than in formula‐fed infants. Urinary PGD₂ metabolite level in breast‐fed term infants was also significantly lower than in formula‐fed term infants. This indicates that human breast milk affects biological metabolism in early infancy.     

Increased urinary excretion of inorganic sulfate in premature infants fed bovine milk protein

We report measurements of urinary inorganic sulfate (iSO4) in 38 very low birth weight (VLBW) premature infants receiving various protein intakes in the first 2 months of life. The primary source of urinary iSO4 is the metabolism of amino acids containing sulfur (methionine, cysteine, taurine). It was hypothesized that urinary iSO4 excretion would be increased in VLBW infants fed the relatively high concentrations of protein in mother's own milk (HM), mother's own milk fortified with 0.85 gm/dl bovine whey (fortified HM), and a special formula for premature infants (Similac Special Care, 20 cal/oz), and that urinary iSO4 excretion would correlate with calcium excretion. VLBW premature infants fed HM (protein intake 3.3 gm/kg day) excreted very small amounts of urinary iSO4 compared with infants fed fortified HM (4.5 gm/kg/day protein), Similac SC (2.9 gm/kg/day protein), or Similac (2.7 gm/kg/day protein), all three of which contain bovine whey. Unlike the case in adults, there was no correlation between either total protein intake and urinary calcium excretion or urinary iSO4 excretion. There was, however, a significant correlation between methionine intake and urinary iSO4 excretion (r = 0.48). We speculate that increased urinary iSO4 excretion is indicative of an overload of sulfur-containing amino acids, namely methionine, present in bovine whey protein. The data also support the ability of premature infants to catabolize relatively large quantities of sulfur-containing amino acids after 2 weeks of age.     

Effect of low-dose dopamine infusion on urinary prostaglandin E2 excretion in sick,preterm infants

In pharmacological doses dopamine (DA) will interact with several endocrine systems and both inhibit (prolactin, thyrotropin) and enhance (renin, angiotensin) hormonal release. In this study we have examined whether DA given to preterm neonates will influence prostaglandin (PG) production. The question is of importance since vasodilatator PGs play a role in postnatal adaptation. We determined the effect of low dose DA infusion on the 24 h urinary PGE₂ excretion rate (an index of renal PGE₂ synthesis) in preterm infants. Six preterm neonates, with a 24-h requirement of 2 g/kg per min DA treatment for oedema, moderate oliguria, poor peripheral perfusion and/or mild systemic hypotension were studied on days 2 (Day 1), 3 (Day 2, the day of DA infusion), and 4 (Day 3, DA discontinued) of life. Six preterm infants (control group) that did not require DA infusion were also studied to monitor possible spontaneous changes in the renal PGE₂ production on days 2, 3 and 4 of life. In the control group urine output (U_v) and PGE₂ excretion rate remained unchanged during the study. In the study group DA administration resulted in nearly two-fold increases in both the U_v (194%) and PGE₂ excretion (182%). Urinary PGE₂ excretion was, however, closely related to urine flow in both the control infants (Day 1–3) and the study group infants (Day 1–2). Since increased diuresis stimulates renal PGE₂ production, our data suggest that the increased PGE₂ excretion on Day 2 in the study group was not due to a direct effect of DA on PGE₂ synthesis. On Day 3, however, urinary PGE₂ excretion in the study group decreased out of proportion to that of the U_v (-66% vs-23%), indicating that discontinuation of the drug infusion directly decreases renal PGE₂ synthesis. In conclusion, the findings of the present study indicate that low dose DA does not directly trigger renal PGE₂ production in the sick preterm infant.Abbreviations DA dopamine - PG prostaglandin - U_v urine output - PGE₂ excr PGE₂ excretion rate - PGE₂ conc PGE₂ concentration - SD standard deviation - U_Na, U_K urinary sodium, potassium excretion     

Human milk feeding enhances the urinary excretion of immunologic factors in low birth weight infants

The effects of fortified human milk feedings on the urinary excretion of lactoferrin, lysozyme, secretory component, IgA, and secretory IgA antibodies to Escherichia coli O antigens were investigated in very low birth wt infants. Infants were maintained on either a human milk or a cow's milk preparation. The amounts of each immune factor that were ingested and excreted were quantified during balance studies conducted at 2.5 and 5 wk of age. Serum levels of these immune factors were similar in both feeding groups. The urinary excretion of all factors except lysozyme was 7- to 150-fold greater in infants fed human milk than in those fed cow's milk formula. IgA was the only factor for which the amount of the factor excreted correlated with the amount ingested. Fragments as well as whole molecules of lactoferrin were found in the urine of the infants fed human milk, but the molecular sizes of the excreted proteins exceeded those normally filtered by the kidneys. Therefore, the genesis of the enhanced levels of host defense factors in the urine of infants fed human milk is not clear. Gastrointestinal absorption and subsequent renal excretion as well as enhanced production of immune factors in the infant's urinary tract are possible explanations.     

Prednisolone excretion in human milk

Six lactating women receiving long-term treatment with prednisolone in doses from 10 to 80 mg/day were studied. Serum and milk samples were assayed for prednisolone and endogenous cortisol by a specific high-performance liquid chromatographic method. The milk and serum concentrations vs time curves for prednisolone were virtually parallel, and the milk concentrations were 5% to 25% of those in serum. The milk/serum concentration ratio increased with increasing serum concentration. At a daily dose of 80 mg prednisolone, the infant would ingest less than 0.1% of that dose; this corresponds to less than 10% of the infant's endogenous cortisol production. Because there is an equilibrium between the concentration of prednisolone in milk and serum, the exposure of the infant is minimized if breast-feeding is avoided during the first 4 hours after the dose. We conclude that from a quantitative point of view the exposure of the infant is minimal, and breast-feeding may be permitted at maternal prednisolone doses of at least 20 mg once or twice daily. At higher doses, exposure may be minimized if nursing is performed greater than 4 hours after the dose.     

Fecal cholesterol excretion in preterm infants fed breast milk or formula with different cholesterol contents

In 44 very low-birth-weight infants, fecal cholesterol excretion was measured and in 29 other infants serum total cholesterol concentrations in response to different cholesterol intakes were studied. The infants received fortified breast milk (mean cholesterol content 15.3mg/dl) or were fed either a standard preterm formula (cholesterol content 5.5mg/dl) or the same formula but with a modified lipid composition (long chain polyunsaturated fatty acid concentration closely related to breast milk fat) and 30 mg of cholesterol/dl. In the group fed the high cholesterol formula, fecal cholesterol excretion was significantly higher (35.5mmol/kg/day) than in the groups fed breast milk or the standard formula (20.1 and 18.2mmol/kg/day). Cholesterol balance in the group fed the high cholesterol formula (21.8mg/kg/day) was significantly higher than in the group fed breast milk (+8.6mg/kg/day). In the infants fed the low cholesterol formula the balance was negative (-7.7 mg/ kg/day). Serum concentrations of total cholesterol were similar in the groups fed breast milk or the high cholesterol formula (3.47 and 3.51 mmol/1), but significantly higher than in the group fed the low cholesterol formula (3.15 mmol/1). The data suggest that preterm infants are able to regulate a higher cholesterol intake than during breast feeding by increasing fecal cholesterol excretion as well as decreasing endogenous synthesis.     

Urinary excretion of lactose and oligosaccharides in preterm infants fed human milk or infant formula

At present, not much is known about the absorption and metabolism of human milk (HM) oligosaccharides in term and preterm infants. We investigated the renal excretion of lactose and complex oligosaccharides in preterm infants fed HM ( n = 9, mean actual body weight 2290 g) or a cow's milk-based infant formula ( n = 9, mean actual body weight 2470 g). We found that the renal excretion of lactose in HM-fed infants was slightly lower than in formula-fed infants (14.0 ± 7.4 versus 20.4 ± 8.7 mg kg^-1 day^-1, mean ± SD). The excretion of neutral sugars deriving from oligosaccharides was similar in HM-fed and formula-fed infants (3.8 ± 2.1 versus 2.9 ± 0.9mgkg^-1 day^1-); the difference between means was not statistically significant. The separation and characterization of oligosaccharides by high-pH anion exchange chromatography with pulsed amperometric detection (HPAE-PAD) and subsequent analysis by fast atom bombardment-mass spectrometry (FAB-MS) revealed a more complex pattern in HM-fed infants compared to the formula-fed group. Lactose-derived oligosaccharides characteristic for HM (e.g lacto- N -tetraose, and lacto- N -fucopentaoses I and II) were excreted in HM-fed but not in formula-fed infants. These results indicate that nutrition has a significant impact on the oligosaccharide composition in urine of preterm infants.     

Aflatoxins in human breast milk

Breast milk from 99 Sudanese mothers was analysed for aflatoxins. Aflatoxins M1 and/or M2 were detected in 37 of the milks. No other aflatoxin was detected. M1 occurred alone in 13 milks, (mean 19.0 pg/ml), M2 in 11 milks (mean 12.2 pg/ml), and in 13 samples both M1 and M2 were detected. There appeared to be a linear relationship between M1 and M2 where both were excreted. No aflatoxin was detected in subcutaneous abdominal wall fat removed during Caesarian section from 15 women, but was present in three out of 14 bloods taken during anaesthesia. The presence of aflatoxins in mothers' milk showed no correlation with duration of lactation, the infants' nutrition, presence of aflatoxin in mothers' blood, or the infant's blood and urine. It is concluded that some Sudanese women excrete aflatoxins in breast-milk at levels similar to or higher than those considered safe in animal milk, for human consumption.     

Enhanced fecal excretion of selected immune factors in very low birth weight infants fed fortified human milk

The amounts of lactoferrin, lysozyme, total IgA, secretory IgA (SIgA), and specific SIgA antibodies to a pool of Escherichia coli O antigens were measured in 96-h collections of feces obtained from 28 very low birth weight infants, 28-30 wk of gestation, studied at 2.5 and 6 wk of age. Eighteen of these infants were fed their mothers' milk fortified with fractions of skim and cream derived from pasteurized, lyophilized, mature human milk (FM) and 10 infants were fed commercial cow's milk-based formula. The concentrations of these selected immune factors in the FM and formula also were measured. Specific SIgA antibodies to E. coli O antigens were detected in the feces of 90% of the FM-fed infants, but in none of the feces of the formula-fed infants. The feces obtained from FM-fed infants had markedly greater quantities of lactoferrin (p less than 0.001), lysozyme (p = 0.006), and IgA (p less than 0.001) than those of cow's milk formula-fed infants. The concentrations of total and secretory IgA were correlated significantly (r = 0.88, p less than 0.001) and 95% of total IgA was SIgA. The fecal concentration of specific SIgA antibodies to E. coli O antigens in FM-fed infants correlated with the concentration of these antibodies in their milk (p less than 0.001). However, there were no direct relationships between the milk concentrations or the infant's intakes of the other selected immune factors and the excretion of these factors in the feces.(ABSTRACT TRUNCATED AT 250 WORDS)