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.     

Metabolic and endocrine events at the time of the first feed of human milk in preterm and term infants.

The first feed of breast milk given to a group of 12 term infants was previously shown to increase the levels of blood glucose and plasma insulin, growth hormone (GH), gastrin, and enteroglucagon. We have now studied the effects of the first feed of breast milk in two similar groups of preterm infants, to compare the results with those obtained for the term infant. One group of 8 preterm infants received a bolus (2.5 ml/kg) of breast milk via a nasogastric tube; the other group of 5 infants received a continuous intragastric infusion (2.5 ml/kg per hour) of breast milk. No change occurred in the concentrations of blood glucose, lactate, pyruvate, or ketone bodies, or in plasma insulin, GH, pancreatic glucagon, or enteroglucagon in either the ''bolus fed'' or the ''infusion fed'' group of preterm infants. Thus the marked metabolic and endocrine changes in term infants after the first feed do not occur in preterm infants with standard methods of feeding.     

DEVELOPMENTAL ASPECTS OF GASTRIC INHIBITORY POLYPEPTIDE (GIP) AND ITS POSSIBLE ROLE IN THE ENTEROINSULAR AXIS IN NEONATES

Abstract. Lucas, A., Sarson, D. L., Bloom, S. R. and Aynsley-Green, A. (University Department of Paediatrics, John Radcliffe Hospital, Oxford and Hammersmith Hospital, London, England). Developmental aspects of gastric inhibitory polypeptide (GIP) and its possible role in the enteroinsular axis in neonates. Acta Paediatr Scand, 69: 321, 1980.—Little is known on the development of the release of gastric inhibitory polypeptide (GIP) in neonates or on its potential role in the enteroinsular axis. Using cross-section data collection we studied: ( a ) 100 preterm neonates either at birth (cord blood), or before or after a feed on the sixth or 24th day and ( b ) 63 term neonates at birth or on the sixth day. Blood samples were assayed for GIP, insulin and glucose. At birth plasma GIP concentrations were low compared with fasting adults ( p > 0.01). Basal plasma levels were significantly higher at six days in fed infants, but not in a group of sick preterm infants who had never been fed orally. On sixth day there was no GIP response to a feed, but by 24th day there was a marked postprandial elevation ( p > 0.01). In preterm infants the insulin response was 68 % greater at 24 days than at six days in spite of a similar glycaemic response. We hypothesize that this increasing postnatal insulin response to enteral feeding may be due to the commencement of the postprandial release of GIP, thought to be an important effector in the enteroinsular axis.     

FEEDING AND THE DEVELOPMENT OF ENTEROINSULAR HORMONE SECRETION IN THE PRETERM INFANT: EFFECTS OF CONTINUOUS GASTRIC INFUSIONS OF HUMAN MILK COMPARED WITH INTERMITTENT BOLUSES

ABSTRACT. Preterm infants receive gastric milk feeds as continuous infusions or intermittent boluses. It is not known whether these feeding methods have different effects on the development of digestive metabolism. We have measured plasma levels of insulin, pancreatic polypeptide (PP), gastric inhibitory polypeptide (GIP), gastrin, motilin, enteroglucagon (EG) and neurotensin (NT) in 19 preterm infants (28-34 weeks gestation) tolerating full enteral feeding from birth. 7 infants received human milk by continuous infusion, 12 infants were bolus fed. Hormones were measured in cord blood and at 6 and 13 days of age; samples were drawn preprandially in bolus fed infants. Both groups showed similar significant increases in plasma motilin, PP, NT and EG levels. At 13 days infusion fed infants had higher insulin. GIP and gastrin levels. No difference in rate of weight gain was seen in the two groups of infants. We conclude that both methods of feeding induce progressive changes in circulating enteroinsular hormone levels. However, the endocrine milieu is different in the two groups, particularly since bolus-fed infants experience marked cyclical surges in hormones after boluses of milk by 13 days of age. These differences in hormone release may affect metabolic homeostasis.     

COW'S MILK ALLERGY, INCIDENCE AND PATHOGENETIC ROLE OF EARLY EXPOSURE TO COW'S MILK FORMULA

Abstract. A study was performed in infants under the age of 12 months born during 1974 and admitted to St. Göran's Children's Hospital with symptoms suggestive of cow's milk allergy (CMA). The aims of the study were to determine the role of early exposure to cow's milk formulas as a predisposing factor to CMA and to estimate the incidence of CMA in infancy. Twenty-five infants fulfilled the criteria for CMA. Available records were reviewed and a careful history was obtained from the mothers on two occasions. The patient group was compared with a control group. Sixteen of the 25 infants were exposed to cow's milk protein during their first week in the nursery for newborns, 6 were exposed before the end of the fourth week of life, and 3 infants were apparently not exposed. All infants were breast fed 3 to 26 weeks before re-exposure and occurrence of symptoms. Infants with CMA were given cow's milk formulas during their first 4 weeks of life significantly more often than infants in the control group ( p <0.01). The incidence of CMA was approximately 1:200. The first 4 weeks after birth seem to be a particularly vulnerable period. Hence, in order to prevent CMA, infant formula should not be given—even occasionally—during this period.     

Differences in the pattern of milk intake between breast and bottle fed infants

Two hundred and nine 6-day-old healthy term infants were test weighed either during bottle feeding (n = 77) or breast feeding (n = 132). Cross-sectional data collection avoided repeated interruptions of individual feeds. Bottle fed infants (fed ad libitum) and breast fed infants consumed a similar feed volume (respectively, 67 ± 2 ml versus 75 ±6 ml, mean ±S.E.M.) over a similar period of time (mean 25 min); yet the pattern of milk flow during feeding was significantly different in the two groups. In bottle fed infants, there was a linear pattern of milk intake over the first 10 min of feeding, by which time 81% of the feed has been consumed, contrasting with a biphasic intake pattern in breast fed infants in whom a total 84% of the feed was consumed either in the first 4 min or between 15 and 19 min after the start of the feed. It is speculated that these differences in the pattern of milk intake could influence the physiological responses to feeding and might account for differences between breast and bottle fed infants in gut hormonal responses to milk feeds.     

The influence of feeding regimens on endogenous digoxin-like immunoreactive substance concentrations in infants

The aim of this study was to investigate serum digoxin-like immunoreactive substance (DLIS) levels in 60 healthy term infants when they reached 1–6 months of age with regard to feeding regimen. Group I consisted of 30 infants fed exclusively on breast milk. Groups II and III each consisted of 15 infants fed on formula and cow's milk, and on formula and cow's milk supplemented by breast milk, respectively. Mean serum DLIS concentrations were 0.03 ± 0.05, 0.18 ± 0.09 and 0.15 ± 0.09 ng/ml in groups I-III, respectively. The difference between the DLIS levels in groups II and III was not significant. Serum DLIS levels of infants in groups II and III, on the other hand, were significantly higher than in group I ( p < 0.05). These findings were interpreted to suggest that artificial nutrients may cause volume expansion and an increase in endogenous DLIS levels. The latter response is possibly a protective mechanism to decrease volume expansion in groups II and III.     

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.     

Cow's milk and intestinal blood loss in late infancy

OBJECTIVES: Young infants commonly show occult intestinal blood loss when fed cow's milk, but in older infants blood loss may be less common. This study examined intestinal blood loss in response to cow's milk feeding in normal 7(1/2)-month-old and 12-month-old infants. STUDY DESIGN: Infants (n = 62) were fed formula for 1 month and then pasteurized cow's milk for 2 months. Stools were collected for quantitative determination of hemoglobin. Iron nutritional status was assessed. RESULTS: Infants fed cow's milk from 7(1/2) months of age showed a significant increase in guaiac-positive stools and in stool hemoglobin concentration. These effects were largely limited to those infants who had been breast fed early in life. Infants fed cow's milk from 12 months of age at baseline had greater stool hemoglobin concentrations than 7(1/2)-month-old infants, but cow's milk produced no significant increase. In neither age group did cow's milk affect iron nutritional status. CONCLUSION: The response to cow's milk is attenuated in infants aged 7(1/2) months compared with younger infants. By 12 months of age, the response has disappeared entirely. We conclude that the gastrointestinal tract of healthy infants gradually loses its responsiveness to cow's milk.     

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.     

CHANGES IN HAIR ZINC AND COPPER CONCENTRATIONS OF BREAST FED AND BOTTLE FED INFANTS DURING THE FIRST SIX MONTHS

ABSTRACT. A longitudinal study of 35 full term breast fed (20 males and 15 females; mean birthweight = 3540 g) and 25 full term bottle fed infants (14 males and 11 females; mean birthweight = 3466 g) was carried out to compare the effect of method of feeding on hair zinc and copper concentrations. Hair samples were collected at 30±2, 90±4 and 180±4 days of age and analysed for zinc and copper by instrumental neutron activation procedures. Mean daily zinc and copper intakes were calculated at monthly intervals using three day diet records and test weigh data for the breast fed group. Only the male bottle fed infants showed a significant decline in hair zinc concentration ( p <0.01) during the six-month study period. These results support the suggestion that male infants have a higher requirement for zinc than females in early infancy. No comparable systematic decline in hair zinc levels was evident in the female bottle fed infants or the male and female breast fed infants. The absence of any fall in hair zinc concentrations in the breast fed infants, despite their significantly lower ( p <0.01) dietary zinc intakes compared to the bottle fed group, is attributed to the superior bioavailability of zinc from breast milk. Hair copper levels rose during the first three months in both groups, subsequently declining between 3-6 months. These changes were not significantly related to sex or method of milk feeding, but are associated with the redistribution of copper which occurs during early infancy.     

The effect of feeds of differing composition on entero-insular hormone secretion in the first hours of life in human neonates.

Little is known on the enteral stimuli for gastro-intestinal hormone release in newborn infants. We have compared the effect of the first feed of human breast milk (5 ml/kg) or 10% dextrose (5 ml/kg) on blood glucose and plasma gastrin, enteroglucagon, Gastric Inhibitory polypeptide (GIP), pancreatic glucagon, and insulin in 21 full-term infants at 4--6 hours of age. The first feed of human milk caused a rise in blood glucose and plasma insulin, gastrin and enteroglucagon, but no change occurred in GIP or pancreatic glucagon. The 10% dextrose feed did not stimulate enteroglucagon release, although similar changes occurred in blood glucose and plasma insulin and gastrin. We conclude that the composition of the feed influences the pattern of gastro-intestinal hormone release during the first hours of life and that the entero-insular responses to feeding differ in the neonate and the adult.     

Serum total and free tryptophan levels in term infants fed cow's milk formula or human milk

We found no significant differences in mean total and free tryptophan concentrations in sera of healthy, full-term infants fed cow's milk formula and healthy, full-term infants who were breast-fed. Serum tryptophan concentrations were measured 1 h after feeding when the infants were 2 and 6 days of age. In this study cow's milk formula compared favourably with human milk as primary nutrition for full-term infants, despite a two-to-three fold higher level of free tryptophan in human colostrum.     

DONOR BREAST MILK

Baum, J. D. (University Department of Paediatrics, John Radcliffe Hospital, Oxford, U.K.). Donor breast milk. Acta Paediatr Scand, Suppl. 299:51, 1982.—A simple system for the collection and storage of human milk, as a voluntary community activity, is described. The case is made for prefering drip breast milk as the main source of human milk for the milk bank. The central place of precise pasterurisation is emphasised as the essential feature for maintaining bacteriological quality control and simplicity of organisation. The suitability of donor breast milk for the nutrition of the low birthweight infant is discussed and evidence presented to indicate that low birthweight infants fed exclusively on donated human milk are of similar size to control term infants when assessed at 18 months corrected postnatal age. Emphasis is placed on the importance of controlled trials in relation to all innovations in feeding of low birthweight infants.     

IMMUNOLOGIC CONSEQUENCES OF FEEDING INFANTS WITH COW MILK AND SOY PRODUCTS

ABSTRACT. Various products and regimens proposed for feeding infants when the mother's milk is not available have been evaluated intensively for capacity to achieve optimal nutrition. The immunologic consequences of feeding the foreign proteins contained in the various products have received much less attention and no systematic investigations have been done for comparable immunologic evaluation. Sera obtained at intervals from normal infants fed cow milk and soybean products from birth in different regimens were analyzed for antibodies to five major milk proteins and a soy protein isolate. Antibody levels increased slowly during the first 4 months, reaching a peak about 6 months of age. In infants fed cow milk products or a soy product from birth to 112 days of age and then given various cow milk products the following antibody responses were observed: The level of serum antibodies attained was highest with pasteurized cow milk and lower with heat-treated cow milk or a milk base formula of lower protein content. Feeding a soy product from birth for 112 days did not prevent a brisk antibody response to cow milk introduced subsequently, comparable to or greater than the antibody response seen when cow milk products were fed from birth. Clinically no immunologic disorders were detected in association with antibody responses to the various products and regimens. The implications of the findings for infant feeding and immunologic disorders are discussed.     

SUPPLEMENTARY FEEDING AND JAUNDICE IN NEWBORNS

ABSTRACT. In a survey it was found that the majority of full-term breast fed infants receive supplementary feeds of water, dextrose solution or infant formula during the first few days of life. Breast fed babies receiving water or dextrose supplements had higher plasma bilirubins on the sixth day of life than bottle fed infants. Supplementation with water or dextrose did not reduce the hyperbilirubinaemia of term, breast fed infants. Since it may prejudice the establishment of breast feeding, we suggest that the practice is abandoned.     

THE EFFECT OF FEEDS OF DIFFERING COMPOSITION ON ENTERO-INSULAR HORMONE SECRETION IN THE FIRST HOURS OF LIFE IN HUMAN NEONATES

Abstract. Little is known on the enteral stimuli for gastro-intestinal hormone release in newborn infants. We have compared the effect of the first feed of human breast milk (5 ml/kg) or 10% dextrose (5 ml/kg) on blood glucose and plasma gastrin, enteroglucagon, Gastric Inhibitory polypeptide (GIP), pancreatic glucagon, and insulin in 21 full-term infants at 4–6 hours of age. The first feed of human milk caused a rise in blood glucose and plasma insulin, gastrin and enteroglucagon, but no change occurred in GIP or pancreatic glucagon. The 10% dextrose feed did not stimulate enteroglucagon release, although similar changes occurred in blood glucose and plasma insulin and gastrin. We conclude that the composition of the feed influences the pattern of gastro-intestinal hormone release during the first hours of life and that the entero-insular responses to feeding differ in the neonate and the adult.     

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.     

METABOLIC AND ENDOCRINE CONSEQUENCES OF DEPRIVING PRETERM INFANTS OF ENTERAL NUTRITION

ABSTRACT. Plasma enteroglucagon, pancreatic polypeptide, gastrin, motilin, neurotensin, gastric inhibitory polypeptide, secretin, vasoactive intestinal peptide and blood glucose, alamine, ketone bodies, lactate and pyruvate were measured on the sixth postnatal day in ( a ) a group of 10 preterm infants who on account of hyaline membrane disease had not received enteral feeding since birth and ( b ) before and at 55, 90, and 120 minutes after feeding in a group of healthy preterm infants fed three-hourly on human milk. Gut hormones were also measured in umbilical venous cord blood. The infants receiving regular boluses of milk from birth demonstrated postnatal surges in preprandial concentrations of gut hormones together with cyclical hormonal responses to feeding. None of these changes were seen in infants receiving intravenous fluids. The latter infants also had lower concentrations of blood alanine, glycerol and hydroxybutyrate and lacked the phasic changes in intermediary metabolites seen in the infants receiving enteral boluses of milk. Thus deprivation of enteral feeding results in a profound alteration of the metabolic and endocrine milieu which may have important effect on the process of adaptation to postnatal life.     

Plasma fatty acid composition during the first week of life following feeding with human milk or formula

Plasma fatty acids were studied in 20 full-term newborn infants fed human milk and in 17 newborn infants of identical characteristics fed an adapted cow's milk formula. Plasma fatty acids were measured in cord blood and at 7-9 days of age. No differences were present at birth but, after a period of feeding, infants receiving breast milk had higher plasma concentrations of stearic acid, di-homo-gamma-linolenic acid and arachidonic acid, while infants receiving formula had a higher plasma concentration of oleic acid. The importance of these findings in relation to the lipidic structure of the nervous system remains to be determined.