Cow's milk versus formula in older infants: consequences for human nutrition

Human milk is the preferred feeding for all infants, including premature and sick newborns, with rare exceptions. However, modern technology has produced alternative, "humanized formulae", which closely mimic the composition of human milk. The ingestion of human milk, "humanized formulae" or whole cow's milk has consequences for human nutrition. Gastroesophageal reflux, iron deficiency, calcium and sodium excesses or deficiencies may be influenced by the type and amount of milk fed to the infant. Likewise, neurological development and the likelihood of developing diabetes or cancer may also be influenced by early dietary practices. Until new information is available, we should continue to pattern formulae for older infants after breast milk, but with sufficient protein, calories, lipid and minerals to support optimal growth.     

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.     

Z-score of weight for age of infants with atopic dermatitis and cow's milk allergy fed with a rice-hydrolysate formula during the first two years of life

Background: Recently, rice-based formulas have been widely used in hypoallergenic diets, but data on nutritional values are scarce. Aim: To evaluate the growth of infants fed with a rice-based hydrolysate formula, compared to those infants fed with a soy formula or an extensively hydrolysed casein formula, in the first 2 y of life. Methods: A total of 88 infants were enrolled between March 2002 and March 2004. Fifty-eight infants with atopic dermatitis (AD) and cow's milk allergy (CMA), confirmed by open challenge, were enrolled as study group: 15 were fed with a rice-based hydrolysate formula (RHF), 17 with a soy-based formula (SF) and 26 with an extensively hydrolysed casein formula (eHCF). Thirty infants with AD without cow's milk allergy were recruited as a control group (CG) and fed with a free diet. Weight was recorded on enrolment and at 3-monthly intervals in the first year of life, and at 6-monthly intervals in the second year. Infants were weighed naked, before feeding, by means of an electronic integrating scale. The z-scores of weight for age were calculated. Statistics: One-way analysis of variance and Student's t -test were used for statistical comparison. Significance was set at p <0.05. Results: No significant differences between the RHF, SF and eHCF groups were observed for the z-score of weight for age during the first 2 y of life, but a significantly lower difference was seen in the RHF group compared to the control group in the intervals 9 mo–1 y ( p =0.025) and 1–1.5 y ( p =0.020) of age. In contrast, the SF and eHCF groups were comparable to the control group, but the eHCF group was significantly lower ( p =0) in the first trimester of life.
Conclusion: Even if our findings show no significant difference between RHF and control, low weight observed in infants fed with RHF raises doubts about the nutritional adequacy of rice-hydrolysate formulas.     

Lipoprotein changes in small-for-gestational-age infants fed nucleotide-supplemented milk formula

Morillas J, Moltó L, Robles R, Gil A, Sánchez-Pozo A. Lipoprotein changes in small-for-gestational-age infants fed nucleotide-supplemented milk formula. Acta Prediatr 1994;83:481–5. Stockholm. ISSN 0803–5253
We determined the effect of supplementing milk formula with nucleotides on plasma lipoproteins in small-for-gestational-age infants: 21 infants were fed a nucleotide-supplemented formula and 20 infants were fed the same nucleotide-free formula. On days 0, 3 and 7 after birth, major plasma lipoprotein fractions were analyzed for apolipoprotein and lipid composition. Compared with the control group, the group receiving nucleotides had increased total apoprotein concentrations in all lipoproteins as well as increased apo A-I in high-density lipoproteins and very low-density lipoproteins, and apo B-100 in very low-density lipoproteins and low-density lipoproteins. Very low-density lipoprotein cholesterol, low-density lipoprotein cholesterol and very low-density lipoprotein triglycerides increased in parallel to the changes in apoproteins. The cholesterol ester to unesterified cholesterol ratio was increased in low-density lipoproteins and, particularly, in high-density lipoproteins. These data support the hypothesis that lipoprotein metabolism in small-for-gestational-age infants is affected by dietary nucleotide supplementation, enhancing lipoprotein synthesis or secretion. Cholesterol esterification capacity paralleled the apo A-I increase, in agreement with the co-factor role of apo A-I on lecithin: cholesterol acyltransferase.     

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.     

Nitric oxide metabolites in the urine of full-term and preterm infants

BACKGROUND: In newborn full-term and preterm infants the urine nitrites and nitrates (NOx) were measured, in order to investigate the effects of different pathological conditions (infection, hypoxia) on systemic nitric oxide production. METHODS: Urine nitrites and nitrates were determined by means of the Griess reaction, after reduction of nitrates to nitrites with nitrate reductase. RESULTS: The NOx level was higher in preterm (278 nmol/mL) than full-term (176 nmol/mL) infants. Low NOx (115 nmol/mL) levels accompanied generalized infections, while its high contents (650 nmol/mL) was found in cytomegalovirus and one case of Pneumocystis carinii infection. Moderate increase of NOx production was observed in infants with local pulmonary infections and encephalopathies. CONCLUSIONS: The results indicate urinary NOx level is lowered in infants with life-threatening generalized infection. A possibility of a rapid test based on newborn urinary NOx level determination is considered.     

Choice of formula and human milk supplement for preterm infants in Australia

Human milk (HM) is considered to be the optimal feed of choice for neonates, however, for preterm infants, HM fortifiers are often added to increase growth. If HM is unavailable, preterm formula is the next best option for preterm infants. Choosing which fortifier, if any, to use or which formula can be confusing. In this paper, the composition of milk feeds available in Australia and New Zealand is reviewed with the aim of assisting paediatricians to decide which feed is most appropriate for their patients.     

Selenium content of human milk,cow's milk and cow's milk infant formulas

The selenium content of human milk, cow's milk and cow's milk infant formula were estimated by instrumental neutron activation analysis. The highest values were found in 3 samples of human colostrum (524–865×10^-9 g/g dry weight). There was a significant decrease with increasing time post partum. Mature human milk exhibited a selenium content of 230±79×10^-9 g/g dry weight.The selenium content of 45 samples of cow's milk from the north-western area of Germany was 200±39×10^-9 g/g dry weight. While there was no significant difference between the values of mature human milk and of cow's milk, cow's milk infant formula exhibited significantly (P<0.01) lower values than human milk. The average selenium content of 107 samples of 10 different commercially available fluid and powdered cow's milk infant formulas (range: 18–171×10^-9 g/g dry weight) amounted to about only one third of that in mature human milk.With support of the Deutsche Forschungsgemeinschaft     

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??Objective To investigate the different clinical characteristics of neonatal respiratory distress syndrome??NRDS?? in infants of various gestational ages and to provide a new basis for clinical treatment. Methods A total of 80 cases of NRDS infants in the First Affiliated Hospital of Harbin Medical University from March 2012 to March 2014 were divided into two groups according to gestational age: early preterm infants group??< 34 weeks??42 cases, M group????and nearly full-term group??≥ 34 weeks??38 cases, N group??.Lung surface active substances (PS) replacement and auxiliary ventilation were used, and the general situation??risk factors??treatment condition??prognosis and complications in each group were analyzed. Results The morbidity of NRDS in the male was higher than in the female. The onset time of M group was earlier than N group. In M group it was due to the fact that glucocorticoid was not used and premature birth . In N group it was due to caesarean section. The higher incidence of NRDS in M group was due to premature rupture of membranes and placental abnormality. The lower incidence of NRDS in M group was due to pregnancy hypertension, diabetes, intrauterine distress and abnormal umbilical cord . The PS use time in M group was less than N group. The secondary utilization rate in M group was higher than the N group. The distress degree of M group was higher, and assisted ventilation time and complications were more, compared to N group. Conclusion There are different clinical characteristics of NRDS in infants of various gestational ages. Correct guidance should be given during pregnancy and childbirth and appropriate treatment should be chosen.     

Allergenicity of milk protein hydrolysate formulae in children with cow's milk allergy

Cow's milk protein hydrolysate formulae have been developed to lower or eliminate the allergenicity of cow's milk proteins, and to reduce the antigenic load and the risk of sensitization. Cross-reactivity between different hydrolysate formulae and cow's milk proteins has been demonstrated. We have studied 20 children (median age 31 months, range 15–76 months) with a history of IgE-mediated cow's milk allergy. All the children had immediate allergic respiratory and/or cutaneous and/or gastro-intestinal reactions to cow's milk ingestion. In addition, the children had positive prick skin tests and positive RAST to cow's milk. Prick skin test, RAST, and double-blind placebo controlled food challenges were performed with three different hydrolysate formulae: a casein hydrolysate formula and two whey formulae, one partially and one extensively hydrolyzed. All 20 children had immediate allergic reactions after the challenge test with cow's milk. Only 2/20 children had a positive challenge test with a casein hydrolysate formula (Alimentum): one developed asthma and one urticaria. Two of the 15 children challenged with an extensively hydrolysed whey formula (Profylac) developed perioral erythema. Nine out of 20 children had a positive challenge test with a partially hydrolysed whey formula (Nidina H.A.): four developed asthma, three urticaria and two lip oedema. All children had positive prick skin tests to cow's milk proteins (casein and/or lactalbumin); 9 to Nidina H.A.; 3 to Profylac, and 3 to Alimentum. Specific IgE antibodies to cow's milk were present in all children; in 13 to Nidina H.A., in 4 to Profylac, and in 3 to Alimentum.     

Thymic size in uninfected infants born to HIV-positive mothers and fed with pasteurized human milk

AIM: To examine the size of the thymus in uninfected infants born to HIV-positive mothers and to study the effects of feeding by human donor milk on the size of the thymus in these infants. METHODS: The absolute and relative thymic size was assessed by sonography as thymic index (Ti), and the Ti/weight-ratio (Ti/w) at birth and at 4 mo of age in 12 healthy uninfected infants born to HlV-infected mothers. All infants were exclusively fed pasteurized donor milk. The results were compared with those obtained from a previous cohort of exclusively breastfed, partially breastfed and exclusively formula-fed infants. RESULTS: At birth the Ti was reduced in infants born to HIV-infected mothers in comparison with that in control infants but this difference disappeared when their birthweights were taken into consideration (Ti/w-ratio). At 4 mo of age the geometric mean Ti of infants fed donor milk was 23.8 and the mean Ti/w-ratio was 4.2. Compared with those of exclusively breastfed infants, the Ti and Ti/w-ratio of infants fed donor milk were significantly reduced (p < 0.01). The Ti/w-ratio increased in donor-milk-fed infants compared with that in the formula-fed infants (p = 0.02). CONCLUSION: At birth the size of the thymus was smaller in uninfected infants of HIV-positive mothers compared with infants of HIV-negative mothers but when birthweight was taken into account this difference disappeared. Feeding by human donor milk seemed to result in an increased size of the thymus at 4 mo of age compared with thymic size in infants that were exclusively formula fed.     

Follow up study of cow's milk protein intolerant infants

Over a period of 4 years, 88 infants with cow's milk protein intolerance (CMPI) were followed prospectively in order to evaluate the persistence of CMPI and its relationship between either serum IgE levels or RAST results for cow's milk. After exclusion of lactose intolerance, two positive cow's milk elimination challenge tests were considered diagnostic for CMPI. At the age of 1, 2, 3 and 4 years respectively, 85%, 78%, 49% and 33% of the children still were cow's milk intolerant. Initial serum values of IgE 10 kU/l indicated a late development of tolerance to cow' milk proteins. At the age of 4 years, 90% of infants with initial IgE levels <10 k U/l had become tolerant to cow's milk while this was the case for only 47% of infants with initial IgE levels 10 k U/l. Initial RAST results for cow's milk bore no obvious relationship to outcome.     

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.     

Longitudinal changes in milk composition of mothers delivering preterm and term infants

The concentrations of protein nitrogen (PN), non-protein nitrogen (NPN), energy, fat, sodium (Na), calcium (Ca), phosphorus (P), magnesium (Mg), and zinc (Zn) were determined in human milk from mothers giving birth to full-term (n = 13) and preterm infants (n = 8). Milk samples were collected under controlled conditions at two-week intervals for 12 weeks postpartum. Statistically significant differences in PN, Ca, and P concentrations were detected between the milk from mothers of preterm and term infants. The mean PN concentration in the preterm milk was statistically higher than that of term milk (198 vs. 164 mg N/dl), in contrast to the lower mean Ca (220 vs. 261 mg/1) and P (125 vs. 153 mg/1) concentrations detected in the preterm milk. No other differences in mean nutrient concentration were observed between the two groups. Concentrations of PN, NPN, Na, P, and Zn decreased over time. The concentration of Mg increased slightly. The content of fat, energy, and Ca did not change.     

A comparative study of a premature infant formula and preterm breast milk for low birthweight infants

Although the unique composition of preterm milk (PTM) has led to its increasing use in feeding of low birthweight (LBW) infants, controversy exists as to whether such milk adequately meets their requirements. This study compares the clinical tolerance and anthropometric, biochemical and haematological parameters of LBW infants fed exclusively with their own mother's PTM, a premature infant formula (Alprem; Nestlé Australia) and a mixture of PTM and Alprem. Of 90 enrolled LBW infants (1000-1750 g birthweight), 78 completed the feeding trial for a mean duration of 42 days. Twenty-eight babies were fed Alprem (Group A), 31 received a mixture of Alprem and PTM (Group B) and 18 received PTM (Group C). Babies in Groups A and B were smaller, less mature and more asphyxiated at birth than those in Group C. Weight gain from full enteral feeding was greater in Group A (18.1 g/kg per day) and Group B (17.6 g/kg per day) than in Group C (13.0 g/kg per day). Throughout the trial, weight gain in Groups A and B exceeded predicted intra-uterine growth rates, whereas that for Group C approximated the predicted intra-uterine growth rates. Growth rates of length and head circumference were also greatest in the Alprem-fed babies. Infants receiving PTM were supplemented with calcium, sodium, vitamins and energy, whereas the only three infants requiring mineral supplementation in the Alprem group were those receiving Frusemide therapy for chronic lung disease. Lower serum concentrations of phosphorus, iron, albumin and urea, and higher zinc and alkaline phosphatase concentrations were found in infants receiving PTM (P<0.05). Overall both PTM and Alprem were well tolerated with the four cases of necrotizing enterocolitis and five cases of transient gastrointestinal intolerance distributed equally among the groups. Alprem is a satisfactory alternative to PTM for the feeding of LBW infants as it provides adequate nutrition and supports a growth rate in excess of that in utero without stressing the infant's metabolic or excretory systems.     

Decreased production of specific antibodies to cow's milk proteins in premature infants during the first six months of life

Concentrations of IgG and IgM antibodies to casein, β-lactoglobulin, lactalbumin and bovine serum albumin (BSA) in sera of premature infants of less than 36 weeks gestation, at 5 weeks of age, were less than in age-matched term infants. At 6 months of age IgG antibodies to BSA in preterms were still significantly lower than in term infants.     

Improved growth of preterm infants receiving mother's own raw milk compared with pasteurized donor milk

Aim: To determine whether growth, feeding tolerance and infectious events of preterm infants is related to the proportion of intake of mother’s own raw milk (maternal milk) versus pooled pasteurized banked breast milk (donor milk). Methods: This is a prospective observational study of 55 premature infants born less than 32 weeks of gestational age admitted to the neonatal intensive care unit at the Children’s Hospital of Toulouse during two 6‐month periods from 2003 to 2005. Enrolled infants were exclusively on enteral feeds with maternal milk ± donor milk. Results: Mean gestational age was 28.6 weeks (SD 1.5) and mean birth weight 1105 grams (SD 282). During the time of exclusively breast milk feeds, weight gain (g/kg/day) was correlated to the proportion of maternal milk consumed (p = 0.0048, r = 0.4). Necrotizing enterocolitis was inversely correlated to the amount of maternal milk. The amount of maternal milk did not impact on infectious events. Conclusion: Mother’s own raw milk improves weight gain compared with donor milk in preterm infants. Lactation strategies should be sought that helps mothers to increase their milk production.     

Randomized, double-blind comparison of growth in infants receiving goat milk formula versus cow milk infant formula

OBJECTIVE: To compare growth of infants fed goat milk infant formula (GMF) or cow milk infant formula (CMF) and to compare tolerability and safety of the two formulas. METHODS: The study was conducted in Auckland, New Zealand. This was a double-blind randomized controlled trial. Newborn term infants were randomized within 72 h of birth to GMF or CMF. Milk formula powder in single serve sachets were reconstituted and fed to infants from trial commencement until age 168 days. No other formula given from randomization until age 168 days. Infant weight, length and head circumference were measured at birth and age 14, 28, 56, 84, 112, 140 and 168 days. Bowel motion frequency and consistency, sleeping and crying patterns and adverse events were also measured. RESULTS: Seventy-two infants were randomized, 36 each to GMF or CMF, with 62 infants completing the intervention. At enrollment the average weight of infants in the GMF group (mean +/- SD) was 3.33 +/- 0.43 kg and in the CMF group 3.43 +/- 0.47 kg; and at study completion 8.07 +/- 0.90 kg (GMF) and 7.87 +/- 0.99 kg (CMF). The difference in average weight gain over the study period for the GMF group versus the CMF group was not significant (+309 g; 95% CI = -49 to +668, P = 0.09). Median daily bowel motion frequency was greater in the GMF group than the CMF group (2.4 vs 1.7, P = 0.01). There were no group differences in bowel motion consistency, duration of crying, ease of settling, or frequency of adverse events. CONCLUSION: Growth of infants fed GMF is not different to that of infants-fed CMF.     

Nitrogen and fat balances in very low birth weight infants fed human milk fortified with human milk or bovine milk protein

The study was designed to compare two different human milk fortifiers in a group of very low birth weight (VLBW) infants by analysing nitrogen and fat balances, serum concentrations of alpha-amino-nitrogen, urea, and prealbumin as well as growth rates when human milk enriched with one of the two studied fortifiers was fed to the infants. Fortifier A contained different bovine proteins, peptides and amino acids and had an amino acid composition comparable to that of the nutritional available proteins in human milk, with carbohydrates, and minerals. Fortifier B was composed of freeze-dried skimmed human milk and minerals to achieve a similar macronutrient composition in both fortifiers.Eleven infants were fed with human milk enriched with fortifier A and 13 with fortifier B. After a 10-day equilibration period, a 3-day metabolic balance was performed. On the 14th day of the study blood was obtained preprandially for serum analysis and growth rates were estimated. The nitrogen absorption rate (93.8% vs 93.5%) as well as the retention rate (80.8% vs 78.5%) were no different between the groups. The fat absorption rate (92.3% vs 91.5%) as well as the weight gain (32.1 vs 31.1 g/day) were similar and there were no differences in the serum parameters studied. The results indicate that feeding VLBW infants with human milk enriched with a well-balanced bovine fortifier fulfil their nutritional requirements as well as diets composed exclusively of human milk protein.