Nutrient balance studies in premature infants fed premature formula or fortified preterm human milk

This report compares fat, nitrogen, calcium, phosphorus, zinc, and copper absorption and retention data from 13 nutritional balance studies performed in 12 appropriate-for-gestational-age premature infants with birth weights less than or equal to 1,600 g fed a proprietary premature formula or their own mother's preterm human milk (PTHM) fortified with a powdered protein-mineral supplement. At the time of each balance study, each infant had a stable condition, was tolerating feedings, and was gaining weight steadily. Stool and urine were collected separately; doses of carmine red given 72 h apart were used to define dietary intake and the stool and urine collections. The balance studies were performed at an average age of 36 postnatal days. Both diets were found to support weight gain and nutrient retention at similar rates. Balance studies (n = 7) with premature formula demonstrated a weight gain of 16.8 +/- 5.2 g/kg/day, with a net fat absorption of 6.36 +/- 0.97 g/kg/day, net nitrogen retention of 427.9 +/- 47.1 mg/kg/day, net calcium retention of 95.0 +/- 14.1 mg/kg/day, net phosphorus retention of 56.7 +/- 5.9 mg/kg/day, net zinc retention of 208 +/- 903 micrograms/kg/day, and net copper retention of 26.4 +/- 30.8 micrograms/kg/day (mean +/- SD). Comparison balance studies (n = 6) with fortified PTHM demonstrated a weight gain of 17.2 +/- 7.1 g/kg/day, net fat absorption of 5.60 +/- 1.55 g/kg/day, net nitrogen retention of 366.0 +/- 84.0 mg/kg/day, net calcium retention of 82.2 +/- 10.8 mg/kg/day, net phosphorus retention of 58.6 +/- 5.9 mg/kg/day, net zinc retention of 685 +/- 363 micrograms/kg/day, and net copper retention of 67.3 +/- 37.2 micrograms/kg/day. These rates of weight gain and of fat, nitrogen, zinc, and copper retention approximate those of the third trimester of intrauterine life; only calcium and phosphorus retention approached the lower range of estimated in utero accretion.     

Growth and development of premature infants fed predominantly human milk, predominantly premature infant formula, or a combination of human milk and premature formula

BACKGROUND: In a recent meta-analysis, human milk feeding of low birth-weight (LBW) infants was associated with a 5.2 point improvement in IQ tests. However, in the studies in this meta-analysis, feeding regimens were used (unfortified human milk, term formula) that no longer represent recommended practice. OBJECTIVE: To compare the growth, in-hospital feeding tolerance, morbidity, and development (cognitive, motor, visual, and language) of LBW infants fed different amounts of human milk until term chronologic age (CA) with those of LBW infants fed nutrient-enriched formulas from first enteral feeding. METHODS: The data in this study were collected in a previous randomized controlled trial assessing the benefit of supplementing nutrient-enriched formulas for LBW infants with arachidonic acid and docosahexaenoic acid. Infants (n = 463, birth weight, 750-1,800 g) were enrolled from nurseries located in Chile, the United Kingdom, and the United States. If human milk was fed before hospital discharge, it was fortified (3,050-3,300 kJ/L, 22-24 kcal/oz). As infants were weaned from human milk, they were fed nutrient-enriched formula with or without arachidonic and docosahexaenoic acids (3,300 kJ/L before term, 3,050 kJ/L thereafter) until 12 months CA. Formula fed infants were given nutrient-enriched formula with or without added arachidonic and docosahexaenoic acids (3,300 kJ/L to term, 3,050 kJ/L thereafter) until 12 months CA. For the purposes of this evaluation, infants were categorized into four mutually exclusive feeding groups: 1) predominantly human milk fed until term CA (PHM-T, n = 43); 2) >/= 50% energy from human milk before hospital discharge (>/= 50% HM, n = 98); 3) < 50% of energy from human milk before hospital discharge (< 50% HM, n = 203); or 4) predominantly formula fed until term CA (PFF-T, n = 119). RESULTS: PFF-T infants weighed approximately 500 g more at term CA than did PHM-T infants. This absolute difference persisted until 6 months CA. PFF-T infants were also longer (1.0-1.5 cm) and had larger head circumferences (0.3-1.1 cm) than both PHM-T and >/= 50% HM infants at term CA. There was a positive association between duration of human milk feeding and the Bayley Mental Index at 12 months CA (P = 0.032 full and P = 0.073 reduced, statistical models) after controlling for the confounding variables of home environment and maternal intelligence. Infants with chronic lung disease fed >/= 50% HM until term CA (n = 22) had a mean Bayley Motor Index about 11 points higher at 12 months CA compared with infants PFF-T (n = 24, P = 0.033 full model). CONCLUSION: Our data suggest that, despite a slower early growth rate, human milk fed LBW infants have development at least comparable to that of infants fed nutrient-enriched formula. Exploratory analysis suggests that some subgroups of human milk fed LBW infants may have enhanced development, although this needs to be confirmed in future studies.     

Growth and biochemical response of premature infants fed pooled preterm milk or special formula

This study compared growth of a group of very low birth weight infants fed a formula specifically developed for such infants (Formula) with another group fed expressed breast milk (EBM). The Formula contained 2.4 g/dl of protein (lactalbumin:casein ratio, 60:40); 4.1 g/dl of fat (40% medium-chain triglycerides); 8.8 g/dl of carbohydrates; and 81 kcal/dl, with more calcium, phosphorus, and electrolytes than are in human milk. Premature babies with birth weights between 1,200 and 1,500 g and gestational age less than 36 weeks were eligible for the study and were fed either pooled EBM or Formula until they reached a weight of 1,800 g. Twenty infants fed EBM and 19 infants fed Formula completed the trial. Weight gain was faster in the Formula-fed infants after a caloric intake of 100 kcal/kg/day was achieved (Formula 27.7 g/day vs. EBM 17.2 g/day; p less than 0.001). Time to reach 1,800 g was 27 days for the Formula group and 39 days for those on EBM (p less than 0.001). Increments in head circumference and skinfold thickness were also greater in the Formula-fed group. Laboratory studies in the two groups of infants showed higher alkaline phosphatase levels, which were not due to vitamin D deficiency, in the EBM-fed infants.     

Feeding tolerance in premature infants fed fortified human milk

BACKGROUND: To evaluate feeding tolerance in premature infants immediately after the addition of human milk fortifier (HMF) to their expressed human milk diet. METHODS: Data on milk intake, feeding tolerance, and related assessments and growth milestones from a prospective study of feeding strategies in premature infants were analyzed. The database was searched for the first day HMF was added to the feeding of infants receiving human milk exclusively. The following assessments were tabulated for the 5 days before and the 5 days after the addition of HMF: milk intake, the number of episodes of abdominal distension, gastric residual volume (GRV) more than 2 ml/kg and more than 50% of the volume fed in the prior 3 hours. bile-stained gastric residual, emesis or regurgitation, blood in the stool, the number of abdominal radiographs, the number of episodes of apnea and bradycardia, changes in findings in the clinical examination, and the number of hours feeding was withheld. The time to achieve full tube feeding, complete oral feeding, and hospital discharge were recorded. RESULTS: Seventy-six exclusively human milk-fed premature infants (birth weight, 1065+/-18 g; gestational age, 27+/-0.1 weeks; mean +/- SEM) who received HMF beginning 22+/-0.8 days of age were evaluated. There were significant increases in milk intake and in the number of episodes of GRV more than 2 ml/kg and emesis after the addition of HMF. There were no differences in the number of hours feeding was withheld or any other assessment after the addition of HMF. Infants with increases in GRV more than 2 ml/kg and/or emesis after the addition of HMF were not more likely to be delayed in the time to achieve full tube feeding, complete oral feeding, or hospital discharge than infants who did not experience these events. CONCLUSION: These data suggest that, when all feeding and related assessments and the time to achieve important growth milestones are considered, the addition of HMF does not adversely affect the outcome of the premature infant.     

Zinc homeostasis in premature infants does not differ between those fed preterm formula or fortified human milk

The objectives of this study were to compare zinc homeostasis in premature infants enterally fed with either preterm infant formula or fortified human milk; to examine interrelationships of variables of zinc homeostasis; and to examine the findings in relation to estimated zinc requirements of preterm infants. Zinc homeostasis was studied in 14 infants (8 male), with mean gestational age of 31 wk and birth weight appropriate for gestational age, who were exclusively fed either preterm formula (n = 9) or own mother's milk with human milk fortifier (n = 5). Zinc stable isotopes were administered intravenously ((70)Zn) and orally as an extrinsic label ((67)Zn) over multiple feeds for determination of fractional absorption by dual isotope tracer ratio in urine; endogenous fecal zinc was determined by isotope dilution; and exchangeable zinc pool (EZP) size was estimated from linear regression of log-transformed urine (70)Zn enrichment data. Results indicated no significant differences in the variables of zinc homeostasis between the feeding groups; data for all subjects were thus combined. Mean (+/- SD) fractional absorption was 0.26 +/- 0.07; net absorbed zinc 0.43 +/- 0.25 mg/d (0.31 +/- 0.19 mg/kg/d). Mean EZP was 20 +/- 10 mg/kg, and was positively correlated with total absorbed zinc and with net absorbed zinc. Feeding type and total absorbed zinc were significantly related to daily weight gain (p = 0.003). Current zinc intakes from fortified human milk or formula are associated with acceptable weight gain, but whether the observed net zinc absorption was optimal in the human milk group cannot be definitively determined from these data.     

Growth and plasma amino acid concentrations in very low birthweight infants fed either human milk protein fortified human milk or a whey-predominant formula

In a prospective, study involving 20 VLBW-infants (AGA), divided into two study groups of 10 infants, we have evaluated the effects on growth and metabolism of human milk fortified with ultrafiltrated human milk protein and a whey-predominant (whey/casein = 60/40) formula containing 2 g/dl of protein. The study was initiated at a mean age of 30 days when an oral intake of 180 ml/kg/d was tolerated and continued until a weight of 2 kg was reached. The protein intake in both groups was about 3.7 g/kg/d. All infants in both groups reached intrauterine rates of growth for the age, weight gain 18.0 g/kg/d, and length 1.2 cm/week. BUN, acid-base status, total protein and albumin were normal and similar in the two groups. Plasma levels of threonine, glycine, citrulline and methionine were significantly greater in the formula-fed infants. Taurine and proline had higher concentrations in the protein fortified human milk group. There was good tolerance of protein from both sources but the differences in plasma amino acid profiles suggest that the dietary protein quality in formulas for preterm infants must be further modified, if the goal of formula feeding is to achieve metabolic indices of protein metabolism similar to those found when human milk protein is used.     

Indices of protein metabolism in term infants fed human milk, whey-predominant formula, or cow's milk formula

Relationships between intakes of amino acids and total nitrogen, and blood indices of protein utilization were studied in 37 term infants fed either human milk, whey-predominant formula, or cow's milk formula as the sole nutritional source for 8 weeks. Biochemical analyses of two-hour fasting blood samples, and intakes calculated using three-day dietary records and direct analyses of milk samples were used to evaluate these relationships. Intakes of total nitrogen were positively correlated with plasma valine, leucine, isoleucine, phenylalanine, and serum urea nitrogen concentrations (r = .46 to .62, P less than .01 to .001). Intakes of the four amino acids whose plasma concentrations were positively correlated with total nitrogen intakes plus four additional amino acids (threonine, tyrosine, histidine, and methionine) were correlated with their respective plasma concentrations (r = .41 to .74, P less than .01 to .001). These relationships have not been previously described in term infants. Compared with values in infants fed human milk, plasma concentrations of valine, phenylalanine, methionine, and serum urea nitrogen were elevated with whey-predominant formula and cow's milk formula feeding. Values for four additional amino acids (threonine, lysine, leucine, and isoleucine) were elevated with whey-predominant formula feeding. Data indicate that altering the whey-to-casein ratio and, thus, the amino acid pattern of formulas will not achieve the desired blood indices characteristic of human milk feeding without a reduction in the total nitrogen content of formulas.     

Utilization of supplemental iron by premature infants fed fortified human milk

We measured red blood cell iron incorporation (RBC-inc) in 13 human milk-fed premature infants (birthweight 1037 +/- 289 g, gestational age 27 +/- 2 wk, weight at start of study 1571 +/- 426 g) who were receiving full tube-feedings of human milk fortified with a commercial human milk fortifier (FortHM). The relative RBC-inc of supplemental iron (2 mg/kg/d of ferrous sulfate) was assessed using 57Fe sulfate mixed directly into a 24-h volume of FortHM, and 54Fe sulfate given as a bolus between two FortHM feedings the next day. RBC-inc was similar between the two methods of supplemental iron administration (4.7 +/- 2.5% vs 4.6 +/- 1.5%, respectively). Although these values are lower than RBC-inc expected from iron native to human milk, the relatively large amount of iron in the supplements contributed most of the iron incorporated into RBC by the infants. There was a significant positive correlation between the reticulocyte count and RBC-inc. As the high nutrient (especially calcium) content of the FortHM did not interfere with iron utilization, adding iron directly to FortHM, or incorporating it into commercial fortifiers, may be a practical method to provide iron to premature infants.     

Growth and metabolic responses in low-birth-weight infants fed human milk fortified with human milk protein or with a bovine milk protein preparation

Unfortified human milk does not normally provide enough protein to secure maximal growth in low-body-weight (LBW) infants. Due to the practical difficulties in obtaining human milk protein (HMP), a bovine milk protein preparation (BMP) was designed by computer calculation to contain as close as possible the amino acid composition of the nutritionally available human milk proteins. Twenty-one AGA, LBW infants (BW of 1,180 to 1,600 g, GA of 27 to 33 weeks) were randomly assigned to be fed HM enriched either with HMP (9 infants) or BMP (12 infants). When full volume intake (170 ml/kg/day) was reached, the protein intakes were 3.6 +/- 0.5 and 3.3 +/- 0.3 g/kg/day, respectively, in the two diet groups. During the study period of 24 days, the infants achieved intrauterine or better weight gains: 32.9 +/- 3.3 g/day (17.7 +/- 1.9 g/kg/day) in the HMP group and 34.7 +/- 7.3 g/day (18.3 +/- 3.5 g/kg/day) in the BMP group. Serum urea nitrogen, acid-base status, and albumin values were normal and similar in both groups of infants. Plasma concentrations of total essential and total amino acids at the end of the study were 3,999 and 1,539 mumol/L and 3,899 and 1,422 mumol/L in the HMP and the BMP groups, respectively. The concentrations of all individual plasma amino acids were similar in both feeding groups. These results show that feeding human milk fortified with a modified bovine milk protein preparation produces satisfactory growth and a plasma amino acid profile similar to that found in LBW infants fed exclusively human milk protein at similar intakes.     

Macromineral balances in premature infants fed their own mothers' milk or formula

The premature infant's own mother's milk (preterm milk) and modified infant formula (SMA, 67 and 80 kcal/dl) were fed to paired groups of seven infants, all of whom were of very low birth weight (VLBW) (less than 1.3 kg) and were studied during the first month of life. Sodium, potassium, magnesium, calcium, and phosphorus status was compared. The apparent retention of sodium from their mother's milk paralleled intrauterine retention rates and was greater than retention from SMA formula (P less than 0.01) during the first two weeks of life. However, when the formula was supplemented with NaHCO3 to intakes of 2.7 mmol Na/kg/24 hr after week 2, the infants retained adequate amounts of sodium. Potassium retention was similar to intrauterine retention rates in both groups throughout the four postnatal weeks. Magnesium intake, but not retention, was consistently higher in the group fed SMA (P less than 0.01), and intrauterine retention rates were achieved only in the group given formula. Calcium and phosphorus intakes from SMA were also higher (P less than 0.01) than from human milk. However, retention of calcium and phosphorus in both groups did not meet intrauterine retention rates, and hypophosphatemia developed in infants who received their mothers' milk. Growth in length and head circumference in both groups approximated intrauterine growth rates. If it is assumed that body composition of the growing VLBW infants should be similar to the composition of the fetus at corresponding gestational ages, then their nutrient requirements should be based on knowledge of intrauterine nutrient accretion rates. Based on this premise, we conclude that, for the growing VLBW infant, early maternal milk provided for sufficient retention of sodium, chloride, and potassium during the first four postnatal weeks. Neither human preterm milk nor SMA supplied adequate calcium and phosphorus for the growing VLBW infant.     

Bone mineralization and mineral homeostasis in very low-birth-weight infants fed either human milk or fortified human milk

Abnormalities in bone mineral metabolism are frequently found in very low-birth-weight infants, especially if fed breast milk. To assess the efficacy of a breast-milk fortifier in the feeding of these very small infants, very low-birth-weight babies (between 1,000 g-1,500 g at birth) were randomly assigned to one of two groups on day 4 of life. The fortified group received the fortifier mixed in equal proportions with their own mother's milk, while the breast-milk group received only their own mother's milk. All infants received an oral vitamin D supplement of 750 IU/day. The study was continued until the infants weighed 1,800 g, at which stage breast feeding was encouraged. Thirty infants in the breast-milk group and 29 in the fortified group completed the study. Infants in the fortified group had significantly lower alkaline phosphatase values, a greater bone mineral content (BMC) and BMC/bone width ratio, and lower urinary calcium excretion than the breast-milk group at a weight of 1,800 g. At follow-up study 3 months after delivery, when most of the infants in both groups had been breast fed for at least 6 weeks, the breast-milk group's biochemical and BMC abnormalities were almost totally corrected and were now similar to those of the fortified group. Thus, the addition of the fortifier to breast milk during the first 4-6 weeks of life decreased the biochemical evidence of abnormal bone mineral homeostasis and increased BMC in very low-birth-weight infants. By 3 months of age, however, the breast-milk group had almost totally corrected its abnormalities.     

Changes in growth and metabolism in very low birthweight infants fed with fortified breast milk

Human milk is often inadequate nutritionally for preterm infants. We investigated the effect of adding a commercially prepared milk fortifier to human (maternal or bank) milk and measured changes in lower leg length velocity (LLLvel) using knemometry, weight gain and biochemical indices of nutrition. Babies were allocated to one of three feed groups, in a semi-randomized fashion, to receive human milk alone (group I), fortified human milk (group II) or a preterm formula (group III). The birthweights (median and R) and birth gestations (median and R) of the three groups were as follows: group I 1099 g (654-1248 g) and 28 wk (26-32 wk); group II 838 g (742-1340g) and 31 wk (28-36); group III 1136g (624-1552g) and 32 wk (27-36 wk). All babies who received fortified milk either showed significant (p = 0.0004) acceleration in LLLvel during the period studied, or maintained their pre-study period velocity. This increase in LLLvel was comparable to that achieved by a group of babies given a standard preterm infant formula (p < 0.001). By comparison, the control group's change in LLLvel was more modest (p = 0.04). Babies who received human milk with the fortifier added had the lowest serum levels of alkaline phosphatase at the end of the study period when compared to the other two groups. Other biochemical indices were similar in the three feed groups. No adverse clinical events were encountered which could be attributed to the use of the breast milk fortifier.     

Selenium status of preterm infants fed human milk, preterm formula, or selenium-supplemented preterm formula

The selenium status of 46 orally fed vitamin E-sufficient preterm infants (birth weight less than 1700 gm) was studied longitudinally for 3 weeks to determine the efficacy of selenium supplementation. Infants were fed either human milk (n = 21; 24 ng selenium/ml), preterm formula (n = 13; 7.8 ng selenium/ml), or preterm formula supplemented with sodium selenite (n = 12; 34.8 ng selenium/ml). Plasma and erythrocyte selenium and glutathione peroxidase activity and urinary and dietary selenium content were evaluated on study day 1 (day enteral feeds reached 100 kcal/kg/day) and weekly for 3 weeks. Throughout the study, selenium intakes of infants fed preterm formula plus sodium selenite were greater than those of infants fed human milk, which were greater than those of infants fed preterm formula (p less than 0.001). After 3 weeks no differences were observed among groups for plasma or erythrocyte selenium or glutathione peroxidase. Plasma selenium and glutathione peroxidase values within all groups were low compared with those reported for term infants fed human milk. Whereas urinary selenium levels of infants fed preterm formula plus sodium selenite were greater than those of infants fed preterm formula at weeks 1 and 2 (p less than 0.01), infants fed human milk and preterm formula had lower levels at week 3 than on study day 1 (p less than 0.05). We conclude that blood selenium measurements typically used to monitor selenium status do not reflect dietary selenium intakes of orally fed preterm infants.     

Supplementation with human milk protein improves growth of small premature infants fed human milk

We investigated the influence of human milk protein and medium-chain triglyceride supplementations of human milk feedings on the growth of very low birth weight infants during their first weeks of life. A group of 44 preterm infants with birth weights of less than 1,520 g and a mean gestational age of 30.3 weeks was randomly divided into four groups to receive plain human milk or human milk supplemented with human milk protein (0.9 g/dL), with medium-chain triglycerides (1 g/dL), or with both. The medium-chain triglyceride oil supplementation did not influence the growth of these infants. The infants given supplementary protein gained weight faster during weeks 4 to 6 than those without (18.5 +/- 0.7 v 15.1 +/- 0.6 g/kg/d; mean +/- SEM; P = .001). After 4 weeks of age the infants given supplementary protein had a mean weight gain equal to the mean intrauterine rate, in contrast to the infants of the other groups, who grew more slowly until age 6 weeks. Furthermore, we found a correlation between serum albumin concentration and weight gain during the seventh week of life (P = .018). The length growth velocity for the infants with protein supplementation was 0.99 +/- 0.06 cm/wk (mean +/- SEM) and for those without 0.83 +/- 0.05 cm/wk (P = .043). There was no difference in growth of head circumference between the groups. We conclude that human milk protein supplementation improves the growth of small premature infants fed human milk, and that the protein concentration of bank milk is insufficient for their adequate growth.     

Growth, biochemical status, and mineral metabolism in very-low-birth-weight infants receiving fortified preterm human milk

We compared the growth, biochemical status, and mineral status of 30 very-low-birth-weight infants randomly assigned to receive preterm human milk (Group I, 10 infants) from their own mothers, fortified preterm human milk (Group II, 8 infants), or a high-caloric-density premature formula (Group III, 12 infants). Added to the infant's own mother's milk, a human milk fortifier at full strength provided additional protein (60:40 whey/casein, 0.7 g/dl), calories (4 kcal/oz), and minerals. Volume of intake, feeding tolerance, and complications were similar in the three groups. Infants receiving fortified preterm human milk showed growth, biochemical status, and mineral status similar to those receiving high-caloric-density formula, but infants receiving fortified preterm human milk grew faster (12.0 +/- 3.2 vs. 8.9 +/- 1.1 days/300 g, p less than 0.05), had higher serum protein (4.6 +/- 0.5 vs. 4.2 +/- 0.2 g/dl, p less than 0.05), and tended to have better mineral status (higher serum calcium, lower alkaline phosphatase, and higher serum phosphorus, none individually significant) than infants receiving preterm human milk alone. This study supports previous observations that fortified preterm human milk provides nutritional advantages for very-low-birth-weight infants.     

Vitamin D metabolism, mineral homeostasis, and bone mineralization in term infants fed human milk, cow milk-based formula, or soy-based formula

The purpose of this study was to evaluate mechanisms of mineral homeostasis and mineralization in term infants with recommended vitamin D intakes. Infants fed human milk (nine), cow milk-based formula (11), or soy-based formula (11) were studied at 2 weeks and at 2, 4, 6, 9, and 12 months of age. While receiving 400 IU of vitamin D, all infants maintained serum vitamin D concentrations higher or equal to normal adult concentrations, and serum 25-hydroxyvitamin D levels were maintained at or above normal adult levels. Serum 1,25-dihydroxyvitamin D concentrations were higher than those of adults in the formula-fed but not in the human milk-fed infants. Serum calcium and phosphorus values were similar in all groups; however, urine phosphorus excretion and urine calcium excretion were adjusted to intakes. Serum parathyroid hormone values were normal in all groups. Bone mineral content significantly increased with age similarly in all groups; however, an apparent plateau occurred at 6 months of age in all groups. Bone width steadily increased with age. Taken as a whole, these data suggest that the vitamin D-sufficient term infant fed human milk, cow milk-based formula, or the soy-based formula studied can regulate mineral metabolism within acceptable physiologic limits to attain similar levels of serum minerals and bone mineral content.     

Plasma amino acids in small preterm infants fed on human milk or formula.

Plasma amino acids were measured in 35 preterm infants, of whom 11 weighed less than 1000 g and 24 weighed between 1000 g and 1500 g at the time of sampling. Repeat samples were obtained in 18 at least seven days later. Seventeen infants were fed with preterm formula milk and 18 with expressed maternal breast milk at one to two hourly intervals during the study period. Formula fed infants gained weight faster than those fed on breast milk but there was little difference in amino acid patterns. Infants fed on breast milk were more likely to have concentrations of essential amino acids below the mid trimester fetal range than formula fed infants, but few infants in either feeding group had values above the fetal range. Those that did were equally distributed between both groups. Only two samples approached toxic concentrations, both in the group fed breast milk. The ratio of branched chain to aromatic amino acids was higher in the group fed on formula after correction for post conceptional age, implying that liver maturation may be accelerated by formula feeding. No correlations were found between plasma amino acid concentrations and nitrogen retention or metabolisable energy intake.