Niels C. R. Räihä

Development of mammalian sulfur metabolism: absence of cystathionase in human fetal tissues.

Extract: Cystathionase activity was absent from human fetal liver and brain as early as 6 weeks of gestation. Hepatic methionine-activating enzyme (26 ± 3 nmoles/mg protein/hr) and hepatic cystathioninesynthase (21 ± 4 nmoles/mg protein/hr) were present (cf. 86 ±16 and 98 ± 19 nmoles/mg protein/hr, respectively, in mature human liver). All three activities were absent from the placenta. Human fetal liver contained higher concentrations of cystathionine (14 ± 2

Studies on the Circulation of the Previable Human Fetus

mUmoles/100 g wet weight) than mature human liver (0) and human fetal brain (4.0 ± 0.6

Effects of Two Different Doses of Amino Acid Supplementation on Growth and Blood Amino Acid Levels in Premature Neonates Admitted to the Neonatal Intensive Care Unit: A Randomized, Controlled Trial

mUmoles/100 g wet weight). Methionine-activating enzyme of human fetal brain, but not liver, showed a tendency to increase with development (coefficient of correlation was 0.62; 0.01 < P < 0.05).35S-l-methionine injected into the umbilical vein of six human fetuses was incorporated into free methionine in liver and brain, but not into free cyst(e)ine, homocyst(e)ine, taurine or, except for the smallest fetus, cystathionine. 35S-l-cysteine similarly injected was incorporated into free cysteine in liver and brain to a greater extent than in plasma, whereas it was incorporated into cystine in plasma to a greater extent than in either liver or brain. Incorporation of 35S into cystathionine in liver was greater from 35S-l-cysteine than from 35S-l-methionine. Both 35S-l-methionine and 36S-l-cysteine were actively incorporated into tissue proteins: methionine > cysteine and liver > kidney > brain.Incorporation of 35S-l-methionine and 35S-l-cysteine incubated with minced liver from four human fetuses showed more active incorporation of methionine (11,836–15,045 dpm/mg protein) than cysteine (7,044–9,856 dpm/mg protein).Speculation: These studies suggest that cysteine is an essential amino acid in human fetuses and in infants for some time after birth, especially if they were born prematurely.

Individualized protein fortification of human milk for preterm infants: comparison of ultrafiltrated human milk protein and a bovine whey fortifier

Extract: The circulation was studied in 33 previable human fetuses (12–272 g) delivered by hysterotomy, while the placenta was still attached. The umbilical vein (UV) and in some instances umbilical or carotid artery (FA) were cannulated. Fetal and maternal pH, PO2, and PCO2 were measured. Radionuclide-labeled microspheres (50 μ in diameter) were injected into the UV on one or more occasions from 1 to 36 min after delivery of the fetus. The distribution of the cardiac output (CO) was calculated from the relative amounts of radioactivity in each organ. In 11 fetuses, FA blood samples were withdrawn during microsphere injection, and CO and actual organ blood flows were measured.With advancing gestational age (10–20 weeks) there was an increase in total inferior vena caval return from 64 to 75% of CO. The proportion of CO to the placenta increased from 17 to 33% and to the gut from 5.5 to 9.2%. Superior vena caval return decreased from 32 to 23%, and the percentage of CO to the kidneys fell from 6.5 to 3.2%. In those fetuses in which repeated observations were made, there was a fairly uniform decrease in proportion of CO distributed to the placenta, probably owing to umbilical vessel constriction. This deterioration was not reflected by UV blood gases which in fact showed a decrease in PCO2 and rise of PO2, when FA showed a rise of PCO2 and fall in PO2 and pH. Associated with the fall in FA pH there was an increase in the proportion of CO to the brain, myocardium, and adrenals. The proportion of CO to the brain increased significantly with increase of FA PCO2.Speculation: The circulation of the previable human fetus may be studied at the time of hysterotomy. It is most important to realize that, even though umbilical venous blood gases may appear to reflect good physiological function, umbilical flow may be markedly decreased. This must be taken into account in all attempts to study placental function.

Protein intake in early infancy: effects on plasma amino acid concentrations, insulin metabolism, and growth

To the Editor.— We read with great interest the article by Clark et al1 on the effects of parenteral amino acid administration to premature infants at 2 different doses (2.5 g/kg per day and 3.5 g/kg per day). In their multicenter study the authors demonstrated that higher parenteral supplementation of amino acids in premature neonates admitted to …

Development of urea-synthesizing enzymes in human liver.

BACKGROUND To improve the nutritional management of pre-term infants, a new individualized human milk fortification system based on presupplementation milk protein analyses was evaluated. METHODS In an open, prospective, randomized multicenter study, 32 healthy preterm infants (birth weights, 920-1750 g) were enrolled at a mean of 21 days of age (range, 9-36 days) when tolerating exclusive enteral feedings of 150 ml/kg per day. All infants were fed human milk and were randomly allocated to fortification with a bovine whey protein fortifier (n = 16) or ultrafiltrated human milk protein (n = 16). All human milk was analyzed for protein content before fortification with the goal of a daily protein intake of 3.5 g/kg. During the study period (mean, 24 days) daily aliquots of the fortified milk were obtained for subsequent analyses of the protein content. RESULTS Both fortifiers were well tolerated, and growth gain in weight, length, and head circumference, as well as final preprandial concentrations of serum urea, transthyretin, transferrin, and albumin were similar in both groups. The ultimate estimated protein intake was equivalent in both groups (mean 3.1+/-0.1 g/kg per day). Serum amino acid profiles were similar in both feeding groups, except for threonine (significantly higher in the bovine fortifier group) and proline and ornithine (significantly higher in the human milk protein group). CONCLUSIONS Protein analyses of the milk before individual fortification provides a new tool for an individualized feeding system of the preterm infant. The bovine whey protein fortifier attained biochemical and growth results similar to those found in infants fed human milk protein exclusively with the corresponding protein intakes.

Growth, serum biochemistries, and amino acids of term infants fed formulas with amino acid and protein concentrations similar to human milk

ABSTRACT: The effects of different protein intakes on wt gain, insulin secretion, and plasma concentrations of amino acids have been evaluated in a prospective study involving 30 normal term infants. The infants were studied from 4.0 to 6.0 mo of age. Ten infants were breast-fed (BF), the others were randomly divided into two groups of 10 infants. One group was fed a formula containing 1.3 g protein/100 mL (F 1.3), the other a formula with 1.8 g protein/100 mL (F 1.8). The formulas were isocaloric (72 kcaI/100 mL), and the fat concentrations were 3.5 g/100 mL (F 1.3) and 3.2 g/100 mL (F 1.8). AH infants received the same supplementary foods. The urinary C-peptide excretion in the infants fed the F 1.8-formula was 4.4 ± 2.1 nmol/mmol creatinine or 19.4 ± 12.9 nmol/m2, significantly higher than that in the infants fed the F 1.3-formula (2.6 ± 1 .5 and 7.9 ± 5.1) or the BF infants (1.7 ± 1.4 and 6.3 ± 6.0). Gain in wt was 18.0 ± 4.3,19.9 ± 3.9, 22.8 ± 1.6 g/kg/wk and corresponded to protein intakes of 1.3 ± 0.2, 1.9 ± 0.3, and 2.6 ± 0.2 g/kg/d, in the BF, F 1.3, and F 1.8 groups, respectively. Gain in length was 6.7 ± 1 .8 (BFgroup), 6.2 ± 2.5 (F 1.3-group), and 7.6 ± 2.2 (F 1.8- group) mm/m/wk. Wt gain correlated with urinary Cpeptide excretion at 6.0 mo (r=0.51, p<0.01) and with protein intake (r=0.43, p<0.01). Furthermore, protein intake correlated with urinary C-peptide excretion (r=0.66, p<0.001). Caloric intake from carbohydrate and fat correlated both with wt gain (r=0.34, p<0.05) and with urinary C-peptide (r=0.44, p<0.05). A higher protein intake during a meal resulted in a higher postprandial excretion of urinary C-peptide. The difference between plasma C-peptide (δC-peptide) before and after a meal was highest in the groups of infants fed the F 1.8-formula. The intakes of the insulin-releasing amino acids (arginine, lysine, leucine, phenylalanine, valine, isoleucine, and threonine) were higher in the F 1.8-group than in the F 1.3- and BF-groups. The sums of the fasting plasma concentrations of these amino acids were 64.8 (BF), 83.6 (F 1.3), and 96.3 (F 1.8) /µ nol/100 mL. The plasma concentrations of the branched-chain amino acids, valine, leucine, and isoleucine correlated with wt gain and plasma valine-glycine ratio increased with higher protein intake. These results suggest that protein amino acid-induced insulin secretion could be a factor promoting growth in infants on high protein intakes.

Fortification of human milk: evaluation of a novel fortification scheme and of a new fortifier

Liver slices from human foetuses of a gestational age between 16 and 20 weeks produce urea when incubated with optimal amounts of substrate.

Inhibition of pyridoxal enzymes by l-canaline

We tested the hypothesis that amino acid intake from infant formulas modified to be similar to human milk would result in indices of protein metabolism more like those in human milk-fed infants. Formula-fed infants received for 12 weeks one of three isocaloric formulations of a whey-adapted formula that differed in protein concentration: 11, 13, or 15 g/L. Infants consumed similar volumes of formula or human milk. Serum urea nitrogen concentrations reflected the protein content of the diets. Plasma indices of protein nutritional status were normal and did not differ among groups. Growth rates of all infants were normal and similar. Serum indicators of protein nutritional status varied with age, which made comparisons of formula-fed infants with human milk-fed infants difficult. Plasma concentrations of leucine and isoleucine at 4 weeks of age were higher in infants fed the formula containing 15 g protein/L when compared with those of infants fed the other two formulas or human milk. At 8 and 12 weeks of age, all formula-fed infants had plasma amino acid profiles that did not differ significantly from each other except for isoleucine, which was lower in the 11-g/L group. We found that providing formulas with an amino acid pattern similar to that of human milk did not produce a plasma amino acid pattern identical to that of the breast-fed infant. This observation suggests that other factors, such as the hormonal response to feeding, differing nutritional bioavailability of amino acids from human and bovine milk proteins, and the changing quantity and type of amino acids with advancing lactation, influence plasma amino acid concentrations.

Phenylalanine Hydoxylase in Human Liver during Development

Human milk fed to very-low-birth-weight infants must be fortified with protein, minerals, and vitamins. We tested a new fortification regimen in which the amount of fortifier was adjusted on the basis of frequent determinations of serum urea nitrogen (SUN). A newly formulated fortifier based on bovine milk proteins was employed either in the new fashion (regimen ADJ) or in the conventional fixed proportion (regimen FIX). Using the fixed proportion, the study also compared the new fortifier with a fortifier based on human milk protein (regimen HMP). Twelve infants were studied with each of the three regimens; nearly all completed 3 weeks of study. Protein intake was generally higher in ADJ than FIX; the difference was significant (p < 0.01) during week 2. Weight gain was somewhat (but not significantly) greater in regimen ADJ (32.3 g/d or 18.8 g/kg/d) than in regimen FIX (30.0 g/d or 18.3 g/kg/d). SUN was higher in ADJ than in FIX, and several other serum chemical values (calcium, phosphorus, potassium) tended to be higher, probably reflecting higher intakes of these nutrients with ADJ than with FIX. Plasma concentrations of several amino acids were higher in ADJ than FIX, but none, including threonine, were outside the physiological range. In comparing regimen FIX to regimen HMP, infants on FIX received similar intakes of protein and showed slightly but not significantly more rapid weight gain. Concentrations of SUN were lower with FIX, but other serum chemical values, including amino acids, were generally similar to HMP. We conclude that use of the new adjustable fortification regimen is feasible and safe and that it should be studied further. It produced the expected increases in nutrient intakes and growth. The new bovine milk-based fortifier appears to be equivalent to the human milk-based fortifier.