Need for riboflavin supplementation in small prematures fed with human milk.

It is the practice in Finland to feed small premature infants with human milk and with no riboflavin supplementation. In this study the riboflavin status was analyzed in 39 such premature infants, 19 with riboflavin supplementation (0.3 mg/day) and 20 without, in their mothers, and in breast-milk samples during a period of 12 wk after delivery. The mean gestational age of the infants was 30.1 wk and their birth weight 1,183 g. Stimulation of erythrocyte glutathione reductase by flavin-adenine-dinucleotide was used as the criterion for riboflavin status in the blood samples. At age 6 wk 47% of the infants without supplementation had activity coefficient values indicative of riboflavin deficiency. The riboflavin status of the infants receiving supplementation was better (p less than 0.01). The concentration of riboflavin in the human milk samples was dependent on the amount of riboflavin supplementation of the mothers during the period from two to twelve weeks after delivery (p less than 0.05-0.01). These data indicate that, in small premature infants the intake of riboflavin may be inadequate without supplementation during the first few weeks after birth.

Vitamin E supplementation in very-low-birth-weight infants: long-term follow-up at two different levels of vitamin E supplementation.

This study evaluates the need of vitamin E supplementation in very-low-birth-weight infants by long-term follow-up of plasma vitamin E status during the first 15 mo of life, with two different levels of supplementation. The subjects were 51 newborn infants with birth weights less than or equal to 1520 g. During hospitalization the infants were fed human milk. On the third day of life oral vitamin E supplementation of less than or equal to 10 mg/d was started in all infants. In addition, 23 infants selected at random were given intramuscular vitamin E (20 mg/kg/d) during the first 3 d. The data indicate that the 10 mg/d supplement resulted in an adequate plasma concentration of vitamin E. After cessation of supplementation at age 3 mo, the risk of low plasma vitamin E levels increased. Although intramuscular administration resulted in long-lasting increments in mean plasma vitamin E values, some later levels in these infants were marginal.

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.

Human milk protein and medium-chain triglyceride oil supplementation of human milk: plasma amino acids in very low-birth-weight infants.

Fifty-one very low-birth-weight infants (birth weight less than 1,520 g) randomly fed either human milk or human milk supplemented with human milk protein and/or with medium-chain triglyceride (MCT) oil were observed. Plasma amino acids from these infants were studied at 2, 8, and 10 weeks. Medium-chain triglyceride oil supplementation had minimal or no influence on plasma amino acids. Human milk protein supplementation resulted in increased concentrations of all amino acids at all ages studied. The concentrations were 1.5- to threefold as compared with values in infants not given protein supplements. However, the concentrations of methionine, tyrosine, phenylalanine, and lysine remained far below values considered harmful. The age at which maximal plasma amino acid concentrations in infants given human milk protein supplementation occur coincides with the age of the lowest serum albumin concentrations in infants fed only human milk. This suggests that high plasma amino acid concentrations may hasten albumin synthesis in very low-birth-weight infants.

Influence of age, time, and peritonitis on peritoneal transport kinetics in children.

OBJECTIVE: To evaluate peritoneal transport kinetics and its changes over time in children with and without peritonitis, and to record possible differences between children under and over 5.0 years of age. DESIGN: A prospective study. The patients underwent a 4-hour peritoneal equilibration test (PET) comprising 2.27% dextrose with a dialysate fill volume of 1000 mL/m2 of body surface area (BSA), at baseline and after a mean of 0.8 +/- 0.4 years of uninterrupted dialysis. PATIENTS: We investigated 28 patients on maintenance peritoneal dialysis at baseline; 10 were under 5.0 years of age. The final PET was performed in 21 patients. MAIN OUTCOME MEASURES: Peritoneal equilibration rates for urea (U), creatinine (C), glucose (G), sodium, potassium, phosphate, and albumin (A) were measured. Initial and final peritoneal equilibration rates were compared. Mass transfer area coefficients (MTAC) were calculated for urea, creatinine, glucose, and albumin. Residual dialysate volume was determined. RESULTS: Median age at first PET was 7.6 years (range 0.3-16.6 yr). The mean (+/- 1 SD) 4-hour dialysate-to-plasma (D/P) ratios for U, C, and A were 0.92 +/- 0.05, 0.70 +/- 0.12, and 0.014 +/- 0.007, respectively. The mean 4-hour D/D0 ratio for G was 0.32 +/- 0.10. D/P and D/D0 results were similar in the two age groups, and peritoneal membrane function remained stable over the study period. Mean MTAC (+/- 1 SD) values were: U, 22.3 +/- 4.8; C, 10.9 +/- 4.1; G, 11.1 +/- 3.3; and A, 0.07 +/- 0.03. MTAC data were similar in the two age groups and no significant changes occurred during the study period. CONCLUSIONS: When the volume tested in children is proportional to BSA, the solute D/P ratios seem to be age-independent. Our data provide evidence that in pediatric patients MTAC is also age-independent.

Peritoneal dialysis in children under 5 years of age.

OBJECTIVE: We report our experience with maintenance peritoneal dialysis (PD) in small children. DESIGN: This is a retrospective analysis of the patient records of all children under the age of 5 years treated with continuous peritoneal dialysis (CPD) between 1986 and 1994 in Finland. SETTING: Treatment was started and the patients were seen at the outpatient clinic at the Hospital for Children and Adolescents, University of Helsinki, every 3 months. Between these visits, they had controls at their local hospital every 2-4 weeks. PATIENTS: The most common primary renal disease in these 34 patients was congenital nephrotic syndrome of the Finnish type (27 patients). Others were: congenital nephrotic syndrome (3 patients), polycystic kidney disease (1), urethral valve (1), neuroblastoma (1), and renal dysplasia (1). RESULTS: Mean age at onset was 1.6 years and median treatment time 9.3 months. Time spent in hospital decreased from 270 days/year in the 1980s to 150 days/year in the 1990s. Two children died (5.9%). The peritonitis rate on continuous cyclic peritoneal dialysis was 1:11.5 patient-months. Hernias were diagnosed in 29% of the patients. After 3 months half of the patients were on antihypertensive medication. Pulmonary edema was diagnosed once in 12 patients and twice in 2 patients. During the first 6 months on PD the mean height standard deviation score (hSDS) increased from -2.13 to -1.66 (p < 0.0001). The 6-month change in hSDS before initiation and 6 months after the start of CPD increased from -0.12 +/-0.68 to +0.59 +/- 0.64 (p = 0.0008). CONCLUSIONS: Our results indicate that peritoneal dialysis is feasible and safe in small children. Mortality was low and growth was good. The major challenges presented by CPD therapy were maintenance of optimal nutrition, avoidance of peritonitis, and control of volemia.

Haemoglobin concentration depends on protein intake in small preterm infants fed human milk.

Studies have shown that early anaemia of prematurity cannot be prevented by iron or vitamin supplementation. We studied 35 infants of birthweight less than 1520 g and mean gestational age 30.4 weeks who were fed either human milk alone or human milk supplemented with human milk protein. The vitamin and iron status were the same in both groups but the concentration of haemoglobin was significantly higher at the ages 4 to 10 weeks in the protein supplemented infants. Reticulocytosis occurred earlier in the protein supplemented infants. The findings on haemoglobin and reticulocytes were similar in 18 infants who received no blood transfusions. We conclude that human milk protein supplementation can increase the haemoglobin concentration of very low birthweight infants in the early weeks of life and that the protein content in human milk may be insufficient to satisfy their needs.

Human milk protein supplementation for the prevention of hypoproteinemia without metabolic imbalance in breast milk-fed, very low-birth-weight infants.

In a group of 18 infants with birth weights of 1,500 gm or less, either preterm transitional or mature human milk was given during the time of initial hospitalization. Half of the infants were given protein supplement isolated from mature human milk which increased the protein content of the ingested milk by 0.8 gm/dl. The protein intake of these infants was increased by 0.6 to 1.6 gm/kg/day between two and 12 weeks after birth. The infants in the unsupplemented group developed hypoproteinemia at 8 to 12 weeks of age whereas those who received protein supplementation did not. We conclude that the hypoproteinemia resulted from nutritional lack of protein and did not represent a physiologic phenomenon of preterm development. There was no difference in the growth of the two groups. There was no evidence of any imbalance in amino acid metabolism even though there were significant correlations between individual protein intakes and plasma concentrations of tyrosine and phenylalanine. Protein intake of more than 3 gm/kg/day resulted in a mean serum urea nitrogen concentration of more than 15 mg/dl at 2 weeks of age, indicating that excessive protein intake should be avoided soon after birth.

Factors limiting the erythropoietin response in rapidly growing infants with congenital nephrosis on a peritoneal dialysis regimen after nephrectomy.

To prevent anemia in seven small children with congenital nephrotic syndrome of the Finnish type (age range 1 to 4 years), we gave recombinant human erythropoietin in a dose up to 150 IU/kg/per week. We then studied the limiting factors during 14 weeks. On a peritoneal dialysis regimen after nephrectomy, the patients grew considerably (range +0.1 to 2.2 kg/14 wk; mean + 1.3 kg/14 wk). The amount of blood taken for laboratory studies was estimated. Although the estimated erythrocyte volume increased, the improvement was masked in most patients by enhanced growth. In two patients the target hemoglobin value of 10 gm/dl was reached, and in three patients transfusions were avoided. The reticulocyte count rose in dose-dependent fashion. In five patients protein malnutrition was not prevented, although intake of protein was as recommended. The gradual decrease in serum ferritin values indicated that mobilization of iron stores was adequate. Serum iron values decreased, although in general remaining within normal limits. In six patients the serum copper concentration was low and in two the serum aluminum concentration was slightly elevated. Two patients had several episodes of infection. We conclude that in rapidly growing infants and small children receiving peritoneal dialysis after nephrectomy, the maintenance or elevation of the hemoglobin concentration depends on several limiting and coinciding factors. We speculate that, when protein is limited, body growth has priority over erythropoiesis. A higher dose of erythropoietin might have evoked a better response in hemoglobin concentration but might also have resulted in progression of the protein deficit.

Mechanism underlying early anaemia in children with familial juvenile nephronophthisis.

Familial juvenile nephronophthisis (NPH) is a hereditary form of chronic tubulointerstitial nephritis with onset in childhood. About one-third of patients develop anaemia before renal insufficiency. We investigated the pathogenetic mechanisms leading to anaemia by comparing 6 patients with NPH and 12 reference patients with other renal diseases. We studied their iron metabolism and measured transferrin receptor-ferritin ratios. There was no evidence for iron deficiency or haemolysis. The serum erythropoietin concentrations of the patients with NPH (12 +/- 2.3 U/I) were low compared with the 12 reference patients (25 +/- 18.9 U/I). In the 2 patients with NPH who were fully investigated, the pharmacokinetics of recombinant human erythropoietin appeared normal. Thus, anaemia in patients with NPH does not result from iron deficiency or correlate with impaired iron status. The mechanism underlying the anaemia of NPH appears to affect the function or regulation of the cells producing erythropoietin.

Biphasic reduction and concanavalin A binding properties of serum alpha-fetoprotein in preterm and term infants.

Reference values for postnatal serum alpha-fetoprotein (AFP) and concanavalin A (ConA) binding subfractions of AFP in preterm and term infants are presented. Preterm infants had 10-fold higher serum concentrations of AFP than did term infants at birth. The reduction of serum values of AFP was biphasic in both groups and differed significantly between the two groups. The first declining phase continued for approximately 4 months in preterm and for 2 months in term infants, and was related to the degree of prematurity. The AFP values reached adult levels by 12 months in preterm and by 9 months in term infants. The developmental pattern of the carbohydrate moiety of AFP was determined by ConA fractioning. The proportion of the ConA nonreactive subfraction of AFP in preterm and term infants at birth was 6% and 13%, respectively; it increased more rapidly in term than in preterm infants but reached 85% to 95% by the age of 6 months in both infant groups. Our results indicate that the postnatal maturation of AFP synthesis is dependent on gestational age. Malignant recurrences of neonatal sacrococcygeal teratomas were associated with an increase in serum concentration of AFP and a decrease in the proportion of the ConA nonreactive subfraction of AFP.