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Heat processing is essential for the preservation of milk-based infant formulas. Heating, however, induces a number of chemical changes during which lysine in the milk proteins reacts with reducing sugars to form Maillard reaction products (MRPs) and also reacts with the dehydroalanine resulting from cystine degradation to form lysinoalanine (LAL). Both products have been reported to induce histological changes in the straight portion of the proximal tubule in the rat kidney. This pilot study was made to investigate the urinary excretion by healthy preterm babies of MRPs and LAL contained in infant formula and to determine their influence on kidney function. Twelve healthy male preterm babies were first fed for 10 days with pooled human milk and then for 5 days with each of two experimental premature infant formulas in a cross-over design. The infant formulas were sterilized either by ultra-high temperature (UHT) treatment or by a conventional retort process to give products with low and high levels of MRPs and LAL, respectively. In total, some 15.6% of the initial lysine had been modified in the in-can-sterilized product, compared to 6.2% in the UHT product. Urinary excretion of MRP lactulosyl-lysine ranged from 1.3 to 3.9% of the ingested amount, whereas that of LAL ranged from 6.2 to 9.3%. The higher level of MRPs and LAL in the formulas compared to breast milk had no influence on creatinine clearance or electrolyte excretion. There was no evidence of tubular damage as determined by the urinary excretion of four kidney-derived enzymes. Feeding of formula, however, did result in a general increase in urinary microprotein levels. This did not seem to be a reflection of tubular impairment and was probably due to a transient and normal adaptation to the higher protein content of the formulas, although an effect of MRPs and LAL could not be ruled out.

Inadequate low intake of phosphorus can induce a hypophosphatemic depletion syndrome resulting in hypercalcemia, hypercalciuria, hypophosphatemia, and rickets. Tubular reabsorption for phosphate per liter glomerular filtration rate (TP/GFR) has been proposed as a reliable index of renal phosphate handling for all age groups. In the present study, carried out in 12 healthy premature babies fed unmodified pooled human milk and then a preterm formula for two periods of 10 days, we demonstrated clearly that TP/GFR as well as calciuria can reflect the poor phosphorus intake and that the kidney of preterm babies is able to rapidly adapt itself to an increase in phosphorus diet content.

The objectives of this paper are (1) to describe the organization of neonatal care in Belgium; (2) to review evaluative studies aiming at assessing the availability, effectiveness and cost of care, and (3) to compare the situation in Belgium with that in other countries. In the future, basic neonatal care should be provided in each maternity unit. This means that many maternities need upgrading in staffing and equipment. For intensive care, there is only a need for 10–12 specialized centers in the country. A policy for rapid transfer of sick neonates to specialized centers should be implemented.

Senterre, J. and Salle, B. (Departments of Neonatology, University hospital, Liege, Belgium and Lyon, France). Calcium and phosphorus economy of the preterm infant and its interaction with vitamin D and its metabolites. Acta Paediatr Scand, Suppl. 296: 85, 1982.—One hundred and seventeen 3-day metabolic balance studies were carried out in 69 preterm infants. Matched groups of infants were fed either banked human milk, an infant formula or a low birthweight infant formula with medium-chain triglycerides. In addition groups were constituted according to the vitamin D intake or the administration of 1,25–dihydroxyvitamin D. In infants fed human milk, mean fat absorption was 77%. Calcium absorption was 49±11% with no vitamin D supplementation and it reached 70±11% with a daily oral dose of 30 g of vitamin D. However in this latter group urinary excretion of calcium was very high because of the low phosphorus intake. With infant formula, mean fat absorption was 73%. Calcium absorption was 20±11% with no vitamin D supplementation, 32±13% with 25 g of vitamin D per day and 49±10% with daily administration of 0.5 g of 1,25-dihydroxyvitamin D. With low birthweight infant formula, mean fat absorption was 90%. Calcium absorption was 32±15% with no vitamin D supplementation, 45±13% with 25 g of vitamin D, 59±10% with 50 g of vitamin D and 58±6% with 0.5 g of 1,25-dihydroxyvitamin D per day. However with this active metabolite of vitamin D, serum level and urinary excretion of calcium were significantly higher. Whatever the milk or the vitamin D intake, phosphorus absorption was about 90%. Phosphorus retention was related to nitrogen plus calcium retentions. This study indicates that vitamin D status is the major factor regulating intestinal absorption of calcium. Activation pathways of vitamin D and gut response to 1,25-dihydroxyvitamin D are operative in preterm infant. However in populations where relative vitamin D deficiency is common as in the present study, it seems necessary to give preterm infants a daily oral dose of 30 to 50 g (1200–2000 IU) of vitamin D for achieving maximal calcium absorption. Preferably, plasma 25-hydroxyvitamin D level should guide the clinician in estimating the sufficiency of vitamin D intake.

Dry blood spot immunoreactive trypsin was measured by radioimmunoassay in 84 preterm babies and in 65 full-term newborns studied daily from the first to the fifth day of life. In a control group of 3858 full-term newborns, trypsin concentrations at days 4-6 of life exhibited a log-normal pattern distribution, the geometric mean being 18 ng/ml serum. Immunoreactive trypsin concentrations did not change significantly between days 1, 2, 3, 4 and 5 after birth. Immunoreactive trypsin was found to be significantly lower (geometric mean 9 ng/ml, P less than 0.01) in preterm newborns before 32 weeks of gestation. In hypotrophic newborns of 34 weeks gestational age, immunoreactive trypsin values were higher than those observed at 31 weeks of gestation in eutrophic newborns, the mean birth weight not being different between both groups. These data suggest that trypsin production by the pancreas is dependent on maturity but does not seem related to intrauterine nutritional status. Immunoreactive trypsin concentrations do not change after 32 weeks gestational age and during the first postnatal week.

Serum threonine concentration was determined during the first month of life in 163 low birthweight infants fed on either human milk, various adapted formulae, or total parenteral nutrition. On the pooled data, a significant positive relationship was found between the serum threonine concentration and threonine intake. However, the increase of the serum threonine level is more marked in the infants with the lowest actual gestational age; with a high threonine intake, the most premature infants have serum threonine levels twice as high (58.1 vs 31.7 microM/dl) as term infants. Therefore, threonine metabolism seems to be impeded in preterm infants. Considering the cord blood concentration of threonine (26.8 +/- 5.1 microM/dl) and the possible hazardous effect of hyperthreoninemia, it is suggested that threonine intake should not exceed 1200 microM (143 mg)/kg bodyweight/day in premature infants and that the amino acid composition of the diet should probably be modified in order to satisfy their protein requirement.

Serum amino acid concentration measurements in infants with low birth weight fed on human milk or on two humanized formulas and in infants on total parenteral nutrition showed that taurine was significantly decreased in the three groups on artificial diet. Infants weighing more than 2,000 g on total parenteral nutrition perfused with a solution containing no taurine and little cystine showed a low taurine concentration despite a significant increase of cystine. These results favor the hypothesis of Sturmanet al, that the human infant cannot synthetize an adequate amount of taurine from cystine and methionine precursors and may be dependent on its diets as a taurine source.

Mortality was studied in 504 infants weighing less than 1501 g at birth and treated in four neonatal intensive care units of South-Belgium between 1976 and 1980. Two hundred and twenty-one babies died during their stay at the hospital, a mortality rate of 438 per 1000 live births. The neonatal mortality rate (mortality during the first 28 days of life) was 373 per 1000 live-births. Thirty-three infants died after the neonatal period, which is 15% of the total number of deaths. Two-thirds of these post-neonatal deaths were related to complications of diseases associated with pre-term delivery. Mortality rates were higher in infants of less than 1001 g than in those of 1001-1250 g or 1251-1500 birth weight. In each birth weight category, patients born in their own obstetrical departments and referred infants has similar mortality rates. Longitudinal analysis showed improving mortality rates between 1976 and 1977 in the total population of VLBW infants, between 1977 and 1978 in infants of less than 1001 g and in 1980 compared to 1976 in the 1251-1500 g group. There were higher incidences of need for ventilatory assistance, patent ductus arteriosus, necrotising enterocolitis and septicaemia in referred patients of less than 1001 g than in patients born in their own obstetrical departments with comparable birth weight. Artificial ventilation was more often required in referred infants of 1251-1500 g. This study confirms the importance of considering at least the complete hospital stay when analysing mortality in VLBW infants. Infants of less than 1001 g had high mortality, particularly after the neonatal period.(ABSTRACT TRUNCATED AT 250 WORDS)

Fourteen 3-day metabolic balance studies were carried out in 8 healthy male preterm infants (birthweight 1 270 +/- 170 g, gestational age 30 +/- 2 weeks) fed 183 +/- 7 ml/kg/day of a human milk formula made of incompletely skimmed human milk enriched with lyophilized whole human milk, minerals, medium chain triglycerides and linoleate. Daily intakes per kilo bodyweight were for protein 3.5 +/- 0.3 g, fat 7.0 +/- 2.1 g, and energy 573 +/- 88 kJ (137 kcal). Weight gain was 29 +/- 5 g per day and nitrogen retention was 317 +/- 52 mg/kg/day. Fat absorption was 76 +/- 12%. Renal acid and solute loads were low and there was no metabolic acidosis, hyperazotemia or hyperaminoacidemia, except for tyrosine. It is concluded that preterm infants fed a human milk formula have similar growth rates and nitrogen retentions as foetuses in utero or preterm infants fed their own mother's milk.

SUMMARY Respiratory quotient and gaseous metabolism were measured in normal full-term and small-for-date infants during the first week of life. In both groups RQ dropped during the first day and rose again during the next few days. However, the RQ was lower during the first 5 days in small-for-date infants. The O2 uptake of the small-for-date babies is initially lower but rises during the first 5 days. Technical problems and clinical implications of the results are discussed.

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Insufficient polyamine intake could play a role in the induction of sensitization to dietary allergens. This proposal is based essentially on investigations made in sucking rats and in children. In sucking rats it has been established that oral administration of spermine can induce all the modifications occurring in the digestive tract at weaning. In the intestine events occur in two phases. The early event consists of desquamation of the epithelium resulting from an activation of apoptosis. The late event appears to involve an hormonal cascade in which adrenocorticotropic hormone, cytokines, bombesin and corticosterone are included. Observations in human subjects show that: (1) the spermine and spermidine concentrations are generally lower in infant formulas than in human breast milk. Mothers seem consistently to have relatively high or relatively low concentrations of spermine and spermidine in their milk. These individual variations may be due to diet, lifestyle or genetic background; (2) the probability of developing allergy can reach 80 % if the mean spermine concentration in the milk is lower than 2 nmol/ml milk. It is approximately 0 % if the mean spermine concentration is higher than 13 nmol/ml milk; (3) preliminary results show that the intestinal permeability to macromolecules differs in premature babies when they are fed on breast milk compared with infant formulas (J Senterre, J Rigo, G Forget, G Dandrifosse and N Romain, unpublished results). This difference does not seem to be present when powdered milk is supplemented with polyamines at the concentration found in breast milk; (4) spermine increases proliferation and differentiation of lymphocytes isolated from the tonsils of children.