Plasma esterified F2-isoprostanes and oxidative stress in newborns: role of nonprotein-bound iron

Nonprotein-bound iron (NPBI) and F2-isoprostanes, reliable markers of oxidative stress, are increased in plasma of newborns and inversely correlated to the gestational age. Because NPBI represents a pro-oxidant stimulus in plasma, we test the hypothesis that the entity of lipid peroxidation is related with NPBI concentrations. Plasma levels of free, esterified, and total F2-isoprostanes were investigated in relation to NPBI levels in 59 newborns and 16 healthy adults. The pro-oxidant role of iron was ascertained in vitro, by measuring all the forms of F2-isoprostanes after incubation with ammonium iron sulfate. Significant positive correlations were found between NPBI and total as well as esterified F2-isoprostanes in plasma of the newborns. The addition of ammonium iron sulfate induced a marked increase in all the forms of F2-isoprostanes after 2 hours of incubation. The higher NPBI concentration, the higher F2-isoprostanes levels. An increase NPBI dose dependent in total F2-isoprostanes formation was observed in dialyzed low density lipoprotein from adult plasma. The results clearly show that once NPBI is generated, whatever its source, it is capable of inducing oxidative stress. NPBI-induced oxidative stress may contribute to the morbidity in preterm infants that are particularly susceptible to free radical damage.     

Fatty acid balance studies in preterm infants fed formula milk containing long-chain polyunsaturated fatty acids (LCP) II

A milk formula (Prematil-LCP) containing long-chain polyunsaturated fatty acids (LCP) and with a fatty acid profile closely resembling breast milk has recently been introduced for preterm infants. A double-blind randomized controlled trial was performed comparing fatty acid absorption from Prematil-LCP (n = 10) and standard Prematil (n = 10). Formula-fed preterm infants underwent 3 d fat balances (once full enteral feeds were established) along with a parallel human milk fed group (n = 11). Plasma samples were taken on the last day. Median total fat excretion (absorption, %) was 2.34 g kg (82.0), 2.64 g kg (82.9) and 1.65 g kg (87.8) with Prematil, Prematil-LCP and human milk feeding, respectively. This reflected differences in the excretion and absorption of long-chain saturated fatty acids. All groups excreted detectable LCP. LCP disappearance was higher in infants fed human milk than in those fed Prematil-LCP, particularly for n -6 LCP (p <0:01). Nevertheless, excreted LCP equated to <30% dietary intake, with Prematil-LCP feeding. Plasma lipid fatty acid composition reflected differences in dietary LCP intake.     

Safety and efficacy of nitric oxide in chronic lung disease

BACKGROUND: Therapies for neonatal chronic lung disease (CLD) of prematurity have had limited success. AIMS: To determine whether inhaled nitric oxide (INO) administered to very low birthweight infants with developing CLD might improve oxygenation without adverse effects. METHODS: Subjects were 10-30 days of age, birth weight < 1250 g, with developing or established CLD, and requiring mechanical ventilation with mean airway pressure > or = 7 cm H2O and FIO2 . or = 0.40. We monitored changes in oxygenation and FIO2 requirement during treatment with INO (initial dose 20 ppm). Tracheal aspirate samples obtained before, during, and after treatment were analysed for interleukin 1beta (IL-1beta), IL-8, 8-epi-prostaglandin F2alpha (8-epi-PGF2alpha), laminin, and endothelin 1 (ET-1) to assess any potential effects of INO on markers of inflammation peroxidation, basement membrane injury, or vasoactivity. RESULTS: Thirty three patients met entry criteria. Mean gestational age was 25 (SD 2) weeks; birth weight was 736 (190 g); age of study infants was 19 (6) days (range 9-29). Mean FIO2 decreased from baseline (0.75) to 0.58 at 72 hours. Duration of therapy was seven days. Tracheal aspirate concentrations of IL-1beta, IL-8, 8-epi-PGF2alpha, ET-1, and laminin were unchanged between baseline and 48 hours of INO, and 48 hours after discontinuation of INO. No new cases of, nor extension of, intraventricular haemorrhage occurred. Four infants died. CONCLUSION: INO (< or = 20 ppm) improved oxygenation in most infants with early CLD, without inducing changes in markers of inflammatory or oxidative injury.     

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.     

Urinary lithogenic and inhibitory factors in preterm neonates receiving either total parenteral nutrition or milk formula

The aim of this study was to evaluate prospectively the influence of nutrition on certain factors which may inhibit or promote nephrocalcinosis in two groups of preterm infants, receiving total parenteral nutrition (TPN) and special preterm milk formula respectively, but not furosemide. A total of 37 preterm infants, 15 on TPN and 22 fed a special preterm formula were studied at the end of the 1st, 2nd and 3rd weeks of life, at which time serum and 8 h urine specimens were collected. High ratios of urinary calcium to urinary creatinine (UCa/cr), urinary oxalate to urinary creatinine (Uox/cr) and urinary calcium to urinary citrate (UCa/cit) indicates an increased risk for nephrocalcinosis while high urinary citrate to urinary creatinine (Ucit/cr) ratio indicates protection. Uox/cr increased significantly (P<0.05) in those infants fed preterm formula, from the end of 2nd week of life and was two-fold higher than in the TPN group of preterm infants (P<0.01). Ucit/cr was higher throughout the study period in the formula fed than in the TPN preterm infants. UCa/cit was five-fold higher (P<0.01) in the TPN group, by the end of the 3rd week. Urinary calcium and magnesium was similar in both groups during the study period. Two of the infants studied (5.4%), one from each group, developed nephrocalcinosis.CONCLUSION: In preterm neonates on total parenteral nutrition, urinary oxalate -to-creatinine ratio (a potent lithogenic factor) was lower and urinary citrate -to-creatinine ratio (a lithoprotective factor) also lower than in formula fed neonates. The type of feeding (total parenteral nutrition or special preterm milk formula) seems to affect urinary oxalate and citrate but not calcium and magnesium in non-furosemide treated preterm infants during the first 3 weeks of life.     

Effect of supplementation of preterm formula with long chain polyunsaturated Fatty acids on mineral balance in preterm infants

BACKGROUND: Incorporation of long chain polyunsaturated fatty acids (LCP) into formulas may interfere with mineral metabolism. We investigate mineral balance in preterm infants who were fed a formula with LCP. METHODS: Infants were randomized in a double-blind manner, 20 infants in each group, to receive a formula with LCP (F+LCP) or without LCP (F) for 30 days. Plasma levels (at the beginning and after 30 days) and nutritional balance (after 1 week) for Ca, P, Mg, Zn, and Cu were obtained for all infants. RESULTS: Groups were similar regarding birth weight, gestational age, weight, and corrected age at study start. During the 30-day study period, the groups had comparable milk intake and reached similar and satisfactory weight gains and longitudinal growth. Within each group, there was no change in plasma mineral concentrations over the course of the study, and there were no differences at each time point between groups. All values were within the normal range for age. No differences in mineral balance were detected between the F and F+LCP groups, with both groups demonstrating comparable intake, net retention, and fecal losses of each mineral. CONCLUSIONS: Adding a content of LCP blend similar to that of human milk to a preterm formula caused no disturbance in Ca, P, Mg, Zn, or Cu nutritional balance.     

Visual evoked potentials and dietary long chain polyunsaturated fatty acids in preterm infants.

The influence of dietary long chain polyunsaturated fatty acid (LCP) supply, and especially of docosahexaenoic acid (DHA), on evoked potential maturation, was studied in 58 healthy preterm infants using flash visual evoked potentials (VEPs), flash electroretinography (ERG), and brainstem acoustic evoked potentials (BAEPs) at 52 weeks of postconceptional age. At the same time, the fatty acid composition of red blood cell membranes was examined. The infants were fed on breast milk (n = 12), a preterm formula supplemented with LCP (PF-LCP) (n = 21), or a traditional preterm formula (PF) (n = 25). In the breast milk and PF-LCP groups the morphology and latencies of the waves that reflect the visual projecting system were similar; in the PF group the morphology was quite different and the wave latencies were significantly longer. This could mean that the maturation pattern of VEPs in preterm infants who did not receive LCP was slower. Moreover, a higher level of erythrocyte LCP, especially DHA, was found in breast milk and PF-LCP groups compared with the PF group. ERG and BAEP recordings were the same in all three groups. These results suggest that a well balanced LCP supplement in preterm formulas can positively influence the maturation of visual evoked potentials in preterm infants when breast milk is not available.     

The influence of dietary nucleotides on erythrocyte membrane fatty acids and plasma lipids in preterm infants

Objective : The objective of this study was to evaluate whether a regular formula for premature infants supplemented with nucleotides has any influence on plasma lipids and erythrocyte membrane fatty acids. Methods : Preterm infants fed either human milk supplemented with human milk protein (HM, n = 14), nucleotide-supplemented preterm formula (NF, n = 13), or a regular preterm formula (F, n = 13) were included in the study. The NF was supplemented with 18.2 mg cytidine monophosphate/1 (CMP), 7.0 mg uridine monophosphate/1 (UMP), 6.4mg adenosine monophosphate/1 (AMP), 3.0mg inosine monophosphate/1 (IMP) and 3.0 mg guanosine monophosphate/1 (GMP). Results : There were significantly higher concentrations of triglycerides (TG) in infants fed NF compared to those fed F (191.42 ± 79.58 vs 108.21 ± 43.73, p < 0.001, mean ± SD lipid concentrations, mg/100ml plasma). Infants fed F had significantly lower concentrations of total cholesterol (94.34 ± 11.71 vs 115.69 ± 39.29, p < 0.01) and TG in plasma (108.21 ± 43.73 vs 172.27 ± 68.19, p < 0.001, mean ± SD lipid concentrations, mg/100ml plasma) when compared to HM-fed infants. There were no significant differences in any of the erythrocyte membrane fatty acids and total long-chain polyunsaturated fatty acids (LC-PUFA) between NF and F during the study period (6 weeks). Furthermore, total LC-PUFA and docosahexaenoic acid (DHA) concentrations in red blood cell were not significantly different when infants fed NF were compared to those fed HM. In contrast, however, infants fed F had significantly lower concentrations of total n-3 LC-PUFA ( p < 0.01) and DHA ( p < 0.01) than those found in HM-fed infants. Conclusions : These results do not suggest an effect of nucleotides on the red blood cell LC-PUFA profile in preterm infants. However, the nucleotides may increase the concentrations of triglycerides in plasma.     

Urinary excretion of prostaglandin E and F 2 alpha in healthy newborn infants and in infants with hyaline membrane disease

Urinary PGE and PGF 2 alpha excretion was estimated in 11 healthy full-term (mean birth weight, 3327 g; mean gestational age, 39.2 weeks). 15 healthy preterm (mean birth weight, 1722 g; mean gestational age, 32.1 weeks) and in 9 preterm infants suffering from hyaline membrane disease (HMD) (mean birth weight: 1454 g, mean gestational age: 31 weeks). Measurements were carried out on the 1st, 3rd and 5th days of life by radioimmunoassay, using Clinical Assays Inc. RIA kits. Urinary PGE excretion on the first day of life was 3.76 +/- 0.41 ng/day, 2.43 +/- 0.65 ng/day and 1.19 +/- 0.27 ng/day for healthy full-term, healthy premature and premature infants with HMD, respectively. The differences were significant at the level of p less than 0.05. With advancing postnatal age urinary PGE excretion markedly increased in each group (p less than 0.05). Urinary PGF 2 alpha excretion on the first day was 10.8 +/- 2.0 ng/day in full-term, 6.6 +/- 2.2 ng/day in healthy premature and 4.35 +/- 1.9 ng/day in premature infants with HMD. Then an inconsistent rise could be observed without statistically significant difference between the individual groups of various postnatal age and between the different groups of the same postnatal age. The decreased renal PGE production is suggested to be involved in the pathomechanism of HMD.     

Calcium, sodium and potassium urinary excretion during the first five days of life in very preterm infants

BACKGROUND: Hypercalciuria has been associated with the risk of nephrocalcinosis and renal stones in both adults and children. Renal calcifications are frequently encountered in preterm infants because this particular population presents most of the risk factors of increased urinary calcium excretion. Urinary calcium excretion has been shown to correlate with sodium and potassium excretions in adult patients, but these correlations have not been demonstrated in the early neonatal period yet. OBJECTIVE: To define the relationship between calcium urinary excretion and sodium or potassium excretions in the first 5 days of life in preterm babies. METHODS: A prospective study was conducted in 16 preterm infants born before 32 weeks of gestation (body weight 1,373 +/- 310 g; gestational age 29.1 +/- 1.6 weeks). Fifteen consecutive 8-hour urine collections were performed for each infant from the 8th hour of life. A plasma sample was obtained at the end of each urine collection. Sodium, potassium, calcium and creatinine were measured in urine and blood samples as often as possible. RESULTS: (1) Urine sodium excretion was 6.56 +/- 4.35 mmol/kg per day. (2) Urinary calcium excretion was 5.9 +/- 5.4 mg/kg per day and the urinary calcium/creatinine ratio was 0.48 +/- 0.39 mg/mg. (3) Urinary calcium and sodium excretion were positively correlated (r = 0.65, p = 0.0001), while an inverse correlation was found between calcium and potassium excretion (r = 0.31, p = 0.004). CONCLUSION: The mean values of urinary calcium excretion and calcium/creatinine ratio observed in our population were higher than 4 mg/kg per day and 0.4 mg/mg, respectively, i.e. boundary values previously associated with an increased risk of nephrocalcinosis. We hypothesize that an increase in urinary sodium excretion in this population may facilitate calcium excretion.     

Growth, fatty acid composition of plasma lipid classes, and plasma retinol and a-tocopherol concentrations in full-term infants fed formula enriched with Zω-6 and u-3 long-chain polyunsaturated fatty acids

Full-term infants fed formula without dietary long-chain polyunsaturated fatty acids (LCF) exhibit significantly lower plasma LCP values than breast-fed infants. We studied prospectively two groups of healthy full-term infants fed conventional infant formula without LCP (F, n = 10) or the same formula enriched with both ω-6 and ω- 3 LCP (LCP-F, n = 12). Anthropometric data were obtained and fatty acid (FA) compositions of plasma phospholipids, triglycerides and sterol esters as well as plasma retinol and α-tocopherol concentrations were determined at 5 days and 1, 2, 3 and 4 months of age. Gains in weight, length and head circumference did not differ between the two groups throughout the study period. Plasma FA values did not differ at 5 days of age. Between 1 and 4 months of age, plasma phospholipids of infants fed LCP-F consistently had significantly (p < 0.05) higher percentages of arachidonic acid (1 month: 9.7 (0.8) versus 7.0 (1.3) %wt/wt, 4 months: 8.7 (0.5) versus 6.6 (1.0) %wt/ wt, median (interquartile range), LCP-F versus F) and docosahexaenoic acid (1 month: 2.9 (0.5) versus 1.6 (0.3) %wt/wt; 4 months: 2.9 (0.4) versus 0.9 (0.3) % wt/wt). Plasma retinol and a-tocopherol concentrations did not differ between the two groups throughout the study. We conclude that this form of LCP enrichment of formula for full-term infants effectively enhances plasma LCP contents without detectable adverse effects. The potential effects on functional outcome need to be studied carefully in prospective clinical trials. Growth, infant formula, infant nutrition, long-chain polyunsaturated fatty acids, retinol, α-tocopherol     

Extensive and partial protein hydrolysate preterm formulas: the effect on growth rate, protein metabolism indices, and plasma amino acid concentrations

BACKGROUND: The use of protein hydrolysate preterm formulas is restricted because data on their nutritional adequacy are scarce. The authors evaluated the rate of growth and indices of protein metabolism in low-birth weight infants fed extensive and partial protein hydrolysate preterm formula followed for 12 weeks. METHODS: A total of 61 low-birth weight infants were assigned randomly to receive extensive protein hydrolysate preterm formula (EH: n = 16), partial protein hydrolysate preterm formula (PH: n = 15), and standard preterm formula (SF; n = 15), or were fed their own mother's fortified breast milk (FBM; n = 15). The infants were investigated at study entry, and at 4, 8, and 12 weeks after study entry. RESULTS: There were no differences with respect to growth rate (weight gain, increments in length and head circumference), urea, albumin, prealbumin, transferrin, and plasma amino acid concentrations (except for tyrosine on a single occasion) according to the degree of hydrolysis. There were also no differences between groups fed hydrolyzed formulas and SF. However, several differences were found when EH and PH were compared with FBM. Weight gain from the entry to 12 weeks, serum urea at 12 weeks, and total plasma essential amino acids at 8 weeks were significantly higher in groups fed EH and PH than in those fed FBM. In addition, valine was significantly higher in groups fed PH (P < 0.05) than in the group fed FBM at 8 and 12 weeks, tyrosine was higher in EH and PH in comparison with FBM at 4 weeks, and in PH versus FBM at 12 weeks after study entry. CONCLUSIONS: This study suggests that experimental EH and PH are at least nutritionally equivalent to SFs.     

Persistent high activity of the fetal adrenal cortex in preterm infants: is there a clinical significance?

BACKGROUND: In preterm infants, the activity of the fetal adrenal cortex continues until term. Dehydroepiandrosterone sulphate can block the synthesis of surfactant in vitro. The incidence of pulmonary disease is higher in male than in female preterm infants. OBJECTIVE: To investigate the relationship between urinary excretion of fetal zone steroids (3beta-OH-5-ene-steroids) and the severity of lung disease in preterm infants with respect to gender. PATIENTS AND METHODS: 3beta-OH-5-ene-steroids were profiled by gas chromatography-mass spectrometry in 24-h urinary samples in 61 preterm infants of less than 30 weeks gestational age. RESULTS: The incidence of respiratory distress syndrome treated with surfactant in females (n = 30) was 47% and in males (n = 31) 71%, p = 0.07. Medians of total excretion rates of fetal zone steroids (microg/kg/d) in female (male) preterm infants were at day 1: 1,317 (895); day 2: 3,154 (7,723), p = 0.03; day 3: 5,502 (9,494), p = 0.08; day 5: 7,140 (10,407); week 2: 8,731 (9,720); week 3: 8,571 (10,079); week 4: 7,620 (7,825). Regression analysis did not reveal a significant influence of maximum excretion rates of fetal zone steroids or gender on the incidence of respiratory distress syndrome treated with surfactant. CONCLUSIONS: Excretion rates of fetal zone steroids were 4-fold higher than previously reported indicating a persistent high activity of the fetal adrenal zone in preterm infants. Excretion rates of fetal zone steroids were significantly higher in male preterm infants compared to females at day 2 (trend at day 3) but did not have a significant influence on the incidence of respiratory distress syndrome.     

Urinary aquaporin-2 excretion in preterm and full-term neonates

The study was undertaken to define the role of aquaporin-2 (AQP2) in renal concentrating performance by measuring urinary AQP2 excretion and urine osmolality in healthy preterm and full-term neonates during early postnatal life. Random urine samples were obtained from 9 full-term newborn infants (mean birth weight 3,218 g, mean gestational age 39.2 weeks) at postnatal ages of 1, 3 and 5 days. Five premature infants with a mean birth weight of 1,570 g and mean gestational age of 30.6 weeks were studied at the end of the 1st week and then weekly up to the 6th week. Urine osmolality (Knauer osmometer), creatinine (modified Jaffé's method) and AQP2 concentrations (radioimmunoassay) were measured. In full-term neonates, urinary AQP2 excretion showed no consistent changes over the age period studied, while urine osmolality decreased significantly with advancing age. In premature infants, urinary AQP2 excretion remained practically unchanged during the first 4 weeks followed by an abrupt increase thereafter. Urine osmolality did not follow the developmental pattern of AQP2 excretion; its mean values varied only from 78 +/- 39 to 174 +/- 146 mosm/l during the experimental period. It is concluded that during the early postnatal period, urinary AQP2 excretion does not serve as a direct marker of the renal action of AVP and the renal capacity to concentrate urine.     

Sympathoadrenal activity in preterm infants during the first five days of life.

We measured plasma concentrations of epinephrine (E), norepinephrine (NE), 3,4-dihydroxyphenylacetic acid (DOPAC), and 3,4-dihydroxyphenylglycol (DHPG) as well as urinary concentrations of metanephrine (M), normetanephrine (NM) and 3-methoxy-4-hydroxymandelic acid (MOMA) on day 2 and day 5 in preterm infants; gestational age less than 30 weeks (G less than 30; n = 16) and gestational age 30-34 weeks (G 30-34; n = 19). Concentrations of E (0.00-2.28 nmol/l) and NE (0.6-9.1 nmol/l) in plasma were much lower than those previously reported during preterm and term delivery. The E:NE ratio decreased from 1:10 on day 2 to 1:30 on day 5, and the M:NM ratio decreased from 1:4 on day 2 to 1:8 on day 5, indicating relatively higher catecholamine secretion from the adrenals than from the sympathetic nerve terminals in preterm infants during postnatal adaptation. Plasma concentrations of DOPAC and DHPG were significantly higher in G less than 30 than in G 30-34 (DOPAC, p = 0.0494; DHPG, p = 0.0092), probably relating to a low urinary excretion rate of catecholamine metabolites in infants in G less than 30. Plasma and urinary concentrations of catecholamines and their metabolites varied considerably, and no significant correlations to postnatal events could be demonstrated.     

A multicenter long-term safety and efficacy trial of preterm formula supplemented with long-chain polyunsaturated fatty acids

BACKGROUND: The tissue accretion of long-chain polyunsaturated fatty acids is compromised in infants born prematurely. Human milk contains long-chain polyunsaturated fatty acids, but most preterm infant formulas do not. The long-term effects of preterm formula supplemented with arachidonic acid and docosahexaenoic acid, in proportions typical of those in human milk, were therefore investigated. METHODS: In this double-blind, randomized study, 288 preterm infants received experimental formula (n = 77), unsupplemented (control) formula (n = 78), or human milk (n = 133) until 48 weeks postconceptional age (PCA). Term formula, without supplemental long-chain polyunsaturated fatty acids, was administered from 48 to 92 weeks PCA to formula-fed infants and to infants weaned from human milk. Anthropometric and fatty acid data were assessed by using analysis of variance. RESULTS: At 92 weeks PCA, no statistically significant anthropometric measurement differences were found except for midarm circumference, which was smaller in human milk-fed infants than in those fed formula. Phospholipid concentrations were similar in the experimental and human milk-fed groups, and docosahexaenoic acid levels were significantly greater than in the control group. The types and incidences of adverse events were similar among the feeding groups. CONCLUSIONS: The results of this study demonstrate the efficacy and long-term safety of preterm formula supplemented with long-chain polyunsaturated fatty acids.     

Urinary arginine vasopressin: pattern of excretion in the neonatal period

The pattern of arginine vasopressin (AVP) secretion in the immediate neonatal period is unclear. Plasma concentrations of AVP are reflected by its urinary excretion, thus providing a noninvasive method for studying the pattern of AVP release in the neonate. In these studies, we determined the pattern of urinary AVP excretion (microU/mg creatinine) during the first 2-4 days after birth in 78 neonates, 53 of whom had various prenatal and/or neonatal complications. In well term (n = 12) and preterm (n = 13) infants mean urinary AVP excretion decreased gradually during the first 24-36 h after birth. Although term and preterm infants with perinatal asphyxia had highest initial levels of urinary AVP (greater than 200 microU/mg creatinine) and a significant negative correlation with the 1-min Apgar score was obtained, their pattern of excretion was similar to respective controls. After delivery, elevated values for urinary AVP excretion were found among infants with neonatal courses complicated by intracranial hemorrhage, hypoxic encephalopathy, and pneumothorax. Urine osmolality did not correlate linearly with urinary AVP levels, but rather attained a maximum value of approximately 400 mosmol/kg at urinary AVP levels less than 200 microU/mg creatinine and then plateaued. It is concluded that the decrease in urinary AVP excretion observed soon after birth generally reflects diminution of the hypersecretion of AVP during parturition; neonates with evidence of intrapartum asphyxia initially have increased urinary AVP excretion; however, the pattern of excretion is similar to normal infants. During the neonatal period insults such as pneumothorax and intracranial hemorrhage may cause hypersecretion of this hormone.     

Postnatal weight gain and serum total protein and albumin levels in very low birthweight (less than or equal to 1500 g) preterm infants

Postnatal weight gain during the first 8 weeks of life of 20 very low birthweight preterm infants (gestational age: 28.9 +/- 1.7 weeks, birthweight: 1098 +/- 199 g, mean +/- SD) was compared to the in utero weight gain of theoretical control fetuses. By the end of the study period preterm infants gained significantly less weight than their controls (155 +/- 15 vs 221 +/- 16%, p less than 0.001). During the first 6 weeks of life daily additional weight gain of the preterm infants was less than that of the controls, but after that time no significant difference was seen (7th-8th week: 12.0 +/- 3.6 vs 13.7 +/- 3.9 g/kg/day, study infants vs controls, ns). During the 7th-8th weeks of life positive correlation was found between calorie intake and weight gain (r = 0.33, F = 2.17, p less than 0.05). The changes in serum total protein and albumin levels, including an initial increase by the age of 2 weeks, were statistically not significant.     

Effect of human breast milk on biological metabolism in infants

The metabolic changes that occur during the postnatal weaning period appear to be particularly important for future health, and human breast milk is considered to provide the optimal source of nutrition for infants. Our previous studies examined the effect of feeding type on antioxidative properties, glucose and insulin metabolism, the lipid profile, metabolomics, and prostaglandin (PG) metabolism in term and preterm infants. A urinary marker of oxidative DNA damage (8‐hydroxy‐2′‐deoxyguanosine) was significantly lower in breast‐fed term and preterm infants than in formula‐fed infants. Markers of insulin sensitivity were significantly lower and atherosclerotic indices were significantly higher in breast‐fed preterm infants than in mixed‐fed infants at discharge. On urinary metabolomics analysis, choline, choline metabolites, and lactic acid were significantly lower in breast‐fed term infants than in formula‐fed infants. Urinary PGD₂ metabolite level in breast‐fed term infants was also significantly lower than in formula‐fed term infants. This indicates that human breast milk affects biological metabolism in early infancy.     

Atrial natriuretic peptide in the preterm infant. Lack of correlation with natriuresis and diuresis

We assessed the relation of atrial natriuretic peptide (ANP) to renal function on postnatal day 2 and day 5 in preterm infants. Plasma ANP concentration was measured by radioimmunoassay in two groups of preterm infants: group 1, gestational age less than 30 weeks, n = 10; and group 2, gestational age 30-34 weeks, n = 11. The identity of the immunoreactivity as ANP-28 was confirmed by HPLC. Plasma ANP was significantly higher in group 1 than in group 2 on day 2 and day 5 (p < 0.01) and ANP concentration decreased by day 5 in both groups (group 1, p < 0.01; group 2, p < 0.02). The results showed no correlation between plasma ANP concentration and urinary sodium excretion or creatinine clearance, which may be due to a blunted renal response to ANP, but other factors may be involved also. We conclude that preterm infants are able to release large amounts of ANP, but a high plasma ANP concentration does not correlate directly with renal regulation of sodium and water balance.