Pharmacokinetic observations of phenytoin disposition in the newborn and young infant

The pharmacokinetic profile of phenytoin (DPH) was studied in 30 infants aged 2 days to 96 weeks. The plasma DPH half-life during the first week of life in term infants was prolonged and very variable (20-7 +/- 11-6 h, mean +/-SD). Thereafter the plasma half-life was much shorter (7-6 +/- 3-5 h). In preterm infants the half-life was much longer (75-4 +/- 64-5 h) and more variable. The mean apparent volume of distribution was similar in these groups of infants: preterm newborn 0-80 +/- 0-22 l/kg, term infants during the first week of life 0-80 +/- 0-26 l/kg, and term infants greater than 2 weeks of age 0-73 +/- 0-18 l/kg. Predictions of steady-state plasma DPH concentrations, based on these kinetic parameters, were confirmed. Very low "trough" plasma DPH concentrations were observed after the 14th postnatal day in 19 infants receiving 8 mg/kg per 24 h orally. On the other hand, infants of less than one week of age receiving the same dose, especially if preterm, frequently showed drug accumulation to toxic plasma DPH concentrations. The impaired binding of DPH to newborn plasma protein was confirmed but "normal adult values" were approached by the age of 3 months. An intravenous loading dose of 8 mg/kg (sodium phenytoin) can be expected to generate a mean plasma DPH concentration of 10 mg/l (40 micronmol/l) in the newborn. Loading doses of up to 12 mg/kg were given without untoward effects. During the first week or so of life plasma Dph half-life is so variable that no fixed dosage regimen can be derived from the available data. Beyond the second week of life, however, a dose of 8 mg/kg per 24 h is probably inadequate for most infants.     

Pharmacokinetic observations of phenytoin disposition in the newborn and young infant.

The pharmacokinetic profile of phenytoin (DPH) was studied in 30 infants aged 2 days to 96 weeks. The plasma DPH half-life during the first week of life in term infants was prolonged and very variable (20-7 +/- 11-6 h, mean +/-SD). Thereafter the plasma half-life was much shorter (7-6 +/- 3-5 h). In preterm infants the half-life was much longer (75-4 +/- 64-5 h) and more variable. The mean apparent volume of distribution was similar in these groups of infants: preterm newborn 0-80 +/- 0-22 l/kg, term infants during the first week of life 0-80 +/- 0-26 l/kg, and term infants greater than 2 weeks of age 0-73 +/- 0-18 l/kg. Predictions of steady-state plasma DPH concentrations, based on these kinetic parameters, were confirmed. Very low "trough" plasma DPH concentrations were observed after the 14th postnatal day in 19 infants receiving 8 mg/kg per 24 h orally. On the other hand, infants of less than one week of age receiving the same dose, especially if preterm, frequently showed drug accumulation to toxic plasma DPH concentrations. The impaired binding of DPH to newborn plasma protein was confirmed but "normal adult values" were approached by the age of 3 months. An intravenous loading dose of 8 mg/kg (sodium phenytoin) can be expected to generate a mean plasma DPH concentration of 10 mg/l (40 micronmol/l) in the newborn. Loading doses of up to 12 mg/kg were given without untoward effects. During the first week or so of life plasma Dph half-life is so variable that no fixed dosage regimen can be derived from the available data. Beyond the second week of life, however, a dose of 8 mg/kg per 24 h is probably inadequate for most infants.     

Selenium status of preterm infants: the effect of postnatal age and method of feeding

Indicators of selenium (Se) status were measured in a longitudinal study of 63 preterm and 46 term infants. Se levels in both groups were similar in the first few days of life. Preterm infants fed parenteral nutrition (PN) for several weeks developed very low plasma Se levels (<10/μg/l). In those receiving either breast milk or formula in conjunction with PN, plasma Se also declined over the first 6 weeks. In the breastfed term infants plasma levels increased by 50%, but there was no increase in the term formula-fed group. In healthy preterm infants who received mainly breast milk, plasma Se concentrations remained constant at newborn levels and were below those of breastfed term infants at 6 weeks. Erythrocyte GSHPx activity did not reflect plasma Se or Se intake. In conclusion, the type of feeding, and hence Se intake, influenced plasma Se concentration in preterm infants. Provision of enteral feeding in conjunction with PN was unable to prevent a decline in plasma Se and at 6 weeks levels were well below those of the reference breastfed term infants.     

Inter-alpha inhibitor proteins in infants and decreased levels in neonatal sepsis

OBJECTIVE: Adjunctive tests are needed to predict sepsis in the newborn and to lower the rate or duration of unnecessary antibiotic use. We evaluated the normal Inter-alpha inhibitor protein (IaIp) values in infants and the association of plasma levels of IaIp with sepsis in term and preterm newborns. METHODS: Plasma IaIp levels were measured by enzyme-linked immunosorbent assay in samples from 135 newborn infants at a wide range of gestational ages (24-42 weeks). IaIp levels were also determined in 19 infants undergoing prospective evaluation for sepsis. RESULTS: IaIp levels in umbilical cord blood and circulating peripheral blood of healthy newborn infants (525+/-66 mg/L) were not significantly different from the level in healthy adults (691+/-80 mg/L). IaIp levels were similar in infants between 24 and 42 weeks gestational age. There was a significant reduction in IaIp levels in infants with sepsis compared with nonseptic controls (169+/-126 mg/L vs 613+/-286 mg/L, P<.0001). CONCLUSIONS: IaIp levels in the blood of newborns are independent of gestational age and similar to adults. IaIp levels are significantly reduced in infants with bacterial sepsis and might serve as an adjunctive diagnostic marker to allow prospective reduction of antibiotic use.     

Nutritional efficacy of preterm formula with a partially hydrolyzed protein source: a randomized pilot study.

BACKGROUND: Decreased nitrogen levels, calcium intestinal absorption rates, and plasma amino acid imbalances were reported for preterm infants who were fed partially hydrolyzed preterm formulas. In this pilot study, we evaluated a new formula with modified nitrogen and calcium sources. METHODS: During their second week of life, 16 preterm infants were randomly assigned to one of two groups: 9 were fed the new partially hydrolyzed formula and 7 were fed a conventional formula. Nutrient balance was performed at the end of the first month of life. Amino acid concentrations and anthropometric parameters were measured at theoretical term. RESULTS: Birth weight and gestational age (mean +/- SD) were similar in the two groups (28.9 +/- 7.0 weeks and 1183 +/- 242 g vs. 27.7 +/- 1.0 weeks and 1139 +/- 162 g). Median nitrogen absorption rates (85% vs. 89%; P = 0.03) and biological values (59% vs. 69%; P = 0.13) were lower for infants who were fed the new formula than for those fed the conventional formula. After correction for difference in nitrogen intake, there was no significant difference in nitrogen retained between the two groups (P = 0.11). Plasma amino acid concentrations were also similar in the two groups. Median calcium absorption tended to be higher in the new-formula group than in the conventional-formula group (54% vs. 45%, P = 0.19). At theoretical term, infants fed the conventional formula were heavier than infants fed the new formula (3559 +/- 362 g vs. 3193 +/- 384 g, P = 0.04). CONCLUSIONS: Because nitrogen content is 10% higher in hydrolyzed-protein formula than in entire-protein formula, appropriate nitrogen retention, plasma amino acid profile, and mineral use can be achieved with the new partially hydrolyzed formula. Further studies with larger groups are needed to evaluate the effect on growth.     

Protein hydrolysate formula maintains homeostasis of plasma amino acids in preterm infants.

BACKGROUND: Plasma amino acid concentrations were measured in preterm infants who were fed either a new hydrolyzed cow's milk protein formula or a standard preterm infant formula. It was hypothesized that feeding with the hydrolysate results in preprandial amino acid concentrations that are significantly different from the concentrations found when feeding with the standard formula. METHODS: Fifteen preterm infants, median gestational age, 29 weeks (range, 24-32 weeks); birth weight, 1241 g (range, 660-1900 g); and postnatal age, 18 days (range, 7-54 days) receiving full enteral feedings (>150 ml/kg x day), were enrolled. The intervention was randomized allocation to the formula with hydrolyzed or natural cow's milk protein (the whey/casein ratio was 60:40 in both formulas). In a crossover design, each formula was fed for 5 days, and plasma amino acids were analyzed on day 4 or 5 of each 5-day period. RESULTS: In spite of the 12% higher amino acid intake with hydrolysate formula, the median individual plasma amino acid concentrations were virtually identical with both formulas, and they were within the 10th and the 90th percentile of the reference of levels in the umbilical cord artery after elective cesarean delivery or of breast-fed newborn infants. The median concentrations of lysine and aspartic acid were higher with hydrolyzed formula feeding (p<0.05; two-tailed Mann-Whitney test). With both formulas, single amino acid concentrations were out of the reference values. CONCLUSION: Virtually identical plasma amino acid concentration patterns were measured with the new hydrolyzed preterm infant formula and the standard preterm infant formula, but longitudinal studies are required before the studied protein hydrolysate can be recommended for preterm feeding in general.     

VASOACTIVE INTESTINAL PEPTIDE (VIP) IN PRETERM AND TERM NEONATES

ABSTRACT. There is a little information on vasoactive intestinal peptide (VIP) in the neonatal period. We have measured plasma concentrations of this biologically important peptide in 159 preterm infants and 98 term neonates. Preterm neonates during the first four days of life had plasma VIP concentrations which were five times greater than the levels in 12 healthy adult controls (9.6±0.7 pmol/1, mean ± S. E. M., compared with 1.95±0.5 pmol/l, p <0.001), and these elevated concentrations persisted throughout the neonatal period. In contrast term infants on the sixth day of life, had plasma VIP concentrations only half those seen in preterm infants at the same post natal age ( p <0.001). Bottle-fed term infants had higher VIP levels than those who were breast fed (5.6±0.4 vs. 4.3±0.4, p <0.05). Plasma VIP concentrations did not change following a feed in any of the groups of neonates studied. The high plasma levels of VIP described may indicate a reduced neuropepitide clearance mechanism in neonates or alternatively, suggest a hitherto unrecognised role for this peptide hormone in the neonatal period.     

Placental transfer and decay of varicella-zoster virus antibodies in preterm infants

OBJECTIVES: To compare the placental transfer of maternal varicella-zoster (VZV) antibodies to preterm and term infants and to investigate antibody decay during the first 6 months of life in the preterm infants.Study design: Maternal and umbilical cord blood samples were taken from 113 healthy mother-newborn pairs: 64 term (gestational age > or =37 weeks) and 49 preterm (gestational age < or =35 weeks). Premature infants were further tested at 1, 2, and 6 months. Anti-VZV antibody to membrane antigen was measured with the immunofluorescent technique. RESULTS: Preterm infants of gestational age < or =28 weeks had positive cord antibody and a geometric mean titer significantly lower than those in preterm infants of gestational age 29 to 35 weeks and term infants (25% vs 95% and 95%, respectively, P <.001 for each, and 2.5 +/- 2.2 vs 10.5 +/- 2.4 and 12.6 +/- 2.4, respectively, P <.001 for each). There was no difference between the preterm 29 to 35 weeks of gestation and term groups. Fetal-maternal ratios for both preterm groups were <1 and were significantly less than the fetal-maternal ratio in the term infants. The transfer of maternal antibodies to term infants was significantly greater than to the 29- to 35-week preterm infants (P =.01). At 2 months of age, 25% of 29- to 35-week preterm infants and no preterm infant < or =28 weeks had a positive titer. At 6 months of age, all preterm infants were seronegative, and the geometric mean titer in both groups declined to undetectable levels. CONCLUSION: Transplacental transfer of maternal VZV antibodies is diminished in preterm infants. VZV antibody levels are significantly lower in preterm infants born at < or =28 weeks' gestational age compared with those in preterm infants 29 to 35 weeks' gestational age and term infants. Anti-VZV titers decrease to undetectable levels in preterm infants by 6 months of age or earlier; thus these infants appear to be susceptible to chickenpox before the scheduled 12-month vaccination.     

Plasma 1.25-dihydroxyvitamin D concentrations in preterm infants

1.25-Dihydroxyvitamin D concentrations were measured in 10 preterm infants (mean gestational age 29 weeks, range 26-32; mean birthweight 1226 g, range 980-1700). Total parenteral nutrition was begun after birth and partial enteral feeding was started at 1 week of age. Total enteral feeding was achieved at a mean age of 26 days (range 16-47). The daily vitamin D3 intake was about 400 I. U. No clinical, chemical or radiological signs of rickets were observed. The mean 1.25-dihydroxyvitamin D concentration +/- SEM was 103.2 +/- 24.0 pmol/l at 1 week (range 9.6-252.0), 141.6 +/- 26.4 at 3 weeks (range 31.2-324.0), 153.6 +/- 21.6 at 6 weeks (range 67.2- 256.8), 165.6 +/- 24.0 at 9 weeks (range 74.4-307.2) and 153.6 +/- 21.6 at 12 weeks (range 76.8-268.8) postnatal age. The mean values at 6, 9 and 12 weeks were significantly higher (p resp. less than 0.01, less than 0.002 and less than 0.005) than in adults (88.8 +/- 7.2; n = 27). 1.25-Dihydroxyvitamin D concentrations were highly variable and did not correlate with 25-hydroxyvitamin D concentrations, plasma calcium and phosphorus concentrations and plasma alkaline phosphatase levels, nor with illness nor postnatal age. The data demonstrate that preterm infants are capable of producing high plasma levels of 1.25-dihydroxyvitamin D.     

Metabolism of methionine in the newborn infant: response to the parenteral and enteral administration of nutrients

The rates of transmethylation and transsulfuration of methionine were quantified using [1-(13)C]methionine and [C2H3]methionine tracers in newborn infants born at term gestation and in prematurely born low birth weight infants. Whole body rate of protein breakdown was also measured using [2H5]phenylalanine. The response to enteral formula feeding and parenteral nutrition was examined in full term and prematurely born babies, respectively. The relative rates of appearance of methionine and phenylalanine were comparable to the amino acid composition of mixed body proteins. Rates of transmethylation were high, both in full term infants (fast 32 +/- 14 micromol kg(-1) x h(-1); fed 21.7 +/- 3.2) and in preterm infants (57.2 +/- 14.8). Significant flux through the transsulfuration pathway was evident (full term: fast 6.0 +/- 4.4, fed 4.1 +/- 2.1; preterm: 24.9 +/- 9.9 micromol kg(-1) x h(-1)). Transsulfuration of methionine is evident in the human newborn in the immediate neonatal period, suggesting that cysteine may not be considered a "conditionally" essential amino acid for the neonate. The high rate of transmethylation may reflect the high methylation demand, whereas high rates of transsulfuration in premature babies may be related to high demands for glutathione and to the amounts of methionine in parenteral amino acid mixtures.     

The ontogeny of serum immunoreactive pancreatic lipase and cationic trypsinogen in the premature human infant

We evaluated the development of the exocrine pancreas in 16 healthy preterm infants (29.3 +/- 1.6 weeks). The infants were fed breast milk with formula supplements (n = 8) or formula alone (n = 8). Growth was monitored weekly for 12 weeks then at 3, 6, 9, 12 months. At the same intervals sera were determined for pancreatic lipase and cationic trypsinogen. In addition, cord blood samples were analysed from another 33 preterm (27.6 +/- 5.2 weeks) and 75 healthy full-term infants. Serum pancreatic lipase in the cord blood of term (3.7 +/- 0.4 micrograms/l) and preterm infants (1.8 +/- 0.2 micrograms/l) was significantly below values reported for older children (10.5 +/- 0.9 micrograms/l; p less than 0.001). In the preterm infant, serum lipase was also significantly lower than values obtained at term (p less than 0.001). At birth, serum trypsinogen for preterm (16.8 +/- 1.3 micrograms/l) and term infants (23.3 +/- 1.9 micrograms/l) were below those for older children (31.4 +/- 3.7 micrograms/l; p less than 0.05). Over the first 3 weeks of life, serum lipase and trypsinogen increased significantly. From 3 weeks to 12 months of age, serum trypsinogen values remained unchanged, but serum lipase increased dramatically after 10 weeks of age. Thus, at 6 and 12 months of age, the preterm infants had significantly higher serum lipase values than infants of the same age born at term. These two pancreatic enzymes appear to show independent age-related maturation in infants born before term. The rate of maturation of lipase appears to be accelerated by exposure to the extrauterine environment.     

Circulating levels of biologically active and immunoreactive intact parathyroid hormone in human newborns

We evaluated circulating levels of biologically active and immunoreactive intact parathyroid hormone [iPTH-(1-84)] in 47 newborns at birth and eight hypocalcemic preterm infants during the first 10 d of life. Use of two sensitive detection systems, the cytochemical bioassay and an immunoradiometric assay specific for intact parathyroid hormone, enabled us to compare plasma concentrations of PTH-like bioactivity (bioPTH) and iPTH-(1-84). Mean umbilical venous plasma bioPTH was elevated in nondiabetic term and preterm newborns [22.5 +/- 3.1 (+/- SEM) and 15.8 +/- 2.5 ng-equiv/L, respectively] compared with normal adult subjects (9.8 +/- 2.6 ng-equiv/L; p less than 0.01). Umbilical bioPTH was suppressed in five term infants of diabetic mothers (2.6 +/- 0.4 ng-equiv/L). In contrast, iPTH-(1-84) was low in term and preterm nondiabetic infants' and term infants of diabetic mothers' umbilical samples (5.4 +/- 1.5, 4.3 +/- 1.5, and 2.4 +/- 1.0 ng/L, respectively). Umbilical venous bioPTH was highly correlated with the magnitude of the transplacental calcium gradient (r = 0.90; p less than 0.05). In eight preterm infants studied longitudinally, by 24-36 h of life, declining plasma total and ionized calcium (1.71 +/- 0.04 and 0.78 +/- 0.03 mmol/L, respectively) were accompanied by a significant rise in both bioPTH (41.2 +/- 6.3 ng-equiv/L) and iPTH-(1-84) (56.3 +/- 11.6 ng/L). These data indicate that the 3rd trimester fetoplacental circulation contains levels of bioPTH several-fold higher than those of immunoreactive intact hormone. We also conclude that even hypocalcemic preterm newborn infants can significantly elevate circulating levels of PTH.     

Circulating levels of endothelin and atrial natriuretic factor during postnatal life

We determined plasma endothelin-1-like immunoreactivity and atrial natriuretic factor concentrations in preterm and full-term newborn infants during the first month of life. Plasma endothelin-1-like immunoreactivity levels were far greater than those of maternal blood in the newborn infants. The highest plasma endothelin-1-like immunoreactivity levels were observed on the first day of life (8.7 +/- 3.7 pmol/l) and gradually decreased with age. There was no significant difference in plasma endothelin-1-like immunoreactivity levels between preterm and full-term infants. A good correlation was observed between plasma endothelin-1-like immunoreactivity levels and atrial natriuretic factor concentrations (p < 0.01). These results suggest that circulating endothelin may regulate the cardiovascular system in the newborn period.     

Fat absorption in premature infants: medium-chain triglycerides and long-chain triglycerides are absorbed from formula at similar rates

Fat absorption from two different premature infant formulas and one full-term formula containing three different fat blends was investigated in two groups of premature infants. The first group of nine infants (gestational age, 29.1 +/- 0.88 weeks; postnatal age, 3.13 +/- 0.71 weeks) was fed alternately for 1 week each SMA preterm formula containing either high levels (50%) of medium-chain triglycerides (MCT) (6:0, 8:0, and 10:0) or high levels (86%) of long-chain triglycerides (LCT) (greater than or equal to C12). Except for fat blends, the formulas were otherwise identical. The second group of 11 infants (gestational age, 30.5 +/- 0.77 weeks, studied at a postnatal age of 4.33 +/- 0.91 weeks) was fed for 1 week a full-term infant formula, S-26, containing 98% LCT. Fat absorption (studied during a 3-day fat balance period) was similar irrespective of fat blend: 89.08 +/- 2.37% during feeding of preterm SMA, 50% MCT; 87.0 +/- 3.81% during feeding of preterm SMA, 86% LCT; and 83.00 +/- 2.89% during feeding of S-26, 98% LCT. Weight gain (grams per day) and increase in length (centimeters per day) were 23.2 +/- 1.7, 21.20 +/- 1.7, and 14.28 +/- 2.9, and 0.17 +/- 0.06, 0.16 +/- 0.04, and 0.22 +/- 0.07 during feeding of the three fat blends, respectively. Lipase activity levels in fasting gastric aspirates were higher during feeding of the LCT than the MCT formula. The possible stimulation of gastric lipase secretion secondary to long-chain fatty acid stimulation of cholecystokinin secretion might be related to the efficient digestion of formula fat, irrespective of triglyceride-fatty acid chain length.(ABSTRACT TRUNCATED AT 250 WORDS)     

Leptin and metabolic hormones in preterm newborns

AIM: To investigate the inter-relation between leptin and other metabolic hormones in preterm and term infants and to explore whether a functional "adipoinsular axis" might exist in preterm newborns. METHODS: A total of 140 preterm and term newborns were prospectively recruited and categorised according to gestation length. Blood samples were taken at 24 hours (day 1), and on day 4-5 of life. RESULTS: Serum leptin, cortisol, free thyroxine, and plasma ACTH on day 1 were significantly higher in term than in preterm infants. The relation between serum leptin and gestation followed a non-linear pattern; the slope of the curve began to increase steeply between 33 and 35 weeks gestation. Serum leptin on day 1 was significantly associated with serum insulin, insulin:glucose ratio, and plasma ACTH in infants less than 34 weeks gestation; serum leptin on day 1 and day 4-5 were significantly correlated with insulin:glucose ratio in infants 34 or more weeks gestation. Significant changes in the pattern of metabolic hormones were observed in the first week of life. Serum insulin and plasma glucose were significantly increased between day 1 and day 4-5; serum leptin was significantly decreased. CONCLUSIONS: The circulating leptin concentration increases markedly after 34 weeks gestation and bears a close temporal relation with the exponential accumulation of body fat mass during that period. The inter-relation between serum leptin and insulin or insulin:glucose ratio before and after 34 weeks gestation indicates that the "adipoinsular axis" is likely to be functional in early (<34 weeks gestation) intrauterine life. The rapid decline in the circulating concentrations of leptin after birth may be of physiological advantage to preterm and term newborns by limiting their body energy expenditure and conserving nutritional reverses for subsequent growth and development.     

Plasma beta-endorphin levels in the umbilical cord blood of preterm human neonates

Maternal venous (MV) and neonatal umbilical venous (UV) and umbilical arterial (UA) plasma beta-endorphin concentrations were measured at birth in two groups of patients undergoing cesarean section (CS). Patients in group 1 carried a term gestation (n = 12, birth weight 3,640 +/- 150 g, 1 SEM). Patients in group 2 (n = 12) carried a preterm gestation (birth weight 1,956 +/- 150 g). In the term neonate the UV and UA plasma beta-endorphin were 11.5 +/- 4 and 13.5 +/- 4 picomoles/liter, respectively. In the preterm neonate the UV and UA values were 23.6 +/- 4 and 23.5 +/- 5 picomoles/liter, respectively. Both values in the preterm neonate were significantly greater than the corresponding value in the term neonate (p less than 0.05). The MV plasma beta-endorphin did not significantly differ among the two groups. Data suggest that in preterm neonates increased plasma beta-endorphin levels occur at the time of birth.     

Pharmacokinetics of a single dose of morphine in preterm infants during the first week of life

We studied morphine pharmacokinetics after a single intravenous dose of 0.1 mg/kg in 20 newborn infants, who were born at 26 to 40 weeks of gestation and were less than 5 days of age. In the 10 infants whose gestational age was less than or equal to 30 weeks, the mean (+/- SD) distribution half-life was 50 +/- 35 minutes, elimination half-life was 10 +/- 3.7 hours, and clearance was 3.39 +/- 3.28 ml/kg/min; the corresponding values for the three term infants were 19 +/- 8 minutes, 6.7 +/- 4.6 hours, and 15.5 +/- 10 ml/kg/min, respectively. The data suggested a trend of decreasing values for distribution and elimination half-lives with increasing gestation, but a considerable degree of variation was seen. The morphine clearance rate increased as a function of gestational age at a rate of 0.9 ml/kg/min per week of gestation. Between 18% and 22% of the drug was found to be protein bound. Four hours after the dose, the drug level remained greater than or equal to 12 ng/ml in 8 of 10 infants born at greater than or equal to 31 weeks of gestation. In 8 of 10 infants born at less than or equal to 30 weeks of gestation, similar levels were maintained at 8 hours after the initial dose. We conclude that (1) there is a marked degree of variation in morphine pharmacokinetics during the neonatal period, (2) nearly 80% of the intravenously infused drug remains free, which might explain the high sensitivity to morphine in this age group, and (3) during the first week of age, adequate blood levels can be maintained by administration of morphine at 4- to 6-hour intervals in term infants and at less frequent intervals in very premature infants (less than or equal to 30 weeks of gestation).     

Intestinal permeability in relation to birth weight and gestational and postnatal age

OBJECTIVE: To determine the relation between intestinal permeability and birth weight, gestational age, postnatal age, and perinatal risk factors in neonates. STUDY DESIGN: Intestinal permeability was measured by the sugar absorption test within two days of birth and three to six days later in preterm and healthy term infants. In the sugar absorption test, the urinary lactulose/mannitol ratio is measured after oral ingestion of a solution (375 mosm) of lactulose and mannitol. RESULTS: A first sugar absorption test was performed in 116 preterm (26-36 weeks gestation) and 16 term infants. A second test was performed in 102 preterm and nine term infants. In the preterm infants, the lactulose/mannitol ratio was not related to gestational age (r = -0.09, p = 0.32) or birth weight (r = 0.07, p = 0.43). The median lactulose/mannitol ratio was higher if measured less than two days after birth than when measured three to six days later (0.427 and 0.182 respectively, p<0.001). The lactulose/mannitol ratio was higher in preterm infants than term infants if measured within the first 2 days of life (0.404 and 0.170 respectively, p < 0.001), but not different three to six days later (0.182 and 0.123 respectively, p = 0.08). In multiple regression analysis of perinatal risk factors, only umbilical arterial pH correlated with the lactulose/mannitol ratio in preterm infants less than 2 days of age (T = -1.98, p = 0.05). CONCLUSIONS: In preterm infants (26-36 weeks gestation), intestinal permeability is not related to gestational age or birth weight but is higher during the first 2 days of life than three to six days later. It is higher in preterm infants than in healthy term infants only if measured within two days of birth. This suggests rapid postnatal adaptation of the small intestine in preterm infants.     

Basal and meal-stimulated pepsinogen secretion in preterm infants: a longitudinal study.

In order to establish longitudinal normal values for basal and meal-stimulated pepsinogen secretory function in preterm infants, we studied 44 preterm infants with gestational ages of 28-36 weeks during the period of nasogastric tube feeding. Three age groups were evaluated: gestational ages of 28-30, 31-33, and 34-36 weeks. Basal pepsinogen did not change with postnatal age in any of the groups. Significant meal-stimulated pepsinogen secretion appeared during the third postnatal week in infants of 28-30 weeks of gestation. In the groups of infants of 31-33 and 34-36 weeks of gestation, significant meal-stimulated pepsinogen secretion was apparent in the first postnatal week. This study suggests that maturation of pepsinogen secretion appears at 31 weeks of gestation, independent of early feeding.     

Sodium potassium adenosine triphosphatase activity in preterm and term infants and its possible role in sodium homeostasis during maturation.

AIM: To investigate sodium (NA(+)) potassium (K(+)) adenosine triphosphatase (ATPase) activity in newborn infants at different gestational ages, to elucidate the mechanism underlying poor renal sodium conservation in preterm infants. METHODS: Fifty three healthy newborn infants, gestational age 30-42 weeks, were studied. Umbilical cord red blood cell Na(+) K(+)ATPase activity, plasma renin activity, and plasma aldosterone activities were measured in all of them. Red blood cell Na(+) K(+)ATPase activity was re-examined in eight preterm infants, one and two weeks after birth. Total and ouabain sensitive ATPase activity was measured spectrophotometrically using a method that couples ATP hydrolysis with NADH oxidation. RESULTS: Red blood cell Na(+) K(+)ATPase activity was significantly lower (p<0.01) in preterm babies with a gestational age below 35 weeks, compared with those with aged 35 weeks and above: 2.3 (0.8) and 6.7 (1.3) nmol NADH/minute/mg protein, respectively. There was no correlation between gestational age, Na(+) K(+)ATPase, plasma renin activity and aldosterone values either in the preterm or term babies. Two weeks after birth, irrespective of gestational age, the enzyme activity of the preterm babies increased to values similar to those observed in the term neonates at birth. CONCLUSION: The differences in sodium homeostasis between term and preterm babies are modulated via changes in Na(+) K(+)ATPase activity.