Randomized, multicenter trial of two different formulas for very early enteral feeding advancement in extremely-low-birth-weight infants.

BACKGROUND: In extremely-low-birth-weight (ELBW) infants, formula feeding is required if human milk is not available. The tolerance of a new 'high' lactose (55 g/L), low protein, low phosphate, hydrolyzed protein formula (HLF) for early enteral feeding advancement of ELBW infants was compared with that of a low lactose (1 g/L) hydrolyzed protein formula (LLF). METHODS: In a randomized multicenter trial, 99 ELBW infants were fed according to a standardized protocol beginning at 48 hours of age with 12 ml/kg daily increments. Primary outcome was the cumulative milk feeding volume (CFV) from days 3 to 14. The authors hypothesized that feeding HLF as a supplement to human milk would increase the CFV at least by 20% in at least 60% of matched pairs compared with LLF. A secondary issue was to investigate whether human milk would increase the CFV compared with formula. RESULTS: The CFV was 720 mL/kg (range, 0-962 mL/kg) with HLF and 613 mL/kg (range, 3-1,283 mL/kg) with LLF feeding. There was no 20% difference. On day 14, the median feeding volume was 103 mL/kg. The CFV was 533 mL/kg (range, 0-962 mL/kg) in infants who received less than 10% of human milk and 832 mL/kg (range, 74-1,283 mL/kg) in infants who received more than 10%. Necrotizing enterocolitis (Bell stage > or =2) occurred only with LLF feeding (n = 5; P < 0.05). CONCLUSIONS: The study failed to find the hypothesized 20% advantage of the new HLF. The observed advantage of human milk supports the hypothesis that it should be the first diet in ELBW infants; however, this hypothesis still must be confirmed in a controlled, randomized trial.

[Effects of oral administration of bifidobacteria on intestinal microflora in premature and newborn infants]. / Wirkungen oral verabreichter Bifidobakterien auf die intestinale Mikroflora von Früh- und Neugeborenen.

In a prospective, randomised study the effects of orally administered bifidobacteria on the intestinal microflora were investigated in 100 preterm and term neonates under intensive care conditions during the first 21 days of life. The 50 infants (group with bifidobacteria) received lyophilized bifidobacteria (Töpfer Bifidus) via nasogastral tube with an initial dosage of 3 times daily 1.25 x 10(8) bifidobacteria on day 2 of life and a daily dosage of 6 times 1.25 x 10(8) bifidobacteria on day 3 until day 21 of life. The other 50 infants (control group) did not receive bifidobacteria. The preterm and term neonates were fed either with pasteurized mother's milk or milk from healthy female donors (n = 79) or with an infant formula (Alfaré, n = 13) or initially with Alfaré and thereafter with mother's milk (n = 8). The intestinal microflora of preterm and term neonates under intensive care conditions could be influenced by the oral administration of bifidobacteria. The administration of bifidobacteria resulted in the group of inoculated infants in a significantly earlier colonization of bifidobacteria (8.1 +/- 3.9 days of life) than in the control group (11.3 +/- 4.7 days of life). On day 7 a bifidobacterial dominance (> 90% of the intestinal microflora) could be found in 26% of infants with inoculation of bifidobacteria and only in 2% of the control group (p < 0.001). These significant differences could be shown until day 21 of life. A difference in septicemia frequency between the two groups could not be demonstrated. At the beginning of the infection a bifidobacterial dominance was found in only one of 23 cases of septicemia.

[Sialic acid, steroids and proteohormones in maternal, cord and retroplacental blood]. / Sialinsäure, Steroid- und Proteohormone im Venenblut der Mutter, im Nabelschnurblut des Neugeborenen und im Retroplazentarblut.

BACKGROUND: To study the storage of sialic acid in newborns reference concentrations for sialic acid were measured in maternal, retroplacental and cord blood and compared with the concentration of human placental lactogen (hPL) and estriol (E3). High serum concentrations of hPL and E3 in retroplacental blood indicate the synthesis of these products in the fetoplacental unit. The comparison of the serum concentrations give first informations for a possible role of the placenta as a place of production and storage of the investigated products. METHODS: The concentrations of sialic acid, hPL and unconjugated E3 were determined in maternal and retroplacental blood samples of 126 pregnant women (16-42 years old) between 28 and 42 weeks of gestation. 84 of these pregnant women had uncomplicated pregnancy with birth after 37 gestational weeks. Measurements of E3 and hPL were performed by solid phase radioimmunoassays. Concentrations of sialic acid were determined by HPLC (high performance liquid chromatography). RESULTS: Means and medians of the three parameters for both groups differentiate hardly. The retroplacental serum concentrations of hPL and E3 are increased significantly compared with maternal blood. The same trend was found for sialic acid without significance. The highest concentrations of E3 were found in the cord blood (298.2 +/- 138.0 ng/ml) (p < 0.01). On the other hand the lowest concentrations of sialic acid (36.1 +/- 19.6 mg/l) (p < 0.01) were estimated in cord blood samples. It was estimated a significant correlation between fetal and retroplacental concentrations of E3. Significant correlations (p < 0.01) were found for sialic acid between maternal and retroplacental blood on the one side and maternal and the cord blood on the other side. Significant increased mean sialic acid concentrations in retroplacental blood (x = 102.67 mg/l) were found in female newborns in comparison with male newborns (x = 80.58 mg/l). There were not significant differences between prematurity and term delivery. CONCLUSION: Increased sialic acid concentrations in retroplacental blood samples are a sign of sialic acid accumulation in the fetomaternal area aiming to induce the tolerance of fetal allotransplantat. There are no evidence for a take up of free sialic acid by fetus.

[Ultrasound and clinical studies of periventricular leukomalacia in high risk newborn infants. II. Perinatal risk factors]. / Sonographische und klinische Untersuchungen zur periventrikulären Leukomalazie bei Risikoneugeborenen. II. Perinatale Risikofaktoren.

The incidence of periventricular leukomalacia (PVL) in risk neonates was evaluated among 300 risk neonates in a prospective ultrasound study at the Pediatric Clinic of the Medical Faculty, University of Rostock. Perinatal risk factors for the development of PVL and gestational age were taken into consideration. Maternal infections during pregnancy were found to be a risk factor for development of PVL. A severe hyaline membrane disease was more frequently diagnosed in highly immature preterm neonates with postnatal PVL. The percentage of highly immature preterm neonates with postnatal PVL and severe hyaline membrane disease was higher in vaginal-born risk neonates. A correlation between 1-minute Apgar scores < or = 3 and postnatal PVL was found in more mature preterm neonates.

[Ultrasound and clinical studies of periventricular leukomalacia in high risk newborn infants. I. Neuro-ultrasound results]. / Sonographische und klinische Untersuchungen zur periventrikulären Leukomalazie bei Risikoneugeborenen. I. Neurosonographische Untersuchungsergebnisse.

The incidence of periventricular leukomalacia (PVL) in risk neonates was evaluated in a prospective ultrasound study at the Pediatric Hospital of the Medical Faculty, University of Rostock. The study was carried out in 300 registered risk neonates. These risk neonates were divided into 3 groups: < or = 31 gestational week (n = 70), 32-36 gestational week (n = 154), > or = 37 gestational week (n = 76). A prenatal PVL was diagnosed in 41 neonates, a postnatal PVL was found in 56 neonates after the 5th day of life. In 77% of all risk neonates with PVL, the diagnosis was made on the first day of life. After the first day of life, PVL was presented mainly in highly immature neonates. A correlation of PVL to gestational age could only be found in neonates with postnatal PVL. Subarachnoid space enlargement was found to be significantly more frequent in risk neonates with prenatal PVL than in risk infants with postnatal PVL. Residual ultrasound findings of PVL were significantly more frequent in male than in female risk neonates.

Evaluation of oro-coecal transit time: a comparison of the lactose-[13C, 15N]ureide 13CO2- and the lactulose H2-breath test in humans.

OBJECTIVE: The lactulose H2-breath test is the most widely used non-invasive approach for evaluation of orocoecal transit time (OCTT). In the present study, doubly-labelled lactose-[13C, 15N]ureide (DLLU) was synthesized to investigate the OCTT in comparison to the conventional lactulose H2-breath test. Additionally the bacterial breakdown rate (BBR) and rate of elimination and the metabolic pathways of the cleavage products of DLLU (13CO2, [15N]urea, and 15NH3) were investigated. DESIGN AND SUBJECTS: In a first study, DLLU was administered as a single oral-pulse-labelling (dosage: one gram) either without and after pretreatment of five grams of unlabelled lactoseureide (LU) on the day prior to the study to twelve healthy adult volunteers after breakfast. Breath and urine were collected in one and two hour-intervals, respectively, over a one-day period. 13C-enrichment in breath as well as 15N-enrichment in urine fractions were measured by continuous flow-isotope ratio mass spectrometry (CF-IRMS). In a second study, lactulose was administered to the same subjects (dosage: ten grams). Breath was collected in quarter, half and one hour-intervals over a ten hour-period. Hydrogen concentration in breath was analysed using an electrochemical detector. RESULTS: The comparison of the lactose-[13C]ureide 13CO2-breath test and the lactulose H2-breath test showed that the mean increase of the 13C-enrichment in CO2 occurred 1.18 h later than the mean increase of H2 in breath. The resulting OCTTs derived from the two methods were 3.02 +/- 1.4 and 1.84 +/- 0.5 h (P < 0.05) and the corresponding BRs were 9.63 +/- 3.4 and 6.07 +/- 1.7 h (P < 0.01), respectively. The 15N-enrichment of urinary urea and ammonia without and after pretreatment with LU started between two and three hours after DLLU-administration. The cumulative percentage urinary excretion of the 15N- and 13C-tracer was 29.9% and 13.6% respectively, and was slightly increased after LU-pretreatment to 32.1% and 14.6% of the dose administered. A total of 35.2% of the 13C was found to be exhaled and remained approximately constant after LU-pretreatment (36.2%). CONCLUSIONS: The use of the lactulose H2-breath test for evaluation of the OCTT showed a statistically significant shortening of 1.18 h in comparison to the lactose-[13C]ureide 13CO2-breath test in healthy adults. The most important limitations of the lactulose H2-breath test are its low specificity and sensitivity due to dose-dependent accelerations of OCTT, interfering H2-rise from malabsorbed dietary fibre and H2-non-producers. In contrast, our lactose-[13C]ureide 13CO2-breath test was confirmed to avoid these disadvantages and to yield reliable results. This test is recommended especially if higher sensitivity and specificity is required, if IRMS-technique is available and if lactulose H2-tests lead to insufficient results.

15N-tracer studies in formula-fed preterm infants: the role of glycine supply in protein turnover.

In preterm infants, protein-turnover rates obtained by [15N]glycine as a tracer are known to be overestimated. This may reflect the insufficient supply of dietary glycine. In this randomized study, the influence of a glycine-rich diet on whole body protein turnover rates in eight male preterm infants (29-32 weeks, 1,200-2,540 g birthweight) using the 15N-tracer technique on days 21 and 28 of life was investigated to evaluate the necessity of supplementing preterm infant formulas with proteins rich in glycine. Before and during the study, the infants were alternately fed with a commercial available preterm infant formula (I, 2% protein, 40 mg glycine/dl) and a variety of this formulation with glycine-rich proteins (II, 2% protein, 130 mg glycine/dl). The protein-turnover rates were computed after 15N-single-pulse labeling with the help of the three-compartment model (TCM) and the urinary ammonia end-product method (AEPM). The tracer used was [15N]glycine (dosage: 2 mg 15N/kg). For the determination of 15N-excess-excretion kinetics, fractionated urine specimens were collected over a 36-h period. The protein-turnover rate calculated by TCM was 8.8 +/- 1.6 g/kg/day (formula I) and 7.7 +/- 2.0 g/kg/day (formula II); using AEPM, the rate was 8.7 +/- 2.5 g/kg/day and 7.5 +/- 1.5 g/kg/day, respectively. We conclude that the presaturation of the precursor pool by an adequate glycine intake minimizes drawbacks that may arise when using [15N]-glycine as a tracer in preterm infants, and a protein concentration of 2%, as in formula I, and consequently, a 170% glycine content when compared with the same human milk volume, meets the glycine requirement.

[Perinatal and neonatal mortality and morbidity in newborn infants up to 1,000 g]. / Perinatale und neonatale Mortalität und Morbidität bei Neugeborenen bis 1000 g.

World-wide intensive efforts have been made for more than 20 years to reduce the rate of preterm delivery, but so far without remarkable success. Preterm delivery accounts for 6-9% of all deliveries and very-low-birth-weight infants (< or = 1000 g) total up to about 60% of perinatal mortality. This study reports on a retrospective analysis of fetal outcome with 33 very-low-birth-weight-infants (< or = 1000 g) delivered at the Women's Hospital (University of Rostock) during the time from 1986 to 1992. The rate of early mortality was at 45.2%, survival rate was at 33% (n = 11). Caesarean section with preservation of fetal membranes proved to offer better results of fetal outcome than spontaneous delivery. Comparing the fetal outcome of all patients concerned, it became obvious that newborns whose mothers enjoyed intensive prenatal care had better chances than those newborns whose mothers came to hospital not before onset of preterm labour. From our experiences we conclude that intensive antenatal care with very early assessment of all possible risk factors for preterm labour is the prerequisite to reduce the rate of preterm delivery.

Whole-body protein parameters in premature infants: a comparison of different 15N tracer substances and different methods.

[15N]glycine, [15N]leucine, and [15N]yeast protein thermitase hydrolysate (YPTH) as tracers for investigating the protein turnover rates in premature infants were studied in nine human milk-fed neonates (born after 32 to 34 wk of gestation) by paired comparison of the tracers. The 15N enrichment of total urinary nitrogen and ammonia after administration of a single oral dose of 15N was measured by emission spectrometry. Flux rates were calculated using a three-compartment model and the ammonia end product method. The mean whole-body protein synthesis rates, as determined by the three-compartment model derived from the three 15N tracers, differed significantly (p less than 0.01) among [15N]glycine (15.9 g/kg/d), [15N] leucine (9.1 g/kg/d), and 15N-YPTH (5.9 g/kg/d). When the corresponding rates were determined from the excretion of label in ammonia, the results showed the opposite tendency; the lowest apparent synthesis rates were found after [15N]glycine (7.5 g/kg/d), followed by [15N]leucine (14.4 g/kg/d), and the highest figure resulted after [15N] YPTH (16.7 g/kg/d). The results of this comparison substantiate the assumption that there are methodologic errors in connection with the use of different tracers and models for the calculation of whole-body protein parameters in preterm infants, with respect to the main requirement for tracer kinetic studies; the tracer nitrogen must be representative of total amino acid nitrogen. Seen in this light, mixtures of completely labeled amino acids such as YPTH may represent the most reliable tracer substance.(ABSTRACT TRUNCATED AT 250 WORDS)

[The effect of food supplements on the bioavailability of breast milk for premature infants--fecal fat and carbohydrate excretion]. / Der Einfluss von Nahrungssupplementen auf die Bioverfügbarkeit der Frauenmilch für Frühgeborene. Die faecale Fett und Kohlenhydratexkretion.

Faecal excretion of fat and carbohydrates was studied in 14 preterm infants fed on raw mother's milk (group I) or banked fortified human milk (group II) at days 7, 14, 21 and 28 of postnatal life: group I: n = 5; 31.0 +/- 2.0 weeks; 1954 +/- 441 g; group II: n = 9; 32.0 +/- 1.0 weeks; 1806 +/- 176 g. Mixtures of amino acids, peptides, minerals, dextrine and maltose were designed for fortifying banked human milk. There were no significant differences between faecal excretion of fat and carbohydrates in both feeding groups. The investigated human milk fortifier helps to realize the protein-energy ratio needed in preterm infants with well tolerable volumes of feeding and without stressing their limited digestive capacity.

Evidence for colonic absorption of protein nitrogen in infants.

The absorption of protein nitrogen by the colon was assessed in 6 infants with colostomy by giving 15N yeast protein in a dosage of 5-20 mg 15N/kg (92.4 atom-% 15N). The absorption of 15N ranged between 87.1 and 98.1% of the administered dose, and the retention in the protein pool ranged between 79.0 and 94.2%. The incorporation of 15N in the plasma proteins was demonstrated by 15N excess values between 0.02 and 0.10 atom-%. The results suggest that the colon can assimilate proteins when insufficient absorption of protein nitrogen in the small intestine occurs. The breakdown of protein is thought to result from the action of colonic flora.

15N tracer techniques for the differential diagnosis of dwarfism and prediction of growth hormone action in children.

[15N]Glycine in a single oral dose was used to study nitrogen turnover in 18 short children, aged 3-14 yr. On the basis of their serum GH responses to insulin-induced hypoglycemia, the patients were divided into 3 groups: complete GH deficiency (GHD; n = 5); partial GH deficiency (pGHD; n = 6), and children with constitutional growth delay and familial short stature (CGD/FSS; n = 7). The mean 48-h renal excretion of 15N by patients with GHD was 66.09 +/- 14.12% (+/- SD) of the tracer dose. This decreased to 27.64 +/- 5.33% after two injections of 10 IU/m2 GH (P less than 0.001). 15N excretion by patients with pGHD was 47.19 +/- 13.42%, and it decreased after GH injection to 22.69 +/- 4.58% (P less than 0.005). Patients with CGD/FSS had 15N excretion of 37.27 +/- 5.68%, and it did not change in response to GH. The mean protein synthesis rate in GHD patients was extremely low, and it increased after GH injection from 0.99 +/- 0.46 to 3.53 +/- 0.43 g/kg X day. In pGHD patients the protein synthesis rate increased from 2.62 +/- 0.84 to 4.50 +/- 1.09 g/kg X day. The CGD/FSS patients had no change in protein synthesis rate after GH. Our results suggest that studies of the metabolism of [15N]glycine might be of value in predicting responsiveness to GH therapy.

[The dose dependence of 15N-incorporation in organ proteins of newborn rats after pulse labeling with different tracers]. / Untersuchungen zur Dosisabhängigkeit der N-Inkorporation in Organproteine neugeborener Ratten nach Pulsmarkierung mit verschiedenen Tracern.

A short-chain 15N-peptide mixture characterized by an average chain length of 2.3 was obtained when 15N-labeled yeast protein has hydrolyzed enzymatically by thermitase from Thermoactinomyces vulgaris. Fifteen newborn Wistar-rats were given a single pulse of [15N]glycine. [15N]H4Cl and [15N]yeast protein-thermitasehydrolysate (YPTH) in a dosage of 50 mg 15N excess kg-1 by gastric tube. In comparison with [15N]glycine the 15N-incorporation rates of brain, muscle and liver were approximately 150% higher after [15N]YPTH-application. Uniform labeling, high 15N-enrichment, almost complete absorption, avoidance of imbalances and the low price make this tracer substance superior to other tracers conventionally used for organ labeling.

15N tracer kinetic studies on the validity of various 15N tracer substances for determining whole-body protein parameters in very small preterm infants.

Reliable 15N tracer substances for tracer kinetic determination of whole-body protein parameters in very small preterm infants are still a matter of intensive research, especially after some doubts have been raised about the validity of [15N]glycine, a commonly used 15N tracer. Protein turnover, synthesis, breakdown, and further protein metabolism data were determined by a paired comparison in four preterm infants. Their post-conceptual age was 32.2 +/- 0.8 weeks, and their body weight was 1670 +/- 181 g. Tracer substances applied in this study were a [15N]amino acid mixture (Ia) and [15N]glycine (Ib). In a second group of three infants with a post conceptual age of 15N-labeled 32.0 +/- 1.0 weeks and a body weight of 1,907 +/- 137 g, yeast protein hydrolysate (II) was used as a tracer substance. A three-pool model was employed for the analysis of the data. This model takes into account renal and fecal 15N losses after a single 15N pulse. Protein turnovers were as follows: 11.9 +/- 3.1 g kg-1 d-1 (Ia), 16.2 +/- 2.5 g kg-1 d-1 (Ib), and 10.8 +/- 3.0 g kg-1 d-1 (II). We were able to demonstrate an overestimation of the protein turnover when Ib was used. There was an expected correspondence in the results obtained from Ia and II. The 15N-labeled yeast protein hydrolysate is a relatively cheap tracer that allows reliable determination of whole-body protein parameters in very small preterm infants.

[The fight against hemolytic disease of the newborn-- an example of interdisciplinary cooperation]. / Die Bekämpfung des Morbus hämolyticus neonatorum--ein Beispiel interdisziplinärer Kooperation.

The practical proceeding used in checking anti-D-immunoprophylaxis, in monitoring carriers of antibodies during gravidity and in treating newborns is represented. Details of patients selecting by means of step by step prenatal diagnostics as well as technique and results of intrauterine transfusion are described. After the general introduction of anti-D-prophylaxis, the morbidity resulting from morbus haemolyticus could be reduced by 80% approximately. The survival rate of foeti intrauterinely transfused amounts to 49%.