[Spontaneous elimination of helicobacter pylori infection in children]. / Spontanelimination bei Helicobacter-pylori-Infektionen im Kindesalter?

BACKGROUND: With the (13)C-urea-breath test, 6.6 % of 3 372 preschool children of the Leipzig area tested H. pylori positive in 1998. PATIENTS: In 2000, 5.6 % of 3 854 grade-two pupils of the same area tested positive. METHOD: 2 235 children participated in both tests campaigns. Therefore, their H. pylori state could be reinvestigated after two years. RESULTS: 30 of the 104 children, who were tested positive in 1998 were negative in 2000. Using questionnaires completed by the corresponding parents and family physicians, possible reasons of individual elimination were analysed. It was found that 18 of the 25 children received a H. pylori triple therapy. Three children had been tested false-positive in 1998. Four children received antibiotics for other reasons and H. pylori was obviously eradicated too. Only three children were not treated with any antibiotics between 1998 and 2000. For these children, spontaneous elimination is assumed. CONCLUSIONS: Conclusions about spontaneous elimination of H. pylori infections are problematic. Further investigations are needed in consideration of this object.

[(15)N(2)]arginine as a first potential inhaled diagnostic agent to characterize respiratory diseases.

Conventional diagnosis of the pulmonary tract uses physical methods such as spirometry and oscillometry. However, the inhalation of a chemical diagnostic agent ought to provide novel ways of more specific diagnosis, for instance of inflammatory states of the bronchial and lung mucosa. The stable isotope technique using a (15)N-labeled substrate appears to be a suitable tool for this application. In a pilot study, defined amounts of the amino acid L-[guanidino-(15)N(2)]arginine monohydrochloride (aqueous solution, 20 atom % (15)N) were inhaled as a diagnostic agent by healthy volunteers and pulmonary patients suffering from asthma bronchiale. The amino acid is resorbed and partly metabolized to (15)NO. The exhaled air was collected under defined conditions in 10-L breath bags and analyzed for NO using chemiluminescence. Under standardized test conditions, healthy persons (n = 6) exhaled 0.97 +/- 0.08 micromol NO/m(3) and asthmatic patients (n = 7) 1.17 +/- 0.14 micromol NO/m(3). A better distinction was expected comparing the (15)NO exhalation. The (15)N abundance of NO was determined using a Cryotrap gas chromatography - mass spectrometry set-up. Between 30 and 80 minutes after inhaling 700 mg [(15)N]arginine, a maximum with a plateau of the (15)NO abundance was found in the exhaled air. At this time, healthy and asthmatic subjects exhibited clear differences in their exhaled (15)NO amounts. Under standardized test conditions, the healthy persons (n = 6) exhaled 102.3 +/- 6.7 nmol (15)NO/m(3), whereas asthmatic patients (n = 7) exhaled only 76.1 +/- 10.9 nmol (15)NO/m(3). It is concluded that (15)NO yielded after the inhalation of (15)N-labeled arginine could be a potential marker for demonstrating pathophysiological changes in the lung epithelium. This method could pave a new diagnostic principle of "inhalative breath test."

Towards an inhalative 13C breath test method.

Customary 13CO2 breath tests--and also 15N urine tests--always start with an oral administration of a test substrate. The test person swallows a stable isotope labelled diagnostic agent. This technique has been used to study several pathophysiological changes in gastrointestinal organs. However, to study pathophysiological changes of the bronchial and lung epithelium, the inhalative administration of a stable isotope labelled agent appeared more suitable to us. [1-13C]Hexadecanol and [1-13C]glucose were chosen. Inhaled [1-13C]hexadecanol did not yield 13CO2 in the exhaled air, but [1-13C]glucose did. To study the practicability of the [1-13C]glucose method and the reproducibility of the results, 18 inhalation tests were performed with healthy subjects. In 6 self-tests, the optimum inhalative dose of [13C]glucose was determined to be 205 mg. Using the APS aerosol provocation system with the nebulizer 'Medic Aid' (Erich Jaeger Würzburg), a 25% aqueous solution was inhaled. Then, breath samples were collected at 15 min. intervals and analysed for 13CO2. 75-120 min after the end of inhalation a well-reproducible maximum delta13C value of 6%o over baseline (DOB) was detected for 12 healthy probands. Speculating that the pulmonary resorption of the [13C]glucose is the rate-limiting step of elimination, decompensations in the epithelium ought to be reflected in changed [1-13C]glucose resorption rates and changed 13CO2 output. Therefore, we speculate that the inhalation of suitable 13C-labelled substrates will pave the way for a new group of 13CO2 breath tests aiding investigations of specific pathophysiological changes in the pulmonary tract, such as inflammations of certain sections and decompensations of cell functions.

Five- to 7-year-old children with Helicobacter pylori infection are smaller than Helicobacter-negative children: a cross-sectional population-based study of 3,315 children.

OBJECTIVE: To test whether Helicobacter pylori-positive children are smaller and weigh less than H pylori-negative children. DESIGN: Cross-sectional population-based study. PARTICIPANTS: In 3,315 5-to 7-year-old preschool and school children, the putative influence of H pylori infection on growth was investigated. Standing height and weight were analyzed in relation to H pylori infection. The diagnosis of H pylori infection was established by 13C-urea-breath test. RESULTS: The prevalence of H pylori infection in boys was 7.2% (95% confidence interval, 5.9-8.9; n = 1,550) and in girls was 6.1% (95% confidence interval, 4.9-7.3; n = 1,552) H pylori-positive children were smaller than noninfected children (117.6 +/- 5.5 cm vs. 118.9 +/- 5.7 cm; P < 0.01). Although H pylori-positive boys were 2.06 cm smaller than H pylori-negative boys (117.4 +/- 5.6 cm vs. 119.5 +/- 5.7 cm; P < 0.001), the difference in girls was not significant (117.9 +/- 5.3 cm vs. 118.4 +/- 5.7 cm). When standing height was adjusted for age, the found differences were more pronounced. Differences between the infected and noninfected children with regard to body weight were not significant (22.4 +/- 4.0 kg vs. 22.1 +/- 4.0 kg), nor was there a significant difference with regard to body-mass index. However, boys with H pylori infection had a lower weight than noninfected boys (21.6 +/- 3.3 kg vs. 22.6 +/- 4.0 kg; P < 0.01), but in girls, these differences were not observed (22.2 +/- 4.0 vs. 22.8 +/- 4.6 kg, respectively). When weight was adjusted for age, H pylori -positive children also had a lower weight than H pylori -negative children because of the lower weight of boys. CONCLUSIONS: H pylori infection is associated with growth delay, growth retardation, or both in affected children.

Helicobacter pylori prevalences and risk factors among school beginners in a German urban center and its rural county.

In 1998, the Helicobacter pylori [(13)C]urea breath test was offered to all school beginners (birth cohort 1991/1992) in the city of Leipzig and in Leipzig County, Germany, to determine the colonization prevalence and potential transmission pathways of the bacterium. A total of 3,347 school beginners participated in the test, and 2,888 parents completed the detailed, self-administered questionnaire. The H. pylori prevalence was 6.5% [95% confidence interval (CI), 5.3-7.6] in the city and 5.7% (CI, 4.2-7.0) in the county. Using cluster analysis (WARD's method, Euclidean distances), we identified different sets of variables (confirmed by multivariate logistic regression analyses [odds ratios (ORs)] that are signficantly associated with H. pylori positivity. Among city children, the risk is significantly increased with contact to a pet hamster (OR = 2.4; 95% CI, 1.2-4.7; p < 0.015) and travels to Asian countries (OR = 3.7; 95% CI, 1.6-8.7; p < 0.002). Among county children, H. pylori positivity increased significantly with drinking of water from nonmunicipal sources (OR = 16.4; 95% CI, 3.1-88.5; p < 0.001), more than 3 children living in a household (OR = 4.2; 95% CI, 1.2-14.6; p < 0.02), and contact with pet hamsters (OR = 2.4; 95% CI, 1.0-5.7; p < 0.04). These data suggest that, in a general population sample, indirect fecal-oral transmission and living conditions are important risk factors in the spread of H. pylori infection. However, clinical symptoms do not necessarily indicate H. pylori positivity.

Effect of sulfur dioxide and particulate pollutants on bronchitis in children--a risk analysis.

The general morbidity is being influenced to a great extent by diseases of the respiratory tract. Since their incidence and prevalence have been increasing, the identification of causal factors, especially of environmental origin, is of importance, not just in view of implementing preventive control strategies. Primary irritative gaseous [like sulfur dioxide (SO2)] as well as particulate pollutants (like TSP) can be regarded as causal constituents. Using the opportunity of changing levels of ambient air pollution in East Germany since 1989, the impact of SO2 and TSP on bronchitis was investigated over the last 10 years as part of several intervention studies in a locally defined homogenous population, children. The data suggest a significant association between SO2 and the prevalence of bronchitis in children but not for TSP. Considering the findings of other studies with respect to air pollution and the epidemiology of adverse health effects (especially respiratory disease), these results would amend the hypothesis put forward in a review of the literature as TSP < ultrafine particles (SO4(2-)) = SO2. Although these data show a significant association with only SO2, this does not imply that ultrafine particles, such as SO4(2-), do not contribute to the association with the observed adverse health effects. Nevertheless, the findings suggest that TSP seems less likely to be a predictor in the association with respiratory diseases, particularly not in the presence of high SO2.

The [15N]methacetin liver function test characterizes multicomponent exposure of children in industrially polluted regions.

The [15N]methacetin urine test for assessing disturbances of the cytochrome P450-aided oxygenation of xenobiotics in the human liver has been approved in several environmental health studies. A recent longitudinal study of kindergarten children near chemical and mining companies undergoing fundamental restructuring showed high, seasonally fluctuating SO2 burden which was well correlated with alterations in the mean liver states of the children. At one point the correlation disappeared, together with indications of large amounts of chlorinated compounds overflowing locally at nighttime. This was finally proven by analyzing urine samples from the children for trichloroacetic acid (TCA). Chlorinated ethanes and ethenes-the precursors of TCA-seemed to dominate the air pollution and to affect the hepatic detoxification capacity. We concluded that the methacetin liver function test reflects multicomponent exposure, including acute monopolization by a dominant pollutant for a time.

Helicobacter pylori in vivo diagnosis after food intake: results of simultaneous [15N]urea urine and [13C]acetate breath tests.

The protocols for 13C and 15N H. pylori tests stipulate that the diagnostic agent should be taken on an empty stomach. It is presumed that food intake prior to the tests leads to less reliable test results due to a prolongation of the gastric residence time of the diagnostic agent urea. This might allow the bacteria to split a higher proportion of urea, resulting in an increased number of false positives. 12 probands received 150mg [15N]urea and 75 mg sodium [13C]acetate in 75 ml orange juice as a test drink. [15N]Urea served as an agent to diagnose gastric H. pylori colonization. The 15N tests were evaluated using a urine sample of the second hour after test start. [13C]Acetate served as a marker of the gastric emptying of water-soluble food including the urea under the influence of food intake. Breath air samples were taken to calculate the gastric emptying half life (EHL) and the apparent resorption time (RT) of the urea. The double tests were carried out four times within four weeks using identical test protocols but different standardized time periods of pretest fasting: overnight, two hours prior to test, one hour prior to test, and no fasting at all. The food intake amount was standardized. Five probands testing positive in the overnight fasting test were also found to be positive in the other test variants with more or less empty stomachs. Seven other probands testing negative after overnight fasting tested negative in the other test variants as well. It is concluded that food intake prior to the test drink does not have much of an influence on the gastric residence time of urea and so on the qualitative H. pylori test results. Due to identical behaviour of [13C]urea and [15N]urea in the stomach, this influence is believed to be independent on the labelling isotope. For survey purpose, no fasting conditions are required for the H. pylori tests.

Helicobacter pylori prevalence in Leipzig's 1998 school entries: methodology and first results.

The non-invasive, stable-isotope-aided Helicobacter pylori (H. pylori) tests--breath and equivalent urine tests--were offered on a voluntary basis as part of the mandatory school entry medical examination to the 1998 school entry cohort of the City of Leipzig (480,000 residents). Parents of participating subjects were asked to fill out a detailed epidemiologic questionnaire. The response rate was 94% (n = 2228 of 2369 school starters born in 1991/92). Parent-completed questionnaires were returned by 1890 (80%) children. The overall H. pylori positive prevalence was 7.2%. The prevalence among children with a test and a parent-completed questionnaire was 6.5%. Prevalences among subsequently tested family members of the positive tested children was 65, 60 and 39% for mothers, fathers and siblings respectively. Though studies have shown that the direct transmission of the bacterium (oral-oral and fecal-oral) is a dominant pathway of infection, the questionnaire analyses indicate associations between H. pylori colonisation and living as well as environmental conditions.

Effects of indoor painting and smoking on airway symptoms in atopy risk children in the first year of life results of the LARS-study. Leipzig Allergy High-Risk Children Study.

INTRODUCTION: The Leipzig Allergy High-Risk Children Study (LARS) is a prospective nested cohort control study about the influence of chemical indoor exposure in dwellings on the health outcome of atopy-risk children during the first years of life. DESIGN AND METHODS: 475 premature children and children with allergic risk factors have been selected out of the 1995/1996 birth cohort in the city of Leipzig. Twenty-five volatile organic compounds (VOC) were measured in the infant's bedrooms using passive sampling systems for 4 weeks after birth. The babies underwent a medical examination at the age of six weeks and 1 year. The parents answered a questionnaire. RESULTS: Correlations between VOC exposures and infections were calculated by multiple logistic regression. Selected VOC show a direct association to actually painted dwellings (OR = 2.4; 95% Cl 1.1-5.3). An increase of risk of pulmonary infections was observed in infants aged 6 weeks if restoration (painting OR 5.6; 95% Cl 1.3-24.0) or flooring connected with painting had occurred during the pregnancy period. Higher concentration of styrene (> 2.0 micrograms/m3, indicator for flooring) elevated the risk of pulmonary infections in six-week-old infants (OR = 2.1; 95% Cl 1.1-4.2). Environmental benzene > 5.6 micrograms/m3 increased the risk of airway infections in six-week-old babies (OR = 2.4; 95% Cl 1.28-4.48). Smoking in the dwelling (OR = 2.0; 95% Cl 1.1-3.5) as well as restoration (OR = 1.9; 95% Cl 1.1-3.5) are also risk factors of the development of wheezing in the one-year-old child. CONCLUSIONS: The data give indications in order to prevent allergies and chronic lung diseases in atopy risk children exposure to chemicals from indoor air should be minimised from birth on.

Diagnosis of Helicobacter pylori infection in children: is the 15N urine test more reliable than the 13C breath test?

BACKGROUND: The [13C]urea breath test is a convenient method to estimate Helicobacter pylori colonization non-invasively. As an alternative method, the [15N]urea urine test has been established. It is hypothesized that the urine test could be advantageous under some circumstances. The diagnostic value of the breath test might, for example, be jeopardized owing to fluctuating 13C isotope dilution by endogenous carbon dioxide. METHODS: To compare the reliability and practicability of the two tests, 13C breath tests and 15N urine tests were performed simultaneously in three groups of patients: A) 36 adults under standardized conditions, B) 67 children who were allowed to move around during the test, and C) 18 children once without and once during standardized physical activity. RESULTS: In the 36 adults there was a close correlation of the test results of the two methods (r = 0.88). In contrast, the correlation in the group of 67 children and infants was poor (r = 0.10). In the children with controlled activity the 13C results fluctuated, whereas the 15N results remained unchanged. CONCLUSIONS: Owing to their identical biochemical basis the breath test and the urine test produce the same diagnostic results in the same individuals if standardized pre-test and test conditions are followed. However, factors such as physical activity during the test may provoke fluctuations with a tendency to decreasing 13C values. This could be due to additional isotope dilution by increases in the endogenous production of 12C-carbon dioxide. We conclude that in very active children the 15N urine test might be advantageous and more reliable than the 13C breath test.

15N investigation into the effect of a pollutant on the nitrogen metabolism of Tetrahymena pyriformis as a model for environmental medical research.

A pilot study was performed to examine the potential of stable isotope techniques for monitoring the impact of a harmful substance on the cellular nitrogen metabolism in the ciliate species Tetrahymena pyriformis. After identical cultivation periods of control cells and toluene-exposed cells in a defined culture medium enriched with [guanidino-15N2]l-arginine, a number of nitrogen-containing pools were analyzed: 1) quantity and 15N abundance of ammonia as the end product of nitrogen metabolism in the system; 2) pattern and 15N abundances of the protein-bound amino acids in the cells; 3) pattern and 15N abundances of free amino acids in the cells; and 4) pattern and 15N abundances of the amino acids in the culture medium. In addition to 15N emission spectrometry, a new gas chromatography/combustion interface-isotope ratio mass spectrometry/mass spectrometry analytical system was used. The production and 15N content of ammonia were higher in the toluene-exposed system by 30% and 43%, respectively, indicating higher deamination rates and greater arginine consumption. The toluene-exposed cells exhibited increased 15N abundances of protein-bound amino acids in alanine, aspartic acid, glutamic acid, and tyrosine. Furthermore, structural analyses revealed the presence of N[Omega]-acetylarginine and pyrrolidonecarboxylic acid--compounds that had not previously been detected in Tetrahymena pyriformis. Differences in the 15N-enrichment of free amino acids were also evident. This new effect-monitoring system designed to investigate the impact of a pollutant on protein metabolism by using a stable isotope-labeled cell culture is a powerful tool for environmental medical research.

Maturation of hepatosomal mono-oxygenation and glucuronidation activities in pre- and full-term infants as studied using the [15N]methacetin urine test.

The non-distressing [15N]methacetin liver function test was modified and applied to newborn healthy infants in order to measure both the total [15N]methacetin metabolites excreted in the urine (total elimination capacity) and the proportion of glucuronated metabolite. By studying pre- and full-term normotrophic neonates 3-168 days old, the age-dependent maturation of the two developing liver function processes can be compared on the basis of either postnatal or postmenstrual age. When solely considering postnatal age, no significant differences between the pre- and full-term infants were observed in the development of the total elimination capacity. However, when postmenstrual age was considered, it became apparent that this development starts earlier in pre-term infants and continues at the same rate as their full-term counterparts, up to the postmenstrual age of approximately 280 days. This increase subsequently diminishes in the pre-terms. In the same study group, the proportion of glucuronidation, another indicator of the hepatic detoxification system, appears to develop at a lower rate in pre-term than in full-term infants. When postmenstrual age is taken into consideration, glucuronidation development is also observed to begin earlier in pre-term infants and the slower maturation is more pronounced. Although these results are not generally applicable, they contribute to a better interpretation of the [15N]methacetin liver function test--for instance when estimating effects due to environmental exposure or accurately calculating age-related drug dosage for neonates.

Hepatic biotransformation capacity in low-birth-weight infants as measured with the [15N]methacetin urine test: influences of gestational age, postnatal age, and intrauterine growth retardation.

The influences of the gestational age (range: 28-36 weeks) and the postnatal age (range: 6-100 days) on the biotransformation capacity of the liver were studied in 51 preterm appropriate-for-gestational-age infants and in 20 preterm small-for-gestational-age infants using the [15N]methacetin urine test. Methacetin is a test drug assessing a two-step pathway of biotransformation including monooxygenation and conjugation. After oral administration of 3 mg [15N]methacetin/kg body-weight, the cumulative 15N excretion in urine during the consecutive 9 h was measured and used as a marker of microsomal biotransformation capacity. In preterm appropriate-for-gestational-age infants, the biotransformation capacity increases with gestational age as well as with postnatal age, but the strongest correlation could be found between cumulative [15N] excretion and postmenstrual age. Intrauterine growth retardation results in lower biotransformation capacity (26.3 +/- 11.3 vs. 36.1 +/- 9.6% [15N] excretion, expressed as percentage of intake) and disturbed postnatal development of this hepatic function. The data indicate that normal intrauterine development is a prerequisite for normal postnatal development of the biotransformation capacity, which might have consequences for the metabolism and efficacy of certain drugs in small-for-gestational-age infants.

Is the [15N]methacetin liver function test suited to estimate environmental effects on the maturity of neonates?

Clinical and paraclinical data of 91 neonates of the Saxon regions of Leipzig and of Torgau/Elbe were reviewed and correlated to the environmental conditions of the places of residence of their mothers during pregnancy. One of the parameters investigated was the hepatic detoxification capacity of the neonates measured by 15N elimination rates in the [15N]methacetin urine test. Because of heavy air pollution in the places of residence of some of the pregnant women, a distinct reflection of environmental influence in the parameters was expected. While some of the parameters considered, such as birth weight and bilirubin levels, did not correlate with mean exposure data of the residences of the pregnant women, the mean rate of the age-dependent maturation of hepatic 15N elimination did. This maturation was seen to be significantly decreased in heavily polluted districts of the Leipzig region compared to lower polluted places of Leipzig and to the lowly polluted region of Torgau/Elbe.

[15N liver function test in underweight infants, hypotrophic at birth]. / 15N-Leberfunktionstests bei untergewichtigen Kleinkindern, die hypotroph geboren wurden.

Fifty-two infants were enrolled in the study: 23 hypotrophically born infants (birth weight < 5th percentile according to Kyank) with present body weights < 3rd percentile according to Prader (group 1), 15 patients suffering from severe liver diseases (group 2), 14 patients without liver diseases (group 3). Usual serum parameters were estimated. Additionally, the hepatic detoxification capacities were measured using the non-invasive, non-radioactive [15N]methacetin urine test. 17 of the 23 infants of group 1 showed 15N elimination rates as low as in severe liver-diseased patients (group 2) whereas their serum parameters were in the normal range, as were those of group 3. The question remains whether intra-uterine malnutrition or postnatal effects, e.g., environmental conditions, caused the functional liver damage.

Effects of two antibiotics on hepatic function in low birth weight infants: ampicillin vs. cefotaxime.

In 21 low birth weight infants with two regimens of antibiotic therapy during the first 3 days of life possible hepatotoxic side effects were studied 8 days after the last administration of the tested drugs. Fourteen of the infants were treated with ampicillin/gentamicin and 7 received cefotaxime/gentamicin. The serum concentrations of total bile acids, the activities of transaminases in serum and the cumulative 15N excretion in urine after administration of 3 mg of 15N-labeled methacetin/kg of body weight were used as markers of hepatotoxic side effects. Neither the concentrations of total bile acids (22.6 +/- 12.1 and 19.4 +/- 10.8 mM, respectively) nor the activities of transaminases (alanine aminotransferase, 0.27 +/- 0.06 vs. 0.30 +/- 0.09 mumol/second/liter; aspartate aminotransferase, 0.46 +/- 0.11 vs. 0.49 +/- 0.10 mumol/second/liter) were different between the two groups. In contrast the cumulative 15N excretion in urine was significantly lower in the group treated with cefotaxime/gentamicin than in the group treated with ampicillin/gentamicin (17.2 +/- 6.4 vs. 33.0 +/- 5.1% of intake; P less than 0.01) and also lower than the reported age-related reference values. On the 28th day of life no differences could be found between the cumulative 15N excretion in the urine of the infants treated with cefotaxime/gentamicin and the reported age-related reference values of this test. The results indicate a limited capacity of the monooxygenase system of the liver of low birth weight infants during the first weeks of life and a specific reversible influence of cefotaxime on this hepatocellular system. Further investigations are required to evaluate the clinical relevance of this drug-specific inhibition of the hepatic monooxygenase pathway.

[15N]methacetin urine test: a method to study the development of hepatic detoxification capacity.

The [15N]methacetin urine test was used to study human O-demethylase activities to characterize the maturation of hepatic detoxification capacity. The study involved 43 healthy subjects aged 1 day-47 years. The urinary 15N elimination rates were measured following oral administrations of an aqueous [15N]methacetin solution. Age-dependent normal values of hepatic drug elimination capacity were established. Parameters were the 15N elimination half-life and cumulative elimination of the 15N dose as a percentage over a 9 h period. The maximum elimination rate (% dose/h) and peak time can give additional information. The 15N method is a simple, non-invasive and non-radioactive liver function test avoiding disadvantages of 14C and 13C breath tests. The [15N]methacetin test is suitable and useful in studying the hepatic development at birth and pathological changes of the microsomal detoxification capacity in early childhood.

Influence of intrauterine growth retardation on parameters of liver function in low birth weight infants.

To establish nutritional management of low birth-weight infants according to their individual metabolic situation, hepatocellular partial function was studied in 13 appropriate (AGA) and 11 small-for-gestational-age (SGA) low birthweight (LBW) infants during the first weeks of postnatal life. The concentrations of total bile acids and of alpha-amino-nitrogen in serum, the renal excretion of urea and ammonia and the renal excretion of 15N after enteral administration of 3 mg 15N-labeled methacetin/kg were measured. In comparison to AGA infants, SGA infants had elevated serum concentrations of total bile acids and of alpha-amino-nitrogen, decreased excretion of urea, increased excretion of ammonia in urine, and lower urinary 15N-excretion after enteral administration of 15N-labeled methacetin. The data suggest that hepatocellular functions are influenced by intrauterine growth retardation resulting in a reduced metabolic capacity in SGA infants. The metabolic differences between SGA and AGA infants should be considered in the nutritional management of LBW infants.