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Biomedical subjects

G Boehm

Publications and source records attributed to G Boehm.

At least 37 records · Page 2Linked to original sources

Mortality in antiepileptic drug development programs.

BACKGROUND: Pooled data from New Drug Applications (NDAs) submitted to the U.S. Food and Drug Administration (FDA) provide an opportunity to study the incidence of and risk factors for rare events. OBJECTIVE: To examine the incidence and causes of mortality in patients with epilepsy participating in clinical trials of antiepileptic drugs (AEDs); and to examine the incidence of and risk factors for sudden unexplained death in such patients. METHODS: Exposure data and death narratives were obtained from the NDAs of five recently reviewed AEDs. Deaths were classified as sudden unexplained, accidental, or other cause using the 1993 Burroughs-Wellcome expert panel criteria, and mortality rates were calculated for each category. Add-on trials were analyzed separately from monotherapy initiation trials. RESULTS: Among 9,144 patients in the add-on trial database, the all-cause and sudden unexplained mortality rates were 9.1 and 3.8 deaths per 1,000 person-years (124 and 52 deaths in 13,617.1 person-years of drug exposure). Sixty-five percent of all deaths were related to the underlying epilepsy. Of the examined risk factors, only age was associated with the incidence of sudden unexplained death. Among 1,293 patients in the monotherapy initiation trials, the all-cause and sudden unexplained mortality rates were 7.1 and 0 deaths per 1,000 person-years (7 and 0 deaths in 982.5 person-years of drug exposure). CONCLUSIONS: A large proportion of the deaths in the add-on cohort was attributable to epilepsy-related causes. Mortality due to sudden death in the add-on cohort falls into the high end of the reported range for patients with epilepsy. The difference in mortality due to sudden death between the add-on and monotherapy initiation cohorts suggests that disease severity is the primary determining factor for risk of sudden unexplained death.

Adolescent↗

An infant formula free of glycomacropeptide prevents hyperthreoninemia in formula-fed preterm infants.

BACKGROUND: Hyperthreoninemia is a well-known phenomenon in infants fed a whey protein-predominant formula. Sweet whey is commonly used for the production of these whey-predominant infant milk formulas. Sweet whey contains not only whey proteins but also the threonine-rich glycomacropeptide (GMP). In the current study, an experimental formula based on acid whey without GMP and a formula based on sweet whey with GMP (threonine content 17.2% higher than in the experimental formula) but otherwise with identical composition were tested with particular respect to threonine metabolism. METHODS: Fourteen preterm infants appropriate for gestational age were enrolled in this randomized cross-over study. After a feeding period of at least 7 days, the nutrition of each infant was switched to the other formula for the second feeding period. At the end of each feeding period, the concentrations of creatinine and amino acids in the plasma and in the urine were measured. RESULTS: In the plasma, the threonine concentration was significantly lower in the group fed the experimental GMP-free formula than in the group fed the sweet whey formula (P < 0.001). Renal excretion of all essential amino acids was generally very low and less than 2% of the intake, indicating that the kidneys had no marked homeostatic function with respect to plasma amino acid. The plasma concentrations of the threonine metabolites glycine and serine, and that of urea were not influenced by diet. CONCLUSION: Feeding a whey protein-predominant bovine milk produced from acid whey protein reduces significantly the hyperthreoninemia commonly found in formula-fed preterm infants. Thus, acid whey formulas should be recommended for feeding preterm infants.

Amino Acids↗

Postprandial plasma amino acids in preterm infants: influence of the protein source.

Preprandial plasma amino acid concentrations have been used extensively as a marker of the nutritional value of dietary proteins in preterm infants. This study investigated the postprandial plasma amino acid profiles of preterm infants fed with different dietary proteins at similar protein intakes during the first weeks of life. In 12 preterm infants, pre- and postprandial plasma amino acid concentrations were measured before the removal of an indwelling central venous catheter placed for parenteral nutrition. All infants received breast milk until the time of study. At the start day of the study, infants were randomized to receive a test meal of 10 ml/kg, either of breast milk fortified with breast milk protein to reach a protein content of 2.0 g/dl or of a bovine milk preterm formula with a protein content of 2.0 g/dl (whey/casein ratio 60/40). Five samples of 100 microl blood were obtained immediately before and 15, 30, 45 and 60 min after the test meal. The plasma amino acid analysis was performed by a reversed-phase high-performance liquid chromatography based on o-phthaldialdehyde/2-mercaptoethanol pre-column derivatization. In both groups, the plasma amino acid concentrations increased within the first 30 min and the levels did not return to the preprandial baseline during the observation period. Fifteen minutes after the test meal, the plasma levels of all essential amino acids with the exception of histidine were higher in the bovine milk formula fed infants than in the fortified breast milk fed infants. The sum of plasma essential amino acid levels found in the formula fed infants were significantly (p < 0.05) higher than the levels found in the fortified breast milk fed infants at 15, 30 and 45 min. The kinetics of individual amino acids were influenced by the different quality of the protein even when the intakes in the groups were similar, as demonstrated for histidine and phenylalanine. The data indicate that postprandial plasma amino acid concentrations depend significantly on the dietary amino acid source and cannot simply be calculated from the amino acid composition of dietary proteins. Therefore, postprandial plasma amino acid concentrations should be included in the nutritional evaluation of dietary proteins in preterm infants.

Amino Acids↗

Usefulness of short-term urine collection in the nutritional monitoring of low birthweight infants.

To establish adequacy of urine collection times shorter than 24h in the metabolic monitoring of low birthweight infants, we collected urine for 24 h in 39 LBW infants during the third and fourth week of life. All urine voidings over the 24-h period were separately collected, the volume of each sampling and the time of voiding were recorded, and 20% of the volume was removed for pooling. All individual and pooled samples were analysed for total nitrogen, urea and ammonia, alpha-amino nitrogen, creatinine, sodium, potassium, calcium and phosphorus, and for each compound the ratio to 1 mol creatinine was established. Individual sample results were "pooled" to obtain 3-, 6- and 12-h period excretion and than related to the 24-h excretion as measured in the pooled 24-h sample. As the volume of urine obtained in any 6-h collecting period depended on the time of sampling (06:00-12:00 h, 17.5+/-3.1% of total; 12:00-18:00 h, 31.6+/-5.1% of total; 18:00-24:00 h, 25.6+/-3.1% of total; and 0:00-06:00h, 25.3+/-2.9% of total), calculations were based on samples obtained from 18:00 to 06:00 h. The correlation between results of 3- and 24 h-collection periods was weakest, while results of the 6-h collection correlated highly with the total daily excretion (r = between 0.82 and 0.93 for the different compounds) and the correlation was only slightly better when the 12-h collection period was considered. The correlation between the mean molar substrate/creatinine ratio of all individual samples of a 24-h collecting period and the and total daily excretion of the respective substrate was weaker (r = between 0.46 and 0.76 for the different compounds) than the correlation between the results of a 6-h collecting period and the daily excretion is not as stable than in later life. The data indicate that 6-h urine sampling may be sufficient for metabolic monitoring of LBW infants. By contrast, urinary substrate/creatinine ratios are not good markers of the daily excretions of the respective substrate during the first weeks of life.

Ammonia↗

Postnatal development of urea synthesis capacity in preterm infants with intrauterine growth retardation.

The postnatal development of the urea-synthesizing capacity was studied in 21 preterm infants with intrauterine growth retardation (IUGR) and compared with results found in 12 infants without IUGR as controls. The urea-synthesizing capacity was estimated by the ratio Q of 15N abundance of ammonia and urea in 6-hour urine samples collected after enteral administration of 3 mg [15N]H4Cl/kg body weight. The measurements were performed on the first day when a protein intake of 3.0-3.5 g/kg/day and an energy intake of 120 kcal/kg/day were tolerated (study day 1: postnatal 14-21 days) and on the day of discharge from the hospital (study day 2: postnatal age 39-56 days). The group of infants with IUGR was subdivided in one group of infants who developed catch-up growth (n = 12) and one group who did not demonstrate catch-up growth (n = 9). On study day 1, the Q values of the IUGR infants without catch-up growth were significantly higher than those of the IUGR infants with catch-up growth (13.4 +/- 2.3 vs. 9.2 +/- 2.2) or of the control infants without IUGR. During the time period from study day 1 to study day 2 the Q values of the IUGR infants with catch-up growth decreased significantly (9.2 +/- 2.2 vs. 4.8 +/- 2.0; p < 0.001) and were in the range of the control infants without IUGR. In contrast, the Q values of the IUGR infants without catch-up growth did not significantly change during the study period (13.4 +/- 2.3 vs. 11.3 +/- 2.8; p = 0.097). On both study days there was a significant correlation between the Q values and the degree of IUGR (study day 1: r = 0.652, p < 0.01; study day 2: r = 0.842, p < 0.001). The data indicate that the urea-synthesizing capacity of preterm infants increases during early postnatal life and that severe IUGR may impair this development. Metabolic investigations using urea as marker for evaluation of optimal quantity or quality of dietary proteins should carefully be interpreted when infants with severe IUGR are studied.

Child Development↗

Effect of increasing dietary threonine intakes on amino acid metabolism of the central nervous system and peripheral tissues in growing rats.

The threonine content of most of the infant formulas currently on the market is approximately 20% higher than the threonine concentration in human milk. Due to this high threonine content the plasma threonine concentrations are up to twice as high in premature infants fed these formulas than in infants fed human milk. To study the effect of different threonine intakes on plasma and tissue amino acid concentrations, 24 young male Wistar rats were fed three experimental diets based on a mixture of bovine proteins with a whey protein/casein ratio of 60/40 with different threonine contents [group A, 0.86 g of threonine/100 g (n = 8); group B, 1.03 g of threonine/100 g (n = 8); group C, 2.21 g of threonine/100 g (n = 8)]. Eight animals were fed a typical rat diet based on bovine casein as controls. After a feeding period of 15 d, amino acids were measured in plasma and in homogenates of the cerebral cortex, brain stem, liver, and muscle. There was a significant correlation between threonine intake and plasma threonine levels (r = 0.687, p < 0.001). The plasma threonine concentration correlated significantly with the threonine concentration in the cortex (r = 0.821, p < 0.01) and the brain stem (r = 0.882, p < 0.01). There was a positive significant correlation between threonine and glycine concentrations in the cortex (r = 0.673, p < 0.01), and the brain stem (r = 0.575, p < 0.01), whereas the glycine concentration decreased with increasing threonine intakes in the liver and muscle. The presented data indicate that increasing the threonine in plasma leads to increasing brain glycine and thereby affects the neurotransmitter balance in the brain. This may have consequences for brain development during early postnatal life. Therefore, excessive threonine intake during infant feeding should be avoided.

Amino Acids↗

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.

Acetamides↗

Docosahexaenoic and arachidonic acid absorption in preterm infants fed LCP-free or LCP-supplemented formula in comparison to infants fed fortified breast milk.

The absorption of long-chain polyunsaturated fatty acids (LCP) with particular respect to docosahexaenoic (DHA) and arachidonic acid (AA) has been studied in 39 very-low-birth-weight infants appropriate for gestational age after a 10-day feeding period. The infants were fed either a LCP-supplemented formula (n = 11), or a LCP-free formula (n = 11) or breast milk fortified with protein and carbohydrates to have similar protein and energy intakes as in the formula-fed infants (n = 17). Total fat content and fatty acid profile were measured in the human milk, the two formulas, and in the stool samples. After a 10-day feeding period, the fecal excretions of total fat, DHA and AA were measured during a 3-day balance period. The total fat apparent absorption rates were similar in all groups (84.1, 82.1 and 80.6% of intake, respectively). The DHA and AA intakes were significantly (p < 0.01) higher in the group fed the fortified breast milk than in the group fed the LCP-supplemented formula (DHA: 75.5 +/- 12.4 vs. 50.2 +/- 4.2 mg/72 h; AA: 45.5 +/- 5.8 vs. 30.2 +/- 2.7 mg/72 h). There was a tendency for lower apparent absorption rates for both LCPs studied in the group fed fortified breast milk when compared to the group fed LCP-supplemented formula (AA: 70.6 +/- 10.9 vs. 73.0 +/- 8.7% of intake, DHA: 69.0 +/- 10.6 vs. 74.2 +/- 9.5% of intakes, but the differences were not significant. As consequence of the different intakes, the net absorption of the two studied LCP fatty acids were significantly (p < 0.01) higher in the breast milk group than in the group fed the LCP-supplemented formula (DHA: 52.6 +/- 6.1 vs. 36.8 +/- 4.5 mg/72 h; AA: 31.4 +/- 3.1 vs. 22.4 +/- 2.3 mg/72 h). The data demonstrate that DHA and AA are absorbed from the studied LCP-supplemented formula at least as effectively as from human milk. The net absorption of these LCP depend on the amount of dietary intake, and seems to be influenced by the dietary LCP source.

Arachidonic Acid↗

Bile acid concentrations in serum and duodenal aspirates of healthy preterm infants: effects of gestational and postnatal age.

In 41 healthy human-milk-fed preterm infants the preprandial total bile acid (BA) concentrations in serum and duodenal juice were simultaneous measured during the first 60 days of life. The infants were subdivided into four groups according to their gestational age: 6 infants with a gestational age of 27 and 28 weeks, 7 infants with a gestational age of 29 and 30 weeks, 21 infants with a gestational age of 31 and 32 weeks and 7 infants with a gestational age of 33 and 34 weeks. The BA levels were enzymatically determined using 3-alpha-hydroxysteroid dehydrogenase. In the duodenal juice, cholic acid (CA), chenodeoxycholic acid (CDCA), deoxycholic acid and lithocholic acid were separately quantified by thin-layer chromatography. During the first month of life, the serum BA concentrations increased significantly with postnatal age (p < 0.01) but remained nearly constant during the second month of life. In the duodenal aspirates, the BA concentrations increased continuously up to the end of the observations period (p < 0.001). In the duodenal aspirates, the CA/CDCA ratio was high immediately after birth and decreased significantly with increasing postnatal age (p < 0.001). During the first weeks of life, the BA levels were preferentially conjugated with taurine, but in spite of the taurine-rich diet during the whole observation period the taurine/glycine ratio decreased with postnatal age (p < 0.001). In all samples of duodenal juice, the sum of primary BA was > 98% of total 3-alpha-hydroxy-BA. These data indicate that the establishment of an intestinal microbial flora necessary for intestinal BA transformation and the development of the enterohepatic BA circulation lasts some months of postnatal life. The serum BA concentration reflects hepatic synthesis, intestinal absorption, renal excretion and hepatocellular transport into bile in a very complex way which may limit the diagnostic value of serum BA during this time. Additionally, a duodenal BA concentration below 4 mmol/l, as found in this study during the first 2 weeks of life, may be of clinical importance due to its possible effects on fat absorption.

Aging↗

Docosahexaenoic and arachidonic acid content of serum and red blood cell membrane phospholipids of preterm infants fed breast milk, standard formula or formula supplemented with n-3 and n-6 long-chain polyunsaturated fatty acids.

UNLABELLED: The contents of docosahexaenoic (DHA) and arachidonic acid (AA) of plasma and red blood cell membrane phospholipids were studied in 41 very low birth weight infants fed either breast milk (n = 18), a standard formula without long-chain polyunsaturated fatty acids with 20 or 22 carbon atoms (LCP) but with alpha-linolenic acid and linoleic acid (n = 11) or a formula additionally supplemented with n-3 and n-6 LCP in relations typical for human milk (n = 12) after 2, 6, and 10 weeks of feeding. The content of DHA and AA in plasma phospholipids declined in the infants fed the LCP-free formula but remained more or less constant during the whole feeding period in those infants fed breast milk as well as in those fed the LCP-supplemented formula. The differences between the group fed the LCP-free standard formula and the two groups fed LCP-containing diets became significant during the first 2 weeks of feeding. In contrast, there were no differences between the group fed breast milk and the group fed the supplemented formula during the study period. Similar effects could be observed regarding the composition of red blood cell membrane phospholipids, but the differences between the infants fed the LCP-free standard formula and the two other groups with LCP-containing diets were significant only for AA. The data indicate that very low birth weight infants are unable to synthesize LCP from alpha-linolenic acid and linoleic acid in sufficient amounts to prevent a decline of LCP in plasma and red blood cell phospholipids. Additionally, the data show, that supplementation of formulas with n-3 and n-6 LCP in amounts typical for human milk fat results in similar fatty acid profiles of plasma and red blood cell membrane phospholipids as found during breast milk feeding. CONCLUSION: Supplementation of formula with long-chain polyunsaturated fatty acids improves the LCP status of very low birth weight infants.

Arachidonic Acids↗

Limited fat digestion in infants with bronchopulmonary dysplasia.

In 10 hyaline membrane disease patients with development of bronchopulmonary dysplasia, 16 hyaline membrane disease patients without development of bronchopulmonary dysplasia, and 12 very-low-birthweight infants without major medical problems, we measured the lipase and trypsin activity as well as the bile acids concentrations in preprandially aspirated duodenal juice. In addition, fat and nitrogen balances were performed during the 5th and 6th weeks of postnatal life. The mean duodenal lipase activity in the patients with bronchopulmonary dysplasia was significantly lower than those of the patients without bronchopulmonary dysplasia (4.41 +/- 3.0 versus 9.95 +/- 3.0 U/ml, p < 0.05) and of the controls (19.94 +/- 6.8 U/ml). The mean total bile acid concentration was below the critical micellar concentration of 4 mmol/L only in the patients with bronchopulmonary dysplasia. The fecal fat excretion rate in the patients with bronchopulmonary dysplasia was significantly higher than in the patients without bronchopulmonary dysplasia (21.4 +/- 4.6% versus 11.3 +/- 3.4% of intake, p < 0.01) as well as that of the controls (7.9 +/- 2.8% of intake). The serum urea concentrations were similar in the patients without bronchopulmonary dysplasia and in the controls (1.97 +/- 0.6 and 1.89 +/- 0.4 mmol/L, respectively) but significantly higher in the patients with bronchopulmonary dysplasia (2.54 +/- 0.5 mmol/L). The lowest weight gain was found in the patients with bronchopulmonary dysplasia (8.2 +/- 4.7 g/kg/day). It was significantly lower than one of the patients without bronchopulmonary dysplasia or the controls (13.5 +/- 4.0 and 16.2 +/- 3.7 g/kg/day, respectively). The data indicate that patients who develop bronchopulmonary dysplasia have a limited fat absorption, which may help to explain the inadequate weight gain.

Bile Acids and Salts↗

Taurine supplementation prevents hyperaminoacidemia in growing term infants fed high-protein cow's milk formula.

Blood urea nitrogen (BUN) and plasma and urine amino acid concentrations were compared between three cohorts of healthy growing term infants who were breast-fed (BF) or randomly assigned to one of two formulas either taurine non-supplemented (FF) or taurine supplemented (FF + T). The infants were studied from 2 to 12 weeks of age. Weight gain and growth in length was normal and similar in all three feeding groups during the study interval. At 12 weeks BUN was significantly higher in the FF group than in the BF and FF + T groups, 16.5 mg/dl vs 7.0 and 7.3 mg/dl, respectively. Total plasma amino acids (FF group: 240.5 +/- 110.1 mumoles/dl; BF group 180.1 +/- 28.7 mumoles/dl; FF + T group: 182.3 +/- 89.4 mumoles/dl) and total essential amino acids (FF group: 89.8 +/- 37.3 mumoles/dl; BF group: 56.1 +/- 16.3 mumoles/dl; FF + T group: 53.0 +/- 24.2 mumoles/dl). The urine amino acid concentrations reflected the plasma levels in all groups. These results indicate that taurine supplementation to a high protein formula lowers BUN levels and the plasma urine amino acid concentrations by some yet unknown mechanism to concentrations similar to those found in breast-fed infants with a much lower protein intake.

Amino Acids↗

Activities of trypsin and lipase in duodenal aspirates of preterm infants: influence of dietary protein and fat composition.

The influence of three different feeding regimens on the activities of pancreatic lipase and trypsin in duodenal aspirates and on fecal nitrogen and fat excretion was studied in 35 healthy preterm infants after a 2-wk feeding period. Eleven infants received a standard preterm formula (without long-chain polyunsaturated fatty acids), 12 were fed with an experimental formula that only differed from the standard formula in fat blend composition (with long-chain polyunsaturated fatty acids), and 12 infants received human milk fortified with protein and energy to have similar nitrogen and energy contents as the two formulas. There were no significant differences in duodenal trypsin activities among the groups. In the group fed the standard formula, lipase activity was significantly lower than in the group fed the experimental formula (standard formula group: 8.4 +/- 3.5 kU/L; experimental formula group: 13.8 +/- 4.8 kU/L; P < 0.05) but there was no significant difference between the experimental formula group and the human milk group (15.1 +/- 4.2 kU/L). Fecal nitrogen as well as fat excretion were similar in the three feeding groups. The data suggest that dietary fat composition can influence the postnatal development of duodenal lipase activity in preterm infants.

Dietary Fats↗

Fecal cholesterol excretion in preterm infants fed breast milk or formula with different cholesterol contents.

In 44 very low-birth-weight infants, fecal cholesterol excretion was measured and in 29 other infants serum total cholesterol concentrations in response to different cholesterol intakes were studied. The infants received fortified breast milk (mean cholesterol content 15.3 mg/dl) or were fed either a standard preterm formula (cholesterol content 5.5 mg/dl) or the same formula but with a modified lipid composition (long chain polyunsaturated fatty acid concentration closely related to breast milk fat) and 30 mg of cholesterol/dl. In the group fed the high cholesterol formula, fecal cholesterol excretion was significantly higher (35.5 mmol/kg/day) than in the groups fed breast milk or the standard formula (20.1 and 18.2 mmol/kg/day). Cholesterol balance in the group fed the high cholesterol formula (21.8 mg/kg/day) was significantly higher than in the group fed breast milk (+8.6 mg/kg/day). In the infants fed the low cholesterol formula the balance was negative (-7.7 mg/kg/day). Serum concentrations of total cholesterol were similar in the groups fed breast milk or the high cholesterol formula (3.47 and 3.51 mmol/l), but significantly higher than in the group fed the low cholesterol formula (3.15 mmol/l). The data suggest that preterm infants are able to regulate a higher cholesterol intake than during breast feeding by increasing fecal cholesterol excretion as well as decreasing endogenous synthesis.

Age Factors↗

Activities of trypsin and lipase in duodenal aspirates of healthy preterm infants: effects of gestational and postnatal age.

Lipase and trypsin activities were estimated in preprandially aspirated duodenal juice of preterm infants with gestational ages between 29 and 32 weeks (group I, n = 33) or between 33 and 36 weeks (group II, n = 22) during the first 6 weeks of postnatal life. The results were compared with the enzyme activities measured in 2- to 6-year-old children. There were no significant differences of the mean lipase or trypsin activities between the two groups lipase; group I 13.7 +/- 7.9, group II 15.9 +/- 9.8 U/ml; trypsin: group I 7.9 +/- 4.7, group II 8.5 +/- 5.1 U/ml). The activities of both enzymes increased significantly and similarly in both groups with postnatal age (lipase: group I r = 0.732, p < 0.01, group II r = 0.743, p < 0.01; trypsin: group I r = 0.705, p < 0.01, group II r = 0.669, p < 0.01). At the end of the study the lipase activities of both groups reached approximately 35% of the values found in the older children, whereas the trypsin activities reached the reference values within the 1st month of life. The results indicate an asynchronously age-related development of lipase and trypsin. The development of the lipase activity is delayed in comparison to the trypsin activity which should be considered in the nutritional management of preterm infants.

Aging↗

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.

Acetamides↗