[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.

[Rate of intrauterine growth retardation at the Leipzig Perinatal Center comparing the years 1982 to 1984 with 1987 to 1989]. / Hypotrophen-Rate am Leipziger Perinatalzentrum im Vergleich der Jahre 1982 bis 1984 und 1987 bis 1989.

Referring to the number of all live-born children, hypotrophic newborn (IUGR) were classified at the Centre for Perinatal Care in Leipzig into two periods of time. Based on the 5th Kyank-percentile 6.5% hypotrophic newborn were classified into period A (1982-1984) and 5.0% hypotrophic newborn were classified in period B (1987-1989). The proportion of hypotrophic newborn with a birth weight < 2500 g amounted to one quarter of all infants (except multiple birth) with low birth weight in period A and to one fifth (20.7%) in period B. The decrease in the rate of hypotrophy in these infants affected nearly exclusively the mature ones. The number of infants with extreme intra-uterine growth retardation amounted to 29% (99 in 329) in period A and to 24% (58 in 238) in period B. The rate of hypotrophy in stillbirths decreased from 44% to 33%. In this process the proportion of extremely hypotrophic stillbirths amounted to 47% in period A, whereas it decreased to only 26% in period B.

[Determination of exocrine pancreatic function in childhood with the pancreozymin-secretin test]. / Bestimmung der exokrinen Pankreasfunktion im Kindesalter mit dem Pankreozymin-Sekretin-Test.

Pancreatic function can only be determined exactly via the pancreozymin-secretin test. We conducted this test in two versions: (1) under conditions of continuous perfusion with the possibility of volume correction and (2) as a simple tubing. We compared the results of 86 tubings with the results of 87 examinations under perfusion. For that purpose all patients were classified into four groups: group a) with 46 and 10 examinations, respectively, in patients suffering from cholestasis in early infancy, group b) with 7 and 12 examinations, respectively, in older patients with liver diseases, group c) with 8 and 17 examinations, respectively, in patients suffering from cystic fibrosis or Shwachman's syndrome and group d) with 25 and 48 examinations, respectively, in children with normal pancreatic function. Both examination methods nearly identical mean values of the enzyme activities in all four patient groups. However, mean variations were found to be higher in case of tubing. Therefore the lower limits (x - 2s) of this test were defined at a lower level than those of the tests under perfusion.

[Failure to thrive in young children--disorders of carbohydrate absorption?]. / Gedeihstörungen bei Kleinkindern--Störungen der Kohlehydratresorption?

We examined 31 formerly hypotrophic newborn children (birth weight < 5th Kyank percentile) with failure to grow in infancy (weight < 3th Prader percentile). The rates of digestion and absorption of carbohydrates were determined by segmental perfusion of the small intestine and compared to the results of 21 patients with florid coeliac disease. Despite the normal structure of the mucous membrane of the small intestine, the rates of absorption of glucose in 14 formerly hypotrophic children and, additionally, in 12 and 10 of these children, respectively, the rates of hydrolysis of lactose and sucrose were nearly as low as in patients with florid coeliac disease. The reduced absorption and digestion of carbohydrates, respectively, could be a cause of subsequent failure to grow in some of the hypotrophic newborn children.

[Development of body weight and height of small-for-gestational-age infants in relation to the degree of intrauterine retardation]. / Gewichts- und Längenentwicklung ehemals hypotroph geborener Kinder in Abhängigkeit vom Schweregrad der intrauterinen Retardierung.

The increase of weight of 238 hypotrophic and 31 eutrophic newborns is analyzed and assigned to 4 clusters in the course of their first 21 months. It is compared with body weight curves by Prader. Cluster 1 Increase in weight about the 50th percentile Cluster 2 Increase in weight between the 50th and 3rd percentile Cluster 3 Increase in weight just below the 3rd percentile Cluster 4 Increase in weight clearly below the 3rd percentile More than a half of all hypotrophic newborns had a body weight below the 3rd percentile by Prader (cluster 3 and 4) on attaining the age of 21 months. The appearance of hypotrophy in the newborns is subdivided into 4 groups by means of gestational age and relative birthweight: Group 1 eutrophic and moderate hypotrophic (n = 77) Group 2 premature and moderate hypotrophic (n = 46) Group 3 eutrophic and distinct hypotrophic (n = 62) Group 4 premature and distinct hypotrophic (n = 53) We found that the increase of weight correspond to cluster 4 in 4% of group 1, in 22% of group 2, in 32% of group 3, and in 43% of group 4. At last the increase of body weight is hard influenced in the first 3 years of life by hypotrophy and degrees of maturity of the newborns.

[Comparative studies of the activity of disaccharidases in the mucosa of the small intestines in dystrophic, formerly hypotrophic-born young children and of patients with flat mucosa of various etiology]. / Vergleichende Untersuchungen über die Aktivitäten von Disaccharidasen in der Dünndarmschleimhaut von dystrophen, ehemals hypotroph geborenen Kleinkindern und von Patienten mit flacher Mucosa unterschiedlicher Genese.

The disaccharidase activities of the mucous membrane of the small intestine were determined in formerly hypotrophic children who showing a dystrophy with a morphological normal mucosa (n = 36), patients with a flat mucosa caused by enteral protein intolerances of different genesis (n = 27), patients with a morphologically and functionally normal mucosa (n = 51). In about half of the former small-for-date children were shown activities lower than the simple standard deviation of the normal value, for lactase n = 17, for sucrase n = 14, for maltase n = 12. Some children showed pathologically reduced activities even below the double standard deviation for the normal value: lactase n = 8, sucrase n = 5, maltase n = 3.

Postnatal development of urea- and ammonia-excretion in urine of very-low-birth-weight infants small for gestational age.

In 12 very-low-birth-weight (VLBW) infants with intrauterine growth retardation and in 14 VLBW-infants appropriate for gestational age (AGA) fed a human milk (HM) formula (HM enriched with 6 g freeze dried HM per 100 ml) the renal excretion of urea and ammonia was studied on the 10th, 21st and 42nd days of life. The lowest excretion of urea was found in both groups on the 10th day of life. Up to the 42nd day of life the excretion raised significantly more in the AGA- than in the small for gestational age (SGA)-infants. In contrast to the urea excretion the excretion of ammonia was highest on the 10th day of life in both groups, but the excretion was significantly higher in the SGA-infants if compared to the AGA-infants. In the AGA-infants excretion of ammonia decreased with postnatal age whereas in the SGA-infants the high excretion remained up to the 42nd day of life. The data suggest that in VLBW-infants the urea synthesizing capacity is decreased and develops within the first weeks of postnatal life. The postnatal development is delayed in SGA-infants when compared to AGA-infants. The differences are more pronounced with increasing degree of intrauterine growth retardation.

[Care of patients with celiac disease in adolescence and young adulthood]. / Betreuung von Zöliakie-Patienten im Adoleszenten- und jungen Erwachsenenalter.

60 patients suffering from coeliac disease were continuously cared for during a longer period. In these patients the diagnosis was established on the basis of the commonly used ESPGAN criteria in their childhood. Another biopsy was performed in adolescence and early adulthood. In 26 patients the diagnosis coeliac disease was confirmed. These patients are recommended to carry on keeping to a strict diet. 4 patients show a normal mucosa (type I) while following normal nutrition for more than 2 up to 5 years in adulthood although in their childhood the diagnosis of coeliac disease was established. While being put an a diet or following a short lasting normal nutrition, respectively, 17 patients have a morphologically intact mucosa of the small intestine, which is, however, in nearly all cases functionally damaged. In these patients the diagnosis is to be clarified definitely by means of a final biopsy of the small intestine after an at least 2-year-lasting exposition to gluten. 13 patients refused a biopsy in adulthood.

Protein supplementation of human milk for the nutrition of VLBW-infants: human milk protein vs. meat protein hydrolysate.

In 25 very low birth weight infants appropriate for gestational age the influences of different human milk (HM) preparations on weight gain, gross indices of nitrogen metabolism and energy balance were studied during the second month of postnatal life. HM was fortified either by HM-protein (HMP) or by an enzymatic meat protein hydrolysate (PH) to protein concentrations between 1.5 and 1.7 g/100 ml. The caloric densities of both HM preparations were similar between 62 and 68 kcal/100 ml. There were no differences in weight gain (MM + HMP: 18.6 +/- 3.4 g/kg/day; HM + PH: 16.5 +/- 4.1 g/kg/day), nitrogen retention (HM + HMP: 31.5 +/- 3.1 mmol/kg/day; HM + PH: 30.0 +/- 3.2 mmol/kg/day), and the preprandial estimated essential amino acid profiles between the both feeding groups. In contrast the serum concentrations of alpha-amino-nitrogen 60 minutes postprandially were elevated in the infants fed HM + PH in comparison to the infants fed HM + HMP. This high postprandial amino acid concentrations in serum in the group fed HM + PH were accompanied by increased bile acids concentrations in serum, higher renal amino acid excretion and increased fecal fat losses. The results suggest that due to the more rapid intestinal absorption of amino acids from PH than from HMP the concentrations of amino acids increase postprandially which results in a detectable increase of the newborn cholestasis in these infants. Nevertheless, the scale of these metabolic responses to feeding protein hydrolysates is small and without detectable influences on nitrogen retention or weight gain.

Relationship between urea and ammonium excretion in the urine of very-low-birth-weight infants appropriate for gestational age.

In 14 very-low-birth-weight infants appropriate for gestational age the serum concentrations of urea and the excretions of urea and ammonium in the urine were studied on the 10th, 21st, and 42nd day of postnatal life. All infants were fed with a human milk preparation (6 g human milk lyophilisate per 100 ml fresh human milk). The enteral feeding could be started on the first day of life so that protein intakes were not different on the three study days (2.94 vs. 2.98 vs 3.13 g/kg.d). The renal excretion of urea increased significantly from the 10th to the 42nd day of life (1.2 +/- 0.13 vs 2.1 +/- 0.24 mmol/kg.d) whereas the excretion of ammonium decreased during the same time (0.53 +/- 0.06 vs 0.29 +/- 0.05 mmol/kg.d). There was a significantly negative correlation between the excretion of urea and of ammonia on all study days. The weight gain was sufficient for the given protein intakes (18.9 +/- 3.4 g/kg.d). The results indicate a transient limited capacity of the urea synthesizing system in the liver of very-low-birth-weight infants during the first weeks of life which should be considered if metabolic responses to protein intake are studied and evaluated in these infants.

[Development and organization of breast milk collection centers in East Germany]. / Zur Entwicklung und Organisation der Frauenmilchsammelstellen in der Deutschen Demokratischen Republik.

Human milk banking has a longstanding tradition in the GDR. We report on the main data of a survey carried out in 1987, actualized in 1989. Whereas human milk banking was widespread during the 1950s, it reached it's lowest level in 1972. In 1988 the amount of collected milk was nearly 200,000 litres (60 milk banks). Thus, the supply met the demand approximately. The development of the human milk banks is characterized by an increase of the number of milk banks (mostly the banks are affiliated to a children's hospital) and the collecting capacity. Half of the milk banks carries out the collection on a daily basis. This makes it possible to provide fresh milk with it's clear-cut advantages, especially in immunological respect. Otherwise the milk is stored after boiling, freezing or pasteurization. The feeding of very low birth weight newborns with fresh human milk is steadily increasing with corresponding consequences for the quality control of donated milk and the management of milk banks.

Metabolic differences between AGA-and SGA-infants of very low birthweight. III. Influence of postnatal age.

Seven very low birthweight (VLBW) infants, small for gestational age (SGA), with moderate intrauterine growth retardation and 7 VLBW-infants, appropriate for gestational age (AGA), fed breast milk fortified with 6 g freeze-dried human milk per 100 ml were studied on the 8th, 21st and 42nd days of life. The protein intake on the study days varied between 2.68 and 3.61 g/kg/day in the SGA-and 2.69 and 3.75 g/kg/day in the AGA-infants. Serum concentrations of total bile acids (BA) and the renal excretion of total nitrogen (TN) as well as alpha-amino-nitrogen (AAN) were measured in all infants on each study day. On the 8th day of life a mean protein intake of 3.2 g/kg/day resulted in higher serum concentrations of BA as well as in a higher renal excretion of TN and AAN in the SGA-infants when compared to the AGA-infants. On the 21st day of life these differences were smaller and only the serum concentration of BA and the renal excretion of AAN were still significantly higher in the SGA-infants. On the 42nd day of life only serum concentrations of total BA were elevated in the SGA-infants when compared to that in the AGA-infants. The observed metabolic differences between moderately SGA-and AGA-infants related to protein and bile acid metabolism diminished during the first weeks of life. The present data suggest that when nutritional management of VLBW-infants is planned, differences in metabolic capacities must be considered and protein intake should be increased with caution and in accordance to the individual metabolic situation of the infants during the first weeks of life.

Effect of gliadin on the distribution of sucrase among different fractions of fetal chick intestine.

The effect of peptic-tryptic digested gliadin (PT-gliadin) on the increase in sucrase activity in different fractions of tissue cultured fetal chick duodenum was investigated and compared with that of monensin, a known perturbant of the Golgi complex. PT-gliadin diminished the rise in sucrase activity in the tissue homogenate, in a brush border fraction, and in the high speed supernatant, whereas the activity in a Ca2+-pelleted fraction including endoplasmic reticulum and Golgi apparatus was unaffected. In contrast, monensin caused a proportional inhibition of the increase in sucrase activity in all fractions examined. The findings might suggest that PT-gliadin is able to affect intracellular processing of sucrase with the site of attack being distal to that of monensin in the biogenesis of the enzyme. Whether the effect of PT-gliadin on fetal gut is relevant also for celiac intestine remains to be established.

Glucose-galactose malabsorption: demonstration of specific jejunal brush border membrane defect.

Jejunal brush border glucose transport was studied in a patient with glucose-galactose malabsorption and in controls, using jejunal brush border membrane vesicles (BBMV) prepared from conventional jejunal biopsies. Whereas BBMV from controls showed a seven-fold enhancement of D-glucose uptake in the presence of an inwardly directed sodium gradient compared with its absence, no such enhancement was seen in the patient's vesicles. In BBMV from the patient, initial D-glucose uptake under sodium gradient conditions was only 10% of the mean control value. In contrast, sodium/proton exchange in BBMV from the patient was intact. These data provide the first unequivocal evidence that the jejunal brush border membrane is the site of a specific defect in sodium dependent glucose transport in glucose-galactose malabsorption. Measurement of glucose uptake by BBMV may well be the optimal diagnostic technique in this disorder.

A carbon-13 breath test to characterize glucose absorption and utilization in children.

After the administration of a 5% glucose-water solution that contained tracer amounts of the stable nonradioactive isotope 13C, breath samples were collected from five children with congenital glucose-galactose malabsorption and five with severe small bowel villous atrophy and chronic diarrhea. The 13CO2 breath test curves of the children with the congenital malabsorption and chronic diarrhea were compared with each other and with those from three healthy children and four infants with severe malnutrition but no diarrhea. The breath test curves from the children with glucose-galactose malabsorption and from those with diarrhea were significantly different from those of the other two groups, a finding consistent with impairment of glucose absorption. The [13C]glucose breath test clearly identified the children with severe glucose malabsorption. Further studies are required to determine whether less severe cases of carbohydrate malabsorption also can be identified using the parameters described in our study.

Metabolic differences between AGA- and SGA-infants of very low birthweight. II. Relationship to protein intake.

The metabolic response to different levels of human milk protein intake was studied in 23 appropriate (AGA) and 19 small for gestational age (SGA) infants of very low birthweight (VLBW) on the eighth day of life. The infants received from birth, either fresh preterm human milk or human milk fortified with lyophilized human milk (6 g per 100 ml). Thus, the protein intake ranged from 1.98 to 3.28 g/kg/d in the AGA- and from 1.94 to 3.34 g/kg/d in the SGA-infants. Alpha-amino-nitrogen and bile acid concentrations in serum and total- as well as alpha-amino-nitrogen excretion in the urine were measured. When the protein intake was less than 2.5 g/kg/d no differences between the groups could be found in any of the parameters directly related to nitrogen metabolism, but a significantly higher concentration of bile acids in serum was found in the SGA-infants. On protein intakes of more than 2.5 g/kg/d the SGA-infants responded with higher alpha-amino-nitrogen as well as total bile acids concentrations in the serum and also with higher excretions of total- as well as alpha-amino-nitrogen in the urine when compared to the AGA-infants. The differences between the groups became more pronounced with an increasing protein intake. The data suggest that on the eighth day of life SGA-infants are more sensitive to an excessive protein intake than AGA-infants. Hepatocellular dysfunctions as a result of intrauterine growth retardation seems to be an important factor in this special metabolic situation. Bile acid concentration in the serum can be used as a good marker to detect this. The observed differences in the metabolic capacity to handle protein between AGA- and SGA-infants on the eighth day of life have to be considered in the nutritional management of VLBW-infants.

Evidence for functional immaturity of the ornithine-urea cycle in very-low-birth-weight infants.

In a randomized, prospective study the response of serum urea concentration to different protein intakes was studied in two groups of preterm infants with different gestational ages on the 8th and the 21st day of life. 16 very-low-birth-weight (VLBW) infants (GA: 29-31 weeks) and 17 low-birth-weight (LBW) infants (GA: 31-33 weeks) were fed either with fresh human milk or with fortified human milk. The protein intake varied between 2.1 and 3.3 g/kg/day. On the 8th day of life the VLBW infants did not respond to higher protein intakes by increased serum urea concentrations, although a clear correlation was found between protein intake and serum alpha-amino-nitrogen concentrations in these infants. The more mature LBW infants responded to a high protein intake by increased serum urea concentrations on the 8th day of life. On the 21st day of life protein intake correlated to both serum urea and alpha-amino-nitrogen concentrations in all infants studied. These findings are consistent with a somewhat limited capacity of the immature infant for expansion of urea production for some time after birth. This immaturity should be considered when metabolic responses to protein intake are studied and evaluated in such infants.

Metabolic differences between AGA- and SGA-infants of very low birthweight. I. Relationship to intrauterine growth retardation.

Metabolic response to human milk feeding was studied in 12 appropriate (AGA) and 12 small for gestational age (SGA) infants of very low birthweight (VLBW) on the eighth day of life. Protein intake ranged from 1.98 to 2.47 g/kg/day and caloric intake from 94 to 126 kcal/kg/day with no significant differences between the groups. Alpha-amino-nitrogen, the total bile acid concentration in serum and total- as well as alpha-amino-nitrogen excretion in the urine were estimated. The alpha-amino-nitrogen and the total bile acid concentration in serum increased with increasing degree of intrauterine growth retardation. Also renal total- and alpha-amino-nitrogen excretion increased significantly in relation to the degree of intrauterine growth retardation. Thus, despite a relatively low protein intake in severely growth retarded VLBW-infants, metabolic changes could be found similar to those observed in AGA-infants on high protein intakes. The data suggest that during the first weeks of postnatal life VLBW-infants with intrauterine growth retardation have a decreased capacity to utilize or to metabolize protein when compared to AGA-infants with comparable birthweights. These metabolic differences have to be considered in the nutritional management of VLBW-infants.