Starch digestion in infancy.
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Digestion↗
Biomedical subjects
L T Weaver
Publications and source records attributed to L T Weaver.
13C and H2 breath tests to study extent and site of starch digestion in children with cystic fibrosis.
BACKGROUND: Starch is an important source of energy for children with cystic fibrosis, but little is known about their capacity to digest it. METHODS: A 13C breath test was used to measure starch digestion and oxidation in 16 children with cystic fibrosis (median [range] age, 7.9 [4-15] years; 7 girls, 9 boys) and 5 normal healthy control subjects (median age, 8.3 [7-13] years; 3 girls, 2 boys). A test meal of 13C flour and lactulose was consumed and breath samples were obtained half-hourly thereafter for 6 hours to measure 13C enrichment by isotope ratio mass spectrometry and H2 by electrochemistry. The test was repeated on 10 children with cystic fibrosis when they were taking pancreatic supplements. RESULTS: The median (range) cumulative percentage 13C dose recovery (cPDR), was 35% (18-52%) in control subjects, 18% (9-33%) in children with cystic fibrosis without enzymes, and 29% (22-51%) in those with pancreatic supplements. cPDR differed significantly between healthy control subjects and children with cystic fibrosis without enzymes (p = 0.01) and between children with cystic fibrosis with and without enzymes (p < 0.0001), but there was no difference between control subjects and children with cystic fibrosis taking enzymes (p = 0.5). Eight children with cystic fibrosis had a cPDR within control range, and in six there was a second peak in 13CO2 enrichment coincident with an increase in H2. CONCLUSIONS: Starch digestion and oxidation are diminished in children with cystic fibrosis, but pancreatic enzymes restored them to near normal levels. A second peak in 13CO2 enrichment, suggestive of colonic starch fermentation was absent in healthy children, but present in some children with cystic fibrosis and abolished by pancreatic enzymes.
Adolescent↗
Development of fat digestion in infancy.
AIM: To measure the development of fat digestion in early life, using a stable isotope breath test. METHODS: A combined longitudinal and cross sectional study was performed on 30 term and preterm infants using 13C-labelled mixed triglyceride (MTG). Seventy six tests were performed in all. Results were expressed as cumulative percentage dose recovered over 6 hours (cPDR). RESULTS: Eighteen of 34 tests performed on infants under 30 days of age showed cPDRs below the normal range for adults and older children. The remainder of tests, performed on infants over 57 days of age, all showed cPDRs within the normal range. Peak PDR correlated significantly (r = 0. 928, p<0.01) with cPDR. CONCLUSION: The capacity to digest fat is incomplete at birth, but quickly develops to normal levels during the first months of life. The MTG breath test is a useful non-invasive method to measure the development of fat digestion in early life.
Breath Tests↗
Helicobacter pylori colonization in early life.
Helicobacter pylori infection is a major cause of upper gastrointestinal disease throughout the world. Colonization begins in childhood, although little is known about its age of onset, rate, or mode of colonization. Our aim was to identify the age of acquisition of H. pylori colonization in Gambian children. A cohort of 248 Gambian children aged 3 to 45 months was studied at intervals of 3 months for 2 years, using the 13C-urea breath test, specific IgM and specific IgG serology. The prevalence of positive breath tests rose from 19% at 3 months of age to 84% by age 30 months. Elevated specific IgG and IgM antibody levels were associated with positive breath tests, although there was discrepancy between breath test results and serology, particularly IgG serology, during the 1st year of life. Neither IgG nor IgM serology could be validated as reliable diagnostic tools for infant H. pylori colonization compared with the 13C-urea breath test. Reversion to negative breath test, in association with declining specific antibody levels, occurred in 48/248 (20%) of children. On the assumption that the 13C-urea breath test is a reliable index of H. pylori colonization, we conclude that the infection is extremely common from an early age in Gambian children. Transient colonization may occur. Previous studies relying on serodiagnosis may have significantly underestimated the true early prevalence of colonization in the developing world, where the target age for intervention studies is probably early infancy.
Antibodies, Bacterial↗
Interpreting the 13C-urea breath test among a large population of young children from a developing country.
The 13C-urea breath test is a noninvasive tool for the diagnosis of gastric Helicobacter pylori infection. However, it has not been validated in young children from the developing world, where infection is very common. 13C urea breath tests were performed on 1532 occasions on 247 Gambian infants and children aged from 3 to 48 mo. The means and variances of the separate sub-populations of 13C enrichment results contained within the overall dataset were estimated by a Genstat procedure using the EM algorithm, thereby identifying a cut-off value to discriminate positive from negative results. To illustrate the appropriateness of this calculated cut-off value, 13C urea breath tests were performed upon a small group of 14 patients aged 6 to 28 mo undergoing diagnostic upper endoscopy. Fixed gastric antral biopsies were examined to identify H. pylori. Two subpopulations were identified within the large dataset. A cut-off value of 5.47 delta per thousand relative to Pee Dee Belemnite limestone above baseline at 30 min identified 95% of the normally distributed negative sub-population and 99.4% of the log normal distributed positive sub-population. Comparison with endoscopic data confirmed that this cut-off value was appropriate for this population, as 7/7 children without H. pylori on their gastric biopsies had negative urea breath tests, and 6/7 children with gastric H. pylori colonization had positive urea breath tests. These findings confirm the value of the urea breath test as a diagnostic tool in young children from developing countries. They also offer a way to calculate the most appropriate cut-off value for use in different populations and the likelihood that it will correctly assign any value into the appropriate sub-population, without the need for endoscopy.
Breath Tests↗
Inflammatory bowel disease in Scottish children.
Most children with inflammatory bowel disease (IBD) require specialist care in a tertiary medical centre. The records of 105 children with IBD who presented to the Royal Hospital for Sick Children, Glasgow between 1976 and 1995 were studied retrospectively. Fifty seven children and Crohn's disease (CD) (median age of presentation 7.9 years) and 48 had ulcerative colitis (UC) (median age of presentation 8.7 years). The number with CD doubled in the decade 1986-95 compared to 1975-85. 23% with CD and 13% with UC developed symptoms before the age of five years. Median time to diagnosis from symptom onset was 45.8 weeks for CD and 12.7 weeks for UC. Histological diagnosis was obtained in all children. The mainstay of treatment was aminosalicylates, and few children underwent surgery (CD 26%, UC 10%). Thirty percent with CD and 23% with UC had no relapses in the study period, and only one child with UC died. Growth was poorly recorded. The majority of children with CD and over 50% with UC had a height-for-age Z score below zero.
Body Height↗
Analysis of tert.-butyldimethylsilyl [1-13C]palmitic acid in stool samples by gas chromatography-mass spectrometry with electron impact ionisation: comparison with combustion isotope-ratio mass spectrometry.
The use of 13C-labelled compounds to study lipid metabolism is increasing. Typically less than 40% of the orally administered label is recovered in breath CO2. The remainder must be either absorbed and not oxidised or not absorbed and remain in the faeces. Two methods of determining how much tracer passes through the body, and is present in the stool, were compared. Compound specific analysis of tert.-butyldimethylsilyl [13C]hexadecanoic acid by gas chromatography-mass spectrometry (GC-MS) with electron impact ionisation was compared with bulk analysis of whole stool and lipid extract by continuous flow isotope ratio mass spectrometry (CF-IRMS) with a combustion interface. The mean difference between the IRMS and GC-MS methods was -0.02 mmol 13C d(-1) with a mean excretion of 14.2 mmol 13C d(-1). Combustion IRMS is both simpler and cheaper, when the objective is to determine how much administered dose appears in stool, and information about the form of the label is not required.
Adult↗
Stable isotope breath tests.
There is a need for non-invasive tests of gastrointestinal and nutritional function. Clinical problems peculiar to infancy and childhood require prompt diagnosis, and methods that are invasive or involve the use of radioisotopes are often impractical or ethically unacceptable. What the pediatrician and clinical scientist seek are tests that are simple, repeatable, and unequivocal in their result for diagnosis, to assess the effects of treatment, and to measure the development of gastrointestinal function during early life. Stable isotope breath tests offer a ready and attractive answer to these needs. They involve the ingestion of substrates labeled with the non-radioactive isotope of carbon (13C), followed by the collection of serial breath samples for analysis of the enrichment of 13CO2, the end product of substrate metabolism. Their non-invasive nature recommends them for use in infancy and childhood, and they can be performed in the ward, clinic, laboratory, and home. In this article I discuss to what degree stable isotope breath tests fulfill the pediatrician's and scientist's needs. I have chosen two examples from the work of myself and my colleagues to illustrate the principles and use of 13C breath tests to detect Helicobacter pylori infection and to measure fat digestion in infancy and childhood.
Adolescent↗
Lactose [13C]Ureide as a marker for colonic fermentation and the deconvolution of a complex 13CO2 breath test curve.
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Breath Tests↗
Importance of measuring CO2-production rate when using 13C-breath tests to measure fat digestion.
Stable isotope breath tests offer a safe, repeatable non-invasive method of measuring fat digestion. They involve the ingestion of a substrate labelled with 13C followed by serial measurements of the 13C:12C ratio in expired CO2, from which the percentage of the 13C dose recovered (PDR) can be calculated. However PDR depends on the CO2-production rate. Our aim was to compare results obtained using directly measured CO2-production rates with those calculated from two predicted values. Twelve normal healthy children and twenty-four children with cystic fibrosis (CF) (without or with the normal dose of enzyme supplementation) were studied with 1,3-distearyl, 2[carboxyl-13C] octanoyl glycerol. The volume of CO2 produced (litres/min) was measured at rest for 30 min approximately 3 h after substrate ingestion, and the results were converted to mmol/min. For each subject the expected BMR was calculated from the equation of Schofield (1985), based on sex, age, weight and height, and from these values, CO2-production rate was derived. Surface area was calculated and an estimated value of 5 mmol/m2 per min (Shreeve et al. 1970) was used. Using these three CO2-production rates, three different PDR were calculated and compared. In healthy children there was a close concordance between measured and predicted CO2-production rates, but children with CF had a mean measured CO2-production rate 39% higher than normal children. This use of normal data for predicted CO2-production rates in children with CF underestimates cumulative PDR. If direct measurements of CO2-production rate are not available or impossible to perform the VCO2 obtained from the BMR calculated using the equations of Schofield (1985) or Shreeve et al. (1970) can be used in normal children. However, if accurate results for PDR are to be obtained, CO2-production rates should be measured when performing breath tests in conditions where energy expenditure and/or CO2-production rate are not expected to be normal.
Breath Tests↗
Bile salt-stimulated lipase and digestion of non-breast milk fat.
BACKGROUND: 13 Carbon (13C)-lipid breath tests are an effective, noninvasive way of repeatedly measuring fat digestion. The purpose of this study was to assess the contribution of bile salt-stimulated lipase (BSSL) in human milk to the digestion of non-breast-milk fat in Gambian infants. METHODS: Twelve Gambian infants (aged 3-8 months) were studied on 4 days. 13C-Trioctanoin (7.5 mg/kg, digested by BSSL preduodenal and pancreatic lipases) and 13C-cholesteryl octanoate (25 mg/kg, digested by BSSL and pancreatic lipases) were used as substrates. The percentage dose recovery (PDR) of 13C in breath during 5 hours was compared after ingestion of each substrate with fresh, expressed breast milk (FBM) or heated, expressed breast milk (HBM). Gas isotope ratio-mass spectrometry was used to measure 13C enrichment, and breast milk samples were analysed for esterase activity. RESULTS: Heating breast milk significantly decreased esterase activity (mean +/- SD values: FBM = 12.2 +/- 2.9 IU/ml; HBM = 0.5 +/- 0.3 IU/ml), and there was no difference in the volumes of milk ingested on each test day (approximately 50 ml). The PDR of 13C was comparable to that previously described in healthy English infants and was not increased by BSSL. The mean +/- SD PDR of 13C from trioctanoin was 36.3 +/- 8.4% for FBM and 34.6 +/- 6.3% for HBM (NS). From cholesteryl octanoate, the mean +/- SD PDR of 13C was 24.3 +/- 8.7% for FBM and 27.1 +/- 7.5% for HBM (NS). CONCLUSIONS: Bile salt-stimulated lipase may enhance fat digestion in younger or malnourished infants who have a greater degree of pancreatic enzyme deficiency. However, this study suggests that it does not increase the digestion of non-breast-milk fat in healthy, well-nourished infants aged 3 to 8 months from an underprivileged background, who typically ingest frequent small quantities of breast milk.
Caprylates↗
Helicobacter pylori infection, gastric acid secretion, and infant growth.
BACKGROUND: Helicobacter pylori infection is very common in Gambian infants and children, who are also at risk of chronic diarrhoea and undernutrition. Acute H. pylori infection is associated with depressed gastric acid secretion, and loss of the gastric acid barrier may predispose to enteric infections. METHODS: In a prospective study a noninvasive test of gastric acid output (measurement of change in urine acid output before and after a feed) was performed on a population of Gambian infants at high risk of H. pylori infection. The 13C urea breath tests was used to measure the prevalence of H. pylori infection and growth was measured by serial anthropometry. RESULTS: In 101 infants aged 3 to 12 months, there was a significant relation between H. pylori infection and depressed urine acid output in those aged 6 months, during weaning when growth failure and malnutrition begin. Those infants with sustained H. pylori infection grew less well than those without. CONCLUSIONS: We speculate that H. pylori, acquired in infancy, could be a "key that opens the door" to enteric infection in childhood, leading to recurrent diarrhoea, malnutrition, and growth failure.
Breath Tests↗
Effects of protein restriction in early life on growth and function of the gastrointestinal tract of the rat.
BACKGROUND: Undernutrition during early life may have both immediate and later consequences. This study was undertaken to measure the long-term effects of perinatal undernutrition on the growth and function of the gastrointestinal tract. METHODS: Pregnant rats were assigned to one of four groups that received isocaloric diets restricted in protein during pregnancy or lactation and during both or neither. Thereafter, their pups were followed until aged 1 year. RESULTS: At 21 days the body weights of the young of those born of dams with postnatal protein restriction were halved, with comparable reductions in the weights of the stomach and caecum, compared with those of control animals. The lengths of the small and large intestines and mucosal weights of the foregut were also significantly reduced. Lactase activities were significantly increased and sucrase and maltase activities significantly reduced. By 42 days all the effects were less marked, and at 1 year the dimensions of the organs of the gastrointestinal tract and the composition and enzyme levels of the mucosa were all insignificantly different relative to body weight. CONCLUSIONS: Prenatal protein restriction alone had no significant long-term negative effects on body weight, growth, or mucosal hydrolase activity of the gastrointestinal tract. Postnatal protein restriction had a marked effect on these indices in early life and delayed the changes in mucosal hydrolases usually seen at weaning. In contrast with other organs and their functions, long-term growth of the gut and activity of small intestinal hydrolases are preserved in the face of perinatal protein restriction.
Animals↗
Human milk IgA concentrations during the first year of lactation.
AIMS: To measure the concentrations of total IgA in the milk secreted by both breasts, throughout the first year of lactation, in a cohort of Gambian mothers of infants at high risk of infection. SUBJECTS AND METHODS: Sixty five women and their infants were studied monthly from the 4th to 52nd postpartum week. Samples of milk were obtained from each breast by manual expression immediately before the infant was suckled. Milk intakes were measured by test weighing the infants before and after feeds over 12 hour periods; IgA concentrations were determined by enzyme linked immunosorbent assay. RESULTS: A total of 1590 milk samples was measured. The median (interquartile range) concentration of IgA for all samples was 0.708 (0.422-1.105) g/l; that in milk obtained from the left breast was 0.785 (0.458-1.247) g/l, and that in milk obtained from the right breast was 0.645 (0.388-1.011) g/l (p < 0.0001). There was no significant change in milk or IgA intakes with advancing infant age, but there was a close concordance of IgA concentrations between the two breasts, with "tracking" of the output of the left and right breasts. There was a significant (p < 0.01) negative correlation between maternal age and parity, and weight of milk ingested by infants. During the dry season (December to May) the median (interquartile range) IgA concentration was significantly higher at 0.853 (0.571-1.254) g/l than during the rainy season (June to November), when it was 0.518 (0.311-0.909) g/l (p < 0.0001). CONCLUSIONS: Sustained IgA secretion is likely to protect suckling infants from microbial infection.
Aging↗
13C mixed triglyceride breath test.
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Adult↗
Effects on birth weight and perinatal mortality of maternal dietary supplements in rural Gambia: 5 year randomised controlled trial .
OBJECTIVE: To test the efficacy in terms of birth weight and infant survival of a diet supplement programme in pregnant African women through a primary healthcare system. DESIGN: 5 year controlled trial of all pregnant women in 28 villages randomised to daily supplementation with high energy groundnut biscuits (4.3 MJ/day) for about 20 weeks before delivery (intervention) or after delivery (control). SETTING: Rural Gambia. SUBJECTS: Chronically undernourished women (twin bearers excluded), yielding 2047 singleton live births and 35 stillbirths. MAIN OUTCOME MEASURES: Birth weight; prevalence of low birth weight (< 2500 g); head circumference; birth length; gestational age; prevalence of stillbirths; neonatal and postneonatal mortality. RESULTS: Supplementation increased weight gain in pregnancy and significantly increased birth weight, particularly during the nutritionally debilitating hungry season (June to October). Weight gain increased by 201 g (P < 0.001) in the hungry season, by 94 g (P < 0.01) in the harvest season (November to May), and by 136 g (P < 0.001) over the whole year. The odds ratio for low birthweight babies in supplemented women was 0.61 (95% confidence interval 0.47 to 0.79, P < 0.001). Head circumference was significantly increased (P < 0.01), but by only 3.1 mm. Birth length and duration of gestation were not affected. Supplementation significantly reduced perinatal mortality: the odds ratio was 0.47 (0.23 to 0.99, P < 0.05) for stillbirths and 0.54 (0.35 to 0.85, P < 0.01) for all deaths in first week of life. Mortality after 7 days was unaffected. CONCLUSION: Prenatal dietary supplementation reduced retardation in intrauterine growth when effectively targeted at genuinely at-risk mothers. This was associated with a substantial reduction in the prevalence of stillbirths and in early neonatal mortality. The intervention can be successfully delivered through a primary healthcare system.
Birth Weight↗
The fate of fat in the infant's colon.
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Bacteria↗
Malnutrition in children with cystic fibrosis: the energy-balance equation.
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Adolescent↗