Rethinking growth failure in Alagille syndrome: the role of dietary intake and steatorrhea

OBJECTIVE: To characterize the energy and nutrient intake, and the degree of fat malabsorption in children with Alagille syndrome (AGS) and to examine their cross-sectional associations with growth and nutritional status. METHODS: Prepubertal children with AGS were evaluated for dietary intake, growth, bone age, and body composition. Children and their families collected a three-day, weighed diet record at home. Stools were collected for 72 hours and the coefficient of fat absorption (COA) was determined. RESULTS: Children (mean age 6.7 +/- 3.6 years) with AGS (n = 26) had low height-for-age z-scores (HAZ), weight-for-age z-scores (WAZ) (-1.9 +/- 1.3 and -1.7 +/- 1.1, respectively), and delayed skeletal maturation (-1.4 +/- 1.8 years). Fifty-eight percent of the subjects were less than the 5th percentile for height and 54% were less than the 5th percentile for weight. At least 20% of children with AGS had low dietary intake for several nutrients including: calories, fat, calcium, vitamin D, and vitamin E. Children who consumed <2/3 Dietary Reference Intake (DRI) for calcium (n = 6) had a statistically significantly lower HAZ (-3.2 +/- 1.3) than those who consumed >2/3 DRI (-1.5 +/- 1.0), (P < 0.003). Ninety-six percent of the subjects had steatorrhea with a mean COA of 75 +/- 16%. CONCLUSIONS: These data suggest that prepubertal children with AGS are at-risk for poor nutrient intake which, compounded with steatorrhea, may have a negative effect on growth and nutritional status. Intervention studies to increase energy and nutrient intake are needed to determine the effect of improved dietary intake on growth and nutritional status of children with AGS.     

Taurine supplementation, fat absorption, and growth in cystic fibrosis

The effect of taurine supplementation (30 to 40 mg/kg/24 hr) on fat absorption and related measurements was examined in 21 preadolescent children with cystic fibrosis (CF) using a 12-month double-blind crossover technique. The mean coefficient of fat absorption was unchanged by taurine both in the unselected study group (without taurine, mean +/- SD 84.0% +/- 11.9%; with taurine, 84.4% +/- 11.8%, n = 20) and in a subgroup of seven children with moderately severe fat malabsorption (without taurine, 75.6% +/- 15.6%; with taurine, 74.8% +/- 14.6%). The mean fecal split fat/total fat ratio, which generally reflects bile acid-related fat malabsorption, was also unchanged. Linoleic and arachidonic acid deficiencies noted in plasma before supplementation showed no significant improvement with taurine supplementation. Likewise, plasma/serum vitamin A, E, and D levels were unchanged. Standard scores for height and weight were not affected significantly. This study does not support the use of taurine supplementation in the nutritional management of CF.     

Dietary intake of healthy children with cystic fibrosis compared with normal control children.

Because a low calorie intake may result in growth failure and malnutrition in patients with cystic fibrosis (CF), the dietary and energy intakes of 22 children with CF who had mild lung disease and excellent Shwachman scores were examined and compared with those of 23 normal control subjects similar in age (5 to 10 years), gender, and weight. The children with CF consumed significantly more calories than the control subjects. Calorie intake was 111 +/- 19.9% (mean +/- SD) of estimated requirements (World Health Organization recommendations) for the CF group and 97 +/- 18.7% for the control group (P = .014). Calories consumed per kilogram of body weight were 117% of World Health Organization (CF) vs 97% (control) (P = .009). Calorie intake compared to the 1989 Recommended Dietary Allowance was 106 +/- 20.6% for the CF group vs 93 +/- 19.1% for the control group. Fat consumed as a percent of total calories was similar: 33.5% (CF) vs 32.2% (control). All children with CF had pancreatic insufficiency and, on average, consumed a large number of pancreatic enzyme supplements, resulting in dietary fat absorption of 86 +/- 12%. It is concluded that these children with CF were able to maintain normal growth and energy stores on a diet that was relatively high in calories compared to control subjects and moderate in percent fat, along with an aggressive pancreatic enzyme supplement regimen.     

Plasma homocysteine levels and folate status in children with sickle cell anemia.

PURPOSE: A sensitive inverse relationship between plasma homocysteine concentration and folate status has been demonstrated. Although children with sickle cell anemia (SCA) are at potential risk for folate deficiency, plasma homocysteine levels have not been reported in such patients. Therefore, a study was designed to assess plasma homocysteine levels as a marker of folate status. DESIGN: Plasma homocysteine concentrations were measured in 120 children with SCA (102 in steady state and 18 during an acute complication) who had never received supplemental folic acid. Folate status was directly assessed in 34 of these patients. RESULTS: Plasma homocysteine levels in the patients with SCA and control subjects were similar. The mean value +/- 1 SD was 5.8+/-2.5 micromol/L (range, 1.6 to 14.1 micromol/L) in the patients with SCA and 6.1+/-2.7 micromol/L (range, 1.7 to 15.3 micromol/L) in 73 pediatric control subjects. In a subpopulation of the study group (34 children), simultaneous serum folate, red cell folate, and total homocysteine concentrations were also measured. Their serum folate and red cell folate concentrations were normal: 12.4+/-10.0 nmol/L (range, 1 to 42 nmol/L) and 604+/-374.7 nmol/L (range, 205 to 1741 nmol/L), respectively. There was no correlation of plasma homocysteine concentration with various clinical or laboratory measures or with red cell folate concentration. CONCLUSION: Folate stores in children with SCA not receiving folic acid supplements are adequate despite an underlying hemolytic anemia.     

Abnormalities in zinc homeostasis in young infants with cystic fibrosis

Low plasma zinc concentrations have been reported in approximately 30% of young infants with cystic fibrosis identified by newborn screening. The objective of this study was to examine zinc homeostasis in this population by application of stable isotope methodology. Fifteen infants with cystic fibrosis (9 male, 6 female; 7 breast-fed, 8 formula-fed) were studied at a mean (+/-SD) age of 1.8 +/- 0.7 mo. On d 1, 70Zn was administered intravenously, and 67Zn was quantitatively administered with all human milk/formula feeds during the day. Three days later, a 3-d metabolic period was initiated, during which time intake was measured and complete urine and fecal collections were obtained. Fractional zinc absorption, total absorbed zinc, endogenous fecal zinc, and net absorbed zinc were measured; fecal fat excretion was also determined. Fractional absorption was significantly higher for the breast-fed infants (0.40 +/- 0.21) compared with the formula-fed group (0.13 +/- 0.06) (p = 0.01), but with the significantly higher dietary zinc intake of the formula-fed group, total absorbed zinc was higher for those receiving formula (p = 0.01). In 1 infants with complete zinc metabolic data, excretion of endogenous zinc was twofold greater for the formula-fed infants (p < 0.05); net absorption (mg zinc/d) was negative for both feeding groups: -0.04 +/- 0.52 for breast-fed; -0.28 +/- 0.57 for formula-fed. Endogenous fecal zinc losses correlated with fecal fat excretion (r = 0.89, n = 9, p = 0.001), suggesting interference with normal conservation of endogenously secreted zinc. These findings indicate impaired zinc homeostasis in this population and suggest an explanation for the observations of suboptimal zinc status in many young infants with cystic fibrosis prior to diagnosis and treatment.     

Decreased levels of nitrosothiols in the lower airways of patients with cystic fibrosis and normal pulmonary function

Airway S-nitrosothiols (SNOs) are naturally occurring bronchodilators. SNOs, nitrate, and nitrite were measured in bronchoalveolar lavage fluid of 23 patients with cystic fibrosis (CF) and mild pulmonary disease (aged 6-16 years) and 13 healthy children (aged 8-15 years). Concentrations of SNOs were decreased in the lower airways of patients with CF and mild pulmonary disease (median, range: 0, 0-320 nmol/L vs 80, 0-970 nmol/L) despite normal levels of the inert nitric oxide metabolites nitrate and nitrite (mean +/- SEM: 3.7 +/- 0.5 micromol/L vs 4.8 +/- 0.9 micromol/L). S-nitrosolation- mediated bioreactivities may be impaired by depletion of the CF airway SNO reservoir.     

Short-chain fatty acid absorption in patients with cystic fibrosis.

Patients with cystic fibrosis (CF) often exhibit malabsorption despite the use of supplemental pancreatic enzymes. Unabsorbed carbohydrates and amino acids can serve as substrates for large intestine anaerobic fermentation, thus increasing excretion of short-chain fatty acids (SCFA) in the feces. Nine patients with CF on regular pancreatic enzyme supplementations in the age range of 5-11 years and one older patient were studied. Three-day stool samples were collected, as were 72-h food records. Stools were analyzed for gross energy, total nitrogen, fat content, and SCFA concentration. A significant difference was found between CF and normal controls in total caloric excretion due to fat malabsorption. No significant difference was found between CF and normal controls in protein or SCFA excretion. Fat excretion as percentage of fat intake was significantly increased in CF patients: 35.3 +/- 10.2% versus 8.0 +/- 3.0%, respectively. These data suggest that carbohydrate supplementation could be more widely used to increase caloric intake in CF patients without causing secondary osmotic diarrhea.     

Child-feeding practices in children with down syndrome and their siblings

OBJECTIVE: To compare parental feeding practices and evaluate their relationship to weight status among children with Down syndrome (DS) and their unaffected siblings. STUDY DESIGN: Cross-sectional study of sibling pairs, one child with DS (n = 36) and one child without DS (n = 36), between 3 and 10 years of age. Parents completed the Child Feeding Questionnaire (CFQ), which assesses six aspects of control in feeding, separately for each child. Children's height and weight were measured using standard research procedures for calculation of body mass index (BMI) and BMI Z scores (BMIZ). RESULTS: Mean BMIZ was higher among children with DS than their siblings (1.1 +/- 0.9 vs 0.1 +/- 1.1; P <.001), but there were no between-group differences in parents' perception of children's weight status. Parents reported greater use of restriction, greater feelings of responsibility for feeding and concern about child weight status, and lower pressure to eat for children with DS than for their siblings. After adjustment for BMIZ, differences remained significant only for concern (10.6 +/- 3.5 vs 6.4 +/- 3.4; P <.002). Perceived child overweight and concern were positively associated with BMIZ, whereas pressure was inversely associated with BMIZ. CONCLUSIONS: Differences in child-feeding practices may play a role in the development of obesity in DS.     

Differences in resting energy expenditure between male and female children with cystic fibrosis

OBJECTIVES: To evaluate which factors might contribute to raised resting energy expenditure (REE) in patients with cystic fibrosis (CF). STUDY DESIGN: REE and anthropometry were measured in 134 (males = 68) children with CF and 100 (males = 51) controls (range, 3-18.7 years) in an outpatient setting. Bacterial colonization, liver disease, inhaled steroid use, pancreatic and pulmonary function, sex, and genotype were determined and regression analysis was used to determine the predictors of REE in the group with CF. RESULTS: REE for children with CF was increased on average by 7.2% compared with controls. This increase was greater for females than for males. REE in males was positively associated with fat-free mass (FFM), pancreatic insufficiency (PI), and liver disease, and negatively associated with pulmonary function, whereas in females, REE was positively associated with FFM and PI. REE (adjusted for FFM) was higher in children with a severe mutation (5495 +/- 47 kJ) compared with a mild mutation (5,176 +/- 124 kJ, P <.02). CONCLUSIONS: PI, severe mutations, and female sex are the main contributing factors to elevated REE in patients with CF with near normal pulmonary function.     

Concentration of plasma beta-carotene in cystic fibrosis children with pancreatic insufficiency

Patients with cystic fibrosis (CF) have significantly decreased plasma concentrations of antioxidant vitamins which is considered to result both from fat malabsorption and from chronic pulmonary infection. The aim of this study was to investigate levels of vitamin A and beta-carotene in plasma of CF subjects with pancreatic exocrine insufficiency. In thirty CF patients mean plasma concentrations of vitamin A (1.17 micromol/l) was lower by 30% and that of beta-carotene (1.3 micromol/l) by 60% than in healthy children. Vitamin A level was positively correlated with beta-carotene (r=0.67; p<0.001). Ratios of beta-carotene to total cholesterol and cholesterol of LDL (low density lipoprotein) were 40% lower than in the control group. We conclude that in our CF patients the concentration of beta-carotene does not seem to be sufficient to inhibit lipid peroxidation especially of LDL fraction.     

Zinc status in well nourished Bangladeshi children suffering from acute lower respiratory infection

This study was done to investigate the association of zinc status of well nourished Bangladeshi children with Acute Lower Respiratory Infection (ALRI). In this case control study, simultaneous estimation of serum and hair zinc was performed in 35 well nourished children, aged 6-60 months suffering from ALRI and 38 normal matched controls. Serum zinc was low in children suffering from ALRI as compared to control (90 +/- 51 pg/dL vs 176 +/- 98 pg/dL, OR: 6, 95% CI: 1.83, 19.66;P <0.05) children. Hair zinc was also found significantly low in children suffering from ALRI as compared to control (158 + 48 1g/g vs 247 154 pg/g, OR: 3, 95% CI: 1.46, 10.04, P < 0.05). We conclude that Bangladeshi children suffering from pneumonia, have decreased levels of serum and hair zinc.     

Aluminum contamination of parenteral nutrition and aluminum loading in children on long-term parenteral nutrition

BACKGROUND: Children who are receiving parenteral nutrition are at risk of aluminum overload, which may contribute to such side effects as osteopenic bone disease. The aim of the present study is to determine the aluminum contamination of parenteral nutrition solutions and their components, and to assess the aluminum status of children on long-term parenteral nutrition. METHODS: Aluminum concentrations were determined by graphite furnace absorption spectroscopy in components and in final parenteral nutrition solutions. The urinary aluminum excretion and plasma aluminum concentration were determined in 10 children on long-term parenteral nutrition. RESULTS: The mean aluminum concentration in the administered parenteral nutrition solutions was 1.6 +/- 0.9 micromol x l(-1)(mean +/- standard deviation (SD)). The resulting mean aluminum daily intake of the 10 patients was 0.08 +/- 0.03 micromol x kg(-1) x day(-1). CONCLUSIONS: Compared to two previous studies performed in 1990 and in 1995 in our hospital, the aluminum contamination of parenteral nutrition solutions and the daily aluminum intake of the children seemed to decrease. However, the plasma aluminum concentration and daily urinary aluminum excretion of the children still remain above normal standards. The children had no clinical symptoms of bone disease but aluminum accumulation in tissue can not be excluded. To prevent this iatrogenic toxicity, the aluminum contamination of parenteral nutrition should be assessed regularly.     

Effect of exocrine pancreatic function on resting energy expenditure in cystic fibrosis

AIM: To prove the hypothesis that exocrine pancreatic function determines resting energy expenditure (REE) in cystic fibrosis (CF). METHOD: Thirty-eight CF individuals, 9-34 (19.98 +/- 1.0) years, were divided into three groups: Six pancreatic sufficient patients (PS; group A), 21 pancreatic insufficient patients (PI), whose pulmonary function was comparable to that of group A (group B1) and 11 PI patients, whose pulmonary function was significantly worse than that of group A (group B2). REE was estimated by indirect calorimetry. Predicted REE was based on Schofield equations. Measured REE was expressed as % of the predicted. BMI, BMI z-scores, serum albumin, cholesterol and triglycerides levels were related to REE. Results were expressed as mean +/- standard error. RESULTS: Groups B1 and B2 had significantly higher REE% (111.7 +/- 2.75% and 119.94 +/- 3.8, respectively) as opposed to group A (98.9 +/- 3.81%; p = 0.022 and 0.035, respectively) whose REE% was similar to that predicted. REE% between group B1 and B2 was not statistically significant. In groups A, B1 and B, mean FEV1% was 86.33 +/- 10.1%, 90.24 +/- 4.39%, 44.54 +/- 3.47%, respectively, mean BMI was 25.6 +/- 2.06, 19.48 +/- 0.64 and 20.09 +/- 8.8, respectively, BMI z-scores were 0.75 +/- 0.51, -0.52 +/- 0.24 and -1.07 +/- 0.37, respectively. Significant correlation was demonstrated between REE%, BMI z-scores and cholesterol levels in group A. CONCLUSION: Clinically stable CF patients, who had comparable pulmonary function, exhibited increased REE% only in the presence of exocrine pancreatic insufficiency. REE% strongly correlated with BMI z-scores in pancreatic sufficiency. These findings support the hypothesis that pancreatic rather than pulmonary function may determine nutritional status as well as REE in CF.     

Index for measuring child feeding practices

Objective The present investigation was undertaken with the objective of creating an Infant and Child Feeding Index (ICFI) from a set of complementary feeding (CF) practices and to determine its association with growth of infants and young children (6-23months). Methods A semi-structured interview schedule was used to collect information for 204 children from one large slum (n=104) and two private pediatric clinics (n=100) of urban Vadodara. Results Results revealed that about half (50.5%) of the children were stunted Ht for Age Z score (HAZ<-2SD), nearly one-fourth (25.5%) were underweight Wt for Age Z score (WAZ<-2SD), but wasting (WHZ Wt for Ht Z score<-2SD) was low (3%). Significant associations were revealed between almost all positive CF practices and nutritional status of the children as measured by HAZ and WAZ (p<0.01), but not with WHZ. Good associations were revealed between ICFI and HAZ and WAZ, but not with WHZ. On multivariate analysis of factors affecting the HAZ, WAZ and WHZ scores, ICFI was not found to be significant whereas maternal education was the most significant factor, which was also found to be associated significantly with ICFI. Conclusion It is concluded that the composite index in its present form can reflect the CF practices more holistically than just one or few behaviors studied separately. More research is needed in the direction of constituting a composite index which can then be used for research, monitoring, evaluation and much needed advocacy for complementary feeding.     

Determinants of Serum Vitamin D Levels in Preadolescent Cystic Fibrosis Children

ABSTRACT. The effects of liver disease, fat malabsorption and sunlight exposure on serum vitamin D levels were determined in 21 optimally treated preadolescent cystic fibrosis (CF) children over a 12-month period. Manifest liver disease and fat malabsorption appeared not to affect the vitamin D level. However, the level fell significantly in winter, although not below the normal range, suggesting that sunlight exposure is a more important determinant of vitamin D levels in preadolescent CF children than liver disease and fat malabsorption.     

Determinants of serum vitamin D levels in preadolescent cystic fibrosis children

The effects of liver disease, fat malabsorption and sunlight exposure on serum vitamin D levels were determined in 21 optimally treated preadolescent cystic fibrosis (CF) children over a 12-month period. Manifest liver disease and fat malabsorption appeared not to affect the vitamin D level. However, the level fell significantly in winter, although not below the normal range, suggesting that sunlight exposure is a more important determinant of vitamin D levels in preadolescent CF children than liver disease and fat malabsorption.     

Relationships between essential fatty acid levels,pulmonary function and fat absorption in pre-adolescent cystic fibrosis children with good clinical scores

Twenty-one pre-adolescent cystic fibrosis (CF) children with good clinical scores had significant (P<0.001) deficiencies of arachidonic (mean 3.8% of total plasma fatty acids ± SD 1.4) and linoleic (18.1±6.3) acids compared with controls (6.0±1.0, and 27.6±3.9, respectively). Despite the presence of pulmonary involvement of varying severity in all the CF children, neither arachidonic nor linoleic acid levels correlated significantly with pulmonary function measured by spirometry. All children had adequate caloric and fat intakes, and the coefficient of fat absorption correlated with none of the deficient fatty acid levels. These findings suggest that deficiencies of arachidonic and linoleic acids are of minor importance in the early development of pulmonary involvement in CF, and that factors other than fat malabsorption and decreased dietary intake probably contribute to fatty acid deficiency.Abbreviations CF Cystic fibrosis - EFA Essential fatty acid - PUFA polyunsaturated fatty acid - FVC forced vital capacity - FEV₁ forced expiratory volume in 1 s - FEF₅₀, FEF₇₅ forced expiratory flows at 50% and 75% of the expired vital capacity - FEF_25–75 forced expiratory flow measured between 25% and 75% of the expired vital capacity     

Supplemental nasogastric feeding in cystic fibrosis patients during treatment for acute exacerbation of chest disease

The use of overnight, nasogastric, nutritional supplementation during hospitalization of children with cystic fibrosis (CF) receiving antibiotic therapy for acute exacerbations of respiratory disease was evaluated in 11 children (mean age = 7.75 years). Supplementary feeding significantly increased inpatient energy intake from 116 +/- 30% to 165 +/- 30% (P less than 0.001) of recommended dietary allowance with minimal effect on oral intake. It also resulted in significantly improved weight gains but neither increased energy intakes nor weights were sustained at short-term (mean = 5.7 weeks) or long-term (mean = 21.6 weeks) follow-up. The notion that short bursts of nasogastric feeding for inpatients with CF improve growth status is not supported. However, the study did show that treatment of chest infections alone does not positively affect spontaneous oral energy intake.     

Growth and nutritional indexes in early life predict pulmonary function in cystic fibrosis

OBJECTIVE: To determine the relation of growth and nutritional status to pulmonary function in young children with cystic fibrosis (CF). STUDY DESIGN: The relation of weight-for-age (WFA), height-for-age (HFA), percent ideal body weight (%IBW), and signs of lung disease at age 3 years with pulmonary function at age 6 years was assessed in 931 patients with CF. Associations of changes in WFA from age 3 to 6 on pulmonary function were also assessed. RESULTS: WFA, HFA, and %IBW were poorly associated with lung disease at age 3 years, but all were strongly associated with pulmonary function at age 6 years. Those with WFA below the 5th percentile at age 3 had lower pulmonary function at age 6 compared with those above the 75th percentile (FEV(1): 86 +/- 20 [SD] versus 102 +/- 18 % predicted, respectively). Pulmonary function was highest in those whose WFA remained >10th percentile from age 3 to 6 (FEV(1): 100 +/- 19 % predicted) and lowest in those who remained <10th percentile (84 +/- 21 % predicted). Patients with signs and symptoms of lung disease at age 3 years had lower pulmonary function at age 6 years. CONCLUSIONS: Aggressive intervention early in life aimed at growth and nutrition and/or lung disease may affect pulmonary function.