Donna Buckley

Relation of activity levels to body fat in infants 6 to 12 months of age

We examined longitudinally the relation between body fatness and physical activity, adjusting for energy intake, in 31 healthy white infants. Measures of physical activity, dietary intake, and body composition were obtained at 6, 9, and 12 months of age. The percentage of body fat was inversely related to activity level, an association that became stronger with increasing age and remained significant after adjustment for dietary energy intake. The percentage of body fat was not related to energy consumed per lean body mass regardless of high or low activity level, nor was energy consumed related to physical activity. We conclude that the percentage of body fat in infants may be related more to their activity levels than to their energy intake.

Micellar solubilisation of cholesterol is essential for absorption in humans

Background and aims: Intralumenal bile acid (BA) concentrations have a profound effect on cholesterol absorption. We performed studies to assess the effects of markedly reduced lumenal BA on cholesterol absorption in children with inborn errors in BA synthesis and the role of micellar solubilisation of cholesterol on its absorption in an animal model using human intestinal contents. Methods: We studied five subjects: two with 3β hydroxy-C27 steroid dehydrogenase isomerase deficiency (3-HSD), two with Δ4-3-oxosteroid 5β reductase deficiency (5β reductase), and one with 2-methylacyl CoA racemase deficiency (racemase). Subjects were studied on supplemental BA therapy and three weeks after withdrawal of supplements. During each treatment period a liquid meal was consumed. Duodenal samples were collected and analysed, and cholesterol absorption and cholesterol fractional synthetic rates were measured. Human intralumenal contents were infused in a bile diverted rat lymph fistula model to assess micellar versus vesicular absorption of cholesterol. Results: Without BA supplementation, intralumenal BA concentrations were below the critical micellar concentration (CMC) whereas intralumenal BAs increased to above the CMC in all subjects on BA supplementation. Lumenal cholesterol was carried primarily as vesicles in untreated subjects whereas it was carried as both micelles and vesicles in treated subjects. Cholesterol absorption increased ≈55% in treated compared with untreated subjects (p = 0.041), with a simultaneous 70% decrease in synthesis rates (p = 0.029). In the rat lymph fistula model, minimal vesicular cholesterol was absorbed whereas vesicular and micellar fatty acid and phospholipid were comparably absorbed. Conclusions: Increasing micellar cholesterol solubilisation by supplemental BA in subjects with inborn errors of BA synthesis leads to an improvement in cholesterol absorption and reduction in cholesterol synthesis due to improved micellar solubilisation of cholesterol.

Serum vitamin D metabolites in very low birth weight infants with and without rickets and fractures.

Seventy-one very low birth weight (less than or equal to 1500 gm) infants were studied to determine the sequential changes in serum vitamin D metabolite concentrations between infants with and without radiographically documented rickets, fractures, or both (R/F). Usual intake of vitamin D included 20 IU/kg/day from parenteral nutrition or 400 IU/day supplementation with enteral feeding. Radiographs of both forearms and serum samples were obtained at 3, 6, 9, and 12 months. Twenty-two infants had R/F. At 3 months, significantly lower mean (+/- SEM) serum phosphorus levels (4.5 +/- 0.4 vs 6.1 +/- 0.2 mg/dl), higher 1,25-dihydroxyvitamin D (1,25-[OH]2D) concentrations (96 +/- 5 vs 77 +/- 4 pg/ml), and higher free 1,25-(OH)2D index (1,25-[OH]2D:vitamin D binding protein ratio; 5.2 +/- 0.3 x 10(5) vs 4.0 +/- 0.2 x 10(5] were found in the R/F group. These values returned to normal and were similar between groups on subsequent measurements. Serum calcium, magnesium, and 25-hydroxyvitamin D (25-OHD) concentrations were normal and similar between groups. In both groups, serum vitamin D binding concentrations increased initially but remained stable and normal beyond 6 months. We conclude that in very low birth weight infants with R/F, the vitamin D status (as indicated by serum 25-OHD concentrations) is normal, and that lowered serum phosphorus levels, higher serum 1,25-(OH)2D levels, and a higher free 1,25-(OH)2D index support the thesis that mineral deficiency (especially of phosphorus) may be important in the pathogenesis of R/F in small preterm infants.

Effective Dose of Dual-Energy X-Ray Absorptiometry Scans in Children as a Function of Age

Effective dose, a parameter utilized to assess biological risk related to radiation exposure, may be used to evaluate risk associated with dual-energy X-ray absorptiometry (DXA). We estimated the effective dose from DXA (Hologic QDR 4500A) scans of the lumbar spine (fast array mode), total body, hip (fast array mode), and forearm for children ages 1, 5, 10, and 15 yr and for adults. Entrance dose incorporating backscatter was determined for each scan type. Depth-dose curves were derived using Plexiglas slabs simulating tissue attenuation. Organ depth was estimated using pediatric phantom models. For all scan types, the effective dose decreased as age increased. The effective dose values for a 1-yr-old and an adult, respectively, were 4.7 microSv and 2.2 microSv for a lumbar spine scan performed in fast array mode, 3.4/3.5 microSv and 1.8/2.1 microSv (male/female) for a total body scan, and 0.14 microSv and 0.03 microSv for a forearm scan. There were marked sex differences in the effective dose associated with hip scans (fast array mode) ranging from 15.2 microSv for a 1-yr-old male to 4.6 microSv for an adult female. A comprehensive uncertainty analysis indicated that the effective dose values were reliable within a factor of 3. With the exception of the hip scans in 1- and 5-yr-olds, the effective doses were below the negligible individual dose limit of 10 microSv/yr.

Elevation of serum 1,25-dihydroxyvitamin D in response to physiologic doses of vitamin D in vitamin D-deficient infants*

mal dysplasia was present, and family histories were negative for significant dental disease. These children probably represent a group who are more susceptible to caries; in them, prolonged nocturnal exposure to human milk should be considered a risk factor. Unfortunately, the susceptibility of the teeth to decay cannot be clinically predicted, and susceptible children may develop extensive caries, especially on the lingual surface of the teeth, before the condition becomes evident to the parent or physician. As more women choose nursing over bottle-feeding, pediatricians are discovering significant, although infrequen t , side effects of inadequate milk composition and supply.6.7 Nursing bottle-type caries in breast-fed infants might be viewed as a problem of improper delivery. Patients 1 and 2 had anatomic findings identical to those in bottle-fed children who sustained nursing bottle caries; most impressive was the total sparing of the lower incisors. Patient 3 sustained the earliest and most rampant caries, with an all-night feeding pattern. Shelton et aL L suggest elimination of the all-night bottle or provision of water only in the bottle in order to prevent nursing bottle caries. In an analogous way, the continuous nocturnal nursing pattern should be discouraged to prevent early dental changes. In women who nurse for longer than one year, frequent intermittent night feedings might represent a risk as well, Weaning, as suggested by Gardner et al., 2 appears to be a drastic step. However, the elimination of nocturnal feeding in children of this age should be possible through adequate conditioning of the child. In this way, the nursing experience can be continued without cariogenic risk to the child.

Reduction of the body burden of PCBs and DDE by dietary intervention in a randomized trial

Serum polychlorinated biphenyls (PCBs) in Anniston, AL, residents have been associated with hypertension and diabetes. There have been no systematic interventions to reduce PCB body burdens in Anniston or other populations. Our objective was to determine the efficacy of 15 g/day of dietary olestra to reduce PCBs in Anniston residents. Blood PCBs and 1,1-bis-(4-chlorophenyl)-2,2-dichloroethene were measured at baseline and 4-month intervals in a double-blind, placebo-controlled, 1-year trial. Participants with elevated serum PCBs were randomized into two groups of 14 and received potato crisps made with olestra or vegetable oil (VO). Elimination rates during the study period were compared with 5-year prestudy rates. Eleven participants in the olestra group and 12 in the VO group completed the study. Except for one participant in the VO group, reasons for dropout were unrelated to treatments. The elimination rate of 37 non-coplanar PCB congeners during the 1-year trial was faster during olestra consumption compared to the pretrial period (-0.0829 ± 0.0357 and -0.00864 ± 0.0116 year(-1), respectively; P=.04), but not during VO consumption (-0.0413 ± 0.0408 and -0.0283 ± 0.0096 year(-1), respectively; P=.27). The concentration of PCBs in two olestra group participants decreased by 27% and 25% during the trial. There was no significant time by group interaction in change from baseline. However, group main effects for total PCBs and PCB 153 were of borderline significance. This pilot study has demonstrated that olestra can safely reduce body burdens of PCBs and supports a larger intervention trial that may also determine whether reduction in PCBs will reduce the risk of hypertension and diabetes.

Treatment of bile acid amidation defects with glycocholic acid

Bile acid amidation defects were predicted to present with fat/fat soluble vitamin malabsorption with minimal cholestasis. We identified and treated five patients (one male, four females) from four families with defective bile acid amidation due to a genetically confirmed deficiency in bile acid CoA:amino acid N‐acyl transferase (BAAT) with the conjugated bile acid, glycocholic acid (GCA). Fast atom bombardment‐mass spectrometry analysis of urine and bile at baseline revealed predominantly unconjugated cholic acid and absence of the usual glycine and taurine conjugated primary bile acids. Treatment with 15 mg/kg GCA resulted in total duodenal bile acid concentrations of 23.3 ± 19.1 mmol/L (mean ± SD) and 63.5 ± 4.0% of the bile acids were secreted in bile in the conjugated form, of which GCA represented 59.6 ± 9.3% of the total biliary bile acids. Unconjugated cholic acid continued to be present in high concentrations in bile because of partial intestinal deconjugation of orally administered GCA. Serum total bile acid concentrations did not significantly differ between pretreatment and posttreatment samples and serum contained predominantly unconjugated cholic acid. These findings confirmed efficient intestinal absorption, hepatic extraction, and biliary secretion of the administered GCA. Oral tolerance tests for vitamin D2 (1,000 IU vitamin D2/kg) and tocopherol (100 IU/kg tocopherol acetate) demonstrated improvement in fat‐soluble vitamin absorption after GCA treatment. Growth improved in 3/3 growth‐delayed prepubertal patients. Conclusion: Oral glycocholic acid therapy is safe and effective in improving growth and fat‐soluble vitamin absorption in children and adolescents with inborn errors of bile acid metabolism due to amidation defects. (Hepatology 2015;61:268–274)

Fat malabsorption in cystic fibrosis: comparison of quantitative fat assay and a novel assay using fecal lauric/behenic acid.

Objectives: The gold standard for the diagnosis of fat malabsorption, the 72-hour fat balance study, requires a 3-day collection to generate a coefficient of fat absorption (CFA). We hypothesized that a new test using behenic acid (behenate test) as a nonabsorbable lipid marker may provide a facile means to assess fat absorption. The study proposed to answer 2 questions: first, whether the behenate test correlated with the gold standard and, second, whether the CFA improved when taking pancreatic enzymes during meals instead of taking them before meals. Patients and Methods: The study compared the behenate test with the gold standard in 15 patients with cystic fibrosis during 3 arms that require 3- to 4-day hospitalization: first, taking pancreatic enzymes before meals; second, taking it during meals; and third, without taking it. Results: The mean CFA was 78.3% when pancreatic enzymes were taken during meals and 80.4% when these enzymes were taken before meals. Correlation between the CFA and the behenate test for collections during all 3 arms was r2 = 0.219 (P = 0.001). Conclusions: Timing of ingestion of pancreatic enzymes does not significantly alter the CFA. Although the CFA correlates with the behenate test, the correlation is not robust enough to justify replacement of the gold standard by this test. It is unclear whether the poor correlation between tests relates to intermeal variability in fat excretion or other factors; however, the behenate test may be suitable as a screening test for the detection of fat malabsorption.

Seasonal differences in serum vitamin D binding protein in exclusively breast-fed infants: negative relationship to sunshine exposure and 25-hydroxyvitamin D

Summary: Vitamin D binding protein (DBP) is the major carrier for vitamin D and its metabolites in serum. DBP increases in pregnancy and decreases in cirrhosis; no seasonal variation has been reported in adults. We observed significant seasonal differences in 41 exclusively breast‐fed infants who were less than 6 months of age. Winter DBP concentrations exceeded summer DBP concentrations: 398 ± 22 versus 297 ± 20 &mgr;g/ml (mean ± SEM). The mean concentration for spring and fall was 329 ± 25 &mgr;g/ml. Maternal DBP concentrations did not differ by season. A sunshine exposure score, previously verified, was used to document time and body surface exposed to the sun. DBP was inversely related to sun exposure (r = −0.46, p = 0.005). Infant DBP was significantly and negatively correlated with 25‐hydroxyvitamin D concentrations (r = − 0.38, p = 0.02). We speculate that serum DBP fluctuations are a response to varying vitamin D needs: increased serum DBP occurs in low vitamin D status to maximize uptake of vitamin D from skin.

OSTEOCALCIN AND CALCIUM RESPONSE TO INTRAVENOUS 1,25 DIHYDROXYVITAMIN D3 |[lpar]|IVD|[rpar]|

Osteocalcin (OC) is the major non-collagenous bone protein, has Ca binding properties and is involved in bone mineralization; elevated serum levels occur with high bone turnover and after 1,25(OH)2 vit D. Its role in infancy is unknown. In a pilot, uncontrolled study, we found oral 1,25(OH)2 D3 did not raise serum Ca in <1500g (VLBW) infants at graduated doses up to 3 mcg/kg/d. In a controlled study, we tested the thesis that high dose IVD elevates serum Ca and OC in VLBW infants. 22 preterm, wt appropriate infants (750-1500g) were matched in 250g ranges and randomly assigned to IVD 4 mcg/kg/d × 3 d from 1st d of life vs controls. Gestation and Apgars were comparable for grps. Serum OC (RIA specific for humans N 4-9 ng/ml, term 4-110, mean 41) rose from 19±6 ng/ml (mean±SEM) to 96 at 34 hr, 122 at 58 hr and 154 at 80 hr (p<.05 ANOVA vs d 1) in IVD but was unchanged in controls. Serum Ca rose from 7.3±0.24 mg/dl to 7.8, 8.5 (p<.005) and 9.2 (p<.05) at corresponding times in IVD, but was unchanged in controls, 7.2, 6.6, 7.1 until last point 9.3 (p <.05). Serum Mg but not serum P increased with age; both were unaffected by IVD. Ca correlated with ionized Ca (r=0.89, p< .001). Furthermore OC correlated with Ca and ionized Ca (r>0.46, p<.04). Thus there is a late response of serum Ca and OC to high 1,25(OH)D doses, supporting the thesis that osteocalcin may be responsive to 1,25 (OH)2D in VLBW infants. We speculate that bone turnover, as reflected by osteocalcin elevations, is involved in the elevation of serum Ca from 1,25(OH)2D in infancy.