Feto-maternal vitamin D status and infant whole-body bone mineral content in the first weeks of life.

BACKGROUND/OBJECTIVES: Compromised vitamin D status is common in pregnancy and may have adverse impacts on fetal development. The purpose of this study was to investigate the association of infant whole-body bone mineral content (WBBMC) at 8-21 days of age with feto-maternal vitamin D status in a multiethnic population in Oakland, California. SUBJECTS/METHODS: This was a cross-sectional study of 120 women and their newborn infants. Maternal and cord blood were collected at delivery. WBBMC was measured by dual-energy X-ray absorptiometry in term-born infants 8-21 days post birth. RESULTS: No significant association was observed between unadjusted or size-adjusted WBBMC and feto-maternal vitamin D status analyzed continuously or categorically. In multivariate modeling, unadjusted WBBMC was predicted by bone area (P<0.0001), weight-for-age (P<0.0001) and weight-for-length (P=0.0005) Z-scores, but not by feto-maternal vitamin D status. Anthropometric predictors but not vitamin D remained significant in the multivariate model after adjustment of WBBMC for weight, bone area (bone mineral density) or logarithmically derived exponents of the denominators. CONCLUSIONS: Results of the present study do not support an association between feto-maternal vitamin D status and early infant WBBMC, raw or adjusted for inter-individual differences in size, in a multiethnic population in Northern California.

Prevalence of fractures among the Thalassemia syndromes in North America.

Historically, fractures are cited as a frequent problem in patients with Thalassemia prior to optimization of transfusion and chelation regimens. The aim of this study was to determine the prevalence of fractures in a contemporary sample of North American patients with Thalassemia. The North American Thalassemia Clinical Research Network (TCRN) database registry was used to gather historical data on 702 patients with common alpha and beta-Thalassemia diagnoses including Thalassemia Major (TM), Intermedia (TI), E/Beta, homozygous alpha Thalassemia (AT), Hemoglobin H disease (HbH) and HbH with Constant Spring (HbH/CS), who consented to a medical record chart review. Bone mineral density (BMD) measurements by DXA were available for review in a subgroup of patients (n = 312). The overall fracture prevalence among all Thalassemia syndromes was 12.1%, equally distributed between females (11.5%) and males (12.7%). Fractures occurred more frequently in TM (16.6%) and TI (12.2%) compared to E/Beta (7.4%) and alpha (2.3%). Prevalence increased with age (2.5% ages 0-10 years, 7.4% ages 11-19 years, 23.2% ages >20 years) and with use of sex hormone replacement therapy (SHRT) (P < 0.01). On average, BMD Z and T scores were 0.85 SD lower among patients with a history of fractures (mean Z/T score -2.78 vs. -1.93, 95% CI for the difference -0.49 to -1.22 SD, P = 0.02). Presence of other endocrinopathies (i.e. hypothyroidism, hypoparathyroidism and diabetes mellitus), anthropometric parameters, heart disease or hepatitis C were not significant independent predictors of fractures. These data indicate that fractures remain a frequent complication among the aging patients with both TM and TI beta-Thalassemia. However, the fracture prevalence has improved compared to published reports from the 1960s to 1970s. In addition, children with Thalassemia appear to have low fracture rates compared to the general population.

The new SQUID biosusceptometer at Oakland: first year of experience.

Liver iron measurements using biosusceptometers have been validated on two low-TC SQUID (Superconducting Quantum Interference Device) systems (New York and Hamburg) built in the 1980's. Recently, two new instruments have been installed in Torino, Italy (2001), and Oakland, California (2003). The design of the Oakland system is similar to those in Hamburg and Torino. Improvements were made to adjust for significant environmental noise, moreover, an active electronic noise cancellation, a computer controlled water coupling reference system using a pressure feedback and a faster data acquisition system using software lockin amplifiers have been implemented. All 3 systems (Hamburg, Torino, Oakland) are using the same standardized operational protocol. Presented herein are the data collected from 276 patients measured with the SQUID biosusceptometer at Oakland since installation. The results from 149 patients with beta-thalassemia (beta-Thal, age: 2-66 y), 76 patients with sickle-cell disease (SCD, age: 5-55 y), 35 patients with various rare diseases (RD, age: 2-80 y), and 16 patients with hereditary hemochromatosis (HHC, age: 6-74 y) are reported. The liver iron concentration in the different groups are 222 - 7570 (beta-Thal), 518 - 7918 (SCD), 511 - 6234 (RD), 258 - 2041 (HHC) microg/g-liver (in vivo wet weight). The long-term reproducibility (12 months) in a patient on constant treatment regimen demonstrated a mean liver iron of 1141 +/- 133 microg/g-liver. The new SQUID Ferritometer located on the US West coast will give more patients access to this non-invasive liver iron assessment.

Interaction of artificial metallic objects with biosusceptometric measurements.

In human subjects, metallic objects cause distortions of the magnetic fields used by magnetic resonance imaging (0.5 - 3.0 T) or by SQUID biomagnetic liver susceptometry (0.1 - 30 mT) and may lead to artifacts in the measurement of the relaxation rate or the magnetic susceptibility. In biosusceptometry, the measured signal will depend not only on the magnetic susceptibility of the object, but also on its distance to the sensor assembly, and in case of ferromagnetic objects, on the direction of its remanent field. The magnetic susceptibility of a vascular access port-a-cath and of surgical clips have been measured by a SQUID biosusceptometer. Additionally, the impact from port-a-caths and dental braces on liver iron concentration (LIC) measurements was measured in vivo with respect to their radial distance from the gradiometer center axis. For the port-a-cath, a mean magnetic volume susceptibility of (83.5 +/- 0.3).10(-6) SI-units was found, which may be compared with the magnetic susceptibility of titanium at room temperature of (180 +/- 2).10(-6) SI demonstrating the absence of ferromagnetic contamination. At a radial distance of 5 cm from the gradiometer center axis, the voltage amplitude is similar to the signal generated by a normal liver. Modern surgical clips have nearly no impact on LIC measurements. However, dental braces although further away from the center axis, often superimpose the signal even from an iron overloaded liver. Depending on the Ni-content, these objects reveal ferromagnetic properties and contribute in first order with a one parameter reciprocal distance function to the measured liver iron signal.

Dual X-ray absorptiometry assessment of body composition in children with altered body posture.

Many children have contractures and/or deformities that preclude positioning in a fully supine position. The purpose of this study was to evaluate the effects of "poor" positioning on the assessment of body composition with dual X-ray absorptiometry (DXA) in thirty-seven normal child volunteers ages 3-16 yr. Multiple whole-body DXA scans of each child were performed: duplicate scans in the correct fully supine position, two scans while simulating different positions typical of children with contractures, and a scan while positioned in the full lateral position as a "worst-case" scenario. Also evaluated were the precision of duplicate measures in the altered positions, the effect of knee flexion contractures, and the impact of metallic orthopedic fixation devices. Errors in body composition assessment did occur from "poor" positioning. In those positions simulating children with contractures, the mean errors were 4-6% for measures of bone mineral content, 1-3% for lean body mass, and 5-11% for fat mass. Measures in the correct fully supine position and the contracted positions were highly correlated. The errors obtained by altering position were small. If errors of this magnitude are of significance, then corrective equations could be utilized to improve accuracy. Precise and reasonably accurate measures of body composition can be obtained with DXA in children with disabilities and deformities that preclude fully supine positioning.

Energy expenditure and intake in children with sickle cell disease during acute illness.

BACKGROUND: Children with sickle cell disease have frequent bouts of pain and infection which may increase energy expenditure, decrease energy intake and lead to a subsequent energy deficit. METHODS: Two groups of African-American children with sickle cell disease-SS genotype were enrolled in this study upon hospital admission for a sickle cell disease related illness: a younger (<6 years, n=14, 7 M) and older group (> or =6 years, n=17, 8 M). Body composition and dietary intake were assessed, and sleeping (younger) or resting energy expenditure (older) were measured by indirect calorimetry at admission and one month later at steady state. RESULTS: Energy expenditure was not different between the two timepoints for younger children, but was slightly elevated at steady state (+50 kcal/d, P=0.049) in the older group. After controlling for gender, changes in fat-free mass and dietary intake, the significance disappeared. Energy intake in both groups was significantly depressed at admission compared to follow-up (P<0.01). CONCLUSIONS: These children and adolescents did not expend excess energy during their acute illness, however, an energy deficit was observed secondary to poor energy intake. Since 20% of patients with sickle cell disease have multiple hospitalizations per year, these results provide justification for the development and evaluation of nutrition care protocols to maintain adequate caloric intake during hospitalization and recovery.

Red blood cell folate and serum vitamin B12 status in children with sickle cell disease.

PURPOSE: To determine red blood cell (RBC) folate and serum vitamin B12 levels in children with sickle cell disease, SS-type, and to evaluate the associations of these nutrient levels with growth and hematologic parameters. PATIENTS AND METHODS: Subjects enrolled in this prospective, cross-sectional study were recruited from one tertiary care setting. Complete blood counts, measurement of red blood cell (RBC) folate and serum vitamin B12, anthropometric measures (height, weight, skinfold measurements), pubertal status, and 24-hour dietary recalls were obtained from 70 patients ages 1 to 19 years. RESULTS: Low RBC folate levels were found in 15% of the children. Fifty-seven percent of the sample had inadequate dietary folate intake. Three percent of the children had low serum vitamin B12 levels. All children and adolescents sampled had adequate dietary intake of vitamin B12. Both RBC folate (P = 0.01) and serum vitamin B12 levels (P < 0.01) decreased with increasing age. CONCLUSIONS: More than half of the subjects had inadequate intake of folate from food, and despite daily folate supplementation, 15% had low RBC folate levels. Low serum vitamin B12 levels were rare, and dietary vitamin B12 intake was adequate. Additional research is needed to explore the effects of improved folate status, the need for folate supplementation, and the relationship of folate, vitamin B12, and homocysteine levels and the risk for vascular damage and stroke in children with sickle cell disease.

Effect of hydroxyurea therapy on resting energy expenditure in children with sickle cell disease.

Effects of hydroxyurea therapy on resting energy expenditure (REE) in children with sickle cell disease have not been evaluated. Eight children with sickle cell disease were examined before hydroxyurea therapy and again 6.9 +/- 3.5 months after hydroxyurea initiation. Resting energy expenditure, dietary intake, and growth were assessed. In six children, baseline REE was elevated, and REE decreased an average of 17% with hydroxyurea. This was associated with a significant increase in fetal hemoglobin. These pilot data suggest that hydroxyurea may curtail the hypermetabolic state observed in children with sickle cell disease and may offer a clinically important secondary benefit.

Estimating energy expenditure in critically ill adults and children.

Designing effective nutrition support regimens for critically ill patients requires an understanding of the energy needs of each patient. Many disease processes result in elevated caloric requirements, whereas some clinical procedures and medications may diminish the metabolic response. Experienced clinicians are unable to predict the extent to which trauma or injury will affect energy requirements for an individual. Both under- and overfeeding a critically ill patient may prolong hospitalization and increase morbidity and mortality. Applying equations that were originally developed for healthy nonhospitalized individuals to predict the energy requirements of critically ill patients will often result in significant errors and may lead to provision of inappropriate nutritional support. The measurement of resting energy expenditure by indirect calorimetry is a valuable tool and can be used to predict energy requirements for most spontaneously breathing critically ill patients, but may lead to spurious results in mechanically ventilated pediatric patients. In the complex and rapidly changing context of critical illness, individualized assessment of energy requirements is crucial. Whichever technique is used initially to assess energy requirements, sequential monitoring and constant reassessment of each patient is essential to provide the appropriate nutritional care regimen. The purpose of this article is to review the equations for estimating and the techniques, practical aspects, and interpretation of measuring energy expenditure in critically ill patients.

A six-month study of growth and energy expenditure in children with cystic fibrosis taking a pulmonary inhalation medication (rhDNase).

OBJECTIVE: To characterize the effects of recombinant human deoxyribonuclease (rhDNase) on growth velocity, body composition, resting energy expenditure (REE) and food intake in children with cystic fibrosis (CF). METHODS: A prospective, six-month pilot study was conducted in twenty-one subjects with CF (twelve male, nine female, ages 11.5+/-3.1 years) measured at baseline, two and six months post-baseline. Repeated measures ANOVA was used to examine the change in variables across time. RESULTS: The majority (75%) of subjects had minimal lung disease at baseline (FEV1: 80%-119% predicted). As expected for growing children, weight and height gains (1.6 kg and 2.5 cm) were observed between baseline and six months (p=0.0001). No change was observed in weight z-scores from six months prior to initiation of rhDNase therapy to six months post, though a significant decline (p=0.049) in Ht z-score was observed over this twelve-month period. Triceps skinfolds and mid-arm muscle circumference increased from baseline to six months (p<0.01); respective z-scores remained stable. Energy intake remained constant during the period it was studied from baseline to two months of therapy: 120%+/-27% RDA. REE, though slightly elevated compared to healthy children (baseline 106%+/-8% predicted), remained stable throughout the study and at a level which may be expected for children with minimal lung disease. A trend (p=0.057) towards a decrease in the number of subjects requiring hospitalization for pulmonary exacerbations during the trial period was observed. CONCLUSIONS: In summary, these pilot data from younger children with milder CF-related lung disease do not confirm anecdotal reports of improved rate of weight gain, caloric intake or decreases in the elevated REE. Future research might focus on documentation of the possible nutritional effects of rhDNase in clinical trials of children with more severe lung disease.

A longitudinal study of calcium homeostasis during human pregnancy and lactation and after resumption of menses.

To clarify the role of the intestine, kidney, and bone in maintaining calcium homeostasis during pregnancy and lactation and after the resumption of menses, a longitudinal comparison was undertaken of 14 well-nourished women consuming approximately 1200 mg Ca/d. Measurements were made before conception (prepregnancy), once during each trimester of pregnancy (T1, T2, and T3), early in lactation at 2 mo postpartum (EL), and 5 mo after resumption of menses. Intestinal calcium absorption was determined from the enrichment of the first 24-h urine sample collected after administration of stable calcium isotopes. Bone mineral of the total body and lumbar spine was measured by dual-energy X-ray absorptiometry and quantitative computerized tomography, respectively. Twenty-four-hour urine and fasting serum samples were analyzed for calcium, calcitropic hormones, and biochemical markers of bone turnover. Despite an increase in calcium intake during pregnancy, true percentage absorption of calcium increased from 32.9+/-9.1% at prepregnancy to 49.9+/-10.2% at T2 and 53.8+/-11.3% at T3 (P < 0.001). Urinary calcium increased from 4.32+/-2.20 mmol/d at prepregnancy to 6.21+/-3.72 mmol/d at T3 (P < 0.001), but only minor changes in maternal bone mineral were detected. At EL, dietary calcium and calcium absorption were not significantly different from that at prepregnancy, but urinary calcium decreased to 1.87+/-1.22 mmol/d (P < 0.001) and trabecular bone mineral density of the spine decreased to 147.7+/-21.2 mg/cm3 from 162.9+/-25.0 mg/cm3 at prepregnancy (P < 0.001). Calcium absorption postmenses increased nonsignificantly to 36.0+/-8.1% whereas urinary calcium decreased to 2.72+/-1.52 mmol/d (P < 0.001). We concluded that fetal calcium demand was met by increased maternal intestinal absorption; early breast-milk calcium was provided by maternal renal calcium conservation and loss of spinal trabecular bone, a loss that was recovered postmenses.

Acute pulmonary exacerbation is not associated with increased energy expenditure in children with cystic fibrosis.

OBJECTIVE: The objective of this study was to document alterations in resting energy expenditure (REE), energy intake, and body composition that occur during admission for management of a pulmonary exacerbation in children with cystic fibrosis. STUDY DESIGN: A prospective study of 14 children with cystic fibrosis (8 male, 12.5 +/- 3.3 years) was conducted throughout a 14-day hospitalization and again 3 weeks after discharge. Repeated measures analysis of variance was used to examine the change in variables across time. RESULTS: Significant increases were documented from days 1 to 14 in weight (37.1 +/- 13.1 kg to 38.4 +/- 13.5 kg) and pulmonary function (forced expiratory volume in 1 second: 67.6% +/- 19.8% to 78.5% +/- 24.5%). Energy intake was not different between hospitalization and follow-up and averaged 175% of the Recommended Dietary Allowance. REE on day 1 was elevated (122% +/- 11% predicted); however, when expressed with fat free mass as a covariate, no significant changes were noted in REE throughout the eight measurements. CONCLUSIONS: These data suggest that an acute pulmonary exacerbation is not associated with an increase above a subject's baseline REE in children with cystic fibrosis with mild to moderate lung disease. Management of an acute pulmonary exacerbation should be associated with sustained improvement in pulmonary function and nutritional status; in contrast, weight loss or failure to improve pulmonary function should be seen as atypical.

Zinc absorption in women during pregnancy and lactation: a longitudinal study.

Zinc is essential for normal fetal growth and development and for milk production during lactation. The metabolic adjustments made in zinc utilization to meet these needs have not been described. The purpose of this study was to determine whether fractional zinc absorption (FZA) is altered during pregnancy and lactation and, if so, to determine whether the change is related to maternal zinc status, specifically, concentrations of zinc in plasma, erythrocytes, urine, and breast milk and dietary zinc intake. Thirteen women were studied at five time points: once preconception; at 8-10, 24-26, and 34-36 wk gestation; and once while they were lactating 7-9 wk postpartum. Zinc intake increased by 35 mumol/d (2.3 mg/d) from preconception to 34-36 wk (P = 0.04); it tended to decrease (P > 0.05) during lactation but did not return to the preconception level. The amount of zinc in breast milk averaged 2.0 mg/d at the lactation time point. FZA measured from urinary enrichments of two stable isotopes of zinc increased from 14% preconception to 25% during lactation (P = 0.023) but the increase to 19% at 34-36 wk gestation was not significant. No increase in FZA occurred in four women who took iron supplements during lactation. FZA was negatively correlated with plasma zinc concentration at 34-36 wk gestation and with urinary zinc excretion at all time points. The nearly twofold increase in zinc absorption during lactation was presumably in response to the demand for zinc to synthesize breast milk.

Efflux of beta-galactosidase products from Escherichia coli.

Several different strains of Escherichia coli were grown on a variety of carbon sources under various growth conditions. Lactose was added (usually at mid-log phase), and the concentrations of the products of beta-galactosidase action on this sugar (galactose, glucose, and allolactose) were determined at various times thereafter in the total culture and in the medium. It was found that with each strain, with all carbon sources, and under all of the conditions studied, a very large proportion of the products were found in the medium. Control studies were carried out which showed that these results were not artifacts of the method of separating the cells from the medium. The results also did not arise from the secretion of beta-galactosidase into the medium, from the diffusion of substrates and products into and out of the cells due to leaks in the membrane, or from faults in the method of sugar analysis. In addition, the results showed that there were very high levels of products inside the cells under the conditions used and that the efflux of the products was rapid. The efflux might be energetically advantageous to the cell as well as being a means of storing excess products until needed.