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Objective: Our purpose was to identify factors associated with the physical activity in young children., Study Design: Participants were 214 children (aged 3-5 years) enrolled in 10 childcare centers who were monitored for physical activity with an accelerometer during 2 continuous days (48 hours). Mean daily activity counts, activity counts between 9 AM and 5 PM, and percentage of time spent in vigorous activity were determined. The factors investigated were age, childcare center, season, sex, body mass index (BMI), history of preterm birth, participation in organized activities, parental BMI, and parental educational level. Regression analyses were used to identify factors associated with each of the activity measures., Results: A statistical model including sex, history of preterm birth, childcare center, and father's BMI accounted for 22%, 37%, and 23% of the variance in total daily counts, counts between 9 AM and 5 PM, and percentage of time spent in daily vigorous activity, respectively. Childcare center was the highest individual predictor of activity. Boys were more active than girls in all activity measures except counts between 9 AM and 5 PM. Children born preterm were less active than children born at term, and high activity levels in the child were associated with a low BMI in fathers., Conclusion: The findings indicate that sex, history of preterm birth, childcare center, and father's BMI influence the daily physical activity of young children.

This study was undertaken to identify factors that influence total body bone area (TBBA), total body bone mineral content (TBBMC), and tibial cortical bone measures in 239 children aged 3-5 years. We obtained information on demographic and anthropometric characteristics and measurements of diet, physical activity, and strength. In multiple regression analysis, TBBA correlated with height (p < 0.001), weight (p < 0.001), percent body fat (p < 0.001), and calcium intake (p = 0.02). TBBMC correlated with TBBA (p < 0.001), age (p = 0.001), and weight (p = 0.02) and inversely correlated with height (p < 0.001) and percent body fat (p < 0.001). Children born preterm had lower TBBMC compared with children born at term (p = 0.02). Both periosteal and endosteal circumferences were correlated with weight (both,p < 0.001) and inversely correlated with age (p = 0.006 and p = 0.003, respectively) and percent body fat (p = 0.002 and p = 0.005 respectively). Endosteal circumference was greater and cortical bone area was lower in children born preterm compared with those born at term (both, p = 0.04). Findings of higher TBBA and lower TBBMC in children with high percent body fat indicate undermineralization of bone and suggest that obesity in preschool children may have detrimental effects on total body bone mass accretion. A smaller tibial periosteal circumference and thus cross-sectional area in children with the same weight but higher percent body fat also would lead to a biomechanical disadvantage in these children. Findings of low TBBMC and cortical bone area among children born preterm need to be confirmed in other populations. We speculate that differences in these measurements between children born preterm and at term may be caused by differences in activity.

Objective: The timing of introduction of complementary food to an infant's diet is variable throughout the world. Our objective was to determine whether early introduction of complementary foods affects iron and zinc status of formulated infants at 12, 24, and 36 months of age., Design: A randomized, prospective trial was conducted. Infants were randomly assigned to receive either a) early introduction (at 3 to 4 months of age) of commercially prepared or parent's choice of complementary foods; or b) late introduction (at 6 months of age) of commercially prepared complementary foods or parent's choice of complementary foods. In addition to complementary foods, infants were fed commercial infant formula as recommended by their pediatrician. Hemoglobin, mean corpuscular volume, and serum ferritin and zinc concentrations were determined at 12, 24, and 36 months of age. Three-day diet diaries were completed at 3, 6, 12, 18, 24, 30, and 36 months of age., Subjects/setting: One hundred seventy-five infants younger than 3 months were recruited by mailings to parents in the Cincinnati area. Of these, 172 were enrolled, 90 in the early-introduction group and 82 in the late-introduction group. One hundred thirty-three infants (n = 67 in the early, n = 66 in the late group) completed the study., Statistical Analyses Performed: Student t test and regression analyses were used to determine whether there were group differences and whether there was a relationship between serum parameters and dietary intake., Results: Infants fed complementary foods early had significantly greater iron intakes until 6 months of age; however, there were no differences in the iron status parameters (ferritin, hemoglobin, and mean corpuscular volume) at 12, 24, or 36 months of age. The early introduction group consumed slightly less zinc than the late introduction group at 5 months (4.4 vs 4.8 mg/day, P < .01) and 6 months (4.4 vs 4.7 mg/day, P < .01). At all other times there were no differences between the early and late group in zinc intakes. The serum zinc concentration was not associated with dietary zinc. Both groups had normal serum zinc concentrations at 12, 24, and 36 months and there were no differences between groups., Applications/conclusions: The iron and zinc status of infants in this study was not influenced by the timing or type of complementary foods introduced. However, the infants were formula fed and the mean iron and zinc intakes that were equal or greater than the Recommended Dietary Allowances for the first 6 months of age.

The purpose of the study was to develop ethnic-specific equations for fat-free mass (FFM) from selected anthropometric dimensions and bioelectrical impedance measures of resistance (R) and reactance (Xc) for use in the NHLBI Growth and Heath Study. Using dual-energy X-ray absorptiometry measures of body composition as the dependent variable and field measures of body composition by anthropometry and bioelectrical impedance as the explanatory variables, ethnic-specific prediction equations were developed on a sample of girls representing a wide range of ages and BMI. The equations were cross-validated using (1) the Prediction of Sum of Squares (PRESS) statistic and (2) an independent sample of 20 girls of each race from a study conducted at the National Institute of Child Health and Human Development (NICHD). Subjects were 65 White and 61 Black girls 6-17 years of age. The best race-specific equations for FFM each explained 99% and 97% of the variance in the White and Black girls, respectively. Root mean square errors (RMSE) ranged from 1.14 to 1.95 kg. The equation for Black girls used Stature2/Resistance (R), weight, and reactance (Xc) as predictor variables; the equation for White girls used Stature2/R, weight, and triceps skinfold thickness. The results indicate that (1) equations to predict FFM in girls should be ethnic-specific and that (2) accurate values for TBF and %BF can be calculated from the predicted FFM.

Objective: To determine whether consumption of 2% milk during the second year of life leads to reduced growth or lower percentage body fat compared with consumption of whole milk., Subjects: Subjects were healthy toddlers who participated in a larger trial examining the effects of the timing of introduction of solid foods on growth., Design: Three-day diet diaries, anthropometric measurements, and body composition determined by dual-energy x-ray absorptiometry were assessed at 12, 18, and 24 months of age. At age 12 months, the toddlers were similar in length, weight, percentage body fat, and total energy intake. From 12 to 24 months of age, milk consumption consisted of whole milk exclusively in one group (n = 23) and 2% milk exclusively in another group (n = 28)., Statistical Analyses: Differences between the 2 groups in anthropometric measurements, changes in anthropometric measurements, and dietary intakes were determined by Student t tests. Mean differences were considered significant at the P = .05 level. Data are presented as mean +/- standard deviation., Results: Despite lower intakes of total fat and saturated fat in the 2% milk group, there were no differences in height, weight, and percentage body fat. Total energy intake was not reduced in the 2% milk group., Applications: Reductions in total fat and saturated fat intake in toddlers can be achieved through the use of 2% milk without compromising growth.

A discussion of observational and longitudinal studies examining the effect of early-life calcium intake on bone health is provided. A critical analysis of pediatric calcium supplementation trials is conducted by determining annualized percent changes in bone mineral density (BMD). The focus of the analysis is to identify consistent findings at specific bone sites, determine whether effects differed by the age of children studied, and establish the relationship between bone changes and baseline calcium intake. We found that increases in BMD owing to higher calcium intake among children appear to occur primarily in cortical bone sites, are most apparent among populations with low baseline calcium intakes, and do not seem to persist beyond the calcium supplementation period. Older (e.g., pubertal) children appear to have greater annual increases in lumbar BMD than younger (e.g., prepubertal) children. The annual percent increase in midradius BMD appears to be greater at higher intakes among the older children, but such a relationship is less apparent among the younger children.

We examined a Hutterite population (n = 243) to determine if their agriculturally diverse, self-sufficient communal lifestyle promotes optimal bone mass attainment because of adequate calcium intake and high physical activity levels during growth and young adulthood. We measured total body (TB) and lumbar bone mineral content (BMC) and bone mineral density (BMD) in 39 school-age (younger) females and 204 working (older) females. Forty-five percent of older females and 79% of younger females currently consumed > or = 3 servings (svg) of dairy per day. Older females had lumbar (0.6 +/- 1.3) and TB (1.1 +/- 1.1) BMD Z scores greater than 0 (both, p < 0.001). The lumbar BMD Z score of younger females was not different from 0 (-0.1 +/- 1.0; p = 0.5). Both lumbar (r = 0.46; p < 0.001) and TB (r = 0.20; p = 0.02) BMD Z scores increased with increasing age. In multiple regression analyses for older females, lumbar bone area (p < 0.001), weight (p < 0.001), current hours on feet per day (p = 0.01), colony workload (p < 0.01), and estrogen status (p = 0.06) predicted lumbar BMC. TB bone area (p < 0.001), current hours on feet per day (p < 0.001), and colony workload (p < 0.01) predicted TB BMC. For younger females, lumbar bone area (p < 0.001), weight (p < 0.01), years in present colony (p = 0.02), and menses (p < 0.001) predicted lumbar BMC. TB bone area (p < 0.001), height (p < 0.01), years in present colony (p = 0.03), and menses (p < 0.01) predicted TB BMC. The effect of colony workload could not be separated from other factors different by colony. A heritability estimate of 0.66 was calculated for lumbar BMD using mother and daughter Z scores. Adequate calcium intake during growth, high physical activity early in life, and genetic factors may be contributing to above normal BMD levels in adult female Hutterites.

Objective: To better understand risk factors for the development of obesity in early childhood, we examined the association between children's adiposity and their parents' eating behavior and body mass index (BMI)., Research Methods and Procedures: Parents of 85 white children 36 months of age (49 boys and 36 girls) completed the Three-Factor Eating Questionnaire measuring three dimensions of parent eating behavior: disinhibited eating, cognitive restraint of eating, and susceptibility to hunger. Parent BMI (kg/m2) was calculated using self-reported height and weight. The children's percentage body fat was assessed by dual energy X-ray absorptiometry analysis., Results: Twenty-six percent of parents were obese (BMI > or = 30 kg/m2). Both maternal and paternal BMI were associated with higher scores for disinhibition (r = 0.69 and r = 0.68, p < 0.001), and maternal BMI was also associated with higher scores for hunger (r = 0.51, p < 0.001). There were no significant relationships between children's percentage body fat and parent eating scores, and the correlation between children's percentage body fat and parent BMI was significant only between mothers and daughters (r = 0.35, p = 0.04). Obese parents were no more likely to have a child who was fatter (upper quintile of percentage body fat for gender)., Discussion: Among 36 month-old white children, parent eating behavior was related to parent BMI, but not to children's adiposity. There was only a weak relationship between parent BMI and child adiposity. Despite the aggregation of adiposity within families due to shared genes and environments, children may not express differences in susceptibility to obesity by 3 years of age.

Dual-energy X-ray absorptiometry (DXA) measures areal bone mineral density (BMD) and is affected by bone size. Peripheral quantitative computed tomography (pQCT) measures volumetric density and should not be affected by bone size. We hypothesized that pQCT could be used to measure geometric parameters in the tibia and that bone size, not density, would correlate with weight and height in 3 and 4 yr olds. Phantom measurements indicate that accurate results for cortical volumetric bone mineral density can be obtained at cortical thickness > 2 mm with voxel/speed sizes of 0.40/20 mm/s. Correlations between pQCT measured geometric bone parameters and phantom calculations were observed (all r > 0.96). Baseline data from an ongoing trial of 101 preschool children (53 male) were used to correlate bone parameters and anthropometrics. Total cross-sectional area, cortical area, and cortical thickness correlated with weight (r = 0.54, p < 0.001; r = 0.52, p < 0. 001; r = 0.30, p = 0.002) and height (r = 0.41, p < 0.001; r = 0.55, p < 0.001; r = 0.41, p < 0.001). Because of the small cortical thickness at this age (mean = 1.2 mm) cortical density was not analyzed. In a regression model including height and weight, weight was the only predictor of total cross-sectional area (p < 0.001); cortical thickness was predicted by height (p = 0.006). Both height (p = 0.005) and weight (p = 0.05) predicted the cortical area. In summary, pQCT accurately measures total cross-sectional area, cortical area, and cortical thickness in children age 3-4 yr.

Objective: To determine the extent of low total-body bone mineral content (BMC) in non-corticosteroid-treated white postpubertal females with juvenile rheumatoid arthritis (JRA) compared with healthy age- and race-matched female controls, and to identify variables that significantly contribute to total-body BMC., Methods: Thirty-six females with definite JRA who had never received corticosteroids and 51 healthy female controls were evaluated. All subjects had had their first menstrual period at least 2 years prior to enrollment. Total-body BMC, lumbar spine bone mineral density, and body composition were determined by dual x-ray absorptiometry. Total-body BMC Z-scores were calculated for JRA patients using data from controls. JRA patients were dichotomized into those with "normal" bone mass (total-body BMC at or above the mean or no more than 1 SD below the mean) and those with "low" bone mass (total-body BMC more than 1 SD below the mean). Comparisons of anthropometric measurements, laboratory measurements of bone metabolism, disease activity, dietary intake, and physical activity were performed. Stepwise logistic regression was utilized to determine the presence or absence of low total-body BMC and to identify associated contributing factors., Results: Total-body BMC was 4.5% lower in JRA patients than in controls (mean +/- SD 2,050 +/- 379 gm versus 2,143 +/- 308 gm; P = 0.21). Twenty-five of 36 patients (69.4%) had "normal" and 11 of 36 (30.6%) had "low" total-body BMC. Comparison of JRA patients with "normal" versus those with "low" total-body BMC revealed significant differences in disease characteristics, anthropometric and physical development characteristics, laboratory measures of bone mineralization, and dietary intake. The final regression model contained only lean mass (P = 0.01), which accounted for 76.3% of the variance in total-body BMC. The odds ratio for lean mass was 0.4451 (95% confidence interval 0.2374-0.8348)., Conclusion: In this study, approximately 30% of the subjects in a sample of postpubertal female patients with mild-to-moderate, non-corticosteroid-treated JRA had low bone mass. The predictor variable that significantly contributed to total-body BMC was lean mass, which demonstrated a protective effect of 0.56 risk reduction for low total-body BMC.

Although increased physical activity early in life is recommended for optimizing bone health, no controlled trials on the effect of activity on bone mass accretion during periods of rapid growth have been reported. The purpose of this study was to determine whether infants randomized to a 1 year gross motor activity program had a greater bone mass accretion than infants randomized to a fine motor activity program. The gross motor program included activities that focused on loading the skeleton and were performed for 15-20 minutes/day, 5 days/week by study personnel. Infants (n = 72) were enrolled at 6 months of age, and total body bone mineral content (BMC), 3-day diet records, and activity levels were obtained at 6, 9, 12, 15, and 18 months. BMC was associated with weight, length, and bone area at all ages and correlated with earlier calcium intakes. Calcium intake appeared to modify the effect of gross motor activity on bone mass accretion; infants in both groups had similar bone accretion at moderately high calcium intakes, but at low calcium intakes infants in the gross motor program had less bone accretion than infants in the fine motor program. Compliant infants in the gross motor group had lower BMC at 18 months compared with noncompliant infants. These results indicate that BMC in infants is related to calcium intake, and we speculate that participation in a gross motor program during rapid bone growth may lead to reduced bone accretion in the presence of a moderate to moderately low calcium intake.

Lactation is a time of calcium flux, because women secrete approximately 210 mg calcium/day in breast milk, and they experience a transient bone loss. The objectives of this study were to determine the effect of calcium supplementation on adaptive responses in calcium homeostasis during lactation and after weaning. Two cohorts of women participated in a 6-month randomized calcium supplementation trial. Lactation cohort women (97 lactating, 99 nonlactating) were studied during the first 6 months post partum, and weaning cohort women (95 lactating, 92 nonlactating) were studied during the second 6 months post partum. Lactating women in the weaning cohort weaned approximately 1.5 months after enrollment. PTH was 18-30% lower in lactating than in nonlactating women (P < 0.01). Serum 1,25-dihydroxyvitamin D was 11-16% higher in lactating than in nonlactating women and remained elevated for approximately 1.5 months after weaning (P = 0.06). Calcium supplementation decreased serum PTH and 1,25-dihydroxyvitamin D in lactating and nonlactating women similarly. At 6 months, the calciuric response to calcium supplementation was less in lactating (compared with nonlactating) women (P = 0.06). Biomarkers of bone turnover were higher in lactating than in nonlactating women during lactation and after weaning but were not effected by calcium supplementation. Calcium supplementation has little effect on lactation-induced changes in the calcium economy.

The ideal therapy for differentiated thyroid cancer is uncertain. Although thyroid hormone treatment is pivotal, the degree of thyrotropin (TSH) suppression that is required to prevent recurrences has not been studied in detail. We have examined the relation of TSH suppression to baseline disease characteristics and to the likelihood of disease progression in a cohort of thyroid cancer patients who have been followed in a multicenter thyroid cancer registry that was established in 1986. The present study describes 617 patients with papillary and 66 patients with follicular thyroid cancer followed annually for a median of 4.5 years (range 1-8.6 years). Cancer staging was assessed using a staging scheme developed and validated by the registry. Cancer status was defined as no residual disease; progressive disease at any follow-up time; or death from thyroid cancer. A mean TSH score was calculated for each patient by averaging all available TSH determinations, where 1 = undetectable TSH; 2 = subnormal TSH; 3 = normal TSH; and 4 = elevated TSH. Patients were also grouped by their TSH scores: group 1: mean TSH score 1.0-1.99; group 2: mean TSH score 2.0-2.99; group 3: mean TSH score 3.0-4.0. The degree of TSH suppression did not differ between papillary and follicular thyroid cancer patients. However, TSH suppression was greater in papillary cancer patients who were initially classified as being at higher risk for recurrence. This was not the case for follicular cancer patients, where TSH suppression was similar for all patients. For all stages of papillary cancer, a Cox proportional hazards model showed that disease stage, patient age, and radioiodine therapy all predicted disease progression, but TSH score category did not. However, TSH score category was an independent predictor of disease progression in high risk patients (p = 0.03), but was no longer significant when radioiodine therapy was included in the model (p = 0.09). There were too few patients with follicular cancer for multivariate analysis. These data suggest that physicians use greater degrees of TSH suppression in higher risk papillary cancer patients. Our data do not support the concept that greater degrees of TSH suppression are required to prevent disease progression in low-risk patients, but this possibility remains in high-risk patients. Additional studies with more patients and longer follow-up may provide the answer to this important question.

Objective: The optimal time and choice of solid foods to introduce to an infant's diet is unknown. The aim of this randomized trial was to determine whether early versus late introduction of solid foods and commercially prepared versus parent's choice of solid foods affects growth or body composition in the first year., Methods: White infants (n = 165) were recruited before 3 months of age and were randomized to receive: 1) commercially prepared solid foods (commercial) from 3 to 12 months, 2) commercially prepared solid foods from 6 to 12 months, 3) parent's choice of solid foods (choice) from 3 to 12 months, or 4) parent's choice of solid foods from 6 to 12 months. Anthropometrics and body composition, using dual energy x-ray absorptiometry, were determined at 3, 6, and 12 months. Three-day diet diaries were completed at 3, 6, 9, and 12 months., Results: There were no differences in growth or body composition between infants in early versus late introduction groups or commercial versus choice groups at any age. The total energy intake was not different among infants in the early compared with the late group at any age. Infants in the commercial group consumed less protein calories at 9 months (80 +/- 3 kcal/d vs 88 +/- 3 kcal/d) and 12 months 101 +/- 5 kcal/d vs 148 +/- 5 kcal/d), less fat calories at 12 months (263 +/- 10 kcal/d vs 343 +/- 10 kcal/d), and less total calories at 12 months (884 +/- 24 kcal/d vs 1022 +/- 25 kcal/d) compared with the choice group., Conclusion: The early introduction of solid foods to an infant's diet does not alter growth or body composition during the first year of life and results in a displacement of energy intake from formula. Infants consuming commercially prepared foods have a decreased caloric intake from protein and fat; however, despite this difference, there is no effect on growth or body composition.

To determine whether children with short bowel syndrome had evidence of metabolic bone disease, total body bone mineral content was measured by dual-energy x-ray absorptiometry in 18 patients and 36 age-, sex-, and race-matched control subjects. Children with short bowel syndrome had decreased bone mineral content compared with control subjects; however, it was not significant when adjusted for differences in weight and height. Whether these children will have normal bone accretion throughout puberty is not known.

Objective: To determine the extent of significant osteopenia in prepubertal patients with juvenile rheumatoid arthritis (JRA) not treated with corticosteroids and to identify variables that are highly related to bone mineralization in this population., Methods: In a cross-sectional study, 48 JRA patients and 25 healthy control subjects ages 4.6-11.0 years were evaluated. Total body bone mineral density (TB BMD) was determined by Hologic dual energy x-ray absorptiometry. All patients were prepubertal (Tanner stage I or II) and had never taken corticosteroids. For comparison, JRA patients were divided into "low" TB BMD (Z score < or =-1) or "normal" TB BMD (Z score >-1)., Results: The overall mean +/- SD TB BMD scores did not differ between the JRA subjects (0.75 +/- 0.06 gm/cm2) and controls (0.73 +/- 0.07 gm/cm2; P > 0.30). However, 29.2% of the JRA patients had low TB BMD, whereas only 16% would be expected to have low TB BMD based on the standard normal distribution (goodness of fit chi(2) = 4.84, P = 0.01). The mean Z score for the JRA patients with low TB BMD was -1.43, and for those with normal TB BMD, it was 0.32. The JRA subjects with low TB BMD were significantly younger, had more active articular disease, greater physical function limitation, higher erythrocyte sedimentation rate, higher joint count severity score, lower body mass index, lower lean body mass, less participation in organized sports, and more protein and vitamin D in their diet compared with JRA patients with normal TB BMD (all P < 0.05). Using logistic regression, a model including age at JRA onset, Juvenile Arthritis Functional Assessment Report (JAFAR) score, triceps skin-fold percentiles, percentage US recommended daily allowance for dietary magnesium intake, and serum 1,25-dihydroxyvitamin D levels was able to accurately segregate 79.6% of the JRA subjects into either the low or normal TB BMD groups (chi(2) = 20.5, P = 0.001)., Conclusion: This study demonstrated that in a mildly to moderately ill prepubertal JRA population that had never been exposed to corticosteroids, almost 30% had significantly low TB BMD. The patients with low TB BMD had more active and severe articular disease and greater physical function limitation. Disease-related parameters in JRA appear to exert a negative effect on bone mineralization even in prepubertal children, which can be demonstrated despite the exclusion of corticosteroid-treated patients.

Background: Women may lose bone during lactation because of calcium lost in breast milk. We studied whether calcium supplementation prevents bone loss during lactation or augments bone gain after weaning., Methods: We conducted two randomized, placebo-controlled trials of calcium supplementation (1 g per day) in postpartum women. In one trial (the study of lactation), 97 lactating and 99 nonlactating women were enrolled a mean (+/-SD) of 16+/-2 days post partum. In the second trial (the study of weaning), 95 lactating women who weaned their infants in the 2 months after enrollment and 92 nonlactating women were enrolled 5.6+/-0.8 months post partum. The bone density of the total body, lumbar spine, and forearm was measured at enrollment and after three and six months., Results: The bone density of the lumbar spine decreased by 4.2 percent in the lactating women receiving calcium and by 4.9 percent in those receiving placebo and increased by 2.2 and 0.4 percent, respectively, in the nonlactating women (P<0.001 for the effect of lactation; P= 0.01 for the effect of calcium). After weaning, the bone density of the lumbar spine increased by 5.9 percent in the lactating women receiving calcium and by 4.4 percent in those receiving placebo; it increased by 2.5 and 1.6 percent, respectively, in the nonlactating women (P<0.001 for the effects of lactation and calcium). There was no effect of either lactation or calcium supplementation on bone density in the forearm, and there was no effect of calcium supplementation on the calcium concentration in breast milk., Conclusions: Calcium supplementation does not prevent bone loss during lactation and only slightly enhances the gain in bone density after weaning.

Objective: The effect of varying mineral intakes on total body bone mass accretion during the first year of life in healthy full-term infants is unknown. The purpose of this study was to determine whether total body bone mass accretion during the first year of life was influenced by the calcium and phosphorus intake of an infant and whether early differences in bone accretion persist through 1 year of age., Design: This prospective, randomized trial was conducted in two phases. In phase I, 67 infants were randomized within the first 2 weeks of life into either a low (439 mg of calcium per liter and 240 mg of phosphorus per liter) or moderate (510 mg of calcium per liter and 390 mg of phosphorus per liter) mineral-containing formula feeding group. An additional group of 34 human milk-fed (low mineral) infants also was enrolled. Phase II involved an additional randomization of all infants at 6 months of age into moderate-mineral formula (see above), high-mineral formula (1350 mg of calcium per liter and 900 mg of phosphorus per liter), or cow milk (1230 mg of calcium per liter and 960 mg of phosphorus per liter) feeding group. Anthropometric measurements, nutrient intake, and total body bone mineral content (BMC) by dual-energy x-ray absorptiometry were measured at 1, 3, 6, 9, and 12 months., Results: During the first 6 months, the moderate-mineral group had a greater increase in weight (3.42 +/- 0.62 kg) compared with the human milk group (2.93 +/- 0.56 kg); the low-mineral group (3.19 +/- 0.62 kg) was intermediate. Bone mass accretion differed in a similar direction, with the moderate-mineral feeding group having a greater increase than the human milk group and the low-mineral group being intermediate of the two. Including weight, length, and bone area as covariates, both the low-mineral formula- and human milk-fed groups had similar BMC, which was lower than that of the moderate-mineral group at 3 and 6 months of age. Adjusted mean BMC values for the moderate-mineral formula-fed group compared with the low-mineral formula- and human milk-fed groups were 127.8 +/- 1.5 (SEM) g vs 119. 2 +/- 1.5 and 122.1 +/- 1.4 g, respectively, at 3 months of age and 168.7 +/- 2.5 g vs 157.6 +/- 2.5 and 158.7 +/- 2.4 g, respectively, at 6 months of age. The BMC at 6 months of age among the formula-fed infants was correlated with both average dietary phosphorus intake (r = .592) and average daily calcium intake (r = .620) during the first 6 months. The relationships between BMC and these minerals remained significant even after controlling for caloric intake. It was not possible to determine the independent effects of dietary calcium and phosphorus on BMC because of the strong correlation of these minerals with each other. Despite significant differences in both calcium and phosphorus intakes during the second 6 months of life, there were no differences in growth parameters or bone mass accretion. Means for BMC, adjusted for body weight, length, and bone area, were not significantly different among feeding groups at either 9 or 12 months of age. Adjusted means were 199 +/- 2 (SEM) and 237 +/- 3 g at 9 and 12 months of age for infants receiving moderate-mineral formula; 198 +/- 2 and 236 +/- 3 g at 9 and 12 months of age for infants receiving the high-mineral formulas and 202 +/- 5 and 233 +/- 5 g at 9 and 12 months of age for infants receiving cow milk. The gain in bone mass during the second 6 months differed by the first 6-month feeding group; mean changes in BMC between 6 and 12 months, adjusted for changes in weight, length, and bone area, were greater in human milk-fed infants than in either the low- or moderate-mineral-containing formula groups: 81 +/- 16 g in human milk-fed infants and 73 +/- 15 and 71 +/- 15 g in the low- and moderate-mineral formula groups, respectively. Infants fed whole cow milk during the second 6 months were excluded from this analysis because of the small number of infants completing the study. By 12 months of age t

The human nephrotic syndrome (NS) is accompanied by important alterations of mineral and bone metabolism. The purpose of the present study was to examine bone metabolism in rats with experimental NS and normal creatinine clearance, and to evaluate the reversibility of this alteration. NS was induced by three injections of puromycin aminonucleoside (PAN) on days 0, 21, and 35 (10, 5, and 5 mg/100 g body weight, respectively). The biochemical markers of bone formation (osteocalcin and alkaline phosphatase) and bone resorption (hydroxyproline and pyridinoline), bone mineral content (BMC), and bone mineral density (BMD), determined by dual-energy x-ray absorptiometry (DEXA), were studied on days 0, 7, 14, 28, 42, 56, 84, and 112. Proteinuria was present throughout the study. Hypoproteinemia was seen on days 7, 28, 42, and 56, returning to control values on days 84 and 112. In serum, osteocalcin (OC) concentration increased (p < 0.001), and alkaline phosphatase (ALP) decreased (p = 0.002). In urine, hydroxyproline increased (p < 0.001), but urinary pyridinoline was not different from the control group throughout the study. Increased serum parathyroid hormone concentration and decreased levels of 25-hydroxy and 1,25-dihydroxyvitamin D were found from day 7. During the intense proteinuria, bone resorption predominates and decreased BMC and BMD ensues in PAN-nephrotic rats. PAN-nephrotic rats showed low BMC and BMD compared to control group (p < 0.001). At the end of the study, when proteinuria persisted but total serum protein returned to control values, the biochemical bone markers, BMC, and BMD returned to normal. In conclusion, PAN-nephrotic rats had reversible bone alterations that were related to the magnitude of proteinuria and the concentration of total serum protein.

Results of trials on the effects of physical activity on bone mineral density (BMD) are conflicting. The current hypothesis was that calcium intake modifies the bone response to physical activity. Published trials on physical activity and bone density were reviewed, and the results of 17 trials are summarized. Physical activity has beneficial effects on BMD at high calcium intakes, with no effect at mean calcium intakes less than a mean of 1000 mg/day. The modifying effect of calcium intake on BMD among exercise groups is more pronounced in the lumbar spine than in the radius. This analysis may explain conflicting results of trials on physical activity and calcium effects on bone. Controlled trials designed to test adequately this hypothesis are needed.

We investigated whether intestinal calcium absorption and serum 1,25-dihydroxycholecalciferol (calcitriol) concentrations are higher in women during lactation and after weaning to compensate for calcium lost in breast milk. Measurements were obtained at 4.6 mo postpartum in 24 lactating women and 24 nonlactating women, at 9.6 mo postpartum in 24 lactating women (2.6 mo after complete weaning) and 24 nonlactating women. One-half of the women in each group were randomly assigned to receive 1 g supplemental Ca/d as calcium carbonate. Fractional calcium absorption was measured by using stable isotopic tracers 42Ca and 44Ca. Fractional absorption was 0.32+/-0.02 (+/-SEM) in both lactating and nonlactating women, but was higher in lactating women after weaning (0.37+/-0.02) compared with nonlactating postpartum control subjects (0.31+/-0.02). These effects were independent of calcium intake. Changes in serum calcitriol paralleled changes in fractional absorption. There were no differences in calcitriol concentrations between lactating and nonlactating women, but calcitriol was greater in women after weaning compared with postpartum control subjects. Lactating women who had resumed menses had higher fractional absorption and serum calcitriol than did lactating women who had not. Serum calcium and phosphorus concentrations were greater in lactating compared with nonlactating women; there were no differences between groups after weaning. We conclude that lactation stimulates increases in fractional calcium absorption and serum calcitriol, but the responses are only apparent after weaning or the resumption of menses.

This study was conducted to determine whether intravenous theophylline, added to inhaled albuterol and intravenous methylprednisolone, provides a clinically significant benefit in the treatment of pediatric status asthmaticus. Patients aged 2 to 10 years were randomized to receive either intravenous theophylline or placebo. All patients received aerosolized albuterol and intravenous methylprednisolone. There was no difference between groups in the improvement of a clinical asthma score over time, in oxygen requirement, or in the number of albuterol treatments required. Theophylline group patients experienced more nausea, emesis, and insomnia. We conclude that there is no benefit in adding theophylline to treatment with methylprednisolone and albuterol for pediatric status asthmaticus. Furthermore, there are significantly more adverse effects associated with the use of theophylline.

Serum carboxy-terminal propeptide of human type I collagen (PICP) concentrations, as a marker for bone formation, and urinary pyridinium (Pyd) cross-link concentrations, as a marker of bone resorption, were determined in 66 healthy infants aged 1-18 months who are being studied longitudinally. We hypothesized that there would be a positive correlation of growth velocity, increase in bone area, and bone mass accretion rates with PICP and Pyd cross-link concentrations. Since osteocalcin is currently used as a marker of bone formation, serum osteocalcin concentrations were also measured. Mean serum PICP and urinary Pyd cross-link concentrations were significantly greater than adult concentrations. Future growth velocity, increase in bone area, and bone mass accretion rates were not associated with PICP, Pyd cross-link, or osteocalcin concentrations. Growth velocity during the 3 months preceding sample collection correlated with serum PICP, Pyd/kg, and osteocalcin concentrations (r = 0.474, p < 0.001; r = 0.379, p < 0.001; and r = 0.516, p < 0.001, respectively). Previous increase in bone area correlated with serum PICP concentrations (r = 0.359, p = 0.01). The relationship between the infant's previous bone mass accretion rate and PICP was of borderline significance (r = 0.281, p = 0.055). In summary, normative data for PICP, Pyd cross-link concentrations, and parameters of bone growth are provided for infants 1-18 months of age and indicate that these markers reflect past and current bone metabolism and may be helpful in monitoring bone disorders in infants.

Objective: To measure daily physical activity in patients with juvenile rheumatoid arthritis (JRA) and in healthy controls, and to identify variables that may influence physical activity in JRA patients., Methods: Twenty-three prepubertal children, ages 5-11 years, with mild to moderate JRA and no prior exposure to systemic glucocorticosteroids, were compared to 23 healthy children of similar age. Physical activity was measured for 3 days (minimum of one weekend day) using 3 standardized methods simultaneously. Total body movement was assessed by the Caltrac accelerometer and the University of Cincinnati Motion Sensor (UCMS). The Caltrac measured movement in the vertical plane; the UCMS measured movement of 10 degrees or more from the horizontal plane. The type and intensity of daily physical activity was measured by the 3-day activity record, which also recorded the number of hours of daily sleep. Participation and duration of involvement in organized sports was ascertained by questionnaire., Results: The mean physical activity was significantly lower in JRA patients than in controls for the activity diary (P = 0.05). However, daily body movement measured by the Caltrac and UCMS were similar for both groups. Differences were seen in the number of hours of sleep per day (P = 0.02) and participation in strenuous activities (P < 0.01). JRA patients had significantly less participation in organized sports (P = 0.01)., Conclusion: There was less daily physical activity by this group of JRA patients than for healthy age- and sex-matched control subjects.

Infants of diabetic mothers (IDMs) have lower bone mineral content than control subjects at birth. We measured cord blood propeptide of type I procollagen (PICP), a marker of bone formation, and telopeptide of type I collagen (ICTP), a marker of bone resorption, in 25 term IDMs and 20 term control subjects. Concentrations of ICTP were higher in IDMs than in control subjects; there was no difference in PICP concentrations. We conclude that osteoclastic activity appears to be higher in IDMs than in control subjects in utero.

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.

Background and Methods: Mutations in the estrogen-receptor gene have been thought to be lethal. A 28-year-old man whose estrogen resistance was caused by a disruptive mutation in the estrogen-receptor gene underwent studies of pituitary-gonadal function and bone density and received transdermal estrogen for six months. Estrogen-receptor DNA, extracted from lymphocytes, was evaluated by analysis of single-strand-conformation polymorphisms and by direct sequencing., Results: The patient was tall (204 cm [80.3 in.]) and had incomplete epiphyseal closure, with a history of continued linear growth into adulthood despite otherwise normal pubertal development. He was normally masculinized and had bilateral axillary acanthosis nigricans. Serum estradiol and estrone concentrations were elevated, and serum testosterone concentrations were normal. Serum follicle-stimulating hormone and luteinizing hormone concentrations were increased. Glucose tolerance was impaired, and hyperinsulinemia was present. The bone mineral density of the lumbar spine was 0.745 g per square centimeter, 3.1 SD below the mean for age-matched normal women; there was biochemical evidence of increased bone turnover. The patient had no detectable response to estrogen administration, despite a 10-fold increase in the serum free estradiol concentration. Conformation analysis of his estrogen-receptor gene revealed a variant banding pattern in exon 2. Direct sequencing of exon 2 revealed a cytosine-to-thymine transition at codon 157 of both alleles, resulting in a premature stop codon. The patient's parents were heterozygous carriers of this mutation, and pedigree analysis revealed consanguinity., Conclusions: Disruption of the estrogen receptor in humans need not be lethal. Estrogen is important for bone maturation and mineralization in men as well as women.

Nutritional inadequacies during lactation may affect the well-being of the mother, infant, or both. Vitamin D and calcium status in vegetarian women may be low, resulting in maternal bone demineralization. Vitamin B-12 deficiency resulting in neurologic damage has been reported in infants of vegetarian women. A review of several studies completed on women in the northeastern United States who were consuming a macrobiotic diet is presented. Supplemental vitamin D does not appear to be necessary given sufficient sun exposure. Calcium intake in vegetarian mothers was low and differences in calcium-regulating hormones were apparent. However, it is not clear whether these hormonal changes resulted in adequate adaptation whether these hormonal changes resulted in adequate adaptation and prevented bone demineralization. The low calcium intake in the vegetarian women did not result in lower milk calcium concentrations. Elevated methylmalonic acid excretion, which is often seen in vitamin B-12 deficiency, was noted in the vegetarian mothers and their infants. Infants with high methylmalonic acid excretion were consuming milk low in vitamin B-12.

Absorption of calcium and its mobilization from bone during lactation are important for delivery of calcium to breast-feeding infants; whether calcium intake offsets bone resorption is not known. We hypothesized that calcium absorption is increased in lactation and greater in women on low calcium diets, resulting in similar rates of bone resorption and accretion. Calcium absorption and kinetic indexes were calculated by using two stable isotopic tracers in 8 women; 6 were studied both during lactation and nonlactation. Women consumed low calcium diets, with half receiving supplemental calcium. Intestinal absorption was related to serum 1,25-dihydroxyvitamin D and did not increase during lactation. Despite decreased urinary calcium excretion during lactation, especially in women with low calcium intake, net balance tended to be lower during lactation. Mean residence time decreased and bone resorption exceeded accretion in almost all lactating women. Calcium need for milk production appears to be met by decreased urinary excretion and increased bone resorption, and not by increased intestinal absorption.

Studies in European and other countries have shown that vitamin D deficiency during pregnancy may adversely affect fetal growth, bone ossification, tooth enamel formation, and neonatal calcium homeostasis. Whether effects of vitamin D deficiency on pregnant or lactating mothers differ from effects observed in nonpregnant or nonlactating women is not clear. Poor maternal vitamin D status during lactation results in low breast-milk vitamin D. However, human milk usually contains small vitamin D amounts and, under normal circumstances, the sunshine exposure of human-milk--fed infants is the major factor affecting their vitamin D status. Mothers at risk of vitamin D deficiency are those who avoid dairy products, which are routinely vitamin D fortified, and live in more northern latitudes. Dark-skinned women also are theoretically at risk of vitamin D deficiency. Sunshine exposure is a major vitamin D source, and given adequate exposure, supplemental vitamin D is not necessary. However, defining adequate sunshine exposure is difficult.

The purpose of this study was to compare estimates of body composition in two ethnic groups, 31 black and 38 white girls 10 through 16 years of age, to establish accurate and precise laboratory standards for field measures of body composition in the NHLBI Growth and Health Study HC 55025. The dual energy X-ray absorptiometry (DXA) measures of fat free mass (FFM) and % body fat (%BF) were made using Hologic QDR-1000/W. Corresponding values of FFM and %BF from underwater weighing (UWW) were determined using the two-component model of Siri, and these were corrected using the model of Lohman for white girls only. In the comparison of the different models and methods, the two-component model overestimated FFM compared to estimates from DXA for black girls, as did the corrected Lohman model for white girls. The two-component model significantly overestimated %BF in both white and black girls compared to corresponding estimates from DXA. The ratio of bone mineral content (BMC)/FFM affected the degree of %BF differences in black girls but not in white girls. Also, as the density of FFM increased or approached adult status in black girls (BMC/FFM increased), differences between the two-component model and estimates from DXA decreased. In both groups of girls, the relationship of %BF from UWW and DXA are a function of the level of body fatness. DXA values of %BF are greater than those from UWW under about 24% body fat, but the converse occurs above 25% body fat. The inability of UWW using the two-component model to account for the body composition in these girls can be corrected in part by measuring the variables for a multicomponent model or more easily by using DXA estimates of body composition. © 1994 Wiley-Liss, Inc., (Copyright © 1994 Wiley-Liss, Inc., A Wiley Company.)

Objective: To assess bone mineral content (BMC) status and serum vitamin D metabolite levels of infants and children with chronic cholestatic liver disease. To determine if severity of bone disease in these patients correlates with serum vitamin D metabolite levels., Methodology: We measured radial BMC with the use of a single-beam photon absorptiometer and serum vitamin D metabolite levels in 56 patients with chronic cholestasis seen at our institution from 1985 through 1991. Patients were divided into two groups according to age., Results: In group 1 (n = 37; age 2 to 22 months), decreased levels of BMC were seen as early as the first few months of life, with sharp decline observed with increasing age (approaching 3 to 5 standard deviations [SD] below the mean, P < .0003). Older patients (group 2, n = 19; age 2 to 20 years) had BMC values which clustered between 2 and 4 SD below the mean throughout the age range. Although a downward trend also was noted with increasing age, this was not statistically significant. Despite correction for weight-age or height-age, BMC was decreased in most of these patients. No correlation between severity of osteopenia and serum levels of 25(OH)-vitamin D and 1,25(OH)2-vitamin D was observed in either infants or older children., Conclusions: Decreased bone mineralization, as a complication of chronic cholestatic conditions, is a disease process that begins early in infancy, rapidly worsens with increasing age and hepatic dysfunction, and remains relatively stable in children with more stable liver disease.

Objective: Hydrostatic enema reduction of intussusception in children has been replaced by pneumatic reduction in a number of institutions. Colonic perforation occurs in as many as 2.8% of enema reductions, and questions persist about the relative safety of enemas performed with air vs fluid. The objectives of this study were to investigate and compare the pathologic patterns of in vivo colonic perforation and fecal spillage in young pigs given air and hydrostatic enemas, with and without the Valsalva maneuver., Materials and Methods: Colonic perforations were induced in 135 juvenile pigs. The pigs were divided into five groups, and enemas with air, barium, and water-soluble contrast material were given with and without the Valsalva maneuver to induce the perforations. During the enemas, the Valsalva maneuver was observed when the animals strained. In each animal, the enema was continued and pressure increased until a perforation was detected with fluoroscopy. Radiographic, gross, and histologic examinations of each animal were performed after perforations occurred. Differences in fecal spillage were noted, and the morphologic variations of the perforations and the surrounding tissue were determined., Results: Perforations with hydrostatic (barium, water-soluble) enemas occurred at approximately 120 mm Hg of pressure (average bag height, 57 in. [143 cm]). No significant variations were found between the type of material used for contrast or the use of the Valsalva maneuver. With air enemas, perforations occurred at a mean pressure of 108 mm Hg without the Valsalva maneuver and at 145 mm Hg with the Valsalva maneuver. Perforations during air enemas did not occur during the Valsalva maneuver (pressures as high as 270 mm Hg), but rather between Valsalva maneuvers. Hydrostatic enemas produced full-thickness tears that were larger than those induced by air enemas in all cases. Air enemas with and without the Valsalva maneuver produced partial-thickness tears in 45% and 10%, respectively, of the pigs. Fecal spillage was diffuse in all hydrostatic perforations. In air enemas, spillage was focal in 55% and 90%, respectively, and absent in 45% and 10%, respectively, of perforations produced with and without the Valsalva maneuver., Conclusion: Our results suggest that air enemas are safer than liquid enemas. Perforations that occurred during air enemas were smaller and associated with less fecal spillage and peritoneal contamination. The Valsalva maneuver appears to prevent colonic perforation during air enemas.

In small for gestational age (SGA) infants, bone mineral content (BMC) is low but the reasons are unclear and the possible relationships between calcium-regulating hormones and BMC have not been studied. We hypothesized that BMC would be lower and concentrations of serum parathyroid hormone and 1,25-dihydroxyvitamin D would be higher at birth in SGA infants than in appropriate for gestational age (AGA) infants. Forty-two term SGA infants and 126 term AGA infants, matched 1:3 specifically by gestation (+/- 1 week) and birth month, were studied prospectively. The BMC of the distal one third of the radius was measured before 3 days of age by photon absorptiometry. The BMC was lower in SGA than in AGA infants. Both SGA and AGA infants had lower BMC in summer or spring than in winter; BMC differences between groups remained significant after adjustment for season (p = 0.0001). Cord serum osteocalcin and 1,25-dihydroxyvitamin D values were lower in SGA than in AGA infants. There were no differences between groups in cord serum levels of intact parathyroid hormone, 25-hydroxyvitamin D, calcium, phosphorus, and magnesium. Relationships were positive between BMC and birth weight and were inverse between BMC and intact parathyroid hormone values. We suggest that reduced uteroplacental blood flow in SGA infants may result in reduced fetal-placental production of 1,25-dihydroxyvitamin D, which results in low BMC and low serum osteocalcin values; fetal serum parathyroid hormone values may be relatively elevated because of reduced placental mineral supply.

As an ancillary project of the National Heart Lung and Blood Institute's Growth and Health Study (NGHS), data of 31 black girls and 38 white girls, 10-16 years of age, were used to develop equations to predict fat-free mass (FFM) from selected anthropometric dimensions and bioelectric impedance measures of resistance and reactance. Subjects were drawn from ongoing projects at the Children's Hospital Medical Center (CHMC) to obtain girls of both races from a wide range of body mass indices. FFM was estimated from measures of dual energy X-ray absorptiometry (DXA). The resulting equations had a root mean square error (RMSE) of 1.9 kg and a coefficient of variation (CV) of 4.9% for black girls using independent variables: stature divided by resistance squared (S 2 /R), thigh circumference, subscapular and suprailiac skinfold thicknesses. The corresponding values for white girls were 1.1 kg and 3.2% using independent variables: S 2 /R, arm circumference, weight, and reactance divided by resistance (R/R c ). In addition to cross-validating the ethnic-specific equations using PRESS statistics, the equation for white girls was also cross-validated using an independent sample of 35 girls from the Fels Longitudinal Study selected to match the CHMC sample. The cross-validation yielded a pure error of 2.4 kg FFM and a CV of 7%. The predicted values for FFM from the equations were used to calculate percentage of body fat in the CHMC sample and the pure errors for estimating percentage of body fat were 3% for blacks and 2% for whites. © 1993 Wiley-Liss, Inc., (Copyright © 1993 Wiley-Liss, Inc., A Wiley Company.)

The clinical usefulness of hepatobiliary scintigraphy was evaluated in pediatric liver transplant recipients. One hundred fifteen hepatobiliary scintigraphic studies were performed in 30 patients who received 22 whole liver and 16 segmental grafts. Parameters that were useful in predicting an adverse outcome were failure to visualize excreted radiopharmaceutical at or beyond the biliary anastomosis on a study performed within 24 hours after transplant, and persistent or increasing delay in the time of visualization of excreted radiopharmaceutical. Abnormalities of liver uptake and excretion were seen in rejection, but they were also seen in patients who remained well without rejection or parenchymal disease. Significant biliary leaks were identified in the three cases in which they were known to be present. In liver transplant recipients, hepatobiliary imaging is useful in predicting graft survival and identifying biliary leaks.

Total exchangeable calcium pool size (TEP) and bone calcium accretion rate (Vo+) were measured using stable isotopes in healthy children and young adults. 42Ca or 46Ca was given intravenously to 10 children aged 10 months to 14 years and 3 women aged 23-33 years. Calcium kinetic parameters were determined using a two- or three-exponential curve of the resultant serum and urine tracer excesses. These data were compared with previously reported (radiotracer) kinetic studies of 21 children and 5 adults without known bone disease. Current results are comparable to those previously obtained, and the data from all studies were analyzed together. Total Vo+ was significantly greater in children aged 3-16 years than in adults (2.8 +/- 1.6 versus 0.7 +/- 0.2 g/day, p less than 0.01). Both TEP and Vo+ were significantly correlated to age independently of variations in body weight (p less than 0.01 for each). The ratio ko+ = Vo+/TEP was greater in children than adults (0.36 +/- 0.15 versus 0.12 +/- 0.03 day-1, p less than 0.001). These data demonstrate increased bone flow of calcium associated with increases in exchangeable calcium pools in children compared to adults. Vo+ and TEP may be maximum in early adolescence, associated with peak rates of net calcium accretion. The use of stable isotopes permits the safe evaluation of calcium kinetics in patients of all ages.

We previously suggested that "late" neonatal hypocalcemia is related to a low calcium-phosphorus ratio of current cow's milk-based formula compared with human milk. However, there are no longitudinal studies of ionized calcium and parathyroid hormone concentrations in neonates receiving formulas with varying Ca/P ratios. Sixty-nine term neonates were studied through 2 weeks of age, and formula-fed neonates were randomized at birth to receive formula with molar ratios of 0.9, 1.2, or 1.4. Serum phosphate concentrations on days 2 and 6 of age were higher, and ionized calcium levels lower on days 6 and 14, in formula-fed vs human milk-fed neonates. Serum intact parathyroid hormone level increased between days 2 and 6 in formula-fed neonates compared with a decrease in human milk-fed neonates. Serum parathyroid hormone level on day 6 correlated with phosphorus intake among formula-fed neonates. No differences were noted in serum mineral or hormone levels among formula-fed groups. We speculate that the lowering of serum ionized calcium concentrations in neonates fed a modern "humanized" cow's milk formula may be a factor in late neonatal hypocalcemia.

There is little information on the effect of lactation on maternal mineral and calcitropic hormone status. Therefore, we prospectively compared 26 lactating women with 32 nonlactating postpartum controls over the first year postpartum. Nineteen of the 26 women breast-fed their infants for fewer than 12 months and seven breast-fed for at least 12 months. During the first 6 months postpartum, serum phosphorus and parathyroid hormone (PTH) concentrations decreased with increasing time (P = .04 and P = .003, respectively) and were higher in lactating compared with nonlactating women (P less than .001 and P = .06, respectively). Mean serum phosphorus concentrations at 1, 3, and 6 months postpartum were 4.45, 4.75, and 4.34 mg/dL, respectively, in lactating women, versus 4.01, 3.64, and 3.44 mg/dL in controls. Mean PTH concentrations were 1.58, 1.48, and 1.36 ng/mL in lactating women, compared with 1.45, 1.20, and 1.16 ng/mL, respectively, in controls. At 12 months, women who were weaning had significantly higher mean serum calcium (10.11 mg/dL) and magnesium (2.36 mg/dL) concentrations than those who had weaned (8.79 and 2.03 mg/dL, respectively) or who had never lactated (8.90 and 1.95 mg/dL, respectively). Serum phosphorus, PTH, and 1,25-dihydroxyvitamin D were similar among women who were weaning (4.02 mg/dL, 1.46 ng/mL, and 54 pg/mL, respectively) and those who had weaned (3.94 mg/dL, 1.68 ng/mL, and 55 pg/mL), and were significantly higher than concentrations in women who had never lactated (3.25 mg/dL, 0.92 ng/mL, and 39 pg/mL). Our findings during lactation and the persistent differences observed during and after weaning are consistent with bone mobilization during lactation and a recovery of bone mass during and after weaning.

Vitamin B-12 status was assessed in a group of 110 adults and 42 children from a macrobiotic community in New England. Dietary and anthropometric information also was obtained. Fifty-one percent of the adults had low concentrations of serum vitamin B-12, which inversely correlated with duration of macrobiotic diet practice. Urinary methylmalonic acid (MMA) excretion was inversely correlated with serum vitamin B-12, and 30% of adults sampled had high urinary MMA. Fifty-five percent of children had high urinary MMA, and MMA was higher in the group that consumed a macrobiotic diet during their entire lifetime. Children were relatively short in stature and weight, and decreased stature was associated with high urinary MMA. In both adults and children vitamin B-12 status was better with more consumption of dairy products or with higher tertile of reported frequencies of vitamin B-12 consumption of various animal products. Vitamin B-12 status appeared to be unrelated to consumption of several vegetarian foods.

In a group of 13 strict vegetarian and 6 omnivorous lactating women, relationships were studied among maternal milk and serum vitamin B-12, and milk vitamin B-12 and infant urinary methylmalonic acid (MMA) excretion. Milk vitamin B-12 concentrations were lower in women consuming a strict vegetarian diet compared with an omnivorous diet. Milk vitamin B-12 was inversely related to length of time on a vegetarian diet and positively correlated with maternal serum vitamin B-12 concentrations. Infant urinary MMA excretion was inversely related to milk vitamin B-12 concentrations less than 362 pmol/L. The 1989 recommended dietary allowance for vitamin B-12 of 221 pmol/d for infants is close to the intake below which infant urinary MMA excretion is increased. We conclude that the current RDA for infants provides little margin of safety.

Fractional absorption of calcium was determined in 9 children aged 4.9 to 16.9 yr with chronic cholestatic liver disease to determine the role of calcium malabsorption in the development of metabolic bone disease. Radiological evidence of rickets was absent in all patients, but bone density, measured by single beam photon absorptiometry of the distal radius, was reduced in eight of nine subjects. Serum calcium and phosphorus concentrations were normal in all except one subject. Serum 25-hydroxyvitamin D concentration was decreased compared with controls in only one of nine patients, but serum 1,25-dihydroxyvitamin D concentrations were diminished in seven of nine subjects. In all subjects, dietary calcium and phosphorus intakes were greater than 80% of the RDA. Fractional absorption of calcium, determined by oral and intravenous administration of stable calcium isotopes, was similar in cholestatic compared with control subjects (37.1% +/- 12.5% vs. 34.0% +/- 16.4%). In the cholestatic subjects, calcium absorption correlated with serum 1,25-dihydroxyvitamin D (r = 0.871, p less than 0.002) but not 25-hydroxyvitamin D concentrations. Calcium balance, assessed by the duplicate diet method, was positive in four of five subjects. Anthropometric measurements were performed to examine the relationship between nutritional status and bone mineral content. Heights of all subjects were less than or equal to the 10th percentile and fat stores and somatic protein stores were less than the 25th percentile in six of nine subjects. We conclude that factors other than calcium malabsorption and decreased serum 25-hydroxyvitamin D concentration contribute to diminished bone mass in children with cholestatic liver disease.

The otologic findings from 197 subjects with repaired and unrepaired clefts and 121 noncleft controls are presented. All data were collected in Sri Lanka during a 3-week period attached to the Sri Lanka Project in 1986. Subjects were examined otoscopically and also tested audiometrically if they were able to perform a pure-tone audiogram, a performance test, or a distraction test. Subjects with clefts of the palate were found to have fewer otoscopically normal ears than the controls. A comparison between subjects with unrepaired and repaired palates revealed a similar rate of otoscopically normal ears in subjects older than 10 years of age. Comparisons for younger ages could not be performed because of a lack of subjects less than 10 years of age who had repaired palates. The impedance data were used to verify the accuracy of otoscopy in detecting effusion.

Serum vitamin B-12 and urinary methylmalonic acid (MMA) concentrations were determined in 62 healthy infants aged 1-6 mo. Urinary MMA was inversely correlated with serum vitamin B-12 concentrations (r = -0.550, p less than 0.001); serum vitamin B-12 was higher (p less than 0.001) and urinary MMA concentrations were lower (p less than 0.001) in formula-fed infants than in infants fed human milk (from the breast). Human-milk-fed infants who had received supplemental formula had higher serum vitamin B-12 concentrations than did infants exclusively fed human milk. It is not clear whether the serum vitamin B-12 and urinary MMA concentrations in infants fed human milk reflect biochemical deficiency of vitamin B-12, and the clinical significance of these findings needs to be investigated.

The effect of maternal diet on serum 1,25-dihydroxyvitamin D has not been determined in human lactation. Serum 1,25-dihydroxyvitamin D, other calcitropic hormones, osteocalcin, and minerals were examined in lactating and nonlactating women consuming a vegetarian or nonvegetarian diet. The vegetarian diet was a macrobiotic diet consisting primarily of whole cereal grains and vegetables; dairy products, eggs, and meats were generally avoided. We tested the thesis that the effect of lactation on serum 1,25-dihydroxyvitamin D is more pronounced in women on vegetarian diets than in those on nonvegetarian diets. Serum 1,25-dihydroxyvitamin D concentrations were significantly higher in lactating women compared with nonlactating women and in vegetarian compared with nonvegetarian women. Among vegetarian women, mean serum 1,25-dihydroxyvitamin D concentrations were 37% higher in the lactating group. For all subjects, serum parathyroid hormone was elevated during lactation compared with nonlactation. Thus, a vegetarian diet appears to be associated with increased serum 1,25-dihydroxyvitamin D during lactation.