Je Williams

Early diet and peak bone mass: 20 year follow-up of a randomized trial of early diet in infants born preterm

BACKGROUND Preterm infants are at risk of metabolic bone disease due to inadequate mineral intake with unknown consequences for later bone health. OBJECTIVE To test the hypotheses that (1) early diet programs peak bone mass and bone turnover; (2) human milk has a beneficial effect on these outcomes; (3) preterm subjects have reduced peak bone mass compared to population reference data. DESIGN 20 year follow-up of 202 subjects (43% male; 24% of survivors) who were born preterm and randomized to: (i) preterm formula versus banked breast milk or (ii) preterm versus term formula; as sole diet or supplement to maternal milk. Outcome measures were (i) anthropometry; (ii) hip, lumbar spine (LS) and whole body (WB) bone mineral content (BMC) and bone area (BA) measured using DXA; (iii) bone turnover markers. RESULTS Infant dietary randomization group did not influence peak bone mass or turnover. The proportion of human milk in the diet was significantly positively associated with WBBA and BMC. Subjects receiving >90% human milk had significantly higher WBBA (by 3.5%, p=0.01) and BMC (by 4.8%, p=0.03) than those receiving <10%. Compared to population data, subjects had significantly lower height SDS (-0.41 (SD 1.05)), higher BMI SDS (0.31 (1.33)) and lower LSBMD SDS (-0.29 (1.16)); height and bone mass deficits were greatest in those born SGA with birthweight <1250 g (height SDS -0.81 (0.95), LSBMD SDS -0.61 (1.3)). CONCLUSION Infant dietary randomization group did not affect peak bone mass or turnover suggesting the observed reduced final height and LS bone mass, most marked in growth restricted subjects with the lowest birthweight, may not be related to sub-optimal early nutrition. The higher WB bone mass associated with human milk intake, despite its low nutrient content, may reflect non-nutritive factors in breast milk. These findings may have implications for later osteoporosis risk and require further investigation.

Pediatric reference data for lean tissue properties: density and hydration from age 5 to 20 y

BACKGROUND Hydrometry and densitometry are widely used to assess pediatric body composition due to their ease of application. The accuracy of these techniques depends on the validity of age- and sex-specific constant values for lean tissue hydration or density. Empirical data on these constants, and their variability between individuals, are lacking. OBJECTIVES The objectives were to measure lean tissue hydration and density in a large sample of children and adolescents and to derive prediction equations. DESIGN Body composition was measured in 533 healthy individuals (91% white) aged 4-23 y by using the 4-component model. Age- and sex-specific median values for hydration and density were obtained by using the LMS (lambda, mu, sigma) method. Regression analysis was used to generate prediction equations on the basis of age, sex, and body mass index SD score (BMI SDS). Values were compared with those in previously published predictions. RESULTS Age-associated changes in density and hydration differed between the sexes. Compared with our empirical values, use of published values resulted in a mean bias of 2.1% fat (P < 0.0001). Age, sex, and BMI SDS were all significant predictors of lean tissue hydration and density. With adjustment for age and sex, hydration was higher, and density lower, in higher-BMI SDS individuals. CONCLUSIONS The chemical maturation of lean tissue is not a linear process and proceeds differently in males and females. Previously published reference values are inaccurate and induce clinically significant bias in percentage fat. New empirical reference values are provided for use in pediatric hydrometry and densitometry. Further research that extends to cover nonwhite ethnic groups is needed.

Body composition in normal weight, overweight and obese children: matched case–control analyses of total and regional tissue masses, and body composition trends in relation to relative weight

Background:Childhood obesity is defined on the basis of weight and height, using body mass index (BMI). There is little detailed information on the body composition characteristic of overweight and obesity.Objective:To evaluate total and regional body composition in overweight, obese and control children aged 7–14 years.Design:Body composition was measured by the four-component model and dual X-ray absorptiometry in 38 age- and sex-matched pairs of obese and control children. Body composition trends were also evaluated by quintile of BMI standard deviation score (SDS) in these and 31 other children (n=107; BMI SDS range −1.0 to 4.3).Results:Obese children were taller than controls (Δ=0.6 SDS; P=0.01) and had greater hydration of fat-free mass (FFM) (Δ=1.8 %, P<0.0001). After adjusting for these variables, obese children had greater FFM, fat mass (FM) and mineral (P<0.0001). Regional analyses showed that these differences were apparent in the arm, leg and trunk, but the three tissues had different proportional distributions of the excess. Fat was primarily in the trunk, but mineral in the leg. FM, FFM, hydration and mineral mass all increased across BMI SDS quintiles (P<0.0001), but the trend for FM was much the steepest.Discussion:The greater weight of obese children is due to excess FFM including mineral as well as excess fatness. Increasing weight has a strong continuous relationship with increasing FM across the whole spectrum of weight.

Body-composition reference data for simple and reference techniques and a 4-component model: a new UK reference child

BACKGROUND A routine pediatric clinical assessment of body composition is increasingly recommended but has long been hampered by the following 2 factors: a lack of appropriate techniques and a lack of reference data with which to interpret individual measurements. Several techniques have become available, but reference data are needed. OBJECTIVE We aimed to provide body-composition reference data for use in clinical practice and research. DESIGN Body composition was measured by using a gold standard 4-component model, along with various widely used reference and bedside methods, in a large, representative sample of British children aged from 4 to ≥20 y. Measurements were made of anthropometric variables (weight, height, 4 skinfold thicknesses, and waist girth), dual-energy X-ray absorptiometry, body density, bioelectrical impedance, and total body water, and 4-component fat and fat-free masses were calculated. Reference charts and SD scores (SDSs) were constructed for each outcome by using the lambda-mu-sigma method. The same outcomes were generated for the fat-free mass index and fat mass index. RESULTS Body-composition growth charts and SDSs for 5-20 y were based on a final sample of 533 individuals. Correlations between SDSs by using different techniques were ≥0.68 for adiposity outcomes and ≥0.80 for fat-free mass outcomes. CONCLUSIONS These comprehensive reference data for pediatric body composition can be used across a variety of techniques. Together with advances in measurement technologies, the data should greatly enhance the ability of clinicians to assess and monitor body composition in routine clinical practice and should facilitate the use of body-composition measurements in research studies.

Evaluation of Arm Anthropometry for Assessing Pediatric Body Composition: Evidence from Healthy and Sick Children

Arm anthropometry is used as a proxy of body composition in clinical and field research but its validity has not been established in children. To address this issue, mid-upper arm circumference (MUAC) and triceps skinfold thickness (TS) were measured in 110 healthy children aged 4.4–13.9 y (55 boys) and 49 cystic fibrosis (CF) patients aged 8.1–13.4 y (22 boys). Reference values were arm and whole-body fat mass (FM) and fat-free mass (FFM) measured by dual x-ray absorptiometry and four-component model, respectively. Arm fat area (AFA), MUAC, and TS correlated well with arm FM (r = 0.84–0.92) and total FM (r = 0.78–0.92). Arm muscle area (AMA) and MUAC correlated well with arm FFM (r = 0.68–0.82) and total FFM (r = 0.60–0.86). After adjusting for age, sex, and height, arm anthropometry correlated strongly with FM but weakly with FFM. AFA, MUAC, and TS explained 67, 63, and 61% of variability in total FM in healthy children and 70, 72, and 63% in CF. AMA and MUAC explained only 24 and 16% of variability in total FFM in healthy children and 33 and 28% in CF. Arm anthropometry is useful for predicting FM and ranking healthy children and patients for fatness. It has poorer success in predicting regional or total FFM.

Composition of the fat-free mass in obese and nonobese children: matched case-control analyses

OBJECTIVE:Most body composition techniques assume constant properties of the fat-free mass (FFM), such as hydration, density and mineralisation. Previous studies suggested that FFM composition may change in childhood obesity; however, this issue has not been investigated in detail.AIM:To compare FFM composition in obese and nonobese children.DESIGN:Observational matched case–control analyses.SUBJECTS:A total of 28 obese children (13 boys, 15 girls) and 22 nonobese children (10 boys, 12 girls) aged 7–14 y. Obesity was defined as body mass index centile >95.METHODS:Measurements were made of weight, height, total body water, and body volume. Bone mineral content was estimated in a subsample. Body composition was calculated using three- and four-component models.RESULTS:According to the three-component model (n=22 matched pairs), obese children had greater hydration (P<0.05), and reduced density (P=0.057) of FFM. According to the four component model (n=11 pairs), obese children had greater hydration (P<0.01) and reduced density (P<0.002) of FFM. The mineralisation of FFM was increased, but not significantly so.CONCLUSION:The greater hydration and reduced density of FFM of obese children should be taken into account if body composition is to be measured with optimum accuracy during treatment programmes. These differences may be addressed by using multicomponent rather than two-component models of body composition. Although the greater mineralisation of FFM in obese children was not significant in the present study, the four-component model is best able to address the combined differences in hydration and mineralisation that occur in childhood obesity.

Validation of BIA in Obese Children and Adolescents and Re-evaluation in a Longitudinal Study

Decrease in fat mass (FM) is a one of the aims of pediatric obesity treatment; however, measurement techniques suitable for routine clinical assessment are lacking. The objective of this study was to validate whole‐body bioelectrical impedance analysis (BIA; TANITA BC‐418MA) against the three‐component (3C) model of body composition in obese children and adolescents, and to test the accuracy of our new equations in an independent sample studied longitudinally. A total of 77 white obese subjects (30 males) aged 5–22 years, BMI‐standard deviation score (SDS) 1.6–3.9, had measurements of weight, height (HT), body volume, total body water (TBW), and impedance (Z). FM and fat‐free mass (FFM) were calculated using the 3C model or predicted from TANITA. FFM was predicted from HT2/Z. This equation was then evaluated in 17 other obese children (5 males) aged 9–13 years. Compared to the 3C model, TANITA manufacturers equations overestimated FFM by 2.7 kg (P < 0.001). We derived a new equation: FFM = −2.211 + 1.115 (HT2/Z), with r2 of 0.96, standard error of the estimate 2.3 kg. Use of this equation in the independent sample showed no significant bias in FM or FFM (mean bias 0.5 ± 2.4 kg; P = 0.4), and no significant bias in change in FM or FFM (mean bias 0.2 ± 1.8 kg; P = 0.7), accounting for 58% (P < 0.001) and 55% (P = 0.001) of the change in FM and FFM, respectively. Our derived BIA equation, shown to be reliable for longitudinal assessment in white obese children, will aid routine clinical monitoring of body composition in this population.

Prediction of total body water in infants and children

Background: In paediatric clinical practice treatment is often adjusted in relation to body size, for example the calculation of pharmacological and dialysis dosages. In addition to use of body weight, for some purposes total body water (TBW) and surface area are estimated from anthropometry using equations developed several decades previously. Whether such equations remain valid in contemporary populations is not known. Methods: Total body water was measured using deuterium dilution in 672 subjects (265 infants aged <1 year; 407 children and adolescents aged 1–19 years) during the period 1990–2003. TBW was predicted (a) using published equations, and (b) directly from data on age, sex, weight, and height. Results: Previously published equations, based on data obtained before 1970, significantly overestimated TBW, with average biases ranging from 4% to 11%. For all equations, the overestimation of TBW was greatest in infancy. New equations were generated. The best equation, incorporating log weight, log height, age, and sex, had a standard error of the estimate of 7.8%. Conclusions: Secular trends in the nutritional status of infants and children are altering the relation between age or weight and TBW. Equations developed in previous decades significantly overestimate TBW in all age groups, especially infancy; however, the relation between TBW and weight may continue to change. This scenario is predicted to apply more generally to many aspects of paediatric clinical practice in which dosages are calculated on the basis of anthropometric data collected in previous decades.

Evaluation of DXA against the four-component model of body composition in obese children and adolescents aged 5-21 years.

Background:Body composition is increasingly measured in pediatric obese patients. Although dual-energy X-ray absorptiometry (DXA) is widely available, and is precise, its accuracy for body composition assessment in obese children remains untested.Objective:We aimed to evaluate DXA against the four-component (4C) model in obese children and adolescents in both cross-sectional and longitudinal contexts.Design:Body composition was measured by DXA (Lunar Prodigy) and the 4C model in 174 obese individuals aged 5–21 years, of whom 66 had a second measurement within 1.4 years. The Bland–Altman method was used to assess agreement between techniques for baseline body composition and change therein.Results:A significant minority of individuals (n=21) could not be scanned successfully due to their large size. At baseline, in 153 individuals with complete data, DXA significantly overestimated fat mass (FM; Δ=0.9, s.d. 2.1 kg, P<0.0001) and underestimated lean mass (LM; Δ=−1.0, s.d. 2.1 kg, P<0.0001). Multiple regression analysis showed that gender, puberty status, LM and FM were associated with the magnitude of the bias. In the longitudinal study of 51 individuals, the mean bias in change in fat or LM did not differ significantly from zero (FM: Δ=−0.02, P=0.9; LM: Δ=0.04, P=0.8), however limits of agreement were wide (FM: ±3.2 kg; LM: ±3.0 kg). The proportion of variance in the reference values explained by DXA was 76% for change in FM and 43% for change in LM.Conclusions:There are limitations to the accuracy of DXA using Lunar Prodigy for assessing body composition or changes therein in obese children. The causes of differential bias include variability in the magnitude of tissue masses, and stage of pubertal development. Further work is required to evaluate this scenario for other DXA models and manufacturers.

Undercarboxylated osteocalcin and bone mass in 8–12 year old children with cystic fibrosis ☆

UNLABELLED Young adults with cystic fibrosis (CF) frequently develop bone disease. One suggested aetiological factor is suboptimal vitamin K status with impaired carboxylation of osteocalcin and abnormal bone formation. METHODS We measured bone mineralization and turnover in thirty-two 8-12 year old CF patients (14 boys) using Dual Energy X-ray absorptiometry (whole body (WB) and lumbar spine (LS)), 25-OH Vitamin D, PTH and markers of bone formation (plasma osteocalcin, N-terminal pro-peptide of type 1 collagen (P1NP)), plus an indirect measure of vitamin K status, undercarboxylated osteocalcin (uc-OC). RESULTS LS bone mineral density (BMD) standard deviation (SD) scores were < -1.0 in 20% of subjects. Size-adjusted LS and WB bone mass was normal. Compared to reference data, % uc-OC was high and P1NP low. LS bone mass was predicted by % uc-OC but not other markers (0.4% decrease in size-adjusted LSBMC (p=0.05); 0.04 SD decrease in LSBMAD (p=0.04) per 1% increase in uc-OC). CONCLUSION Markers suggestive of sub-optimal vitamin K status and low bone formation were present despite normal size-adjusted bone mass. The association between LSBMC and % uc-OC is consistent with the hypothesis that sub-optimal vitamin K status is a risk factor for CF bone disease. This should ideally be investigated in an intervention trial.