International estimated fetal weight standards of the INTERGROWTH-21st Project.

OBJECTIVE: Estimated fetal weight (EFW) and fetal biometry are complementary measures used to screen for fetal growth disturbances. Our aim was to provide international EFW standards to complement the INTERGROWTH-21st Fetal Growth Standards that are available for use worldwide. METHODS: Women with an accurate gestational-age assessment, who were enrolled in the prospective, international, multicenter, population-based Fetal Growth Longitudinal Study (FGLS) and INTERBIO-21st Fetal Study (FS), two components of the INTERGROWTH-21st Project, had ultrasound scans every 5 weeks from 9-14 weeks' until 40 weeks' gestation. At each visit, measurements of fetal head circumference (HC), biparietal diameter, occipitofrontal diameter, abdominal circumference (AC) and femur length (FL) were obtained blindly by dedicated research sonographers using standardized methods and identical ultrasound machines. Birth weight was measured within 12 h of delivery by dedicated research anthropometrists using standardized methods and identical electronic scales. Live babies without any congenital abnormality, who were born within 14 days of the last ultrasound scan, were selected for inclusion. As most births occurred at around 40 weeks' gestation, we constructed a bootstrap model selection and estimation procedure based on resampling of the complete dataset under an approximately uniform distribution of birth weight, thus enriching the sample size at extremes of fetal sizes, to achieve consistent estimates across the full range of fetal weight. We constructed reference centiles using second-degree fractional polynomial models. RESULTS: Of the overall population, 2404 babies were born within 14 days of the last ultrasound scan. Mean time between the last scan and birth was 7.7 (range, 0-14) days and was uniformly distributed. Birth weight was best estimated as a function of AC and HC (without FL) as log(EFW) = 5.084820 - 54.06633 × (AC/100)3 - 95.80076 × (AC/100)3 × log(AC/100) + 3.136370 × (HC/100), where EFW is in g and AC and HC are in cm. All other measures, gestational age, symphysis-fundus height, amniotic fluid indices and interactions between biometric measures and gestational age, were not retained in the selection process because they did not improve the prediction of EFW. Applying the formula to FGLS biometric data (n = 4231) enabled gestational age-specific EFW tables to be constructed. At term, the EFW centiles matched those of the INTERGROWTH-21st Newborn Size Standards but, at < 37 weeks' gestation, the EFW centiles were, as expected, higher than those of babies born preterm. Comparing EFW cross-sectional values with the INTERGROWTH-21st Preterm Postnatal Growth Standards confirmed that preterm postnatal growth is a different biological process from intrauterine growth. CONCLUSIONS: We provide an assessment of EFW, as an adjunct to routine ultrasound biometry, from 22 to 40 weeks' gestation. However, we strongly encourage clinicians to evaluate fetal growth using separate biometric measures such as HC and AC, as well as EFW, to avoid the minimalist approach of focusing on a single value. © 2016 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Serum 25-Hydroxyvitamin D associated with indicators of body fat and insulin resistance in prepubertal chilean children.

BACKGROUND: Consistent data on the relation between vitamin D, body fat and insulin resistance (IR) in children are lacking. OBJECTIVES: (1) To evaluate the association between serum 25-Hydroxyvitamin D [25(OH)D] and key indicators of: adiposity (total and central), IR, and (2) to estimate serum 25(OH)D cut-offs that best reflect IR and total and central adiposity in children. SUBJECTS/METHODS: Prepubertal children (n=435, ~53% girls; ~age 7 years) from the Growth and Obesity Chilean Cohort Study were evaluated for potential associations between serum 25(OH)D and indicators of: (1) total adiposity (body mass index by age (BAZ), body fat (including three-component model)), central adiposity (waist circumference and trunk fatness); (2) IR (homeostasis model assessment of IR) and insulin sensitive (quantitative insulin sensitivity check index) using standardized multiple regression models with standardized coefficients and receiver operating characteristic curves. RESULTS: Overall, mean serum 25(OH)D was 32.1±9.2 ng ml(-1), while 19.4% of children were obese (BAZ⩾2 s.d.). Serum 25(OH)D was inversely associated with indicators of total and central adiposity and with IR indicators. Effect sizes were moderate in girls (~0.3 for adiposity and IR indicators), while, weaker values were found in boys. Serum 25(OH)D estimated cut-offs that best predicted total, central adiposity and IR were~30 ng ml(-1). Children with suboptimal serum 25(OH)D (<30 ng ml(-1)) had a higher risk (two to three times) of being obese (high BAZ, body fat percent and/or central adiposity); and three to four times greater risk for IR. CONCLUSIONS: Serum 25(OH)D was inversely associated with adiposity (total and central) and IR indicators in prepubertal Chilean children. The conventional cut-off of vitamin D sufficiency (⩾30 ng ml(-1)) was adequate to assess obesity and IR risk in this age group.

Early adiposity rebound is associated with metabolic risk in 7-year-old children.

BACKGROUND: Early adiposity rebound (AR <5 years) has been consistently associated with increased obesity risk, but its relationship with metabolic markers is less clear; in addition, the biologic mechanisms involved in these associations have not been established. OBJECTIVE: The objective of this study was to assess the association between timing of AR and metabolic status at age 7 years, evaluating the potential role of adiposity, adipose functionality and skeletal maturation in this association. DESIGN: We estimated the age of AR from the body mass index (BMI) trajectories from 0 to 7 years in 910 children from the Growth and Obesity Chilean Cohort Study (GOCS). At 7 years, we measured waist circumference (WC) and blood glucose, insulin, triglycerides and high-density lipoprotein-cholesterol levels and constructed a metabolic risk score. We also measured percent fat mass (adiposity), plasma concentrations of leptin and adiponectin (adipose functionality) and bone age using wrist ultrasound (skeletal maturation). RESULTS: We found that 44% of the children had an AR <5 years. Earlier AR was associated with larger WC (ß: 5.10 (95% confidence interval (CI): 4.29-5.91)), higher glucose (ß: 1.02 (1.00-1.03)), insulin resistance (ß Homeostatic Model Assessment: 1.06 (1.03-1.09)), triglycerides (ß: 10.37 (4.01-6.73)) and adverse metabolic score (ß: 0.30 (0.02-0.37)). Associations decreased significantly if adiposity was added to the models (i.e. ß WC: 0.85 (0.33-1.38)) and, to a lesser extent, when adipokines (i.e. ß WC: 0.73 (0.14-1.32)) and skeletal maturation (i.e. ß WC: 0.65 (0.10-1.20)) were added. CONCLUSION: In GOCS children, AR at a younger age predicts higher metabolic risk at 7 years; these associations are mostly explained by increased adiposity, but adipose dysfunction and accelerated skeletal maturation also have a role.

Nutrition economics - food as an ally of public health.

Non-communicable diseases (NCD) are a major and increasing contributor to morbidity and mortality in developed and developing countries. Much of the chronic disease burden is preventable through modification of lifestyle behaviours, and increased attention is being focused on identifying and implementing effective preventative health strategies. Nutrition has been identified as a major modifiable determinant of NCD. The recent merging of health economics and nutritional sciences to form the nascent discipline of nutrition economics aims to assess the impact of diet on health and disease prevention, and to evaluate options for changing dietary choices, while incorporating an understanding of the immediate impacts and downstream consequences. In short, nutrition economics allows for generation of policy-relevant evidence, and as such the discipline is a crucial partner in achieving better population nutritional status and improvements in public health and wellness. The objective of the present paper is to summarise presentations made at a satellite symposium held during the 11th European Nutrition Conference, 28 October 2011, where the role of nutrition and its potential to reduce the public health burden through alleviating undernutrition and nutrition deficiencies, promoting better-quality diets and incorporating a role for functional foods were discussed.

Conceptual basis for prescriptive growth standards from conception to early childhood: present and future.

BACKGROUND: Healthy growth in utero and after birth is fundamental for lifelong health and wellbeing. The World Health Organization (WHO) recently published standards for healthy growth from birth to 6 years of age; analogous standards for healthy fetal growth are not currently available. Current fetal growth charts in use are not true standards, since they are based on cross-sectional measurements of attained size under conditions that do not accurately reflect normal growth. In most cases, the pregnant populations and environments studied are far from ideal; thus the data are unlikely to reflect optimal fetal growth. A true standard should reflect how fetuses and newborns 'should' grow under ideal environmental conditions. OBJECTIVE: The development of prescriptive intrauterine and newborn growth standards derived from the INTERGROWTH-21(st) Project provides the data that will allow us for the first time to establish what is 'normal' fetal growth. METHODS: The INTERGROWTH-21(st) study centres provide the data set obtained under pre-established standardised criteria, and details of the methods used are also published. DESIGN: Multicentre study with sites in all major geographical regions of the world using a standard evaluation protocol. RESULTS: These standards will assess risk of abnormal size at birth and serve to evaluate potentially effective interventions to promote optimal growth beyond securing survival. DISCUSSION: The new normative standards have the potential to impact perinatal and neonatal survival and beyond, particularly in developing countries where fetal growth restriction is most prevalent. They will help us identify intrauterine growth restriction at earlier stages of development, when preventive or corrective strategies might be more effective than at present. CONCLUSION: These growth standards will take us one step closer to effective action in preventing and potentially reversing abnormal intrauterine growth. Achieving 'optimal' fetal growth requires that we act not only during pregnancy but that we optimize the maternal uterine environment from the time before conception, through embryonic development until fetal growth is complete. The remaining challenge is how 'early' will we be able to act, now that we can better monitor fetal growth.

Fish consumption and cognitive function among older people in the UK: baseline data from the OPAL study.

BACKGROUND: Observational epidemiological data suggest that habitual consumption in later life of oily fish, rich in n-3 long-chain polyunsaturated fatty acids (n-3 LCPs), is associated with better cognitive function, slower rates of cognitive decline and a lower risk of dementia. In this paper we present data on baseline fish consumption and cognitive function in cognitively healthy older people randomised onto the Older People And n- 3 Long-chain polyunsaturated fatty acid (OPAL) study. METHODS: In total, 867 older people were recruited to join the OPAL study from 20 general practices in England and Wales. Participants were aged 70-79 years at baseline were free of dementia and diabetes, had a Mini-Mental State Examination score of 24 or greater and did not report daily fish oil supplement consumption. Self-reported habitual fish consumption was assessed at baseline via questions on frequency and type of fish consumption. Cognitive function at baseline was assessed via validated cognitive tests assessing memory, executive function, psychomotor speed and attention, including the Californian Verbal Learning Test (CVLT), the primary outcome of the OPAL study. Reported age at leaving full time education was recorded as a measure of educational achievement and psychological health was measured using the GHQ-30 questionnaire. RESULTS: Unadjusted analysis revealed significant positive associations between reported fish consumption and the CVLT scores with a mean increase of approximately 0.24 words remembered for each increase in level of reported fish consumption. These associations were noticeably attenuated on adjustment for age, gender and reported age at leaving full-time education and did not remain significant on further adjustment for GHQ-30 score. Similar associations were also observed between fish consumption and the global cognitive z-score, memory score, executive function score and delay scores in unadjusted analysis with the associations again attenuated on adjustment. CONCLUSIONS: Baseline data from participants randomised into the OPAL study provide support for the hypothesis that higher fish consumption is associated with better cognitive function in later life. However, although in the main associations remain after adjusting for education and psychological health, the data do not allow us to rule out the possibility of residual confounding e.g. from socioeconomic status or other health behaviours. Evidence is needed from randomised clinical trials to clarify the role of n-3 LCPs in cognitive health in later life in the normal older person population.

Uptake of cholesterol-rich remnant lipoproteins by human monocyte-derived macrophages is mediated by low density lipoprotein receptors.

The uptake and degradation of cholesterol-rich remnant lipoproteins, referred to as beta-VLDL, are shown in the present study to be mediated by LDL receptors (apoB,E(LDL) receptors), not by unique beta-VLDL receptors. Human blood monocytes cultured for 5-7 d bound apoB- and/or apoE-containing lipoproteins from different species with affinities equivalent to those demonstrated for the receptors on cultured human fibroblasts. Low density lipoproteins competed effectively and completely with 125I-beta-VLDL for binding to and degradation by monocyte-derived macrophages. Specific polyclonal antibodies to bovine apoB,E(LDL) receptors abolished both LDL and beta-VLDL uptake by normal human monocyte-macrophages. Immunoblots of monocyte-macrophage extracts with these antibodies revealed a single protein in human macrophages with an apparent molecular weight identical to that of the apoB,E(LDL) receptor found on human fibroblasts. Like receptors on cultured human fibroblasts, the apoB,E(LDL) receptors on monocyte-macrophages responsible for 125I-beta-VLDL and 125I-LDL uptake were efficiently down regulated by preincubation of the cells with beta-VLDL or LDL. Finally, monocyte-macrophages from seven homozygous familial hypercholesterolemia subjects were unable to metabolize beta-VLDL or LDL, but demonstrated normal uptake of acetoacetylated LDL. The classic apoB,E(LDL) receptors on human monocyte-macrophages thus mediate the uptake of beta-VLDL by these cells.

Anthropometric indicators as predictors of total body fat and cardiometabolic risk factors in Chilean children at 4, 7 and 10 years of age.

BACKGROUND/OBJECTIVE: To compare the association between anthropometric indicators of global and central obesity as predictors of total body fat (TBF) and cardiometabolic risk factors in children. SUBJECTS/METHODS: A total of 1044 children were evaluated at 4 years (n=320), 7 years (n=1044) and 10 years (n=483). The following anthropometric indices were determined: body mass index (BMI) for age (BAZ, WHO), waist circumference (WC), waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR). To estimate TBF we used validated predictive equations. We measured blood sample concentrations of glucose, insulin, triglycerides, total cholesterol, Low-density lipoprotein (LDL) and High-density lipoprotein (HDL), adiponectin, C-reactive protein (CRP) and Insulin-like growth factor-1 (IGF-1). RESULTS: Adiposity and cardiometabolic markers, particularly those related to glucose metabolism increased from 4 years to 10 years. BAZ and WC were highly correlated to body fat at all ages (all r>0.8) but at 10 years WC was more strongly correlated than BAZ (r=0.94 WC vs r=0.88 BAZ, P<0.05); conversely, WHtR was significantly associated with body fat from 7 years (r=0.85) and 10 years (r=0.88). WHR was unrelated all over the period studied at all ages. Anthropometrical adiposity indicators became associated to cardiometabolic markers only from 7 years on with associations being slightly higher at 10 years, particularly for adiponectin and lipid markers. At all ages, BAZ, WC and WHtR performed similarly as cardiometabolic markers (P<0.05) while WHR was a slightly weaker marker. CONCLUSIONS: Relationship between anthropometrical indicators of adiposity and cardiometabolic markers becomes stronger from 7 years onwards; BAZ, WC and WHtR perform similarly as markers of cardiometabolic risk at least until 10 years of age.

Impact of baseline vitamin B12 status on the effect of vitamin B12 supplementation on neurologic function in older people: secondary analysis of data from the OPEN randomised controlled trial.

BACKGROUND/OBJECTIVES: The available evidence from randomised controlled trials suggests that vitamin B12 supplementation does not improve neurologic function in older people with marginal but not deficient Vitamin B12 status. This secondary analysis used data from the Older People and Enhanced Neurological function (OPEN) randomised controlled trial to assess whether baseline vitamin B12 status or change in vitamin B12 status over 12 months altered the effectiveness of dietary vitamin B12 supplementation on neurologic function in asymptomatic older people with depleted vitamin B12 status at study entry. SUBJECTS/METHODS: Vitamin B12 status was measured as serum concentrations of vitamin B12, holotranscobalamin, homocysteine and via a composite indicator (cB12). Neurological function outcomes included eleven electrophysiological measures of sensory and motor components of peripheral and central nerve function. Linear regression analyses were restricted to participants randomised into the intervention arm of the OPEN trial (n=91). RESULTS: Analyses revealed an inconsistent pattern of moderate associations between some measures of baseline vitamin B12 status and some neurological responses to supplementation. The directions of effect varied and heterogeneity in effect across outcomes could not be explained according to type of neurological outcome. There was no evidence of differences in the neurological response to vitamin B12 supplementation according to change from baseline over 12 months in any indicator of B12 status. CONCLUSIONS: This secondary analysis of high-quality data from the OPEN trial provides no evidence that baseline (or change from baseline) vitamin B12 status modifies the effect of vitamin B12 supplementation on peripheral or central nerve conduction among older people with marginal vitamin B12 status. There is currently insufficient evidence of efficacy for neurological function to support population-wide recommendations for vitamin B12 supplementation in healthy asymptomatic older people with marginal vitamin B12 status.

GOCS cohort: children's eating behavior scores and BMI.

BACKGROUND/OBJECTIVE: In Chile, approximately one in three children under 6 years of age reported overweight/obese, while one in four children in elementary school suffer from obesity. There is a paucity of population-based information on the influence of childhood eating behavior on anthropometric measures related to obesity. To assess the association between eating behavior scores and Body Mass Index (BMI) z-scores in 7-10-year-old Chilean children. SUBJECTS/METHODS: We conducted a cross-sectional study in 1058 children aged 7-10 (51% girls) from the 'Growth and Obesity Chilean Cohort Study' (GOCS). Direct measures of weight and height were used to compute BMI z-scores according to World Health Organization (WHO) curves. Children were classified as normal weight (-1<1 s.d.), overweight (1<2 s.d.) and obese (⩾2 s.d.). Eating behavior scores were measured through the Child Eating Behavior Questionnaire (CEBQ), previously adapted and validated for Chilean children. Multiple linear regressions were carried out using BMI z-score as the outcome and eating behavior scores as explanatory variables. All models were adjusted by age and gender. RESULTS: BMI z-scores were positively associated with pro-intake scores in the subscales 'enjoyment of food', 'emotional overeating' and 'food responsiveness' (P<0.0001). Contrary to other studies, 'desire for drinks' scores were also associated with BMI z-scores (P<0.0001). In contrast, food-avoidant 'satiety responsiveness', 'slowness in eating' and 'food-fussiness' scores were negatively associated with BMI z-scores (P<0.0001). CONCLUSION: We found a significant relationship between eating behavior scores and BMI z-scores in Chilean children, showing that BMI in 7-10-year-old Chilean children is positively associated with pro-intake eating behavior scores and negatively associated with anti-intake eating behavior scores. The identification of specific eating behaviors patterns related to obesity will provide important information for the implementation of prevention programs for this disease.

Pre-gestational overweight in guinea pig sows induces fetal vascular dysfunction and increased rate of large and small fetuses.

In humans, obesity before and during pregnancy is associated with both fetal macrosomia and growth restriction, and long-term cardiovascular risk in the offspring. We aimed to determine whether overweighted pregnant guinea pig sows results in an increased fetal weight at term and the effects on the vascular reactivity in fetal systemic and umbilical arteries. Pregnant guinea pigs were classified as control (n=4) or high weight (HWS, n=5) according to their pre-mating weight, and their fetuses extracted at 0.9 gestation (~60 days). Segments of fetal femoral and umbilical arteries were mounted in a wire myograph, where the contractile response to KCl (5-125 mM), and the relaxation to nitric oxide synthase-dependent agents (insulin, 10-10-10-7 and acetylcholine, 10-10-10-5) and nitric oxide [sodium nitroprusside (SNP), 10-10-10-5] were determined. Fetuses from HWS (HWSF) were grouped according to their body weight as low (85 g) fetal weight, based on the confidence interval (76.5-84.9 g) of the control group. No HWSF were observed in the normal range. Umbilical arteries from HWSF showed a lower response to KCl and insulin compared with controls, but a comparable response with SNP. Conversely, femoral arteries from HWSF showed an increased response to KCl and acetylcholine, along with a decreased sensitivity to SNP. These data show that overweight sows have altered fetal growth along gestation. Further, large and small fetuses from obese guinea pig sows showed altered vascular reactivity at umbilical and systemic vessels, which potentially associates with long-term cardiovascular risk.

Regulation of copper uptake and transport in intestinal cell monolayers by acute and chronic copper exposure.

Adaptation to high and low copper intake in mammals depends on the cellular control of influx, efflux and storage mechanisms of cellular copper concentrations. In the present study, we used an intestinal cell line (Caco-2), grown in bicameral chambers to study the effect of equilibrium loading with copper. We analyzed (64)Cu uptake from the apical surface, intracellular metal (Cu, Zn, Fe) content, (64)Cu transport into the basal chamber, and total copper, zinc and iron in the basal chamber. We found that the (64)Cu uptake is saturable, shows a linear response phase up to 1.5 microM reaching a plateau at 4-6 microM extracellular Cu. Intracellular copper increased 21.6-fold, from 1.5 to 32.4 mM (at 0.2-20.2 microM extracellular copper respectively). The time course for (64)Cu uptake and transport was linear when the cells were incubated with different copper concentrations. Uptake increased 10-fold when intracellular copper concentration was raised. Fluxes were lowest at 1.5 mM and highest at 32.4 mM Cu intracellular copper (2.03 and 20. 98 pmole (64)Cu insert(-1) h(-1), respectively). The apical-to-basolateral copper transfer rate was lower at 32.4 mM as compared to 1.5 mM intracellular copper (0.55-1.95 pmole (64)Cu insert(-1) h(-1), respectively). The total copper in the basal chamber increased 4.2-fold (from 3.04 to 12.85 pmole Cu insert(-1) h(-1)) when the intracellular copper concentration was raised. If cells are preincubated in a low copper medium most of the newly incorporated copper (64%) is transferred to the basolateral compartment. In contrast, under preloading with high copper concentration, only 4% of the fresh copper is transferred to the basal chamber; however, the intracellular copper contribution to this chamber increases by 4.2-fold. Thus, the process results in an increase in both storage and intracellular-to-basolateral flux of copper. In summary, our results indicate that copper fluxes from apical-to-cell and apical-to-basolateral domains are affected by intracellular copper concentration suggesting that mechanisms of copper transport involved in cellular adaptation to low and high copper exposure are different.

Oxidative stress as common trait of endothelial dysfunction in chorionic arteries from fetuses with IUGR and LGA.

INTRODUCTION: Fetal macrosomia and intrauterine growth restriction (IUGR) associate with increased morbidity in the neonate. Placental vascular relaxation is impaired in fetal macrosomia, as well as in IUGR, and this could result from increased oxidative stress present in both conditions. We determined the role of pro- and anti-oxidants on NOS dependent relaxation in placental chorionic arteries from pregnancies with LGA babies from overweight and/or obese mothers (LOOM) and IUGR fetuses from normal BMI women. METHODS: Chorionic arteries were mounted in a wire-myograph, where responses to the NOS-dependent agent CGRP in presence or absence of the antioxidant N-acetyl cysteine (NAC), the pro-oxidant SIN-1, the SOD inhibitor DDC, and the GPx inhibitor MS were determined. Additionally the presence of pro- and antioxidant enzymes (NOX-4, SOD-1, SOD-2 and GPx-1) and eNOS in chorionic and umbilical vessels were addressed by immunohistochemistry. RESULTS: Maximal CGRP-induced relaxation was comparable to controls but presented a reduced potency in chorionic arteries from LOOM placentae, whilst in IUGR vessels both maximal response and potency were reduced. NAC increased maximal relaxation in controls, IUGR and LOOM arteries, whilst SIN-1 completely abolished the CGRP-induced relaxation only in IUGR and LOOM samples, the later effect was paralleled by SOD or GPx inhibition. These responses associated with the presence of NOX-4, SOD-1 and GPx-1 in the endothelium and vascular wall of chorionic and umbilical arteries in the different groups studied. DISCUSSION: These data suggest that NOS dependent relaxation in placental vessels from IUGR and LOOM pregnancies present a higher sensitivity to oxidative stress.

Evaluation of simple body composition methods: assessment of validity in prepubertal Chilean children.

BACKGROUND/OBJECTIVE: The aim of this study was to assess the validity of body fatness estimations based on skinfolds and bioelectrical iImpedance analyses (BIA) measurements compared to a three-component model (3C model) in prepubertal Chilean children, considering potential differences by sex and nutritional status. SUBJECTS/METHODS: Four hundred and twenty four Chilean children (198 females and 226 males) were assessed for body composition. Body fat percentage (BF%) was evaluated by Skinfold equations (Slaughter, Ramirez and Huang) and Bioelectrical impedance (BIA: Tanita BC-418MA) using both the equipment and the Ramirez equation. Measurements based on a 3C model constructed from total body water estimates by isotope dilution and from body volume estimates by air displacement plethysmography were used as gold standard. RESULTS: Coefficient of determination (R2) values were higher in overweight and in the whole group of both gender. All slopes were differed significantly from 1, and most intercepts were significantly different from 0. Skinfold Equations: an underestimation of BF% was found for all equations, being higher with the Slaughter equation. BIA: Tanita underestimated BF% in all groups, whereas Ramirez equation shows an overestimation. CONCLUSIONS: Skinfolds and bio-impedance equations serve well to rank children according to their BF%. However, these methods are not accurate for describing body composition in prepubertal Chilean children.

Coinheritance of two mild defects in low density lipoprotein receptor function produces severe hypercholesterolemia.

A family is described in which the probands, twin girls, had severe hypercholesterolemia suggestive of familial hypercholesterolemia (FH). The mother of the twins had normal plasma cholesterol levels, and the father had only moderate hypercholesterolemia. Moreover, low density lipoprotein (LDL) binding studies in cultured fibroblasts and isolated lymphocytes in the parents failed to reveal significantly reduced LDL receptor activity that is typical of FH heterozygotes. Turnover studies of LDL in the parents, however, revealed low fractional clearance rates (FCRs) for LDL. In cultured fibroblasts and isolated lymphocytes from the twin probands, binding of normal LDL was half normal or less. LDL turnover studies in the twins revealed a marked reduction in FCRs for LDL. When the twins were treated with lovastatin, however, FCRs for LDL increased significantly, suggesting enhancement of LDL receptor activity. This finding along with LDL binding studies in the cultured cells infer that the twins did not have homozygous FH. In addition, all family members tested negative for familial defective apolipoprotein-B-100, and LDL isolated from the mother and twins showed normal binding to normal fibroblasts. The overall data suggest that the severe hypercholesterolemia in the offspring was due to inheritance of mild to moderate defects of LDL receptor function from both parents. Although the latter defects could not be detected with certainty by in vitro tests in each parent, they were evident from LDL turnover tests. Coinheritance of these defects apparently produced severe hypercholesterolemia in the offspring.

Copper as an essential nutrient.

Animal and human studies have shown that copper is involved in the function of several enzymes. Studies have also shown that copper is required for infant growth, host defense mechanisms, bone strength, red and white cell maturation, iron transport, cholesterol and glucose metabolism, myocardial contractility, and brain development. Copper deficiency can result in the expression of an inherited defect such as Menkes syndrome or in an acquired condition. Acquired deficiency is mainly a pathology of infants; however, it has been diagnosed also in children and adults. Most cases of copper deficiency have been described in malnourished children. The most constant clinical manifestations of acquired copper deficiency are anemia, neutropenia, and bone abnormalities. Other, less frequent manifestations are hypopigmentation of the hair, hypotonia, impaired growth, increased incidence of infections, alterations of phagocytic capacity of the neutrophils, abnormalities of cholesterol and glucose metabolism, and cardiovascular alterations. Measurements of serum copper and ceruloplasmin concentrations are currently used to evaluate copper status. These indexes are diminished in severe to moderate copper deficiency; however, they are less sensitive to marginal copper deficiency. Erythrocyte superoxide dismutase and platelet cytochrome c activities may be more promising indexes for evaluating marginal copper deficiency.

Limits of metabolic tolerance to copper and biological basis for present recommendations and regulations.

Acute copper toxicity is infrequent in humans. The evidence for chronic toxicity is derived principally from patients with Wilson disease and cases of infantile cirrhosis that were related to excessive copper intakes. The evaluation of the safety of a nutrient requires toxicologic studies to determine the limits of safe exposure. The acceptable daily intake (ADI) is calculated by determining the highest no-observed-adverse-effect level (NOAEL). When it is not possible to identify the NOAEL, the lowest observed-adverse-effect level (LOAEL) may be used. For the calculation of human ADI, the NOAEL or LOAEL obtained is divided by an arbitrary safety factor to provide an adequate margin of security. Drinking water standards have been adopted by the United States, the European Community, the World Health Organization, and other countries. The upper limits of copper concentration in water are based on organoleptic considerations and on debatable toxicity information. Given the importance of copper as an essential mineral for human health, it is conceivable that this and other essential minerals with health significance should be approached differently from nonessential minerals.

Copper deficiency impairs growth of infants recovering from malnutrition.

To evaluate the effect of copper deficiency on growth in humans we performed a prospective case-control study in 11 infants identified as Cu deficient based on low plasma Cu (less than 70 micrograms/dL [11.0 mumol/L]) and low ceruloplasmin (less than 200 mg/L). Growth was evaluated with anthropometric indices 1 mo before and 1 mo after onset of Cu supplementation of 80 micrograms.kg-1.d-1. Plasma Cu and ceruloplasmin rose significantly after 1 mo of supplementation. Weight-for-age and weight-for-length indices increased significantly after supplementation only in the Cu-deficient group. Daily energy intake was significantly higher in the Cu-deficient group after supplementation than it was in the control group. Daily weight gain after supplementation increased significantly in the Cu-deficient group and the value for daily weight gain after supplementation was significantly higher than that of the control group for the equivalent amount of time. Cu supplementation improves the growth of Cu-deficient infants recovering from malnutrition.

PIP: To evaluate the effect of copper deficiency on growth in humans a prospective case-control study was performed in Chile on a group of 11 infants identified as Cu deficient based on low plasma Cu (70 mcg/dL (11.0 mcmol/L) and low ceruloplasmin (200 mg/L). Growth was evaluated with anthropometric indices 1 month before and 1 month after onset of Cu supplementation of 80 mcg x 1/kg x 1/d. Plasma Cu and ceruloplasmin rose significantly after 1 month of supplementation. Weight-for-age and weight-for-length indices increased significantly after supplementation only in the Cu-deficient group. Daily energy intake was significantly higher in the Cu-deficient group after supplementation than it was in the control group. Daily weight gain after supplementation increased significantly in the Cu-deficient group and the value for daily weight gain after supplementation was significantly higher than that of the control group for the equivalent amount of time. Cu supplementation improves the growth of Cu-deficient infants recovering from malnutrition.

Essential fat requirements of preterm infants.

The interest in factors that modify early infant development has led investigators to focus on n-3 and n-6 long-chain polyunsaturated fatty acids (LCPUFAs) in the past 2 decades. The presence of docosahexaenoic acid (DHA) and arachidonic acid (AA) in breast milk, compared with their absence from infant formulas available in the United States, has prompted clinical trials designed to examine whether LCPUFA enrichment of infant formula has beneficial effects on maturational events of the visual system. These trials have shown significant functional advantages of LCPUFA supplementation for preterm infants, whereas benefits for full-term infants remain controversial. The growth and safety of preterm infants was not compromised by LCPUFA enrichment, although these issues remain to be resolved in clinical trials with full-term infants.