Gail R. Goldberg

Measurements of total energy expenditure provide insights into the validity of dietary measurements of energy intake

The quantification of errors inherent in methods of measuring dietary intake has been handicapped by the absence of independent markers for testing their validity. The doubly labeled water technique permits a precise measure of energy expenditure in free-living persons. Because energy expenditure must equal energy intake in populations in energy balance, this technique may be used to validate the assessment of energy intake. A series of studies demonstrated good agreement between mean energy intake and mean energy expenditure when food intake was recorded by observers or when it was self-reported by normal-weight, self-selected, highly motivated volunteer subjects using weighed records. However, in randomly recruited men and women, energy intake by weighed records was 82% and 81%, of energy expenditure, respectively, indicating underestimation of habitual intake. Men and women in the lowest third of reported intake recorded energy expenditure of only 69% and 61%, respectively. Reported intake of obese and previously obese women was only 73% and 64% of expenditure, whether measured by weighed record or by diet history, confirming suspicions that these subjects misrepresented their intake. Acceptable weighed records were obtained from 7- and 9-year-olds whereas 15- and 18-year-olds underestimated intake. Diet histories taken from the same children tended to overestimate intake. These studies suggest that, ideally, all dietary studies should include independent measures of validity.

Critical windows for nutritional interventions against stunting.

An analysis of early growth patterns in children from 54 resource-poor countries in Africa and Southeast Asia shows a rapid falloff in the height-for-age z score during the first 2 y of life and no recovery until ≥5 y of age. This finding has focused attention on the period −9 to 24 mo as a window of opportunity for interventions against stunting and has garnered considerable political backing for investment targeted at the first 1000 d. These important initiatives should not be undermined, but the objective of this study was to counteract the growing impression that interventions outside of this period cannot be effective. We illustrate our arguments using longitudinal data from the Consortium of Health Oriented Research in Transitioning collaboration (Brazil, Guatemala, India, Philippines, and South Africa) and our own cross-sectional and longitudinal growth data from rural Gambia. We show that substantial height catch-up occurs between 24 mo and midchildhood and again between midchildhood and adulthood, even in the absence of any interventions. Longitudinal growth data from rural Gambia also illustrate that an extended pubertal growth phase allows very considerable height recovery, especially in girls during adolescence. In light of the critical importance of maternal stature to her childrens health, our arguments are a reminder of the importance of the more comprehensive UNICEF/Sub-Committee on Nutrition Through the Life-Cycle approach. In particular, we argue that adolescence represents an additional window of opportunity during which substantial life cycle and intergenerational effects can be accrued. The regulation of such growth is complex and may be affected by nutritional interventions imposed many years previously.

Consensus Statement: Global Consensus Recommendations on Prevention and Management of Nutritional Rickets

BACKGROUND Vitamin D and calcium deficiencies are common worldwide, causing nutritional rickets and osteomalacia, which have a major impact on health, growth, and development of infants, children, and adolescents; the consequences can be lethal or can last into adulthood. The goals of this evidence-based consensus document are to provide health care professionals with guidance for prevention, diagnosis, and management of nutritional rickets and to provide policy makers with a framework to work toward its eradication. EVIDENCE A systematic literature search examining the definition, diagnosis, treatment, and prevention of nutritional rickets in children was conducted. Evidence-based recommendations were developed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system that describe the strength of the recommendation and the quality of supporting evidence. PROCESS Thirty-three nominated experts in pediatric endocrinology, pediatrics, nutrition, epidemiology, public health, and health economics evaluated the evidence on specific questions within five working groups. The consensus group, representing 11 international scientific organizations, participated in a multiday conference in May 2014 to reach a global evidence-based consensus. RESULTS This consensus document defines nutritional rickets and its diagnostic criteria and describes the clinical management of rickets and osteomalacia. Risk factors, particularly in mothers and infants, are ranked, and specific prevention recommendations including food fortification and supplementation are offered for both the clinical and public health contexts. CONCLUSION Rickets, osteomalacia, and vitamin D and calcium deficiencies are preventable global public health problems in infants, children, and adolescents. Implementation of international rickets prevention programs, including supplementation and food fortification, is urgently required.

Energy-sparing adaptations in human pregnancy assessed by whole-body calorimetry.

The hypothesis that the energy cost of human pregnancy can be minimized by energy-sparing metabolic adaptations was tested using serial 24 h whole-body calorimetry. Eight healthy, well-nourished women were studied prepregnant and at 6, 12, 18, 24, 30 and 36 weeks gestation. Basal metabolic rate (BMR) showed highly characteristic changes within each subject and large inter-individual differences (F 3.5, P less than 0.01). Some subjects showed a highly significant depression of metabolism up to 24 weeks gestation in support of the initial hypothesis. At 36 weeks BMR ranged from +8.6 to +35.4% relative to the prepregnant baseline. This wide variability was not explained by differences in the amount of lean tissue gained. Women displaying the energy-sparing suppression of BMR tended to be thin, suggesting that changes in metabolism may be responsive to initial energy status (delta BMR v. prepregnant body fat: r 0.84, P less than 0.005). Changes in 24 h energy expenditure closely paralleled changes in BMR (r 0.98, P less than 0.001), since the energy cost of minor voluntary activity and thermogenesis remained very constant within each individual. Pregnancy decreased the net cost of weight-dependent and weight-independent standard exercises when expressed per kg body-weight: stepping -10 (SD 2)%, P less than 0.001 at 18-36 weeks, cycling -26 (SD 7)%, P less than 0.01 at 12-36 weeks. The average integrated maintenance costs of pregnancy matched previous group estimates from well-nourished women, but individual estimates ranged from -16 to +276 MJ (coefficient of variation 93%). This high level of variability has important implications for the prescription of incremental energy intakes during pregnancy. It may also have had evolutionary significance.

Energy adaptations in human pregnancy: limits and long-term consequences

The very slow rate of human fetal growth generates a lower incremental energy stress than in any other mammalian species. This creates a situation in which adaptive changes in metabolic rate and in the amount of additional maternal fat stored during gestation can make a profound difference to the overall energy needs of pregnancy. Comparisons of women in affluent and poor countries have recorded mean population energy needs ranging from as high as 520 MJ to as low as -30 MJ per pregnancy. These energy costs are closely correlated with maternal energy status when analyzed both between and within populations, suggesting that they represent functional adaptations that have been selected for their role in protecting fetal growth. Although this metabolic plasticity represents a powerful mechanism for sustaining pregnancy under very marginal nutritional conditions, it must not be construed as a perfect mechanism that obviates the need for optimal nutritional care of pregnant women. The fact that fetal weight represents up to 60% of total pregnancy weight gain in many pregnancies in poor societies (compared with a well-nourished norm of 25%) indicates that the fetus is developing under suboptimal nutritional and physiologic conditions. It has long been recognized that this has immediate consequences for the offspring in terms of increased perinatal mortality. The more recent appreciation that impaired fetal growth may also precipitate longer-term defects in terms of adult susceptibility to noncommunicable and infectious diseases reinforces the view that pregnancy may be the most sensitive period of the life cycle in which nutritional intervention may reap the greatest benefits.

Symposium on ‘Nutrition and health in children and adolescents’ Session 1: Nutrition in growth and development: Nutrition and bone growth and development

The growth and development of the human skeleton requires an adequate supply of many different nutritional factors. Classical nutrient deficiencies are associated with stunting (e.g. energy, protein, Zn), rickets (e.g. vitamin D) and other bone abnormalities (e.g. Cu, Zn, vitamin C). In recent years there has been interest in the role nutrition may play in bone growth at intakes above those required to prevent classical deficiencies, particularly in relation to optimising peak bone mass and minimising osteoporosis risk. There is evidence to suggest that peak bone mass and later fracture risk are influenced by the pattern of growth in childhood and by nutritional exposures in utero, in infancy and during childhood and adolescence. Of the individual nutrients, particular attention has been paid to Ca, vitamin D, protein and P. There has also been interest in several food groups, particularly dairy products, fruit and vegetables and foods contributing to acid–base balance. However, it is not possible at the present time to define dietary reference values using bone health as a criterion, and the question of what type of diet constitutes the best support for optimal bone growth and development remains open. Prudent recommendations (Department of Health, 1998; World Health Organization/Food and Agriculture Organization, 2003) are the same as those for adults, i.e. to consume a Ca intake close to the reference nutrient intake, optimise vitamin D status through adequate summer sunshine exposure (and diet supplementation where appropriate), be physically active, have a body weight in the healthy range, restrict salt intake and consume plenty of fruit and vegetables.

The effect of exercise and improved physical fitness on basal metabolic rate

1. The suggestion that there is a sustained enhancement in metabolic rate after exercise was investigated during the course of a study in which six normal-weight volunteers (three men, three women) took part in a 9-week training programme. Baseline values were assessed in a 3-5 week control period of minimal activity before training. At the end of the study the subjects were capable of running for 1 h/d, 5 d/week. 2. Throughout the entire study the subjects were maintained on a constant diet. Measurement of energy expenditure by the doubly-labelled water (2H2(18)O) method showed that the subjects had an energy imbalance of +3% in the control and -20% at the end of the training period. The subjects were in positive (1.1 (SE 0.2) g) nitrogen balance in the second week of the control, and in negative (-0.6 (SE 0.3) g) N balance in the last week of the exercise period. 3. Over the course of the study maximum oxygen consumption (VO2max) and high-density-lipoprotein-cholesterol levels increased by 30%. Heart rate at rest and when performing a standard step test fell significantly. 4. Body composition was assessed weekly by 40K counting and skinfold thickness measurements, in addition to 2H2 dilution at the beginning and end of the study. Fat-free mass was apparently gained in the early phases of the study, but there was lack of agreement between the different methods of assessing body composition. Changes in body-weight were not significant. 5. Basal metabolic rate (BMR), overnight metabolic rate (OMR) and sleeping metabolic rate (SMR) were measured on three occasions: in the control period, and the beginning and end of the training periods. Average BMR in the control period was 5.91 (SE 0.39) MJ/24 h and was not changed with activity. There were no changes in OMR (5.71 (SE 0.27) MJ/24 h in the control) nor in SMR (5.18 (SE 0.27) MJ/24 h in the control), nor in BMR, OMR or SMR when expressed per kg body-weight, or per kg fat-free mass. 6. These results do not support the suggestions that there is a sustained increase in BMR following exercise that can usefully assist in weight-loss programmes.

Maternal plasma 25-hydroxyvitamin D concentration and birthweight, growth and bone mineral accretion of Gambian infants.

Maternal vitamin D deficiency during pregnancy is a recognized risk factor for rickets and osteomalacia in infancy (1). The circulating plasma concentration of 25-hydroxyvitamin D (25OHD), a long-lived metabolite of vitamin D, is used to judge vitamin D status; values below 25 nmol/L are associated with an increased risk of rickets and osteomalacia (1). There is evidence that a low maternal plasma 25OHD in pregnancy may influence the growth and bone mineral accrual of the offspring during foetal life, infancy and childhood. Positive associations have been reported between maternal vitamin D status in pregnancy and birthweight, birth length, length at 1 year and bone mineral accretion at 9 years (2–6), although evidence is conflicting (7,8). These relationships have been observed at concentrations of 25OHD higher than those associated with rickets and osteomalacia, and there are calls to raise the accepted lower threshold of vitamin D sufficiency for pregnant women, most recently to 80 nmol/L (9). On a population basis, plasma 25OHD concentrations above 80 nmol/L are relatively uncommon in countries at temperate latitudes but are more common among people living in the tropics who have abundant skin sunshine exposure (10). To contribute to the debate on the definition of vitamin D sufficiency in pregnancy, we have investigated the influence of maternal plasma 25OHD concentration on foetal and infant growth in a rural area of The Gambia, West Africa (13°N). In this region, there is tropical sunshine all year, the women are farmers who work out-of-doors for much of each day, and local female dress does not restrict regular sunshine exposure to the face, neck, shoulders, arms and feet, especially during farm work and gardening. The study was a secondary analysis of biochemical, anthropometric and bone data from a subset of 125 women and infants collected during a calcium supplementation study of blood pressure in pregnant Gambian women (International Trial Registry: ISRCTN96502494). No significant benefits for foetal and infant growth of maternal calcium supplementation were identified despite the low customary calcium intake in The Gambia (11). The protocol, methods, maternal characteristics and infant data from the detailed study have been published (11). Briefly, women from the rural villages of Keneba and Manduar, West Kiang, The Gambia were recruited at 20 weeks of pregnancy (P20) and randomized to a daily calcium supplement or a matching placebo tablet until parturition (1500 mg Ca as calcium carbonate and microcellulose-lactose, respectively; Nycomed Pharma AS, Asker, Norway). Fasting, early morning blood was collected and anthropometry performed at P20 and 36 weeks of pregnancy (P36). The mean (± SD) age, weight, height and dietary calcium intake of the women at P20 were 27.4 ± 7.5 years, 56.3 ± 6.7 kg, 1.61 ± 0.05 m and 356 ± 190 mg/day, respectively. The median parity (range) was 3 (0–10). Infant birthweight was measured within 24 h of delivery. Weight, crown-heel length and head circumference were measured at 2, 13 and 52 weeks postpartum. In addition, infant bone mineral content (BMC), bone mineral density (BMD) and bone width (BW) or bone area (BA), were measured by single photon absorptiometry of the midshaft radius (Lunar SP2, Lunar Corporation, Madison, WI, USA) and, for a subset (n = 44, 47 and 52 at 2, 13 and 52 weeks, respectively), by whole-body dual-energy X-ray absorptiometry (Lunar DPX+, software version 4.7b, Lunar Corporation). Plasma 25OHD was measured a using radioimmunometric assay (Diasorin Ltd, Wokingham, Berks, UK), with assay performance monitored through the Vitamin D External Quality Assessment Scheme (DEQAS; Endocrine/Oncology Laboratory, Charing Cross Hospital, London, UK). The intra- and inter-assay coefficients of variation were 4% and 100); possible trends in the data with p = 0.01–0.1 were noted. The analysis was conducted on 123 mother–infant pairs; blood samples from two subjects were not available. Mean ± SD 25OHD (range) was: P20 = 103 ± 25 (53–167) nmol/L; P36 = 111 ± 27 (51–189) nmol/L. No subject had a 25OHD value <50 nmol/L, 20% and 16% had 25OHD <80 nmol/L, at P20 and P36, respectively. There was a high degree of within-subject consistency in 25OHD at P20 and P36 (25OHDP36 = 33.2 + [0.79 ± 0.07]× 25OHDP20, p ≤ 0.001, R2 adjusted 51.5%, n = 121); 11% of women had 25OHD <80 nmol/L at both P20 and P36. The mean birthweight of the infants was 2.99 ± 0.36 kg. The infant anthropometric and bone measures during the first year are given in Table 1. No significant relationships or trends in the data were observed between maternal 25OHD concentration using the values at P20, P36 or the mean of the two and any of the following infant measures: birthweight, infant weight, length, head circumference, BMC, BW (or BA), BMD and size-adjusted BMC of the midshaft radius and whole body at any time postpartum. This is illustrated in Figure 1 for birthweight as a function of maternal 25OHD concentration at P20. Comparing the results for mothers with 25OHD above and below 80 nmol/L did not alter this finding. Table 1 Anthropometric and bone measures of Gambian infants Figure 1 Lack of a significant relationship between infant birthweight and maternal vitamin D status at 20 weeks of pregnancy (p = 0.8). Multiple regression model included season, maternal height, weight, weight gain, supplement group and sex of the infant. No significant interaction between supplement group and maternal 25OHD concentration was observed for any infant variable. Trends in the data were observed in a few instances for a supplement group × 25OHD interaction among the bone measures but no consistent picture emerged and they were considered to have arisen by chance. We conclude that there is no evidence for an influence of vitamin D status during pregnancy on infant growth and bone mineral accrual in the conditions prevailing in The Gambia. The children in this study, as is common in this region of The Gambia (13), were born small, grew well for the first months of life but experienced growth faltering during later infancy compared to Western children (11,14), as demonstrated by their weight and length SDS. The 25OHD concentrations of the women were >50 nmol/L in the second half of pregnancy, and no distinction could be drawn in infant outcomes between mothers with concentrations above or below 80 nmol/L. Thus, our study suggests that, for women with regular, adventitious UVB sunshine exposure and in situations where foetal and infant growth may be constrained by multiple factors, there would be no benefit for foetal and infant growth or bone mineral accrual in aiming to increase the vitamin D status of individual mothers during pregnancy above 50 or 80 nmol/L.

Effect of calcium supplementation in pregnancy on maternal bone outcomes in women with a low calcium intake

Background: Mobilization of maternal bone mineral partly supplies calcium for fetal and neonatal bone growth and development. Objective: We investigated whether pregnant women with low calcium intakes may have a more extensive skeletal response postpartum that may compromise their short- or long-term bone health. Design: In a subset of participants (n = 125) in a double-blind, randomized, placebo-controlled trial (International Trial Registry: ISRCTN96502494) in pregnant women in The Gambia, West Africa, with low calcium intakes (≈350 mg Ca/d), we measured bone mineral status of the whole body, lumbar spine, and hip by using dual-energy X-ray absorptiometry and measured bone mineral status of the forearm by using single-photon absorptiometry at 2, 13, and 52 wk lactation. We collected blood and urine from the subjects at 20 wk gestation and at 13 wk postpartum. Participants received calcium carbonate (1500 mg Ca/d) or a matching placebo from 20 wk gestation to parturition; participants did not consume supplements during lactation. Results: Women who received the calcium supplement in pregnancy had significantly lower bone mineral content (BMC), bone area (BA), and bone mineral density (BMD) at the hip throughout 12 mo lactation (mean ± SE difference: BMC = −10.7 ± 3.7%, P = 0.005; BA = −3.8 ± 1.9%, P = 0.05; BMD = −6.9 ± 2.6%, P = 0.01). The women also experienced greater decreases in bone mineral during lactation at the lumbar spine and distal radius and had biochemical changes consistent with greater bone mineral mobilization. Conclusions: Calcium supplementation in pregnant women with low calcium intakes may disrupt metabolic adaptation and may not benefit maternal bone health. Further study is required to determine if such effects persist long term or elicit compensatory changes in bone structure.

Calcium economy in human pregnancy and lactation

Pregnancy and lactation are times of additional demand for Ca. Ca is transferred across the placenta for fetal skeletal mineralisation, and supplied to the mammary gland for secretion into breast milk. In theory, these additional maternal requirements could be met through mobilisation of Ca from the skeleton, increased intestinal Ca absorption efficiency, enhanced renal Ca retention or greater dietary Ca intake. The extent to which any or all of these apply, the underpinning biological mechanisms and the possible consequences for maternal and infant bone health in the short and long term are the focus of the present review. The complexities in the methodological aspects of interpreting the literature in this area are highlighted and the inter-individual variation in the response to pregnancy and lactation is reviewed. In summary, human pregnancy and lactation are associated with changes in Ca and bone metabolism that support the transfer of Ca between mother and child. The changes generally appear to be independent of maternal Ca supply in populations where Ca intakes are close to current recommendations. Evidence suggests that the processes are physiological in humans and that they provide sufficient Ca for fetal growth and breast-milk production, without relying on an increase in dietary Ca intake or compromising long-term maternal bone health. Further research is needed to determine the limitations of the maternal response to the Ca demands of pregnancy and lactation, especially among mothers with marginal and low dietary Ca intake, and to define vitamin D adequacy for reproductive women.