Macrosomia is associated with high weight-for-height in children aged 1-3 years in Shanghai, China.

OBJECTIVE: To investigate the association between macrosomia and high weight-for-length/height in 1-3 years old Chinese infants. DESIGN: A retrospective longitudinal study. SUBJECTS: 918 children aged 1-3 years in Shanghai, China. MEASUREMENTS: Body weight and length/height, illness status and feeding modalities were obtained during follow-up. Macrosomia was defined as birth weight >/=90th percentile of sex specific birth weight distribution. High weight-for-length/height was defined as a weight-for-length/height z-score >/=1.68 using the WHO growth reference. RESULTS: The odds ratios (ORs) for high weight-for-length/height were 3.60 (95% confidence interval (CI), 1.74-7.42) for boys and 1.39 (95% CI, 0.51-3.81) for girls who were macrosomic compared with the nonmacrosomic counterparts after adjustment for age. The ORs were attenuated to 3.48 (95% CI, 1.63-7.43) for boys and were still nonsignificant for girls (OR, 1.38; 95% CI, 0.49-3.91) after further controlling for illness status, the age of breast-feeding cessation and the age at introduction of complementary foods. From the analysis of boys and girls combined, the ORs were 2.48 (95% CI, 1.40-4.40) with adjustment for age and sex and 2.33 (95% CI, 1.29-4.22) with all covariates. CONCLUSION: Macrosomia is an important predictor for high weight-for-length/height in Chinese children aged 1-3 years.

Iron depletion without anemia and physical performance in young women.

Studies in laboratory animals found that iron deficiency without anemia decreased oxidative capacity and increased reliance on carbohydrate as the substrate for energy, thereby causing impaired endurance. The purpose of this cross-sectional study was to investigate the relation between iron deficiency without anemia and physical performance in healthy active women aged 19-36 y. Iron-status assessment included determination of hemoglobin, hematocrit, transferrin saturation, and serum ferritin values. Dietary iron intake was assessed by frequency questionnaires and physical activity level was estimated by frequency questionnaires and 2-wk records. Fifteen women with normal iron status and 15 women with iron depletion (serum ferritin < 12 micrograms/L) were chosen randomly from a group of 69 nonanemic women and given physical-performance tests, including determinations of maximum oxygen consumption (VO2max), ventilatory threshold, and delta-efficiency. There were no significant differences between the two groups in body size, body composition, physical activity level, dietary iron intake, delta-efficiency, or ventilatory threshold. Compared with the iron-depleted group, the iron-sufficient group had significantly higher hemoglobin, transferrin saturation, and serum ferritin values and a significantly greater tendency to use iron supplements. When physical activity level and fat-free mass were controlled for, the iron-depleted group had a significantly lower VO2max. The difference in VO2max was significantly associated with serum ferritin concentration; hemoglobin value was not a significant confounder. Therefore, reduction of VO2max in nonanemic women with iron depletion was likely caused by factors related to reduced body iron storage but was unrelated to decreased oxygen-transport capacity of the blood.

Response of serum transferrin receptor to iron supplementation in iron-depleted, nonanemic women.

Serum transferrin receptor (sTfR) concentration has been recognized recently as a reliable indicator of functional iron deficiency, but its response to iron supplementation has not been investigated in marginally iron-deficient women. In this randomized, double-blinded trial, 37 female subjects aged 19-35 y with iron depletion without anemia (hemoglobin > 120 g/L and serum ferritin < 16 microg/L) received an iron supplement or placebo for 8 wk. Iron status was measured before treatment, after 4 wk of treatment, and posttreatment (ie, after 8 wk of treatment). Iron supplementation of these iron-depleted, nonanemic women resulted in a progressive and significant decrease in sTfR and a significant increase in serum ferritin, and prevented a fall in hemoglobin. The responsiveness of sTfR to iron treatment indicated that sTfR is a sensitive indicator of marginal iron deficiency in iron-depleted, nonanemic women, even when their body iron stores were being replenished.

Consequences for maternal nutrition of reproductive stress across consecutive pregnancies.

Frequent cycles of reproduction increase the risk that lactation will overlap with pregnancy and shorten the duration of the recuperative interval (nonpregnant and nonlactating portion) within the reproductive cycle, thereby increasing the risk of maternal nutritional depletion. Nutritional responses to these stresses have been demonstrated by contrasting groups of women with different experiences; however, these relationships may be spurious and the result of third factors. In this study, responses to changing stress over consecutive pregnancies were studied and contrasted within individual Guatemalan women; biases caused by factors constant to women were eliminated. Stress was assessed by examining responses in maternal supplement intake, maternal fat stores, and birth weight. Overlap and short recuperative intervals were found to be stressful (in that order) for mothers as shown by increased supplement intake and reduced fat stores. Birth weight in term gestations was not affected, indicating that fetal growth is being protected at the cost of maternal nutritional status.

Functional anemia of complicated protein-energy malnutrition at high altitude.

The effect of severe protein-energy malnutrition (PEM) on erythropoiesis in children living in the highlands of Bolivia, altitude 3700 m, was studied. Forty percent reduced hemoglobin concentrations, significantly lower arterial oxygen tensions, and a right-shifted, oxygen-dissociation curve were observed compared to high-altitude controls. Serum and erythrocyte folate concentrations were 44% and 82%, respectively, of control values. Low initial transferrin saturation decreased significantly during the 10-wk refeeding period. Thus, iron and folate deficiency contributed significantly to the poor red cell response. Results suggest that the anemia associated with severe PEM has a more significant impact on oxygen transport at high altitude than at sea level and requires an adaptive response in the oxygen-dissociation curve to satisfy tissue-oxygen demands. Furthermore, marginal iron and folate status and an inflammatory block of iron supply may limit the reestablishment of a normal tissue mass during refeeding.

Distribution of hemoglobin and functional consequences of anemia in adult males at high altitude.

In order to assess better the normal hemoglobin (Hb) range among adult males at high altitude, a hematological survey was completed in La Paz, Bolivia (3700 m). Two statistical methodologies were utilized to identify the anemic and polycythemic contributions to the Hb distribution of normal healthy men (n = 526). The Hb of normal men has a Gaussian distribution with mean and SD of 18.8 +/- 1.4 g/dl. Cutoff levels of 15.8 and 22.0 g/dl Hb were selected to identify the anemic and polycythemic subpopulations. Iron status in this high altitude population is similar to that of low altitude populations, and iron deficiency is the cause of most anemia found. An exercise test on a subsample of 56 men was utilized to validate the anemia cutoff level. Anemics as identified by the 15.8 g/dl Hb level showed a significant reduction in aerobic capacity as measured by PWC150 and estimated VO2max.

Iron deficiency and behavior: criteria for testing causality.

The association between iron deficiency and poor behavioral-test performance is well established. The question of causality, however, remains unanswered. This paper presents the essential criteria for a valid test of causality. Internal validity is examined in terms of positive and negative findings. Plausibility of the findings requires analyzing the congruency of the results; for example, those who respond to the iron treatment are also those who respond behaviorally. External validity describes the extent to which inferences may be made about other populations or circumstances.

Testing the effects of nutrient deficiencies on behavioral performance.

The association between specific nutrient deficiencies and poor performance on behavioral tests has been documented for several nutrients. The determination of causality, however, remains elusive. This paper presents the essential criteria for a valid test of causality. Findings from experimental studies in which a nutritional treatment was randomly allocated can be summarized in a statistical statement about the probability that the nutrient treatment caused the behavioral response. Criteria for assessing the internal validity of these studies are examined in terms of whether alleviation of a nutrient deficiency did or did not produce a detectable behavioral response. The plausibility of such a causal inference is dependent on its congruency with known or theorized biological and behavioral mechanisms. External validity describes the extent to which inferences from internally valid studies may be applicable to other populations or circumstances. In addition to these scientific considerations, some of the ethical issues of nutrient-treatment trials are also discussed. All of these considerations provide a better basis for judging whether public health action would be worthwhile than do observed associations that could actually be due to other causes.

Accuracy of heart-rate monitoring and activity diaries for estimating energy expenditure.

The accuracy of heart-rate monitoring and activity diaries for measuring energy expenditure in free-living individuals was studied in 12 women. Estimates of energy expenditure were calculated from heart-rate monitoring by use of four different prediction equations to describe the relationship between heart rate and energy expenditure. Estimates of energy expenditure from activity diaries were calculated using both individually measured and published values for the energy cost of activities. Energy intake adjusted for changes in body-energy stores was used as a reference. Heart-rate monitoring overestimated group energy expenditure from 2 to 9% and the errors in estimating individual energy expenditure ranged from -53 to 67%. Activity diaries underestimated group energy expenditure by 2-6% and the errors in estimating individual energy expenditure ranged from -39 to 56%. Heart-rate monitoring and activity diaries may prove useful for estimating the energy expenditure of groups but not individuals.

Predicting body composition from anthropometry and bioimpedance in marginally undernourished adolescents and young adults.

Body-composition prediction equations were developed using data from a sample of 201 female and male Guatemalan ladinos (ie, people of Amerindian-European descent) aged 11-25 y. Fat-free mass (FFM) values were estimated from body density by using the two-component model and age- and sex-specific values for the density of FFM. The root-mean-square error (RMSE) of the best model predicting FFM from a set of simple anthropometric variables was 1.59 kg for females and 1.90 kg for males. The addition of more extensive anthropometry to the set of candidate predictors reduced the RMSE to 1.42 kg for females and 1.88 kg for males. The subsequent addition of a bioelectrical impedance measure (Ht2/R) further reduced the RMSE to 1.32 kg for females and 1.82 kg for males. These results suggest that for a marginally undernourished population with relatively little body fat, simple anthropometrics are as useful as more sophisticated measures for the prediction of body composition.

Body composition and energy intake: do overweight women overeat and underreport?

The relationship between energy consumption and body composition was evaluated in 63 women by use of energy-intake values that were precisely measured in a metabolic unit and corrected for deviations from energy balance. Energy requirement for the maintenance of body weight was not significantly correlated with adiposity expressed as percent body fat. However, energy requirement was positively associated with lean mass (p less than 0.0001) whereas fat mass added no predictive value to the same multivariate regression equation. Self-reported energy intake (before the experiments) was not correlated with lean mass and was underestimated by lean subjects at least as much as by obese subjects. Discrepant findings in the literature concerning relationships between obesity and energy intake may be explained by reporting error and by the relative lean mass of obese vs nonobese women but not by systematic underreporting unique to obese subjects.

Effects of exercise on riboflavin requirements of young women.

The riboflavin requirement of young women during periods of sedentary living and exercise was determined during a 12-wk metabolic study. The study was divided into a 6-wk no exercise period followed by a 6-wk exercise period in which subjects jogged around a track for 20 to 50 min/day. Twelve subjects, aged 19 to 27 yr, were fed a basic diet containing 0.6 mg riboflavin/1000 kcal of intake. Riboflavin intake was increased by 0.2 mg/1000 kcal increments by provision of riboflavin in a glucose polymer mixture. Linear regression analysis was used to estimate the riboflavin intake required for an erythrocyte glutathione reductase activity coefficient of 1.25 during both the no exercise and exercise periods. Individual riboflavin requirements ranged from 0.62 to 1.21 mg/1000 kcal before exercise and 0.63 to 1.4 mg/1000 kcal during the exercise periods. Riboflavin requirement could not be related to the kilocalorie intake or lean body mass of the subjects. It is concluded that healthy young women require more riboflavin to achieve biochemical normality than the 1980 Recommended Dietary Allowances and that exercise increases riboflavin requirements.

On the factors which contribute to thinning of the villous membrane in human placentae at high altitude. I. Thinning and regional variation in thickness of trophoblast.

Sections of human term placentae delivered at low and high altitude to indigenous and non-indigenous populations in Bolivia were analysed by stereological methods. Estimates were obtained of the arithmetic and harmonic mean thicknesses of villous membrane and of trophoblast. These values were then used to derive indices of thickness variation. No significant ethnic, sex or interaction effects were found. At high altitude, the villous membrane was significantly more variable in thickness owing to a lower harmonic mean but the same arithmetic mean thickness. Alterations in the arithmetic and harmonic mean thicknesses of the trophoblast contributed to the thinning of the villous membrane. The trophoblast was thinner and more irregular in thickness at high altitude. These findings are discussed in the context of placental diffusing capacity and the possible mechanisms for formation of vasculosyncytial membranes.

On the factors which contribute to thinning of the villous membrane in human placentae at high altitude. II. An increase in the degree of peripheralization of fetal capillaries.

The contribution made by fetal capillary peripheralization to the thinning of the villous membrane seen in human placentae from high-altitude pregnancies is examined by stereological methods. Variables characterizing the shape of the villous core and the spatial relationships between trophoblast and capillaries are quantified. They shed light on the relative importance of dynamic versus mechanistic processes of villous membrane attenuation. Highland villi differ from lowland villi in several ways. On average, they possess a thinner barrier due to closer approximation of capillaries to overlying trophoblast; in consequence, the villous core is more irregular in outline and its surface (that of the inner aspect of the trophoblast) exceeds in area that of the outer aspect of the trophoblast. These results suggest that the dynamic process (protoplasmic streaming within syncytiotrophoblast) cannot alone explain thinning of the villous membrane. A mechanistic process (capillary peripheralization and obtrusion into the trophoblastic epithelium) is sufficient to account for the differences observed, although the possibility that both processes operate concurrently cannot be discounted. This report completes a study into factors contributing to villous membrane thinning at high altitude.

Oxygen diffusive conductances of human placentae from term pregnancies at low and high altitudes.

A morphometric model of oxygen diffusion is employed to calculate the partial, total and specific conductances of human placentae from low- and high-altitude term pregnancies. Placentae were obtained from indigenous and non-indigenous populations and the diffusion pathway dissected into six tissue compartments. Birthweights were reduced at high altitude but were greater in natives versus non-natives. The altitudinal differences were associated with changes in placental diffusive conductances. The partial conductance of the villous trophoblast was conserved but the conductance on the maternal side was increased as was the conductance of the villous stroma. Fetal conductances were conserved (plasma) or diminished (erythrocytes). We conclude that birthweights are reduced at high altitude despite the attempts to increase the total placental diffusive conductance for oxygen. The mechanisms underlying these adaptations are discussed.

Morphometric studies on villi in human term placentae and the effects of altitude, ethnic grouping and sex of newborn.

Stereological methods were used to test whether or not altitudinal, ethnic and sex differences in birthweight in Bolivia are associated with differences in placental morphology. Estimates of the volumes, surface areas, lengths and diameters of villi and of fetal capillaries were obtained by analysing paraffin sections of tissue. The average highland placenta contains villi of smaller overall volume, surface area and length. These villi possess a less voluminous fetal vascular space, and the capillaries are smaller in mean diameter. The average Amerindian placenta has longer but thinner capillaries than the average placenta delivered by non-indigenous women. Altitude and ethnic grouping interact to have an effect on total villous length, whilst ethnic grouping and sex interact to influence fetal capillary length. These structural differences are discussed in the context of their likely impact on placental functioning, notably on exchange by passive diffusion.

Microscopical morphology of the human placenta and its effects on oxygen diffusion: a morphometric model.

A combination of stereological and physicochemical data was used to estimate the oxygen-diffusing capacity of the human term placenta. The effects on this morphometric diffusing capacity of isolated changes in placental structure were investigated by permitting volumes, surface areas and harmonic mean diffusion distances to deviate from normal baseline (term) values. Diffusion performance could be monitored effectively by estimating only three structural quantities. The most influential variable was the harmonic mean thickness of the villous membrane followed by the surface areas of villi and of fetal capillaries. Blood space volumes and plasma diffusion distances had negligible effects on diffusing capacity. Conclusions are discussed in the context of published findings on changes in placental anatomy which occur during gestation, abnormal pregnancies and pregnancies at high altitude.

Stereological studies on the true thickness of the villous membrane in human term placentae: a study of placentae from high-altitude pregnancies.

Stereological principles were used to calculate functionally significant dimensions of the human villous membrane, its arithmetic mean thickness (Ta) and its harmonic mean thickness (Th). The former is proportional to tissue mass and oxygen consumption, the latter to diffusional resistance. For a group of 15 term placentae from uncomplicated pregnancies at high altitude, the average values were Ta = 4.44 micron, Th = 3.56 micron and Ta/Th = 1.26. The latter figure provides a useful quantitative expression for the efficiency of the membrane in gas and metabolite diffusion. It implies that vasculosyncytial membranes and syncytial knots decrease resistance to diffusion by 26 per cent, compared with that of a membrane with uniform thickness throughout. The methods are simple to apply and provide better estimates of true thickness than do measurements confined to thin sections.

The comparison of mixed distribution analysis with a three-criteria model as a method for estimating the prevalence of iron deficiency anaemia in Costa Rican children aged 12-23 months.

BACKGROUND: A maximum likelihood method of mixed distribution analysis (MDA) is presented as a method to estimate the prevalence of iron deficiency anaemia (IDA) in Costa Rican infants 12-23 months old. MDA characterizes the parameters of the admixed distributions of iron deficient anaemics and non-iron-deficient-anaemics (NA) from the frequency distribution of haemoglobin concentration of the total sample population. METHODS: Data collected by Lozoff et al. (1986) from 345 Costa Rican infants 12-23 months old were used to estimate the parameters of the IDA and NA haemoglobin distributions determined by MDA and the widely used three-criteria model of iron deficiency. The estimates of the prevalence of IDA by each of the methods were compared. The sensitivity and specificity of MDA compared to diagnosis by the three-criteria method were assessed. Simulations were carried out to assess the comparability of MDA and the three-criteria method in low and high prevalence scenarios. RESULTS: The mean and standard deviation (SD) of the NA haemoglobin distribution determined by both methods was 12.1 +/- 1.0 g/dL. The IDA haemoglobin distribution determined by MDA had a mean and SD of 10.2 +/- 1.3 g/dL while the IDA distribution by the three-criteria method had a mean and SD of 10.4 +/- 1.3 g/dL. The prevalences of IDA as estimated by MDA and the three-criteria method were 24% and 29%, respectively. The sensitivity and specificity of MDA were 95% and 97%, respectively. The performance of MDA was similar to the three-criteria method at a simulated high prevalence of IDA and less similar at a low prevalence of IDA. CONCLUSIONS: Compared to the reference three-criteria method MDA provides a more accurate estimate of the true prevalence of IDA than the haemoglobin cutoff method in a population of children aged 12-23 months with a moderate to high prevalence of IDA. MDA is a less costly method for estimating the severity of IDA in populations with moderate to high prevalences of IDA, and for assisting in the design, monitoring and evaluation of iron intervention programmes.

PIP: A maximum likelihood method of mixed distribution analysis (MDA) is presented as a method to estimate the prevalence of iron deficiency anemia (IDA) in Costa Rican infants aged 12-23 months old. MDA characterizes the parameters of the ad-mixed distributions of iron deficient anemics and non-iron-deficient anemics (NA) from the frequency distribution of hemoglobin concentration of the total sample population. Data collected by Lozoff et al. from 345 Costa Rican infants aged 12-23 months old were used to estimate the parameters of the IDA and NA hemoglobin distributions determined by MDA and the 3-criteria model of iron deficiency. The mean and standard deviation (SD) of the NA hemoglobin distribution determined by both methods was 12.1 +or- 1.0 g/dl. The IDA hemoglobin distribution determined by MDA had a mean and SD of 10.2 +or- 1.3 g/dl, while the IDA distribution by the 3-criteria method had a mean and SD of 10.4 +or- 1.3 g/dl. The prevalences of IDA as estimated by MDA and the 3-criteria method were 24% and 29%, respectively. The sensitivity and specificity of MDA were 95% and 97%, respectively. MDA performed similarly to the 3-criteria method at a simulated high prevalence of IDA and less similar at a low prevalence of IDA.

Early nutrition and later physical work capacity.

PIP: Several important studies within the past 20 years have examined the impact of acute nutrient deficiencies upon physical work capacity. Spurr et al. and Satyanarayana et al. extended that line of research to explore the apparent effects of chronic or lifelong undernutrition upon the work capacity of adolescent males. These studies conducted in Colombia and India, as well as others in Tanzania and Guatemala, are discussed. The authors believe that there is enough evidence to conclude that poor early childhood nutritional status, as indicated by the low dietary energy intakes and subsequent stunted growth, leads to many undesirable functional consequences. The studies of physical work capacity, together with other measures such as cognitive functioning and reproductive performance, provide strong evidence in support of policies and programs designed to eliminate the causes of environmental stunting in poor populations.^ieng