Ana Lydia Sawaya

Effects of Low Birth Weight in 8- to 13-Year-Old Children: Implications in Endothelial Function and Uric Acid Levels

Low birth weight has been associated with an increased incidence of adult cardiovascular disease. Endothelial dysfunction and high levels of serum uric acid are associated with hypertension. In this study, we have determined whether uric acid is related to blood pressure and vascular function in children with low birth weight. We evaluated vascular function using high-resolution ultrasound, blood pressure, and uric acid levels in 78 children (35 girls, 43 boys, aged 8 to 13 years). Increasing levels of uric acid and systolic blood pressure were observed in children with low birth weight. Birth weight was inversely associated with both systolic blood pressure and uric acid; on the other hand, uric acid levels were directly correlated with systolic blood pressure in children of the entire cohort. Low birth weight was associated with reduced flow-mediated dilation (r=0.427, P<0.001). Because the children with low birth weight had elevated uric acid as well as higher systolic blood pressure levels, we evaluated the correlation between these variables. In the low birth weight group, multiple regression analysis revealed that uric acid (&bgr;=−2.886; SE=1.393; P=0.040) had a graded inverse relationship with flow-mediated dilation, which was not affected in a model adjusting for race and gender. We conclude that children with a history of low birth weight show impaired endothelial function and increased blood pressure and uric acid levels. These findings may be early expressions of vascular compromise, contributing to susceptibility to disease in adult life.

Stunting and future risk of obesity: principal physiological mechanisms

There is a fair amount of epidemiological evidence showing that nutritional stunting causes increased risks of obesity. Obesity is increasing dramatically not only in developed countries but also in developing countries, such as Brazil, especially among the poorer. The mere coexistence of undernutrition and obesity among poor people has a great impact, as the burden in the social, economic, and health care systems is remarkable. In addition, an increasing number of studies have shown that nutritional stunting causes a series of important long-lasting changes such as lower energy expenditure, higher susceptibility to the effects of high-fat diets, lower fat oxidation, and impaired regulation of food intake. These findings suggest that a broader and more detailed understanding of the long-lasting effects of early undernutrition, direct cause of nutritional stunting, is needed. Within this context, we present data of some physiological mechanisms that substantiate the association between previous undernutrition and future obesity.

Mild Stunting Is Associated with Higher Susceptibility to the Effects of High Fat Diets: Studies in a Shantytown Population in São Paulo, Brazil

Previous studies by our group and others have suggested that nutritional stunting may increase the risk of obesity. To investigate mechanisms that could explain a link between stunting and obesity, a 22-mo follow-up study was conducted in two groups of shantytowns school girls (7-11 y old) in São Paulo, Brazil. One group (n = 15) had mild stunting (defined using a cutoff of -1.4 Z-scores of height-for-age) but normal weight-for-height; the control group (n = 15) had normal weight and height. Similar energy intake, dietary macronutrient composition and energy expenditure were observed in the two groups. Both groups showed comparable levels of IGF-1 that were below the normal range. A significant and positive association between baseline IGF-1 and the change in height-for-age during follow-up was found in all subjects combined (P = 0.044). A significant association was found between the baseline percentage of dietary energy supplied by fat and the gain in weight-for-height during follow-up in girls with mild stunting (P = 0.048), but not in the nonstunted control girls (P = 0.245); however, the slopes of these relationships were not significantly different. This study raises the question of whether a diet high in fat may increase the susceptibility to excess body fat gain in children who are mildly stunted. Further studies are need to explore this issue and to examine the possible etiological role of low levels of IGF-1.

Stunted children gain less lean body mass and more fat mass than their non-stunted counterparts: a prospective study

The aim of the present study was to analyse the changes in body composition of stunted children during a follow-up period and to test the hypothesis of a tendency to accumulate body fat as a consequence of undernutrition early in life. We selected fifty boys and girls aged 11 to 15, who were residents of slums in Sao Paulo, Brazil. Twenty were stunted (S) and thirty had normal stature (NS). The childrens nutritional status and body composition were assessed through anthropometry and dual-energy X-ray absorptiometry, at the beginning of the present study and after 3 years, and changes in lean mass (LM and LM%) and fat mass (FM and FM%) were calculated. Stunted boys accumulated more body fat (FM%: S=1.62%, NS=-3.40%; P=0.003) and gained less lean mass (LM%: S=-1.46, NS=3.21%; P=0.004). Stunted girls gained less lean mass (S=7.87 kg, NS=11.96 kg; P=0.032) and had significantly higher values of FM% at follow-up when compared with their baseline values (P=0.008), whereas non-stunted girls had a non-significant difference in FM% over time (P=0.386). These findings are important to understand the factors involved in the increased prevalence of overweight and obesity among poor populations, which appear to be associated with hunger during infancy and/or childhood.

Long-Lasting Effects of Undernutrition

Undernutrition is one of the most important public health problems, affecting more than 900 million individuals around the World. It is responsible for the highest mortality rate in children and has long-lasting physiologic effects, including an increased susceptibility to fat accumulation mostly in the central region of the body, lower fat oxidation, lower resting and postprandial energy expenditure, insulin resistance in adulthood, hypertension, dyslipidaemia and a reduced capacity for manual work, among other impairments. Marked changes in the function of the autonomic nervous system have been described in undernourished experimental animals. Some of these effects seem to be epigenetic, passing on to the next generation. Undernutrition in children has been linked to poor mental development and school achievement as well as behavioural abnormalities. However, there is still a debate in the literature regarding whether some of these effects are permanent or reversible. Stunted children who had experienced catch-up growth had verbal vocabulary and quantitative test scores that did not differ from children who were not stunted. Children treated before 6 years of age in day-hospitals and who recovered in weight and height have normal body compositions, bone mineral densities and insulin production and sensitivity.

Biomarkers of Oxidative Stress and Antioxidant Status in Children Born Small for Gestational Age: Evidence of Lipid Peroxidation

Children born small for gestational age are known to be at increased risk for adult diseases such as hypertension, diabetes, and coronary heart disease. Oxidative stress is a common feature of these pathogenic conditions and can be the key link between size at birth and increased morbidity later in life. The purpose of this study was to analyze the parameters of lipoperoxidation and changes in antioxidant defense system as well as assess their relationship to birth weight. Concentrations of thiobarbituric-acid-reactive-substances and F2-isoprostanes, total antioxidant status, and the activity of both superoxide dismutase and glutathione peroxidase were measured in 65 children (33 boys, 32 girls; ages 8–13 y). Thiobarbituric-acid-reactive-substances and F2-isoprostane levels were significantly elevated in children born small for gestational age. Nevertheless, superoxide dismutase activity was significantly elevated in these children and the levels of both glutathione peroxidase activity and total antioxidant status were unchanged. Moreover, we found that systolic blood pressure was positively associated with thiobarbituric-acid-reactive-substances levels in race- and gender-adjusted models but not in a multivariable regression model. In conclusion, the current study revealed that there is evidence of oxidative stress in children born small for gestational age as supported by increased lipid peroxidation.

Short stature, obesity and arterial hypertension in a very low income population in North-eastern Brazil

BACKGROUND AND AIM This cross-sectional study involved the adult population (age >18 and <60 years) of a 315-shack slum on the outskirts of the city of Maceió in North-eastern Brazil. The purpose was to investigate whether short stature in adults (an indicator of undernutrition in early life) is associated with arterial hypertension and obesity. METHODS AND RESULTS We collected the subjects socio-economic data, and arterial hypertension (AH), weight, height, waist circumference and waist/hip (W/H) circumference ratio measurements. Hypertension was diagnosed as diastolic AH f 90 mmHg and/or systolic AH f 140 mmHg. The body mass index (BMI) was used to determine nutritional status, with overweight/obesity being defined on the basis of a cut-off point of 25 kg/m2. A W/H ratio of f 0.80 for women or f 0.95 for men was considered indicative of abdominal obesity. Short stature was defined as falling into the 1st quartile (Q) of height distribution. Hypertension was prevalent in 28.5% of the population (women=38.5%; men=18.4%). The systolic and diastolic AH readings were significantly higher in women in the 1st Q than in those in the 4th Q, and the same was true of W/H. The prevalence of hypertension was statistically significant for the first two Qs in comparison with the last two: 22.1% vs 14.6% (men), and 42.4% vs 34.6% (women). Hypertension was more prevalent in women who were obese and short (50%) than in those who were obese but not short (OR=1.98; CI=1.22-2.96). CONCLUSIONS Living conditions were extremely precarious and the prevalence of hypertension was quite high. Stature negatively correlated with hypertension and overweight in women but not in men.

Food consumed does not account for the higher prevalence of obesity among stunted adults in a very-low-income population in the Northeast of Brazil (Maceió, Alagoas)

Objective: To study the food pattern of stunted and nonstunted, obese and nonobese individuals in a very-low-income population.Design: A household survey.Setting: Slum set up by the ‘Homeless Movement’, city of Maceió (Alagoas), Brazil.Subjects and methods: A total of 532 adults classified by sex, stature (Z≤ and Z > −2s.d. of the NCHS curves), and body mass index (BMI) were compared using the following variables: waist circumference, waist–hip circumference ratio (W/H), percentage body fat (skinfold thickness and bioelectrical impedance), and food intake (24-h recall).Results: The prevalence of stunting was 22.6%. In all, 30% of the stunted subjects were overweight or obese, compared with 23% for the nonstunted individuals (P<0.05). In women, logistic regression analysis showed a strong association among weight, abdominal fat, and stunting (r=0.81). No significant differences were observed in the values of W/H or in the qualitative menu of the different categories. Energy intake was below the RDA figures (about 63%). There was similarity among the groups regarding the proportion of macronutrients, except for the fact that stunted obese women ingested less fat and protein than nonstunted obese women. Stunted obese individuals consumed less energy (5962 kJ) than the population as a whole (6213 kJ), an amount far lower than their average needs, which were calculated on the basis of their shorter stature (8109 kJ).Conclusion: The observed energy consumption seems compatible with the panorama of undernutrition present in the population, but it does not explain the high prevalence of obesity detected.Sponsorship: Alagoas State Foundation for the Support of Research (FAPEAL) and the National Agency for the Advancement of College Graduates (Ministry of Education and Sports), Brazil.

Circulating renin-angiotensin system and catecholamines in childhood: is there a role for birthweight?

There have been only a few reports on the sympathoadrenal and renin-angiotensin systems in children of small gestational age. The purpose of the present study was to investigate plasma levels of ACE (angiotensin-converting enzyme) activity, angiotensin and catecholamines in 8- to 13-year-old children and to determine whether there are correlations between the components of these systems with both birthweight and BP (blood pressure) levels. This clinical study included 66 children (35 boys and 31 girls) in two groups: those born at term with an appropriate birthweight [AGA (appropriate-for-gestational age) group, n=31] and those born at term but with a small birthweight for gestational age [SGA (small-for-gestational age) group, n=35]. Concentrations of angiotensin, catecholamines and ACE activity were determined in plasma. Circulating noradrenaline levels were significantly elevated in SGA girls compared with AGA girls (P=0.036). In addition, angiotensin II and ACE activity were higher in SGA boys (P=0.024 and P=0.050 respectively). There was a significant association of the circulating levels of both angiotensin II and ACE activity with BP levels in our study population. Although the underlying mechanisms that link restricted fetal growth with later cardiovascular events are not fully understood, the findings in the present study support the link between low birthweight and overactivity of both sympathoadrenal and renin-angiotensin systems into later childhood.

Lower resting metabolic rate and higher velocity of weight gain in a prospective study of stunted vs nonstunted girls living in the shantytowns of São Paulo, Brazil.

Objective:Previous studies have shown that stunting increases the risk of obesity in developing countries, particularly among girls and women, but the underlying reasons are not known. This study aimed to investigate the relationship between stunting, weight gain, and resting metabolic rate.Design and subjects:A prospective study was conducted over 36 months with girls from shantytowns in São Paulo, Brazil. A total of 15 stunted girls (S) were compared with 15 nonstunted (N) ones of similar weight for height ratio.Interventions:Resting metabolic rate was measured using indirect calorimetry, and the socioeconomic status was determined by interviews in the household. In addition, body composition was measured by skinfold thickness, while the growth rate was calculated dividing the change in weight and the change in height by the follow-up period.Results:The results of the present study, when combined, revealed that the S group had a lower resting metabolic rate throughout the follow-up period with the differences being significant at 24 and 36 months of follow-up, associated with an increase in the rate of weight gain and a decrease in lean mass, when compared to the N group.Conclusions:These changes are known to be risk factors for obesity and may help to explain the particularly higher prevalence of obesity in women in urban areas of developing countries.