Developmental origins of metabolic diseases.

Almost 2 billion adults in the world are overweight, and more than half of them are classified as obese, while nearly one-third of children globally experience poor growth and development. Given the vast amount of knowledge that has been gleaned from decades of research on growth and development, a number of questions remain as to why the world is now in the midst of a global epidemic of obesity accompanied by the "double burden of malnutrition," where overweight coexists with underweight and micronutrient deficiencies. This challenge to the human condition can be attributed to nutritional and environmental exposures during pregnancy that may program a fetus to have a higher risk of chronic diseases in adulthood. To explore this concept, frequently called the developmental origins of health and disease (DOHaD), this review considers a host of factors and physiological mechanisms that drive a fetus or child toward a higher risk of obesity, fatty liver disease, hypertension, and/or type 2 diabetes (T2D). To that end, this review explores the epidemiology of DOHaD with discussions focused on adaptations to human energetics, placental development, dysmetabolism, and key environmental exposures that act to promote chronic diseases in adulthood. These areas are complementary and additive in understanding how providing the best conditions for optimal growth can create the best possible conditions for lifelong health. Moreover, understanding both physiological as well as epigenetic and molecular mechanisms for DOHaD is vital to most fully address the global issues of obesity and other chronic diseases.

Preconception Micronutrient Supplementation Affects Maternal BMI and Body Composition Postpartum: A Randomized Controlled Trial in Vietnam.

BACKGROUND: Although there is growing evidence on the role of preconception nutrition for birth outcomes, limited evidence exists for its effects on maternal health. OBJECTIVES: This study evaluates the impact of preconception micronutrient supplementation on maternal BMI (kg/m2) and body composition at 6 to 7 y postpartum (PP). METHODS: We followed females who participated in a randomized controlled trial of preconception supplementation in Vietnam and delivered live offspring (n = 1599). Females received weekly supplements containing either 2800 µg folic acid (FA) only, 60 mg iron and 2800 µg FA (IFA), or multiple micronutrients (MMs) (15 micronutrients including IFA) from baseline until conception followed by daily prenatal IFA supplements until delivery. Height, weight, mid-upper arm circumference, triceps skinfold, and waist-hip circumference were measured at recruitment and at 1, 2, and 6 to 7 y PP. Body fat was assessed using bioelectric impedance at 6 to 7 y PP (n = 867). Group comparisons were made using analysis of variance or chi-square tests and general linear models for adjusted models. RESULTS: At 6 to 7 y PP, we found significant differences (P < 0.05) by treatment group for mean percent fat (MM: 29.2%; IFA: 27.6%; FA: 27.8%), absolute fat mass (MM: 15.1 kg; IFA: 14.0 kg; FA: 14.3 kg), and prevalence of underweight based on BMI < 18.5 (MM: 5.8%; IFA: 10.3%; FA: 14.3%). Mean BMI and triceps skinfold thickness were higher in the MM group, but these differences were not statistically significant; the differences in absolute fat mass were also attenuated after controlling for body weight. No differences were observed for fat-free mass, prevalence of overweight (BMI >23), or other anthropometric measurements. CONCLUSIONS: Preconception MM supplementation was associated with lower prevalence of underweight and higher percent fat when compared with IFA and/or FA only. Preconception micronutrient interventions may have long-term effects on maternal health and merit further examination. This trial was registered at clinicaltrials.gov as NCT01665378.

The relationship between total energy expenditure and physical activity level in women living in an impoverished Brazilian urban area.

OBJECTIVE: This study aimed to describe how strong is the relationship between TEE and PAL in women living in an impoverished Brazilian urban area. METHODS: Anthropometric, hormonal (insulin, TSH, FT4 , and FT3 ), body composition (deuterium), TEE (doubly labeled water) and PAL (metabolic equivalent task [MET]-7-day triaxial accelerometer, ActivPAL®) data were collected from 55 women (mean age: 31y, mean BMI: 27.4 kg/m2 ). Adjusted-TEE models were calculated incorporating the residuals of anthropometric, hormonal, and body composition variables in the TEE, to assess the relation between MET and adjusted-TEE, through three different analyzes: linear regression, nonlinear regression and change-point regression. RESULTS: Most participants (89.1%, n = 49) were classified as low-active. There was no association between crude TEE and MET.h/d (R2  = 0.05; p = 0.09). There was a positive, although weak, linear relationship between adjusted-TEE and MET.h/d (ß = 2705.26 kcal; 95% CI: 436.25; 4974.27; adj-R2  = 0.08). A change point of this relationship was identified in the MET.h/d value of 1.53 (SD = 0.02; adj-R2 = 0.13). The association between adjusted-TEE and MET.h/d before the change point (ß = 5101.46 kcal; 95%CI: 978.84; 9224.08; adj-R2  = 0.11) was stronger than the association in the full linear model, nevertheless, it was still weak. This association stop existing when it is assessed in individuals after the change point (ß = -6609.92 kcal; 95%CI: -16773.24; 3553.40; adj-R2  = 0.08). CONCLUSIONS: These results suggest that the relationship between TEE and PAL is weak and it is not completely linear in women living in an impoverished Brazilian urban area.

Pre-pregnancy dietary pattern is associated with newborn size: results from ProcriAr study.

Babies born small-for-gestational age (SGA) have an increased risk of mortality, morbidity and adverse functional consequences. Studies suggest that pre-pregnancy maternal diet may influence newborns' size. This study aimed to determine whether maternal pre-pregnancy dietary patterns (DP) are associated with delivering SGA newborns in the ProcriAr Cohort Study, Sao Paulo-Brazil. Pre-pregnancy DP of 299 women were investigated using factor analysis with principal component's estimation, based on intake reported on a validated 110-item FFQ. Newborns were classified as SGA if their weight and/or length, adjusted by gestational age and sex, were below the 10th percentile of the INTERGROWTH-21st standards. Multivariate Poisson regression modelling with robust error variance was performed to examine associations between the different DP (in quintiles) and SGA. In a model adjusted by maternal sociodemographic and health behaviours, women who scored in the highest quintile of the DP 'Snacks, sandwiches, sweets and soft drinks' (in relation to the women who scored in the lowest quintile) were significantly more likely to deliver SGA babies (relative risk 1·92; 95 % CI 1·08, 3·39). This study verified that women's pre-pregnancy dietary behaviour characterised by an energy-dense nutrient-poor food intake was a risk factor for delivering SGA newborns. Investments in education and improved access to healthful food and nutritional information before pregnancy should be prioritised due to their potential positive impact on child health. However, further studies are warranted to identify specific metabolic pathways that may be underlying these associations.

Development of population-specific prediction equations for bioelectrical impedance analyses in Vietnamese children.

There is a need for accurate, inexpensive and field-friendly methods to assess body composition in children. Bioelectrical impedance analysis (BIA) is a promising approach; however, there have been limited validation and use among young children in resource-poor settings. We aim to develop and validate population-specific prediction equations for estimating total fat mass (FM), fat free-mass (FFM) and percentage body fat (PBF) in Vietnamese children (4-7 years) using reactance and resistance from BIA, anthropometric variables and demographic information. We conducted a cross-sectional survey of 120 children. Body composition was measured using dual-energy X-ray absorptiometry (DXA), BIA and anthropometry. To develop prediction equations, we split all data into development (70 %) and validation datasets (30 %). The model performance was evaluated using predicted residual error sum of squares, root mean squared error (RMSE), mean absolute error (MAE) and R2. We identified a top performing model with the least number of parameters (age, sex, weight and resistance index or resistance and height), low RMSE (FM 0·70, FFM 0·74, PBF 3·10), low MAE (FM 0·55, FFM 0·62, PBF 2·49), high R2 (FM 0·95, FFM 0·92, PBF 0·82) and the least difference between predicted values and actual values from DXA (FM 0·03 kg or 0·01 sd, FFM 0·06 kg or 0·02 sd, PBF 0·27 % or 0·04 sd). In conclusion, we developed the first valid and highly predictive equations to estimate FM, FFM and PBF in Vietnamese children using BIA. These findings have important implications for future research on the double burden of disease and risks associated with overweight and obesity in young children.

Longitudinal associations between ultra-processed foods and blood lipids in childhood.

Emerging evidence suggests that the consumption of ultra-processed foods (UPF) plays a role in the development of chronic diseases, but evidence of their influence in children is limited. Our objective was to study longitudinal trends of UPF intake and determine their impact on blood lipids in young children. The present study was a follow-up of a randomised field trial of children (n 308) from Porto Alegre, Brazil. Dietary intake was collected using two 24-h recalls at 3 and 6 years of age, and consumption of UPF was classified according to the NOVA system, a food classification based on the extent and purpose of industrial food processing. At age 6 years, blood tests were performed to measure lipid profile. Contribution of UPF to total energy intake increased by 10 % during the follow-up period, from 43·4 % at 3 years to 47·7 % at 6 years of age. Linear regression models showed that children in the highest tertile of UPF consumption at age 3 years had higher levels of total cholesterol (TC; ß 0·22 mmol/l; 95 % CI 0·04, 0·39) and TAG at age 6 years (ß 0·11 mmol/l, 95 % CI 0·01, 0·20) compared with those in the lowest tertile. A positive dose-response was observed for an absolute increment of 10 % of UPF on TC (ß 0·07 mmol/l, 95 % CI 0·00, 0·14) and TAG (ß 0·04 mmol/l, 95 % CI 0·01, 0·07). Based on our data, consumption of UPF increased significantly over time and was associated with higher blood lipid levels in children from a low-income community. Our findings highlight the need for effective strategies to minimise the consumption of UPF in early life.

Height Trajectory During Early Childhood Is Inversely Associated with Fat Mass in Later Childhood in Mexican Boys.

BACKGROUND: Childhood obesity continues to be a global health problem. Previous research suggests that linear growth retardation or stunting during early childhood increases the risk of obesity, but others have reported that rapid linear growth poses a greater concern than early nutritional status. OBJECTIVE: The objective of this study was to determine if growth trajectories are associated with body composition at age 8-10 y. METHODS: Study participants consisted of 255 girls and 281 boys who participated in a follow-up of the Prenatal Omega-3 Fatty Acid Supplementation and Child Growth and Development (POSGRAD) Study. Sex-specific latent height class (LHC) trajectories were derived from 11 measures of height from birth to 5 y of age and used to calculate 3 distinct growth classes for boys (low, intermediate, and high) and 2 distinct classes for girls (low and high). Body composition at age 8-10 y was estimated using bioelectrical impedance analysis. Multivariable linear regression analysis was used to determine the relationship between growth trajectory classes and fat mass (FM) and fat-free mass (FFM) in late childhood, controlling for confounding factors. RESULTS: In girls, there were no significant associations between LHC and FM or FFM. In boys, relative to the intermediate LHC, the low LHC had higher FM (ß = 0.69 kg; 95% CI: 0.26-1.11 kg) and the high LHC had lower FM (ß = -0.40 kg; 95% CI: -0.76 to -0.05 kg). Boys in the low LHC had significantly less FFM (ß = -0.69 kg; 95% CI: -1.11 to -0.26 kg), and boys in the high LHC had more FFM (ß = 0.40 kg; 95% CI: 0.05-0.76 kg) compared with the intermediate LHC. CONCLUSION: Gain in height among boys, but not girls, in early childhood was associated with lower adiposity in late childhood compared with children with a slower rate of growth. Clinical trial registration number: NCT00646360.

Microbiome, growth retardation and metabolism: are they related?

CONTEXT: Despite an improvement in food security and the delivery of nutritional supplements to children living in impoverished parts of the world, poor growth is still highly prevalent. Given that the microbiome is related to both nutrient absorption, as well as overweight/obesity, it may play a central role in limiting or modifying normal growth processes while contributing to chronic disease risks. OBJECTIVE: The objective of this paper is to describe normal growth processes, the role of the microbiome in supporting or disrupting normal growth processes, and its potential impact on long-term health. METHODS: A literature search of relevant human and laboratory research on growth, microbiome and the relationship between poor growth and chronic diseases was conducted. This review focuses on potential mechanisms that implicate the microbiome as a mediator of poor growth and later metabolic outcomes. In this relationship, attention was given to the potential for gastrointestinal infections to disrupt the microbiome. RESULTS: Based on the studies reviewed, it is clear that exposure to infections disturbs both intestinal functioning as well as normal growth and changes in the microbiome may influence micronutrient availability and metabolic processes. CONCLUSIONS: The microbiome may play a significant role in limiting human growth, but little is known about changes in the microbiome during periods of undernutrition. Thus, it is of great scientific and public health importance to improve the understanding of how the microbiome changes during nutrient deprivation. To best address the issue of the double burden and poor growth in low-income countries, research is warranted to advance the knowledge of the long-term role of the microbiome in the health of children exposed to undernutrition.

Normal cortisol response to cold pressor test, but lower free thyroxine, after recovery from undernutrition.

Undernutrition is a stressor with long-term consequences, and the effect of nutritional recovery on cortisol and thyroid hormone status is unknown. To investigate basal thyroid hormones and the cortisol response to a cold pressor test in children recovered from undernutrition, a cross-sectional study was undertaken on children (6-16 years) separated into four groups: control (n 41), stunted (n 31), underweight (n 27) and recovered (n 31). Salivary cortisol was collected over the course of 10 h: upon awakening, before and after an unpleasant and a pleasant stimulus. Cortisol upon awakening was highest in the stunted and lowest in the underweight groups: control=5·05 (95% CI 3·71, 6·89) nmol/l, stunted=6·62 (95% CI 3·97, 11·02) nmol/l, underweight=2·51 (95% CI 1·75, 3·63) nmol/l and recovered=3·46 (95% CI 2·46, 4·90) nmol/l (P=0·005). Girls had higher cortisol concentrations upon awakening compared with boys (P=0·021). The undernourished groups showed an elevated cortisol response both to the unpleasant stimulus and at the last measurement (16.00 hours) compared with that of the recovered group: AUC, control=2·07 (95% CI 1·69, 2·45) nmol/l×30 min, stunted=2·48 (95% CI 1·91, 3·06) nmol/l×30 min, underweight=2·52 (95% CI 2·07, 2·97) nmol/l×30 min, recovered=1·68 (95% CI 1·26, 2·11) nmol/l×30 min (P=0·042); and control=2·03 (95% CI 1·75, 2·39) nmol/l×30 min, stunted=2·51 (95% CI 1·97, 3·19) nmol/l×30 min, underweight=2·61 (95% CI 2·16, 3·16) nmol/l×30 min, recovered=1·70 (95% CI 1·42, 2·03) nmol/l×30 min (P=0·009). Lower free thyroxine (T4) was found in the recovered and stunted groups: control=1·28 (95% CI 1·18, 1·39) pmol/l, stunted=0·98 (95% CI 0·87, 1·10) pmol/l, underweight=1·10 (95% CI 1·01, 1·21) pmol/l and recovered=0·90 (95% CI 0·83, 0·99) pmol/l (P<0·001). Multivariate analysis showed a lower cortisol concentration along 10 h (06.00-16.00 hours) in the recovered compared with the other groups (P=0·017), and similar concentrations between the recovered and control group. In conclusion, the children with recovery in weight and height had a cortisol stress response similar to control but a lower basal free T4. Longitudinal studies are warranted to determine the extent of these endocrine changes after recovery of undernutrition and in adulthood.

Maternal fat mass at mid-pregnancy and birth weight in Brazilian women.

BACKGROUND: The relationship between maternal body composition and foetal development is unclear. AIM: To determine the relationship between maternal body composition [fat mass (FM) and fat-free mass (FFM)] and foetal growth and birth weight, independent of potential confounding factors. SUBJECTS AND METHODS: This study consisted of 92 women, normal and overweight/obese, recruited from the Instituto Fernandes Figueira in Rio de Janeiro, Brazil. Body composition (FM and FFM) was estimated using bioelectrical impedance. Foetal growth was assessed using serial ultrasound measurements at the second and third trimester and infant's weight and length were measured at birth. Multiple linear regression analyses were used to determine the association between maternal FM and FFM and birth weight adjusted for gestational age (BWt) and change in estimated foetal weight (ΔEFW), controlling for infant gender, maternal serum glucose, energy intake, parity, height and income. RESULTS: Maternal FM, but not FFM, was positively associated with BWt (p = 0.02) and borderline with ΔEFW (p = 0.05). FM expressed as a percentage of body weight (%FM) showed a significant positive association with BWt (p < 0.001) and ΔEFW (p < 0.01). Using backward linear regression analysis, FM was a significant predictor of BWt (p < 0.001) and ΔEFW (p = 0.03), but not change in femur length. CONCLUSION: In this small sample of normal and overweight/obese women, maternal FM at mid-pregnancy is associated with neonatal BW and foetal growth.

Consumption of a high-fat soup preload leads to differences in short-term energy and fat intake between PROP non-taster and super-taster women.

Taste blindness to the bitterness of PROP (6-n-propylthiouracil) has been used as a genetic marker for food selection and adiposity. We have shown that PROP non-taster (NT) women have higher BMIs and habitually consume more fat and energy than either medium-taster (MT) or super-taster (ST) women. These data imply that differences in dietary selection underlie the body weight differences among PROP taster groups. However, no studies investigated energy compensation in women classified by PROP status. We investigated if NTs would compensate less accurately for the calories and fat in a high-fat soup preload in a subsequent test meal compared to MTs and STs. Energy intake from a buffet meal was measured in 75 healthy non-diet-restrained, lean women 30 min after the ingestion of a high-fat soup preload (0.8 kcal/g; 55% calories from fat), calculated to represent 10% of resting energy expenditure for each subject, or the same volume of water. Subjects (n = 20-28/taster group) ate a standard breakfast followed 3 hr later by an ad-libitum buffet lunch, on two occasions. There were no differences in energy intake or macronutrient selection across taster groups after water. After soup, NTs consumed more energy than STs. Fat intake (as %-energy) was higher in NTs (46.4% ± 2.4) compared to either MTs (36.1 ± 1.9%) or STs (38.1% ± 2.3; p < 0.05). NTs overate by 11% ± 5 after the soup compared to MTs and STs who underrate by 16% ± 6 and 26% ± 10, respectively (p < 0.01). These data suggest that small discrepancies in short-term energy compensation and selection of fat after a mixed-nutrient, high-fat preload may play a role in positive energy balance and increased adiposity in women with the PROP non-taster phenotype.

ß-carotene-producing bacteria residing in the intestine provide vitamin A to mouse tissues in vivo.

Vitamin A deficiency (VAD) is an overwhelming public health problem that affects hundreds of millions of people worldwide. A definitive solution to VAD has yet to be identified. Because it is an essential nutrient, vitamin A or its carotenoid precursor ß-carotene can only be obtained from food or supplements. In this study, we wanted to establish whether ß-carotene produced in the mouse intestine by bacteria synthesizing the provitamin A carotenoid could be delivered to various tissues within the body. To achieve this, we took advantage of the Escherichia coli MG1655*, an intestine-adapted spontaneous mutant of E. coli MG1655, and the plasmid pAC-BETA, containing the genes coding for the 4 key enzymes of the ß-carotene biosynthetic pathway (geranylgeranyl pyrophosphate synthase, phytoene synthase, phytoene desaturase, and lycopene cyclase) from Erwinia herbicola. We engineered the E. coli MG1655* to produce ß-carotene during transformation with pAC-BETA (MG1655*-ßC) and gavaged wild-type and knockout mice for the enzyme ß-carotene 15,15'-oxygenase with this recombinant strain. Various regimens of bacteria administration were tested (single vs. multiple and low vs. high doses). ß-Carotene concentration was measured by HPLC in mouse serum, liver, intestine, and feces. Enumeration of MG1655*-ßC cells in the feces was performed to assess efficiency of intestinal colonization. We demonstrated in vivo that probiotic bacteria could be used to deliver vitamin A to the tissues of a mammalian host. These results have the potential to pave the road for future investigations aimed at identifying alternative, novel approaches to treat VAD.

Diet quality from pre-school to school age in Brazilian children: a 4-year follow-up in a randomised control study.

A previous study demonstrated that dietary counselling for mothers during the first year of life improved overall diet quality of children at pre-school age in a low-income population. Thus, the objective of the present study was to assess the long-term effect of this intervention on diet quality of children at school age and examine the tracking of dietary intake throughout childhood. The present study was a follow-up of a randomised controlled trial with children who were assessed at 3-4 years (n 345) and 7-8 years (n 307) of age. We collected two 24 h dietary recalls and assessed diet quality using the Healthy Eating Index (HEI). Analyses were performed by group using a paired t test and a Student's t test for independent samples. Diet quality did not differ between the intervention and control groups at 7-8 years of age (HEI score 65·2 (SD 9·5) v. 64·9 (SD 8·5)). Regarding changes in diet quality from pre-school to school age, we observed the tracking of diet quality in the control group and the loss of the intervention effect in the intervention group. In both groups, the score for fruit and milk intake decreased, while that for saturated fat and dietary variety intake increased. The score for the intakes of grains, meat and legumes, and total fat remained constant for all children. The present data provide evidence that diet quality tracks during childhood since the total HEI score did not differ over time in the control group. The decrease in score for some HEI components did not affect the overall diet quality due to the increase in score for other HEI components.