Associations between DNA methylation and BMI vary by metabolic health status: a potential link to disparate cardiovascular outcomes.

BACKGROUND: Body mass index (BMI), a well-known risk factor for poor cardiovascular outcomes, is associated with differential DNA methylation (DNAm). Similarly, metabolic health has also been associated with changes in DNAm. It is unclear how overall metabolic health outside of BMI may modify the relationship between BMI and methylation profiles, and what consequences this may have on downstream cardiovascular disease. The purpose of this study was to identify cytosine-phosphate-guanine (CpG) sites at which the association between BMI and DNAm could be modified by overall metabolic health. RESULTS: The discovery study population was derived from three Women's Health Initiative (WHI) ancillary studies (n = 3977) and two Atherosclerosis Risk in Communities (ARIC) ancillary studies (n = 3520). Findings were validated in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort (n = 1200). Generalized linear models regressed methylation ß values on the interaction between BMI and metabolic health Z score (BMI × MHZ) adjusted for BMI, MHZ, cell composition, chip number and location, study characteristics, top three ancestry principal components, smoking, age, ethnicity (WHI), and sex (ARIC). Among the 429,566 sites examined, differential associations between BMI × MHZ and DNAm were identified at 22 CpG sites (FDR q < 0.05), with one site replicated in MESA (cg18989722, in the TRAPPC9 gene). Three of the 22 sites were associated with incident coronary heart disease (CHD) in WHI. For each 0.01 unit increase in DNAm ß value, the risk of incident CHD increased by 9% in one site and decreased by 6-10% in two sites over 25 years. CONCLUSIONS: Differential associations between DNAm and BMI by MHZ were identified at 22 sites, one of which was validated (cg18989722) and three of which were predictive of incident CHD. These sites are located in several genes related to NF-kappa-B signaling, suggesting a potential role for inflammation between DNA methylation and BMI-associated metabolic health.

Standardization and validation of assay of selected omega-3 and omega-6 fatty acids from phospholipid fraction of red cell membrane using gas chromatography with flame ionization detector.

BACKGROUND: Docosahexaenoic acid (DHA) is an important structural component of human brain and retina. Evidence exists linking nutritional status of pregnant mothers and cognitive functions of their born infants. The DHANI (Maternal DHA Supplementation and Offspring Neurodevelopment in India) trial was implemented to evaluate the effect of maternal supplementation with DHA during pregnancy and for 6 months following delivery on motor and mental development of infants at 1 and 12 months. We describe here the standardization and validation of an assay for measurement of selected omega-3 and omega-6 fatty acids from the phospholipid fraction of red blood cells to assess their status in mothers at baseline, delivery and 6 months post-delivery and for infants in cord blood and at 1 and 12 months of age. The validated method has been used for the analysis of samples for DHANI. METHODS: Lipids were extracted from a pool of red blood cells, separated using thin layer chromatography. The phospholipid fraction was esterified, and fatty acids were separated by gas chromatography using a flame ionization detector. RESULT: The method accuracy for DHA was between 97 - 98% and between 91 - 95% for arachidonic acid (AA) at three different concentrations. The intra-assay and inter-assay coefficient of variation for the fatty acids ranged from 1.19 to 5.7% and 0.78 to 13.0% respectively. Intraclass correlation (ICC), as a measure of reproducibility, ranged between 0.689 and 0.996. A good linearity was observed for all the fatty acids between concentrations of 0.2-4 µg/ml. CONCLUSION: The standardized and validated method is suitable for implementation in large epidemiological studies for evaluation of fatty acids and in nutritional trials for assessment of fatty acid content of various lipid classes.

Cabbage and Sauerkraut Consumption in Adolescence and Adulthood and Breast Cancer Risk among US-Resident Polish Migrant Women.

BACKGROUND: Breast cancer (BC) incidence and mortality are lower in Poland than in the United States (US). However, Polish-born migrant women to US approach the higher BC mortality rates of US women. We evaluated the association between consumption of cabbage/sauerkraut foods and BC risk in Polish-born migrants to US. METHODS: We conducted a case-control study of BC among Polish-born migrants in Cook County and the Detroit Metropolitan Area. Cases (n = 131) were 20-79 years old with histological/cytological confirmation of invasive BC. Population-based controls (n = 284) were frequency matched to cases on age and residence. Food frequency questionnaires assessed diet during adulthood and age 12-13 years. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated with conditional logistic regression. Consumption of total, raw/short-cooked, and long-cooked cabbage/sauerkraut foods was categorized as low, medium, or high (frequency of servings/week). RESULTS: Higher consumption of total and raw/short-cooked cabbage/sauerkraut foods, during both adolescence and adulthood, was associated with a significantly lower BC risk. Consumption of long-cooked cabbage/sauerkraut foods was low and not significantly associated with risk. The multivariate OR for total cabbage/sauerkraut consumption, high vs. low (>4 vs. ≤2 servings/week) during adolescence was 0.36 (95% CI = 0.18-0.71, ptrend < 0.01) and 0.50 (95% CI = 0.23-1.06, ptrend = 0.08) during adulthood. For raw/short-cooked cabbage/sauerkraut (>3 vs. ≤1.5 servings/week), the ORs were 0.35 (95% CI = 0.16-0.72, ptrend < 0.01) during adolescence and 0.37 (95% CI = 0.17-0.78, ptrend < 0.01) during adulthood. For joint adolescent/adult consumption of raw/short-cooked cabbage/sauerkraut foods, (high, high) vs. (low, low), the OR was 0.23 (95% CI = 0.07-0.65). The significant association for high adolescent consumption of raw/short-cooked cabbage/sauerkraut foods and reduced BC risk was consistent across all levels of consumption in adulthood. CONCLUSION: Greater consumption of total and raw/short-cooked cabbage/sauerkraut foods either during adolescence or adulthood was associated with significantly reduced BC risk among Polish migrant women. These findings contribute to the growing literature suggesting a protective effect of a potentially modifiable factor, cruciferous vegetable intake, on breast cancer risk.

Initial engagement and persistence of health risk behaviors through adolescence: longitudinal findings from urban South Africa.

BACKGROUND: Little is known about longitudinal patterns of adolescent health risk behavior initial engagement and persistence in low- and middle-income countries. METHODS: Birth to Twenty Plus is a longitudinal birth cohort in Soweto-Johannesburg, South Africa. We used reports from Black African participants on cigarette smoking, alcohol, cannabis, illicit drug, and sexual activity initial engagement and adolescent pregnancy collected over 7 study visits between ages 11 and 18 y. We fit Kaplan-Meier curves to estimate behavior engagement or adolescent pregnancy, examined current behavior at age 18 y by age of first engagement, and performed a clustering analysis to identify patterns of initial engagement and their sociodemographic predictors. RESULTS: By age 13 y, cumulative incidence of smoking and alcohol engagement were each > 21%, while the cumulative incidence of other behaviors and adolescent pregnancy were < 5%. By age 18 y (15 y for cannabis), smoking, alcohol, and sexual activity engagement estimates were each > 65%, cannabis and illicit drug engagement were each > 16%; adolescent pregnancy was 31%. Rates of engagement were higher among males. Current risk behavior activity at age 18 y was generally unrelated to age of initial engagement. We identified three clusters reflecting low, moderate, and high-risk patterns of initial risk behavior engagement. One-third of males and 17% of females were assigned to the high-risk cluster. Sociodemographic factors were not associated with cluster membership. CONCLUSIONS: Among urban dwelling Black South Africans, risk behavior engagement across adolescence was common and clustered into distinct patterns of initial engagement which were unrelated to the sociodemographic factors assessed. Patterns of initial risk behavior engagement may inform the timing of primary and secondary public health interventions and support integrated prevention efforts that consider multiple behaviors simultaneously.

Epigenome-wide association study of diet quality in the Women's Health Initiative and TwinsUK cohort.

BACKGROUND: Diet quality is a risk factor for chronic disease and mortality. Differential DNA methylation across the epigenome has been associated with chronic disease risk. Whether diet quality is associated with differential methylation is unknown. This study assessed whether diet quality was associated with differential DNA methylation measured across 445 548 loci in the Women's Health Initiative (WHI) and the TwinsUK cohort. DESIGN: The discovery cohort consisted of 4355 women from the WHI. The replication cohort consisted of 571 mono- and dizygotic twins from the TwinsUK cohort. DNA methylation was measured in whole blood using the Illumina Infinium HumanMethylation450 Beadchip. Diet quality was assessed using the Alternative Healthy Eating Index 2010 (AHEI-2010). A meta-analysis, stratified by study cohort, was performed using generalized linear models that regressed methylation on AHEI-2010, adjusting for cell composition, chip number and location, study characteristics, principal components of genetic relatedness, age, smoking status, race/ethnicity and body mass index (BMI). Statistical significance was defined as a false discovery rate < 0.05. Significant sites were tested for replication in the TwinsUK cohort, with significant replication defined by P < 0.05 and a consistent direction. RESULTS: Diet quality was significantly associated with differential DNA methylation at 428 cytosine-phosphate-guanine (CpG) sites in the discovery cohort. A total of 24 CpG sites were consistent with replication in the TwinsUK cohort, more than would be expected by chance (P = 2.7x10-4), with one site replicated in both the blood and adipose tissue (cg16379999 located in the body of SEL1L). CONCLUSIONS: Diet quality was associated with methylation at 24 CpG sites, several of which have been associated with adiposity, inflammation and dysglycaemia. These findings may provide insight into pathways through which diet influences chronic disease.

Consumption of Foods Derived from Subsidized Crops Remains Associated with Cardiometabolic Risk: An Update on the Evidence Using the National Health and Nutrition Examination Survey 2009-2014.

In this study, we examined the associations between the consumption of foods derived from crops subsidized under the 2008 United States (US) Farm Bill and cardiometabolic risk factors and whether the magnitude of these associations has changed since the 2002 US Farm Bill. Four federal databases were used to estimate daily consumption of the top seven subsidized commodities (corn, soybeans, wheat, rice, sorghum, dairy, and livestock) and to calculate a subsidy score (0-1 scale) for Americans' daily dietary intake during 2009-2014, with a higher score indicative of a higher proportion of the diet derived from subsidized commodities. The cardiometabolic risk factors included obesity, abdominal adiposity, hypertension, dyslipidemia, and dysglycemia. Linear and logistic regression models were adjusted for age, sex, race/ethnicity, the poverty-income ratio, the smoking status, educational attainment, physical activity, and daily calorie intake. During 2009-2014, adults with the highest subsidy score had higher probabilities of obesity, abdominal adiposity, and dysglycemia compared to the lowest subsidy score. After the 2002 Farm Bill (measured using data from 2001-2006), the subsidy score decreased from 56% to 50% and associations between consuming a highly-subsidized diet and dysglycemia did not change (p = 0.54), whereas associations with obesity (p = 0.004) and abdominal adiposity (p = 0.002) significantly attenuated by more than half. The proportion of calories derived from subsidized food commodities continues to be associated with adverse cardiometabolic risk factors, though the relationship with obesity and abdominal adiposity has weakened in recent years.

Prenatal exposure to environmental pollutants and child development trajectories through 7 years.

BACKGROUND: Prenatal exposure to environmental pollutants such as mold, lead, pesticides, tobacco, and air pollutants has been suggested to impair cognitive development. Evidence is needed from longitudinal studies to understand their joint impact on child development across time. OBJECTIVE: To study associations between exposure to indoor environmental pollutants or outdoor air pollution during pregnancy and offspring cognitive development trajectories through 7 years. METHODS: We included 718 Mexican mother-child pairs. Prenatal exposure to indoor environmental pollutants (mold, ventilation, pesticides, tobacco smoke, and use of vidiartred clay pots) was self-reported by the mothers and integrated into an index, or objectively measured in the case of outdoor air pollutants (nitrogen oxides, benzene, toluene, and xylene). Child global cognitive development was measured at 12, 18, 60, or 84 months. Using Latent Class Growth Analysis, we identified three developmental trajectories (positive = 108, average = 362, low = 248). We used multinomial logistic models to test associations between environmental pollutant score (EPS) or outdoor air pollutants, and cognitive development trajectories. RESULTS: After adjustment for sociodemographic covariates, EPS was associated with the average (OR = 1.26 95%CI = 1.01, 1.55) and low (OR = 1.41 95%CI = 1.11, 1.79) trajectories compared to positive; where a unit increase in EPS means an additional prenatal exposure to a pollutant. There was no association between outdoor air pollutants and cognitive development trajectories. CONCLUSION: Children of women who reported higher exposure to indoor environmental pollutants during pregnancy were more likely to follow worse developmental trajectories through 7 years. These results support the development and testing of interventions to reduce exposure to environmental pollutants during pregnancy and early childhood as a potential strategy to improve long-term cognitive development.

A Nutrition Education Program in Rural Bangladesh Was Associated with Improved Feeding Practices but Not with Child Growth.

Background: Childhood undernutrition is a major public health problem in Bangladesh. Evaluating child nutrition programs is a priority.Objective: The objective of this study was to evaluate a community-based nutrition education program (implemented from 2011 to 2013) aimed at improving infant and young child feeding (IYCF) practices and growth in rural Bangladesh.Methods: A cohort-based evaluation was conducted that included 2400 women (1200 from Karimganj, the intervention subdistrict, and 1200 from Katiadi, the control subdistrict) enrolled at 28-31 wk gestation in 3 waves between January and October 2011. Follow-up occurred at 3, 9, 16, and 24 mo of offspring age. The main outcomes were exclusive breastfeeding (EBF), measured at 3 mo, timing of complementary feeding (CF) initiation and minimum acceptable diet (MAD), measured at 9 mo, and child growth [assessed via length-for-age z score (LAZ) and weight-for-length z score], measured at all follow-ups. The main exposures were subdistrict of residence and wave of enrollment. For IYCF practices as outcome, logistic regressions were used. Generalized estimating equations were used for child growth as outcome.Results: EBF rates at 3 mo remained unchanged between waves 1 and 3 in Karimganj (55.6% compared with 57.3%), but the proportion of infants receiving timely CF initiation and MAD at 9 mo increased significantly (CF: 27.1-54.7%; MAD: 8.4-35.3%). Mean LAZ at 24 mo remained unchanged between waves 1 and 3 in Karimganj (-2.18 compared with -1.98).Conclusions: The program was successful in improving the quality of infant diet at 9 mo and timely CF initiation, but not EBF at 3 mo or LAZ. These findings support the case for implementing simple messages in all programs aimed at improving infant diet, especially in settings in which supplementing overall household diet may not be feasible.

Perceptions of diet, physical activity, and obesity-related health among black daughter-mother pairs in Soweto, South Africa: a qualitative study.

BACKGROUND: The prevalence of overweight and obesity is on the rise in South Africa, particularly among females living in urban environments. The purpose of this qualitative study was to explore the emic perspectives of black young adult daughter and mother pairs living in Soweto, South Africa on diet, physical activity, and obesity-related health within their social and cultural context. METHODS: Purposeful sampling was used to recruit daughters with a normal body mass index (BMI) who have obese mothers. Individual semi-structured in-depth interviews were conducted with 17 daughters (age 24 years) and 15 of their mothers in Soweto, South Africa. Interview questions related to: a) eating and physical activity behaviors and perceptions, b) perceptions of social and community level factors, c) cultural beliefs about diet and body image, and d) intergenerational relationships. Data were analyzed using four-phases of thematic analysis and the constant comparison approach. RESULTS: Daughters and mothers had similar ideas of the definition of healthy food and the importance of eating healthy, but mothers were more likely to report eating healthy because of their age, adverse health experiences, and a desire to live longer. Daughters and mothers engaged in physical activity for reasons related to weight maintenance and feeling better, but mothers reported being more likely to start exercising as a result of a health concern. Daughters and mothers had comparable views of what makes a person healthy. Daughters and mothers relied on each other for food purchasing and food preparation. CONCLUSION: Daughters and mothers shared some similar perceptions of diet, physical activity, and health that were rooted in their daily life in Soweto. However, mothers generally reported being more likely to exhibit healthy eating and physical activity behaviors despite being obese. The mothers may have adopted these perceptions and behaviors later in life linked to ageing and ill-health. It is possible that through exposure, their daughters have assimilated these perceptions earlier in childhood or adolescence. It is important to focus health promotion efforts around preventing the otherwise expected increase of obesity among the young adult generation.

Prenatal famine exposure and adult mortality from cancer, cardiovascular disease, and other causes through age 63 years.

Nutritional conditions in early life may affect adult health, but prior studies of mortality have been limited to small samples. We evaluated the relationship between pre-/perinatal famine exposure during the Dutch Hunger Winter of 1944-1945 and mortality through age 63 years among 41,096 men born in 1944-1947 and examined at age 18 years for universal military service in the Netherlands. Of these men, 22,952 had been born around the time of the Dutch famine in 6 affected cities; the remainder served as unexposed controls. Cox proportional hazards models were used to estimate hazard ratios for death from cancer, heart disease, other natural causes, and external causes. After 1,853,023 person-years of follow-up, we recorded 1,938 deaths from cancer, 1,040 from heart disease, 1,418 from other natural causes, and 523 from external causes. We found no increase in mortality from cancer or cardiovascular disease after prenatal famine exposure. However, there were increases in mortality from other natural causes (hazard ratio = 1.24, 95% confidence interval: 1.03, 1.49) and external causes (hazard ratio = 1.46, 95% confidence interval: 1.09, 1.97) after famine exposure in the first trimester of gestation. Further follow-up of the cohort is needed to provide more accurate risk estimates of mortality from specific causes of death after nutritional disturbances during gestation and very early life.

Consumption of less than 10% of total energy from added sugars is associated with increasing HDL in females during adolescence: a longitudinal analysis.

BACKGROUND: Atherosclerotic changes associated with dyslipidemia and increased cardiovascular disease risk are believed to begin in childhood. While previous studies have linked added sugars consumption to low high-density lipoprotein (HDL), little is known about the long-term impact of this consumption. This study aims to assess the association between added sugars intake and HDL cholesterol levels during adolescence, and whether this association is modified by obesity. METHODS AND RESULTS: We used data from the National Heart Lung and Blood Institute's Growth and Health Study, a 10-year cohort study of non-Hispanic Caucasian and African-American girls (N=2379) aged 9 and 10 years at baseline recruited from 3 sites in 1987-1988 with biennial plasma lipid measurement and annual assessment of diet using a 3-day food record. Added sugars consumption was dichotomized into low (0% to <10% of total energy) and high (≥10% of total energy). In a mixed model controlling for obesity, race, physical activity, smoking, maturation stage, age, and nutritional factors, low compared with high added sugar consumption was associated with a 0.26 mg/dL greater annual increase in HDL levels (95% CI 0.48 to 0.04; P=0.02). Over the 10-year study period, the model predicted a mean increase of 2.2 mg/dL (95% CI 0.09 to 4.32; P=0.04) among low consumers, and a 0.4 mg/dL decrease (95% CI -1.32 to 0.52; P=0.4) among high consumers. Weight category did not modify this association (P=0.45). CONCLUSION: Low added sugars consumption is associated with increasing HDL cholesterol levels throughout adolescence.

Infant feeding and school attainment in five cohorts from low- and middle-income countries.

BACKGROUND: Performance in intelligence tests tends to be higher among individuals breastfed as infants, but little is known about the association between breastfeeding and achieved schooling. We assessed the association of infant feeding with school achievement in five cohorts from low- and middle-income countries. Unlike high-income country settings where most previous studies come from, breastfeeding is not positively associated with socioeconomic position in our cohorts, thus reducing the likelihood of a spurious positive association. METHODOLOGY AND PRINCIPAL FINDINGS: Participants included 10,082 young adults from five birth cohorts (Brazil, India, Guatemala, the Philippines, and South Africa). The exposures variables were whether the subject was ever breastfed, total duration of breastfeeding, and age at introduction of complementary foods. We adjusted the estimates for age at follow up, sex, maternal age, smoking during pregnancy, birthweight and socioeconomic position at birth. The key outcome was the highest grade achieved at school. In unadjusted analyses, the association between ever breastfeeding and schooling was positive in Brazil, inverse in the Philippines, and null in South Africa; in adjusted analyses, these associations were attenuated. In Brazil, schooling was highest among individuals breastfed for 3-12 months whereas in the Philippines duration of breastfeeding was inversely associated with schooling; and null associations were observed in South Africa and Guatemala. These associations were attenuated in adjusted models. Late introduction of solid foods was associated with lower schooling achievement in Brazil and South Africa. CONCLUSION: Measures of breastfeeding are not consistently related to schooling achievement in contemporary cohorts of young adults in lower and middle-income countries.

Comparing three body mass index classification systems to assess overweight and obesity in children and adolescents / Comparación de tres sistemas de clasificación de los índices de masa corporal para evaluar el sobrepeso y la obesidad en niños y adolescentes

OBJECTIVE: To compare the International Obesity Task Force (IOTF) 2005, Centers for Disease Control and Prevention (CDC) 2000, and World Health Organization (WHO) 2007 body mass index (BMI) classification systems in terms of prevalence estimation and association with demographic factors. METHODS: The 18 265 children and adolescents ages 5 to 18 years (mean = 11.2 years, standard deviation = 3.9 years) in the nationally representative Colombian National Nutrition Survey of 2005 were classified as overweight or obese according to IOTF, CDC, and WHO criteria. Prevalence estimates were compared according to each system and associations with age, sex, socioeconomic status, and population density were tested. RESULTS: Prevalence estimates of combined overweight and obesity differed by system (males: IOTF = 8.5%, CDC = 10.8%, WHO = 14.1%; females: IOTF = 14.6%, CDC = 13.8%, WHO = 17.1%; P < 0.001). The association between combined overweight and obesity and age and sex varied by system. The odds of having overweight and obesity in children (5 to 10 years) compared with adolescents (11 to 18 years) were: IOTF, odds ratio (OR) = 0.87 and 95% confidence interval (CI) = 0.77-0.98; CDC, OR = 1.27 and CI = 1.14-1.42; WHO, OR = 1.21 and CI = 1.08-1.35. The values for females compared with males were: IOTF, OR = 1.84 and CI = 1.6-2.10; CDC, OR = 1.33 and CI = 1.17-1.51; WHO, OR = 1.25 and CI = 1.12-1.41. CONCLUSIONS: There is a lack of consistency among the three main international systems in assessing overweight and obesity in children and adolescents. Appreciably different estimates of prevalence and associations with age and sex are obtained depending on which system is used. Future studies should assess how well each system reflects valid measures of body composition.

OBJETIVO: Comparar los sistemas de clasificación de los índices de masa corporal (IMC) del Grupo de Trabajo Internacional sobre la Obesidad (IOTF) de 2005, de los Centros para el Control y la Prevención de Enfermedades (CDC) de 2000, y de la Organización Mundial de la Salud (OMS) de 2007, en cuanto a la estimación de la prevalencia y la asociación con factores demográficos. MÉTODOS: Los 18 265 niños y adolescentes de ambos sexos y de edades comprendidas entre 5 y 18 años (media = 11,2 años, desviación estándar = 3,9 años) que participaron en la Encuesta Nacional de la Situación Nutricional en Colombia del 2005, representativa a escala nacional, fueron clasificados como afectados de sobrepeso u obesidad según los criterios del IOTF, los CDC y la OMS. Se compararon los cálculos de la prevalencia según cada sistema y se analizaron las asociaciones con la edad, el sexo, la situación socioeconómica y la densidad de población. RESULTADOS: Los cálculos de la prevalencia del sobrepeso y la obesidad combinados diferían según el sistema (varones: IOTF = 8,5%, CDC = 10,8%, OMS = 14,1%; mujeres: IOTF = 14,6%, CDC = 13,8%, OMS = 17,1%; P < 0,001). La asociación entre el sobrepeso y la obesidad combinados y la edad y el sexo también variaban según el sistema de clasificación. Las probabilidades de tener sobrepeso y obesidad en los niños (de 5 a 10 años) en comparación con los adolescentes (de 11 a 18 años) fueron: IOTF, razón de posibilidades (OR) = 0,87 e intervalo de confianza del 95% (IC) 0,77-0,98; CDC, OR = 1,27 e IC 1,14-1,42; OMS, OR = 1,21 e IC 1,08-1,35. Los valores observados en las mujeres en comparación con los varones fueron: IOTF, OR = 1,84 e IC 1,6-2,10; CDC, OR = 1,33 e IC 1,17-1,51; OMS, OR = 1,25 e IC 1,12-1,41. CONCLUSIONES: Existe una falta de uniformidad entre los tres principales sistemas internacionales en la evaluación del sobrepeso y la obesidad en niños y adolescentes. Se obtienen cálculos apreciablemente diferentes de la prevalencia y de las asociaciones con la edad y el sexo según el sistema que se adopte. Los estudios futuros deben evaluar hasta qué punto cada sistema refleja adecuadamente mediciones válidas de la composición corporal.

Infant-feeding patterns and cardiovascular risk factors in young adulthood: data from five cohorts in low- and middle-income countries.

BACKGROUND: Infant-feeding patterns may influence lifelong health. This study tested the hypothesis that longer duration of breastfeeding and later introduction of complementary foods in infancy are associated with reduced adult cardiovascular risk. METHODS: Data were pooled from 10 912 subjects in the age range of 15-41 years from five prospective birth-cohort studies in low-/middle-income countries (Brazil, Guatemala, India, Philippines and South Africa). Associations were examined between infant feeding (duration of breastfeeding and age at introduction of complementary foods) and adult blood pressure (BP), plasma glucose concentration and adiposity (skinfolds, waist circumference, percentage body fat and overweight/obesity). Analyses were adjusted for maternal socio-economic status, education, age, smoking, race and urban/rural residence and infant birth weight. RESULTS: There were no differences in outcomes between adults who were ever breastfed compared with those who were never breastfed. Duration of breastfeeding was not associated with adult diabetes prevalence or adiposity. There were U-shaped associations between duration of breastfeeding and systolic BP and hypertension; however, these were weak and inconsistent among the cohorts. Later introduction of complementary foods was associated with lower adult adiposity. Body mass index changed by -0.19 kg/m(2) [95% confidence interval (CI) -0.37 to -0.01] and waist circumference by -0.45 cm (95% CI -0.88 to -0.02) per 3-month increase in age at introduction of complementary foods. CONCLUSIONS: There was no evidence that longer duration of breastfeeding is protective against adult hypertension, diabetes or overweight/adiposity in these low-/middle-income populations. Further research is required to determine whether 'exclusive' breastfeeding may be protective. Delaying complementary foods until 6 months, as recommended by the World Health Organization, may reduce the risk of adult overweight/adiposity, but the effect is likely to be small.

Childhood nutrition and later fertility: pathways through education and pre-pregnant nutritional status.

Better childhood nutrition is associated with earlier physical maturation during adolescence and increased schooling attainment. However, as earlier onset of puberty and increased schooling can have opposing effects on fertility, the net effect of improvements in childhood nutrition on a woman's fertility are uncertain. Using path analysis, we estimate the strength of the pathways between childhood growth and subsequent fertility outcomes in Guatemalan women studied prospectively since birth. Height for age z score at 24 months was positively related to body mass index (BMI kg/m2) and height (cm) in adolescence and to schooling attainment. BMI was negatively associated (-0.23 +/- 0.09 years per kg/m2; p < .05) and schooling was positively associated (0.38 +/- 0.06 years per grade; p < .001) with age at first birth. Total associations with the number of children born were positive from BMI (0.07 +/- 0.02 per kg/m2; p < .05) and negative from schooling (-0.18 +/- 0.02 per grade; p < .01). Height was not related to age at first birth or the number of children born. Taken together, childhood nutrition, as reflected by height at 2 years, was positively associated with delayed age at first birth and fewer children born. If schooling is available for girls, increased growth during childhood will most likely result in a net decrease infertility.

Associations of gestational exposure to famine with energy balance and macronutrient density of the diet at age 58 years differ according to the reference population used.

Individuals exposed to the Dutch Famine of 1944-45 during gestation have increased adiposity, which might be due to changes in energy intake, physical activity, or metabolic efficiency. We studied 357 persons born between January 1945 and March 1946 whose mothers experienced famine during or immediately preceding pregnancy, 298 persons born in the same 3 institutions during 1943 or 1947 (time controls), and 311 same-sex sibling controls. We obtained food frequency and physical activity data by questionnaire between 2003 and 2005 (mean age 58 y). We defined gestational exposure as exposure to a ration of <3762 kJ/d (<900 kcal/d) for at least 10 wk. For the whole study population, energy intake was 9225 +/- 2650 kJ/d and physical activity was 7380 +/- 4331 metabolic equivalents (MET).min/wk. Compared with time controls, gestational famine exposure was associated with 113 kJ/d (95% CI, -272, 502) higher energy intake, 0.01 percentage point (95% CI, -0.88, 0.89) higher fat density, 688 MET.min/wk (95% CI, -1398, 23) lower physical activity, and 63 kJ/d (95% CI, -130, 259) higher predicted energy expenditure (pEE). Compared with sibling controls, gestational famine exposure was associated with 4 kJ/d (95% CI, -702, 711) higher energy intake, 2.01 percentage points (95% CI, 0.38, 3.63) higher fat density, 97 MET.min/wk) (95% CI, -1243, 1050) lower physical activity score, and 188 kJ/d (95% CI, -163, 539) higher pEE. Gender-specific associations (P < 0.05 for heterogeneity) emerged for protein density and pEE using time controls and for energy intake using sibling controls. Associations were weak, differed by choice of control, and may reflect sampling variability or methodological differences. Persistent small energy imbalances could explain the increased weight of famine-exposed individuals.

A fingerprint marker from early gestation associated with diabetes in middle age: the Dutch Hunger Winter Families Study.

BACKGROUND: Fetal programming of diabetes might originate in early pregnancy when fingerprints are permanently established. The mean dermatoglyphic ridge count difference between fingertips 1 and 5 ('Md15') varies with the early prenatal environment. We hypothesized that Md15 would be associated with adult-onset diabetes. METHODS: We obtained Md15 from 577 Dutch adults (aged 58.9 years, SD 1.1) whose births in 1943-47 were documented in maternity records and from 260 of their same-sex siblings for whom birth weights were not available. Of these 837 participants, complete anthropometry and diabetes status (from history or glucose tolerance test) were obtained for 819. RESULTS: After adjustment for age, sex, parental diabetes and adult anthropometry, fingerprint Md15 was associated with prevalent diabetes [odds ratio (OR) = 1.37 per 1 SD (95% confidence interval 1.02-1.84)]. This relationship held [OR = 1.40 (1.03-1.92)] for diabetic cases restricted to those recently diagnosed (within 7 years). In the birth series restricted to recently diagnosed cases, the mutually adjusted ORs were 1.34 (1.00-1.79) per SD of Md15 and 0.83 (0.62-1.10) per SD of birth weight. Further adjustments for maternal smoking, conception season or prenatal famine exposure in 1944-45 did not alter these estimates. Among 42 sibling pairs discordant for diabetes, the diabetic sibling had higher Md15 by 3.5 (0.6-6.3) after multivariable adjustment. CONCLUSIONS: Diabetes diagnosed at age 50+ years was associated with a fingerprint marker established in early gestation, irrespective of birth weight. Fingerprints may provide a useful tool to investigate prenatal developmental plasticity.

Tumor growth rates derived from data for patients in a clinical trial correlate strongly with patient survival: a novel strategy for evaluation of clinical trial data.

PURPOSE: The slow progress in developing new cancer therapies can be attributed in part to the long time spent in clinical development. To hasten development, new paradigms especially applicable to patients with metastatic disease are needed. PATIENTS AND METHODS: We present a new method to predict survival using tumor measurement data gathered while a patient with cancer is receiving therapy in a clinical trial. We developed a two-phase equation to estimate the concomitant rates of tumor regression (regression rate constant d) and tumor growth (growth rate constant g). RESULTS: We evaluated the model against serial levels of prostate-specific antigen (PSA) in 112 patients undergoing treatment for prostate cancer. Survival was strongly correlated with the log of the growth rate constant, log(g) (Pearson r = -0.72) but not with the log of the regression rate constants, log(d) (r = -0.218). Values of log(g) exhibited a bimodal distribution. Patients with log(g) values above the median had a mortality hazard of 5.14 (95% confidence interval, 3.10-8.52) when compared with those with log(g) values below the median. Mathematically, the minimum PSA value (nadir) and the time to this minimum are determined by the kinetic parameters d and g, and can be viewed as surrogates. CONCLUSIONS: This mathematical model has applications to many tumor types and may aid in evaluating patient outcomes. Modeling tumor progression using data gathered while patients are on study, may help evaluate the ability of therapies to prolong survival and assist in drug development.

A simple index to measure hygiene behaviours.

BACKGROUND: Spot checks are becoming a popular method to assess hygiene behaviours; however, little is known about their repeatability or predictability. We evaluated the within-household repeatability of hygiene indices created from spot checks and their ability to predict incidence of diarrhoea in young Guatemalan children. METHODS: We observed hygiene behaviours in 588 households in four rural Guatemalan communities over 36 months. Four indices related to drinking water (DWI; score = 0-3), food (FI; score = 0-3), personal hygiene (PHI; score = 0-3), and domestic household hygiene (DHI; score = 0-6) and one summary hygiene index (SHI; range 0-15) were created. Morbidity of 694 children aged birth to 36 months living in the study households was assessed using biweekly recall. Intraclass correlation coefficients were calculated to assess within-household repeatability; the generalized estimating equations approach was employed to analyse diarrhoea morbidity. RESULTS: Households were observed a mean of 22.1 +/- 11.2 times. All indices decreased with duration of follow-up (SHI = -0.67 +/- 0.05 points/year; WI = -0.04 +/- 0.01; FI = -0.07 +/- 0.01; PHI = -0.21 +/- 0.01; DHI = -0.37 +/- 0.02; all P < 0.05). Intraclass correlations were low to moderate (SHI = 0.35-0.51; DWI = 0.17-0.21; FI = 0.16-0.18; PHI = 0.27-0.32; DHI = 0.27-0.38). Six separate spot checks would be needed to estimate a household's underlying level of hygiene within 20%. SHI and PHI scores were inversely associated with diarrhoea morbidity (both P < 0.05). CONCLUSIONS: Hygiene indices created using spot checks can be a rapid and efficient method for assessing hygiene and useful for predicting diarrhoea morbidity in young children. Multiple measures are required to accurately estimate the true hygiene pattern of a household.