Wei Perng

A prospective study of maternal prenatal weight and offspring cardiometabolic health in midchildhood

PURPOSE To examine the relations of maternal prepregnancy body mass index (ppBMI) and gestational weight gain (GWG) with offspring cardiometabolic health. DESIGN We studied 1090 mother-child pairs in Project Viva, a Boston-area prebirth cohort. We measured overall (dual x-ray absorptiometry total fat; body mass index z-score) and central adiposity (dual x-ray absorptiometry trunk fat), and systolic blood pressure in offspring at 6 to 10 years. Fasting bloods (n = 687) were assayed for insulin and glucose (for calculation of homeostatic model assessment of insulin resistance), triglycerides, leptin, adiponectin, high sensitivity C-reactive protein, and interleukin 6. Using multivariable linear regression, we examined differences in offspring outcomes per 1 SD maternal ppBMI and GWG. RESULTS After adjustment for confounders, each 5 kg/m² higher ppBMI corresponded with 0.92 kg (95% confidence interval, 0.70-1.14) higher total fat, 0.27 BMI z-score (0.21-0.32), and 0.39 kg (0.29-0.49) trunk fat. ppBMI was also positively associated with homeostatic model assessment of insulin resistance, leptin, high sensitivity C-reactive protein, interleukin 6, and systolic blood pressure; and lower adiponectin. Each 5 kg of GWG predicted greater adiposity (0.33 kg [0.11-0.54] total fat; 0.14 kg [0.04-0.23] trunk fat) and higher leptin (6% [0%-13%]) in offspring after accounting for confounders and ppBMI. CONCLUSIONS Children born to heavier mothers have more overall and central fat and greater cardiometabolic risk. Offspring of women with higher GWG had greater adiposity and higher leptin.

Metabolomic profiles and childhood obesity

To identify metabolite patterns associated with childhood obesity, to examine relations of these patterns with measures of adiposity and cardiometabolic risk, and to evaluate associations with maternal peripartum characteristics.

Adherence to a snacking dietary pattern and soda intake are related to the development of adiposity: a prospective study in school-age children.

OBJECTIVE Snacking has been related to increased prevalence of overweight among school-age children in cross-sectional studies. It is uncertain, however, whether snacking influences the development of adiposity over time. DESIGN We examined whether adherence to a snacking dietary pattern was associated with greater increases in childrens BMI, subscapular:triceps skinfold thickness ratio and waist circumference over a median 2·5-year follow-up. Dietary patterns were identified through principal component analysis of an FFQ administered at recruitment in 2006. Anthropometric follow-up was conducted annually. Linear mixed-effects models were used to estimate rates of change in each indicator according to quartiles of adherence to the snacking pattern. We also examined change in BMI, subscapular:triceps skinfold thickness ratio and waist circumference in relation to intake of the food items in the snacking pattern. SUBJECTS Children (n 961) 5-12 years of age. SETTING Public schools in Bogotá, Colombia. RESULTS After adjustment for age, sex, total energy intake and socio-economic status, children in the highest quartile of adherence to the snacking pattern had a 0·09 kg/m2 per year higher BMI gain than children in the lowest quartile (P trend = 0·05). A similar association was observed for mean change in subscapular:triceps skinfold thickness ratio (highest v. lowest quartile difference = 0·012/year; P = 0·03). Of the food items in the snacking pattern, soda intake was positively and significantly associated with change in BMI (P trend = 0·01) and waist circumference (P trend = 0·04) in multivariable analysis. CONCLUSIONS Our results indicate that snacking and soda intake are associated with development of adiposity in school-age children.

Micronutrient status and global DNA methylation in school-age children.

Aberrations in global LINE-1 DNA methylation have been related to risk of cancer and cardiovascular disease. Micronutrients including methyl-donors and retinoids are involved in DNA methylation pathways. We investigated associations of micronutrient status and LINE-1 methylation in a cross-sectional study of school-age children from Bogotá, Colombia. Methylation of LINE-1 repetitive elements was quantified in 568 children 5–12 years of age using pyrosequencing technology. We examined the association of LINE-1 methylation with erythrocyte folate, plasma vitamin B12, vitamin A ferritin (an indicator of iron status) and serum zinc concentrations using multivariable linear regression. We also considered associations of LINE-1 methylation with socio-demographic and anthropometric characteristics. Mean (± SD) LINE-1 methylation was 80.25 (± 0.65) percentage of 5-mC (%5-mC). LINE-1 methylation was inversely related to plasma vitamin A. After adjustment for potential confounders, children with retinol levels higher than or equal to 1.05 µmol/L showed 0.19% 5-mC lower LINE-1 methylation than children with retinol levels lower than 0.70 µmol/L. LINE-1 methylation was also inversely associated with C-reactive protein, a marker of chronic inflammation, and female sex. We identified positive associations of maternal body mass index and socioeconomic status with LINE-1 methylation. These associations were not significantly different by sex. Whether modification of these exposures during school-age years leads to changes in global DNA methylation warrants further investigation.

Early Weight Gain, Linear Growth, and Mid-Childhood Blood Pressure A Prospective Study in Project Viva

In recent years, the prevalence of hypertension and prehypertension increased markedly among children and adolescents, highlighting the importance of identifying determinants of elevated blood pressure early in life. Low birth weight and rapid early childhood weight gain are associated with higher future blood pressure. However, few studies have examined the timing of postnatal weight gain in relation to later blood pressure, and little is known regarding the contribution of linear growth. We studied 957 participants in Project Viva, an ongoing US prebirth cohort. We examined the relations of gains in body mass index z-score and length/height z-score during 4 early life age intervals (birth to 6 months, 6 months to 1 year, 1 to 2 years, and 2 to 3 years) with blood pressure during mid-childhood (6–10 years) and evaluated whether these relations differed by birth size. After accounting for confounders, each additional z-score gain in body mass index during birth to 6 months and 2 to 3 years was associated with 0.81 (0.15, 1.46) and 1.61 (0.33, 2.89) mm Hg higher systolic blood pressure, respectively. Length/height gain was unrelated to mid-childhood blood pressure, and there was no evidence of effect modification by birth size for body mass index or length/height z-score gain. Our findings suggest that more rapid gain in body mass index during the first 6 postnatal months and in the preschool years may lead to higher systolic blood pressure in mid-childhood, regardless of size at birth. Strategies to reduce accrual of excess adiposity during early life may reduce mid-childhood blood pressure, which may also impact adult blood pressure and cardiovascular health.

A Prospective Study of LINE-1DNA Methylation and Development of Adiposity in School-Age Children

Background Repetitive element DNA methylation is related to prominent obesity-related chronic diseases including cancer and cardiovascular disease; yet, little is known of its relation with weight status. We examined associations of LINE-1 DNA methylation with changes in adiposity and linear growth in a longitudinal study of school-age children from Bogotá, Colombia. Methods We quantified methylation of LINE-1 elements from peripheral leukocytes of 553 children aged 5–12 years at baseline using pyrosequencing technology. Anthropometric characteristics were measured periodically for a median of 30 months. We estimated mean change in three age-and sex-standardized indicators of adiposity: body mass index (BMI)-for-age Z-score, waist circumference Z-score, and subscapular-to-triceps skinfold thickness ratio Z-score according to quartiles of LINE-1 methylation using mixed effects regression models. We also examined associations with height-for-age Z-score. Results There were non-linear, inverse relations of LINE-1 methylation with BMI-for-age Z-score and the skinfold thickness ratio Z-score. After adjustment for baseline age and socioeconomic status, boys in the lowest quartile of LINE-1 methylation experienced annual gains in BMI-for-age Z-score and skinfold thickness ratio Z-score that were 0.06 Z/year (P = 0.04) and 0.07 Z/year (P = 0.03), respectively, higher than those in the upper three quartiles. The relation of LINE-1 methylation and annual change in waist circumference followed a decreasing monotonic trend across the four quartiles (P trend = 0.02). DNA methylation was not related to any of the adiposity indicators in girls. There were no associations between LINE-1 methylation and linear growth in either sex. Conclusions Lower LINE-1 DNA methylation is related to development of adiposity in boys.

Preterm birth and long-term maternal cardiovascular health.

PURPOSE To investigate whether preterm birth (PTB) is associated with greater cardiovascular disease (CVD) risk in a longitudinal cohort. METHODS We examined differences in systolic blood pressure (SBP), diastolic blood pressure, insulin resistance (Homeostatic model assessment of insulin resistance), total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein, triglycerides, C-reactive protein, and interleukin 6 at 3 years postpartum between women who delivered preterm (gestation <37 weeks; n = 54) versus term (≥37 weeks; n = 751) using multivariable linear regression. We also assessed relations with body mass index, weight change from prepregnancy, and waist circumference at 3 and 7 years postpartum. RESULTS Median age at enrollment was 33.9 years (range: 16.4-44.9). After adjusting for age, race, prepregnancy body mass index, parity, marital status, education, and SBP during early pregnancy, women with PTB had 3.99 mm Hg (95% confidence interval, 0.82-7.16) higher SBP and 7.01 mg/dL (1.54-12.50) lower HDL than those who delivered at term. The association with SBP was attenuated after accounting for hypertension before or during pregnancy (2.78 mm Hg [-0.30 to 5.87]). PTB was not related to other postpartum outcomes. CONCLUSIONS PTB is related to greater CVD risk by 3 years postpartum as indicated by higher SBP and lower HDL. Although these associations may be due to preexisting conditions exacerbated during pregnancy, PTB may flag high-risk women for more vigilant CVD monitoring and lifestyle interventions.

Maternal inflammation during pregnancy and childhood adiposity

Maternal pre‐pregnancy obesity is associated with offspring obesity. Underlying mechanisms may involve a maternal obesity‐mediated proinflammatory state during pregnancy. Maternal C‐reactive protein (CRP) level during pregnancy is a biomarker of low‐grade systemic inflammation.

Metabolomics in the developmental origins of obesity and its cardiometabolic consequences.

In this review, we discuss the potential role of metabolomics to enhance understanding of obesity-related developmental origins of health and disease (DOHaD). We first provide an overview of common techniques and analytical approaches to help interested investigators dive into this relatively novel field. Next, we describe how metabolomics may capture exposures that are notoriously difficult to quantify, and help to further refine phenotypes associated with excess adiposity and related metabolic sequelae over the life course. Together, these data can ultimately help to elucidate mechanisms that underlie fetal metabolic programming. Finally, we review current gaps in knowledge and identify areas where the field of metabolomics is likely to provide insights into mechanisms linked to DOHaD in human populations.

Promoters of and barriers to cervical cancer screening in a rural setting in Tanzania

To investigate promoters and barriers for cervical cancer screening in rural Tanzania.