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1.
Child Obes ; 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31618046

RESUMO

Background: Previous studies show inconsistent relations between child care and obesity, but few assessed longitudinal associations during infancy and even fewer included racially diverse children. We examined associations of time infants spent in child care, both overall and in different types of care, with weight status at 6 and 12 months. Methods: We examined 664 infants living in central North Carolina. We conducted adjusted multivariable linear regressions examining (1) child care from birth to 6 months and 6-month weight-for-length (WFL) z-score, and (2) child care from birth to 12 months and 12-month WFL z-score. We assessed any child care and child care by type, including relative care, informal care by a nonrelative, formal child care, and a combination of care (e.g., relative and informal care). Results: Nearly 70% of infants were black and 49% were female. After adjustment for potential confounders, any child care was not associated with WFL z-score at 6 months (0.07; 95% confidence intervals [CI] -0.02 to 0.16; p = 0.13) or 12 months (0.05; 95% CI -0.02 to 0.12; p = 0.19). However, greater combination care was associated with higher WFL z-score at 6 months (0.68; 95% CI 0.23-1.13; p = 0.003) and greater care by a relative was associated with higher WFL z-score at 12 months (0.16; 95% CI 0.05-0.26; p = 0.005). Conclusions: Although we did not observe associations with any child care, combination care and relative care during infancy were associated with higher weight. Interventions aimed at preventing excessive weight gain in early life may target relatives who provide regular care for infants.

2.
Epigenomics ; 11(13): 1487-1500, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31536415

RESUMO

Aim: Cigarette smoking influences DNA methylation genome wide, in newborns from pregnancy exposure and in adults from personal smoking. Whether a unique methylation signature exists for in utero exposure in newborns is unknown. Materials & methods: We separately meta-analyzed newborn blood DNA methylation (assessed using Illumina450k Beadchip), in relation to sustained maternal smoking during pregnancy (9 cohorts, 5648 newborns, 897 exposed) and adult blood methylation and personal smoking (16 cohorts, 15907 participants, 2433 current smokers). Results & conclusion: Comparing meta-analyses, we identified numerous signatures specific to newborns along with many shared between newborns and adults. Unique smoking-associated genes in newborns were enriched in xenobiotic metabolism pathways. Our findings may provide insights into specific health impacts of prenatal exposure on offspring.

3.
BMJ Open ; 9(9): e030186, 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31494614

RESUMO

OBJECTIVES: To assess associations between maternal prenatal diet quality and infant adiposity. DESIGN: The design was a prospective birth cohort. SETTING: We used data from the Nurture study, a cohort of women and their infants residing in the southeastern USA. PARTICIPANTS AND EXPOSURE ASSESSMENT: Between 2013 and 2015, we enrolled 860 women between 20 and 36 weeks' gestation. After reconsenting at delivery and excluding women with implausible calorie intakes, we measured dietary intake using the Block food frequency questionnaire, and assessed diet quality using a modified Alternate Healthy Eating Index 2010 (AHEI-2010), which assessed intake of 10 food categories, including fruits, vegetables, whole grains, nuts/legumes, fats, meats, beverages and sodium (excluding alcohol). OUTCOMES: We assessed birth weight for gestational age z-score, small and large for gestational age, low birth weight and macrosomia. Outcomes at 6 and 12 months were weight-for-length z-score, sum of subscapular and triceps skinfold thickness (SS+TR) and subscapular-to-triceps skinfold ratio (SS:TR). RESULTS: Among mothers, 70.2% were black and 20.9% were white; less than half (45.2%) reported having a high school diploma or less. Among infants, 8.7% were low birth weight and 8.6% were small for gestational age. Unadjusted estimates showed that a higher AHEI-2010 score, was associated with a higher birth weight for gestational z-score (ß=0.01; 95% CI 0.002 to 0.02; p=0.02) and a greater likelihood of macrosomia (OR=1.04; 95% CI 1.004 to 1.09; p=0.03). After adjustment, maternal diet quality was not associated with infant adiposity at birth, 6 or 12 months. CONCLUSIONS: Although poor maternal diet quality during pregnancy was not associated with infant adiposity in our study, maternal diet during pregnancy may still be an important and modifiable factor of public health importance.

4.
BMC Public Health ; 19(1): 1062, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31391077

RESUMO

BACKGROUND: Approximately 17% of children in the U.S. are obese. Children that are overweight or obese are also more likely to be obese as adults and suffer from various chronic diseases and premature death. Maternal obesity can affect the weight status of her offspring through intrauterine mechanisms like excessive gestational weight gain (GWG). Current literature shows a positive association between maternal weight status and GWG on child obesity, yet the direct and indirect effects have not been decomposed or quantified. The purpose of this study was to estimate the effect of maternal obesity on child obesity, mediated by GWG, which is a modifiable risk factor. METHODS: The study participants were a birth cohort of offspring from women who received prenatal care in the Duke/Durham Regional health care system in Durham, NC between 2005 and 2009. Anthropomorphic data was collected via electronic medical records (EMRs) during each voluntary visit to a health care facility. The exposure of interest was maternal obesity, measured by pre-pregnancy body mass index, the mediator was GWG, dichotomized into excessive and not excessive based on maternal prenatal BMI, and the outcome was child obesity at age 4, measured as BMI z-scores from the last recorded height and weight. A counterfactual theory-based product method analysis estimated the mediated effects of GWG, adjusted for maternal race, socioeconomic status, and smoking status. RESULTS: Of the 766 children, 25% were overweight or obese, and among all mothers, 25 and 31% were overweight and obese, respectively. Maternal BMI was associated with an overall increase of 0.04 in offspring z-score. The proportion of the effect of maternal obesity on child age 4 obesity mediated by GWG was 8.1%. CONCLUSION: GWG, in part, mediated the relationship between maternal BMI and childhood adiposity. Even when the mediator is fixed, children are at an increased risk of a higher BMI if the mother is obese. These findings highlight an important public health education opportunity to stress the impact of a pre-pregnancy weight and excessive GWG on the risk of child obesity for all mothers.


Assuntos
Ganho de Peso na Gestação , Mães/estatística & dados numéricos , Obesidade/epidemiologia , Obesidade Pediátrica/epidemiologia , Adulto , Pré-Escolar , Feminino , Humanos , Masculino , Gravidez , Fatores de Risco
5.
Appetite ; 142: 104369, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31302102

RESUMO

Understanding the relationship between snacking and dietary intake in early life years is one key but understudied area. In this study, we examined snacking patterns in toddlers and preschool children and the associations between snacking frequency and daily energy intake. We analyzed data from children aged 12-72 months (N = 1186) in the Newborn Epigenetic STudy (NEST). We used Bonferroni multiple comparison methods to examine the differences in snacking patterns across subgroups. Linear and quantile regression models were fit to investigate the association between dietary intake and snacking frequency. Our estimates suggest that Non-Hispanic blacks had the highest total daily energy intake from snacks (334 kcal/day) compared to non-Hispanic whites (270 kcal/day) and Hispanics (274 kcal/day) in 12-to-24-month-olds. In 2-to-6-year-olds, mean energy intake from snacks was 296 kcal/day without a significant racial/ethnic difference. Carbohydrate, fat and protein from snacks contributed about 17%, 9% and 4% respectively of the total energy intake in 12-to-24-month-olds while they contributed about 15%, 7% and 2% respectively of the total energy intake in the other age group. Snacking frequency was positively and significantly associated with total daily energy intake in both 12-to-24-month-olds and 2-to-6-year-olds as indicated by regression coefficient estimates of snacking frequency (ß = 31.3 kcal/day with P = 0.027 and ß = 175.4 kcal/day with P < 0.0001, respectively, indicating a higher snacking frequency was associated with a greater total daily energy intake). In conclusion, snacking frequency was positively associated with daily energy intake. Carbohydrates and fats from snacks are significant energy contributors. Age differentiation was apparent regarding the relationship between snacking frequency and dietary intake. Differentiated interventions that are age-specific and focus on the dietary quality of snacks instead of quantity are needed.

6.
Ann Clin Microbiol Antimicrob ; 18(1): 18, 2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31226994

RESUMO

BACKGROUND: Prenatal antibiotic exposure has been associated with an altered infant gut microbiome composition and higher risk of childhood obesity, but no studies have examined if prenatal antibiotics simultaneously alter the gut microbiome and adiposity in infants. METHOD: In this prospective study (Nurture: recruitment 2013-2015 in North Carolina, United States), we examined in 454 infants the association of prenatal antibiotic exposure (by any prenatal antibiotic exposure; by trimester of pregnancy; by number of courses; by type of antibiotics) with infant age- and sex-specific weight-for-length z score (WFL-z) and skinfold thicknesses (subscapular, triceps, abdominal) at 12 months of age. In a subsample, we also examined whether prenatal antibiotic exposure was associated with alterations in the infant gut microbiome at ages 3 and 12 months. RESULTS: Compared to infants not exposed to prenatal antibiotics, infants who were exposed to any prenatal antibiotics had 0.21 (95% confidence interval [CI] 0.02, 0.41) higher WFL-z at 12 months, and 0.28 (95% CI 0.02, 0.55) higher WFL-z if they were exposed to antibiotics in the second trimester, after adjustment for potential confounders, birth weight, and gestational age. We also observed a dose-dependent association (P-value for trend = 0.006) with infants exposed to ≥ 3 courses having 0.41 (95% CI 0.13, 0.68) higher WFL-z at 12 months. After further adjustment for delivery method, only second-trimester antibiotic exposure remained associated with higher infant WFL-z (0.27, 95% CI 0.003, 0.54) and subscapular skinfold thickness (0.49 mm, 95% CI 0.11, 0.88) at 12 months. Infants exposed to second-trimester antibiotics versus not had differential abundance of 13 bacterial amplicon sequence variants (ASVs) at age 3 months and 17 ASVs at 12 months (false discovery rate adjusted P-value < 0.05). CONCLUSIONS: Prenatal antibiotic exposure in the second trimester was associated with an altered infant gut microbiome composition at 3 and 12 months and with higher infant WFL-z and subscapular skinfold thickness at 12 months.

7.
Clin Epigenetics ; 11(1): 87, 2019 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-31182156

RESUMO

BACKGROUND: Numerous studies have demonstrated that DNA methylation levels in the aryl hydrocarbon receptor repressor (AHRR) gene measured in cord blood are significantly associated with prenatal tobacco smoke exposure and can be used as a fetal exposure biomarker. The mechanism driving this demethylation has not been determined and it is unclear if all cord blood cell types are impacted. Nucleated red blood cells (nRBCs/CD235a+ cells) are developmentally immature RBCs that display genome-wide hypomethylation and are observed at increased frequency in the cord blood of smoking mothers. We tested if AHRR methylation levels in CD235a+ nRBCs or nRBC counts influenced AHRR methylation in whole cord blood. METHODS: Cord blood was collected from smoking (n = 34) and nonsmoking (n = 19) mothers and DNA was prepared from whole cord blood, isolated CD235a+ nRBCs, and CD14+ monocytes. AHRR methylation in cord blood DNA was measured using Illumina 850K arrays (cg05575921, chr5:373378). Pyrosequencing was used to compare methylation levels among cord blood, CD235a+, and CD14+ cells. We measured nRBC percentages using conventional complete blood counts and estimated percent nRBCs by a deconvolution model. RESULTS: Methylation levels in AHRR were significantly lower in nRBCs relative to whole cord blood and CD14+ monocytes. While AHRR methylation levels in the cell types were significantly correlated across all subjects, methylation values at the chr5:373378 CpG averaged 14.6% lower in nRBCs (range 0.4 to 24.8%; p = 3.8E-13) relative to CD14+, with nonsmokers showing a significantly greater hypomethylation (- 4.1%, p = 1.8E-02). Methylation level at the AHRR chr5:373378 CpG was strongly associated with self-reported smoking in both CD14+ monocytes (t test p = 5.7E-09) and nRBCs (p = 4.8E-08), as well as cotinine levels (regression p = 1.1E-07 and p = 3.6E-04, respectively). For subjects with whole blood 850K data, robust linear regression models adjusting for estimated cell type composition, either including nRBCs counts or estimates, modestly increased the association between smoking and cg05575921 methylation. CONCLUSIONS: Prenatal smoke exposure was highly significantly associated with AHRR methylation in cord blood, CD14+ monocytes, and CD235a+ nRBCs. AHRR methylation levels in nRBCs and nRBC counts had minimal effect on cord blood methylation measurements. However, regression models using estimated nRBCs or actual nRBC counts outperformed those lacking these covariates.

8.
Environ Health Perspect ; 127(4): 47009, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31039056

RESUMO

BACKGROUND: Maternal tobacco smoke exposure has been associated with altered DNA methylation. However, previous studies largely used methylation arrays, which cover a small fraction of CpGs, and focused on whole cord blood. OBJECTIVES: The current study examined the impact of in utero exposure to maternal tobacco smoke on the cord blood [Formula: see text] DNA methylome. METHODS: The methylomes of 20 Hispanic white newborns ([Formula: see text] exposed to any maternal tobacco smoke in pregnancy; [Formula: see text] unexposed) from the Maternal and Child Health Study (MACHS) were profiled by whole-genome bisulfite sequencing (median coverage: [Formula: see text]). Statistical analyses were conducted using the Regression Analysis of Differential Methylation (RADMeth) program because it performs well on low-coverage data (minimizes false positives and negatives). RESULTS: We found that 10,381 CpGs were differentially methylated by tobacco smoke exposure [neighbor-adjusted p-values that are additionally corrected for multiple testing based on the Benjamini-Hochberg method for controlling the false discovery rate (FDR) [Formula: see text]]. From these CpGs, RADMeth identified 557 differentially methylated regions (DMRs) that were overrepresented ([Formula: see text]) in important regulatory regions, including enhancers. Of nine DMRs that could be queried in a reduced representation bisulfite sequencing (RRBS) study of adult [Formula: see text] cells ([Formula: see text] smokers; [Formula: see text] nonsmokers), four replicated ([Formula: see text]). Additionally, a CpG in the promoter of SLC7A8 (percent methylation difference: [Formula: see text] comparing exposed to unexposed) replicated ([Formula: see text]) in an EPIC (Illumina) array study of cord blood [Formula: see text] cells ([Formula: see text] exposed to sustained maternal tobacco smoke; [Formula: see text] unexposed) and in a study of adult [Formula: see text] cells across two platforms (EPIC: [Formula: see text] smokers; [Formula: see text] nonsmokers; 450K: [Formula: see text] smokers; [Formula: see text] nonsmokers). CONCLUSIONS: Maternal tobacco smoke exposure in pregnancy is associated with cord blood [Formula: see text] DNA methylation in key regulatory regions, including enhancers. While we used a method that performs well on low-coverage data, we cannot exclude the possibility that some results may be false positives. However, we identified a differentially methylated CpG in amino acid transporter SLC7A8 that is highly reproducible, which may be sensitive to cigarette smoke in both cord blood and adult [Formula: see text] cells. https://doi.org/10.1289/EHP3398.

9.
JPEN J Parenter Enteral Nutr ; 43(5): 627-637, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30997688

RESUMO

The goal of the 2018 American Society for Parenteral and Enteral Nutrition (ASPEN) Research Workshop was to explore the influence of nutrition and dietary exposure to xenobiotics on the epigenome during critical periods in development and how these exposures influence both disease incidence and severity transgenerationally. A growing compendium of research indicates that the incidence and severity of common and costly human diseases may be influenced by dietary exposures and deficiencies that modify the epigenome. The greatest periods of vulnerability to these exposures are the periconception period and early childhood. Xenobiotics in the food chain, protein malnutrition, and methyl donor deficiencies could have a profound bearing on the risk of developing heart disease, diabetes, obesity, hypertension, and mental illness over multiple generations. The financial impact and the life burden of these diseases are enormous. These and other aspects of nutrition, epigenetics, and health are explored in this research workshop.

10.
Cancer Med ; 8(5): 2503-2513, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31001917

RESUMO

An association between genetic variants in the vitamin D receptor (VDR) gene and epithelial ovarian cancer (EOC) was previously reported in women of African ancestry (AA). We sought to examine associations between genetic variants in VDR and additional genes from vitamin D biosynthesis and pathway targets (EGFR, UGT1A, UGT2A1/2, UGT2B, CYP3A4/5, CYP2R1, CYP27B1, CYP24A1, CYP11A1, and GC). Genotyping was performed using the custom-designed 533,631 SNP Illumina OncoArray with imputation to the 1,000 Genomes Phase 3 v5 reference set in 755 EOC cases, including 537 high-grade serous (HGSOC), and 1,235 controls. All subjects are of African ancestry (AA). Logistic regression was performed to estimate odds ratios (OR) and 95% confidence intervals (CI). We further evaluated statistical significance of selected SNPs using the Bayesian False Discovery Probability (BFDP). A significant association with EOC was identified in the UGT2A1/2 region for the SNP rs10017134 (per allele OR = 1.4, 95% CI = 1.2-1.7, P = 1.2 × 10-6 , BFDP = 0.02); and an association with HGSOC was identified in the EGFR region for the SNP rs114972508 (per allele OR = 2.3, 95% CI = 1.6-3.4, P = 1.6 × 10-5 , BFDP = 0.29) and in the UGT2A1/2 region again for rs1017134 (per allele OR = 1.4, 95% CI = 1.2-1.7, P = 2.3 × 10-5 , BFDP = 0.23). Genetic variants in the EGFR and UGT2A1/2 may increase susceptibility of EOC in AA women. Future studies to validate these findings are warranted. Alterations in EGFR and UGT2A1/2 could perturb enzyme efficacy, proliferation in ovaries, impact and mark susceptibility to EOC.

11.
Nat Commun ; 10(1): 1893, 2019 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-31015461

RESUMO

Birthweight is associated with health outcomes across the life course, DNA methylation may be an underlying mechanism. In this meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, we find that DNA methylation in neonatal blood is associated with birthweight at 914 sites, with a difference in birthweight ranging from -183 to 178 grams per 10% increase in methylation (PBonferroni < 1.06 x 10-7). In additional analyses in 7,278 participants, <1.3% of birthweight-associated differential methylation is also observed in childhood and adolescence, but not adulthood. Birthweight-related CpGs overlap with some Bonferroni-significant CpGs that were previously reported to be related to maternal smoking (55/914, p = 6.12 x 10-74) and BMI in pregnancy (3/914, p = 1.13x10-3), but not with those related to folate levels in pregnancy. Whether the associations that we observe are causal or explained by confounding or fetal growth influencing DNA methylation (i.e. reverse causality) requires further research.


Assuntos
Peso ao Nascer/genética , DNA/metabolismo , Epigênese Genética , Genoma Humano , Adolescente , Adulto , Índice de Massa Corporal , Criança , Ilhas de CpG , DNA/genética , Metilação de DNA , Feminino , Desenvolvimento Fetal/genética , Feto , Ácido Fólico/sangue , Estudo de Associação Genômica Ampla , Humanos , Recém-Nascido , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/sangue , Efeitos Tardios da Exposição Pré-Natal/etiologia , Efeitos Tardios da Exposição Pré-Natal/genética , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Fumar/efeitos adversos , Fumar/sangue , Fumar/genética
12.
J Nutr Sci ; 8: e8, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30854201

RESUMO

Insufficient vitamin D during pregnancy increases risk of adverse outcomes, with known differences by race/ethnicity. We sought to determine whether predictors of vitamin D insufficiency vary by race/ethnicity in an ethnically diverse pregnancy cohort. Plasma 25-hydroxyvitamin D concentrations and patient characteristics were measured at first prenatal visit to prenatal clinics in south-eastern USA between 2009 and 2011 (n 504). Prevalence ratios (PR) and 95 % CI were estimated using multivariable regression to quantify predictors of vitamin D insufficiency, overall and by race/ethnicity. In race/ethnicity-stratified models, season was most associated with vitamin D insufficiency among non-Hispanic white women; PR for winter v. summer were 3·58 (95 % CI 1·64, 7·81) for non-Hispanic white, 1·52 (95 % CI 1·18, 1·95) for Hispanic and 1·14 (95 % CI 0·99, 1·30) for non-Hispanic black women. Although women with darker skin tones are most vulnerable to prenatal vitamin D insufficiency, season may be more strongly associated with insufficiency among women with lighter skin tones.

13.
Artigo em Inglês | MEDLINE | ID: mdl-30823531

RESUMO

This study examines pre-pregnancy Body Mass Index (BMI) and gestational weight gain (GWG) in relation to early childhood Attention Deficit Hyperactivity Disorder (ADHD) symptoms and related executive self-regulation behaviors. The analyses sample (n = 331) included a subsample of participants from a birth cohort recruited from prenatal clinics and hospital facilities from April 2005 to June 2011 in Durham, North Carolina. Pre-pregnancy BMI was calculated from weight at the last menstrual period and height was extracted from medical records. Gestational weight gain was calculated from pre-pregnancy weight and weight measured at the time of delivery. ADHD symptoms and executive self-regulation behaviors were assessed by maternal report (mean age = 3 years). Multivariable regression methods with inverse probability weighting (IPW) were used to evaluate associations accounting for sample selection bias and confounding. Pre-pregnancy BMI at levels ≥35 was positively associated with higher ADHD symptoms and worse executive self-regulation behaviors (inhibitory control and attention). Compared to adequate GWG, less than adequate GWG was related to more ADHD hyperactive-impulsive symptoms, whereas greater than adequate GWG was related to more problematic behaviors related to working memory and planning. The findings support a link between maternal weight and child neurodevelopment. Continued research that help identify biological mechanisms are needed.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/etiologia , Índice de Massa Corporal , Função Executiva , Ganho de Peso na Gestação , Efeitos Tardios da Exposição Pré-Natal/etiologia , Adulto , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Masculino , North Carolina , Gravidez , Efeitos Tardios da Exposição Pré-Natal/psicologia , Análise de Regressão , Fatores de Risco
14.
Epigenetics ; 14(4): 325-340, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30773972

RESUMO

Pre-pregnancy obesity is an established risk factor for adverse sex-specific cardiometabolic health in offspring. Epigenetic alterations, such as in DNA methylation (DNAm), are a hypothesized link; however, sex-specific epigenomic targets remain unclear. Leveraging data from the Newborn Epigenetics Study (NEST) cohort, linear regression models were used to identify CpG sites in cord blood leukocytes associated with pre-pregnancy obesity in 187 mother-female and 173 mother-male offsprings. DNAm in cord blood was measured using the Illumina HumanMethylation450k BeadChip. Replication analysis was conducted among the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort. Associations between pre-pregnancy obesity-associated CpG sites and offspring BMI z-score (BMIz) and blood pressure (BP) percentiles at 4-5-years of age were also examined. Maternal pre-pregnacy obesity was associated with 876 CpGs in female and 293 CpGs in male offspring (false discovery rate <5%). Among female offspring, 57 CpG sites, including the top 18, mapped to the TAPBP gene (range of effect estimates: -0.83% decrease to 4.02% increase in methylation). CpG methylation differences in the TAPBP gene were also observed among males (range of effect estimates: -0.30% decrease to 2.59% increase in methylation). While technically validated, none of the TAPBP CpG sites were replicated in ALSPAC. In NEST, methylation differences at CpG sites of the TAPBP gene were associated with BMI z-score (cg23922433 and cg17621507) and systolic BP percentile (cg06230948) in female and systolic (cg06230948) and diastolic (cg03780271) BP percentile in male offspring. Together, these findings suggest sex-specific effects, which, if causal, may explain observed sex-specific effects of maternal obesity.

15.
Nicotine Tob Res ; 2018 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-30590728

RESUMO

Introduction: Both prenatal smoke exposure and depression have been linked to lower birth weight, a risk factor for morbidity and mortality. Few studies have looked at the interaction between these risk factors and none have used a biomarker to objectively measure prenatal smoke exposure. The current study sought to examine independent and interactive effects of cotinine and depression on birth weight. The effect of race was also explored. Method: Data were drawn from a prospective study of pregnant women (N=568) in the southeastern U.S. Maternal demographic, health information, depressive symptoms, and birth data were collected via self-report and medical record abstraction. Prenatal blood samples were assayed for cotinine. Results: Controlling for covariates, multiple regression analyses indicated that both cotinine and depressive symptoms independently predicted lower birth weight and a significant interaction was also observed. Upon probing the interaction, a negative association between cotinine levels and birth weight was found in the context of higher depression but not lower depression scores. Similarly, logistic regression analyses revealed a significant interaction between cotinine and depression, such that cotinine predicted having a baby < 2500 g among women who fell above the indicated cut-off score. African American women had the highest levels of cotinine and lowest weight babies; however, race was not a significant moderator. Conclusions: Results suggest prenatal smoke exposure has a greater negative effect on birth weight for women endorsing co-occurring depressive symptoms. Findings can inform targeted interventions and assist medical providers with identifying women at increased risk for poor perinatal outcomes. Implications: Despite the common occurrence of smoking during pregnancy and prenatal depression, the interaction between these risk factors on birth weight has rarely been examined. Further, the extant results have been mixed, likely due in part to difficulties in measurement. The current study was the first to use prenatal cotinine to assess bias-free, continuous levels of prenatal smoke exposure. Results indicate that prenatal cotinine was a significant predictor of birth weight only in the context of maternal depressive symptoms. These findings have important implications for mitigating negative perinatal outcomes for pregnant women and their children.

16.
Int J Obes (Lond) ; 2018 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-30349009

RESUMO

BACKGROUND: Potentially driven by the lack of mother-to-infant transmission of microbiota at birth, cesarean delivery has been associated with higher risk of offspring obesity. Yet, no studies have examined when delivery-mode differences in adiposity begin to emerge. In this study, we examine differences in infant weight and adiposity trajectories from birth to 12 months by delivery mode. METHODS: From 2013 to 2015, we recruited pregnant women into the Nurture Study and followed up their 666 infants. We ascertained maternal delivery method and infant birth weight from medical records. We measured weight, length, and skinfold thicknesses (subscapular, triceps, abdominal) when infants were 3, 6, 9, and 12 months of age. The main outcome, infant weight-for-length z score, was derived based on the WHO Child Growth Standards. We used linear regression models to assess the difference at each time point and used linear mixed models to examine the growth rate for infant weight and adiposity trajectories. We controlled for maternal age, race, marital status, education level, household income, smoking status, maternal pre-pregnancy body mass index, and infant birth weight. RESULTS: Of the 563 infants in our final sample, 179 (31.8%) were cesarean delivered. From birth to 12 months, the rate of increase in weight-for-length z score was 0.02/month (p = 0.03) greater for cesarean-delivered than vaginally-delivered infants. As a result of more rapid growth, cesarean-delivered infants had higher weight-for-length z score (0.26, 95% CI: 0.05, 0.47) and sum of subscapular and triceps (SS + TR) skinfold thickness (0.95 mm, 95% CI: 0.30, 1.60)-an indicator for overall adiposity-at 12 months, compared to vaginally-delivered infants. CONCLUSIONS: Compared to vaginal delivery, cesarean delivery was associated with greater offspring rate of weight gain over the first year and differences in adiposity that appear as early as 3 months of age. Monitoring cesarean-delivered infants closely for excess weight gain may help guide primordial prevention of obesity later in life.

17.
Front Cell Dev Biol ; 6: 107, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30246009

RESUMO

Background: Maternal diet during pregnancy has been shown to influence the child neuro-developmental outcomes. Studies examining effects of dietary patterns on offspring behavior are sparse. Objective: Determine if maternal adherence to a Mediterranean diet is associated with child behavioral outcomes assessed early in life, and to evaluate the role of differentially methylated regions (DMRs) regulating genomically imprinted genes in these associations. Methods: Among 325 mother/infant pairs, we used regression models to evaluate the association between tertiles of maternal periconceptional Mediterranean diet adherence (MDA) scores derived from a Food Frequency Questionnaire, and social and emotional scores derived from the Infant Toddler Social and Emotional Assessment (ITSEA) questionnaire in the second year of life. Methylation of nine genomically imprinted genes was measured to determine if MDA was associated with CpG methylation. Results: Child depression was inversely associated with maternal MDA (Bonferroni-corrected p = 0.041). While controlling for false-discovery, compared to offspring of women with the lowest MDA tertile, those with MDA scores in middle and high MDA tertiles had decreased odds for atypical behaviors [OR (95% CI) = 0.40 (0.20, 0.78) for middle and 0.40 (0.17, 0.92) for highest tertile], for maladaptive behaviors [0.37 (0.18, 0.72) for middle tertile and 0.42 (0.18, 0.95) for highest tertile] and for an index of autism spectrum disorder behaviors [0.46 (0.23, 0.90) for middle and 0.35 (0.15, 0.80) for highest tertile]. Offspring of women with the highest MDA tertile were less likely to exhibit depressive [OR = 0.28 (0.12, 0.64)] and anxiety [0.42 (0.18, 0.97)] behaviors and increased odds of social relatedness [2.31 (1.04, 5.19)] behaviors when compared to low MDA mothers. Some associations varied by sex. Perinatal MDA score was associated with methylation differences for imprinted control regions of PEG10/SGCE [females: Beta (95% CI) = 1.66 (0.52, 2.80) - Bonferroni-corrected p = 0.048; males: -0.56 (-1.13, -0.00)], as well as both MEG3 and IGF2 in males [0.97 (0.00, 1.94)] and -0.92 (-1.65, -0.19) respectively. Conclusion: In this ethnically diverse cohort, maternal adherence to a Mediterranean diet in early pregnancy was associated with favorable neurobehavioral outcomes in early childhood and with sex-dependent methylation differences of MEG3, IGF2, and SGCE/PEG10 DMRs.

18.
Clin Epigenetics ; 10(1): 98, 2018 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-30029617

RESUMO

BACKGROUND: Epigenetic modifications, including DNA methylation, act as one potential mechanism underlying the detrimental effects associated with prenatal tobacco smoke (PTS) exposure. Methylation in a gene called AXL was previously reported to differ in response to PTS. METHODS: We investigated the association between PTS and epigenetic changes in AXL and how this was related to childhood asthma phenotypes. We tested the association between PTS and DNA methylation at multiple CpG loci of AXL at birth using Pyrosequencing in two separate study populations, the Children's Health Study (CHS, n = 799) and the Newborn Epigenetic Study (NEST, n = 592). Plasma cotinine concentration was used to validate findings with self-reported smoking status. The inter-relationships among AXL mRNA and miR-199a1 expression, PTS, and AXL methylation were examined. Lastly, we evaluated the joint effects of AXL methylation and PTS on the risk of asthma and related symptoms at age 10 years old. RESULTS: PTS was associated with higher methylation level in the AXL gene body in both CHS and NEST subjects. In the pooled analysis, exposed subjects had a 0.51% higher methylation level in this region compared to unexposed subjects (95% CI 0.29, 0.74; p < 0.0001). PTS was also associated with 21.2% lower expression of miR-199a1 (95% CI - 37.9, - 0.1; p = 0.05), a microRNA known to regulate AXL expression. Furthermore, the combination of higher AXL methylation and PTS exposure at birth increased the risk of recent episodes of bronchitic symptoms in childhood. CONCLUSIONS: PTS was associated with methylation level of AXL and the combination altered the risk of childhood bronchitic symptoms.

19.
Clin Epigenetics ; 10: 90, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29988473

RESUMO

Background: This study assessed the associations between nine differentially methylated regions (DMRs) of imprinted genes in DNA derived from umbilical cord blood leukocytes in males and females and (1) birth weight for gestational age z score, (2) weight-for-length (WFL) z score at 1 year, and (3) body mass index (BMI) z score at 3 years. Methods: We conducted multiple linear regression in n = 567 infants at birth, n = 288 children at 1 year, and n = 294 children at 3 years from the Newborn Epigenetics Study (NEST). We stratified by sex and adjusted for race/ethnicity, maternal education, maternal pre-pregnancy BMI, prenatal smoking, maternal age, gestational age, and paternal race. We also conducted analysis restricting to infants not born small for gestational age. Results: We found an association between higher methylation of the sequences regulating paternally expressed gene 10 (PEG10) and anthropometric z scores at 1 year (ß = 0.84; 95% CI = 0.34, 1.33; p = 0.001) and 3 years (ß = 1.03; 95% CI = 0.37, 1.69; p value = 0.003) in males only. Higher methylation of the DMR regulating mesoderm-specific transcript (MEST) was associated with lower anthropometric z scores in females at 1 year (ß = - 1.03; 95% CI - 1.60, - 0.45; p value = 0.001) and 3 years (ß = - 1.11; 95% CI - 1.98, - 0.24; p value = 0.01). These associations persisted when we restricted to infants not born small for gestational age. Conclusion: Our data support a sex-specific association between altered methylation and weight status in early life. These methylation marks can contribute to the compendium of epigenetically regulated regions detectable at birth, influencing obesity in childhood. Larger studies are required to confirm these findings.

20.
Epigenomics ; 10(7): 1011-1026, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29957030

RESUMO

AIM: Imprinted genes exhibit expression in a parent-of-origin-dependent manner and are critical for child development. Recent limited evidence suggests that prenatal exposure to phthalates, ubiquitous endocrine disruptors, can affect their epigenetic dysregulation. MATERIALS & METHODS: We quantified DNA methylation of nine imprinted gene differentially methylated regions by pyrosequencing in 296 cord blood DNA samples in a Mexican-American cohort. Fetal exposure was estimated by phthalate metabolite concentrations in maternal urine samples during pregnancy. RESULTS: Several differentially methylated regions of imprinted genes were associated with high molecular weight phthalates. The most consistent, positive, and false discovery rate significant associations were observed for MEG3. CONCLUSION: Phthalate exposure in utero may affect methylation status of imprinted genes in newborn children.

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