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1.
Pediatr Obes ; : e12763, 2020 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-33381912

RESUMO

BACKGROUND: Although maternal systemic inflammation is hypothesized to link maternal pre-pregnancy obesity to offspring metabolic dysfunction, patient empirical data are limited. OBJECTIVES: In this study, we hypothesized that pre-pregnancy obesity alters systemic chemo/cytokines concentrations in pregnancy, and this alteration contributes to obesity in children. METHODS: In a multi-ethnic cohort of 361 mother-child pairs, we measured prenatal concentrations of plasma TNF-α, IL-6, IL-8, IL-1ß, IL-4, IFN-γ, IL-12 p70 subunit, and IL-17A using a multiplex ELISA and examined associations of pre-pregnancy obesity on maternal chemo/cytokine levels, and associations of these cytokine levels with offspring body mass index z score (BMI-z) at age 2-6 years using linear regression. RESULTS: After adjusting for maternal smoking, ethnicity, age, and education, pre-pregnancy obesity was associated with increased concentrations of TNF-α (P = .026) and IFN-γ (P = .06). While we found no evidence for associations between TNF-α concentrations and offspring BMI-z, increased IFN-γ concentrations were associated with decreased BMI-z (P = .0002), primarily in Whites (P = .0011). In addition, increased maternal IL-17A concentrations were associated with increased BMI-z in offspring (P = .0005) with stronger associations in African Americans (P = .0042) than Whites (P = .24). CONCLUSIONS: Data from this study are consistent with maternal obesity-related inflammation during pregnancy, increasing the risk of childhood obesity in an ethnic-specific manner.

2.
BJOG ; 2020 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-33338292

RESUMO

OBJECTIVE: C-section interrupts mother-to-newborn microbial transfer at birth. Beyond the neonatal period, the impact of C-section on offspring gut microbiota and their short chain fatty acids (SCFAs) remains unclear. Here we examine delivery mode (C-section vs. vaginal) with the infant gut microbiota and fecal SCFAs measured 3 and 12 months after birth. DESIGN: Longitudinal study. SETTING: North Carolina. POPULATION: In 2013-2015 we enrolled pregnant women and followed up their offspring for 12 months. We asked a subset of participants, enrolled over a 3-month period, to provide fecal samples at the 3-month and 12-month follow-up visits. METHODS/MAIN OUTCOMES: We sequenced the 16S rRNA V4 region with Illumina MiSeq and quantified SCFA concentrations using gas chromatography. We examined delivery mode with differential abundance of microbiota amplicon sequence variants (ASVs) using beta-binomial regression and fecal SCFAs using linear regression. We adjusted models for confounders. RESULTS: Of the 70 infants in our analytic sample, 25 (36%) were C-section delivered. C-section (vs. vaginal) delivery was associated with differential abundance of 14 infant bacterial ASVs at 3 months and 13 ASVs at 12 months. C-section infants had a higher abundance of the potential pathobionts C. neonatale (p = 0.04) and C. perfringens (p = 0.04), and a lower abundance of potentially beneficial Bifidobacterium and Bacteroides spp. C-section infants also had higher fecal butyrate at 3 months (p < 0.005). CONCLUSIONS: C-section infants were more likely to be colonized by pathobionts in lieu of beneficial microbes, and they excreted more butyrate at 3 months of life.

3.
Genome Med ; 12(1): 105, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33239103

RESUMO

BACKGROUND: DNA methylation has been shown to be associated with adiposity in adulthood. However, whether similar DNA methylation patterns are associated with childhood and adolescent body mass index (BMI) is largely unknown. More insight into this relationship at younger ages may have implications for future prevention of obesity and its related traits. METHODS: We examined whether DNA methylation in cord blood and whole blood in childhood and adolescence was associated with BMI in the age range from 2 to 18 years using both cross-sectional and longitudinal models. We performed meta-analyses of epigenome-wide association studies including up to 4133 children from 23 studies. We examined the overlap of findings reported in previous studies in children and adults with those in our analyses and calculated enrichment. RESULTS: DNA methylation at three CpGs (cg05937453, cg25212453, and cg10040131), each in a different age range, was associated with BMI at Bonferroni significance, P < 1.06 × 10-7, with a 0.96 standard deviation score (SDS) (standard error (SE) 0.17), 0.32 SDS (SE 0.06), and 0.32 BMI SDS (SE 0.06) higher BMI per 10% increase in methylation, respectively. DNA methylation at nine additional CpGs in the cross-sectional childhood model was associated with BMI at false discovery rate significance. The strength of the associations of DNA methylation at the 187 CpGs previously identified to be associated with adult BMI, increased with advancing age across childhood and adolescence in our analyses. In addition, correlation coefficients between effect estimates for those CpGs in adults and in children and adolescents also increased. Among the top findings for each age range, we observed increasing enrichment for the CpGs that were previously identified in adults (birth Penrichment = 1; childhood Penrichment = 2.00 × 10-4; adolescence Penrichment = 2.10 × 10-7). CONCLUSIONS: There were only minimal associations of DNA methylation with childhood and adolescent BMI. With the advancing age of the participants across childhood and adolescence, we observed increasing overlap with altered DNA methylation loci reported in association with adult BMI. These findings may be compatible with the hypothesis that DNA methylation differences are mostly a consequence rather than a cause of obesity.

4.
Nicotine Tob Res ; 2020 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-33249470

RESUMO

INTRODUCTION: Many children suffer from secondhand smoke exposure (SHSe), which leads to a variety of negative health consequences. However, there is no consensus on how clinicians can best query parents for possible SHSe among children. We employed a data-driven approach to create an efficient screening tool for clinicians to quickly and correctly identify children at risk for SHSe. METHODS: Survey data from mothers and biospecimens from children were ascertained from the Neurodevelopment and Improving Children's Health following Environmental Tobacco Smoke Exposure (NICHES) study. Included were mothers and their children whose saliva were assayed for cotinine (n = 351 pairs, mean child age = 5.6 years). Elastic net regression predicting SHSe, as indicated from cotinine concentration, was conducted on available smoking-related questions and cross-validated with 2015-2016 National Health and Nutrition Examination Survey (NHANES) data to select the most predictive items of SHSe among children (n = 1,670, mean child age = 8.4 years). RESULTS: Answering positively to at least one of the two final items ("During the past 30 days, did you smoke cigarettes at all?" and "Has anyone, including yourself, smoked tobacco in your home in the past 7 days?") showed AUC = .82, and good specificity (.88) and sensitivity (.74). These results were validated with similar items in the nationally-representative NHANES sample, AUC = .82, specificity = .78, and sensitivity = .77. CONCLUSIONS: Our data-driven approach identified and validated two items that may be useful as a screening tool for a speedy and accurate assessment of SHSe among children. IMPLICATIONS: The current study used a rigorous data-driven approach to identify questions that could reliably predict secondhand smoking exposure (SHS) among children.Using saliva cotinine concentration levels as a gold standard for determining SHS exposure, our analysis employing elastic net regression identified two questions that served as good classifier for distinguishing children who might be at risk for SHS exposure. The two items that we validated in the current study can be readily used by clinicians, such as pediatricians, as part of screening procedures to quickly identify whether children might be at risk for secondhand smoking exposure.

5.
Transl Psychiatry ; 10(1): 398, 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33184255

RESUMO

Attention-deficit and hyperactivity disorder (ADHD) is a common childhood disorder with a substantial genetic component. However, the extent to which epigenetic mechanisms play a role in the etiology of the disorder is unknown. We performed epigenome-wide association studies (EWAS) within the Pregnancy And Childhood Epigenetics (PACE) Consortium to identify DNA methylation sites associated with ADHD symptoms at two methylation assessment periods: birth and school age. We examined associations of both DNA methylation in cord blood with repeatedly assessed ADHD symptoms (age 4-15 years) in 2477 children from 5 cohorts and of DNA methylation at school age with concurrent ADHD symptoms (age 7-11 years) in 2374 children from 9 cohorts, with 3 cohorts participating at both timepoints. CpGs identified with nominal significance (p < 0.05) in either of the EWAS were correlated between timepoints (ρ = 0.30), suggesting overlap in associations; however, top signals were very different. At birth, we identified nine CpGs that predicted later ADHD symptoms (p < 1 × 10-7), including ERC2 and CREB5. Peripheral blood DNA methylation at one of these CpGs (cg01271805 in the promoter region of ERC2, which regulates neurotransmitter release) was previously associated with brain methylation. Another (cg25520701) lies within the gene body of CREB5, which previously was associated with neurite outgrowth and an ADHD diagnosis. In contrast, at school age, no CpGs were associated with ADHD with p < 1 × 10-7. In conclusion, we found evidence in this study that DNA methylation at birth is associated with ADHD. Future studies are needed to confirm the utility of methylation variation as biomarker and its involvement in causal pathways.

6.
Toxics ; 8(4)2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33092103

RESUMO

Prenatal cadmium exposure at non-occupational levels has been associated with poor birth outcomes. The intake of essential metals, such as iron and selenium, may mitigate cadmium exposure effects. However, at high levels, these metals can be toxic. The role of dietary patterns rich in these metals is less studied. We used a linear and logistic regression in a cohort of 185 mother-infant pairs to assess if a Mediterranean diet pattern during pregnancy modified the associations between prenatal cadmium exposure and (1) birth weight and (2) preterm birth. We found that increased cadmium exposure during pregnancy was associated with lower birth weight (ß = -210.4; 95% CI: -332.0, -88.8; p = 0.008) and preterm birth (OR = 0.11; 95% CI: 0.01, 0.72; p = 0.04); however, these associations were comparable in offspring born to women reporting high adherence to a Mediterranean diet (ß = -274.95; 95% CI: -701.17, 151.26; p = 0.20) and those with low adherence (ß = -64.76; 95% CI: -359.90, 230.37; p = 0.66). While the small sample size limits inference, our findings suggest that adherence to a Mediterranean dietary pattern may not mitigate cadmium exposure effects. Given the multiple organs targeted by cadmium and its slow excretion rate, larger studies are required to clarify these findings.

7.
Obesity (Silver Spring) ; 28(12): 2389-2396, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33098275

RESUMO

OBJECTIVE: The purpose of this study was to investigate the association between maternal employment and infant BMI z score. METHODS: Longitudinal data from 520 mother-infant dyads participating in the Nurture Study, an observational cohort in the southeastern United States, were leveraged. Women were categorized as employed or nonemployed at 3, 6, 9, and 12 months, and measured anthropometrics were used to calculate infants' BMI z scores at the corresponding time points. BMI z score was defined using the World Health Organization standard. Household income was an effect modifier. Therefore, income-stratified (≤$40,000/y vs. >$40,000/y) linear regression models, with individual fixed effects, were used to examine associations between change in maternal employment status and BMI z scores among infants aged 3 to 12 months. Fixed effects controlled for time-invariant confounders (race/ethnicity, infant gender). This study also controlled for marital status and infant age. RESULTS: More women from higher-income (68.4%) versus lower-income households (52.6%) were employed. Among lower-income households, change from nonemployment to employment was associated with higher infant BMI z scores (ß = 0.12; 95% CI: -0.01 to 0.25, P = 0.07). Among higher-income households, change in maternal employment status was associated with lower infant BMI z scores (ß = -0.72; 95% CI: -1.17 to -0.27, P = 0.02). CONCLUSIONS: Maternal employment was related to infant adiposity. The direction of the association varied by household-level income.

8.
Epigenetics ; : 1-11, 2020 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-32660355

RESUMO

Studies have suggested that abrogated expression of detoxification enzymes, UGT2B15 and UGT2B17, are associated with prostate tumour risk and progression. We investigated the role of EGF on the expression of these enzymes since it interacts with signalling pathways to also affect prostate tumour progression and is additionally associated with decreased DNA methylation. The expression of UGT2B15, UGT2B17, de novo methyltransferases, DNMT3A and DNMT3B was assessed in prostate cancer cells (LNCaP) treated with EGF, an EGFR inhibitor PD16893, and the methyltransferase inhibitor, 5-azacytidine, respectively. The results showed that EGF treatment decreased levels of expression of all four genes and that their expression was reversed by PD16893. Treatment with 5-azacytidine, markedly decreased expression of UGT2B15 and UGT2B17 over 85% as well as significantly decreased expression of DNMT3B, but not the expression of DNMT3A. DNMT3B siRNA treated LNCaP cells had decreased expression of UGT2B15 and UGT2B17, while DNMT3A siRNA treated cells had only moderately decreased UGT2B15 expression. Treatment with DNMT methyltransferase inhibitor, RG108, significantly decreased UGT2B17 expression. Additionally, methylation differences between prostate cancer samples and benign prostate samples from an Illumina 450K Methylation Array study were assessed. The results taken together suggest that hypomethylation of the UGT2B15 and UGT2B17 genes contributes to increased risk of prostate cancer and may provide a putative biomarker or epigenetic target for chemotherapeutics. Mechanistic studies are warranted to determine the role of the methylation marks in prostate cancer.

9.
Pediatr Obes ; 15(7): e12631, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32119190

RESUMO

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) symptoms have been linked with eating behaviors and obesity adolescence and young adulthood. Yet, little is known about whether these associations occur during early childhood and few studies have examined these associations prospectively. OBJECTIVES: To assess magnitude and direction of associations between childhood ADHD symptoms and eating behaviors. METHODS: Participants were from the Newborn Epigenetics Study (N = 470, M age = 4 years). Multivariable linear regression models were used to examine cross-sectional associations between ADHD symptoms and eating behaviors. Latent Change Score (LCS) modeling was performed to examine prospective association among a subset of children with available follow-up data. (N = 100, M age = 7 years). RESULTS: The cross-sectional results showed that attention problem (AP) and hyperactivity (HY) were positively associated with food responsiveness, emotional overeating, desire to drink, and slowness in eating. AP, but not HY, was inversely associated with enjoyment of food. Results of the LCS models revealed AP and HY were both positively associated with prospective changes in emotional overeating and satiety responsiveness. AP was further positively associated with prospective changes in food responsiveness. The reverse relationship predicting changes in ADHD symptoms from earlier assessments of eating behaviors was not significant. CONCLUSION: Results suggest a link between ADHD symptoms and obesity-related eating behaviors in early childhood, highlighting the need to address self-regulation and healthy eating behaviors in the prevention of childhood obesity.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Comportamento Alimentar/psicologia , Obesidade Pediátrica/etiologia , Adolescente , Adulto , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Hiperfagia/psicologia , Masculino , Obesidade Pediátrica/prevenção & controle , Estudos Prospectivos , Adulto Jovem
10.
BMC Microbiol ; 20(1): 56, 2020 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-32160858

RESUMO

BACKGROUND: Early introduction of complementary foods has been associated with various immune disorders, oxidative stress, and obesity in childhood. The gut microbiota and the short chain fatty acids (SCFAs) they produce are postulated to be on the causal pathway. The objective of this study was to determine if early complementary feeding (i.e. consumption of solids or non-water/formula liquids at or before 3 months) is prospectively associated with infant gut microbiota composition, diversity and SCFAs at 3 and 12 months of age in the Nurture birth cohort. RESULTS: Mother-infant dyads in the early complementary feeding group (n = 18) had similar baseline characteristics to those in the later feeding group (n = 49). We assessed differential abundance of microbial taxa (measured by 16S rRNA gene sequencing of the V4 region) by timing of complementary feeding using beta-binomial regression models (considering a two-sided FDR corrected p-value of < 0.05 as significant), and we fittted linear regression models to assess the association between early complementary feeding and SCFA concentrations (quantified using gas chromatography). After multivariable adjustment for breastfeeding, delivery method, birth weight, and gestational age, there were 13 differentially abundant microbial amplicon sequence variants (ASVs) by timing of introduction to complementary foods at 3 months and 20 ASVs at 12 months. Infants introduced to complementary foods early (vs. later) had higher concentrations of the SCFA butyric acid (mean difference = 0.65, 95% CI: 0.27, 1.04, p < 0.01) and total SCFAs (mean difference = 38.8, 95% CI: 7.83, 69.7) at 12 months. Bilophila wadsworthia and Lachnospiraceae Roseburia were associated with early (vs. later) complementary feeding and with higher butyric acid concentrations at 3 and 12 months, respectively. CONCLUSIONS: Our findings are consistent with the hypothesis that early (vs. later) introduction to complementary foods is associated with altered gut microbiota composition and butyric acid concentrations measured in stool until at least 1 year of age. Further research is needed to determine if these changes mediate future development of metabolic and immune conditions.

11.
Curr Med Res Opin ; 36(6): 1025-1032, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32212939

RESUMO

Objectives: Childhood asthma is a common chronic illness that has been associated with mode of delivery. However, the effect of cesarean delivery alone does not fully account for the increased prevalence of childhood asthma. We tested the hypothesis that neuraxial anesthesia used for labor analgesia and cesarean delivery alters the risk of developing childhood asthma.Methods: Within the Newborn Epigenetics Study birth cohort, 196 mother and child pairs with entries in the electronic anesthesia records were included. From these records, data on maternal anesthesia type, duration of exposure, and drugs administered peripartum were abstracted and combined with questionnaire-derived prenatal risk factors and medical records and questionnaire-derived asthma diagnosis data in children. Logistic regression models were used to evaluate associations between type of anesthesia, duration of anesthesia, and the development of asthma in males and females.Results: We found that longer duration of epidural anesthesia was associated with a lower risk of asthma in male children (OR = 0.80; 95% CI = 0.66-0.95) for each hour of epidural exposure. Additionally, a unit increase in the composite dose of local anesthetics and opioid analgesics administered via the spinal route was associated with a lower risk of asthma in both male (OR = 0.59, 95% CI = 0.36-0.96) and female children (OR 0.26, 95% CI 0.09-0.82).Conclusion: Our data suggest that peripartum exposure to neuraxial anesthesia may reduce the risk of childhood asthma primarily in males. Larger human studies and model systems with longer follow-up are required to elucidate these findings.

12.
Nicotine Tob Res ; 22(1): 40-47, 2020 01 27.
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 United States. 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 less than 2500 g among women who fell above the indicated cutoff 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.


Assuntos
Peso ao Nascer/efeitos dos fármacos , Depressão/complicações , Recém-Nascido de Baixo Peso , Exposição Materna/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/etiologia , Poluição por Fumaça de Tabaco/efeitos adversos , Adolescente , Adulto , Biomarcadores/sangue , Cotinina/sangue , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/patologia , Estudos Prospectivos , Fatores de Risco , Adulto Jovem
13.
Child Obes ; 16(2): 122-128, 2020 03.
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.

14.
Epigenomics ; 11(13): 1487-1500, 2019 10.
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.

15.
Environ Epigenet ; 5(3): dvz014, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31528362

RESUMO

Cadmium (Cd) is a ubiquitous environmental pollutant associated with a wide range of health outcomes including cancer. However, obscure exposure sources often hinder prevention efforts. Further, although epigenetic mechanisms are suspected to link these associations, gene sequence regions targeted by Cd are unclear. Aberrant methylation of a differentially methylated region (DMR) on the MEG3 gene that regulates the expression of a cluster of genes including MEG3, DLK1, MEG8, MEG9 and DIO3 has been associated with multiple cancers. In 287 infant-mother pairs, we used a combination of linear regression and the Getis-Ord Gi* statistic to determine if maternal blood Cd concentrations were associated with offspring CpG methylation of the sequence region regulating a cluster of imprinted genes including MEG3. Correlations were used to examine potential sources and routes. We observed a significant geographic co-clustering of elevated prenatal Cd levels and MEG3 DMR hypermethylation in cord blood (P = 0.01), and these findings were substantiated in our statistical models (ß = 1.70, se = 0.80, P = 0.03). These associations were strongest in those born to African American women (ß = 3.52, se = 1.32, P = 0.01) compared with those born to White women (ß = 1.24, se = 2.11, P = 0.56) or Hispanic women (ß = 1.18, se = 1.24, P = 0.34). Consistent with Cd bioaccumulation during the life course, blood Cd levels increased with age (ß = 0.015 µg/dl/year, P = 0.003), and Cd concentrations were significantly correlated between blood and urine (ρ > 0.47, P < 0.01), but not hand wipe, soil or house dust concentrations (P > 0.05). Together, these data support that prenatal Cd exposure is associated with aberrant methylation of the imprint regulatory element for the MEG3 gene cluster at birth. However, neither house-dust nor water are likely exposure sources, and ingestion via contaminated hands is also unlikely to be a significant exposure route in this population. Larger studies are required to identify routes and sources of exposure.

16.
BMJ Open ; 9(9): e030186, 2019 09 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.

17.
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
18.
Appetite ; 142: 104369, 2019 11 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.

19.
Clin Epigenetics ; 11(1): 87, 2019 06 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.

20.
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.


Assuntos
Adiposidade/efeitos dos fármacos , Antibacterianos/efeitos adversos , Microbioma Gastrointestinal/efeitos dos fármacos , Obesidade/microbiologia , Efeitos Tardios da Exposição Pré-Natal/microbiologia , Adulto , Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/isolamento & purificação , Feminino , Humanos , Lactente , Masculino , Obesidade/etiologia , Obesidade/fisiopatologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/etiologia , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Estudos Prospectivos , Adulto Jovem
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