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1.
J Dev Orig Health Dis ; : 1-13, 2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-31391133

RESUMO

BACKGROUND: Childhood obesity is a global issue. Excessive weight gain in early pregnancy is independently associated with obesity in the next generation. Given the uptake of e-health, our primary aim was to pilot the feasibility of an e-health intervention, starting in the first trimester, to promote healthy lifestyle and prevent excess weight gain in early pregnancy. METHODS: Women were recruited between 8 and 11 weeks gestation and randomised to the intervention or routine antenatal care. The intervention involved an e-health program providing diet, physical activity and well-being advice over 12 weeks. RESULTS: Women (n = 57, 43.9% overweight/obese) were recruited at 9.38 ± 1.12 (control) and 9.06 ± 1.29 (intervention) weeks' gestation, mainly from obstetric private practices (81.2%). Retention was 73.7% for the 12-week intervention, 64.9% at birth and 55.8% at 3 months after birth.No difference in gestational weight gain or birth size was detected. Overall treatment effect showed a mean increase in score ranking the perceived confidence of dietary change (1.2 ± 0.46, p = 0.009) and score ranking readiness to exercise (1.21 ± 0.51, p = 0.016) over the intervention. At 3 months, infants weighed less in the intervention group (5405 versus 6193 g, p = 0.008) and had a lower ponderal index (25.5 ± 3.0 versus 28.8 ± 4.0 kg/m3) compared with the control group. CONCLUSION AND DISCUSSION: A lifestyle intervention starting in the first-trimester pregnancy utilising e-health mode of delivery is feasible. Future studies need strategies to target recruitment of participants of lower socio-economic status and ensure maximal blinding. Larger trials (using technology and focused on early pregnancy) are needed to confirm if decreased infant adiposity is maintained.

2.
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
3.
PLoS Med ; 16(2): e1002744, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30742624

RESUMO

BACKGROUND: Maternal obesity and excessive gestational weight gain may have persistent effects on offspring fat development. However, it remains unclear whether these effects differ by severity of obesity, and whether these effects are restricted to the extremes of maternal body mass index (BMI) and gestational weight gain. We aimed to assess the separate and combined associations of maternal BMI and gestational weight gain with the risk of overweight/obesity throughout childhood, and their population impact. METHODS AND FINDINGS: We conducted an individual participant data meta-analysis of data from 162,129 mothers and their children from 37 pregnancy and birth cohort studies from Europe, North America, and Australia. We assessed the individual and combined associations of maternal pre-pregnancy BMI and gestational weight gain, both in clinical categories and across their full ranges, with the risks of overweight/obesity in early (2.0-5.0 years), mid (5.0-10.0 years) and late childhood (10.0-18.0 years), using multilevel binary logistic regression models with a random intercept at cohort level adjusted for maternal sociodemographic and lifestyle-related characteristics. We observed that higher maternal pre-pregnancy BMI and gestational weight gain both in clinical categories and across their full ranges were associated with higher risks of childhood overweight/obesity, with the strongest effects in late childhood (odds ratios [ORs] for overweight/obesity in early, mid, and late childhood, respectively: OR 1.66 [95% CI: 1.56, 1.78], OR 1.91 [95% CI: 1.85, 1.98], and OR 2.28 [95% CI: 2.08, 2.50] for maternal overweight; OR 2.43 [95% CI: 2.24, 2.64], OR 3.12 [95% CI: 2.98, 3.27], and OR 4.47 [95% CI: 3.99, 5.23] for maternal obesity; and OR 1.39 [95% CI: 1.30, 1.49], OR 1.55 [95% CI: 1.49, 1.60], and OR 1.72 [95% CI: 1.56, 1.91] for excessive gestational weight gain). The proportions of childhood overweight/obesity prevalence attributable to maternal overweight, maternal obesity, and excessive gestational weight gain ranged from 10.2% to 21.6%. Relative to the effect of maternal BMI, excessive gestational weight gain only slightly increased the risk of childhood overweight/obesity within each clinical BMI category (p-values for interactions of maternal BMI with gestational weight gain: p = 0.038, p < 0.001, and p = 0.637 in early, mid, and late childhood, respectively). Limitations of this study include the self-report of maternal BMI and gestational weight gain for some of the cohorts, and the potential of residual confounding. Also, as this study only included participants from Europe, North America, and Australia, results need to be interpreted with caution with respect to other populations. CONCLUSIONS: In this study, higher maternal pre-pregnancy BMI and gestational weight gain were associated with an increased risk of childhood overweight/obesity, with the strongest effects at later ages. The additional effect of gestational weight gain in women who are overweight or obese before pregnancy is small. Given the large population impact, future intervention trials aiming to reduce the prevalence of childhood overweight and obesity should focus on maternal weight status before pregnancy, in addition to weight gain during pregnancy.


Assuntos
Índice de Massa Corporal , Análise de Dados , Ganho de Peso na Gestação/fisiologia , Obesidade Pediátrica/epidemiologia , Austrália/epidemiologia , Estudos de Coortes , Europa (Continente)/epidemiologia , Feminino , Humanos , América do Norte/epidemiologia , Sobrepeso/diagnóstico , Sobrepeso/epidemiologia , Obesidade Pediátrica/diagnóstico , Gravidez , Fatores de Risco
4.
J Clin Endocrinol Metab ; 104(7): 3012-3024, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30785999

RESUMO

CONTEXT: "Accelerated aging," assessed by adult DNA methylation, predicts cardiovascular disease (CVD). Adolescent accelerated aging might predict CVD earlier. We investigated whether epigenetic age acceleration (assessed age, 17 years) was associated with adiposity/CVD risk measured (ages 17, 20, and 22 years) and projected CVD by middle age. DESIGN: DNA methylation measured in peripheral blood provided two estimates of epigenetic age acceleration: intrinsic (IEAA; preserved across cell types) and extrinsic (EEAA; dependent on cell admixture and methylation levels within each cell type). Adiposity was assessed by anthropometry, ultrasound, and dual-energy x-ray absorptiometry (ages 17, 20, and 22 years). CVD risk factors [lipids, homeostatic model assessment of insulin resistance (HOMA-IR), blood pressure, inflammatory markers] were assessed at age 17 years. CVD development by age 47 years was calculated by Framingham algorithms. Results are presented as regression coefficients per 5-year epigenetic age acceleration (IEAA/EEAA) for adiposity, CVD risk factors, and CVD development. RESULTS: In 995 participants (49.6% female; age, 17.3 ± 0.6 years), EEAA (per 5 years) was associated with increased body mass index (BMI) of 2.4% (95% CI, 1.2% to 3.6%) and 2.4% (0.8% to 3.9%) at 17 and 22 years, respectively. EEAA was associated with increases of 23% (3% to 33%) in high-sensitivity C-reactive protein, 10% (4% to 17%) in interferon-γ-inducible protein of 10 kDa, and 4% (2% to 6%) in soluble TNF receptor 2, adjusted for BMI and HOMA-IR. EEAA (per 5 years) results in a 4% increase in hard endpoints of CVD by 47 years of age and a 3% increase, after adjustment for conventional risk factors. CONCLUSIONS: Accelerated epigenetic age in adolescence was associated with inflammation, BMI measured 5 years later, and probability of middle age CVD. Irrespective of whether this is cause or effect, assessing epigenetic age might refine disease prediction.

5.
Int J Obes (Lond) ; 43(5): 974-988, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30622309

RESUMO

BACKGROUND: The early life environment may influence susceptibility to obesity and metabolic disease in later life through epigenetic processes. SLC6A4 is an important mediator of serotonin bioavailability, and has a key role in energy balance. We tested the hypothesis that methylation of the SLC6A4 gene predicts adiposity across the life course. METHODS: DNA methylation at 5 CpGs within the SLC6A4 gene identified from a previous methyl binding domain array was measured by pyrosequencing. We measured DNA methylation in umbilical cord (UC) from children in the Southampton Women's Survey cohort (n = 680), in peripheral blood from adolescents in the Western Australian Pregnancy Cohort Study (n = 812), and in adipose tissue from lean and obese adults from the UK BIOCLAIMS cohort (n = 81). Real-time PCR was performed to assess whether there were corresponding alterations in gene expression in the adipose tissue. RESULTS: Lower UC methylation of CpG5 was associated with higher total fat mass at 4 years (p = 0.031), total fat mass at 6-7 years (p = 0.0001) and % fat mass at 6-7 years (p = 0.004). Lower UC methylation of CpG5 was also associated with higher triceps skinfold thickness at birth (p = 0.013), 6 months (p = 0.038), 12 months (p = 0.062), 2 years (p = 0.0003), 3 years (p = 0.00004) and 6-7 years (p = 0.013). Higher maternal pregnancy weight gain (p = 0.046) and lower parity (p = 0.029) were both associated with lower SLC6A4 CpG5 methylation. In adolescents, lower methylation of CpG5 in peripheral blood was associated with greater concurrent measures of adiposity including BMI (p ≤ 0.001), waist circumference (p = 0.011), subcutaneous fat (p ≤ 0.001) and subscapular, abdominal and suprailiac skinfold thicknesses (p = 0.002, p = 0.008, p = 0.004, respectively). In adipose tissue, methylation of both SLC6A4 CpG5 (p = 0.019) and expression of SLC6A4 (p = 0.008) was lower in obese compared with lean adults. CONCLUSIONS: These data suggest that altered methylation of CpG loci within SLC6A4 may provide a robust marker of adiposity across the life course.

6.
Sleep ; 2018 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-30521022

RESUMO

Objectives: Longitudinal data on the course and relationship of concurrent psychopathology in youth are scarce but are of need for better practical patient care and prevention. This study explores the course of (and relationships over time) between sleep problems and concurrent dimensional difficulties relating to anxiety/depression, attention deficiency and aggressive behaviors in childhood and adolescence. The latter three may jointly form a broad syndrome, the dysregulation profile. Methods: Young people from the Raine Study, a large community cohort-sample (N = 1625) were followed from age 5 to 17 years. Developmental courses of sleep problems and its concurrent regulatory difficulties were estimated separately and jointly. Results: The majority of adolescents reported low levels of problems and which appeared to be stable over time, while a small group (rates between 7.8%-10.1%) reported enduring problematic developmental courses. Sleep problems and regulatory difficulties shared a strong association in their development over time (individual's probabilities of having the same courses, i.e., low-low and high-high, were between 89.8%-92.3%). Furthermore, having persistent sleep problems over time was associated with an increased risk of having regulatory difficulties by approximately 10 times, and vice versa. Conclusion: Findings from this study provide empirical evidence for a strong mutual association in the development of sleep problems and difficulties of dysregulation with emotion, cognition and aggression. It may be suggested that a positive screening of one such psychopathological dimension should lead to a carful assessment, not only to reduce the problem in question but also to prevent the youth from further problems.

7.
PLoS One ; 13(12): e0209355, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30576345

RESUMO

OBJECTIVE: This study aimed to examine the association between age at menarche and a range of cardiovascular disease (CVD) risk factors at 17 and 20 years of age, and whether this was influenced by childhood body mass index (BMI). METHODS: Of the 1413 girls born in the Western Australian Pregnancy Cohort (Raine) Study, 846 had age at menarche recorded. Subsequently 557 underwent metabolic assessment at 17 years and 541 at 20 years. Associations between age at menarche and cardiovascular risk factors, and being in a high-risk metabolic cluster at 17 and 20 years, or having the metabolic syndrome at 20 years, were investigated by linear mixed effects and logistic regressions, respectively. RESULTS: Each year later of onset of menarche was associated with a 0.75 kg/m2 reduction in BMI (coefficient -0.75 [95%CI -1.06, -0.44]), and an approximate 30% reduction in the odds of being in the high-risk metabolic cluster at 17 years (OR = 0.73 [95%CI 0.57, 0.94]) and 20 years of age (OR = 0.68 [95%CI 0.52, 0.87]), and a 40% reduction in the odds of having the metabolic syndrome at 20 years (OR = 0.60 [95% CI 0.41, 0.88]). These data show earlier age at menarche was associated with increased BMI and odds of being in the high-risk metabolic cluster at 17 and 20 years, and increased odds of having the metabolic syndrome at 20 years. However, these associations were no longer statistically significant after adjustment for BMI at age 8 years. Current smoking, alcohol consumption, physical activity, socio-economic status, or hormonal contraceptives use did not affect these associations. CONCLUSIONS: Earlier age at menarche may be indicative of a higher risk profile for CVD in young adulthood. Our findings suggest that targeted interventions to reduce BMI in girls who experience menarche at younger age may reduce CVD risk in the future.


Assuntos
Índice de Massa Corporal , Doenças Cardiovasculares/epidemiologia , Menarca/fisiologia , Síndrome Metabólica/epidemiologia , Adolescente , Adulto , Fatores Etários , Austrália , Peso ao Nascer/fisiologia , Estatura , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/prevenção & controle , Criança , Feminino , Seguimentos , Humanos , Modelos Logísticos , Estudos Longitudinais , Síndrome Metabólica/metabolismo , Síndrome Metabólica/prevenção & controle , Estudos Prospectivos , Fatores de Risco , Adulto Jovem
8.
BMC Med ; 16(1): 201, 2018 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-30396358

RESUMO

BACKGROUND: Gestational weight gain differs according to pre-pregnancy body mass index and is related to the risks of adverse maternal and child health outcomes. Gestational weight gain charts for women in different pre-pregnancy body mass index groups enable identification of women and offspring at risk for adverse health outcomes. We aimed to construct gestational weight gain reference charts for underweight, normal weight, overweight, and grades 1, 2 and 3 obese women and to compare these charts with those obtained in women with uncomplicated term pregnancies. METHODS: We used individual participant data from 218,216 pregnant women participating in 33 cohorts from Europe, North America, and Oceania. Of these women, 9065 (4.2%), 148,697 (68.1%), 42,678 (19.6%), 13,084 (6.0%), 3597 (1.6%), and 1095 (0.5%) were underweight, normal weight, overweight, and grades 1, 2, and 3 obese women, respectively. A total of 138, 517 women from 26 cohorts had pregnancies with no hypertensive or diabetic disorders and with term deliveries of appropriate for gestational age at birth infants. Gestational weight gain charts for underweight, normal weight, overweight, and grade 1, 2, and 3 obese women were derived by the Box-Cox t method using the generalized additive model for location, scale, and shape. RESULTS: We observed that gestational weight gain strongly differed per maternal pre-pregnancy body mass index group. The median (interquartile range) gestational weight gain at 40 weeks was 14.2 kg (11.4-17.4) for underweight women, 14.5 kg (11.5-17.7) for normal weight women, 13.9 kg (10.1-17.9) for overweight women, and 11.2 kg (7.0-15.7), 8.7 kg (4.3-13.4) and 6.3 kg (1.9-11.1) for grades 1, 2, and 3 obese women, respectively. The rate of weight gain was lower in the first half than in the second half of pregnancy. No differences in the patterns of weight gain were observed between cohorts or countries. Similar weight gain patterns were observed in mothers without pregnancy complications. CONCLUSIONS: Gestational weight gain patterns are strongly related to pre-pregnancy body mass index. The derived charts can be used to assess gestational weight gain in etiological research and as a monitoring tool for weight gain during pregnancy in clinical practice.

9.
Pediatrics ; 142(1)2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29884682

RESUMO

BACKGROUND: Omega-3 long-chain polyunsaturated fatty acid (n-3 LCPUFA) supplementation during infancy may reduce adult cardiovascular risk as observed in animals. We assessed the effect of n-3 LCPUFA supplementation in infancy on growth, body composition, and cardiometabolic risk factors at 5 years of age. METHODS: Infants were randomly assigned to a daily supplement of n-3 LCPUFA or olive oil (control) from birth to 6 months (n = 420). Measurements included weight, length, cord blood adipokines at birth and anthropometry, skinfolds, blood pressure, heart rate, fasting blood adipokines, and biochemistry at 5 years. RESULTS: The infants who received n-3 LCPUFA had a smaller waist circumference at 5 years (coefficient: 1.1 cm; 95% confidence interval [CI]: 0.01 to 2.14), which remained significant after adjustments for confounders (coefficient: 0.8 cm; 95% CI: 0.19 to 1.30). Five-year-old boys who received n-3 LCPUFA supplementation as infants had a 21% reduction in insulin concentrations (ratio: 0.79; 95% CI: 0.66 to 0.94) and a 22% reduction in insulin resistance (ratio: 0.78; 95% CI: 0.64 to 0.95) compared with the control group. There were no other differences in growth and cardiometabolic risk factors between the groups for the whole cohort at birth, 2.5, or 5 years. CONCLUSIONS: Supplementation with n-3 LCPUFA in infancy revealed a reduction in waist circumference at 5 years. Boys in the n-3 LCPUFA group showed reduced insulin concentrations and insulin resistance at 5 years, which may have beneficial outcomes for later health. No effects were seen in girls. Longer term follow-up of the cohort is warranted to determine whether these differences are maintained into adolescence.

10.
Brain Behav Immun ; 69: 428-439, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29339318

RESUMO

BACKGROUND: Observational studies suggest that dietary patterns may impact mental health outcomes, although biologically plausible pathways are yet to be tested. We aimed to elucidate the longitudinal relationship between dietary patterns, adiposity, inflammation and mental health including depressive symptoms in a population-based cohort of adolescents. METHODS: Data were provided from 843 adolescents participating in the Western Australian Pregnancy Cohort (Raine) Study at 14 and 17 years (y) of age. Structural equation modelling was applied to test our hypothesised models relating dietary patterns, energy intake and adiposity (body mass index) at 14 y to adiposity and the pro-inflammatory adipokine (leptin) and inflammation (high sensitivity C-reactive protein - hs-CRP) at 17 y, and these inflammatory markers to depressive symptoms (Beck Depression Inventory) and Internalising and Externalising Behavioral Problems (Child Behavior Check List Youth Self- Report) at 17 y. We further tested a reverse hypothesis model, with depression at 14 y as a predictor of dietary patterns at the same time-point. RESULTS: The tested models provided a good fit to the data. A 'Western' dietary pattern (high intake of red meat, takeaway, refined foods, and confectionary) at 14 y was associated with higher energy intake and BMI at 14 y, and with BMI and biomarkers of inflammation at 17 y (all p < .05). A 'Healthy' dietary pattern (high in fruit, vegetables, fish, whole-grains) was inversely associated with BMI and inflammation at 17 y (p < .05). Higher BMI at 14 y was associated with higher BMI (p < .01), leptin (p < .05), hs-CRP (p < .05), depressive symptoms (p < .05) and mental health problems (p < .05), all at 17 y. CONCLUSION: A 'Western' dietary pattern associates with an increased risk of mental health problems including depressive symptoms in adolescents, through biologically plausible pathways of adiposity and inflammation, whereas a 'Healthy' dietary pattern appears protective in these pathways. Longitudinal modelling into adulthood is indicated to confirm the complex associations of dietary patterns, adiposity, inflammation and mental health problems, including depressive symptoms.

12.
Br J Nutr ; 118(11): 971-980, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29173199

RESUMO

Resolution of inflammation is an active process involving specialised pro-resolving mediators (SPM) generated from the n-3 fatty acids EPA and DHA. n-3 Fatty acid supplementation during pregnancy may provide an intervention strategy to modify these novel SPM. This study aimed to assess the effect of n-3 fatty acid supplementation in pregnancy on offspring SPM at birth and 12 years of age (12 years). In all, ninety-eight atopic pregnant women were randomised to 3·7 g daily n-3 fatty acids or a control (olive oil), from 20 weeks gestation until delivery. Blood was collected from the offspring at birth and at 12 years. Plasma SPM consisting of 18-hydroxyeicosapentaenoic acid (18-HEPE), E-series resolvins, 17-hydroxydocosahexaenoic acid (17-HDHA), D-series resolvins, 14-hydroxydocosahexaenoic acid (14-HDHA), 10 S,17S-dihydroxydocosahexaenoic acid, maresins and protectin 1, were measured by liquid chromatography-tandem MS. We identified the resolvins RvE1, RvE2, RvE3, RvD1, 17R-RvD1 and RvD2 for the first time in human cord blood. n-3 Fatty acids increased cord blood 18-HEPE (P<0·001) derived from EPA relative to the control group. DHA-derived 17-HDHA at birth was significantly increased in the n-3 fatty acid group relative to the controls (P=0·001), but other SPM were not different between the groups. n-3 Fatty acid supplementation during pregnancy was associated with an increase in SPM precursors in the offspring at birth but the effects were not sustained at 12 years. The presence of these SPM, particularly at birth, may have functions relevant in the newborn that remain to be established, which may be useful for future investigations.


Assuntos
Suplementos Nutricionais , Ácidos Graxos Ômega-3/administração & dosagem , Ácidos Graxos Ômega-3/sangue , Fenômenos Fisiológicos da Nutrição Pré-Natal , Antígenos CD59/sangue , Criança , Pré-Escolar , Ácidos Docosa-Hexaenoicos/sangue , Método Duplo-Cego , Ácido Eicosapentaenoico/análogos & derivados , Ácido Eicosapentaenoico/sangue , Feminino , Humanos , Lactente , Masculino , Azeite de Oliva/administração & dosagem , Gravidez , Cuidado Pré-Natal
13.
Hum Mol Genet ; 26(20): 4067-4085, 2017 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-29016858

RESUMO

Pre-pregnancy maternal obesity is associated with adverse offspring outcomes at birth and later in life. Individual studies have shown that epigenetic modifications such as DNA methylation could contribute. Within the Pregnancy and Childhood Epigenetics (PACE) Consortium, we meta-analysed the association between pre-pregnancy maternal BMI and methylation at over 450,000 sites in newborn blood DNA, across 19 cohorts (9,340 mother-newborn pairs). We attempted to infer causality by comparing the effects of maternal versus paternal BMI and incorporating genetic variation. In four additional cohorts (1,817 mother-child pairs), we meta-analysed the association between maternal BMI at the start of pregnancy and blood methylation in adolescents. In newborns, maternal BMI was associated with small (<0.2% per BMI unit (1 kg/m2), P < 1.06 × 10-7) methylation variation at 9,044 sites throughout the genome. Adjustment for estimated cell proportions greatly attenuated the number of significant CpGs to 104, including 86 sites common to the unadjusted model. At 72/86 sites, the direction of the association was the same in newborns and adolescents, suggesting persistence of signals. However, we found evidence for acausal intrauterine effect of maternal BMI on newborn methylation at just 8/86 sites. In conclusion, this well-powered analysis identified robust associations between maternal adiposity and variations in newborn blood DNA methylation, but these small effects may be better explained by genetic or lifestyle factors than a causal intrauterine mechanism. This highlights the need for large-scale collaborative approaches and the application of causal inference techniques in epigenetic epidemiology.


Assuntos
Herança Materna/genética , Obesidade/complicações , Resultado da Gravidez/genética , Adulto , Índice de Massa Corporal , Estudos de Coortes , Metilação de DNA/genética , Epigênese Genética/genética , Epigenômica/métodos , Feminino , Humanos , Recém-Nascido , Masculino , Herança Materna/fisiologia , Mães , Gravidez/fisiologia , Resultado da Gravidez/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/genética , Efeitos Tardios da Exposição Pré-Natal/metabolismo
14.
Epigenomics ; 9(8): 1143-1150, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28749184

RESUMO

Excitement about DNA methylation biomarkers has been tempered by a growing appreciation of the complex causal relations with cell fate. Intersample differences in DNA methylation can be partitioned into those that are independent of cellular heterogeneity and those that are caused by differential mixtures of cell types. Generally, the field has assumed that the former are more likely to be causative of disease. The latter has been considered a likely consequence of disease and a confounder to be removed. We argue that the conceptual separation of these signals is artificial and not necessarily informative about causation. DNA methylation is a very sensitive measure of cell fate mix and therefore reveals much about underlying disease etiology including aspects of causation.


Assuntos
Epigênese Genética , Heterogeneidade Genética , Estudo de Associação Genômica Ampla/métodos , Animais , Metilação de DNA , Estudo de Associação Genômica Ampla/normas , Humanos
15.
Am J Clin Nutr ; 106(2): 568-580, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28659295

RESUMO

Background: Growth patterns of breastfed and formula-fed infants may differ, with formula-fed infants growing more rapidly than breastfed infants into childhood and adulthood.Objective: Our objectives were to identify growth patterns and investigate early nutritional programming potential on growth patterns at 6 y and on body composition at 20 y.Design: The West Australian Pregnancy Cohort (Raine) Study and 3 European cohort studies (European Childhood Obesity Trial, Norwegian Human Milk Study, and Prevention of Coeliac Disease) that collaborate in the European Union-funded Early Nutrition project combined, harmonized, and pooled data on full breastfeeding, anthropometry, and body composition. Latent growth mixture modeling was applied to identify growth patterns among the 6708 individual growth trajectories. The association of full breastfeeding for <3 mo compared with ≥3 mo with the identified trajectory classes was assessed by logistic regression. Differences in body composition at 20 y among the identified trajectory classes were tested by analysis of variance.Results: Three body mass index (BMI; in kg/m2) trajectory patterns were identified and labeled as follows-class 1: persistent, accelerating, rapid growth (5%); class 2: early, nonpersistent, rapid growth (40%); and class 3: normative growth (55%). A shorter duration of full breastfeeding for <3 mo was associated with being in rapid-growth class 1 (OR: 2.66; 95% CI: 1.48, 4.79) and class 2 (OR: 1.96; 95% CI: 1.51, 2.55) rather than the normative-growth class 3 after adjustment for covariates. Both rapid-growth classes showed significant associations with body composition at 20 y (P < 0.0001).Conclusions: Full breastfeeding for <3 mo compared with ≥3 mo may be associated with rapid growth in early childhood and body composition in young adulthood. Rapid-growth patterns in early childhood could be a mediating link between infant feeding and long-term obesity risk.


Assuntos
Composição Corporal , Índice de Massa Corporal , Aleitamento Materno , Dieta , Fórmulas Infantis , Leite Humano , Ganho de Peso , Adulto , Austrália , Criança , Pré-Escolar , Estudos de Coortes , Europa (Continente) , Humanos , Lactente , Fenômenos Fisiológicos da Nutrição do Lactente , Recém-Nascido , Modelos Logísticos , Razão de Chances , Obesidade Pediátrica/etiologia , Adulto Jovem
16.
EBioMedicine ; 19: 60-72, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28473239

RESUMO

Experimental studies show a substantial contribution of early life environment to obesity risk through epigenetic processes. We examined inter-individual DNA methylation differences in human birth tissues associated with child's adiposity. We identified a novel association between the level of CpG methylation at birth within the promoter of the long non-coding RNA ANRIL (encoded at CDKN2A) and childhood adiposity at age 6-years. An association between ANRIL methylation and adiposity was also observed in three additional populations; in birth tissues from ethnically diverse neonates, in peripheral blood from adolescents, and in adipose tissue from adults. Additionally, CpG methylation was associated with ANRIL expression in vivo, and CpG mutagenesis in vitro inhibited ANRIL promoter activity. Furthermore, CpG methylation enhanced binding to an Estrogen Response Element within the ANRIL promoter. Our findings demonstrate that perinatal methylation at loci relevant to gene function may be a robust marker of later adiposity, providing substantial support for epigenetic processes in mediating long-term consequences of early life environment on human health.


Assuntos
Adiposidade/genética , Inibidor de Quinase Dependente de Ciclina p18/genética , Regiões Promotoras Genéticas , RNA Longo não Codificante/genética , Adolescente , Adulto , Idoso , Biomarcadores , Linhagem Celular Tumoral , Criança , Ilhas de CpG , Metilação de DNA , Epigênese Genética , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Obesidade/genética , Adulto Jovem
17.
Front Psychol ; 7: 1874, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27990129

RESUMO

Although the prevalence rates of sleep disorders at different stages of childhood and adolescence have been well established, little is known about the developmental course of general sleep problems. This also holds true for the bidirectional relationship between sleep problems and emotional as well as behavioral difficulties. This longitudinal study investigated the general pattern and the latent trajectory classes of general sleep problems from a large community sample aged 5-14 years. In addition, this study examined the predictive value of emotional/behavioral difficulties (i.e., anxiety/depression, attention problems, and aggressive behavior) on sleep problems latent trajectory classes, and vice-versa. Participants (N = 1993) were drawn from a birth cohort of Western Australian children born between 1989 and 1991 who were followed until 14 years of age. Sleep problems were assessed at ages 5, 8, 10, and 14, respectively, whereas anxiety/depression, attention problems, and aggressive behavior were assessed at ages 5 and 17 years. Latent growth curve modeling revealed a decline in an overall pattern of sleep problems during the observed 10-year period. Anxiety/depression was the only baseline factor that predicted the longitudinal course of sleep problems from ages 5 to 14 years, with anxious and depressed participants showing faster decreasing patterns of sleep problems over time than those without anxiety or depression. Growth mixture modeling identified two classes of sleep problem trajectories: Normal Sleepers (89.4%) and Troubled Sleepers (10.6%). Gender was randomly distributed between these groups. Childhood attention problems, aggressive behavior, and the interaction between gender and anxiety/depression were significantly predictive of membership in the group of Troubled Sleepers. Group membership in Troubled Sleepers was associated with higher probability of having attention problems and aggressive behavior in mid-adolescence. Boys and girls with behavioral difficulties, and girls with emotional difficulties were at increased risk of having sleep problems during later childhood and adolescence. Developmental trajectories of sleep problems were also predictive of behavioral difficulties in later life. Findings from this study provide empirical evidence for the heterogeneity of sleep problems and their development, and emphasize the importance of understanding sleep problems and their relationship to children and adolescents' mental health.

19.
Br J Nutr ; 115(11): 1994-2002, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27153206

RESUMO

Evidence associating serum 25-hydroxyvitamin D (25(OH)D) concentrations and cardiometabolic risk factors is inconsistent and studies have largely been conducted in adult populations. We examined the prospective associations between serum 25(OH)D concentrations and cardiometabolic risk factors from adolescence to young adulthood in the West Australian Pregnancy Cohort (Raine) Study. Serum 25(OH)D concentrations, BMI, homoeostasis model assessment for insulin resistance (HOMA-IR), TAG, HDL-cholesterol and systolic blood pressure (SBP) were measured at the 17-year (n 1015) and 20-year (n 1117) follow-ups. Hierarchical linear mixed models with maximum likelihood estimation were used to investigate associations between serum 25(OH)D concentrations and cardiometabolic risk factors, accounting for potential confounders. In males and females, respectively, mean serum 25(OH)D concentrations were 73·6 (sd 28·2) and 75·4 (sd 25·9) nmol/l at 17 years and 70·0 (sd 24·2) and 74·3 (sd 26·2) nmol/l at 20 years. Deseasonalised serum 25(OH)D3 concentrations were inversely associated with BMI (coefficient -0·01; 95 % CI -0·03, -0·003; P=0·014). No change over time was detected in the association for males; for females, the inverse association was stronger at 20 years compared with 17 years. Serum 25(OH)D concentrations were inversely associated with log-HOMA-IR (coefficient -0·002; 95 % CI -0·003, -0·001; P<0·001) and positively associated with log-TAG in females (coefficient 0·002; 95 % CI 0·0008, 0·004; P=0·003). These associations did not vary over time. There were no significant associations between serum 25(OH)D concentrations and HDL-cholesterol or SBP. Clinical trials in those with insufficient vitamin D status may be warranted to determine any beneficial effect of vitamin D supplementation on insulin resistance, while monitoring for any deleterious effect on TAG.


Assuntos
Doenças Cardiovasculares/etiologia , Resistência à Insulina , Deficiência de Vitamina D/complicações , Vitamina D/análogos & derivados , Adolescente , Adulto , Pressão Sanguínea , Índice de Massa Corporal , Doenças Cardiovasculares/sangue , HDL-Colesterol/sangue , Estudos de Coortes , Feminino , Humanos , Masculino , Fatores de Risco , Fatores Sexuais , Triglicerídeos/sangue , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Austrália Ocidental , Adulto Jovem
20.
Nutrients ; 8(3): 175, 2016 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-27007392

RESUMO

DNA telomere shortening associates with the age-related increase cardiovascular disease (CVD) risk. Reducing oxidative stress, could modify telomere erosion during cell replication, and CVD risk in patients with chronic kidney disease (CKD). The effect of n-3 fatty acids and coenzyme Q10 (CoQ) on telomere length was studied in a double-blind placebo-controlled trial in CKD. Eighty-five CKD patients were randomized to: n-3 fatty acids (4 g); CoQ (200 mg); both supplements; or control (4 g olive oil), daily for 8 weeks. Telomere length was measured in neutrophils and peripheral blood mononuclear cells (PBMC) at baseline and 8 weeks, with and without correction for cell counts. Main and interactive effects of n-3 fatty acids and CoQ on telomere length were assessed adjusting for baseline values. F2-isoprostanes were measured as markers of oxidative stress. There was no effect of n-3 fatty acids or CoQ on neutrophil or PBMC telomere length. However, telomere length corrected for neutrophil count was increased after n-3 fatty acids (p = 0.015). Post-intervention plasma F2-isoprostanes were negative predictors of post-intervention telomere length corrected for neutrophil count (p = 0.025).The effect of n-3 fatty acids to increased telomere length corrected for neutrophil count may relate to reduced oxidative stress and increased clearance of neutrophils with shorter telomeres from the circulation. This may be a novel mechanism of modifying CVD risk in CKD patients.


Assuntos
Antioxidantes/uso terapêutico , Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos/uso terapêutico , Ácido Eicosapentaenoico/uso terapêutico , Leucócitos Mononucleares/efeitos dos fármacos , Neutrófilos/efeitos dos fármacos , Insuficiência Renal Crônica/tratamento farmacológico , Homeostase do Telômero/efeitos dos fármacos , Telômero/efeitos dos fármacos , Ubiquinona/análogos & derivados , Adulto , Idoso , Antioxidantes/efeitos adversos , Biomarcadores/sangue , Suplementos Nutricionais/efeitos adversos , Ácidos Docosa-Hexaenoicos/efeitos adversos , Método Duplo-Cego , Combinação de Medicamentos , Ácido Eicosapentaenoico/efeitos adversos , F2-Isoprostanos/sangue , Feminino , Humanos , Leucócitos Mononucleares/metabolismo , Masculino , Pessoa de Meia-Idade , Neutrófilos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/genética , Telômero/metabolismo , Fatores de Tempo , Resultado do Tratamento , Ubiquinona/efeitos adversos , Ubiquinona/uso terapêutico , Austrália Ocidental
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