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1.
Epigenomics ; 12(17): 1483-1499, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32901515

RESUMO

Aim: We conducted a methylome-wide association study to examine associations between DNA methylation in whole blood and central adiposity and body fat distribution, measured as waist circumference, waist-to-hip ratio and waist-to-height ratio adjusted for body mass index, in 2684 African-American adults in the Atherosclerosis Risk in Communities study. Materials & methods: We validated significantly associated cytosine-phosphate-guanine methylation sites (CpGs) among adults using the Women's Health Initiative and Framingham Heart Study participants (combined n = 5743) and generalized associations in adolescents from The Raine Study (n = 820). Results & conclusion: We identified 11 CpGs that were robustly associated with one or more central adiposity trait in adults and two in adolescents, including CpG site associations near TXNIP, ADCY7, SREBF1 and RAP1GAP2 that had not previously been associated with obesity-related traits.

2.
Environ Health Perspect ; 128(9): 97003, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32930613

RESUMO

BACKGROUND: Fetal exposure to maternal smoking during pregnancy is associated with the development of noncommunicable diseases in the offspring. Maternal smoking may induce such long-term effects through persistent changes in the DNA methylome, which therefore hold the potential to be used as a biomarker of this early life exposure. With declining costs for measuring DNA methylation, we aimed to develop a DNA methylation score that can be used on adolescent DNA methylation data and thereby generate a score for in utero cigarette smoke exposure. METHODS: We used machine learning methods to create a score reflecting exposure to maternal smoking during pregnancy. This score is based on peripheral blood measurements of DNA methylation (Illumina's Infinium HumanMethylation450K BeadChip). The score was developed and tested in the Raine Study with data from 995 white 17-y-old participants using 10-fold cross-validation. The score was further tested and validated in independent data from the Northern Finland Birth Cohort 1986 (NFBC1986) (16-y-olds) and 1966 (NFBC1966) (31-y-olds). Further, three previously proposed DNA methylation scores were applied for comparison. The final score was developed with 204 CpGs using elastic net regression. RESULTS: Sensitivity and specificity values for the best performing previously developed classifier ("Reese Score") were 88% and 72% for Raine, 87% and 61% for NFBC1986 and 72% and 70% for NFBC1966, respectively; corresponding figures using the elastic net regression approach were 91% and 76% (Raine), 87% and 75% (NFBC1986), and 72% and 78% for NFBC1966. CONCLUSION: We have developed a DNA methylation score for exposure to maternal smoking during pregnancy, outperforming the three previously developed scores. One possible application of the current score could be for model adjustment purposes or to assess its association with distal health outcomes where part of the effect can be attributed to maternal smoking. Further, it may provide a biomarker for fetal exposure to maternal smoking. https://doi.org/10.1289/EHP6076.

3.
J Endocr Soc ; 4(8): bvaa061, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32803089

RESUMO

Context: Adolescents with polycystic ovary syndrome (PCOS) have increased incidence of cardiometabolic risk factors including dyslipidemia. Atherogenic apolipoprotein (apo) B-lipoprotein remnants are associated with increased cardiovascular disease (CVD) risk. Objective: The aim of this study was to determine the concentrations of fasting plasma apoB-lipoprotein remnants, apoB48 and apoB100, and their association with cardiometabolic risk factors and androgen indices in adolescent girls with and without PCOS. Design setting and participants: Participants (n = 184) aged 17 years were recruited in the Menstruation in Teenagers Study from the Western Australian Pregnancy Cohort (Raine) Study. The main outcome measures: Fasting plasma apo-B48 and -B100 lipoprotein remnant concentrations in adolescent girls with and without PCOS. Results: Fasting plasma apoB48-lipoprotein remnants but not apoB100-lipoprotein remnants were elevated in adolescent girls with increased cardiometabolic risk compared with those with lower cardiometabolic risk (13.91 ± 5.06 vs 12.09 ± 4.47 µg/mL, P < .01). ApoB48-lipoprotein remnants were positively correlated with fasting plasma triglycerides (b = .43, P < .0001). The prevalence of increased cardiometabolic risk factors was 2-fold higher in those diagnosed with PCOS (35.3%) than in those without PCOS (16.3%).Conclusion: Adolescents with PCOS have a 2-fold higher incidence of cardiometabolic risk factors than those without PCOS. Fasting apoB48-lipoprotein remnants are elevated in adolescent girls with a high prevalence of cardiometabolic risk factors.

4.
Eur J Epidemiol ; 35(7): 709-724, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32705500

RESUMO

Early life is an important window of opportunity to improve health across the full lifecycle. An accumulating body of evidence suggests that exposure to adverse stressors during early life leads to developmental adaptations, which subsequently affect disease risk in later life. Also, geographical, socio-economic, and ethnic differences are related to health inequalities from early life onwards. To address these important public health challenges, many European pregnancy and childhood cohorts have been established over the last 30 years. The enormous wealth of data of these cohorts has led to important new biological insights and important impact for health from early life onwards. The impact of these cohorts and their data could be further increased by combining data from different cohorts. Combining data will lead to the possibility of identifying smaller effect estimates, and the opportunity to better identify risk groups and risk factors leading to disease across the lifecycle across countries. Also, it enables research on better causal understanding and modelling of life course health trajectories. The EU Child Cohort Network, established by the Horizon2020-funded LifeCycle Project, brings together nineteen pregnancy and childhood cohorts, together including more than 250,000 children and their parents. A large set of variables has been harmonised and standardized across these cohorts. The harmonized data are kept within each institution and can be accessed by external researchers through a shared federated data analysis platform using the R-based platform DataSHIELD, which takes relevant national and international data regulations into account. The EU Child Cohort Network has an open character. All protocols for data harmonization and setting up the data analysis platform are available online. The EU Child Cohort Network creates great opportunities for researchers to use data from different cohorts, during and beyond the LifeCycle Project duration. It also provides a novel model for collaborative research in large research infrastructures with individual-level data. The LifeCycle Project will translate results from research using the EU Child Cohort Network into recommendations for targeted prevention strategies to improve health trajectories for current and future generations by optimizing their earliest phases of life.

5.
Atherosclerosis ; 302: 20-26, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32413793

RESUMO

BACKGROUND AND AIMS: Cardiovascular disease (CVD) begins in youth, and is exacerbated by obesity and metabolic syndrome. Apolipoprotein (Apo)B-remnant cholesterol is considered a primary contributor to CVD risk. Fasting plasma apoB48 can be used as a biomarker of intestinal remnant cholesterol as well as postprandial dyslipidemia. In adults, elevated fasting plasma apoB48 strongly associates with cardiometabolic risk factors and obesity, whereas in adolescents there is limited data. The aim of this study was to measure fasting plasma apoB48 and determine the relationship with cardiometabolic risk factors in adolescents. METHODS: This is a cross-sectional study of fasting plasma apoB48 from the Western Australian Pregnancy Cohort (Raine) Study. Subjects were adolescent males and females aged 17 years with complete fasting plasma apoB48, biochemical, and anthropometry data (n = 1045). The relationship between fasting plasma apoB48 and other cardiometabolic risk factors was determined. The high-risk metabolic cluster variable was defined using elevated BMI, HOMA-IR, fasting plasma triglycerides, and systolic blood pressure. RESULTS: Fasting plasma apoB48 was significantly higher in male (15.28 ± 2.95 µg/mL) compared to female (12.45 ± 2.43 µg/mL) adolescents (p = 0.0003), and was increased by 21% (3.60 µg/mL; p = 0.0000) in the high-risk metabolic cluster group and more pronounced in males (31%, 6.15 µg/mL; p = 0.0000). Fasting plasma apoB48 was positively associated with fasting plasma triglycerides, total-cholesterol (but not LDL-C), insulin, leptin, HOMA-IR, and the anthropometric parameters, waist-circumference and skinfold-thickness. Fasting plasma apoB48 was inversely associated with fasting plasma HDL-C, and adiponectin. CONCLUSIONS: Plasma apoB48 remnant lipoproteins associate with cardiometabolic risk factors in adolescents and provide support for the screening of remnant cholesterol in youth.

6.
J Med Internet Res ; 22(6): e17845, 2020 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-32442153

RESUMO

BACKGROUND: Early excess and inadequate gestational weight gain (GWG) have been associated with negative outcomes for mother and child. The use of digital media to deliver pregnancy lifestyle interventions is increasing, but there is little data on participant engagement. The Pregnancy Lifestyle Activity and Nutrition (PLAN) intervention pilot study was an electronic health and dietetic-delivered intervention program promoting healthy GWG in early pregnancy. OBJECTIVE: This study aims to explore the interactions of participants with the program and to assess its acceptability. METHODS: This study uses both quantitative and qualitative methods using data from parent randomized controlled trial (ACTRN12617000725369). Quantitative data from 22 participants in the intervention arm who completed the study provided measures of the interactions participants had with the digital components of the program and with dietetic consultations. A descriptive qualitative analysis employed semistructured interviews with 9 participants to elicit views on the acceptability of the intervention and its components. RESULTS: The electronic delivery of information and recording of weight from 8 to 20 weeks of gestation were universally accepted. Component (face-to-face dietitian, weight tracker, website information delivery, and SMS goal prompting) acceptability and engagement differed between individuals. A total of 4 key themes emerged from the qualitative analysis: supporting lifestyle change, component acceptability and value, delivery platforms, and engagement barriers. CONCLUSIONS: The PLAN intervention and its delivery via a blend of personal dietetic consultations and digital program delivery was found to be acceptable and valuable to pregnant women. Individuals responded differently to various components, emphasizing the importance of including women in the development of lifestyle interventions and allowing participants to choose and tailor programs. Larger randomized controlled trials using these insights in a broader section of the community are needed to inform the iterative development of practical, time-efficient, and cost-effective ways of supporting optimal GWG with the potential to optimize outcomes for pregnant women and their child.

7.
Sleep ; 2020 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-32280974

RESUMO

Sleep disorders in adults are associated with adverse health effects including reduced quality of life and increased mortality. However, there is little information on sleep disorders in young adults. A cross-sectional observational study was undertaken in 1,227 young adults participating in the Western Australian Pregnancy (Raine) Study (2012-2014) to describe the prevalence of common sleep disorders. In-laboratory polysomnography (PSG) and validated survey methods were used, including the Epworth Sleepiness Scale, Pittsburgh Sleep Symptom Questionnaire-Insomnia and International Restless Legs Syndrome Study Group criteria. 1,146 participants completed a core questionnaire, 1,051 completed a sleep-focused questionnaire and 935 had analysable PSG data. Participants had a mean age of 22.2 years and female to male ratio of 1.1 to 1. The respective sleep disorder prevalences in females and males were: obstructive sleep apnea (OSA) [apnea hypopnea index (AHI): ≥5events/hour] 14.9% (95%CI:11.8-18.5) and 26.9% (95%CI:22.9-31.2), chronic insomnia, 19.3% (95%CI:16.7-23.9) and 10.6% (95%CI:8.3-13.9); restless legs syndrome , 3.8% (95%CI:2.4-5.6) and 1.9% (95%CI:0.9-3.4); and abnormal periodic leg movements during sleep (>5movements/hour), 8.6% (95%CI:6.3-11.5) and 9.6% (95%CI:7.1-12.7). There were statistically significant differences in prevalence between sexes for OSA and insomnia, which persisted after adjustment for body mass index and education. In those with complete data on all sleep-related assessments (n=836), at least one sleep disorder was present in 41.0% of females and 42.3% of males. Sleep disorders are very common in young adults. Health practitioners should be aware of these high prevalences, as early identification and treatment can improve quality of life and may reduce later morbidity and mortality.

8.
J Dev Orig Health Dis ; 11(1): 58-70, 2020 Feb.
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.

9.
Nutrients ; 11(12)2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31816850

RESUMO

High sugar-sweetened beverage (SSB) consumption has been linked with obesity. The present study examined the associations between adolescent SSB intake and body mass index (BMI), waist circumference (WC), and overweight status in early adulthood, and modelled the association of alternative beverage substitution with BMI and WC. Data of offspring from the Western Australian Pregnancy Cohort (Raine) Study at ages 14 and 22 years were used (n = 667). SSB intake at 14 years (100 g/day) was associated with higher BMI (ß = 0.19 kg/m2, 95% CI 0.04, 0.33), WC (ß = 0.41cm, 95% CI 0.04, 0.78), and being overweight at 22 years (OR 1.10, 95% CI 1.02, 1.18). Every 100g modelled substitution of SSB with milk at age 14 years was associated with lower BMI (-0.19 kg/m2) and WC (-0.52 cm) at age 22 years. Replacement of SSB with diet drink was associated with higher BMI and WC. No association was found for substitutions of SSB with water, tea/coffee, or 100% fruit juice with BMI or WC. SSB intake during adolescence was associated with higher BMI, WC, and being overweight in early adulthood. Milk as an alternative to SSB was associated with less adiposity. Caution is necessary in recommending diet drinks as a SSB alternative.

10.
Front Genet ; 10: 770, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31616461

RESUMO

Background: Several studies have shown effects of current and maternal smoking during pregnancy on DNA methylation of CpG sites in newborns and later in life. Here, we hypothesized that there are long-term and persistent epigenetic effects following maternal smoking during pregnancy on adolescent offspring DNA methylation, independent of paternal and postnatal smoke exposure. Furthermore, we explored the association between DNA methylation and cardiometabolic risk factors at 17 years of age. Materials and Methods: DNA methylation was measured using the Illumina HumanMethylation450K BeadChip in whole blood from 995 participants attending the 17-year follow-up of the Raine Study. Linear mixed effects models were used to identify differential methylated CpGs, adjusting for parental smoking during pregnancy, and paternal, passive, and adolescent smoke exposure. Additional models examined the association between DNA methylation and paternal, adolescent, and passive smoking over the life course. Offspring CpGs identified were analyzed against cardiometabolic risk factors (blood pressure, triacylglycerols (TG), high-density lipoproteins cholesterol (HDL-C), and body mass index). Results: We identified 23 CpGs (genome-wide p level: 1.06 × 10-7) that were associated with maternal smoking during pregnancy, including associated genes AHRR (cancer development), FTO (obesity), CNTNAP2 (developmental processes), CYP1A1 (detoxification), MYO1G (cell signalling), and FRMD4A (nicotine dependence). A sensitivity analysis showed a dose-dependent relationship between maternal smoking and offspring methylation. These results changed little following adjustment for paternal, passive, or offspring smoking, and there were no CpGs identified that associated with these variables. Two of the 23 identified CpGs [cg00253568 (FTO) and cg00213123 (CYP1A1)] were associated with either TG (male and female), diastolic blood pressure (female only), or HDL-C (male only), after Bonferroni correction. Discussion: This study demonstrates a critical timing of cigarette smoke exposure over the life course for establishing persistent changes in DNA methylation into adolescence in a dose-dependent manner. There were significant associations between offspring CpG methylation and adolescent cardiovascular risk factors, namely, TG, HDL-C, and diastolic blood pressure. Future studies on current smoking habits and DNA methylation should consider the importance of maternal smoking during pregnancy and explore how the persistent DNA methylation effects of in utero smoke exposure increase cardiometabolic risk.

11.
Front Genet ; 10: 816, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31552104

RESUMO

Background: Association studies of epigenome-wide DNA methylation and disease can inform biological mechanisms. DNA methylation is often measured in peripheral blood, with heterogeneous cell types with different methylation profiles. Influences such as adiposity-associated inflammation can change cell-type proportions, altering measured blood methylation levels. To determine whether associations between loci-specific methylation and outcomes result from cellular heterogeneity, many studies adjust for estimated blood cell proportions, but high correlations between methylation and cell-type proportions could violate the statistical assumption of no multicollinearity. We examined these assumptions in a population-based study. Methods: CDKN2A promoter CpG methylation was measured in peripheral blood from 812 adolescents aged 17 years (Western Australian Pregnancy Cohort Study). Loge adolescent BMI was used as the outcome in a regression analysis with DNA methylation as predictor, adjusting for age/sex. Further regression analyses additionally adjusted for estimated cell-type proportions using the reference-based Houseman method, and simulations modeled the effects of varying levels of correlation between cell proportions and methylation. Correlations between estimated cell proportions and CpG methylation from Illumina 450K were measured. Results: Lower DNA methylation was associated with higher BMI when cell-type adjustment was not included; for CpG4, ß = -0.004 logeBMI/%methylation (95% CI -0.0065, -0.001; p = 0.003). The direction of association reversed when adjustment for six cell types was made; for CpG4, ß = 0.004 logeBMI/%methylation (-0.0002, 0.0089; p = 0.06). Correlations between CpG methylation and cell-type proportions were high, and variance inflation factors (VIFs) were extremely high (25 to 113.7). Granulocyte count was correlated with BMI, and removing granulocytes from the regression model reduced all VIFs to <3.1, with persistence of a positive association between methylation and BMI [CpG4 ß = 0.004 logeBMI/%methylation (-0.0002, 0.0088; p = 0.06)]. Simulations supported major effects of multicollinearity on regression results. Conclusions: Where cell types are highly correlated with other covariates in regression models, the statistical assumption of no multicollinearity may be violated. This can result in reversal of direction of association, particularly when examining associations with phenotypes related to inflammation, as CpG methylation may associate with changes in cell-type proportions. Removing predictors with high correlations from regression models may remove the multicollinearity. However, this might hinder biological interpretability.

12.
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
13.
J Clin Endocrinol Metab ; 104(7): 3012-3024, 2019 07 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.

14.
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
15.
Int J Obes (Lond) ; 43(5): 974-988, 2019 05.
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.


Assuntos
Adiposidade/genética , Metilação de DNA/fisiologia , Epigênese Genética/fisiologia , Doenças Metabólicas/genética , Obesidade/genética , Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismo , Absorciometria de Fóton , Adolescente , Adulto , Austrália/epidemiologia , Biomarcadores/metabolismo , Criança , Pré-Escolar , Estudos de Coortes , Metilação de DNA/genética , Feminino , Interação Gene-Ambiente , Predisposição Genética para Doença , Humanos , Recém-Nascido , Masculino , Doenças Metabólicas/epidemiologia , Obesidade/epidemiologia , Regiões Promotoras Genéticas/genética
16.
Sleep ; 42(3)2019 03 01.
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% and 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% and 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 careful assessment, not only to reduce the problem in question but also to prevent the youth from further problems.


Assuntos
Comportamento Problema/psicologia , Transtornos do Sono-Vigília/fisiopatologia , Transtornos do Sono-Vigília/psicologia , Adolescente , Agressão/psicologia , Criança , Pré-Escolar , Estudos de Coortes , Depressão/psicologia , Emoções/fisiologia , Feminino , Humanos , Masculino , Psicopatologia , Fatores de Risco
17.
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
18.
BMC Med ; 16(1): 201, 2018 11 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.


Assuntos
Índice de Massa Corporal , Ganho de Peso na Gestação/fisiologia , Adulto , Europa (Continente) , Feminino , Humanos , América do Norte , Oceania , Gravidez , Complicações na Gravidez , Resultado da Gravidez , Fatores de Risco
19.
Pediatrics ; 142(1)2018 07.
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.


Assuntos
Desenvolvimento Infantil/fisiologia , Suplementos Nutricionais/estatística & dados numéricos , Ácidos Graxos Ômega-3/administração & dosagem , Adipocinas/sangue , Antropometria/métodos , Pressão Sanguínea/fisiologia , Composição Corporal/fisiologia , Doenças Cardiovasculares/etiologia , Feminino , Seguimentos , Frequência Cardíaca/fisiologia , Humanos , Lactente , Recém-Nascido , Insulina/sangue , Resistência à Insulina/fisiologia , Masculino , Fatores de Risco
20.
Brain Behav Immun ; 69: 428-439, 2018 03.
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.


Assuntos
Índice de Massa Corporal , Transtorno Depressivo/psicologia , Dieta/psicologia , Inflamação/psicologia , Transtornos Mentais/psicologia , Saúde Mental , Adolescente , Austrália , Feminino , Humanos , Masculino , Modelos Teóricos
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