scholarly journals Lifestyle Intervention in Pregnant Women With Obesity Impacts Cord Blood DNA Methylation Which Associates With Body Composition in the Offspring

2021 ◽  
Author(s):  
Josefine Jönsson ◽  
Kristina M. Renault ◽  
Sonia García-Calzón ◽  
Alexander Perfilyev ◽  
Angela C. Estampador ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Body Composition ◽  
Cord Blood ◽  
Pregnant Women ◽  
Lifestyle Intervention ◽  
Lean Mass ◽  
Maternal Obesity ◽  
Standard Of Care ◽  
Dietary Advice ◽  
Lifestyle Interventions

Maternal obesity may lead to epigenetic alterations in the offspring and might thereby contribute to disease later in life. We investigated whether a lifestyle intervention in pregnant women with obesity is associated with epigenetic variation in cord blood and body composition in the offspring.<b> </b>Genome-wide DNA methylation was analyzed in cord blood from 208 offspring from the TOP-study, which includes pregnant women with obesity randomized to lifestyle interventions comprised of physical activity with or without dietary advice versus controls (standard of care). DNA methylation was altered at 379 sites, annotated to 370 genes, in cord blood from offspring of mothers following a lifestyle intervention versus controls (<i>FDR</i><5%) when using the Houseman reference-free method to correct for cell composition and three of these sites were significant based on Bonferroni correction. These 370 genes are overrepresented in gene ontology terms including response to fatty acids and adipose tissue development. Offspring of mothers included in a lifestyle intervention were born with more lean mass compared to controls. Methylation at 17 sites, annotated to e.g. <i>DISC1</i>, <i>GBX2</i>, <i>HERC2</i> and <i>HUWE1</i>, partially mediates the effect of the lifestyle intervention on lean mass in the offspring (FDR<5%). Moreover, 22 methylation sites were associated with offspring BMI z-scores during the first 3 years of life (<i>p</i><0.05). Overall,<b> </b>lifestyle interventions in pregnant women with obesity are associated with epigenetic changes in offspring, potentially influencing the offspring’s lean mass and early growth.

scholarly journals Lifestyle Intervention in Pregnant Women With Obesity Impacts Cord Blood DNA Methylation Which Associates With Body Composition in the Offspring

2021 ◽  
Author(s):  
Josefine Jönsson ◽  
Kristina M. Renault ◽  
Sonia García-Calzón ◽  
Alexander Perfilyev ◽  
Angela C. Estampador ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Body Composition ◽  
Cord Blood ◽  
Pregnant Women ◽  
Lifestyle Intervention ◽  
Lean Mass ◽  
Maternal Obesity ◽  
Standard Of Care ◽  
Dietary Advice ◽  
Lifestyle Interventions

Maternal obesity may lead to epigenetic alterations in the offspring and might thereby contribute to disease later in life. We investigated whether a lifestyle intervention in pregnant women with obesity is associated with epigenetic variation in cord blood and body composition in the offspring.<b> </b>Genome-wide DNA methylation was analyzed in cord blood from 208 offspring from the TOP-study, which includes pregnant women with obesity randomized to lifestyle interventions comprised of physical activity with or without dietary advice versus controls (standard of care). DNA methylation was altered at 379 sites, annotated to 370 genes, in cord blood from offspring of mothers following a lifestyle intervention versus controls (<i>FDR</i><5%) when using the Houseman reference-free method to correct for cell composition and three of these sites were significant based on Bonferroni correction. These 370 genes are overrepresented in gene ontology terms including response to fatty acids and adipose tissue development. Offspring of mothers included in a lifestyle intervention were born with more lean mass compared to controls. Methylation at 17 sites, annotated to e.g. <i>DISC1</i>, <i>GBX2</i>, <i>HERC2</i> and <i>HUWE1</i>, partially mediates the effect of the lifestyle intervention on lean mass in the offspring (FDR<5%). Moreover, 22 methylation sites were associated with offspring BMI z-scores during the first 3 years of life (<i>p</i><0.05). Overall,<b> </b>lifestyle interventions in pregnant women with obesity are associated with epigenetic changes in offspring, potentially influencing the offspring’s lean mass and early growth.

scholarly journals Lifestyle Intervention in Pregnant Women With Obesity Impacts Cord Blood DNA Methylation Which Associates With Body Composition in the Offspring

2021 ◽  
Author(s):  
Josefine Jönsson ◽  
Kristina M. Renault ◽  
Sonia García-Calzón ◽  
Alexander Perfilyev ◽  
Angela C. Estampador ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Body Composition ◽  
Cord Blood ◽  
Pregnant Women ◽  
Lifestyle Intervention ◽  
Lean Mass ◽  
Maternal Obesity ◽  
Standard Of Care ◽  
Dietary Advice ◽  
Lifestyle Interventions

Maternal obesity may lead to epigenetic alterations in the offspring and might thereby contribute to disease later in life. We investigated whether a lifestyle intervention in pregnant women with obesity is associated with epigenetic variation in cord blood and body composition in the offspring.<b> </b>Genome-wide DNA methylation was analyzed in cord blood from 208 offspring from the TOP-study, which includes pregnant women with obesity randomized to lifestyle interventions comprised of physical activity with or without dietary advice versus controls (standard of care). DNA methylation was altered at 379 sites, annotated to 370 genes, in cord blood from offspring of mothers following a lifestyle intervention versus controls (<i>FDR</i><5%) when using the Houseman reference-free method to correct for cell composition and three of these sites were significant based on Bonferroni correction. These 370 genes are overrepresented in gene ontology terms including response to fatty acids and adipose tissue development. Offspring of mothers included in a lifestyle intervention were born with more lean mass compared to controls. Methylation at 17 sites, annotated to e.g. <i>DISC1</i>, <i>GBX2</i>, <i>HERC2</i> and <i>HUWE1</i>, partially mediates the effect of the lifestyle intervention on lean mass in the offspring (FDR<5%). Moreover, 22 methylation sites were associated with offspring BMI z-scores during the first 3 years of life (<i>p</i><0.05). Overall,<b> </b>lifestyle interventions in pregnant women with obesity are associated with epigenetic changes in offspring, potentially influencing the offspring’s lean mass and early growth.

scholarly journals Lifestyle Intervention in Pregnant Women With Obesity Impacts Cord Blood DNA Methylation Which Associates With Body Composition in the Offspring

Diabetes ◽  
2021 ◽  
pp. db200487
Author(s):  
Josefine Jönsson ◽  
Kristina M. Renault ◽  
Sonia García-Calzón ◽  
Alexander Perfilyev ◽  
Angela C. Estampador ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Body Composition ◽  
Cord Blood ◽  
Pregnant Women ◽  
Lifestyle Intervention

scholarly journals Maternal dysglycaemia, changes in the infant’s epigenome modified with a diet and physical activity intervention in pregnancy: Secondary analysis of a randomised control trial

PLoS Medicine ◽  
2020 ◽  
Vol 17 (11) ◽  
pp. e1003229
Author(s):  
Elie Antoun ◽  
Negusse T. Kitaba ◽  
Philip Titcombe ◽  
Kathryn V. Dalrymple ◽  
Emma S. Garratt ◽  
...  
Keyword(s):  
Physical Activity ◽  
Dna Methylation ◽  
Cord Blood ◽  
Pregnant Women ◽  
Lifestyle Intervention ◽  
Standard Care ◽  
Physical Activity Intervention ◽  
Randomised Control Trial ◽  
Oral Glucose ◽  
In Pregnancy

Background Higher maternal plasma glucose (PG) concentrations, even below gestational diabetes mellitus (GDM) thresholds, are associated with adverse offspring outcomes, with DNA methylation proposed as a mediating mechanism. Here, we examined the relationships between maternal dysglycaemia at 24 to 28 weeks’ gestation and DNA methylation in neonates and whether a dietary and physical activity intervention in pregnant women with obesity modified the methylation signatures associated with maternal dysglycaemia. Methods and findings We investigated 557 women, recruited between 2009 and 2014 from the UK Pregnancies Better Eating and Activity Trial (UPBEAT), a randomised controlled trial (RCT), of a lifestyle intervention (low glycaemic index (GI) diet plus physical activity) in pregnant women with obesity (294 contol, 263 intervention). Between 27 and 28 weeks of pregnancy, participants had an oral glucose (75 g) tolerance test (OGTT), and GDM diagnosis was based on diagnostic criteria recommended by the International Association of Diabetes and Pregnancy Study Groups (IADPSG), with 159 women having a diagnosis of GDM. Cord blood DNA samples from the infants were interrogated for genome-wide DNA methylation levels using the Infinium Human MethylationEPIC BeadChip array. Robust regression was carried out, adjusting for maternal age, smoking, parity, ethnicity, neonate sex, and predicted cell-type composition. Maternal GDM, fasting glucose, 1-h, and 2-h glucose concentrations following an OGTT were associated with 242, 1, 592, and 17 differentially methylated cytosine-phosphate-guanine (dmCpG) sites (false discovery rate (FDR) ≤ 0.05), respectively, in the infant’s cord blood DNA. The most significantly GDM-associated CpG was cg03566881 located within the leucine-rich repeat-containing G-protein coupled receptor 6 (LGR6) (FDR = 0.0002). Moreover, we show that the GDM and 1-h glucose-associated methylation signatures in the cord blood of the infant appeared to be attenuated by the dietary and physical activity intervention during pregnancy; in the intervention arm, there were no GDM and two 1-h glucose-associated dmCpGs, whereas in the standard care arm, there were 41 GDM and 160 1-h glucose-associated dmCpGs. A total of 87% of the GDM and 77% of the 1-h glucose-associated dmCpGs had smaller effect sizes in the intervention compared to the standard care arm; the adjusted r2 for the association of LGR6 cg03566881 with GDM was 0.317 (95% confidence interval (CI) 0.012, 0.022) in the standard care and 0.240 (95% CI 0.001, 0.015) in the intervention arm. Limitations included measurement of DNA methylation in cord blood, where the functional significance of such changes are unclear, and because of the strong collinearity between treatment modality and severity of hyperglycaemia, we cannot exclude that treatment-related differences are potential confounders. Conclusions Maternal dysglycaemia was associated with significant changes in the epigenome of the infants. Moreover, we found that the epigenetic impact of a dysglycaemic prenatal maternal environment appeared to be modified by a lifestyle intervention in pregnancy. Further research will be needed to investigate possible medical implications of the findings. Trial registration ISRCTN89971375.

scholarly journals Differential DNA methylation profile in infants born small-for-gestational-age: association with markers of adiposity and insulin resistance from birth to age 24 months

2020 ◽  
Vol 8 (1) ◽  
pp. e001402
Author(s):  
Marta Diaz ◽  
Edurne Garde ◽  
Abel Lopez-Bermejo ◽  
Francis de Zegher ◽  
Lourdes Ibañez
Keyword(s):  
Insulin Resistance ◽  
Dna Methylation ◽  
Body Composition ◽  
Cord Blood ◽  
Gestational Age ◽  
Small For Gestational Age ◽  
Diabetes Risk ◽  
Metabolic Dysfunction ◽  
A Genome ◽  
Methylation Profiling

IntroductionPrenatal growth restraint followed by rapid postnatal weight gain increases lifelong diabetes risk. Epigenetic dysregulation in critical windows could exert long-term effects on metabolism and confer such risk.Research design and methodsWe conducted a genome-wide DNA methylation profiling in peripheral blood from infants born appropriate-for-gestational-age (AGA, n=30) or small-for-gestational-age (SGA, n=21, with postnatal catch-up) at age 12 months, to identify new genes that may predispose to metabolic dysfunction. Candidate genes were validated by bisulfite pyrosequencing in the entire cohort. All infants were followed since birth; cord blood methylation profiling was previously reported. Endocrine-metabolic variables and body composition (dual-energy X-ray absorptiometry) were assessed at birth and at 12 and 24 months.ResultsGPR120 (cg14582356, cg01272400, cg23654127, cg03629447), NKX6.1 (cg22598426, cg07688460, cg17444738, cg12076463, cg10457539), CPT1A (cg14073497, cg00941258, cg12778395) and IGFBP 4 (cg15471812) genes were hypermethylated (GPR120, NKX6.1 were also hypermethylated in cord blood), whereas CHGA (cg13332653, cg15480367, cg05700406), FABP5 (cg00696973, cg10563714, cg16128701), CTRP1 (cg19231170, cg19472078, cg0164309, cg07162665, cg17758081, cg18996910, cg06709009), GAS6 (N/A), ONECUT1 (cg14217069, cg02061705, cg26158897, cg06657050, cg15446043) and SLC2A8 (cg20758474, cg19021975, cg11312566, cg12281690, cg04016166, cg03804985) genes were hypomethylated in SGA infants. These genes were related to β-cell development and function, inflammation, and glucose and lipid metabolism and associated with body mass index, body composition, and markers of insulin resistance at 12 and 24 months.ConclusionIn conclusion, at 12 months, abnormal methylation of GPR120 and NKX6.1 persists and new epigenetic marks further involved in adipogenesis and energy homeostasis arise in SGA infants. These abnormalities may contribute to metabolic dysfunction and diabetes risk later in life.

scholarly journals Cord Metabolic Profiles in Obese Pregnant Women: Insights Into Offspring Growth and Body Composition

2017 ◽  
Vol 103 (1) ◽  
pp. 346-355 ◽  
Author(s):  
Nashita Patel ◽  
Christian Hellmuth ◽  
Olaf Uhl ◽  
Keith Godfrey ◽  
Annette Briley ◽  
...  
Keyword(s):  
Cord Blood ◽  
Lifestyle Intervention ◽  
Metabolic Profile ◽  
Maternal Obesity ◽  
Physical Activity Intervention ◽  
Controlled Trial ◽  
In Utero ◽  
Obese Women ◽  
Blood Concentrations ◽  
Increased Risk

Abstract Context Offspring exposed in utero to maternal obesity have an increased risk of later obesity; however, the underlying mechanisms remain unknown. Objective To assess the effect of an antenatal lifestyle intervention in obese women on the offspring’s cord blood metabolic profile and to examine associations of the cord blood metabolic profile with maternal clinical characteristics and offspring anthropometry at birth and age 6 months. Design Randomized controlled trial and cohort study. Setting The UK Pregnancies Better Eating and Activity Trial. Participants Three hundred forty-four mother-offspring pairs. Intervention Antenatal behavioral lifestyle (diet and physical activity) intervention. Main Outcome Measures Targeted cord blood metabolic profile, including candidate hormone and metabolomic analyses. Results The lifestyle intervention was not associated with change in the cord blood metabolic profile. Higher maternal glycemia, specifically fasting glucose at 28 weeks gestation, had a linear association with higher cord blood concentrations of lysophosphatidylcholines (LPCs) 16.1 (β = 0.65; 95% confidence interval: 0.03 to 0.10) and 18.1 (0.52; 0.02 to 0.80), independent of the lifestyle intervention. A principal component of cord blood phosphatidylcholines and LPCs was associated with infant z scores of birth weight (0.04; 0.02 to 0.07) and weight at age 6 months (0.05; 0.00 to 0.10). Cord blood insulin growth factor (IGF)-1 and adiponectin concentrations were positively associated with infant weight z score at birth and at 6 months. Conclusions Concentrations of LPCs and IGF-1 in cord blood are related to infant weight. These findings support the hypothesis that susceptibility to childhood obesity may be programmed in utero, but further investigation is required to establish whether these associations are causally related.

scholarly journals Association of Methylation-Related Nutrient Intake and Status with Offspring DNA Methylation in Pregnant Women with and Without Gestational Diabetes Mellitus

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1016-1016
Author(s):  
Xinyin Jiang ◽  
Chauntelle Jack-Roberts ◽  
Kaydine Edwards ◽  
Ella Gilboa ◽  
Ikhtiyor Djuraev ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Dna Methylation ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Cord Blood ◽  
Pregnant Women ◽  
Nutrient Intake ◽  
Blood Levels ◽  
Global Dna Methylation ◽  
Blood Samples

Abstract Objectives Gestational diabetes mellitus (GDM) is associated with alterations in DNA methylation in the placenta and offspring tissues. Nutrients participating in the methionine cycle (e.g., choline, betaine, folate, vitamin B12, methionine) influence the supply of methyl groups. The objective of this research was to determine whether maternal intake and status of these nutrients during pregnancy may interact with the GDM status to shape the offspring epigenome. Methods We conducted 3-day dietary recalls and collected blood samples from pregnant women with and without GDM (n = 22/group) to quantify methylation-related nutrient intakes and status. At delivery, we collected cord blood samples and measured global DNA methylation. Results GDM was associated with a 25% increase (P = 0.041) in global DNA methylation in the cord blood. Maternal choline intake (r = −0.602, P = 0.006) as well as cord blood methionine (r = −0.553, P = 0.014) and betaine (r = −0.566, P = 0.011) levels were negatively correlated with cord blood DNA methylation only in non-GDM women, while intakes and maternal blood levels of other methylation-related nutrients were not related to cord blood DNA methylation. Conclusions GDM and methyl nutrient intake/status interact to modify offspring DNA methylation in humans. Funding Sources Egg Nutrition Center.

scholarly journals Dietary interventions to improve body composition in men treated with androgen deprivation therapy for prostate cancer: a solution for the growing problem?

2021 ◽  
Author(s):  
Lisa Umlauff ◽  
Manuel Weber ◽  
Nils Freitag ◽  
Ciaran M. Fairman ◽  
Axel Heidenreich ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Body Composition ◽  
Androgen Deprivation Therapy ◽  
Fat Mass ◽  
Lean Mass ◽  
Muscle Wasting ◽  
Meta Analysis ◽  
Androgen Deprivation ◽  
Dietary Advice ◽  
Dietary Interventions

Abstract Background Androgen deprivation therapy (ADT) has adverse effects on body composition, including muscle wasting and body fat accumulation, which may be attenuated by nutrition therapy. This systematic review summarises available evidence on the effects of dietary interventions on lean mass, fat mass and body mass index (BMI) in men treated with ADT for prostate cancer. Methods MEDLINE, Embase, Web of Science and ClinicalTrials.org were searched from inception through December 2020. We included all controlled trials evaluating effects of supplementation or dietary interventions on body composition in men with prostate cancer receiving continuous ADT. Methodological quality of the studies was assessed using the Cochrane Collaboration’s risk of bias tool. Meta-analysis was performed using a random effects model to calculate standardised mean differences between intervention and comparator groups. (PROSPERO; CRD42020185777). Results Eleven studies (n = 536 participants) were included. Seven studies investigated the effects of dietary advice interventions, e.g. individual or group counselling, and four studies included a nutritional supplement. Eight studies combined the dietary intervention with exercise. Nine studies reported sufficient data for inclusion in the meta-analysis. Dietary advice and supplementation interventions combined were not associated with significant changes in lean mass (0.05 kg; 95% CI: −0.17, 0.26; p = 0.674; n = 355), fat mass (−0.22 kg; 95% CI: −0.45, 0.01; p = 0.064; n = 336) or BMI (−0.16 kg*m−2; 95% CI: −0.37, 0.04; p = 0.121; n = 399). Dietary advice interventions alone were associated with a significant fat mass reduction (−0.29 kg; 95% CI: −0.54, −0.03; p = 0.028; n = 266). Conclusions Most studies were dietary advice interventions targeting caloric restriction, which showed the potential to reduce fat mass but did not increase lean mass in men treated with ADT. Future interventions should investigate whether a combination of dietary advice and protein supplementation with concomitant resistance exercise could counteract ADT-induced muscle wasting.

Treatment of maternal hyperthyroidism with antithyroid agents and changes in thyrotrophin and thyroxine in the newborn

1981 ◽  
Vol 97 (2) ◽  
pp. 186-195 ◽  
Author(s):  
B.-A. Lamberg ◽  
E. Ikonen ◽  
K. Teramo ◽  
G. Wägar ◽  
K. Österlund ◽  
...  
Keyword(s):  
Laboratory Test ◽  
Cord Blood ◽  
Pregnant Women ◽  
Newborn Infants ◽  
Antithyroid Drug ◽  
Clinical Indication ◽  
Antithyroid Drugs ◽  
Serum Thyroxine ◽  
Antithyroid Agents ◽  
Serum Tsh

Abstract. Eleven pregnant women with concomitant hyperthyroidism were treated with antithyroid drugs. At monthly intervals serum thyroxine (T4) and triiodothyronine (T3) were measured with radioimmunoassay, the Sephadex uptake of radioactive triiodothyronine (T3U) determined and the free T4 and T3 indices calculated (FT4I, FT3I). TSH-binding inhibiting immunoglobulins (TBII) were determined by the radiomembrane assay. Serum TSH and T4 were measured at delivery from cord blood and/or from the newborn infants some days after birth. Serum TSH was significantly elevated in one infant. There was an inadequate post-partal rise in serum T4 concentration in this child and in another who showed only a marginal elevation of TSH. The mothers of these infants were given carbimazole in doses of 30 and 25 mg/day, respectively, at the time of delivery. No significant changes were seen in other infants, the daily doses being 20 mg of carbimazole or less. There was no clinical indication of hypo- or hyperthyroidism in any of the newborn. The TBII were positive in most patients and there was a trend of normalization during treatment. No relationship between the dose of antithyroid drug and the level of TBII could be seen. During treatment the dose was adjusted according to the FT3I values. This seems to be an adequate laboratory test for this purpose.

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