Dataset Information

Association of Periconception Paternal Body Mass Index With Persistent Changes in DNA Methylation of Offspring in Childhood.

ABSTRACT: Importance:While prenatal nutrition and maternal obesity are recognized as important contributors to epigenetic changes and childhood obesity, the role of paternal obesity in the epigenome of offspring has not been well studied. Objectives:To test whether periconception paternal body mass index (BMI) is associated with DNA methylation patterns in newborns, to examine associations between maternal and paternal BMI and the epigenome of offspring, and to examine persistence of epigenetic marks at ages 3 and 7 years. Design, Setting, and Participants:Project Viva is a prebirth cohort study of mothers and children including 2128 live births that enrolled mothers from April 1999 to July 2002 and followed offspring to adolescence. This study analyzed the subset of participants with available data on paternal BMI and DNA methylation in offspring blood in the newborn period, at age 3 years, and at age 7 years. Data were analyzed from July 2017 to October 2019. Exposures:The primary exposure was paternal periconception BMI; associations were adjusted for maternal prepregnancy BMI and stratified according to maternal BMI above or below 25. Main Outcomes and Measures:The primary outcome was genome-wide DNA methylation patterns in offspring blood collected at birth, age 3 years, and age 7 years. Results:A total of 429 father-mother-infant triads were included. The mean (SD) periconception paternal BMI was 26.4 (4.0) and mean maternal prepregnancy BMI was 24.5 (5.2); 268 fathers had BMI greater than or equal to 25 (mean [SD], 28.5 [3.3]) and 161 had BMI less than 25 (mean [SD], 22.8 [1.8]). Paternal BMI greater than or equal to 25 was associated with increased offspring birth weight compared with paternal BMI less than 25 (mean [SD] z score, 0.38 [0.91] vs 0.11 [0.96]; P?=?.004). Cord blood DNA methylation at 9 CpG sites was associated with paternal BMI independent of maternal BMI (q?

SUBMITTER: Noor N

PROVIDER: S-EPMC6991200 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Association of Periconception Paternal Body Mass Index With Persistent Changes in DNA Methylation of Offspring in Childhood.

Noor Nudrat N Cardenas Andres A Rifas-Shiman Sheryl L SL Pan Hui H Dreyfuss Jonathan M JM Oken Emily E Hivert Marie-France MF James-Todd Tamarra T Patti Mary-Elizabeth ME Isganaitis Elvira E

JAMA network open 20191202 12

<h4>Importance</h4>While prenatal nutrition and maternal obesity are recognized as important contributors to epigenetic changes and childhood obesity, the role of paternal obesity in the epigenome of offspring has not been well studied.<h4>Objectives</h4>To test whether periconception paternal body mass index (BMI) is associated with DNA methylation patterns in newborns, to examine associations between maternal and paternal BMI and the epigenome of offspring, and to examine persistence of epigen ...[more]

PMID: 31880793

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Project description:Excessive early childhood adiposity is a prevalent and increasing concern in many parts of the world. Parental obesity is one of the several factors previously associated with infant and early childhood weight, length and adiposity. Parental obesity represents a surrogate marker of the complex interplay among genetic, epigenetic and shared environmental factors, and is potentially modifiable. The relative contributions of maternal and paternal body mass index (BMI) to infant and early childhood growth, as well as the timing of such effects, have not been firmly established.Utilizing serial infant measurements and growth curve modelling, this is the largest study to fully characterize and formally compare associations between maternal and paternal BMI and offspring growth across the entire infancy and early childhood period. Maternal obesity is a stronger determinant of offspring BMI than paternal obesity at birth and from 2 to 3 years of age, suggesting that prevention efforts focused particularly on maternal lifestyle and BMI may be important in reducing excess infant BMI. The observation that maternal BMI effects are not constant, but rather present at birth, wane and re-emerge during late infancy, suggests that there is a window of opportunity in early infancy when targeted interventions on children of obese mothers may be most effective.Parental obesity influences infant body size. To fully characterize their relative effects on infant adiposity, associations between maternal and paternal body mass index (BMI) category (normal: ?25?kg?m(-2) , overweight: 25?- <30?kg?m(-2) , obese: ?30?kg?m(-2) ) and infant BMI were compared in Fels Longitudinal Study participants.A median of 9 serial weight and length measures from birth to 3.5 years were obtained from 912 European American children born in 1928-2008. Using multivariable mixed effects regression, contributions of maternal vs. paternal BMI status to infant BMI growth curves were evaluated. Cubic spline models also included parental covariates, infant sex, age and birth variables, and interactions with child's age.Infant BMI curves were significantly different across the three maternal BMI categories (Poverall ?<?0.0001), and offspring of obese mothers had greater mean BMI at birth and between 1.5 and 3.5 years than those of over- and normal weight mothers (P???0.02). Average differences between offspring of obese and normal weight mothers were similar at birth (0.8?kg?m(-2) , P?=?0.0009) and between 2 and 3.5 years (0.7-0.8?kg?m(-2) , P?<?0.0001). Infants of obese fathers also had BMI growth curves distinct from those of normal weight fathers (P?=?0.02). Infant BMI was more strongly associated with maternal than paternal obesity overall (P?<?0.0001); significant differences were observed at birth (1.11?kg?m(-2) , P?=?0.006) and from 2 to 3 years (0.62?kg?m(-2) , P3 years ?=?0.02).At birth and in later infancy, maternal BMI has a stronger influence on BMI growth than paternal BMI, suggesting weight control in reproductive age women may be of particular benefit for preventing excess infant BMI.

Project description:ImportanceThe incidence of ischemic stroke among young adults is rising and is potentially due to an increase in stroke risk factors occurring at younger ages, such as obesity.ObjectivesTo investigate whether childhood body mass index (BMI) and change in BMI are associated with adult ischemic stroke and to assess whether the associations are age dependent or influenced by birth weight.Design, setting, and participantsThis investigation was a population-based cohort study of schoolchildren born from 1930 to 1987, with follow-up through national health registers from 1977 to 2012 in Denmark. Participants were 307?677 individuals (8899 ischemic stroke cases) with measured weight and height at ages 7 to 13 years. The dates of the analysis were September 1, 2015, to May 27, 2016.Main outcomes and measuresChildhood BMI, change in BMI, and birth weight. Ischemic stroke events were divided into early (?55 years) or late (>55 years) age at diagnosis.ResultsThe study cohort comprised 307?677 participants (approximately 49% female and 51% male). During the study period, 3529 women and 5370 men experienced an ischemic stroke. At all ages from 7 to 13 years, an above-average BMI z score was positively associated with early ischemic stroke. At age 13 years, a BMI z score of 1 was associated with hazard ratios (HRs) of 1.26 (95% CI, 1.11-1.43) in women and 1.21 (95% CI, 1.10-1.33) in men. No significant associations were found for below-average BMI z scores. Among children with above-average BMI z scores at age 7 years, a score increase of 0.5 from ages 7 to 13 years was positively associated with early ischemic stroke in women (HR, 1.10; 95% CI, 1.01-1.20) and in men (HR, 1.08; 95% CI, 1.00-1.16). Similarly, among children with below-average BMI z scores at age 7 years, a score increase of 0.5 from ages 7 to 13 years was positively associated with early ischemic stroke in women (HR, 1.14; 95% CI, 1.06-1.23) and in men (HR, 1.10; 95% CI, 1.04-1.18). Adjusting for birth weight minimally affected the associations.Conclusions and relevanceIndependent of birth weight, above-average childhood BMI and increases in BMI during childhood are positively associated with early adult ischemic stroke. To avoid the occurrence of early ischemic stroke associated with childhood overweight and obesity, these results suggest that all children should be helped to attain and maintain healthy weights.

Project description:BackgroundLittle is known about whether associations between childhood adiposity and later adverse cardiovascular health outcomes are driven by tracking of overweight from childhood to adulthood and/or by vascular and metabolic changes from childhood overweight that persist into adulthood. Our objective is to characterise associations between trajectories of adiposity across childhood and a wide range of cardiovascular risk factors measured in adolescence, and explore the extent to which these are mediated by fat mass at age 15.Methods and findingsUsing data from the Avon Longitudinal Study of Parents and Children, we estimated individual trajectories of ponderal index (PI) from 0-2 years and BMI from 2-10 years using random-effects linear spline models (N?=?4601). We explored associations between PI/BMI trajectories and DXA-determined total-body fat-mass and cardiovascular risk factors at 15 years (systolic and diastolic blood pressure, fasting LDL- and HDL-cholesterol, triglycerides, C-reactive protein, glucose, insulin) with and without adjustment for confounders. Changes in PI/BMI during all periods of infancy and childhood were associated with greater DXA-determined fat-mass at age 15. BMI changes in childhood, but not PI changes from 0-2 years, were associated with most cardiovascular risk factors in adolescence; associations tended to be strongest for BMI changes in later childhood (ages 8.5-10), and were largely mediated by fat mass at age 15.ConclusionChanges in PI/BMI from 0-10 years were associated with greater fat-mass at age 15. Greater increases in BMI from age 8.5-10 years are most strongly associated with cardiovascular risk factors at age 15, with much of these associations mediated by fat-mass at this age. We found little evidence supporting previous reports that rapid PI changes in infancy are associated with future cardiovascular risk. This study suggests that associations between early overweight and subsequent adverse cardiovascular health are largely due to overweight children tending to remain overweight.

Dataset Information

Association of Periconception Paternal Body Mass Index With Persistent Changes in DNA Methylation of Offspring in Childhood.

Publications

Association of Periconception Paternal Body Mass Index With Persistent Changes in DNA Methylation of Offspring in Childhood.

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