Abstract
BackgroundDifferences between an individual’s estimated epigenetic gestational age (EGA) and their actual gestational age (GA) are defined as gestational age acceleration (GAA). GAA is associated with increased birthweight and birth length. Whether these associations persist through childhood is yet to be investigated.MethodsWe examined the association between GAA and trajectories of height and weight from birth to 10 years (n = 785) in a British birth cohort study, the Avon Longitudinal Study of Parents and Children (ALSPAC). EGA of participants was estimated using DNA methylation data from cord blood using a recently developed prediction model. GAA of participants, measured in weeks, was calculated as the residuals from a regression model of EGA on actual GA. Analyses were performed using linear spline multilevel models and adjusted for maternal age, maternal pre-pregnancy BMI, maternal smoking during pregnancy, and maternal education.ResultsIn adjusted analyses, offspring with a one-week greater GAA were born on average 0.14 kg heavier (95% confidence interval (CI) 0.09, 0.19) and 0.55 cm taller (95% CI 0.33, 0.78) at birth. These differences in weight persisted up to approximately age 9 months but thereafter began to attenuate. From age 5 years onwards, the association between GAA and weight reversed such that GAA was associated with lower weight and this association strengthened with age (mean difference at age 10 years − 0.60 kg, 95% CI − 1.19, − 0.01). Differences in height persisted only up to age 9 months (mean difference at 9 months 0.15 cm, 95% CI − 0.09, 0.39). From age 9 months to age 10 years, offspring with a one-week greater GAA were of comparable height with those with no GAA (mean difference at age 10 years − 0.07 cm, 95% CI − 0.64, 0.50).ConclusionsGestational age acceleration is associated with increased birth weight and length and these differences persist to age 9 months. From age 5 years onwards, the association of GAA and weight reverses such that by age 10 years, greater GAA is associated with lower childhood weight. Further work is required to examine whether the weight effects of GAA strengthen through adolescence and into early adulthood.
Highlights
Differences between an individual’s estimated epigenetic gestational age (EGA) and their actual gestational age (GA) are defined as gestational age acceleration (GAA)
We examine the association between GAA and trajectories of weight and height from birth to age 10 years, using data derived from the Accessible Resource for Integrated Epigenomic Studies (ARIES) project, a substudy of 1018 mother-offspring pairs from the Avon Longitudinal Study of Parents and Children (ALSPAC)
Mothers of offspring included in the analysis (n = 785) were likely to be older, be married, have attained a higher level of education, and were less to likely to smoke during pregnancy relative to the rest of the ALSPAC study population excluded due to missing data on exposure, outcome, or confounders (n = 13,446) (Additional file 1: Table S2)
Summary
Differences between an individual’s estimated epigenetic gestational age (EGA) and their actual gestational age (GA) are defined as gestational age acceleration (GAA). GAA is associated with increased birthweight and birth length. DNA methylation (DNAm) is one type of epigenetic mechanism involving methylation of the cytosine nucleotide at cytosine-phosphate-guanine (CpG) dinucleotide sites [1]. Environmental exposures such as tobacco smoking [2] and alcohol consumption [3] are associated with altered patterns of DNAm. DNAm levels change with age across some CpG sites. Differences between an individual’s epigenetic age and their chronological age are defined as age acceleration (AA). Positive AA (i.e. having a higher epigenetic than chronological age) is generally associated with a variety of adverse health outcomes including obesity [6], Alzheimer’s disease [7], cancer [8], lower physical and cognitive fitness [9], and all-cause mortality [9]
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