Epigenetic gestational age and trajectories of weight and height during childhood: a prospective cohort study
Epigenetic gestational age and trajectories of weight and height during childhood: a prospective cohort study
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DOI：
10.1186/s13148-019-0761-7
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发表时间：
2019-12-16
影响因子：
5.7
通讯作者：
O'Keeffe, Linda M.
中科院分区：
文献类型：
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作者：
Bright, Harold D.;Howe, Laura D.;O'Keeffe, Linda M.
背景资料：个体的估计表观遗传胎龄（EGA）与其实际胎龄（GA）之间的差异被定义为胎龄加速（GAA）。GAA与出生体重和出生身长增加有关。这些协会是否持续到童年期还有待investigated.Methods：我们研究了GAA和轨迹的身高和体重从出生到10年（n = 785）在英国出生队列研究，雅芳纵向研究的父母和孩子（ALSPAC）之间的关联。使用最近开发的预测模型，使用来自脐带血的DNA甲基化数据估计参与者的EGA。参与者的GAA（以周为单位测量）计算为EGA对实际GA的回归模型的残差。采用线性样条多水平模型进行分析，并对母亲年龄、母亲孕前BMI、母亲怀孕期间吸烟和母亲受教育程度进行调整。在调整后的分析中，具有一周更大GAA的后代出生时平均重0.14 kg（95%置信区间（CI）0.09，0.19）和出生时高0.55 cm（95% CI 0.33，0.78）。这些体重差异一直持续到大约9个月大，但此后开始减弱。从5岁开始，GAA与体重之间的相关性逆转，使得GAA与较低体重相关，并且这种相关性随着年龄的增加而加强（10岁时的平均差异- 0.60 kg，95% CI - 1.19，- 0.01）。身高差异仅持续至9个月龄（9个月时的平均差异为0.15 cm，95% CI - 0.09，0.39）。从9个月到10岁，一个星期的更大的GAA的后代与那些没有GAA（平均差异在10岁-0.07厘米，95%CI- 0.64，0.50）。结论：孕龄加速与出生体重和长度增加，这些差异持续到9个月大。从5岁开始，GAA和体重的关系逆转，到10岁时，更大的GAA与更低的儿童体重相关。需要进一步的工作来检查GAA的体重影响是否会在青春期和成年早期加强。
Background: 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. Whether these associations persist through childhood is yet to be investigated.Methods: We 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.Results: In 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 9months (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).Conclusions: Gestational 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.