Abstract
Low birthweight, premature birth, intrauterine growth retardation, and maternal malnutrition have been related to an increased risk of cardiovascular disease, type 2 diabetes mellitus, obesity, and neuropsychiatric disorders later in life. Conversely, high birthweight has been linked to future risk of cancer. Global DNA methylation estimated by the methylation of repetitive sequences in the genome is an indicator of susceptibility to chronic diseases. We used data and biospecimens from an epigenetic birth cohort to explore the association between trajectories of fetal and maternal weight and LINE-1 methylation in 319 mother-child dyads. Newborns with low or high birthweight had significantly lower LINE-1 methylation levels in their cord blood compared to normal weight infants after adjusting for gestational age, sex of the child, maternal age at delivery, and maternal smoking during pregnancy (p = 0.007 and p = 0.036, respectively), but the magnitude of the difference was small. Infants born prematurely also had lower LINE-1 methylation levels in cord blood compared to term infants, and this difference, though small, was statistically significant (p = 0.004). We did not find important associations between maternal prepregnancy BMI or gestational weight gain and global methylation of the cord blood or fetal placental tissue. In conclusion, we found significant differences in cord blood LINE-1 methylation among newborns with low and high birthweight as well as among prematurely born infants. Future studies may elucidate whether chromosomal instabilities or other functional consequences of these changes contribute to the increased risk of chronic diseases among individuals with these characteristics.
Highlights
The Developmental Origins of Health and Disease (DOHaD) suggest lifelong health implications of fetal and maternal growth trajectories
Newborns with low or high birthweight had significantly lower LINE-1 methylation levels of their cord blood DNA compared to normal weight infants after adjusting for gestational age, maternal age at delivery, maternal smoking prior to or during pregnancy, ethnicity of the mother, and sex of the child, but the magnitude of the difference was small (Table 2)
Infants born prematurely had lower LINE-1 methylation levels of cord blood DNA compared to term infant, and this difference, though small, was statistically significant (p = 0.004)
Summary
The Developmental Origins of Health and Disease (DOHaD) suggest lifelong health implications of fetal and maternal growth trajectories. Premature birth, maternal underweight and/or malnutrition, and intrauterine growth retardation (IUGR) have been related to an increased risk of hypertension, cardiovascular disease, type 2 diabetes mellitus, obesity and neuropsychiatric disorders later in life [1,2,3,4,5,6]. High birthweight, maternal obesity, high weight gain during pregnancy, and gestational diabetes have been linked to future risk of cancer, obesity, and type 2 diabetes in the offspring [7,8]. The mechanisms underlying these associations are poorly understood. It has recently been suggested that epigenetic mechanisms may be important contributors to fetal programming [9,10]
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