Associations between prenatal physical activity, birth weight, and DNA methylation at genomically imprinted domains in a multiethnic newborn cohort.
Birth weight is a commonly used indicator of the fetal environment and a predictor of future health outcomes. While the etiology of birth weight extremes is likely multifactorial, epidemiologic data suggest that prenatal physical activity (PA) may play an important role. The mechanisms underlying this association remain unresolved, although epigenetics has been proposed. This study aimed to estimate associations between prenatal PA, birth weight, and newborn DNA methylation levels at differentially methylated regions (DMRs) regulating 4 imprinted genes known to be important in fetal development. Study participants (N = 1281) were enrolled as part of the Newborn Epigenetics Study. Prenatal PA was ascertained using the Pregnancy Physical Activity Questionnaire, and birth weight data obtained from hospital records. Among 484 term mother-infant pairs, imprinted gene methylation levels were measured at DMRs using bisulfite pyrosequencing. Generalized linear and logistic regression models were used to estimate associations. After adjusting for preterm birth and race/ethnicity, we found that infants born to mothers in the highest quartile of total non-sedentary time had lower birth weight compared to infants of mothers in the lowest quartile (β = -81.16, SE = 42.02, P = 0.05). These associations appeared strongest among male infants (β = -125.40, SE = 58.10, P = 0.03). Methylation at the PLAGL1 DMR was related to total non-sedentary time (P < 0.05). Our findings confirm that prenatal PA is associated with reduced birth weight, and is the first study to support a role for imprinted gene plasticity in these associations. Larger studies are required.
a Department of Epidemiology; University of North Carolina Chapel Hill ; Chapel Hill , NC , USA.
Lauren E
LE
McCullough
Michelle A
MA
Mendez
Erline E
EE
Miller
Amy P
AP
Murtha
Susan K
SK
Murphy
Cathrine
C
Hoyo
D000293:Adolescent; D001724:Birth Weight / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics; D015331:Cohort Studies; D019175:DNA Methylation; D005260:Female; D056726:Genetic Association Studies; D018392:Genomic Imprinting; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009043:Motor Activity / Q000235:genetics*; D011247:Pregnancy; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000235:genetics; D055815:Young Adult
D018797:Cell Cycle Proteins; C106464:PLAGL1 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins
BMI, body mass index; BW, birth weight; DMR, differentially methylated regions; DOHaD, developmental origins of health and disease; HIV, human immunodeficiency virus; IGF, insulin-like growth factor; LBW, low birth weight; LMP, last menstrual period; MET, metabolic equivalent; NEST, Newborn Epigenetic Study; PA, physical activity; SE, standard error.; birth weight; epidemiology; epigenetics; imprinted genes; methylation; physical activity