TY - JOUR
T1 - Associations between antibiotic exposure during pregnancy, birth weight and aberrant methylation at imprinted genes among offspring
AU - Vidal, A. C.
AU - Murphy, S. K.
AU - Murtha, A. P.
AU - Schildkraut, J. M.
AU - Soubry, A.
AU - Huang, Z.
AU - Neelon, S. E.B.
AU - Fuemmeler, B.
AU - Iversen, E.
AU - Wang, F.
AU - Kurtzberg, J.
AU - Jirtle, R. L.
AU - Hoyo, C.
N1 - Funding Information:
We are grateful to the participants in the NEST study project, without whom this work would not have been possible. We thank Carole Grenier, Erin Erginer, Allison Barrat and Cara Davis for excellent technical assistance, and Francine Overcash and Stacy Murray for their recruiting efforts. This work was funded by NIH R01-ES016772. The Newborn Epigenetics Study (NEST) was funded through the US National Institutes of Health (agreement no. R01ES016772) and R01CA142983-02S1.
PY - 2013/7
Y1 - 2013/7
N2 - Objectives: Low birth weight (LBW) has been associated with common adult-onset chronic diseases, including obesity, cardiovascular disease, type II diabetes and some cancers. The etiology of LBW is multi-factorial. However, recent evidence suggests exposure to antibiotics may also increase the risk of LBW. The mechanisms underlying this association are unknown, although epigenetic mechanisms are hypothesized. In this study, we evaluated the association between maternal antibiotic use and LBW and examined the potential role of altered DNA methylation that controls growth regulatory imprinted genes in these associations. Methods: Between 2009-2011, 397 pregnant women were enrolled and followed until delivery. Prenatal antibiotic use was ascertained through maternal self-report. Imprinted genes methylation levels were measured at differentially methylated regions (DMRs) using bisulfite pyrosequencing. Generalized linear models were used to examine associations among antibiotic use, birth weight and DMR methylation fractions. Results: After adjusting for infant gender, race/ethnicity, maternal body mass index, delivery route, gestational weight gain, gestational age at delivery, folic acid intake, physical activity, maternal smoking and parity, antibiotic use during pregnancy was associated with 138 g lower birth weight compared with non-antibiotic use (β-coefficient=-132.99, s.e.=50.70, P=0.008). These associations were strongest in newborns of women who reported antibiotic use other than penicillins (β-coefficient=-135.57, s.e.=57.38, P=0.02). Methylation at five DMRs, IGF2 (P=0.05), H19 (P=0.15), PLAGL1 (P=0.01), MEG3 (P=0.006) and PEG3 (P=0.08), was associated with maternal antibiotic use; among these, only methylation at the PLAGL1 DMR was also associated with birth weight. Conclusion: We report an inverse association between in utero exposure to antibiotics and lower infant birth weight and provide the first empirical evidence supporting imprinted gene plasticity in these associations.
AB - Objectives: Low birth weight (LBW) has been associated with common adult-onset chronic diseases, including obesity, cardiovascular disease, type II diabetes and some cancers. The etiology of LBW is multi-factorial. However, recent evidence suggests exposure to antibiotics may also increase the risk of LBW. The mechanisms underlying this association are unknown, although epigenetic mechanisms are hypothesized. In this study, we evaluated the association between maternal antibiotic use and LBW and examined the potential role of altered DNA methylation that controls growth regulatory imprinted genes in these associations. Methods: Between 2009-2011, 397 pregnant women were enrolled and followed until delivery. Prenatal antibiotic use was ascertained through maternal self-report. Imprinted genes methylation levels were measured at differentially methylated regions (DMRs) using bisulfite pyrosequencing. Generalized linear models were used to examine associations among antibiotic use, birth weight and DMR methylation fractions. Results: After adjusting for infant gender, race/ethnicity, maternal body mass index, delivery route, gestational weight gain, gestational age at delivery, folic acid intake, physical activity, maternal smoking and parity, antibiotic use during pregnancy was associated with 138 g lower birth weight compared with non-antibiotic use (β-coefficient=-132.99, s.e.=50.70, P=0.008). These associations were strongest in newborns of women who reported antibiotic use other than penicillins (β-coefficient=-135.57, s.e.=57.38, P=0.02). Methylation at five DMRs, IGF2 (P=0.05), H19 (P=0.15), PLAGL1 (P=0.01), MEG3 (P=0.006) and PEG3 (P=0.08), was associated with maternal antibiotic use; among these, only methylation at the PLAGL1 DMR was also associated with birth weight. Conclusion: We report an inverse association between in utero exposure to antibiotics and lower infant birth weight and provide the first empirical evidence supporting imprinted gene plasticity in these associations.
KW - Antibiotics
KW - Birth weight
KW - Epigenetics
KW - Newborns
KW - Pregnancy
KW - Race
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U2 - 10.1038/ijo.2013.47
DO - 10.1038/ijo.2013.47
M3 - Article
C2 - 23609933
AN - SCOPUS:84880303991
VL - 37
SP - 907
EP - 913
JO - International Journal of Obesity
JF - International Journal of Obesity
SN - 0307-0565
IS - 7
ER -