Journal Article

Associations between antibiotic exposure during pregnancy, birth weight and aberrant methylation at imprinted genes among offspring

Vidal, A C, Jirtle, R L, Murphy, S K, Huang, Z, Wang, F, Hoyo, C, Iversen, E, Soubry, A, Kurtzberg, J, Schildkraut, J M, Neelon, S E B, Fuemmeler, B, Murtha, A P

2013

Overview

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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/337/176/1988 / 631/92/436 / 692/700/1720 / Adult / Analysis / Anti-Bacterial Agents - adverse effects / Antibiotics / Babies / Biological and medical sciences / Birth Weight / Birth weight, Low / Births / Cancer / Cardiovascular diseases / Cardiovascular Diseases - genetics / Cell Cycle Proteins - genetics / Deoxyribonucleic acid / Diabetes / DNA / DNA methylation / DNA Methylation - genetics / Epidemiology / Epigenesis, Genetic / Epigenetics / Etiology / Exposure / Female / Fetal Development - genetics / Folic acid / Generalized linear models / Genes / Genomic Imprinting / Gestational age / Gynecology / Health Promotion and Disease Prevention / Humans / Infant, Low Birth Weight / Infant, Newborn / Infants / Insulin-Like Growth Factor II - genetics / Intercellular Signaling Peptides and Proteins - genetics / Internal Medicine / Kruppel-Like Transcription Factors - genetics / Medical sciences / Medicine / Medicine & Public Health / Membrane Proteins - genetics / Metabolic Diseases / Neoplasms - genetics / Nerve Tissue Proteins - genetics / Newborn babies / Obesity / Obesity - genetics / Obstetrics / Offspring / Oncology / Pediatric Original / pediatric-original-article / Plasticity / Pregnancy / Prenatal drug exposure / Prenatal Exposure Delayed Effects - epidemiology / Prenatal Exposure Delayed Effects - genetics / Prospective Studies / Proteins - genetics / Public Health / RNA, Long Noncoding - genetics / Sarcoglycans - genetics / Sequence Analysis, DNA / Transcription Factors - genetics / Tumor Suppressor Proteins - genetics / United States - epidemiology / Womens health