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Associations of long interspersed nuclear element-1 DNA methylation with preterm birth in a prospective cohort study

Published online by Cambridge University Press:  29 February 2012

H. H. Burris*
Affiliation:
Department of Neonatology, Beth Israel Deaconess Medical Center, Division of Newborn Medicine, Children's Hospital Boston, Harvard Medical School, Boston, MA, USA
S. L. Rifas-Shiman
Affiliation:
Obesity Prevention Program, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA
A. Baccarelli
Affiliation:
Department of Environmental Health, Harvard School of Public Health, Boston, MA, USA
L. Tarantini
Affiliation:
Department of Preventive Medicine and Department of Environmental and Occupational Health, University of Milan and IRCCS Maggiore Hospital, Mangiagalli and Regina Elena Foundation, Milan, Italy
C. E. Boeke
Affiliation:
Department of Nutrition, Harvard School of Public Health, Boston, MA, USA Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA
K. Kleinman
Affiliation:
Obesity Prevention Program, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA
A. A. Litonjua
Affiliation:
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard School of Public Health, Boston, MA, USA Division of Pulmonary and Critical Care, Brigham and Women's Hospital, Boston, MA, USA
J. W. Rich-Edwards
Affiliation:
Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA Women's Health, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
M. W. Gillman
Affiliation:
Obesity Prevention Program, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA Department of Nutrition, Harvard School of Public Health, Boston, MA, USA
*
*Address for correspondence: H. H. Burris, Department of Neonatology, Beth Israel Deaconess Medical Center, Division of Newborn Medicine, Children's Hospital Boston, Harvard Medical School, Boston, MA, USA (Email [email protected])

Abstract

Preterm birth affects over 12% of all infants born in the United States; yet the biology of early delivery remains unclear, including whether epigenetic mechanisms are involved. We examined associations of maternal and umbilical cord blood long interspersed nuclear element-1 (LINE-1) DNA methylation with length of gestation and odds of preterm birth in singleton pregnancies in Project Viva. In white blood cells from maternal blood during first trimester (n = 914) and second trimester (n = 922), and from venous cord blood at delivery (n = 557), we measured LINE-1 by pyrosequencing [expressed as %5 methyl cytosines within the LINE-1 region analyzed (%5mC)]. We ran linear regression models to analyze differences in gestation length, and logistic models for odds of preterm birth (<37 v. ⩾37 weeks’ gestation), across quartiles of LINE-1. Mean (s.d.) LINE-1 levels were 84.3 (0.6), 84.5 (0.4) and 84.6 (0.7) %5mC for first trimester, second trimester and cord blood, respectively. Mean (s.d.) gestational age was 39.5 (1.8) weeks, and 6.5% of infants were born preterm. After adjustment for maternal age, race/ethnicity, body mass index, education, smoking status and fetal sex, women with the highest v. lowest quartile of first trimester LINE-1 had longer gestations [0.45 weeks (95% CI 0.12, 0.78)] and lower odds of preterm birth [OR 0.40 (0.17, 0.94)], whereas associations with cord blood LINE-1 were in the opposite direction (−0.45 weeks, −0.83, −0.08) and [OR 4.55 (1.18, 17.5)]. In conclusion, higher early pregnancy LINE-1 predicts lower risk of preterm birth. In contrast, preterm birth is associated with lower LINE-1 in cord blood.

Type
Original Article
Copyright
Copyright © Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2012

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