Abstract

Inorganic arsenic (iAs) is an established transplacental agent known to affect fetal development in animal studies. However, iAs has not been adequately studied in the general population with respect to iAs exposure during pregnancy and its impact on the health status of newborns. The aims of this study were to 1) elucidate the association between arsenic exposure and oxidative/methylated DNA damage in pregnant women, and 2) determine the association with birth outcomes. A birth cohort study of 299 pregnant mother-newborn pairs was recruited during 2001–2002 in Taiwan. We collected maternal urine samples during the 3rd trimester for measuring iAs and its metabolites. We used high-performance liquid chromatography/inductively coupled plasma mass spectrometry (HPLC-ICP-MS) for quantifications of the arsenic species. Liquid chromatography/tandem mass spectrometer (LC-MS/MS) was used to measure the 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) and N7-methylguanosine (N7-MeG) DNA damage biomarkers. Birth outcomes were collected to assess the associations with maternal arsenic exposure and the DNA damage biomarkers. Multiple regression analyses showed that maternal urinary iAs had positive associations with the methylated N7-MeG (beta = 0.35, p<0.001) and oxidative 8-oxodG (beta = 0.24, p<0.001) DNA damage biomarkers, and a decreased one-minute (1-min) Apgar score (beta = -0.23, p = 0.041). Maternal N7-MeG was also associated with a decreased 1-min Apgar score (beta = −0.25, p = 0.042). Mutual adjustment for iAs and N7-MeG showed an independent and significant prediction for a decreased 1-min Apgar score of iAs (beta = −0.28, p = 0.036). Maternal iAs exposure was associated with both maternal DNA damage and adverse newborn health. Maternal N7-MeG levels might be a novel biomarker for monitoring fetal health related to iAs.

Highlights

  • Health status at birth is an important determinant of morbidity and mortality in early childhood [1] and of chronic disease in adulthood [2]

  • Disrupted placentation [13] and endocrine disturbance [14] have been reported for arsenic-related adverse pregnancy outcomes

  • We found decreased Apgar score was associated prenatal arsenic exposure, and the maternal methylated DNA damage as the biomarker in a general population from central Taiwan

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Summary

Introduction

Health status at birth is an important determinant of morbidity and mortality in early childhood [1] and of chronic disease in adulthood [2]. Birth weight is reflective of maternal health status, and predictive of the probability for newborn survival, development, and long-term health [3]. The Apgar score is a routine for evaluating the physical condition of the newborn, including heart rate, respiratory effort, muscle tone, reflex irritability, and skin color shortly after delivery. A score $7 indicates that the condition of the newborn is good-to-excellent [4]. Newborns with low birth weight (LBW) or low Apgar scores often develop various negative health consequences. Long-term effects of LBW include increased risk of cardiovascular disease, type 2 diabetes mellitus, and impaired reproductive function [5]. Arsenic is a well-known toxicant and carcinogen, and increasing evidence indicates that arsenic may adversely affect pregnancy outcomes and development of the newborn

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