Epigenetic Alterations and Exposure to Air Pollutants: Protocol for a Birth Cohort Study to Evaluate the Association Between Adverse Birth Outcomes and Global DNA Methylation

Abstract

Background: Prenatal exposure to air pollutants can increase the risk of adverse birth outcomes and susceptibility to a number of complex disorders later in life. Despite this general understanding, the molecular and cellular responses to air pollution exposure during early life are not completely clear.

Objective: The aims of this study are to test the association between air pollution and adverse pregnancy outcomes, and to determine whether the levels of maternal and cord blood and of placental DNA methylation during pregnancy predict adverse birth outcomes in polluted areas.

Methods: This is a birth cohort study. We will enroll pregnant healthy women attending prenatal care clinics in Tehran, Iran, who are resident in selected polluted and unpolluted regions before the 14th week of pregnancy. We will calculate the regional background levels of fine particulate matter (particles with a diameter between 2.5 and 10 μm) and nitrogen dioxide for all regions of by using data from the Tehran Air Quality Control Company. Then, we will select 2 regions as the polluted and unpolluted areas of interest. Healthy mothers living in the selected polluted and non polluted regions will be enrolled in this study. A maternal health history questionnaire will be completed at each trimester. During the first and second trimester, we will draw mothers' blood for biochemical and DNA methylation analyses. At the time of delivery time, we will collect maternal and cord blood for biochemical, gene expression, and DNA methylation analyses. We will also record birth outcomes (the newborn's sex, birth date, birth weight and length, gestational age, Apgar score, and level of neonatal care required).

Results: The project was funded in March 2016 and enrollment will be completed in August 2017. Data analysis is under way, and the first results are expected to be submitted for publication in November 2017.

Conclusions: We supposed that prenatal exposures to air pollutants can influence fetal reprogramming by epigenetic modifications such as DNA methylation. This could explain the association between air pollution and adverse pregnancy outcomes.

Keywords: DNA methylation; adverse birth outcomes; air pollutants; epigenomics; placenta; pregnancy.

Figure 1

Study design. Flow diagram of selection of pregnant women living in polluted and unpolluted regions of Tehran. PM2.5: particulate matter with particle diameter 2.5 μm; PM10: particulate matter with particle diameter 10 μm.