DNA Methylation and Preterm Birth Among African Americans

Purpose: The purpose of this study is to provide a comprehensive review on DNA methylation and preterm birth with a focus on health disparities and studies done in minority populations. Preterm birth is the leading contributor to infant mortality in the US (Martin, Hamilton, Osterman, Curtin, & Matthews, 2015) with a complex and multifactorial etiology. The care of infants born preterm is costly, over 26 million dollars annually (March of Dimes, 2013). Infants born preterm (<37 weeks gestation) or who experience stressors in utero such as maternal hypertension, pre-eclampsia or restricted growth have significant sequelae throughout life (Platt, 2014). African American women are disproportionately affected by adverse pregnancy outcomes, and have higher rates of preterm birth (16%) than Caucasian women (11%) (Martin et al., 2015). Despite knowledge of several demographic (race, socioeconomic status, age), biomedical (infection, hypertension, multiple gestation, prior preterm birth) and environmental risk factors (substance use, stress, poor access to health care) for preterm birth and other adverse pregnancy outcomes, researchers have been unable to fully understand the causal mechanisms or how to prevent them (Burris, Baccarelli, Wright, & Wright, 2015). The science of epigenomics first identified how both genetics and environmental factors interact to affect fetal programming (stressors experienced in utero) and influence phenotype (variation in coat color) with early studies of the agouti mouse (Wolff, Kodell, Moore, & Cooney, 1998). Epigenomics is a promising field of study to understand the modulating factors that may lend itself to understanding and reducing preterm birth, yet there is a paucity of research in this area (Parets, Bedient, Menon, & Smith, 2014).

Methods: We conducted a systematic review of the literature to critically examine the research on preterm birth utilizing DNA methylation. Search terms included DNA methylation, preterm birth, birthweight, gestational age, pregnancy, women and complications. Resulting articles and relevant references from those articles were reviewed. After discarding non-relevant studies, a total of 23 articles were found, and 10 studies included African Americans and were included in the final review.

Results: The existing studies in this area were limited by small sample sizes, cross-sectional study designs, inconsistent methodologies for epigenomic analysis, and choice of tissue samples. Less than half of studies reviewed included African Americans, and in most studies, they comprised less than half of the study sample. Despite these limitations, there was a consistent positive relationship between DNA methylation and gestational age, term birth and fetal growth. 

Conclusion: Few studies have examined the association between epigenomics and preterm birth among African Americans, who are at high risk for this adverse outcome. Future research should be longitudinal in design, have increased participation of African American mother-child dyads for adequate power and examine DNA methylation over time, including baseline (pre-pregnancy), during pregnancy (minimally at least once per trimester), and post-partum measurements. Identification and use of clear definitions of preterm birth is important, as well as having a clear explanation of methodology for genomic analysis.  Rationale for tissue sample selection should also be considered as this burgeoning field of scientific inquiry will require extensive study replication. This path of inquiry has the potential to provide important information to identify women who are at risk for preterm birth and other adverse pregnancy outcomes, and to aid in the reduction of health disparities. Once these mechanisms are better understood, we will be better informed to guide the research agenda for reduction of health disparities, with the ultimate goal of providing information for nurses in the clinical setting on how to better care for vulnerable members of our communities and to prevent adverse pregnancy and birth outcomes. This presentation is relevant to the planned Genomics Symposium for the July 2016 STTI meeting and would add to it significantly by reviewing the literature, identifying gaps in the research, and making recommendations for future study.