The epigenetics of maternal cigarette smoking during pregnancy and effects on child development

Abstract

The period of in utero development is one of the most critical windows during which adverse intrauterine conditions and exposures can influence the growth and development of the fetus as well as the child's future postnatal health and behavior. Maternal cigarette smoking during pregnancy remains a relatively common but nonetheless hazardous in utero exposure. Previous studies have associated prenatal smoke exposure with reduced birth weight, poor developmental and psychological outcomes, and increased risk for diseases and behavioral disorders later in life. Researchers are now learning that many of the mechanisms whereby maternal smoke exposure may affect key pathways crucial for proper fetal growth and development are epigenetic in nature. Maternal cigarette smoking during pregnancy has been associated with altered DNA methylation and dysregulated expression of microRNA, but a deeper understanding of the epigenetics of maternal cigarette smoking during pregnancy as well as how these epigenetic changes may affect later health and behavior remain to be elucidated. This article seeks to explore many of the previously described epigenetic alterations associated with maternal cigarette smoking during pregnancy and assess how such changes may have consequences for both fetal growth and development, as well as later child health, behavior, and well-being. We also outline future directions for this new and exciting field of research.

Figure 1. in utero Stimuli-Associated Epigenetic Alterations and Maternal Forecasts

in utero stimuli comprise the plethora of exposures that may characterize the intrauterine environment – exposure to nutrients, stress, and drugs. A largely positive and healthy intrauterine environment may result in the mother imparting a rich maternal forecast on her developing fetus, predicting a rich post-birth environment where resources are predicted to be plentiful and negative exposures at a minimum level. A relatively negative or adverse intrauterine environment may result in the mother imparting a poor maternal forecast, often characterized by a “thrifty phenotype”, on her developing fetus, thereby preparing her child to survive in a poor post-birth environment where resources are predicted to be scarce and/or negative exposures (e.g., secondhand smoke exposure) to be frequent and abundant. Maternal forecasts which do not accurately predict the post-birth environment have been hypothesized to lead to negative consequences for the health of the child over its life course – such as increased risk for metabolic diseases in offspring born into a rich environment with a poor maternal forecast. in utero stimuli may influence maternal forecasting through epigenetic mechanisms, both directly and indirectly. These epigenetic-mediated maternal forecasts may be accessible to measurement through techniques established for measuring changes to epigenetic modes of regulation. Additionally, these epigenetic marks, such as DNA methylation profiles or miRNA expression, may have utility as diagnostic biomarkers capable of predicting increased risk for diseases or disease progression but also as therapeutic targets. Scientific artwork by Jennifer Z. Joukhadar.