New research indicates that environmental factors during the periconceptional stages of pregnancy (pre-conception to early months of carrying) are associated with neurodevelopmental outcomes in offspring. Specifically, children born to mothers who adhered to a Mediterranean diet rich in fresh vegetables, whole grains, healthy fats, nuts, legumes and dairy, along with decreased red meat consumption, were found to exhibit more favorable behaviors in the second year of life. Utilizing data based on more than 300 mother/child pairs, the goals of the study were to determine if, and to what extent, a mother’s dietary patterns around the time of conception affected her child’s epigenetics and behavior.
Epigenetics, the study of DNA alterations that affect the reading and regulation of DNA, but not the sequence itself, has seen tremendous growth in recent years. Dr. John House, an NC State scientist within both the the Bioinformatics Research Center (BRC) and the Center for Human Health and the Environment (CHHE), led the research efforts. He stated that, “10 years ago, we thought a person’s inherited genetic variation would be the largest determinant of human disease susceptibility in complex diseases. We’ve since realized that epigenetic differences play just as large or a larger role than genetics in explaining both disease susceptibility and the relationship between environmental exposures and human disease. ”
The NEST cohort was started by Dr. Cathrine Hoyo of NC State’s Center for Human Health and the Environment (CHHE) and has yielded over 55 publications to date linking maternal exposures to offspring outcomes and epigenetic. For this study, data was collected on maternal diet around the time of conception and on child behavioral characteristics in the second year of life for 325 mother/child pairs. Child behavior was assessed using the Infant Toddler Social and Emotional Assessment (ITSEA) questionnaire at 12-24 months of age. For a smaller subset, the methylation percentage of 49 CpG sites in the control regions of 9 imprinted regions were also examined in relation to maternal diet and child behaviors. These were conducted on cord-blood DNA from offspring. Initial research efforts focused on maternal Mediterranean diet adherence (MDA) as it remains one of the most highly researched dietary pattern.
Maternal Mediterranean diet adherence was associated with favorable offspring behavioral patterns, as well as with epigenetic changes in control regions of imprinted genes. Compared to children born to mothers least adherent to a Mediterranean diet around the time of conception, children born to mom’s with high MDA were less likely to display depressive and anxiety-related behaviors, and less likely to display atypical, maladaptive and autism-related behaviors. Furthermore, maternal MDA was also associated with changes in the methylation of the control regions of MEG3, IGF2, and SGCE/PEG10, which have been associated with multiple environmental exposures and offspring outcomes. Although the study was not designed with to demonstrate that the observed methylation changes in these genes mediated the associations of maternal MDA and offspring behavior, the directions of effect were consistent (see figure link).
Maternal obesity has been linked to increased incidence of neurodevelopmental offspring outcomes such as ADHD. Although the Mediterranean diet has been associated favorably with many human health outcomes, this is the first time that this periconceptional dietary pattern in human mothers has been associated with favorable offspring neurodevelopmental outcomes. The exciting thing is that people can change their diets and this may be a way to positively impact neurodevelopmental outcomes such as ADHD and autism, each of which have experience increased incidence in the last 3 decades. Ultimately, understanding the role epigenetics plays in linking environmental exposures such as maternal diet to offspring outcomes will offer insights into the development and testing of early intervention measures, either in utero or during the early stages of childhood development.
These efforts require a multi-disciplinary approach, pulling from several research fields to truly understand how such insights can be leveraged. The collaborative environment at NCSU is critical to this. House said, “I am fortunate to be a part of both the Bioinformatics Research Center and the Center for Human Health and the Environment. The BRC fosters a rich, collaborative environment which has afforded me exposure to a myriad of bioinformatics data science. And it was a colleague at the BRC that introduced me to Cathrine from the CHHE, which is what allowed me to conduct this research in the first place.”
While the MDA-centric study uncovered valuable insights, House plans to expand research efforts by examining other dietary patterns including diets high in glycemic loading. House: “I want to determine exactly what maternal nutrient clusters are associated with favorable and unfavorable offspring behaviors.” With new information regarding these patterns, specifically the impacts of glycemic loading consumption patterns in expecting mothers, early intervention studies will be the next step. House explains that “we have a current NIH proposal interrogate the entire methylome of these children to identify epigenetic signatures that are associated with increased risk of future adverse child behaviors at birth. The hope is to ameliorate such risks with early intervention of caregiving attributes and adjusting child dietary habits.”
Periconceptional Maternal Mediterranean Diet Is Associated With Favorable Offspring Behaviors and Altered CpG Methylation of Imprinted Genes (2018). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6137242/
Researchers and co-authors involved with this study include John S. House, Michelle Mendez, Rachel L. Maguire, Sarah Gonzalez-Nahm, Zhiqing Huang, Julie Daniels, Susan K. Murphy, Bernard F. Fuemmeler, Fred A. Wright, and Cathrine Hoyo.
The research was supported by National Institute of Environmental Health Sciences of the National Institutes of Health (P01ES022831, R21ES014947, R01ES016772, R01HD084487, and P30ES025128) and by the U.S. Environmental Protection Agency (RD-83543701). Additional support was provided by the National Center for Advancing Translational Sciences (UL1TR001117).