Plancental Microbes as an Indicator of Neurocognitive Outcomes in Children Born Preterm

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  • March 21, 2019
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  • Tomlinson, Martha
    • Affiliation: Gillings School of Global Public Health, Department of Environmental Sciences and Engineering
Abstract
  • Prenatal exposure to various stressors can influence both early and later childhood health. Microbial infection of the intrauterine environment, and specifically within the placenta, has been associated with deleterious pregnancy outcomes, such as preterm birth. Children that are born prematurely experience a higher rate of developmental problems throughout their lives, including neurocognitive impairment which persists into school-age and manifests as poor performance in school. The relationships among microorganisms in the placenta, placental function and fetal development are not well understood. Microorganisms have been associated with epigenetic modifications in other tissue types and are known to trigger an inflammatory response. Inflammatory proteins can damage the developing fetal brain. This goal of this research was to explore microorganisms in preterm placentas, their association with inflammation and DNA methylation, as well as later-life neurocognitive function. Using data from the Extremely Low Gestational Age Newborn (ELGAN) cohort we assessed the relationship between 15 microorganisms and three outcomes: (1) neurocognitive and social-communicative outcomes at age 10, (2) genome-wide DNA CpG methylation of the placenta, and (3) placental mRNA expression of inflammation-related genes. Through these studies we demonstrated that different bacterial species have differential effects on the placenta and the child. The presence of certain microorganisms in the placenta were associated with neurocognitive delays at age 10. In contrast, the presence of Lactobacillus sp. was associated with a lower risk of impaired neurocognitive functions. In the placenta, we found that the presence of bacteria led to differential methylation of 1,789 CpG sites, corresponding to 1,079 genes. The altered genes encode for proteins that are involved in immune/inflammatory responses, specifically the NF-κB signaling pathway. Through evaluation of mRNA expression, we discovered that in the presence of certain bacteria there was an upregulation of inflammation-related genes. Taken together, these findings increase the understanding of mechanisms by which microbial presence in the placenta contributes to the outcomes of the children later in life.
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  • In Copyright
Advisor
  • Marsit, Carmen
  • Fry, Rebecca
  • Lu, Kun
  • O'Shea, Michael
  • Stewart, Jill
Degree
  • Doctor of Philosophy
Degree granting institution
  • University of North Carolina at Chapel Hill Graduate School
Graduation year
  • 2018
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