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PLoS One. 2017 May 11;12(5):e0176953. doi: 10.1371/journal.pone.0176953. eCollection 2017.

Genomic biomarkers of prenatal intrauterine inflammation in umbilical cord tissue predict later life neurological outcomes.

Author information

1
Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, United States of America.
2
Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, Massachusetts, United States of America.
3
Department of Pediatrics, Boston University School of Medicine, Boston, Massachusetts, United States of America.
4
Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, Massachusetts, United States of America.
5
Department of Pediatrics, University of North Carolina, Chapel Hill, North Carolina, United States of America.
6
Curriculum in Toxicology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina, United States of America.

Abstract

BACKGROUND:

Preterm birth is a major risk factor for neurodevelopmental delays and disorders. This study aimed to identify genomic biomarkers of intrauterine inflammation in umbilical cord tissue in preterm neonates that predict cognitive impairment at 10 years of age.

STUDY DESIGN:

Genome-wide messenger RNA (mRNA) levels from umbilical cord tissue were obtained from 43 neonates born before 28 weeks of gestation. Genes that were differentially expressed across four indicators of intrauterine inflammation were identified and their functions examined. Exact logistic regression was used to test whether expression levels in umbilical cord tissue predicted neurocognitive function at 10 years of age.

RESULTS:

Placental indicators of inflammation were associated with changes in the mRNA expression of 445 genes in umbilical cord tissue. Transcripts with decreased expression showed significant enrichment for biological signaling processes related to neuronal development and growth. The altered expression of six genes was found to predict neurocognitive impairment when children were 10 years old These genes include two that encode for proteins involved in neuronal development.

CONCLUSION:

Prenatal intrauterine inflammation is associated with altered gene expression in umbilical cord tissue. A set of six of the differentially expressed genes predict cognitive impairment later in life, suggesting that the fetal environment is associated with significant adverse effects on neurodevelopment that persist into later childhood.

PMID:
28493900
PMCID:
PMC5426658
DOI:
10.1371/journal.pone.0176953
[Indexed for MEDLINE]
Free PMC Article

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