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

• Published in: PloS one 2017-05, Vol.12 (5), p.e0176953
• Main Authors: Tilley, Sloane K, Joseph, Robert M, Kuban, Karl C K, Dammann, Olaf U, O'Shea, T Michael, Fry, Rebecca C
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Age; Biological activity; Biological markers; Biology and Life Sciences; Biomarkers; Child; Children; Cognition; Cognition Disorders - etiology; Cognition Disorders - genetics; Cognitive ability; Disorders; Environmental science; Female; Fetal diseases; Fetal Diseases - genetics; Fetuses; Gene expression; Gene Expression Regulation; Genes; Genetic aspects; Genetic Markers - genetics; Genomes; Gestation; Health aspects; Health risks; Humans; Impairment; Indicators; Infant, Newborn; Infant, Premature - physiology; Inflammation; Inflammation - genetics; Kinases; Medicine; Medicine and Health Sciences; Neonates; Neurodegenerative diseases; Neurodevelopmental disorders; Neurogenesis; Neurosciences; Newborn babies; Pediatrics; People and Places; Placenta; Pregnancy; Premature birth; Proteins; Public health; Ribonucleic acid; Risk factors; RNA; RNA, Messenger - genetics; Side effects; Transcriptome; Umbilical cord; Umbilical Cord - metabolism; Young Adult
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0176953

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. 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. 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. 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.