Abstract
BackgroundPreterm 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 designGenome-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.ResultsPlacental 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.ConclusionPrenatal 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.
Highlights
Preterm birth, defined as delivery at < 37 completed weeks gestation, is currently the leading cause of neonatal morbidity and mortality in the United States [1]
Placental indicators of inflammation were associated with changes in the messenger RNA (mRNA) expression of 445 genes in umbilical cord tissue
Prenatal intrauterine inflammation is associated with altered gene expression in umbilical cord tissue
Summary
Preterm birth, defined as delivery at < 37 completed weeks gestation, is currently the leading cause of neonatal morbidity and mortality in the United States [1]. Individuals born prematurely are at increased risk for other adverse health outcomes, and those born at less than 28 weeks gestation are at high risk [2]. Indicators of intrauterine inflammation are present in as many as 40–70% of preterm births, versus only 1–13% of full term births [7]. These data support the hypothesis that risk of preterm birth is increased by pathological, environmental, and/or genetic factors that contribute to delivery-inducing inflammation [4,8]. 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
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