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Activation of inflammation/NF-kappaB signaling in infants born to arsenic-exposed mothers.

ABSTRACT: The long-term health outcome of prenatal exposure to arsenic has been associated with increased mortality in human populations. In this study, the extent to which maternal arsenic exposure impacts gene expression in the newborn was addressed. We monitored gene expression profiles in a population of newborns whose mothers experienced varying levels of arsenic exposure during pregnancy. Through the application of machine learning-based two-class prediction algorithms, we identified expression signatures from babies born to arsenic-unexposed and -exposed mothers that were highly predictive of prenatal arsenic exposure in a subsequent test population. Furthermore, 11 transcripts were identified that captured the maximal predictive capacity to classify prenatal arsenic exposure. Network analysis of the arsenic-modulated transcripts identified the activation of extensive molecular networks that are indicative of stress, inflammation, metal exposure, and apoptosis in the newborn. Exposure to arsenic is an important health hazard both in the United States and around the world, and is associated with increased risk for several types of cancer and other chronic diseases. These studies clearly demonstrate the robust impact of a mother's arsenic consumption on fetal gene expression as evidenced by transcript levels in newborn cord blood.

SUBMITTER: Fry RC

PROVIDER: S-EPMC2082467 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundMaternal asthma is associated with serious pregnancy complications, but newborn morbidity is understudied.ObjectiveWe wanted to determine whether infants of asthmatic mothers have more neonatal complications.MethodsThe Consortium on Safe Labor (2002-2008), a retrospective cohort, included 223,512 singleton deliveries at ? 23 weeks' gestation. Newborns of mothers with asthma (n = 17,044) were compared with newborns of women without asthma by using logistic regression models with generalized estimating equations to calculate adjusted odds ratios (ORs) and 95% CIs. Electronic medical record data included gestational week at delivery, birth weight, resuscitation, neonatal intensive care unit (NICU) admission, NICU length of stay, hyperbilirubinemia, respiratory distress syndrome, apnea, sepsis, anemia, transient tachypnea of the newborn, infective pneumonia, asphyxia, intracerebral hemorrhage, seizure, cardiomyopathy, periventricular or intraventricular hemorrhage, necrotizing enterocolitis, aspiration, retinopathy of prematurity, and perinatal mortality.ResultsPreterm delivery was associated with maternal asthma for each week after 33 completed weeks of gestation and not earlier. Maternal asthma also increased the adjusted odds of small for gestational age (OR = 1.10; 95% CI, 1.05-1.16), NICU admission (OR = 1.12; 95% CI, 1.07-1.17), hyperbilirubinemia (OR = 1.09; 95% CI, 1.04-1.14), respiratory distress syndrome (OR = 1.09; 95% CI, 1.01-1.19), transient tachypnea of the newborn (OR = 1.10; 95% CI, 1.02-1.19), and asphyxia (OR = 1.34; 95% CI, 1.03-1.75). Findings persisted for term infants (? 37 weeks) who had additional increased odds of intracerebral hemorrhage (OR = 1.84; 95% CI, 1.11-3.03) and anemia (OR = 1.30; 95% CI, 1.04-1.62).ConclusionsMaternal asthma was associated with prematurity and small for gestational age. Adverse neonatal outcomes, including respiratory complications, hyperbilirubinemia, and NICU admission, were increased in association with maternal asthma even among term deliveries.

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Activation of inflammation/NF-kappaB signaling in infants born to arsenic-exposed mothers.

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