Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Transcriptional profiling of neonatal cord blood from babies born with or without prolonged rupture of membranes.

ABSTRACT: Prolonged rupture of membranes (PROM) is thought to incur higher risk of neonatal infection, leading to expedited delivery and/or the use of empirical perinatal antibiotics. Here, we compared the transcriptional profile of neonatal cord blood between babies where rupture of membranes occurred greater than 24 hours before delivery (= PROM cases) and babies where rupture of membranes occurred less than 24 hours before delivery (= Control cases). On the basis that perinatal infection is more likely in births associated with PROM than those without, we tested the hypothesis that perinatal infection in a subset of births following PROM, exhibit immune responses evident in the neonatal cord blood transcriptome.

ORGANISM(S): Homo sapiens

SUBMITTER: Carolin Turner

PROVIDER: E-MTAB-6431 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:The long-term effects of neonatal intermittent hypoxia (IH), an accepted model of apnea-induced hypoxia, are unclear. We have previously shown lasting âprogrammingâ effects on the HPA axis in adult rats exposed to neonatal IH. We hypothesized that neonatal rat exposure to IH will subsequently result in a heightened inflammatory state in the adult. Rat pups were exposed to normoxia (control) or six cycles of 5% IH or 10% IH over one hour daily from postnatal day 2 â 6. Plasma samples from blood obtained at 114 days of age were analyzed by assessing the capacity to induce transcription in a healthy peripheral blood mononuclear cell (PBMC) population and read using a high-density microarray. The analysis of plasma from adult rats previously exposed to neonatal 5% IH vs. 10% IH resulted in 2,579 significantly regulated genes including increased expression of Cxcl1, Cxcl2, Ccl3, Il1a, and Il1b. We conclude that neonatal exposure to intermittent hypoxia elicits a long-lasting programming effect in the adult resulting in an upregulation of inflammatory-related genes. Apnea is the most common cause of neonatal hypoxia affecting about 50% of preterm births (30 Ã¢ÂÂ 31 weeks), usually due to immature respiratory development. Upregulation of inflammatory genes and pathways in children 7 Ã¢ÂÂ 10 years of age has been shown, and there is a known increased risk of insulin resistance in adulthood when the fetus is exposed to maternal hypoxia, but the mechanism is unclear. The long-term metabolic, endocrine, and immunological effects of neonatal intermittent hypoxia (IH) exposure, an accepted model of apnea-induced hypoxia, have not been thoroughly evaluated. Recent studies in rats have shown that perinatal IH exposure can result in oxidative stress, causing a permanent immune response subsequently resulting in features of diabetes mellitus. We have previously examined adult rats exposed to neonatal intermittent hypoxia and perinatal continuous hypoxia, and have found lasting Ã¢ÂÂprogrammingÃ¢ÂÂ effects on the HPA axis. We now assess the long term effects of an accepted model of apnea-induced hypoxia using a validated transcriptional bioassay to study the extracellular milieu of adult rats exposed to neonatal intermittent hypoxia. We hypothesize that exposure to neonatal intermittent hypoxia will result in an increased inflammatory state in the adult as a result of long-lasting programming. Sprague-Dawley (SD) rat pups were treated with neonatal normoxia (21% O2, control), 5% intermittent hypoxia (IH), or 10% IH on postnatal days (PD) 2-6, daily over 1 hr. They were reared normally by birth dams and weaned at PD22. Males were allowed to mature and sacrificed at age PD114 after an overnight fast. Whole blood collected by decapitation into tubes with EDTA, and plasma saved for further analysis. Two adult (~180 day) male Brown Norway (BN) rats served as PBMC donors. Cells were incubated with 20% plasma that was either autologous BN (self-control), or one of 3 pools: a) SD normoxic N=8, b) SD 5% IH treated N=5, and c) SD 10% IH N=3.

Project description:We performed genome-wide association studies (GWAS) to study the Spontaneous Preterm birth (SPTB). Maternal and neonatal DNA from 743 SPTB (20 to and less than 34 weeks), and 752 controls (39 to and less than 42 weeks) who fully consented for public research usage were collected from participants in several clinical centers in Alabama, Illinois, New York, North Carolina, Rhode Island, Texas, and Utah. Cases were 1:1-matched with controls according to race/ethnicity (White, Hispanics, African Americans, and Others), maternal age (<20, 20-29, 30-39, 40+), and parity (yes or no). To determine the case-control status for each participant, a Gestational Age (GA) was determined. DNA samples were taken from blood or saliva if blood was not available. Automated DNA extractions were performed on the Qiagen M48 robot, and samples were organized in 96-well plates with barcoding and sample tracking systems. Subsequent manipulations were performed on the Biomek FX liquid handling workstation with 96-channel pipetting. DNA quantitation was performed by dye-based assay on a Molecular Devices SpectraMax Plus plate reader. Samples were genotyped using Affymetrix Genome-Wide Human SNP Array 6.0. This work was conducted at the Microarray Facility at the University of Pennsylvania. Patient data were collected through chart reviews and patient interviews, which included Demographic information (parental age, race, ethnicity, etc.); Medical history (pre-pregnancy weight, height, medications, STD history, medical conditions, etc.); Social history (marital status, years of education, alcohol use and tobacco use); Obstetrical history including outcome of all prior pregnancies and dates of termination; History of preterm labor or premature rupture of membranes symptoms, evaluation or hospitalization for those symptoms in current pregnancy; Medications taken during current pregnancy; History of cervical evaluation (manually or ultrasonographically) or fetal fibronectin measurements; Pregnancy complications; Labor (type, indications, membrane status, and induction method); Delivery type and indications for cesarean section; Neonatal outcome (sex, weight, length, Apgar score, neonatal complications, admission to intensive care unit, etc.); and Maternal family history of SPTB.

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Transcriptional profiling of neonatal cord blood from babies born with or without prolonged rupture of membranes.

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