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Performing discovery-driven neonatal research by transcriptomic analysis of routinely discarded biofluids.

ABSTRACT: To perform discovery-driven research on the neonatal salivary and cord blood transcriptomes.Two separate cohorts of infants were enrolled in this study. In one, cord blood (n = 10) and in the other, saliva samples (n = 10) were collected at term gestation. Total RNA was extracted, amplified and hybridized onto Affymetrix HG U133a gene expression microarrays. Following normalization, genes expressed in the highest quintile (? 80%) across all subjects in each biofluid were analyzed with Ingenuity Pathway Analysis. Over-represented pathways relating to organ specific development and physiological functions in the newborn were explored.There were 303 genes in neonatal saliva and 282 genes in umbilical cord blood that met statistical criteria. Of these, 114 were common to both biofluids. Pathway analyses revealed the important roles of redox balance, cellular proliferation, and smooth muscle relaxation. In blood, hematopoiesis and immune response pathways predominated. In saliva, pathways associated with the gastrointestinal system were highlighted.Neonatal cord blood and saliva provide a wealth of transcriptomic information. These normally discarded biofluids should be considered an important source of real-time gene expression data that may elucidate key pathways in neonatal physiology and pathology.

SUBMITTER: Maron JL

PROVIDER: S-EPMC4511475 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

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Performing discovery-driven neonatal research by transcriptomic analysis of routinely discarded biofluids.

Maron Jill L JL Dietz Jessica A JA Parkin Christopher C Johnson Kirby L KL Bianchi Diana W DW

The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 20120827 12

<h4>Objective</h4>To perform discovery-driven research on the neonatal salivary and cord blood transcriptomes.<h4>Methods</h4>Two separate cohorts of infants were enrolled in this study. In one, cord blood (n = 10) and in the other, saliva samples (n = 10) were collected at term gestation. Total RNA was extracted, amplified and hybridized onto Affymetrix HG U133a gene expression microarrays. Following normalization, genes expressed in the highest quintile (≥ 80%) across all subjects in each biof ...[more]

PMID: 22920923

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Project description:BackgroundTherapeutic hypothermia is standard of care in high-income countries for babies born with signs of hypoxic ischaemic encephalopathy, but optimal feeding during treatment is uncertain and practice is variable. This study aimed to assess the association between feeding during therapeutic hypothermia and clinically important outcomes.MethodsWe did a population-level retrospective cohort study using the UK National Neonatal Research Database. We included all babies admitted to National Health Service neonatal units in England, Scotland, and Wales between Jan 1, 2010, and Dec 31, 2017, who received therapeutic hypothermia for 72 h or died during this period. For analysis, we created matched groups using propensity scores and compared outcomes in babies who were fed versus unfed enterally during therapeutic hypothermia. The primary outcome was severe necrotising enterocolitis, either confirmed at surgery or causing death. Secondary outcomes include pragmatically defined necrotising enterocolitis (a recorded diagnosis of necrotising enterocolitis in babies who received at least 5 consecutive days of antibiotics while also nil by mouth during their neonatal unit stay), late-onset infection (pragmatically defined as 5 consecutive days of antibiotic treatment commencing after day 3), survival to discharge, measures of breastmilk feeding, and length of stay in neonatal unit.Findings6030 babies received therapeutic hypothermia, of whom 1873 (31·1%) were fed during treatment. Seven (0·1%) babies were diagnosed with severe necrotising enterocolitis and the number was too small for further analyses. We selected 3236 (53·7%) babies for the matched feeding analysis (1618 pairs), achieving a good balance for all recorded background variables. Pragmatically defined necrotising enterocolitis was rare in both groups (incidence 0·5%, 95% CI 0·2-0·9] in the fed group vs 1·1% [0·7-1·4] in the unfed group). The enterally fed group had fewer pragmatically defined late-onset infections (difference -11·6% [95% CI -14·0 to -9·3]; p<0·0001), higher survival to discharge (5·2% [3·9-6·6]; p<0·0001), higher proportion of breastfeeding at discharge (8·0% [5·1-10·8]; p<0·0001), and shorter neonatal unit stays (-2·2 [-3·0 to -1·2] days; p<0·0001) compared with the unfed group.InterpretationNecrotising enterocolitis is rare in babies receiving therapeutic hypothermia. Enteral feeding during hypothermia is safe and associated with beneficial outcomes compared with not feeding, although residual confounding could not be completely ruled out. Our findings support starting milk feeds during therapeutic hypothermia.FundingUK National Institute for Health Research Health Technology Assessment programme 16/79/13.

Dataset Information

Performing discovery-driven neonatal research by transcriptomic analysis of routinely discarded biofluids.

Publications

Performing discovery-driven neonatal research by transcriptomic analysis of routinely discarded biofluids.

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