title: Assessing the fetal effects of maternal obesity via transcriptomic analysis of cord blood: a prospective case-control study.
abstract: OBJECTIVE
  To analyse fetal gene expression at term using umbilical cord blood, in order to provide insights into the effects of maternal obesity on human development.
  
  
  METHODS
  Prospective case-control study.
  
  
  METHODS
  Academic tertiary care centre.
  
  
  METHODS
  Eight obese (body mass index ≥30 kg/m(2)) and eight lean (body mass index <25 kg/m(2)) pregnant women undergoing prelabour caesarean delivery at term.
  
  
  METHODS
  Women were matched for gestational age and fetal sex. Cord blood RNA was extracted and hybridised to gene expression arrays. Differentially regulated genes were identified using paired t-tests and the Benjamini-Hochberg correction. Functional analyses were performed using Ingenuity Pathway Analysis, BioGPS and Gene Set Enrichment Analysis with a fetal-specific annotation. Z-scores ≥2.0 or P-values <0.01 were considered significant.
  
  
  METHODS
  Functions of differentially regulated genes in fetuses of obese women.
  
  
  RESULTS
  A total of 701 differentially regulated genes were identified, producing an expression profile implicating neurodegeneration, decreased survival of sensory neurons, and decreased neurogenesis in the fetuses of obese women. Upstream regulators related to inflammatory signalling were significantly activated; those related to insulin receptor signalling, lipid homeostasis, regulation of axonal guidance, and cellular response to oxidative stress were significantly inhibited. Of 26 tissue-specific genes that were differentially regulated in fetuses of obese women, six mapped to the fetal brain.
  
  
  CONCLUSIONS
  Maternal obesity affects fetal gene expression at term, implicating dysregulated brain development, inflammatory and immune signalling, glucose and lipid homeostasis, and oxidative stress. This may have implications for postnatal neurodevelopment and metabolism.
authors: Mother Infant Research Institute and Department of Obstetrics and Gynecology, Tufts Medical Center, Boston, MA, USA.
authors: A G
authors: AG
authors: Edlow
authors: Mother Infant Research Institute and Department of Obstetrics and Gynecology, Tufts Medical Center, Boston, MA, USA.|Department of Perinatal Medicine, Mercy Hospital for Women, Heidelberg, Vic., Australia.
authors: L
authors: L
authors: Hui
authors: Department of Computer Science, Tufts University, Medford, MA, USA.
authors: H C
authors: HC
authors: Wick
authors: Department of Computer Science, Tufts University, Medford, MA, USA.
authors: I
authors: I
authors: Fried
authors: Mother Infant Research Institute and Department of Obstetrics and Gynecology, Tufts Medical Center, Boston, MA, USA.
authors: D W
authors: DW
authors: Bianchi
mesh_terms: D000328:Adult; D015992:Body Mass Index; D016022:Case-Control Studies; D005260:Female; D005312:Fetal Blood; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D007333:Insulin Resistance; D008297:Male; D009765:Obesity / Q000097:blood* / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D011247:Pregnancy; D011248:Pregnancy Complications / Q000097:blood / Q000235:genetics*; D011297:Prenatal Exposure Delayed Effects / Q000097:blood / Q000235:genetics*; D011446:Prospective Studies; D014481:United States / Q000453:epidemiology
keywords: Brain; cord blood; fetal; fetal programming; maternal obesity; metabolic; transcriptome