title: Alcohol Use During Pregnancy is Associated with Specific Alterations in MicroRNA Levels in Maternal Serum.
abstract: BACKGROUND
  Given the challenges of confirming prenatal alcohol exposure (PAE) during pregnancy using currently established biomarkers of alcohol consumption, we examined whether serum microRNAs (miRNAs) may serve as stable biomarkers for PAE. Alterations in the levels of specific circulating miRNAs have been associated with various disease states and in animal models of fetal alcohol spectrum disorder.
  
  
  METHODS
  Pregnant women in this prospective study were recruited from substance abuse and general maternity clinics affiliated with the University of New Mexico. Serum was collected at the time of admission for delivery from 14 subjects who reported ≥1 binge-drinking episode or ≥3 drinks/wk during pregnancy and 16 subjects who reported abstinence during pregnancy and tested negative for 5 ethanol biomarkers. Total RNA was isolated from serum and used for microarray analysis.
  
  
  RESULTS
  False discovery rate-corrected analyses of covariance revealed that 55 miRNAs were significantly altered between the 2 groups. Hierarchical clustering using only the significantly altered miRNAs grouped samples into alcohol-consuming and non-alcohol-consuming individuals. Discriminant analysis then identified miRs-122*, -126, -216b, -221*, -3119, -3942-5p, -4704-3p, -4743, -514-5p, and -602 as the top 10 discriminators between the 2 groups. Ingenuity Pathway Analysis of putative miRNA targets illustrated that miRNAs identified in this study are involved in biological pathways that mediate the effects of alcohol, such as brain-derived neurotrophic factor, ERK1/2, and PI3K/AKT signaling.
  
  
  CONCLUSIONS
  This is the first report of alterations in serum miRNA expression that are associated with alcohol use during human pregnancy. These results suggest that serum miRNAs could be useful as biomarkers of alcohol exposure.
authors.affiliation: Department of Neurosciences, University of New Mexico Health Sciences Center, Albuquerque, New Mexico.
authors.forename: Amy S
authors.initials: AS
authors.lastname: Gardiner
authors.affiliation: Department of Pharmacy Practice and Administrative Sciences, University of New Mexico Health Sciences Center, Albuquerque, New Mexico.
authors.forename: Hilda L
authors.initials: HL
authors.lastname: Gutierrez
authors.affiliation: Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, New Mexico.
authors.forename: Li
authors.initials: L
authors.lastname: Luo
authors.affiliation: Department of Neurosciences, University of New Mexico Health Sciences Center, Albuquerque, New Mexico.
authors.forename: Suzy
authors.initials: S
authors.lastname: Davies
authors.affiliation: Department of Neurosciences, University of New Mexico Health Sciences Center, Albuquerque, New Mexico.|Department of Pediatrics, University of New Mexico Health Sciences Center, Albuquerque, New Mexico.
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Savage
authors.affiliation: Department of Pharmacy Practice and Administrative Sciences, University of New Mexico Health Sciences Center, Albuquerque, New Mexico.|Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, New Mexico.|Department of Family and Community Medicine, University of New Mexico Health Sciences Center, Albuquerque, New Mexico.
authors.forename: Ludmila N
authors.initials: LN
authors.lastname: Bakhireva
authors.affiliation: Department of Neurosciences, University of New Mexico Health Sciences Center, Albuquerque, New Mexico.|Department of Psychiatry and Behavioral Sciences, University of New Mexico Health Sciences Center, Albuquerque, New Mexico.
authors.forename: Nora I
authors.initials: NI
authors.lastname: Perrone-Bizzozero
mesh_terms: D000328:Adult; D000428:Alcohol Drinking / Q000009:adverse effects / Q000097:blood* / Q000235:genetics; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D005260:Female; D053263:Gene Regulatory Networks / Q000502:physiology; D006801:Humans; D039382:Maternal Nutritional Physiological Phenomena / Q000502:physiology*; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics; D011247:Pregnancy; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D015415:Biomarkers; D035683:MicroRNAs
keywords: Biomarkers; Maternal Alcohol Consumption; Microarrays; Prenatal Alcohol Exposure; Serum miRNAs