Increasing evidence indicates that the majority of children adversely affected by prenatal alcohol exposure (PAE) do not present with the physical features characteristic of Fetal Alcohol Syndrome (FAS). In the absence of these features, a confirmation of maternal drinking is required both for diagnosing Fetal Alcohol Spectrum Disorder (FASD) and initiating interventions. However, maternal self-report of drinking can be unreliable and conventional ethanol biomarkers are not sensitive enough for a diagnosis of drinking in many pregnant women, especially those who are moderate drinkers. The advent of high-throughput screening technologies for assessing the expression of genes, proteins and other metabolites in biological fluids has created new opportunities for developing more sensitive and specific biomarkers. MicroRNAs (miRNAs) are particularly appealing in this respect as they are very stable in plasma and serum and have shown great promise as biomarkers of a variety of disease conditions from cancer to myocardial infarction. Thus far, the utility of miRNAs as biomarkers for diagnosis of FASD has not been explored in detail. Our preliminary data suggest that alterations in the levels of at least two serum miRNAs could be used to reliably detect alcohol consumption during pregnancy. Furthermore, given that one of these miRNAs is expressed in the maternal reproductive system and the other in the fetal brain, these miRNAs could also serve as biomarkers of alcohol-induced tissue damage. The establishment of a panel of miRNAs as a clinically useful diagnostic tool will require replication of these findings in a larger clinical sample as well as a systematic evaluation of various factors that could affect the levels of circulating miRNAs during pregnancy. Thus, the goals of this translational research proposal are twofold.
Aim 1 : To identify a panel of serum miRNAs that predicts maternal alcohol consumption in pregnant women with higher specificity and sensitivity than conventional biomarkers, even in the presence of co-exposures with other drugs such as nicotine and opioids. The tissue origin and targets of these miRNAs will also be evaluated to assess potential mechanisms of alcohol-induced teratogenicity.
In Aim 2. we will use a rodent model of prenatal alcohol exposure to further examine the specificity of these novel biomarkers in relationship to co-exposure with either methadone (Aim 2A) or nicotine (Aim 2B), the """"""""window of detectability"""""""" after the last drinking episode (Aim 2C) and the impact of ethanol dose (Aim 2D). It is expected that this highly translational project will advance the field of FASD by providing novel biomarkers for an earlier and more accurate diagnosis of affected children.

Public Health Relevance

Most children adversely affected by prenatal alcohol exposure do not present with the physical features characteristic of Fetal Alcohol Syndrome making diagnosis difficult. This project will investigate the potential utility of microRNAs as a novel laboratory indicator to ascertain if drinking occurred during pregnancy.

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Specialized Center (P50)
Project #
Application #
Study Section
Special Emphasis Panel (ZAA1-GG (50))
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of New Mexico Health Sciences Center
United States
Zip Code
Bird, Clark W; Taylor, Devin H; Pinkowski, Natalie J et al. (2018) Long-term Reductions in the Population of GABAergic Interneurons in the Mouse Hippocampus following Developmental Ethanol Exposure. Neuroscience 383:60-73
Hamidovic, Ajna; Candelaria, Lionel; Rodriguez, Ihsan et al. (2018) Learning and memory performance following acute intranasal insulin administration in abstinent smokers. Hum Psychopharmacol 33:e2649
Harvey, Ryan E; Rutan, Stephanie A; Willey, Gabrielle R et al. (2018) Linear Self-Motion Cues Support the Spatial Distribution and Stability of Hippocampal Place Cells. Curr Biol 28:1803-1810.e5
Varaschin, Rafael K; Allen, Nyika A; Rosenberg, Martina J et al. (2018) Prenatal Alcohol Exposure Increases Histamine H3 Receptor-Mediated Inhibition of Glutamatergic Neurotransmission in Rat Dentate Gyrus. Alcohol Clin Exp Res 42:295-305
Caldwell, Kevin K; Solomon, Elizabeth R; Smoake, Jane J W et al. (2018) Sex-specific deficits in biochemical but not behavioral responses to delay fear conditioning in prenatal alcohol exposure mice. Neurobiol Learn Mem 156:1-16
Robinson, Shenandoah; Winer, Jesse L; Chan, Lindsay A S et al. (2018) Extended Erythropoietin Treatment Prevents Chronic Executive Functional and Microstructural Deficits Following Early Severe Traumatic Brain Injury in Rats. Front Neurol 9:451
Oliver, R J; Brigman, J L; Bolognani, F et al. (2018) Neuronal RNA-binding protein HuD regulates addiction-related gene expression and behavior. Genes Brain Behav 17:e12454
Vanderwall, Arden G; Noor, Shahani; Sun, Melody S et al. (2018) Effects of spinal non-viral interleukin-10 gene therapy formulated with d-mannose in neuropathic interleukin-10 deficient mice: Behavioral characterization, mRNA and protein analysis in pain relevant tissues. Brain Behav Immun 69:91-112
Kenton, Johnny A; Castillo, Rebecca; Holmes, Andrew et al. (2018) Cortico-hippocampal GluN2B is essential for efficient visual-spatial discrimination learning in a touchscreen paradigm. Neurobiol Learn Mem 156:60-67
Thompson, Shannon M; Berkowitz, Laura E; Clark, Benjamin J (2018) Behavioral and Neural Subsystems of Rodent Exploration. Learn Motiv 61:3-15

Showing the most recent 10 out of 46 publications