Journal Article

Plasma miRNA Profiles in Pregnant Women Predict Infant Outcomes following Prenatal Alcohol Exposure

Zymak-Zakutnya, Natalya, Yevtushok, Lyubov, Miranda, Rajesh C., Balaraman, Sridevi, Chambers, Christina D., Wertelecki, Wladimir, Schafer, Jordan J., Tseng, Alexander M.

2016

Overview

Fetal alcohol spectrum disorders (FASD) are difficult to diagnose since many heavily exposed infants, at risk for intellectual disability, do not exhibit craniofacial dysmorphology or growth deficits. Consequently, there is a need for biomarkers that predict disability. In both animal models and human studies, alcohol exposure during pregnancy resulted in significant alterations in circulating microRNAs (miRNAs) in maternal blood. In the current study, we asked if changes in plasma miRNAs in alcohol-exposed pregnant mothers, either alone or in conjunction with other clinical variables, could predict infant outcomes. Sixty-eight pregnant women at two perinatal care clinics in western Ukraine were recruited into the study. Detailed health and alcohol consumption histories, and 2nd and 3rd trimester blood samples were obtained. Birth cohort infants were assessed by a geneticist and classified as unexposed (UE), heavily prenatally exposed and affected (HEa) or heavily exposed but apparently unaffected (HEua). MiRNAs were assessed in plasma samples using qRT-PCR arrays. ANOVA models identified 11 miRNAs that were all significantly elevated in maternal plasma from the HEa group relative to HEua and UE groups. In a random forest analysis classification model, a combination of high variance miRNAs, smoking history and socioeconomic status classified membership in HEa and UE groups, with a misclassification rate of 13%. The RFA model also classified 17% of the HEua group as UE-like, whereas 83% were HEa-like, at least at one stage of pregnancy. Collectively our data indicate that maternal plasma miRNAs predict infant outcomes, and may be useful to classify difficult-to-diagnose FASD subpopulations.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adult / Alcohol Drinking - adverse effects / Alcohol use / Alcoholic beverages / Alcohols / Analysis / Angiogenesis / Animal models / Animals / Babies / Bioindicators / Biology and life sciences / Biomarkers / Biomarkers - blood / Birth defects / Blood / Blood circulation / Cell division / Cohort Studies / Collaboration / Drinking (Alcoholic beverages) / Endocrinology / Ethanol / Exposure / Female / Fetal Alcohol Spectrum Disorders - diagnosis / Fetal Alcohol Spectrum Disorders - etiology / Fetal Alcohol Spectrum Disorders - genetics / Fetal alcohol syndrome / Heart attacks / Humans / Infant / Infant, Newborn / Infants / Intellectual disabilities / Male / Mathematical models / Medicine / Medicine and Health Sciences / Metabolites / MicroRNA / MicroRNAs / MicroRNAs - blood / MicroRNAs - classification / MicroRNAs - genetics / miRNA / Neurosciences / Pediatrics / People and Places / Perinatal Care / Physical Sciences / Placenta / Plasma / Predictive Value of Tests / Pregnancy / Pregnant women / Prenatal experience / Prenatal Exposure Delayed Effects - diagnosis / Prenatal Exposure Delayed Effects - etiology / Prenatal Exposure Delayed Effects - genetics / Prognosis / Public health / Research and Analysis Methods / Reverse Transcriptase Polymerase Chain Reaction / Sensitivity and Specificity / Smoking / Socioeconomics / Subpopulations / Ukraine / Variance analysis / Womens health / Young Adult