The association between prenatal alcohol exposure and protein expression in human placenta

Bradley D. Holbrook, Suzy Davies, Sandra Cano, Shikhar Shrestha, Lauren L. Jantzie, William F. Rayburn, Ludmila N. Bakhireva, Daniel D. Savage

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Background: The need for earlier recognition of children at risk for neurobehavioral problems associated with prenatal ethanol exposure (PAE) has prompted investigations of biomarkers prognostic for altered fetal development. Here, we examined whether PAE alters the expression of angiogenesis-related proteins and cytokines in human placenta in subjects from an Ethanol, Neurodevelopment, Infant and Child Health prospective cohort. Methods: PAE was ascertained by screening questionnaires, Time-line Follow-back interviews and a panel of ethanol biomarkers at two study visits. After delivery, placental tissue samples were collected for protein analysis. Results: No significant differences in the prevalence of substance use, demographic or medical characteristics were observed between the No PAE and PAE groups. PAE was associated with significant reductions in placental expression of VEGFR2 and annexin-A4, while the levels of VEGFR1 and CCM-3 trended downward. A trend toward higher expression of the cytokines TNF-α and IL-13 was also observed in the PAE group. Receiver operating characteristic analyses of the data demonstrated a moderate-to-high degree of diagnostic accuracy for individual placental proteins. Combinations of proteins substantially increased their ability to differentiate between PAE and No PAE subjects. Conclusions: These results establish the feasibility of harvesting placental tissue for protein analyses of PAE in a prospective manner. In addition, given the importance of vascular remodeling in both placenta and developing brain, the role of angiogenic and cytokine proteins in this process warrants further investigation for their utility for predicting alterations in brain development, as well as their mechanistic role in PAE-induced pathology.

Original languageEnglish (US)
Pages (from-to)749-759
Number of pages11
JournalBirth Defects Research
Issue number12
StatePublished - Jul 15 2019
Externally publishedYes


  • angiogenesis
  • annexin-A4
  • cytokines
  • fetal alcohol spectrum disorder
  • placenta
  • prenatal alcohol exposure
  • vascular endothelial growth factor receptor 2

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Embryology
  • Toxicology
  • Developmental Biology
  • Health, Toxicology and Mutagenesis


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