Cord Blood-Derived Exosomal CNTN2 and BDNF: Potential Molecular Markers for Brain Health of Neonates at Risk for Iron Deficiency

• Published in: Psychoneuroendocrinology Vol. 160; p. 106747
• Main Authors: Train, Phu, Marell, Paulina S., Blohowiak, Sharon E., Evans, Michael D., Georgieff, Michael K., Kling, Pamela J.
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01.02.2024
• ISSN: 0306-4530; 1873-3360
• DOI: 10.1016/j.psyneuen.2023.106747

Maternal iron deficiency anemia, obesity, and diabetes are prevalent during pregnancy and are associated with neonatal brain iron deficiency (ID) and neurodevelopmental impairment. Exosomes are extracellular vesicles involved in cell–cell communication. Contactin-2 (CNTN2), a neural-specific glycoprotein, and brain-derived neurotrophic factor (BDNF) are important in neurodevelopment and found in exosomes. We hypothesized that exosomal CNTN2 and BDNF identify infants at risk for brain ID. Umbilical cord blood samples were measured for iron status in 79 neonates (37 female). Maternal anemia, diabetes, and body mass index (BMI) were recorded. Cord blood exosomes were isolated and validated for the exosomal marker CD81 and the neural-specific exosomal marker CNTN2. Exosomal CNTN2 and BDNF levels were quantified by ELISA. CNTN2 was positively associated with ferritin in all neonates (p=0.02). BDNF was inversely correlated with ferritin (p=0.03), especially in female neonates (p = 0.06). Analysis of maternal risk factors for neonatal brain ID as predictors of exosomal CNTN2 and BDNF showed sex-specific relationships between infants of diabetic mothers (IDMs) and CNTN2 (p=0.0005). While male IDMs exhibited a negative correlation (p=0.02), female IDMs showed a positive correlation (p=0.01) with CNTN2. Maternal BMI was negatively associated with BNDF, with a stronger association in female neonates (p=0.04). These findings suggest CNTN2 and BNDF are respective molecular markers for male and female neonates at risk for brain ID. This study supports the potential of exosomal markers to assess neonatal brain status in at-risk infants.