Endogenous Methanol Derived Formic Acid Correlates with Cognitive Dysfunction in Children Born to Drinking Mothers

Abstract

Background: We have recently shown that formic acid (FA) can be produced from methanol, either present endogenously or as a congener in alcoholic beverages, in concentrations that can cause neuronal cell death. There is evidence that the enzymes required to metabolize methanol to FA, such as cytochrome P450 2E1, are present in the fetal compartment, suggesting that FA formation may contribute to the brain injury induced by prenatal exposure to alcohol. Purpose: The purpose of this study was to test the hypothesis that FA present in the maternal-fetal unit is associated with cognitive and motor deficits in young children born to alcohol drinking mothers. Methods: Maternal and cord blood samples were obtained at the time of delivery and tested for FA by gas chromatography-mass spectroscopy. Routine biochemical tests including cortisol, ACTH, plasma folic acid were also done. Information on maternal drug and alcohol use was collected for all mother-baby pairs. Bayley Scales of Infant and Toddler Development, 3rd Ed. was administered to infants/toddlers at 6 month intervals from 16 days to 3 years of age. The Scales measured cognition, motor functioning, language, and adaptive behavior. Results: This interim report describes outcome measurements obtained in eighteen babies who have reached 12 months of age. The average age of mothers in this study was 27.15 years old (range 16 to 41 years). 17 mothers admitted to drinking regularly, 16 used crack cocaine, 5 smoked marijuana, 2 used opiates and 1 used MDMA during pregnancy. FA measurements were obtained for twelve mother-baby pairs. (FA mom: 43.9 + 31.9nmol/L; cord blood 159.6 + 148ng/mL (normal <140ng/mL). Cognitive function in the children was negatively correlated to formic acid concentration in maternal/ cord blood at 12 months of age (r=6154, p=0.025, n=12). Conclusion: These preliminary data suggests that FA formed in the maternal-fetal unit during pregnancy contributes to cognitive dysfunction in this cohort of children.