title: Adverse placental effect of formic acid on hCG secretion is mitigated by folic acid.
abstract: OBJECTIVE
  Formic acid has recently been detected in maternal blood and umbilical cord blood of infants born to alcohol abusing mothers. This toxic metabolite of methanol requires folate for detoxification. We hypothesized that formic acid produced in the maternal circulation will transfer across the placenta and will be toxic to the placenta. Our objectives were, first, to determine whether formic acid transfers across the human placenta and whether it is toxic to the placenta and second, to determine whether folate can decrease transplacental transfer of formic acid and mitigate toxicity.
  
  
  METHODS
  Dual perfusion of a single placental lobule ex vivo was used to characterize the transfer of formic acid across the placenta. After a 1-h control period, formic acid (2 mM) was introduced into the maternal circulation with (n = 4) or without folate (1 µM) (n = 4) and was allowed to equilibrate for 3 h.
  
  
  RESULTS
  Formic acid transferred rapidly from the maternal to the fetal circulation, and transfer was not altered with the addition of folate. Compared with the control period, there was a significant decrease in hCG secretion (P = 0.03) after addition of formic acid. The addition of folic acid to the perfusate mitigated the decrease in hCG.
  
  
  CONCLUSIONS
  Formic acid rapidly transfers across the placenta and thus has the potential to be toxic to the developing fetus. Formic acid decreases hCG secretion in the placenta, which may alter steroidogenesis and differentiation of the cytotrophoblasts, and this adverse effect can be mitigated by folate.
authors: Division of Clinical Pharmacology and Toxicology, Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada.
authors: J R
authors: JR
authors: Hutson
authors: A
authors: A
authors: Lubetsky
authors: J
authors: J
authors: Eichhorst
authors: R
authors: R
authors: Hackmon
authors: G
authors: G
authors: Koren
authors: B M
authors: BM
authors: Kapur
mesh_terms: D000328:Adult; D006063:Chorionic Gonadotropin / Q000378:metabolism*; D005260:Female; D005333:Fetus / Q000378:metabolism; D005492:Folic Acid / Q000494:pharmacology*; D005561:Formates / Q000009:adverse effects* / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D008431:Maternal-Fetal Exchange / Q000187:drug effects*; D010920:Placenta / Q000187:drug effects* / Q000473:pathology; D011247:Pregnancy
chemical_list: D006063:Chorionic Gonadotropin; D005561:Formates; C030544:formic acid; D005492:Folic Acid