title: Placental passage of antiepileptic drugs at delivery and neonatal outcomes.
abstract: Children of women treated with antiepileptic drugs (AEDs) are at increased risk of adverse outcomes detectable in the neonatal period, which may be associated with the amount of AEDs in the fetal circulation. Placental passage of AEDs can be measured by calculating the ratio of umbilical cord to maternal AED concentrations collected at delivery. The aims of this study were to determine the umbilical cord concentrations and umbilical-to-maternal ratios for AEDs, and whether higher cord concentrations are associated with increased risk of neonatal complications. AED cord and maternal blood concentrations from 70 mother-newborn dyads and neonatal complications were recorded. Logistic regressions were performed to determine the association between AED concentrations and complications. Mean umbilical-to-maternal ratios for total concentrations ranged from 0.79 for carbamazepine to 1.20 for valproic acid, and mean umbilical-to-maternal ratios for free concentrations ranged from 0.86 for valproic acid to 1.42 for carbamazepine, indicating complete placental passage. Neither umbilical cord concentrations nor umbilical-to-maternal ratios were associated with adverse neonatal outcomes. Additional investigations are warranted to delineate the relationship between quantified fetal AED exposure and neonatal complications.
authors.affiliation: Brigham and Women's Hospital, Boston, Massachusetts, U.S.A.|Massachusetts General Hospital, Boston, Massachusetts, U.S.A.|Harvard Medical School, Boston, Massachusetts, U.S.A.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Bank
authors.affiliation: University of Arkansas for Medical Sciences, Little Rock, Arkansas, U.S.A.|Arkansas Children's Hospital Research Institute, Little Rock, Arkansas, U.S.A.
authors.forename: Zachary N
authors.initials: ZN
authors.lastname: Stowe
authors.affiliation: University of Miami Miller School of Medicine, Miami, Florida, U.S.A.
authors.forename: D Jeffrey
authors.initials: DJ
authors.lastname: Newport
authors.affiliation: Emory University School of Medicine, Atlanta, Georgia, U.S.A.
authors.forename: James C
authors.initials: JC
authors.lastname: Ritchie
authors.affiliation: Brigham and Women's Hospital, Boston, Massachusetts, U.S.A.|Harvard Medical School, Boston, Massachusetts, U.S.A.
authors.forename: Page B
authors.initials: PB
authors.lastname: Pennell
mesh_terms: D000927:Anticonvulsants / Q000009:adverse effects* / Q000493:pharmacokinetics*; D001714:Bipolar Disorder / Q000097:blood* / Q000188:drug therapy*; D036861:Delivery, Obstetric; D004305:Dose-Response Relationship, Drug; D004827:Epilepsy / Q000097:blood* / Q000188:drug therapy*; D005260:Female; D005312:Fetal Blood; D006801:Humans; D007231:Infant, Newborn; D008431:Maternal-Fetal Exchange / Q000502:physiology*; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000097:blood* / Q000188:drug therapy*; D011256:Pregnancy Outcome; D012307:Risk Factors
chemical_list: D000927:Anticonvulsants
keywords: Antiepileptic drugs; Epilepsy; Placental passage; Pregnancy; Umbilical cord concentrations