title: Sirenomelia after phenobarbital and carbamazepine therapy in pregnancy.
abstract: BACKGROUND
  Epilepsy still remains a serious challenge for any obstetrician due to the potential teratogenicity of all antiepileptics. However, without appropriate maternal therapy the seizures can reappear, with direct negative impact on fetus. Currently, sirenomelia is the most severe caudal pole dysgenesis, consequent to an abnormal vascular supply development in the fetal lower body.
  
  
  METHODS
  We report a stillborn, GA/LMP = 37 weeks, delivered by an epileptic woman, who received in the first four months of pregnancy phenobarbital (PH) 0.1 g/day and carbamazepine (CMZ) 0.4 g/day, followed only by PH 0.1 g/day, until delivery. The stillborn, weighing 2200 g, presented sirenomelia type II, with some of its "classic" features: oligohydramnios, absence of kidneys, bladder, rectum, uterus, and a single umbilical artery. Some other "particularities" included: no Potter's facies and no significant cardio-pulmonary abnormalities.
  
  
  CONCLUSIONS
  Since PH and CMZ alone are responsible, commonly, for mild abnormalities, we hypothesized that combined therapy with PH and CMZ (both strong enzyme-inductors, especially PH) potentiated their teratogenicity, by producing supplementary quantities of epoxides and/or other oxides, which accumulated in the fetal tissues. Except for sirenomelia, all other mild abnormalities, theoretically associated with "fetal CMZ and/or PH syndrome," are rarely observed, fact which demonstrates the drug-drug interactions between the two antiepileptics.
  
  
  CONCLUSIONS
  This report highlights the possibility that PH/CBZ therapy during fetal organogenesis can induce sirenomelia, by a synergistic teratogenic effect and support the recommendation to use only one drug in pregnant epileptic women. A careful ultrasound monitoring of these patients is mandatory due to the teratogenic risk of both seizures and therapy.
authors.affiliation: Department of Mother and Child, University of Medicine and Pharmacy, Craiova, Romania.
authors.forename: Oana Sorina
authors.initials: OS
authors.lastname: Tica
authors.forename: Andrei Adrian
authors.initials: AA
authors.lastname: Tica
authors.forename: Cristina Gabriela
authors.initials: CG
authors.lastname: Brailoiu
authors.forename: Nicolae
authors.initials: N
authors.lastname: Cernea
authors.forename: Vlad Iustin
authors.initials: VI
authors.lastname: Tica
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000473:pathology*; D002220:Carbamazepine / Q000009:adverse effects*; D004480:Ectromelia / Q000139:chemically induced*; D004827:Epilepsy / Q000188:drug therapy*; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D010634:Phenobarbital / Q000009:adverse effects*; D011247:Pregnancy
chemical_list: D002220:Carbamazepine; D010634:Phenobarbital