title: Maternal allopurinol during fetal hypoxia lowers cord blood levels of the brain injury marker S-100B.
abstract: BACKGROUND
  Fetal hypoxia is an important determinant of neonatal encephalopathy caused by birth asphyxia, in which hypoxia-induced free radical formation plays an important role.
  
  
  OBJECTIVE
  Maternal treatment with allopurinol, will cross the placenta during fetal hypoxia (primary outcome) and reduce S-100B and free radical formation (secondary outcome).
  
  
  METHODS
  In a randomized, double-blind feasibility study, 53 pregnant women in labor (54 fetuses) with a gestational age of >36 weeks and fetal hypoxia, as indicated by abnormal/nonreassuring fetal heart rate tracing or fetal scalp pH of <7.20, received 500 mg of allopurinol or placebo intravenously. Severity of fetal hypoxia, brain damage and free radical formation were assessed by arterial cord blood lactate, S-100B and non-protein-bound-iron concentrations, respectively. At birth, maternal and cord blood concentrations of allopurinol and its active metabolite oxypurinol were determined.
  
  
  RESULTS
  Allopurinol and oxypurinol concentrations were within the therapeutic range in the mother (allopurinol > 2 mg/L and/or oxypurinol > 4 mg/L) but not always in arterial cord blood. We therefore created 3 groups: a placebo (n = 27), therapeutic allopurinol (n = 15), and subtherapeutic allopurinol group (n = 12). Cord lactate concentration did not differ, but S-100B was significantly lower in the therapeutic allopurinol group compared with the placebo and subtherapeutic allopurinol groups (P < .01). Fewer therapeutic allopurinol cord samples had measurable non-protein-bound iron concentrations compared with placebo (P < .01).
  
  
  CONCLUSIONS
  Maternal allopurinol/oxypurinol crosses the placenta during fetal hypoxia. In fetuses/newborns with therapeutic allopurinol/oxypurinol concentrations in cord blood, lower plasma levels of the brain injury marker protein S-100B were detected. A larger allopurinol trial in compromised fetuses at term seems warranted. The allopurinol dosage must be adjusted to achieve therapeutic fetal allopurinol/oxypurinol concentrations.
authors: Perinatal Center, University Medical Center/Wilhelmina Children's Hospital, Utrecht, Netherlands;. h.torrance@umcutrecht.nl
authors: Helen L
authors: HL
authors: Torrance
authors: Manon J
authors: MJ
authors: Benders
authors: Jan B
authors: JB
authors: Derks
authors: Carin M A
authors: CM
authors: Rademaker
authors: Arie F
authors: AF
authors: Bos
authors: Paul
authors: P
authors: Van Den Berg
authors: Mariangela
authors: M
authors: Longini
authors: Giuseppe
authors: G
authors: Buonocore
authors: MariaElena
authors: M
authors: Venegas
authors: Hernando
authors: H
authors: Baquero
authors: Gerard H A
authors: GH
authors: Visser
authors: Frank
authors: F
authors: Van Bel
mesh_terms: D000328:Adult; D000493:Allopurinol / Q000008:administration & dosage* / Q000097:blood; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004311:Double-Blind Method; D005240:Feasibility Studies; D005260:Female; D005312:Fetal Blood / Q000378:metabolism*; D005311:Fetal Hypoxia / Q000378:metabolism* / Q000517:prevention & control; D005333:Fetus / Q000187:drug effects / Q000502:physiology; D016166:Free Radical Scavengers / Q000008:administration & dosage* / Q000097:blood; D006801:Humans; D008431:Maternal-Fetal Exchange / Q000502:physiology*; D009414:Nerve Growth Factors / Q000097:blood*; D010865:Pilot Projects; D011247:Pregnancy; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000097:blood*; D055815:Young Adult
chemical_list: D016166:Free Radical Scavengers; D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; D000493:Allopurinol