Maternal allopurinol during fetal hypoxia lowers cord blood levels of the brain injury marker S-100B.
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.
Torrance
Helen L
HL
Perinatal Center, University Medical Center/Wilhelmina Children's Hospital, Utrecht, Netherlands;. h.torrance@umcutrecht.nl
Benders
Manon J
MJ
Derks
Jan B
JB
Rademaker
Carin M A
CM
Bos
Arie F
AF
Van Den Berg
Paul
P
Longini
Mariangela
M
Buonocore
Giuseppe
G
Venegas
MariaElena
M
Baquero
Hernando
H
Visser
Gerard H A
GH
Van Bel
Frank
F
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
D016166:Free Radical Scavengers; D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; D000493:Allopurinol