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Published on: June 28, 2024
Maternal allopurinol administration during suspected fetal hypoxia: a novel neuroprotective intervention? A
Joepe J Kaandorp1, Manon J N L Benders1, Ewoud Schuit2
1Department of Perinatology, University Medical Center, Utrecht, The Netherlands.
Objective:
To determine whether maternal allopurinol treatment during suspected fetal hypoxia would reduce the release of biomarkers associated with neonatal brain damage.
Design:
A randomised double-blind placebo controlled multicentre trial.
Patients:
We studied women in labour at term with clinical indices of fetal hypoxia, prompting immediate delivery.
Setting:
Delivery rooms of 11 Dutch hospitals.
Intervention:
When immediate delivery was foreseen based on suspected fetal hypoxia, women were allocated to receive allopurinol 500 mg intravenous (ALLO) or placebo intravenous (CONT).
Main Outcome Measures:
Primary endpoint was the difference in cord S100ß, a tissue-specific biomarker for brain damage.
Results:
222 women were randomised to receive allopurinol (ALLO, n=111) or placebo (CONT, n=111). Cord S100ß was not significantly different between the two groups: 44.5 pg/mL (IQR 20.2-71.4) in the ALLO group versus 54.9 pg/mL (IQR 26.8-94.7) in the CONT group (difference in median -7.69 (95% CI -24.9 to 9.52)). Post hoc subgroup analysis showed a potential treatment effect of allopurinol on the proportion of infants with a cord S100ß value above the 75th percentile in girls (ALLO n=5 (12%) vs CONT n=10 (31%); risk ratio (RR) 0.37 (95% CI 0.14 to 0.99)) but not in boys (ALLO n=18 (32%) vs CONT n=15 (25%); RR 1.4 (95% CI 0.84 to 2.3)). Also, cord neuroketal levels were significantly lower in girls treated with allopurinol as compared with placebo treated girls: 18.0 pg/mL (95% CI 12.1 to 26.9) in the ALLO group versus 32.2 pg/mL (95% CI 22.7 to 45.7) in the CONT group (geometric mean difference -16.4 (95% CI -24.6 to -1.64)).
Conclusions:
Maternal treatment with allopurinol during fetal hypoxia did not significantly lower neuronal damage markers in cord blood. Post hoc analysis revealed a potential beneficial treatment effect in girls.
Trial Registration Number:
NCT00189007, Dutch Trial Register NTR1383.
