Abstract
OBJECTIVE:
Perinatal hypoxia-induced free radical formation is an important cause of hypoxic-ischaemic encephalopathy and subsequent neurodevelopmental disabilities. Allopurinol reduces the formation of free radicals, which potentially limits hypoxia-induced brain damage. We investigated placental transfer and safety of allopurinol after maternal allopurinol treatment during labour to evaluate its potential role as a neuroprotective agent in suspected fetal hypoxia.
DESIGN:
We used data from a randomised, double-blind multicentre trial comparing maternal allopurinol versus placebo in case of imminent fetal hypoxia (NCT00189007).
PATIENTS:
We studied 58 women in labour at term, with suspected fetal hypoxia prompting immediate delivery, in the intervention arm of the study.
SETTING:
Delivery rooms of 11 Dutch hospitals.
INTERVENTION:
500 mg allopurinol, intravenously to the mother, immediately prior to delivery.
MAIN OUTCOME MEASURES:
Drug disposition (maternal plasma concentrations, cord blood concentrations) and drug safety (maternal and fetal adverse events).
RESULTS:
Within 5 min after the end of maternal allopurinol infusion, target plasma concentrations of allopurinol of ≥2 mg/L were present in cord blood. Of all analysed cord blood samples, 95% (52/55) had a target allopurinol plasma concentration at the moment of delivery. No adverse events were observed in the neonates. Two mothers had a red and/or painful arm during infusion.
CONCLUSIONS:
A dose of 500 mg intravenous allopurinol rapidly crosses the placenta and provides target concentrations in 95% of the fetuses at the moment of delivery, which makes it potentially useful as a neuroprotective agent in perinatology with very little side effects.
TRIAL REGISTRATION:
The study is registered in the Dutch Trial Register (NTR1383) and the Clinical Trials protocol registration system (NCT00189007).
Perinatal hypoxia-induced free radical formation is an important cause of hypoxic-ischaemic encephalopathy and subsequent neurodevelopmental disabilities. Allopurinol reduces the formation of free radicals, which potentially limits hypoxia-induced brain damage. We investigated placental transfer and safety of allopurinol after maternal allopurinol treatment during labour to evaluate its potential role as a neuroprotective agent in suspected fetal hypoxia.
DESIGN:
We used data from a randomised, double-blind multicentre trial comparing maternal allopurinol versus placebo in case of imminent fetal hypoxia (NCT00189007).
PATIENTS:
We studied 58 women in labour at term, with suspected fetal hypoxia prompting immediate delivery, in the intervention arm of the study.
SETTING:
Delivery rooms of 11 Dutch hospitals.
INTERVENTION:
500 mg allopurinol, intravenously to the mother, immediately prior to delivery.
MAIN OUTCOME MEASURES:
Drug disposition (maternal plasma concentrations, cord blood concentrations) and drug safety (maternal and fetal adverse events).
RESULTS:
Within 5 min after the end of maternal allopurinol infusion, target plasma concentrations of allopurinol of ≥2 mg/L were present in cord blood. Of all analysed cord blood samples, 95% (52/55) had a target allopurinol plasma concentration at the moment of delivery. No adverse events were observed in the neonates. Two mothers had a red and/or painful arm during infusion.
CONCLUSIONS:
A dose of 500 mg intravenous allopurinol rapidly crosses the placenta and provides target concentrations in 95% of the fetuses at the moment of delivery, which makes it potentially useful as a neuroprotective agent in perinatology with very little side effects.
TRIAL REGISTRATION:
The study is registered in the Dutch Trial Register (NTR1383) and the Clinical Trials protocol registration system (NCT00189007).
| Original language | Undefined/Unknown |
|---|---|
| Pages (from-to) | F144-148 |
| Number of pages | 5 |
| Journal | Archives of Disease in Childhood Fetal and Neonatal Edition |
| Volume | 99 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 2014 |
Keywords
- Econometric and Statistical Methods: General
- Geneeskunde (GENK)
- Geneeskunde(GENK)
- Medical sciences
- Bescherming en bevordering van de menselijke gezondheid