Kaandorp, J.van Den Broek, M.Benders, M.Oudijk, M.Porath, M.Oetomo, S.Wouters, M.van Elburg, R.Franssen, M.Bos, A.Mol, B.Visser, G.van Bel, F.Rademaker, C.Derks, J.De Haan, T.Boon, J.De Boer, I.Rijnders, R.Jacobs, C.et al.2016-01-052016-01-052014Archives of Disease in Childhood: Fetal and Neonatal Edition, 2014; 99(2):F144-F1481359-29981468-2052http://hdl.handle.net/2440/97632OBJECTIVE: 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).enCopyright status unknownALLO-trial Study GroupFetal BloodFetusPlacentaHypoxia-Ischemia, BrainFree RadicalsAllopurinolNeuroprotective AgentsFree Radical ScavengersDouble-Blind MethodPregnancyLabor, ObstetricMaternal-Fetal ExchangeInfant, NewbornFetal HypoxiaJournal article003002319810.1136/archdischild-2013-3048760003353237000122-s2.0-84894061711173946Mol, B. [0000-0001-6887-0262] [0000-0001-8337-550X]