Rapid target allopurinol concentrations in the hypoxic fetus after maternal administration during labour.

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).

The value of umbilical artery Doppler velocimetry in the antenatal surveillance of uncomplicated monochorionic twin pregnancies.

OBJECTIVES: To investigate the predictive value of abnormal umbilical artery Doppler findings on outcome in uncomplicated monochorionic (MC) twin pregnancies. METHODS: Sixty-seven MC twin pregnancies, with antenatal care and delivery at the University Medical Center, Utrecht, The Netherlands, between 1999 and 2004, were studied. Pregnancies with antenatal signs of twin-to-twin transfusion syndrome were excluded. We analyzed the data according to both the last Doppler measurement of the umbilical artery before delivery and the presence of any abnormal Doppler measurement during the course of pregnancy. Risks of mortality and total neonatal morbidity were stratified according to the Doppler findings in one or both fetuses at the time of each standard ultrasound assessment in order to estimate the risk associated with an abnormal Doppler finding at or before that specific gestational age. RESULTS: Mortality rates were similar in the normal and abnormal Doppler groups. Using both group definitions, total neonatal morbidity was higher in the abnormal Doppler group; this was significant at > 32 weeks' gestation, and was due to lower birth weight and earlier gestational age at delivery. There was no mortality at > or = 36 weeks in the abnormal Doppler group, but there were four perinatal deaths in the normal Doppler group. Gestational age at delivery was significantly lower when one or more abnormal Doppler findings had been present (median, 34 + 1 weeks vs. 36 + 3 weeks) and infants with abnormal Doppler findings weighed on average 261 g (95% CI, 21-502 g) less than those with normal findings. CONCLUSIONS: In MC twins, abnormal Doppler flow of the umbilical artery identifies a subgroup at risk for preterm delivery, low birth weight and neonatal morbidity, but with a similar mortality risk to those with normal Doppler flow. At term, mortality occurred only in the group with normal Doppler findings, suggesting that fetal surveillance is insufficient in uncomplicated term MC twin pregnancies.