Allopurinol for fetal neuro- and cardiovascular protection

The studies presented in this thesis indicate that maternally administered allopurinol rapidly crosses the placenta, is effective in suppressing xanthine oxidase activity, has little adverse side effects (as long as clinically compatible dosages are used) and is potentially effective in preventing hypoxic ischemic damage to the heart and brain in fetal sheep and human female neonates. The latter, however, is based on post-hoc analyses and should be more intensively investigated before being implemented in perinatal medicine. Maternally administered allopurinol seems to have too little beneficial effects when used as a solemn therapeutic approach for perinatal asphyxia in a clinical setting, probably because fetal surveillance during labor is still too insensitive to optimally detect imminent fetal asphyxia. This may result in a suboptimal selection of patients really needing the treatment. Future research could therefore combine fetal allopurinol (pre)treatment (prevention) with another promising fetal neuroprotective agent like melatonin, and postnatal neuroprotective interventions (repair), such as hypothermia, postnatally administered allopurinol, 2-IB, erythropoietin or stem cells if the newborn infant appears to be really asphyxiated at birth (i.e. Apgar score <7 at 5 minutes, pH umbilical artery <7.05). Alternatively, in case of unexpected birth asphyxia, allopurinol treatment via the umbilical cord at the resuscitation table might result in a more optimal selection of infants needing treatment. This approach bypasses any placental problems, which may result in suboptimal placental transfer of allopurinol. And finally, any future research focusing on perinatal neuroprotective strategies should always take gender differences into account.