Kim Annink

186 Chapter 8 The ALBINO study group extensively discussed the various ethical implications of need for additional treatment for HIE, need to administer allopurinol very early for best efficacy, need for parental consent to ensure patient autonomy and burden to the parents in the emergency situation of perinatal HIE. The European Foundation for the Care of Newborn Infants (EFCNI), which is composed of parents, healthcare experts, scientists and politicians, has been asked for advice. The EFCNI endorsed the conduct of the ALBINO trial in a letter of support in September 2016. Because perinatal HIE occurs rarely and unpredictably and because of the need for very early administration of allopurinol, the EFCNI agreed with the approach of deferred consent. Furthermore, independent ethics experts provided advice. Whereas all experts agreed that regular informed consent by the parents, which includes appropriate time for reflection and further questions is not feasible before administration of the first dose of study medication in the context of ALBINO due to the unpredictable emergency situation. Opinions within the group as well as among external experts ranged from ‘deferred consent is unacceptable’ to ‘deferred consent is justified and the better option’, so that the decision was left to the national leading ethics committees in each country. Currently, we are conducting a survey among parents-to-be and parents of infants with a history of HIE to better understand how parents might feel about deferred versus short oral consent. An additional survey will follow parents of infants enrolled in the ALBINO trial to capture their satisfaction with the various approaches and to inform future trials in similar situations. CONCLUSIONS In conclusion, infants with HIE still suffer from death and long-term NDI despite improved standards of care including therapeutic hypothermia. The neurodevelopmental outcome of infants with HIE should be further improved with additional neuroprotective interventions. The aim of the ALBINO trial is to investigate the neuroprotective effect of very early allopurinol within 45 minutes after birth aiming to reduce the formation of the toxic superoxide and subsequent secondary energy failure and apoptosis.