Neonatal Hypoxia Ischaemia: Mechanisms, Models, and Therapeutic Challenges
We evaluated the effect of phenobarbital (PB) on two sequelae of hypoxic-ischemic insult in prematures, early intraventricular hemorrhage (IVH) and late handicap due to neuronal damage. Infants weighing ≤1500g admitted before 4 hr of age were randomly assigned into a phenobarbital group (PB+), to receive 15 mg/kg iv twice at a 4 hr interval, followed by 5 mg/kg every 24 hr for 5 days, or into a control group (PB-). 45 infants were enrolled into the PB+ and 49 into the PB- group; 7 PB+ and 3 PB- infants died neonatally. IVH was diagnosed by ultrasound (US) in 13 PB+ infants (29%), 4 of them severe (grades III-IV). 28 PB- infants (57%) had IVH, 7 of them severe. Overall incidence of IVH was significantly higher in the PB-group α2=8.8, p<0.01), but when considering only severe IVH there was no significant difference between the groups. At follow-up 13 (39%) PB+ and 17 (40%) PB- infants had ventricular dilatation on US; marked dilatation or hydrocephalus was found in 5 PB+ and 12 PB- infants (NS difference). Neurodevelopmental status at 15 months of age revealed mild abnormality in 4 (11%) PB+ and 4 (9%) PB- infants, whereas it was clearly abnormal in 5 (14%) PB+ and 4 (9%) PB- infants.Our results indicate that early high-dose PS-treatment of small prematures decreased the incidence of mild to moderate IVH. However, follow-up so far has failed to show a difference between treatment and control groups in neurodevelopmental outcome or incidence of ventricular dilatation. Routine administration of PB to small prematures cannot be recommended.