Efficacy and safety of prenatal allopurinol treatment in low birth weight piglets with special emphasis on learning ability

Abstract

Allopurinol is a medicine which is currently studied in a clinical trial in humans to possibly prevent brain damage caused by acute shortage of oxygen around birth. Earlier studies showed that allopurinol can limit brain damage by reducing the formation of free radicals after acute asphyxia/hypoxia. However, no research has yet been conducted on the long-term cognitive effects after chronic, prenatal treatment of prolonged but mild asphyxia during pregnancy. In the present study, pigs were used as model species for studying the long-term effects of allopurinol on cognition. In addition, we investigated possible side effects of this treatment. Six sows were treated with allopurinol during the last trimester of pregnancy. Six untreated sows served as controls. After birth, piglets and placentas were measured, and umbilical cord mixed blood samples were taken. For cognitive tests, piglets with normal birth weight (NBW) and low birth weight (LBW) were selected per sow. It is believed that low birth weight reflects intra-uterine growth restriction, caused by a shortage of oxygen, i.e. mild asphyxia and/or nutrients that reach the fetus. An Open Field test was conducted, and learning ability was assessed using the cognitive Holeboard task. Treatment reduced placenta length and increased piglet length, but did not affect other measures. LBW piglets vocalized more in the Open Field test than NBW piglets, suggesting that they are more easily stressed. No differences were found in Holeboard task performance, although there are indications that allopurinol might reduce learning ability. Further research is needed to elucidate these indications.