Chronic Allopurinol Treatment during the Last Trimester of Pregnancy in Sows: Effects on Low and Normal Birth Weight Offspring

Abstract

Low-birth-weight (LBW) children are born with several risk factors for disease, morbidity and neonatal mortality, even if carried to term. Placental insufficiency leading to hypoxemia and reduced nutritional supply is the main cause for LBW. Brain damage and poor neurological outcome can be the consequence. LBW after being carried to term gives better chances for survival, but these children are still at risk for poor health and the development of cognitive impairments. Preventive therapies are not yet available. We studied the risk/efficacy of chronic prenatal treatment with the anti-oxidative drug allopurinol, as putative preventive treatment in piglets. LBW piglets served as a natural model for LBW. A cognitive holeboard test was applied to study the learning and memory abilities of these allopurinol treated piglets after weaning. Preliminary analysis of the plasma concentrations in sows and their piglets suggested that a daily dose of 15 mg.kg−1 resulted in effective plasma concentration of allopurinol in piglets. No adverse effects of chronic allopurinol treatment were found on farrowing, birth weight, open field behavior, learning abilities, relative brain, hippocampus and spleen weights. LBW piglets showed increased anxiety levels in an open field test, but cognitive performance was not affected by allopurinol treatment. LBW animals treated with allopurinol showed the largest postnatal compensatory body weight gain. In contrast to a previous study, no differences in learning abilities were found between LBW and normal-birth-weight piglets. This discrepancy might be attributable to experimental differences. Our results indicate that chronic prenatal allopurinol treatment during the third trimester of pregnancy is safe, as no adverse side effects were observed. Compensatory weight gain of treated piglets is a positive indication for the chronic prenatal use of allopurinol in these animals. Further studies are needed to assess the possible preventive effects of allopurinol on brain functions in LBW piglets.

Very low birth weight piglets show improved cognitive performance in the spatial cognitive holeboard task

“… *For further information about the operational definitions of these variables, see Gieling et al ( 2014 ) . …”

“…Memory scores improved and latencies declined over the course of the experiment for all piglets. Although we attempted to test the piglets in our study at a younger age than previous studies using the holeboard task for pigs (Arts et al, 2009 (9 weeks); Haagensen et al, 2013 (6–7 weeks, minipigs); Gieling et al, 2014 (7–8 weeks)), the piglets were not able to perform the task until they were approximately 7 weeks of age. It can therefore be assumed that a certain level of physical and mental development needs to be achieved in order to perform the holeboard task, which the piglets reach at about 7 weeks of age.…”

Judgement bias in pigs is independent of performance in a spatial holeboard task and conditional discrimination learning

“…Low-birth-weight (LBW) pigs weighed at least 1SD below the litter mean, while normal-birth-weight (NBW) pigs were those closest to an adjusted litter mean (mean excluding LBW pig weights) as in Gieling et al (2014) †  Five sows had been treated with 15 mg kg −1 Allopurinol for the 30 days (±2 days) before farrowing ‡  All piglets from 8 litters were weighed at birth. One or two male piglets and one or two corresponding female piglets weighing closest to the litter mean (calculated separately for male and female piglets) were selected from each litter…”

Pre-weaning dietary iron deficiency impairs spatial learning and memory in the cognitive holeboard task in piglets

“… Performance of ID and control animals in the spatial cognitive holeboard task during habituation (hab) (A), and the acquisition (Acq), transition (Trans), and reversal (Rev) phases (B) . * For further information about the operational definitions of these variables, see Gieling et al ( 2014 ). …”