Impact of postnatal nutrition on neurodevelopmental outcome in rat model of intrauterine growth restriction.

Abstract

There are limited data on nutritional management of infants with intrauterine growth restriction (IUGR). Postnatal protein supplementation for promoting growth is a common clinical practice in neonatology. The present study aims to investigate the consequences of protein supplementation on long-term growth, brain and body weight, brain histology and behavioral outcome in a rat model of IUGR. Twenty-four IUGR-formed rat puppies and 12 healthy puppies were included in the study. IUGR model was established by low (10%) protein diet throughout pregnancy together with intraperitoneal injection of lipopolysaccharide (LPS). Pups were started to be fed with either standard protein (SP), or high protein (HP) diet until postnatal day (PN) 35. Puppies in the control group were given SP diet for 35 days. Six pups from each group were sacrificed at PN7, remaining six were evaluated by Morris water maze test between PN 30 to 35 days and then sacrificed at PN35. Histologic evaluation of brain tissue was performed at PN7 and PN35. IUGR group displayed lower body and brain weights at PN7 when compared with control. At PN35, SP group achieved similar brain/body weight ratios with control, whereas HP group displayed lowest brain/body weight ratio. The number of TUNEL positive cells was significantly higher and myelin basic protein and oligodendrocyte marker O4 immunoreactivity were significantly lower in HP group when compared with SP at PN35. Neuronal density in prefrontal cortex and hippocampus at PN7 were similar among SP and HP groups, but significantly lower in HP group when compared with SP at PN35. SP group displayed better results in the Morris water maze test when compared with HP group. Although postnatal HP support is associated with increase in body weight at PN35, it did not result in better brain/body weight ratios in the rat model of IUGR. In IUGR rats, HP diet was associated with increased apoptosis in brain tissue with lower neuronal density and decreased myelination when compared to SP. Furthermore, better neurodevelopmental scores were achieved by SP diet rather than HP support in IUGR.