Animal models for small-for-gestational-age (SGA) neonates and infants-at-risk (IAR)

Abstract

In this study, the body weight changes seen in rat dams and brain and body weights seen in pups as sequelae of either an overt or a hidden form of chronic protein deprivation have been examined. In the overt model, the 6% casein-diet pups showed SGA brain and body weight deficits and irreversible central and peripheral chemical changes at birth. In contrast, the hidden form of prenatal deprivation did not result in brain and body weight deficits in the 8% casein-diet pups at birth, but their SGA-like irreversible peripheral and central chemical profiles categorizes them as IAR-neonates. In cross-fostering experiments it was shown that pups from dams fed an 8% casein-diet cross-fostered onto 25% casein-diet dams at birth showed no significant differences in brain or body weight at weaning, whereas pups from 6% casein-diet dams cross-fostered onto 25% casein-diet dams at birth continued to show significantly lower brain and body weights at weaning. These studies show that the 8% casein-diet rat at birth is an IAR model because of its irreversible peripheral and central chemical changes dating form birth, even though the body and brain weights are essentially the same as the pups from 25% casein-diet dams. On the other hand, the pups from 6% casein-diet dams are SGA animals at birth and these brain and body weight deficits at birth cannot be completely reversed at weaning even when the pup is cross-fostered to a 25% casein-diet dam at birth. In both the IAR (8%) and SGA (6%) neonates, the following central and peripheral chemical changes were demonstrated: markedly elevated plasma non-esterified fatty acids (NEFA); markedly elevated regional brain levels of phenylalanine, norepinephrine (NE), tryptophan, 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA). These chemical changes were not reversed by cross-fostering the 6% or 8% casein-diet neonates by 25% casein-diet dams. Such chemical data at birth were not necessary to characterize the 6% casein-diet pups as SGA, because of their marked decrease in body and brain weights. This is also true for the 6% casein diet pups cross-fostered by 25% casein-diet dams. The possible implications of these findings in humans is discussed.