Exploring the Effects of Early Nutritional Interventions on Growth, Metabolic Profiles, and Neurodevelopment in Preterm Rat Models

Background: During the critical window of development, malnutrition can have long-term metabolic and neurodevelopmental consequences. Objective: To evaluate the effect of early postnatal malnutrition and catch-up growth on metabolic profile and neurodevelopment in a preterm rat model, while adjusting for current body weight. Methods: This experimental study was conducted on 142 neonatal rats. Rats were randomly allocated to normal (N) and malnourished (R) groups, from days 2-11 of postnatal life. Using litter size modification, malnourished rats were divided into three subgroups based on catch-up growth patterns (accelerated (RC), normal (RN) or no (RR) catchup), from days 11-21. Rats were provided food ad libitum from day 21 to 60. Growth velocity, serum glucose, insulin, leptin, triglycerides, and neurodevelopmental outcomes were compared among groups at day 60 while adjusting for body weight. Results: During the catch-up growth phase, rats with accelerated growth (RC) exhibited significantly higher growth velocity (p<0.001) than normally fed rats (N), but this difference diminished by the study's end. Serum glucose concentrations were significantly higher in rats with rapid catch-up growth compared to those with normal (p=0.003) or no (p<0.001) catch-up growth. Serum insulin (p=0.15) and leptin (p=0.97) levels did not significantly differ among subgroups. Malnourished rats with normal catch-up growth demonstrated better-learned behaviour than rats with rapid (p=0.013) or no (p=0.009) catch-up growth. Conclusion: Catch-up growth at a normal velocity after early postnatal malnutrition preserves metabolic health while limiting neurodevelopmental deficit. Accelerated catch-up growth, though transiently beneficial for growth, can increase vulnerability to neurodevelopmental deficits. These findings urge a nuanced approach in developmental biology and pediatric medicine for effective interventions and improved outcomes among preterm infants.