Parenteral Nutrition Compromises Neurodevelopment of Preterm Pigs

Background: Despite advances in nutritional support and intensive care, preterm infants are at higher risk of compromised neurodevelopment. Objective: This study evaluated the contribution of total parenteral nutrition (PN) to compromised neurodevelopment after preterm birth. Methods: Preterm pigs were provided PN or enteral nutrition (EN) for 10 d. Neurodevelopment was assessed by observations of motor activity and evaluation of sensory/motor reflexes, brain weight, MRI, and cerebellar histology. Results: Despite similar gains in body weight, PN pigs had smaller brains (32 ± 0.4 vs. 35 ± 0.6 g; P = 0.0002) including the cerebellum, as well as reduced motor activity (P = 0.005), which corresponded to underdeveloped myelination (P = 0.004) measured by diffusion tensor imaging. PN resulted in lower serum triglycerides (17 ± 5.9 vs. 27 ± 3.1 mg/dL; P = 0.05), total cholesterol (31 ± 9.6 vs. 85 ± 8.1 mg/dL; P = 0.04), VLDL cholesterol (3.7 ± 1.2 vs. 5.7 ± 0.7 mg/dL; P = 0.04), and HDL cholesterol (16 ± 4.6 vs. 57 ± 7.3 mg/dL; P = 0.03) and nonsignificantly lower LDL cholesterol (10.7 ± 4.4 vs. 22.7 ± 2.9 mg/dL; P = 0.09). Conclusions: The compromised neurodevelopment caused by total PN is a novel finding, was independent of confounding variables (disease, inconsistent gestational ages, diverse genetics, extrauterine growth retardation, and inconsistent neonatal intensive care unit protocols), and highlights a need to improve current PN solutions. The preterm pig is a translational animal model for improving nutrition support to enhance neurodevelopment of preterm infants requiring PN.