New generation lipid emulsions increase brain DHA and improve body composition, but not short-term neurodevelopment in parenterally-fed preterm piglets

Authors: MOLINA, TIFFANY - Baylor College Of Medicine; STOLL, BARBARA - Children'S Nutrition Research Center (CNRC); MOHAMMAD, MAHMOUD - Children'S Nutrition Research Center (CNRC); MOHILA, CARRIE - Baylor College Of Medicine; CALL, LEE - Children'S Nutrition Research Center (CNRC); CUI, LIWEI - Children'S Nutrition Research Center (CNRC); GUTHRIE, GREGORY - Children'S Nutrition Research Center (CNRC); KUNICHOFF, DENNIS - Children'S Nutrition Research Center (CNRC); LIN, SEN - Sichuan Institute; WELCH-JERNIGAN, REBECCA - Baylor College Of Medicine; NIELSEN, JON - Rigshospitalet - Copenhagen University Hospital; PREMKUMAR, MURALIDHAR - Baylor College Of Medicine; ROBINSON, JASON - Children'S Nutrition Research Center (CNRC); SMITH, VICTORIA - California Polytechnic State University; TEETS, HALEY - California Polytechnic State University; OBELITZ-RYOM, KARINA - Copenhagen University; HAGAN, JOSEPH - Baylor College Of Medicine; CRUZ, STEPHANIE - Copenhagen University; LAU, PATRICIO - Baylor College Of Medicine; PUYAU, MAURICE - Children'S Nutrition Research Center (CNRC); FANG, ZHENGFENG - Sichuan Institute; SHYPAILO, ROMAN - Children'S Nutrition Research Center (CNRC); MANJARIN, RODRIGO - California Polytechnic State University; BUTTE, NANCY - Children'S Nutrition Research Center (CNRC); Burrin, Douglas - Doug; OLUTOYE, OLUYINKA - Baylor College Of Medicine; THYMANN, THOMAS - Copenhagen University; SANGILD, PER - Copenhagen University

Submitted to: Brain Behavior and Immunity
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/23/2019
Publication Date: 4/23/2019
Citation: Molina, T.L., Stoll, B., Mohammad, M., Mohila, C.A., Call, L., Cui, L., Guthrie, G., Kunichoff, D., Lin, S., Welch-Jernigan, R., Nielsen, J., Premkumar, M., Robinson, J., Smith, V., Teets, H., Obelitz-Ryom, K., Hagan, J., Cruz, S., Lau, P., Puyau, M., Fang, Z., Shypailo, R., Manjarin, R., Butte, N., Burrin, D.G., Olutoye, O., Thymann, T., Sangild, P. 2019. New generation lipid emulsions increase brain DHA and improve body composition, but not short-term neurodevelopment in parenterally-fed preterm piglets. Brain Behavior and Immunity. https://doi.org/10.1016/j.bbi.2019.04.031.
DOI: https://doi.org/10.1016/j.bbi.2019.04.031

Interpretive Summary: Many infants born prematurely in the United States each year rely on intravenous nutrition support for survival and growth. Infants rely on the technique called total parenteral nutrition (TPN) where they are fed intravenously with an emulsion of fluid, electrolytes, amino acids, glucose, fats, vitamins and minerals. Fats are especially important to preterm infants because they need key fatty acids to support normal brain growth and development, mainly, docosahexaenoic acid (DHA) and arachidonic acid (AA). The current soybean-oil lipid emulsions (Intralipid) approved for use in preterm infants does not contain DHA, and new generation lipid emulsions (SMOFlipid) with multiple-component oil blends may have inappropriate ratios of DHA and AA. The goal of this study was to test an experimental lipid emulsion (EXP) with increased DHA and AA content on brain fatty acid profiles and neurodevelopment in a preterm pig model designed to simulate what happens in premature infants. Our results showed that SMOFlipid and EXP treatments for three weeks after birth increased red blood cell and brain DHA content, lower markers of brain inflammation, but did not result in increased brain growth, neuron density or improved behavioral measures. Interestingly, we observed lower physical activity levels in pigs given TPN compared to those fed formula enterally. We conclude that new generation, multicomponent lipid emulsions enriched with DHA and AA resulted in increased brain DHA and improved body composition without affecting short term neurodevelopmental outcomes.

Technical Abstract: New generation, multicomponent parenteral lipid emulsions provide key fatty acids for brain growth and development, such as docosahexaenoic acid (DHA) and arachidonic acid (AA), yet the content may be suboptimal for preterm infants. Our aim was to test whether DHA and AA-enriched lipid emulsions would increase activity, growth, and neurodevelopment in preterm piglets and limit brain inflammation. Cesarean-delivered preterm pigs were given three weeks of either enteral preterm infant formula (ENT) or TPN with one of three parenteral lipid emulsions: Intralipid (IL), SMOFlipid (SMOF) or an experimental emulsion (EXP). Activity was continuously monitored and weekly blood sampling and behavioral field testing performed. At termination of the study, whole body and tissue metrics were collected. Neuronal density was assessed in sections of hippocampus (HC), thalamus, and cortex. Frontal cortex (FC) and HC tissue were assayed for fatty acid profiles and expression of genes of neuronal growth and inflammation. After 3 weeks of treatment, brain DHA content in SMOF, EXP and ENT pigs was higher (P < 0.01) in FC but not HC vs. IL pigs. There were no differences in brain weight or neuron density among treatment groups. Inflammatory cytokine TNFa and IL-1beta expression in brain regions were increased in IL pigs (P < 0.05) compared to other groups. Overall growth velocity was similar among groups, but IL pigs had higher percent body fat and increased insulin resistance compared to other treatments (P < 0.05). ENT pigs spent more time in higher physical activity levels compared to all TPN groups, but there were no differences in exploratory behavior among groups. We conclude that a soybean oil emulsion increased select brain inflammatory cytokines and multicomponent lipid emulsions enriched with DHA and AA in parenteral lipids results in increased cortical DHA and improved body composition without affecting short term neurodevelopmental outcomes.