Related Experiment Video
Updated: Jul 12, 2025
Effect of Hyaluronic Acid 35 kDa on an In Vitro Model of Preterm Small Intestinal Injury and Healing Using Enteroid-Derived Monolayers
Published on: July 28, 2022
Ultra-High Temperature Treatment of Liquid Infant Formula, Systemic Immunity, and Kidney Development in Preterm
Jing Sun1, Halise Gül Akıllıoğlu2, Jingren Zhong1
1Comparative Pediatrics and Nutrition, Department of Veterinary and Animal Sciences, University of Copenhagen, Denmark.
Insights
Prolonged storage of ultra-high temperature (UHT)-treated infant formula (IF) may negatively impact preterm infant immunity and kidney development. Careful processing and storage are crucial for UHT-treated IF intended for vulnerable newborns.
Area of Science:
- Neonatal nutrition
- Developmental immunology
- Pediatric nephrology
Background:
- Ready-to-feed liquid infant formulas (IFs) are vital for preterm infants when human milk is unavailable.
- Ultra-high temperature (UHT) sterilization of IFs generates Maillard reaction products (MRPs).
- MRPs may pose risks to systemic immune and kidney development in neonates.
Purpose of the Study:
- To investigate the effects of UHT-treated IF, with and without prolonged storage (SUHT), on immune and kidney outcomes in preterm pigs.
- To compare SUHT and UHT-treated IF with pasteurized IF (PAST) as controls.
- To assess systemic immunity, inflammation markers, and kidney development in a preterm pig model.
Main Methods:
- Newborn preterm pigs were fed PAST, UHT, or SUHT infant formulas for 5 days.
- Evaluated blood leukocytes, systemic immunity markers, and inflammation.
- Assessed kidney structure, function, and gene expression related to inflammation and oxidative stress.
Main Results:
- SUHT feeding increased plasma TNFα and IL-6 and reduced neutrophils and LPS response.
- SUHT pigs exhibited upregulated kidney inflammation and oxidative stress gene expressions.
- SUHT pigs showed glomerular mesangial expansion and cell injury, suggesting impaired kidney development.
Conclusions:
- SUHT infant formula may impair systemic immunity and kidney development in preterm newborns.
- The systemic effects of SUHT may stem from local gut inflammatory responses to MRPs.
- Optimal processing and storage duration are critical for UHT-treated liquid IFs for preterm infants.
Scope:
Ready-to-feed liquid infant formulas (IFs) are increasingly being used for newborn preterm infants when human milk is unavailable. However, sterilization of liquid IFs by ultra-high temperature (UHT) introduces Maillard reaction products (MRPs) that may negatively affect systemic immune and kidney development.
Methods And Results:
UHT-treated IF without and with prolonged storage (SUHT) are tested against pasteurized IF (PAST) in newborn preterm pigs as a model for preterm infants. After 5 days, blood leukocytes, markers of systemic immunity and inflammation, kidney structure and function are evaluated. No consistent differences between UHT and PAST pigs are observed. However, SUHT increases plasma TNFα and IL-6 and reduces neutrophils and in vitro response to LPS. In SUHT pigs, the immature kidneys show minor upregulation of gene expressions related to inflammation (RAGE, MPO, MMP9) and oxidative stress (CAT, GLO1), together with glomerular mesangial expansion and cell injury. The increased inflammatory status in SUHT pigs appears unrelated to systemic levels of MRPs.
Conclusion:
SUHT feeding may impair systemic immunity and affect kidney development in preterm newborns. The systemic effects may be induced by local gut inflammatory effects of MRPs. Optimal processing and length of storage are critical for UHT-treated liquid IFs for preterm infants.
