Metabolomics Analysis of Low Birth-Weight Infants Using UHPLC-MS/MS Following Lipid Emulsion

A recent study by scientists from the Hangzhou Women's Hospital (Hangzhou, China) compared the impact of two different lipid emulsions, specifically a soybean oil-based emulsion and a multiple oil emulsion (soybean oil, medium-chain triglycerides, olive oil, and fish oil, SMOF), on serum metabolites of very low birth weight (VLBW) infants using untargeted metabolomics analysis. The team conducted the metabolomics analysis on the serum samples using ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). An article based on the findings from this study was published in BMC Pediatrics (1).

Although the survival rate of VLBW infants has been gradually improving, the reduction of the infants’ complication rates the enhancement of their quality of life remains increasingly important (2.3). Among the common complications VLBW infants can experience are bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), neurological damage, necrotizing enterocolitis (NEC), infections, and parenteral nutrition-associated cholestasis (PNAC) (2,4). As the pathogenesis of these complications is closely related to oxidative stress and inflammatory responses (3,5), the reduction of inflammation and oxidative reactions in VLBW infants is critical (3).

Eligible infants were identified based on the following inclusion criteria: birth weight of less than 1500 g; immediate transfer to the neonatal intensive care unit (NICU) after birth; and signing of relevant informed consent forms by the families of the infants. Exclusion criteria included incomplete data collection; receipt of parenteral nutrition for fewer than 14 days; and the presence of congenital genetic metabolic diseases or severe congenital malformations. To ensure the protection of subject identity and maintain confidentiality, all personal identifiers were removed from the collected data, and a unique study identifier was assigned to each participant. Informed consent was obtained from the families of the infants prior to any study-related procedures, including the collection of samples and clinical information. A simple random sampling method was employed to randomly assign eligible VLBW infants into two groups: the SMOF group and the soybean oil group. To ensure fairness in allocation, the randomization sequence was determined by computer-generated random numbers. During the study period, both groups of subjects adhered to the same parenteral and enteral nutrition protocols. (1).

Initially, 32 VLBW infants met the inclusion criteria for this study. However, three subjects were excluded due to receiving parenteral nutrition for less than 14 days, two subjects were excluded because their families chose to discontinue intervention, and another two subjects were excluded as they were transferred to another hospital. Consequently, a total of 25 VLBW infants were included in the final study cohort. Specifically, the SMOF group consisted of 13 cases, while the soybean oil group comprised 12 cases. Umbilical cord blood at birth and blood samples of parenteral nutrition were collected at 14 days from both groups for analysis via UHPLC-MS/MS. To ensure the accuracy and reliability of the results, all samples were processed and analyzed according to standard protocols (1).

Although the authors reported no substantial metabolite differences in the cord blood samples from both groups, after 14 days of parenteral nutrition, significant changes were observed in 84 metabolites within the SMOF group compared to the soybean oil group, with 56 (69%) of these metabolites belonging to the lipid category. This observation confirms earlier research indicating that various lipid emulsions have differing impacts on the metabolism of premature infants (1,6,7).

While the authors state that significant alterations observed in glycerophospholipid metabolic pathways, along with the identification of potential biomarkers, may provide additional guidance for the selection of suitable lipid emulsions for VLBW infants, they believe, to comprehensively understand the impact of SMOF lipid emulsion on the metabolism and overall health of VLBW infants, further validation and investigation are required through large-scale, longitudinal studies (1).

Low-weight newborn baby foot and leg. © Wanmongkhol - stock.adobe.com

References

1. Zeng, X.; Yu, T.; Xia, L.; Ruan Z. Untargeted Metabolomics Analysis of Glycerophospholipid Metabolism in Very Low Birth Weight Infants Administered Multiple Oil Lipid Emulsions. BMC Pediatr. 2024, 24 (1), 849. DOI: 10.1186/s12887-024-05343-4

2. Cao, Y.; Jiang, S.; Sun, J.; Hei, M.; Wang, L.; Zhang, H.; Ma, X. et al. Assessment of Neonatal Intensive Care Unit Practices, Morbidity, and Mortality Among Very Preterm Infants in China. JAMA Netw. Open. 2021, 4 (8), e2118904. DOI: 10.1001/jamanetworkopen.2021.18904

3. Deshpande, G. C.; Cai, W. Use of Lipids in Neonates Requiring Parenteral Nutrition. Journal of Parenteral and Enteral Nutrition 2020, 44, S45-S54. DOI: 10.1002/jpen.1759

4. Torgalkar, R.; Dave, S.; Shah, J.; Ostad, N.; Kotsopoulos, K.; Unger, S.; Shah, P. S. Multi-Component Lipid Emulsion vs. Soy-Based Lipid Emulsion for Very Low Birth Weight Preterm Neonates: A Pre-Post Comparative Study. J. Perinatol. 2019, 39 (8), 1118-1124. DOI: 10.1038/s41372-019-0425-7

5. Hsiao, C. C.; Lin, H. C.; Chang, Y. J.; Yang, S. P.; Tsao, L. Y.; Lee, C. H.; Chen, H. N.;Chen, J. Y.; Tsai, Y. G. Intravenous Fish Oil Containing Lipid Emulsion Attenuates Inflammatory Cytokines and the Development of Bronchopulmonary Dysplasia in Very Premature Infants: A Double-Blind, Randomized Controlled Trial. Clin. Nutr. 2019, 38 (3), 1045-1052. DOI: 10.1016/j.clnu.2018.06.929

6. D'Ascenzo, R.; Savini, S.; Biagetti, C.; Bellagamba, M. P.; Marchionni, P.; Pompilio, A.; Cogo, P. E.; Carnielli, V. P. Higher Docosahexaenoic Acid, Lower Arachidonic Acid and Reduced Lipid Tolerance with High Doses of a Lipid Emulsion Containing 15% Fish Oil: A Randomized Clinical Trial. Clin. Nutr. 2014, 33 (6), 1002-1009. DOI: 10.1016/j.clnu.2014.01.009

7. Savini, S.; D'Ascenzo, R.; Biagetti, C.; Serpentini, G.; Pompilio, A.; Bartoli, A.; Cogo,P. E.; Carnielli, V. P. The Effect of 5 Intravenous Lipid Emulsions on Plasma Phytosterols in Preterm Infants Receiving Parenteral Nutrition: A Randomized Clinical Trial. Am. J. Clin. Nutr. 2013, 98 (2), 312-318. DOI: 10.3945/ajcn.112.056556