Analyzing Blood Metabolite Characteristics in Recently Born Preterm Infants with Bronchopulmonary Dysplasia Using LC–MS/MS
After collecting dried blood spots from preterm infants with gestational age (GA) of less than 32 weeks within 24 hours after birth, researchers used liquid chromatography-tandem mass spectrometry (LC–MS/MS) to perform targeted measurements of metabolites to identify differential metabolites in preterm infants with bronchopulmonary dysplasia and uncovering circulating biomarkers for the early prediction of this chronic lung disease.
Researchers from the Department of Pediatrics at Peking University Shenzhen Hospital (Shenzhen, China) analyzed the characteristics of blood metabolites within 24 hours after birth in preterm infants with bronchopulmonary dysplasia (BPD) and to identify biomarkers for predicting the occurrence of BPD. Metabolites were measured using liquid chromatography-tandem mass spectrometry (LC–MS/MS). A paper based on this research was published in Frontiers in Pediatrics (1).
A common chronic lung disease among premature infants, the survival rate of extremely preterm infants with BPD has significantly improved with advances in medical care, rising from 56.4% in 2010 to 67.1% in 2019 (2). The incidence of BPD, however, has not noticeably decreased and remains high (3,4). BPD not only prolongs hospital stays and increases medical costs for preterm infants, but also results in adverse short- and long-term respiratory and neurological outcomes and can even lead to death (5–9).
The researchers collected venous blood DBS and used LC–MS/MS to analyze 86 metabolites. The results reveal significant metabolic differences in amino acids and carnitines between infants with BPD and those without. The researchers identified four differential metabolites in those with gestational age (GA) of less than 28 weeks: histidine, ornithine/citrulline, propionylcarnitine/carnitine, and valerylcarnitine/carnitine, which suggests that histidine may have potential value in the early prediction of BPD in preterm infants with GA of less than 28 weeks (1).
The authors state that their study has its limitations. They conducted targeted metabolomics analysis using samples collected within the first 24 hours after birth. The limited variety of detected metabolites prevented the identification of significant metabolic pathways, potentially overlooking important metabolites. Furthermore, the subgroup analyses were restricted to gestational age and birth weight due to the small sample size, without precise adjustment for other influencing factors. Therefore, based on the preliminary results of this study, the team reported that they have collaborated with the Shenzhen Neonatal Data Network to establish a prospective, multicenter, large-scale, long-term follow-up cohort of infants born preterm at less than 32 weeks of gestation (1).
Premature baby kept under neonatal care. © RFBSIP - stock.adobe.com
References
1. Guo, Y.; Chen, J.; Zhang, Z.; Liu, C.; Li, J.; Liu, Y. Analysis of Blood Metabolite Characteristics at Birth in Preterm Infants with Bronchopulmonary Dysplasia: An Observational Cohort Study. Front. Pediatr. 2024, 12, 1474381. DOI: 10.3389/fped.2024.1474381
2. Zhu, Z.; Yuan, L.; Wang, J.; Li, Q.; Yang, C.; Gao, X.; Chen, S.; Han, S.; Liu, J.; Wu, H.; Yue, S.; Shi, J.; Cheng, R.; Cheng, X.; Han, T.; Jiang, H.; Bao, L.; Chen, C. Mortality and Morbidity of Infants Born Extremely Preterm at Tertiary Medical Centers in China From 2010 to 2019. JAMA Netw. Open. 2021, 4 (5), e219382. DOI: 10.1001/jamanetworkopen.2021.9382
3. Cao, Y.; Jiang, S.; Sun, J.; Hei, M.; Wang, L.; Zhang, H.; Ma, X.; Wu, H.; Li, X.; Sun, H.; Zhou, W.; Shi, Y.; Wang, Y.; Gu, X.; Yang, T.; Lu, Y.; Du, L.; Chen, C.; Lee, S. K.; Zhou, W. 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
4. Bell, E. F.; Hintz, S. R.; Hansen, N. I,; Bann, C. M.; Wyckoff, M. H.; DeMauro, S. B.; Walsh, M. C,.; Vohr, B. R.; Stoll, B. J.; Carlo, W. A.; Van Meurs, K. P.; Rysavy, M.A.; Patel, R. M.; Merhar, S. L.; Sánchez, P. J.; Laptook, A. R.; Hibbs, A. M.; Cotton, C. M.; D'Angio, C. T,.; Winter, S.; Fuller, J.; Das, A. Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Mortality, In-Hospital Morbidity, Care Practices, and 2-Year Outcomes for Extremely Preterm Infants in the US, 2013-2018. JAMA 2022, 327 (3), 248-263. DOI: 10.1001/jama.2021.23580
5. Jeon, G. W.; Oh, M.; Chang, Y. S. Definitions of Bronchopulmonary Dysplasia and Long-Term Outcomes of Extremely Preterm Infants in Korean Neonatal Network. Sci. Rep. 2021, 11 (1), 24349OI: 10.1038/s41598-021-03644-7
6. Jeon, G. W. Oh, M.; Lee, J.; Jun, Y. H.; Chang, Y. S. Comparison of Definitions of Bronchopulmonary Dysplasia to Reflect the Long-Term Outcomes of Extremely Preterm Infants. Sci. Rep. 2022, 12 (1), 18095. DOI: 10.1038/s41598-022-22920-8
7. Katz, T. A.; Vliegenthart, R. J. S.; Aarnoudse-Moens, C. S. H.; Leemhuis, A. G.; Beuger, S.; Blok, G. J.; van Brakel, M. J. M.; van den Heuvel, M. E. N.; van Kempen, A. A. M. W.; Lutterman, C.; Rijpert, M.; Schiering, I. A.; Ran, N. C.; Visser, F.; Wilms, J.; van Kaam, A. H.; Onland, W. Severity of Bronchopulmonary Dysplasia and Neurodevelopmental Outcome at 2 and 5 Years Corrected Age. J. Pediatr. 2022, 243, 40-46.e2. DOI: 10.1016/j.jpeds.2021.12.018
8. Katz, T. A.; van Kaam, A. H.; Schuit, E.; Mugie, S. M.; Aarnoudse-Moens, C. S. H.; Weber, E. H.; de Groof,F.; van Laerhoven, H.; Counsilman, C. E.; van der Schoor, S. R. D.; Rijpert, M.; Schiering, I. A.; Wilms, J.; Leemhuis, A. G.; Onland, W. Comparison of New Bronchopulmonary Dysplasia Definitions on Long-Term Outcomes in Preterm Infants. J Pediatr. 2023, 253, 86-93.e4. DOI: 10.1016/j.jpeds.2022.09.022
9. Jensen, E. A.; Edwards, E. M.; Greenberg, L. T.; Soll, R. F.; Ehret, D. E. Y.; Horbar, J. D. Severity of Bronchopulmonary Dysplasia Among Very Preterm Infants in the United States. Pediatrics 2021, 148 (1), e2020030007. DOI: 10.1542/peds.2020-030007
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