Metabolomic Profiling of Human Feces and Plasma from Extrauterine Growth Restriction Infants

Overview

Journal Pediatr Res

Specialties Biology
Pediatrics

Date 2024 Nov 4

PMID 39496876

Authors

Jiang Duan

Qinghua Zhong

Liyan Luo

Yue Ning

Zhiye Qi

Sixian Wang

Kun Liang

Affiliations

Soon will be listed here.

Abstract

Background: Extrauterine growth restriction (EUGR) affects a substantial proportion of preterm infants and may influence both short-term complications and long-term sequelae. While many preterm infants with EUGR are secondary to small for gestational age (SGA) or very low birth weight (VLBW), a subset of EUGR infants do not exhibit these conditions. The purpose of this study is to investigate the metabolic profiles and biomarkers of EUGR infants in the absence of SGA and VLBW.

Methods: A total of 100 feces (n = 50) and plasma samples (n = 50) were collected from participants categorized as either EUGR (EUGR group) or non-EUGR (NonEUGR group) in the absence of SGA and VLBW. Metabolites were characterized via UPLC-MS/MS using the Discovery HD4 platform. Data normalization, partial least squares discriminant analysis (PLSDA), and KEGG enrichment analysis of metabolite profiles were performed using the MetaboAnalyst 6.0.

Results: The clinical characteristics of preterm infants differed significantly between the EUGR and NonEUGR groups at discharge, including length of stay, weight Z-score, weight, height Z-score, height, head circumference, and fat-free mass. The PLSDA model exhibited clustering within groups and separation between groups. A total of 58 and 71 differential metabolites were identified in feces and plasma samples, respectively. They were involved in pathways such as caffeine, galactose, glutathione, cysteine, and methionine metabolisms. In the feces sample, 1-palmitoyl-galactosylglycerol exhibited a significant negative correlation with the growth characteristics of preterm infants, while 1-palmitoyl-2-palmitoleoyl-GPC displayed the opposite pattern. In plasma samples, androsterone glucuronide displayed a significant positive correlation with the growth characteristics of preterm infants, whereas 2-methoxyhydroquinone sulfate generated an opposite pattern. Moreover, 2-oleoylglycerol and sphinganine-1-phosphate exhibited the highest area under the curve in feces and plasma samples, respectively, according to diagnostic ROC curves.

Conclusion: Preterm infants with EUGR, in the absence of SGA and VLBW, exhibit specific clinical characteristics and metabolomic profiles. Sphinganine-1-phosphate and 2-oleoylglycerol may hold promise as diagnostic markers for EUGR in the absence of SGA and VLBW.

Impact: The objective of this study is to identify the differential metabolites in preterm infants with extrauterine growth restriction (EUGR) in the absence of small for gestational age (SGA) or very low birth weight (VLBW). Preterm infants with EUGR without SGA and VLBW exhibit specific clinical characteristics and metabolomic profiles. Sphinganine-1-phosphate and 2-oleoylglycerol emerged as potential diagnostic biomarkers for EUGR. This study enhances our understanding of the metabolomic profile in preterm infants with EUGR without SGA or VLBW. Our findings will offer valuable evidence for improving nutritional management and shedding light on the associated pathophysiological mechanisms of EUGR.

Citing Articles

Metabolic and inflammatory status in prepuberty and early adulthood for individuals with a history of extrauterine growth restriction: a cohort study.

Palomino-Fernandez L, Velasco I, Pastor-Villaescusa B, Flores-Rojas K, de la Cruz Rico M, Roa J J Transl Med. 2025; 23(1):67.

PMID: 39810203 PMC: 11731142. DOI: 10.1186/s12967-024-06053-2.

References

Blencowe H, Cousens S, Oestergaard M, Chou D, Moller A, Narwal R . National, regional, and worldwide estimates of preterm birth rates in the year 2010 with time trends since 1990 for selected countries: a systematic analysis and implications. Lancet. 2012; 379(9832):2162-72. DOI: 10.1016/S0140-6736(12)60820-4. View

Liu L, Johnson H, Cousens S, Perin J, Scott S, Lawn J . Global, regional, and national causes of child mortality: an updated systematic analysis for 2010 with time trends since 2000. Lancet. 2012; 379(9832):2151-61. DOI: 10.1016/S0140-6736(12)60560-1. View

Perin J, Mulick A, Yeung D, Villavicencio F, Lopez G, Strong K . Global, regional, and national causes of under-5 mortality in 2000-19: an updated systematic analysis with implications for the Sustainable Development Goals. Lancet Child Adolesc Health. 2021; 6(2):106-115. PMC: 8786667. DOI: 10.1016/S2352-4642(21)00311-4. View

Walani S . Global burden of preterm birth. Int J Gynaecol Obstet. 2020; 150(1):31-33. DOI: 10.1002/ijgo.13195. View

Catalano P, Shankar K . Obesity and pregnancy: mechanisms of short term and long term adverse consequences for mother and child. BMJ. 2017; 356:j1. PMC: 6888512. DOI: 10.1136/bmj.j1. View

Koletzko B, Godfrey K, Poston L, Szajewska H, van Goudoever J, de Waard M . Nutrition During Pregnancy, Lactation and Early Childhood and its Implications for Maternal and Long-Term Child Health: The Early Nutrition Project Recommendations. Ann Nutr Metab. 2019; 74(2):93-106. PMC: 6397768. DOI: 10.1159/000496471. View

Das J, Lassi Z, Hoodbhoy Z, Salam R . Nutrition for the Next Generation: Older Children and Adolescents. Ann Nutr Metab. 2018; 72 Suppl 3:56-64. DOI: 10.1159/000487385. View

Clark R, Thomas P, Peabody J . Extrauterine growth restriction remains a serious problem in prematurely born neonates. Pediatrics. 2003; 111(5 Pt 1):986-90. DOI: 10.1542/peds.111.5.986. View

Fenton T, Cormack B, Goldberg D, Nasser R, Alshaikh B, Eliasziw M . "Extrauterine growth restriction" and "postnatal growth failure" are misnomers for preterm infants. J Perinatol. 2020; 40(5):704-714. DOI: 10.1038/s41372-020-0658-5. View

10.

Bonnar K, Fraser D . Extrauterine Growth Restriction in Low Birth Weight Infants. Neonatal Netw. 2019; 38(1):27-33. DOI: 10.1891/0730-0832.38.1.27. View

11.

Martinez-Jimenez M, Gomez-Garcia F, Gil-Campos M, Perez-Navero J . Comorbidities in childhood associated with extrauterine growth restriction in preterm infants: a scoping review. Eur J Pediatr. 2020; 179(8):1255-1265. DOI: 10.1007/s00431-020-03613-8. View

12.

Finken M, van der Steen M, Smeets C, Walenkamp M, de Bruin C, Hokken-Koelega A . Children Born Small for Gestational Age: Differential Diagnosis, Molecular Genetic Evaluation, and Implications. Endocr Rev. 2018; 39(6):851-894. DOI: 10.1210/er.2018-00083. View

13.

Gidi N, Goldenberg R, Nigussie A, McClure E, Mekasha A, Worku B . Incidence and associated factors of extrauterine growth restriction (EUGR) in preterm infants, a cross-sectional study in selected NICUs in Ethiopia. BMJ Paediatr Open. 2020; 4(1):e000765. PMC: 7552851. DOI: 10.1136/bmjpo-2020-000765. View

14.

Khasawneh W, Khassawneh M, Mazin M, Al-Theiabat M, Alquraan T . Clinical and Nutritional Determinants of Extrauterine Growth Restriction Among Very Low Birth Weight Infants. Int J Gen Med. 2020; 13:1193-1200. PMC: 7682780. DOI: 10.2147/IJGM.S284943. View

15.

Crestani E, Harb H, Charbonnier L, Leirer J, Motsinger-Reif A, Rachid R . Untargeted metabolomic profiling identifies disease-specific signatures in food allergy and asthma. J Allergy Clin Immunol. 2019; 145(3):897-906. PMC: 7062570. DOI: 10.1016/j.jaci.2019.10.014. View

16.

Bu Y, Wang H, Ma X, Han C, Jia X, Zhang J . Untargeted Metabolomic Profiling of the Correlation Between Prognosis Differences and PD-1 Expression in Sepsis: A Preliminary Study. Front Immunol. 2021; 12:594270. PMC: 8046931. DOI: 10.3389/fimmu.2021.594270. View

17.

Bruschi M, Bartolucci M, Petretto A, Buffelli F, Kajana X, Parodi A . Proteomic profiling of human amnion for preterm birth biomarker discovery. Sci Rep. 2021; 11(1):23144. PMC: 8633292. DOI: 10.1038/s41598-021-02587-3. View

18.

Fan S, Zhang K, Lv A, Ma Y, Fang X, Zhang J . Characteristics of the intestinal microbiota and metabolism in infants with extrauterine growth restriction. Transl Pediatr. 2021; 10(5):1259-1270. PMC: 8193004. DOI: 10.21037/tp-20-431. View

19.

Pang Z, Zhou G, Ewald J, Chang L, Hacariz O, Basu N . Using MetaboAnalyst 5.0 for LC-HRMS spectra processing, multi-omics integration and covariate adjustment of global metabolomics data. Nat Protoc. 2022; 17(8):1735-1761. DOI: 10.1038/s41596-022-00710-w. View

20.

Yu V . Extrauterine growth restriction in preterm infants: importance of optimizing nutrition in neonatal intensive care units. Croat Med J. 2005; 46(5):737-43. View