{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T15:57:41Z","timestamp":1764172661248,"version":"build-2065373602"},"reference-count":63,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T00:00:00Z","timestamp":1754870400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T00:00:00Z","timestamp":1754870400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/100020595","name":"National Science and Technology Council, R.O.C","doi-asserted-by":"crossref","award":["111-2113-M-182-002"],"award-info":[{"award-number":["111-2113-M-182-002"]}],"id":[{"id":"10.13039\/100020595","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Metabolomics"],"DOI":"10.1007\/s11306-025-02298-0","type":"journal-article","created":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T16:12:34Z","timestamp":1754928754000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Metabolic profiling of amniotic fluid by differential 12C-\/13C-isotope dansylation labeling LC-MS for application in trisomy 21 fetuses"],"prefix":"10.1007","volume":"21","author":[{"given":"Ya-Ju","family":"Hsieh","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yao-Lung","family":"Chang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi-Hsin","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheng-Yu","family":"Hung","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liang","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jau-Song","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chih-Hsiang","family":"Chang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei-Ju","family":"Tu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi-Ting","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,8,11]]},"reference":[{"key":"2298_CR1","doi-asserted-by":"publisher","first-page":"2637","DOI":"10.1021\/acs.analchem.5b03609","volume":"88","author":"D Achaintre","year":"2016","unstructured":"Achaintre, D., Bulete, A., Cren-Olive, C., Li, L., Rinaldi, S., & Scalbert, A. (2016). Differential isotope labeling of 38 dietary polyphenols and their quantification in urine by liquid chromatography electrospray ionization tandem mass spectrometry. Analytical Chemistry, 88, 2637\u201344. https:\/\/doi.org\/10.1021\/acs.analchem.5b03609","journal-title":"Analytical Chemistry"},{"key":"2298_CR2","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/j.chroma.2018.05.017","volume":"1558","author":"D Achaintre","year":"2018","unstructured":"Achaintre, D., Gicquiau, A., Li, L., Rinaldi, S., & Scalbert, A. (2018). Quantification of 38 dietary polyphenols in plasma by differential isotope labelling and liquid chromatography electrospray ionization tandem mass spectrometry. Journal of Chromatograpy A, 1558, 50\u201358. https:\/\/doi.org\/10.1016\/j.chroma.2018.05.017","journal-title":"Journal of Chromatograpy A"},{"key":"2298_CR3","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1007\/s11010-011-1015-y","volume":"359","author":"AM Amorini","year":"2012","unstructured":"Amorini, A. M., et al. (2012). Metabolic profile of amniotic fluid as a biochemical tool to screen for inborn errors of metabolism and fetal anomalies. Molecular Cell Biochemistry, 359, 205\u201316. https:\/\/doi.org\/10.1007\/s11010-011-1015-y","journal-title":"Molecular Cell Biochemistry"},{"key":"2298_CR4","doi-asserted-by":"publisher","first-page":"10491","DOI":"10.1038\/s41598-020-67195-z","volume":"10","author":"F Antonaros","year":"2020","unstructured":"Antonaros, F., et al. (2020). Plasma metabolome and cognitive skills in Down syndrome. Scientific Reports, 10, 10491. https:\/\/doi.org\/10.1038\/s41598-020-67195-z","journal-title":"Scientific Reports"},{"key":"2298_CR5","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1053\/j.semperi.2005.12.003","volume":"29","author":"BR Benacerraf","year":"2005","unstructured":"Benacerraf, B. R. (2005). The role of the second trimester genetic sonogram in screening for fetal Down syndrome. Seminars Perinatology, 29, 386\u201394. https:\/\/doi.org\/10.1053\/j.semperi.2005.12.003","journal-title":"Seminars Perinatology"},{"key":"2298_CR6","doi-asserted-by":"publisher","first-page":"1155","DOI":"10.1093\/humrep\/15.5.1155","volume":"15","author":"S B\u00f6hlandt","year":"2000","unstructured":"B\u00f6hlandt, S., von Kaisenberg, C. S., Wewetzer, K., Christ, B., Nicolaides, K. H., & Brand-Saberi, B. (2000). Hyaluronan in the nuchal skin of chromosomally abnormal fetuses. Human Reproduction, 15, 1155\u20138. https:\/\/doi.org\/10.1093\/humrep\/15.5.1155","journal-title":"Human Reproduction"},{"key":"2298_CR7","doi-asserted-by":"publisher","first-page":"2977","DOI":"10.1038\/s41598-018-20834-y","volume":"8","author":"M Caracausi","year":"2018","unstructured":"Caracausi, M., et al. (2018). Plasma and urinary metabolomic profiles of Down syndrome correlate with alteration of mitochondrial metabolism. Scientific Reports, 8, 2977. https:\/\/doi.org\/10.1038\/s41598-018-20834-y","journal-title":"Scientific Reports"},{"key":"2298_CR8","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1016\/j.tjog.2017.08.019","volume":"56","author":"YL Chang","year":"2017","unstructured":"Chang, Y. L., et al. (2017). Monozygotic twins discordant for trisomy 21: Discussion of etiological events involved. Taiwan Journal of Obstetrics Gynecology, 56, 681\u2013685. https:\/\/doi.org\/10.1016\/j.tjog.2017.08.019","journal-title":"Taiwan Journal of Obstetrics Gynecology"},{"key":"2298_CR9","doi-asserted-by":"crossref","unstructured":"Chang, Y. L., Chao, A. S., You, S. H., Cheng, P. J. (2020). Increased hyaluronic acid level in mid-trimester amniotic fluid of trisomy 21 fetuses with hydrops. Research square.","DOI":"10.21203\/rs.3.rs-48035\/v1"},{"key":"2298_CR10","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1016\/j.talanta.2018.01.084","volume":"182","author":"AJ Chetwynd","year":"2018","unstructured":"Chetwynd, A. J., & David, A. (2018). A review of nanoscale LC-ESI for metabolomics and its potential to enhance the metabolome coverage. Talanta, 182, 380\u2013390. https:\/\/doi.org\/10.1016\/j.talanta.2018.01.084","journal-title":"Talanta"},{"key":"2298_CR11","doi-asserted-by":"publisher","first-page":"2917","DOI":"10.1007\/s00204-016-1843-3","volume":"90","author":"F Coppede","year":"2016","unstructured":"Coppede, F. (2016). Risk factors for Down syndrome. Archives of Toxicology, 90, 2917\u20132929. https:\/\/doi.org\/10.1007\/s00204-016-1843-3","journal-title":"Archives of Toxicology"},{"key":"2298_CR12","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.ajog.2015.03.023","volume":"213","author":"AG Edlow","year":"2015","unstructured":"Edlow, A. G., Slonim, D. K., Wick, H. C., Hui, L., & Bianchi, D. W. (2015). The pathway not taken: understanding \u2019omics data in the perinatal context. American Journal of Obstetrics and Gynecology, 213, 59. https:\/\/doi.org\/10.1016\/j.ajog.2015.03.023","journal-title":"American Journal of Obstetrics and Gynecology"},{"key":"2298_CR13","doi-asserted-by":"publisher","first-page":"2477","DOI":"10.1105\/tpc.111.086272","volume":"23","author":"AR Fernie","year":"2011","unstructured":"Fernie, A. R., et al. (2011). Recommendations for reporting metabolite data. The Plant Cell, 23, 2477\u201382. https:\/\/doi.org\/10.1105\/tpc.111.086272","journal-title":"The Plant Cell"},{"key":"2298_CR14","doi-asserted-by":"publisher","first-page":"3919","DOI":"10.1021\/ac900166a","volume":"81","author":"K Guo","year":"2009","unstructured":"Guo, K., & Li, L. (2009). Differential 12C-\/13C-isotope dansylation labeling and fast liquid chromatography\/mass spectrometry for absolute and relative quantification of the metabolome. Analytical Chemistry, 81, 3919\u201332. https:\/\/doi.org\/10.1021\/ac900166a","journal-title":"Analytical Chemistry"},{"key":"2298_CR15","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1093\/humupd\/dmg008","volume":"9","author":"MC Haak","year":"2003","unstructured":"Haak, M. C., & van Vugt, J. M. (2003). Pathophysiology of increased nuchal translucency: a review of the literature. Human Reproduction Update, 9, 175\u201384. https:\/\/doi.org\/10.1093\/humupd\/dmg008","journal-title":"Human Reproduction Update"},{"key":"2298_CR16","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1007\/978-1-4939-7592-1_14","volume":"1730","author":"W Han","year":"2018","unstructured":"Han, W., & Li, L. (2018). Chemical isotope labeling LC-MS for human blood metabolome analysis. Methods Molecular Biology, 1730, 213\u2013225. https:\/\/doi.org\/10.1007\/978-1-4939-7592-1_14","journal-title":"Methods Molecular Biology"},{"key":"2298_CR17","doi-asserted-by":"publisher","first-page":"1720","DOI":"10.1002\/mds.27173","volume":"32","author":"W Han","year":"2017","unstructured":"Han, W., Sapkota, S., Camicioli, R., Dixon, R. A., & Li, L. (2017). Profiling novel metabolic biomarkers for Parkinson\u2019s disease using in-depth metabolomic analysis. Movement Disorders, 32, 1720\u20131728. https:\/\/doi.org\/10.1002\/mds.27173","journal-title":"Movement Disorders"},{"key":"2298_CR18","doi-asserted-by":"publisher","first-page":"7378","DOI":"10.1021\/acs.analchem.6b01930","volume":"88","author":"K Hooton","year":"2016","unstructured":"Hooton, K., Han, W., & Li, L. (2016). Comprehensive and quantitative profiling of the human sweat submetabolome using high-performance chemical isotope labeling LC-MS. Analytical Chemistry, 88, 7378\u201386. https:\/\/doi.org\/10.1021\/acs.analchem.6b01930","journal-title":"Analytical Chemistry"},{"key":"2298_CR19","doi-asserted-by":"publisher","first-page":"7847","DOI":"10.1021\/acs.analchem.7b01988","volume":"89","author":"K Hooton","year":"2017","unstructured":"Hooton, K., & Li, L. (2017). Nonocclusive sweat collection combined with chemical isotope labeling LC-MS for human sweat metabolomics and mapping the sweat metabolomes at different skin locations. Analytical Chemistry, 89, 7847\u20137851. https:\/\/doi.org\/10.1021\/acs.analchem.7b01988","journal-title":"Analytical Chemistry"},{"key":"2298_CR20","doi-asserted-by":"publisher","DOI":"10.1016\/j.aca.2021.339218","volume":"1189","author":"YJ Hsieh","year":"2022","unstructured":"Hsieh, Y. J., et al. (2022). Development of a method for dansylation of metabolites using organic solvent-compatible buffer systems for amine\/phenol submetabolome analysis. Analytica Chimica Acta, 1189, Article 339218. https:\/\/doi.org\/10.1016\/j.aca.2021.339218","journal-title":"Analytica Chimica Acta"},{"key":"2298_CR21","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1016\/j.aca.2018.10.070","volume":"1050","author":"CW Hsu","year":"2019","unstructured":"Hsu, C. W., et al. (2019). Integrated analyses utilizing metabolomics and transcriptomics reveal perturbation of the polyamine pathway in oral cavity squamous cell carcinoma. Analytica Chimica Acta, 1050, 113\u2013122. https:\/\/doi.org\/10.1016\/j.aca.2018.10.070","journal-title":"Analytica Chimica Acta"},{"key":"2298_CR22","doi-asserted-by":"publisher","first-page":"32272","DOI":"10.1038\/srep32272","volume":"6","author":"T Huan","year":"2016","unstructured":"Huan, T., Troyer, D. A., & Li, L. (2016). Metabolite analysis and histology on the exact same tissue: comprehensive metabolomic profiling and metabolic classification of prostate cancer. Scientific Reports, 6, 32272. https:\/\/doi.org\/10.1038\/srep32272","journal-title":"Scientific Reports"},{"key":"2298_CR23","doi-asserted-by":"publisher","first-page":"670","DOI":"10.1089\/omi.2016.0112","volume":"20","author":"T Huan","year":"2016","unstructured":"Huan, T., Xian, J. W., Leung, W. N., Li, L., & Chan, C. W. (2016). Cerebrospinal fluid metabolomics after natural product treatment in an experimental model of cerebral ischemia. OMICS, 20, 670\u2013680. https:\/\/doi.org\/10.1089\/omi.2016.0112","journal-title":"OMICS"},{"key":"2298_CR24","doi-asserted-by":"publisher","first-page":"7405","DOI":"10.3892\/mmr.2017.7507","volume":"16","author":"J Huang","year":"2017","unstructured":"Huang, J., et al. (2017). Application of the amniotic fluid metabolome to the study of fetal malformations, using Down syndrome as a specific model. Molecular Medicine Reports, 16, 7405\u20137415. https:\/\/doi.org\/10.3892\/mmr.2017.7507","journal-title":"Molecular Medicine Reports"},{"key":"2298_CR25","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1055\/s-0038-1666974","volume":"36","author":"DJ Hussamy","year":"2019","unstructured":"Hussamy, D. J., Herrera, C. L., Twickler, D. M., McIntire, D. D., & Dashe, J. S. (2019). Number of risk factors in down syndrome pregnancies. American Journal of Perinatology, 36, 79\u201385. https:\/\/doi.org\/10.1055\/s-0038-1666974","journal-title":"American Journal of Perinatology"},{"key":"2298_CR26","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1515\/jpm-2018-0314","volume":"47","author":"A Iuculano","year":"2019","unstructured":"Iuculano, A., et al. (2019). Metabolic characterization of amniotic fluids of fetuses with enlarged nuchal translucency. Journal of Perinatal Medicine, 47, 311\u2013318. https:\/\/doi.org\/10.1515\/jpm-2018-0314","journal-title":"Journal of Perinatal Medicine"},{"key":"2298_CR27","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1111\/j.1528-1167.2005.00705.x","volume":"46","author":"RM Kaminski","year":"2005","unstructured":"Kaminski, R. M., Marini, H., Kim, W. J., & Rogawski, M. A. (2005). Anticonvulsant activity of androsterone and etiocholanolone. Epilepsia, 46, 819\u201327. https:\/\/doi.org\/10.1111\/j.1528-1167.2005.00705.x","journal-title":"Epilepsia"},{"key":"2298_CR28","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1002\/ana.410210416","volume":"21","author":"AD Kay","year":"1987","unstructured":"Kay, A. D., Schapiro, M. B., Riker, A. K., Haxby, J. V., Rapoport, S. I., & Cutler, N. R. (1987). Cerebrospinal fluid monoaminergic metabolites are elevated in adults with Down\u2019s syndrome. Annals of Neurology, 21, 408\u201311. https:\/\/doi.org\/10.1002\/ana.410210416","journal-title":"Annals of Neurology"},{"key":"2298_CR29","doi-asserted-by":"publisher","first-page":"1143","DOI":"10.1002\/jms.4292","volume":"53","author":"AD Kennedy","year":"2018","unstructured":"Kennedy, A. D., et al. (2018). Metabolomics in the clinic: A review of the shared and unique features of untargeted metabolomics for clinical research and clinical testing. Journal of Mass Spectrometry, 53, 1143\u20131154. https:\/\/doi.org\/10.1002\/jms.4292","journal-title":"Journal of Mass Spectrometry"},{"key":"2298_CR30","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22189879","author":"A Krupa","year":"2021","unstructured":"Krupa, A., & Kowalska, I. (2021). The kynurenine pathway-new linkage between innate and adaptive immunity in autoimmune endocrinopathies. International Journal of Molecular Science. https:\/\/doi.org\/10.3390\/ijms22189879","journal-title":"International Journal of Molecular Science"},{"key":"2298_CR31","doi-asserted-by":"publisher","DOI":"10.3390\/antiox11061208","author":"G Lazzarino","year":"2022","unstructured":"Lazzarino, G., et al. (2022). Biochemical discrimination of the down syndrome-related metabolic and oxidative\/nitrosative stress alterations from the physiologic age-related changes through the targeted metabolomic analysis of serum. Antioxidants (Basel). https:\/\/doi.org\/10.3390\/antiox11061208","journal-title":"Antioxidants (Basel)"},{"key":"2298_CR32","doi-asserted-by":"publisher","first-page":"17774","DOI":"10.1038\/s41598-018-35631-w","volume":"8","author":"CC Lee","year":"2018","unstructured":"Lee, C. C., et al. (2018). Bretschneider solution-induced alterations in the urine metabolome in cardiac surgery patients. Scientific Reports, 8, 17774. https:\/\/doi.org\/10.1038\/s41598-018-35631-w","journal-title":"Scientific Reports"},{"key":"2298_CR33","doi-asserted-by":"publisher","DOI":"10.1002\/jcla.23089","volume":"34","author":"X Liu","year":"2020","unstructured":"Liu, X., et al. (2020). Study on amniotic fluid metabolism in the second trimester of Trisomy 21. Journal of Clinical Laboratory Analysis, 34, Article e23089. https:\/\/doi.org\/10.1002\/jcla.23089","journal-title":"Journal of Clinical Laboratory Analysis"},{"key":"2298_CR34","doi-asserted-by":"publisher","first-page":"35981","DOI":"10.1021\/acsomega.2c05152","volume":"7","author":"Y Liu","year":"2022","unstructured":"Liu, Y., et al. (2022). Sex differences in protein expression and their perturbations in amniotic fluid cells of down syndrome fetuses. ACS Omega, 7, 35981\u201335992. https:\/\/doi.org\/10.1021\/acsomega.2c05152","journal-title":"ACS Omega"},{"key":"2298_CR35","doi-asserted-by":"publisher","first-page":"8314","DOI":"10.1021\/acs.analchem.8b01726","volume":"90","author":"X Luo","year":"2018","unstructured":"Luo, X., An, M., Cuneo, K. C., Lubman, D. M., & Li, L. (2018). High-performance chemical isotope labeling liquid chromatography mass spectrometry for exosome metabolomics. Analytical Chemistry, 90, 8314\u20138319. https:\/\/doi.org\/10.1021\/acs.analchem.8b01726","journal-title":"Analytical Chemistry"},{"key":"2298_CR36","doi-asserted-by":"publisher","first-page":"11664","DOI":"10.1021\/acs.analchem.7b03100","volume":"89","author":"X Luo","year":"2017","unstructured":"Luo, X., & Li, L. (2017). Metabolomics of small numbers of cells: metabolomic profiling of 100, 1000, and 10000 human breast cancer cells. Analytical Chemistry, 89, 11664\u201311671. https:\/\/doi.org\/10.1021\/acs.analchem.7b03100","journal-title":"Analytical Chemistry"},{"key":"2298_CR37","doi-asserted-by":"publisher","first-page":"1306","DOI":"10.1016\/j.clinbiochem.2008.08.077","volume":"41","author":"I Marin-Valencia","year":"2008","unstructured":"Marin-Valencia, I., et al. (2008). Biochemical diagnosis of dopaminergic disturbances in paediatric patients: analysis of cerebrospinal fluid homovanillic acid and other biogenic amines. Clinical Biochemistry, 41, 1306\u201315. https:\/\/doi.org\/10.1016\/j.clinbiochem.2008.08.077","journal-title":"Clinical Biochemistry"},{"key":"2298_CR38","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.6b03737","author":"D Mung","year":"2017","unstructured":"Mung, D., & Li, L. (2017). Development of chemical isotope labeling LC-MS for milk metabolomics: comprehensive and quantitative profiling of the amine\/phenol submetabolome. Analytical Chemistry. https:\/\/doi.org\/10.1021\/acs.analchem.6b03737","journal-title":"Analytical Chemistry"},{"key":"2298_CR39","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1016\/j.aca.2017.11.019","volume":"1001","author":"D Mung","year":"2018","unstructured":"Mung, D., & Li, L. (2018). Applying quantitative metabolomics based on chemical isotope labeling LC-MS for detecting potential milk adulterant in human milk. Analytica Chimica Acta, 1001, 78\u201385. https:\/\/doi.org\/10.1016\/j.aca.2017.11.019","journal-title":"Analytica Chimica Acta"},{"key":"2298_CR40","doi-asserted-by":"publisher","DOI":"10.3390\/life11090913","author":"F Murgia","year":"2021","unstructured":"Murgia, F., et al. (2021). Metabolomics analysis of amniotic fluid in euploid foetuses with thickened nuchal translucency by gas chromatography-mass spectrometry. Life (Basel). https:\/\/doi.org\/10.3390\/life11090913","journal-title":"Life (Basel)"},{"key":"2298_CR41","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000002","volume":"17","author":"PJ O'Shaughnessy","year":"2019","unstructured":"O\u2019Shaughnessy, P. J., et al. (2019). Alternative (backdoor) androgen production and masculinization in the human fetus. PLoS Biology, 17, Article e3000002. https:\/\/doi.org\/10.1371\/journal.pbio.3000002","journal-title":"PLoS Biology"},{"key":"2298_CR42","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1038\/nrm3314","volume":"13","author":"GJ Patti","year":"2012","unstructured":"Patti, G. J., Yanes, O., & Siuzdak, G. (2012). Innovation: Metabolomics: the apogee of the omics trilogy. Nature Review Molecular Cell Biolology, 13, 263\u20139. https:\/\/doi.org\/10.1038\/nrm3314","journal-title":"Nature Review Molecular Cell Biolology"},{"key":"2298_CR43","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1186\/s10020-020-00225-8","volume":"26","author":"L Pecze","year":"2020","unstructured":"Pecze, L., Randi, E. B., & Szabo, C. (2020). Meta-analysis of metabolites involved in bioenergetic pathways reveals a pseudohypoxic state in Down syndrome. Molecular Medicine, 26, 102. https:\/\/doi.org\/10.1186\/s10020-020-00225-8","journal-title":"Molecular Medicine"},{"key":"2298_CR44","doi-asserted-by":"publisher","first-page":"6540","DOI":"10.1021\/ac5011684","volume":"86","author":"J Peng","year":"2014","unstructured":"Peng, J., Chen, Y. T., Chen, C. L., & Li, L. (2014). Development of a universal metabolome-standard method for long-term LC-MS metabolome profiling and its application for bladder cancer urine-metabolite-biomarker discovery. Analytical Chemistry, 86, 6540\u20137. https:\/\/doi.org\/10.1021\/ac5011684","journal-title":"Analytical Chemistry"},{"key":"2298_CR45","doi-asserted-by":"publisher","DOI":"10.3390\/jcm11030702","author":"T Reischer","year":"2022","unstructured":"Reischer, T., et al. (2022). Clinical course and outcome of non-immune fetal hydrops in singleton pregnancies. Journal of Clinical Medicine. https:\/\/doi.org\/10.3390\/jcm11030702","journal-title":"Journal of Clinical Medicine"},{"key":"2298_CR46","doi-asserted-by":"publisher","first-page":"1093","DOI":"10.1093\/humrep\/17.4.1093","volume":"17","author":"P Rozenberg","year":"2002","unstructured":"Rozenberg, P., et al. (2002). Down\u2019s syndrome screening with nuchal translucency at 12(+0)-14(+0) weeks and maternal serum markers at 14(+1)-17(+0) weeks: a prospective study. Human Reproduction, 17, 1093\u20138. https:\/\/doi.org\/10.1093\/humrep\/17.4.1093","journal-title":"Human Reproduction"},{"issue":"1157\u201364","key":"2298_CR47","doi-asserted-by":"publisher","first-page":"e1","DOI":"10.1016\/j.fertnstert.2012.07.1145","volume":"98","author":"I Sanchez-Ribas","year":"2012","unstructured":"Sanchez-Ribas, I., et al. (2012). Differential metabolic profiling of non-pure trisomy 21 human preimplantation embryos. Fertility and Sterility, 98(1157\u201364), e1-2. https:\/\/doi.org\/10.1016\/j.fertnstert.2012.07.1145","journal-title":"Fertility and Sterility"},{"key":"2298_CR48","doi-asserted-by":"publisher","first-page":"1897","DOI":"10.1007\/s13361-016-1469-y","volume":"27","author":"AC Schrimpe-Rutledge","year":"2016","unstructured":"Schrimpe-Rutledge, A. C., Codreanu, S. G., Sherrod, S. D., & McLean, J. A. (2016). Untargeted metabolomics strategies-challenges and emerging directions. Journal of the American Society for Mass Spectrometry, 27, 1897\u20131905. https:\/\/doi.org\/10.1007\/s13361-016-1469-y","journal-title":"Journal of the American Society for Mass Spectrometry"},{"key":"2298_CR49","doi-asserted-by":"publisher","first-page":"470","DOI":"10.1016\/j.tjog.2013.10.003","volume":"52","author":"SW Shaw","year":"2013","unstructured":"Shaw, S. W., Chen, C. P., & Cheng, P. J. (2013). From Down syndrome screening to noninvasive prenatal testing: 20 years\u2019 experience in Taiwan. Taiwan Journal of Obstetrics Gynecology, 52, 470\u20134. https:\/\/doi.org\/10.1016\/j.tjog.2013.10.003","journal-title":"Taiwan Journal of Obstetrics Gynecology"},{"key":"2298_CR50","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1002\/pd.307","volume":"22","author":"TD Shipp","year":"2002","unstructured":"Shipp, T. D., & Benacerraf, B. R. (2002). Second trimester ultrasound screening for chromosomal abnormalities. Prenatal Diagnosis, 22, 296\u2013307. https:\/\/doi.org\/10.1002\/pd.307","journal-title":"Prenatal Diagnosis"},{"key":"2298_CR51","doi-asserted-by":"publisher","first-page":"1005","DOI":"10.1016\/j.ajog.2004.12.093","volume":"192","author":"AP Souka","year":"2005","unstructured":"Souka, A. P., Von Kaisenberg, C. S., Hyett, J. A., Sonek, J. D., & Nicolaides, K. H. (2005). Increased nuchal translucency with normal karyotype. American Journal of Obstetrics and Gynecology, 192, 1005\u201321. https:\/\/doi.org\/10.1016\/j.ajog.2004.12.093","journal-title":"American Journal of Obstetrics and Gynecology"},{"key":"2298_CR52","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1016\/j.tips.2023.04.006","volume":"44","author":"TW Stone","year":"2023","unstructured":"Stone, T. W., & Williams, R. O. (2023). Modulation of T cells by tryptophan metabolites in the kynurenine pathway. Trends in Pharmacological Science, 44, 442\u2013456. https:\/\/doi.org\/10.1016\/j.tips.2023.04.006","journal-title":"Trends in Pharmacological Science"},{"key":"2298_CR53","doi-asserted-by":"publisher","first-page":"1006891","DOI":"10.3389\/fmed.2022.1006891","volume":"9","author":"B Vione","year":"2022","unstructured":"Vione, B., et al. (2022). One-carbon pathway metabolites are altered in the plasma of subjects with Down syndrome: Relation to chromosomal dosage. Frontiers in Medicine (Lausanne), 9, 1006891. https:\/\/doi.org\/10.3389\/fmed.2022.1006891","journal-title":"Frontiers in Medicine (Lausanne)"},{"key":"2298_CR54","doi-asserted-by":"publisher","DOI":"10.1016\/j.aca.2022.340255","volume":"1226","author":"CF Wang","year":"2022","unstructured":"Wang, C. F., & Li, L. (2022). Instrument-type effects on chemical isotope labeling LC-MS metabolome analysis: Quadrupole time-of-flight MS vs. Orbitrap MS. Analytica Chimica Acta, 1226, Article 340255. https:\/\/doi.org\/10.1016\/j.aca.2022.340255","journal-title":"Analytica Chimica Acta"},{"key":"2298_CR55","doi-asserted-by":"publisher","first-page":"D622","DOI":"10.1093\/nar\/gkab1062","volume":"50","author":"DS Wishart","year":"2022","unstructured":"Wishart, D. S., et al. (2022). HMDB 5.0: the Human Metabolome Database for 2022. Nucleic Acids Research, 50, D622\u2013D631. https:\/\/doi.org\/10.1093\/nar\/gkab1062","journal-title":"Nucleic Acids Research"},{"key":"2298_CR56","doi-asserted-by":"publisher","first-page":"10723","DOI":"10.1021\/ac3025625","volume":"84","author":"Y Wu","year":"2012","unstructured":"Wu, Y., & Li, L. (2012). Determination of total concentration of chemically labeled metabolites as a means of metabolome sample normalization and sample loading optimization in mass spectrometry-based metabolomics. Analytical Chemistry, 84, 10723\u201331. https:\/\/doi.org\/10.1021\/ac3025625","journal-title":"Analytical Chemistry"},{"key":"2298_CR57","doi-asserted-by":"publisher","first-page":"W251","DOI":"10.1093\/nar\/gkv380","volume":"43","author":"J Xia","year":"2015","unstructured":"Xia, J., Sinelnikov, I. V., Han, B., & Wishart, D. S. (2015). MetaboAnalyst 3.0\u2013making metabolomics more meaningful. Nucleic Acids Research, 43, W251-7. https:\/\/doi.org\/10.1093\/nar\/gkv380","journal-title":"Nucleic Acids Research"},{"key":"2298_CR58","doi-asserted-by":"publisher","first-page":"2342","DOI":"10.1093\/bioinformatics\/btq418","volume":"26","author":"J Xia","year":"2010","unstructured":"Xia, J., & Wishart, D. S. (2010). MetPA: a web-based metabolomics tool for pathway analysis and visualization. Bioinformatics, 26, 2342\u20134. https:\/\/doi.org\/10.1093\/bioinformatics\/btq418","journal-title":"Bioinformatics"},{"key":"2298_CR59","doi-asserted-by":"publisher","first-page":"829","DOI":"10.1021\/ac503619q","volume":"87","author":"W Xu","year":"2015","unstructured":"Xu, W., et al. (2015). Development of high-performance chemical isotope labeling LC-MS for profiling the human fecal metabolome. Analytical Chemistry, 87, 829\u201336. https:\/\/doi.org\/10.1021\/ac503619q","journal-title":"Analytical Chemistry"},{"key":"2298_CR60","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2020.144461","volume":"738","author":"SH You","year":"2020","unstructured":"You, S. H., Lee, Y. S., Chang, Y. J., Lin, C. Y., Wang, T. H., & Chang, Y. L. (2020). Gene expression profiling of amniotic fluid mesenchymal stem cells of monozygotic twins discordant for trisomy 21. Gene, 738, Article 144461. https:\/\/doi.org\/10.1016\/j.gene.2020.144461","journal-title":"Gene"},{"key":"2298_CR61","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1002\/pd.1970090805","volume":"9","author":"M Zeitune","year":"1989","unstructured":"Zeitune, M., Aitken, D. A., Graham, G. W., Crossley, J. A., & Ferguson-Smith, M. A. (1989). Amniotic fluid alpha-fetoprotein, gamma-glutamyltranspeptidase, and autosomal trisomies. Prenatal Diagnosis, 9, 559\u201368. https:\/\/doi.org\/10.1002\/pd.1970090805","journal-title":"Prenatal Diagnosis"},{"key":"2298_CR62","doi-asserted-by":"publisher","first-page":"10802","DOI":"10.1021\/ac3028307","volume":"84","author":"J Zheng","year":"2012","unstructured":"Zheng, J., Dixon, R. A., & Li, L. (2012). Development of isotope labeling LC-MS for human salivary metabolomics and application to profiling metabolome changes associated with mild cognitive impairment. Analytical Chemistry, 84, 10802\u201311. https:\/\/doi.org\/10.1021\/ac3028307","journal-title":"Analytical Chemistry"},{"key":"2298_CR63","doi-asserted-by":"publisher","first-page":"4675","DOI":"10.1021\/ac5009089","volume":"86","author":"R Zhou","year":"2014","unstructured":"Zhou, R., Tseng, C. L., Huan, T., & Li, L. (2014). IsoMS: automated processing of LC-MS data generated by a chemical isotope labeling metabolomics platform. Analytical Chemistry, 86, 4675\u20139. https:\/\/doi.org\/10.1021\/ac5009089","journal-title":"Analytical Chemistry"}],"container-title":["Metabolomics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11306-025-02298-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11306-025-02298-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11306-025-02298-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T23:42:40Z","timestamp":1761867760000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11306-025-02298-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,11]]},"references-count":63,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["2298"],"URL":"https:\/\/doi.org\/10.1007\/s11306-025-02298-0","relation":{},"ISSN":["1573-3890"],"issn-type":[{"type":"electronic","value":"1573-3890"}],"subject":[],"published":{"date-parts":[[2025,8,11]]},"assertion":[{"value":"13 November 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 June 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 August 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"106"}}