Reference Intervals for the ratio of Soluble FMS-like Tyrosine Kinase-1 and Placental Growth Factor in Pregnant and Non-Pregnant Females in Pakistani Population
Keywords:
Reference intervals, sFlt-1/PGF ratio, pre-eclampsia, rank based methodAbstract
Introduction: To derive the reference intervals of serum soluble FMS like tyrosine kinase -1/Placental growth factor ratio in pregnant and non-pregnant females.
Aims & Objectives: To derive the reference intervals of serum soluble FMS like tyrosine kinase -1/Placental growth factor ratio in pregnant and non-pregnant females.
Place and Duration of Study: A comparative Cross-sectional study conducted in department of Chemical Pathology and Immunology, Chughtai Institute of Pathology, Lahore from February 2024 till May 2024
Material & Method: Blood samples from 120 pregnant and 120 non-pregnant females from 14±1 to 27±1 weeks were taken. All participants were of reproductive age group, disease free, non-hypertensive, non-diabetic, without any inherited or autoimmune disorders and not any significant drug history. Levels of placental growth factor (PGF) and soluble FMS like tyrosine kinase -1(sFlt-1) were estimated by Elecsys cobas e601. Data was analysed by SPSS 21. Shapiro-Wilk test and Kolmogorov Smirnov test were applied. p value <0.05 revealed that data findings were non- Gaussian. Reference intervals were calculated by rank-based method.
Results: The reference intervals of serum sFlt-1/PGF ratio in non-pregnant females were 5.36 to 18.40 and in pregnant females 0.61 to 24.45 and they were determined on 2.5th and 97.5th centiles using 90% confidence interval.
Conclusion: sFlt-1/PGF ratio can act as a predictive biomarker for cardiovascular disease in non-pregnant females and for pre-eclampsia in pregnant females. Current study findings would be helpful for healthcare providers to identify high- risk groups. The identification of low-risk groups results in a shorter duration of hospitalizations with potential economic benefits.
References
Feroz A, Saleem S, Seto E. Exploring perspectives, preferences and needs of a telemonitoring program for women at high risk for preeclampsia in a tertiary health facility of Karachi: a qualitative study protocol. Reprod Health. 2020;17:135. doi:10.1186/s12978-020-00979-8.
Khan B, Allah Yar R, Khakwani AK, Karim S, Arslan Ali H. Preeclampsia incidence and its maternal and neonatal outcomes with associated risk factors. Cureus. 2022 Nov 6;14(11). doi:10.7759/cureus.31143. PMID: 36483900; PMCID: PMC9723483.
Fishel Bartal M, Lindheimer MD, Sibai BM. Proteinuria during pregnancy: definition, pathophysiology, methodology, and clinical significance. Am J Obstet Gynecol. 2022 Feb;226(2S). doi:10.1016/j.ajog.2020.08.108. Epub 2020 Sep 1. PMID: 32882208.
Verlohren S, Dröge LA. The diagnostic value of angiogenic and antiangiogenic factors in differential diagnosis of preeclampsia. Am J Obstet Gynecol. 2022 Feb;226(2S). doi:10.1016/j.ajog.2020.09.046. Epub 2020 Sep 28. PMID: 33002498.
Ogunlola M, Reddy P, Sibiya MN, O'Connor L, Borg D, Haffejee F, et al. Circulating soluble fms-like tyrosine kinase-1, soluble endoglin, and placental growth factor during pregnancy in normotensive women in KwaZulu-Natal, South Africa. Afr Health Sci. 2019 Jun;19(2):1821-32. doi:10.4314/ahs.v19i2.4. PMID: 31656464; PMCID: PMC6794537.
Rana S, Burke SD, Karumanchi SA. Imbalances in circulating angiogenic factors in the pathophysiology of preeclampsia and related disorders. Am J Obstet Gynecol. 2022 Feb;226(2S). doi:10.1016/j.ajog.2020.10.022. Epub 2020 Oct 20. PMID: 33096092; PMCID: PMC8884164.
Cim N, Kurdoglu M, Ege S, Yoruk I, Yaman G, Yildizhan R. An analysis on the roles of angiogenesis-related factors including serum vitamin D, soluble endoglin (sEng), soluble fms-like tyrosine kinase 1 (sFlt1), and vascular endothelial growth factor (VEGF) in the diagnosis and severity of late-onset preeclampsia. J Matern Fetal Neonatal Med. 2017 Jul;30(13):1602-7. doi:10.1080/14767058.2016.1219986. Epub 2016 Sep 23. PMID: 27658884.
Fillion A, Guerby P, Lachance C, Comeau MP, Bussières MC, Doucet-Gingras FA, et al. Placental growth factor and soluble FMS-like tyrosine kinase-1 in preeclampsia: a case-cohort (pearl) study. J Obstet Gynaecol Can. 2020;42(10):1235-42. doi:10.1016/j.jogc.2020.03.024.
Theilade S, Lajer M, Jorsal A, Tarnow L, Parving H, Rossing P. Evaluation of placental growth factor and soluble Fms-like tyrosine kinase 1 as predictors of all-cause and cardiovascular mortality in patients with Type 1 diabetes with and without diabetic nephropathy. Diabet Med. 2012;29(3):337-44. doi:10.1111/j.1464-5491.2011.03482.x. PMID: 21988672.
Horn PS, Pesce AJ. Reference intervals: a user’s guide. Clin Chim Acta. 2006;52(3):544-5. doi:10.1016/s0009-8981(03)00133-5.
Clinical and Laboratory Standards Institute. How to define and determine reference intervals in the clinical laboratory: approved guideline – second edition. CLSI document C28-A2. Wayne, PA, USA: CLSI; 2000.
Badrick T. Biological variation: understanding why it is so important?. Pract Lab Med. 2021;23:199. doi:10.1016/j.plabm.2020.e00199.
Horowitz G, Jones RD. Establishment and use of reference intervals: clinical chemistry and immunology. 1st South Asia edition. New Delhi: Elsevier; 2018. p. 183-4.
Ahmed AR, Khan MD, Batool H, Chughtai O, Chughtai AS, Sarwar S. Reference interval of soluble FMS-like tyrosine kinase 1 in non-pregnant and pregnant females: a novel biomarker for preeclampsia. J Coll Physicians Surg Pak. 2023;33(12):1395-9. doi:10.29271/jcpsp.2023.12.1395. PMID: 38062595.
Verlohren S, Herraiz I, Lapaire O, Schlembach D, Zeisler H, Calda P, et al. New gestational phase-specific cutoff values for the use of the soluble FMS-like tyrosine kinase-1/placental growth factor ratio as a diagnostic test for preeclampsia. Hypertension. 2014;63(2):346-52. doi:10.1161/HYPERTENSIONAHA.113.01787.
Mitlid-Mork B, Bowe S, Gran JM, Bolstad N, Berg JP, Redman CW, et al. Maternal placental growth factor and soluble fms-like tyrosine kinase-1 reference ranges in post-term pregnancies: a prospective observational study. PLoS One. 2020 Oct 20;15(10). doi:10.1371/journal.pone.0240473. PMID: 33079955; PMCID: PMC7575115.
Andersen LB, Frederiksen-Møller B, Havelund KW, Dechend R, Jørgensen JS, Jensen BL, et al. Diagnosis of preeclampsia with soluble Fms-like tyrosine kinase 1/placental growth factor ratio: an inter-assay comparison. J Am Soc Hypertens. 2015 Feb;9(2):86-96. doi:10.1016/j.jash.2014.11.008. Epub 2014 Dec 3. PMID: 25600419.
Stepan H, Galindo A, Hund M, Schlembach D, Sillman J, Surbek D, Vatish M. Clinical utility of sFlt-1 and PlGF in screening, prediction, diagnosis and monitoring of preeclampsia and fetal growth restriction. Ultrasound Obstet Gynecol. 2023 Feb;61(2):168-80. doi:10.1002/uog.26032. PMID: 35816445.
Schoofs K, Grittner U, Engels T, Pape J, Denk B, Henrich W, Verlohren S. The importance of repeated measurements of the sFlt-1/PlGF ratio for the prediction of preeclampsia and intrauterine growth restriction. J Perinat Med. 2014 Jan;42(1):61-8. doi:10.1515/jpm-2013-0074. PMID: 23929878.
Hughes RCE, Phillips I, Florkowski CM, Gullam J. The predictive value of the sFlt-1/PlGF ratio in suspected preeclampsia in a New Zealand population: a prospective cohort study. Aust N Z J Obstet Gynaecol. 2023 Feb;63(1):34-41. doi:10.1111/ajo.13549. Epub 2022 Jun 7. PMID: 35670085.
Tarasevi?iene V, Grybauskieneb R, Ma?iulevi?ien R. sFlt-1, PlGF, sFlt-1/PlGF ratio and uterine artery Doppler for preeclampsia diagnostics. Medici. 2016;52(6):11-8. doi:10.1016/j.medi.2016.11.008.
Wright D, Krajewska K, Bogdanova A, Wright A, Nicolaides KH. Maternal serum soluble fms-like tyrosine kinase-1 at 22 and 32 weeks in the prediction of preeclampsia. Ultrasound Obstet Gynecol. 2016 Jun;47(6):755-61. doi:10.1002/uog.15807.
Valencia-Ortega J, Villagómez-Rico N, Parra-Llorente L, Campos A, Díaz L, Ortiz-Pérez O, et al. Predictive value of angiogenic/anti-angiogenic factors for preeclampsia: sFlt-1/PlGF ratio, sEng, and PlGF in patients with early-onset preeclampsia and fetal growth restriction. Hypertens Pregnancy. 2018 Nov;37(4):202-7. doi:10.1080/10641955.2018.1507387. Epub 2018 Aug 14. PMID: 30106355.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2024 Proceedings
This work is licensed under a Creative Commons Attribution 4.0 International License.
This work is licensed under a 