Verification of bile acid determination method and establishing reference intervals for biochemical and haematological parameters in third-trimester pregnant women
-
Lara Zorić
, Petra Glad Štritof , Helena Čičak , Paulo Zekan , Maria Gotić Pavasović , Vladimir Blagaić, Miran Čoklo
, Ana-Maria Šimundićand Lora Dukić
Abstract
Objectives
The aims of this study were to verify the bile acids (BA) method and to establish reference intervals (RIs) for bile acids (BA) and biochemical and haematological parameters in Croatian pregnant women.
Methods
BA spectrophotometric method verification was performed on Siemens Atellica Solution CH 930 automated analyser using Sentinel reagent. Stability, precision, trueness, linearity, and RIs, as well as lipemia interference were tested according to CLSI guidelines. BA, biochemical, and haematological parameters were measured in serum (BA, biochemical) and whole blood (haematological) samples of fasting healthy third-trimester pregnant women from Croatia (n=121). The establishment of the RIs was done a priori according to the CLSI EP28-A3C:2010 guideline. Selected reference individuals’ data were analysed using parametric, non-parametric, and robust methods.
Results
Stability study showed that BA are stable in serum samples for 2 days at 20 °C, 14 days at 4–8 °C, and 22 days at −20 °C. The precision study and adult RIs verification met the criteria. Linearity was verified for the concentration range of 3.5–172.1 μmol/L whereas the lipemia interference test showed a positive bias (%) in BA concentration. The determined reference limits generally exhibited better precision for haematological parameters, being lower than the upper recommended value 0.2, unlike biochemical parameters. Haematological parameters showed notable differences between pregnant and non-pregnant women, while many biochemical parameters’ RIs remained similar. Only ALT and GGT showed lower non-comparable RI upper limits in the population pregnant women.
Conclusions
Spectrophotometric BA method showed satisfactory performance and all examined parameters were within the set criteria. Moreover, RIs for key biochemical and haematological parameters, including BAs, have been established for the first time in the population of Croatian pregnant women.
Acknowledgments
We are very grateful to all those who played a role in the success of this project. A special thank you to our colleagues from Clinical Department of Chemistry at the University Hospital Centre Sestre Milosrdnice for their valuable contributions to the practical facets of this publication.
-
Research ethics: The research related to human subjects has complied with all relevant national regulations, institutional policies adn in accordance with tenets of Helsinki Declaration, and has been approved by the authors’ Review board (01-03/721/15).
-
Informed consent: Informed consent was obtained from all individuals included in this study, or their legal guardians or wards.
-
Author contributions: The authors have accepted responsibility for the entire content of this manuscript and approved its submission.
-
Competing interests: The authors state no conflict of interest.
-
Research funding: None declared.
-
Data availability: The raw data can be obtained on request from the corresponding author.
References
1. Hill, CC, Pickinpaugh, J. Physiologic changes in pregnancy. Surg Clin North Am 2008;88:391–401, vii. https://doi.org/10.1016/j.suc.2007.12.005.Search in Google Scholar PubMed
2. Tran, HA. Biochemical tests in pregnancy. Aust Prescr 2005;28:136–9. https://doi.org/10.18773/austprescr.2005.076.Search in Google Scholar
3. Teasdale, S, Morton, A. Changes in biochemical tests in pregnancy and their clinical significance. Obstet Med 2018;11:160–70. https://doi.org/10.1177/1753495X18766170.Search in Google Scholar PubMed PubMed Central
4. Chen, HM, Kuo, FC, Chen, CC, Wu, CF, Sun, CW, Chen, ML, et al.. New trimester-specific reference intervals for clinical biochemical tests in Taiwanese pregnant women-cohort of TMICS. PLoS One 2020;15:e0243761. https://doi.org/10.1371/journal.pone.0243761.Search in Google Scholar PubMed PubMed Central
5. Soma-Pillay, P, Nelson-Piercy, C, Tolppanen, H, Mebazaa, A. Physiological changes in pregnancy. Cardiovasc J Afr 2016;27:89–94. https://doi.org/10.5830/CVJA-2016-021.Search in Google Scholar PubMed PubMed Central
6. Padoan, A. Laboratory tests to monitoring physiological pregnancy. J Lab Precis Med 2020;5:7. https://doi.org/10.21037/jlpm.Search in Google Scholar
7. Piechota, J, Jelski, W. Intrahepatic cholestasis in pregnancy: review of the literature. J Clin Med 2020;9:1361. https://doi.org/10.3390/jcm9051361.Search in Google Scholar PubMed PubMed Central
8. Williamson, C, Miragoli, M, Abdul Kadir, SS, Abu-Hayyeh, S, Papacleovoulou, G, Geenes, V, et al.. Bile acid signaling in fetal tissues: implications for intrahepatic cholestasis of pregnancy. Dig Dis 2011;29:58–61.10.1159/000324130Search in Google Scholar PubMed
9. Floreani, A, Gervasi, MT. New insights on intrahepatic cholestasis of pregnancy. Clin Liver Dis 2016;20:177–89.10.1016/j.cld.2015.08.010Search in Google Scholar PubMed
10. Gao, XX, Ye, MY, Liu, Y, Li, JY, Li, L, Chen, W, et al.. Prevalence and risk factors of intrahepatic cholestasis of pregnancy in a Chinese population. Sci Rep 2020;10:16307. https://doi.org/10.1038/s41598-020-73378-5.Search in Google Scholar PubMed PubMed Central
11. Geenes, V, Chappell, LC, Seed, PT, Steer, PJ, Knight, M, Williamson, C. Association of severe intrahepatic cholestasis of pregnancy with adverse pregnancy outcomes: a prospective population-based case-control study. Hepatology 2014;59:1482–91. https://doi.org/10.1002/hep.26617.Search in Google Scholar PubMed PubMed Central
12. Sahni, A, Jogdand, SD. Effects of intrahepatic cholestasis on the foetus during pregnancy. Cureus 2022;14:e30657. https://doi.org/10.7759/cureus.30657.Search in Google Scholar PubMed PubMed Central
13. Ozkan, S, Ceylan, Y, Ozkan, OV, Yildirim, S. Review of a challenging clinical issue: intrahepatic cholestasis of pregnancy. World J Gastroenterol 2015;21:7134–41. https://doi.org/10.3748/wjg.v21.i23.7134.Search in Google Scholar PubMed PubMed Central
14. Marschall, HU, Wikström Shemer, E, Ludvigsson, JF, Stephansson, O. Intrahepatic cholestasis of pregnancy and associated hepatobiliary disease: a population-based cohort study. Hepatology 2013;58:1385–91. https://doi.org/10.1002/hep.26444.Search in Google Scholar PubMed
15. Pauli-Magnus, C, Meier, PJ, Stieger, B. Genetic determinants of drug-induced cholestasis and intrahepatic cholestasis of pregnancy. Semin Liver Dis 2010;30:147–59. https://doi.org/10.1055/s-0030-1253224.Search in Google Scholar PubMed
16. Dixon, PH, Williamson, C. The molecular genetics of intrahepatic cholestasis of pregnancy. Obstet Med 2008;1:65–71. https://doi.org/10.1258/om.2008.080010.Search in Google Scholar PubMed PubMed Central
17. Dixon, PH, Williamson, C. The pathophysiology of intrahepatic cholestasis of pregnancy. Clin Res Hepatol Gastroenterol 2016;40:141–53. https://doi.org/10.1016/j.clinre.2015.12.008.Search in Google Scholar PubMed
18. Arrese, M, Reyes, H. Intrahepatic cholestasis of pregnancy: a past and present riddle. Ann Hepatol 2006;5:202–5.10.1016/S1665-2681(19)32012-5Search in Google Scholar
19. Lammert, F, Marschall, HU, Glantz, A, Matern, S. Intrahepatic cholestasis of pregnancy: molecular pathogenesis, diagnosis and management. J Hepatol 2000;33:1012–21. https://doi.org/10.1016/s0168-8278(00)80139-7.Search in Google Scholar PubMed
20. Ovadia, C, Seed, PT, Sklavounos, A, Geenes, V, Di Ilio, C, Chambers, J, et al.. Association of adverse perinatal outcomes of intrahepatic cholestasis of pregnancy with biochemical markers: results of aggregate and individual patient data meta-analyses. Lancet 2019;393:899–909. https://doi.org/10.1016/S0140-6736(18)31877-4. Erratum in: Lancet 2019;393:1100.Search in Google Scholar PubMed PubMed Central
21. Williamson, C, Gorelik, J, Eaton, BM, Lab, M, de Swiet, M, Korchev, Y. The bile acid taurocholate impairs rat cardiomyocyte function: a proposed mechanism for intra-uterine fetal death in obstetric cholestasis. Clin Sci 2001;100:363–9.10.1042/cs1000363Search in Google Scholar
22. Sepúlveda, WH, González, C, Cruz, MA, Rudolph, MI. Vasoconstrictive effect of bile acids on isolated human placental chorionic veins. Eur J Obstet Gynecol Reprod Biol 1991;42:211–5. https://doi.org/10.1016/0028-2243(91)90222-7.Search in Google Scholar PubMed
23. Majsterek, M, Wierzchowska-Opoka, M, Makosz, I, Kreczyńska, L, Kimber-Trojnar, Ż, Leszczyńska-Gorzelak, B. Bile acids in intrahepatic cholestasis of pregnancy. Diagnostics 2022;12:2746. https://doi.org/10.3390/diagnostics12112746.Search in Google Scholar PubMed PubMed Central
24. Pusl, T, Beuers, U. Intrahepatic cholestasis of pregnancy. Orphanet J Rare Dis 2007;2:26. https://doi.org/10.1186/1750-1172-2-26.Search in Google Scholar PubMed PubMed Central
25. Pillarisetty, LS, Sharma, A. Pregnancy intrahepatic cholestasis. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023.Search in Google Scholar
26. Markanović Mišan, M, Zoričić, D, Honović, L. Referentni intervali laboratorijskih pretraga u trudnoći. Med Flum 2014;50:54–60.Search in Google Scholar
27. Cornes, M, Simundic, AM, Cadamuro, J, Costelloe, SJ, Baird, G, Kristensen, GBB, et al.. The CRESS checklist for reporting stability studies: on behalf of the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) working Group for the Preanalytical Phase (WG-PRE) Clin Chem Lab Med 2020;59:59–69. https://doi.org/10.1515/cclm-2020-0061.Search in Google Scholar PubMed
28. CLSI. EP15-A3 – user verification of precision and estimation of bias; approved guideline, 3rd ed. Wayne, PA, USA: Clinical and Laboratory Standards Institute; 2014.Search in Google Scholar
29. CLSI. EP06 – a evaluation of the linearity of quantitative measurement procedures: a statistical approach; approved guideline. Wayne, USA: Clinical and Laboratory Standards Insititute; 2003, 23.Search in Google Scholar
30. CLSI. EP9-A3 – procedure comparison and bias estimation using patient samples. Wayne, PA, USA; Clinical and Laboratory Standards Institute; 2013.Search in Google Scholar
31. CLSI. EP28-A3c – defining, establishing, and verifying reference intervals in the clinical laboratory; approved guideline, 3rd ed. Wayne, PA, USA; Clinical and Laboratory Standards Institute; 2010.Search in Google Scholar
32. Zhu, B, Yin, P, Ma, Z, Ma, Y, Zhang, H, Kong, H, et al.. Characteristics of bile acids metabolism profile in the second and third trimesters of normal pregnancy. Metabolism 2019;95:77–83.10.1016/j.metabol.2019.04.004Search in Google Scholar PubMed
33. Danese, E, Negrini, D, Pucci, M, De Nitto, S, Ambrogi, D, Donzelli, S, et al.. Bile acids quantification by liquid chromatography-tandem mass spectrometry: method validation, reference range, and interference study. Diagnostics 2020;10:462. https://doi.org/10.3390/diagnostics10070462.Search in Google Scholar PubMed PubMed Central
34. Zhang, GH, Cong, AR, Xu, GB, Li, CB, Yang, RF, Xia, TA. An enzymatic cycling method for the determination of serum total bile acids with recombinant 3alpha-hydroxysteroid dehydrogenase. Biochem Biophys Res Commun 2005;326:87–92. https://doi.org/10.1016/j.bbrc.2004.11.005.Search in Google Scholar PubMed
35. Monte, MJ, Marin, JJ, Antelo, A, Vazquez-Tato, J. Bile acids: chemistry, physiology, and pathophysiology. World J Gastroenterol 2009;15:804–16. https://doi.org/10.3748/wjg.15.804.Search in Google Scholar PubMed PubMed Central
36. Solter, PF, Hoffmann, WE, Hoffman, JW. Evaluation of an automated serum bile acids assay and the effect of bilirubin, hemoglobin, and lipid on the apparent bile acids yield. Vet Clin Pathol 1992;21:114–8. https://doi.org/10.1111/j.1939-165X.1992.tb00596.x.Search in Google Scholar PubMed
37. Shen, Y, Liu, K, Luo, X, Guan, Q, Cheng, L. A simple and reliable bile acid assay in human serum by LC-MS/MS. J Clin Lab Anal 2022;36:e24279. https://doi.org/10.1002/jcla.24279.Search in Google Scholar PubMed PubMed Central
38. Yadav, S, Goel, A, Lingaiah, R, Pradhan, M, Katiyar, H, Rakesh, A. Serum bile acid levels in women with intrahepatic cholestasis of pregnancy in India. J Clin Exp Hepatol 2022;12:379–83. https://doi.org/10.1016/j.jceh.2021.07.008.Search in Google Scholar PubMed PubMed Central
39. Egan, N, Bartels, A, Khashan, AS, Broadhurst, DI, Joyce, C, O’Mullane, J, et al.. Reference standard for serum bile acids in pregnancy. BJOG 2012;119:493–8. https://doi.org/10.1111/j.1471-0528.2011.03245.x.Search in Google Scholar PubMed
40. Huri, M, Seravalli, V, Lippi, C, Tofani, L, Galli, A, Petraglia, F, et al.. Intrahepatic cholestasis of pregnancy – time to redefine the reference range of total serum bile acids: a cross-sectional study. BJOG 2022;129:1887–96. https://doi.org/10.1111/1471-0528.17174.Search in Google Scholar PubMed PubMed Central
41. Lee, RH, Goodwin, TM, Greenspoon, J, Incerpi, M. The prevalence of intrahepatic cholestasis of pregnancy in a primarily Latina Los Angeles population. J Perinatol 2006;26:527–32. https://doi.org/10.1038/sj.jp.7211545.Search in Google Scholar PubMed
42. Fulton, IC, Douglas, JG, Hutchon, DJR, Beckett, GJ. Is normal pregnancy cholestatic? Clin Chim Acta 1983; 130: 171–6.10.1016/0009-8981(83)90114-6Search in Google Scholar PubMed
43. Mutua, DN, Mwaniki Njagi, EN, Orinda, G. Liver function tests in normal pregnant women. J Liver 2018;7:228. https://doi.org/10.4172/2167-0889.1000228.Search in Google Scholar
44. Mohammed, M, Fiseha, M, Belay, G, Kindie, S, Tsegaye, A. Reference intervals for common renal and liver function clinical chemistry parameters among apparently healthy pregnant and non-pregnant women in South Wollo Zone, Amhara National Regional State, Northeast Ethiopia. Int J Gen Med 2022;15:5145–57. https://doi.org/10.2147/IJGM.S363129.Search in Google Scholar PubMed PubMed Central
45. Dai, Y, Liu, J, Yuan, E, Li, Y, Wang, Q, Jia, L, et al.. Gestational age-specific reference intervals for 15 biochemical measurands during normal pregnancy in China. Ann Clin Biochem 2018;55:446–52. https://doi.org/10.1177/0004563217738801.Search in Google Scholar PubMed
46. Mikolasevic, I, Filipec-Kanizaj, T, Jakopcic, I, Majurec, I, Brncic-Fischer, A, Sobocan, N, et al.. Liver disease during pregnancy: a challenging clinical issue. Med Sci Monit 2018;24:4080–90. https://doi.org/10.12659/MSM.907723.Search in Google Scholar PubMed PubMed Central
47. Fiseha, M, Mohammed, M, Ebrahim, E, Demsiss, W, Tarekegn, M, Angelo, A, et al.. Common hematological parameters reference intervals for apparently healthy pregnant and non-pregnant women of South Wollo Zone, Amhara Regional State, Northeast Ethiopia. PLoS One 2022;17:e0270685. https://doi.org/10.1371/journal.pone.0270685.Search in Google Scholar PubMed PubMed Central
48. Bakrim, S, Motiaa, Y, Benajiba, M, Ouarour, A, Masrar, A. Establishment of the hematology reference intervals in a healthy population of adults in the Northwest of Morocco (Tangier-Tetouan region). Pan Afr Med J 2018;29:169. https://doi.org/10.11604/pamj.2018.29.169.13042.Search in Google Scholar PubMed PubMed Central
49. Morton, A. Hematological normal ranges in pregnancy. Glob Libr Women’s Med 2021;8. https://doi.org/10.3843/GLOWM.413403.Search in Google Scholar
50. Chandra, S, Tripathi, AK, Mishra, S, Amzarul, M, Vaish, AK. Physiological changes in hematological parameters during pregnancy. Indian J Hematol Blood Transfus 2012;28:144–6. https://doi.org/10.1007/s12288-012-0175-6.Search in Google Scholar PubMed PubMed Central
51. Reese, JA, Peck, JD, Deschamps, DR, McIntosh, JJ, Knudtson, EJ, Terrell, DR, et al.. Platelet counts during pregnancy. N Engl J Med 2018;379:32-43. https://doi.org/10.1056/NEJMoa1802897.Search in Google Scholar PubMed PubMed Central
52. Myers, B. Diagnosis and management of maternal thrombocytopenia in pregnancy. Br J Haematol 2012;158:3–15. https://doi.org/10.1111/j.1365-2141.2012.09135.x.Search in Google Scholar PubMed
53. Feriel, J, Tchipeva, D, Depasse, F. Effects of circadian variation, lifestyle and environment on hematological parameters: a narrative review. Int J Lab Hematol 2021;43:917–26. https://doi.org/10.1111/ijlh.13590.Search in Google Scholar PubMed
© 2024 Walter de Gruyter GmbH, Berlin/Boston
Articles in the same Issue
- Frontmatter
- Editorial
- Six years of progress – highlights from the IFCC Emerging Technologies Division
- IFCC Papers
- Skin in the game: a review of single-cell and spatial transcriptomics in dermatological research
- Bilirubin measurements in neonates: uniform neonatal treatment can only be achieved by improved standardization
- Validation and verification framework and data integration of biosensors and in vitro diagnostic devices: a position statement of the IFCC Committee on Mobile Health and Bioengineering in Laboratory Medicine (C-MBHLM) and the IFCC Scientific Division
- Linearity assessment: deviation from linearity and residual of linear regression approaches
- HTA model for laboratory medicine technologies: overview of approaches adopted in some international agencies
- Considerations for applying emerging technologies in paediatric laboratory medicine
- A global perspective on the status of clinical metabolomics in laboratory medicine – a survey by the IFCC metabolomics working group
- The LEAP checklist for laboratory evaluation and analytical performance characteristics reporting of clinical measurement procedures
- General Clinical Chemistry and Laboratory Medicine
- Assessing post-analytical phase harmonization in European laboratories: a survey promoted by the EFLM Working Group on Harmonization
- Potential medical impact of unrecognized in vitro hypokalemia due to hemolysis: a case series
- Quantification of circulating alpha-1-antitrypsin polymers associated with different SERPINA1 genotypes
- Targeted ultra performance liquid chromatography tandem mass spectrometry procedures for the diagnosis of inborn errors of metabolism: validation through ERNDIM external quality assessment schemes
- Improving protocols for α-synuclein seed amplification assays: analysis of preanalytical and analytical variables and identification of candidate parameters for seed quantification
- Evaluation of analytical performance of AQUIOS CL flow cytometer and method comparison with bead-based flow cytometry methods
- IgG and kappa free light chain CSF/serum indices: evaluating intrathecal immunoglobulin production in HIV infection in comparison with multiple sclerosis
- Reference Values and Biological Variations
- Reference intervals of circulating secretoneurin concentrations determined in a large cohort of community dwellers: the HUNT study
- Sharing reference intervals and monitoring patients across laboratories – findings from a likely commutable external quality assurance program
- Verification of bile acid determination method and establishing reference intervals for biochemical and haematological parameters in third-trimester pregnant women
- Confounding factors of the expression of mTBI biomarkers, S100B, GFAP and UCH-L1 in an aging population
- Cancer Diagnostics
- Exploring evolutionary trajectories in ovarian cancer patients by longitudinal analysis of ctDNA
- Diabetes
- Evaluation of effects from hemoglobin variants on HbA1c measurements by different methods
- Letters to the Editor
- Are there any reasons to use three levels of quality control materials instead of two and if so, what are the arguments?
- Issues for standardization of neonatal bilirubinemia: a case of delayed phototherapy initiation
- The routine coagulation assays plasma stability – in the wake of the new European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) biological variability database
- Improving HCV diagnosis following a false-negative anti-HCV result
Articles in the same Issue
- Frontmatter
- Editorial
- Six years of progress – highlights from the IFCC Emerging Technologies Division
- IFCC Papers
- Skin in the game: a review of single-cell and spatial transcriptomics in dermatological research
- Bilirubin measurements in neonates: uniform neonatal treatment can only be achieved by improved standardization
- Validation and verification framework and data integration of biosensors and in vitro diagnostic devices: a position statement of the IFCC Committee on Mobile Health and Bioengineering in Laboratory Medicine (C-MBHLM) and the IFCC Scientific Division
- Linearity assessment: deviation from linearity and residual of linear regression approaches
- HTA model for laboratory medicine technologies: overview of approaches adopted in some international agencies
- Considerations for applying emerging technologies in paediatric laboratory medicine
- A global perspective on the status of clinical metabolomics in laboratory medicine – a survey by the IFCC metabolomics working group
- The LEAP checklist for laboratory evaluation and analytical performance characteristics reporting of clinical measurement procedures
- General Clinical Chemistry and Laboratory Medicine
- Assessing post-analytical phase harmonization in European laboratories: a survey promoted by the EFLM Working Group on Harmonization
- Potential medical impact of unrecognized in vitro hypokalemia due to hemolysis: a case series
- Quantification of circulating alpha-1-antitrypsin polymers associated with different SERPINA1 genotypes
- Targeted ultra performance liquid chromatography tandem mass spectrometry procedures for the diagnosis of inborn errors of metabolism: validation through ERNDIM external quality assessment schemes
- Improving protocols for α-synuclein seed amplification assays: analysis of preanalytical and analytical variables and identification of candidate parameters for seed quantification
- Evaluation of analytical performance of AQUIOS CL flow cytometer and method comparison with bead-based flow cytometry methods
- IgG and kappa free light chain CSF/serum indices: evaluating intrathecal immunoglobulin production in HIV infection in comparison with multiple sclerosis
- Reference Values and Biological Variations
- Reference intervals of circulating secretoneurin concentrations determined in a large cohort of community dwellers: the HUNT study
- Sharing reference intervals and monitoring patients across laboratories – findings from a likely commutable external quality assurance program
- Verification of bile acid determination method and establishing reference intervals for biochemical and haematological parameters in third-trimester pregnant women
- Confounding factors of the expression of mTBI biomarkers, S100B, GFAP and UCH-L1 in an aging population
- Cancer Diagnostics
- Exploring evolutionary trajectories in ovarian cancer patients by longitudinal analysis of ctDNA
- Diabetes
- Evaluation of effects from hemoglobin variants on HbA1c measurements by different methods
- Letters to the Editor
- Are there any reasons to use three levels of quality control materials instead of two and if so, what are the arguments?
- Issues for standardization of neonatal bilirubinemia: a case of delayed phototherapy initiation
- The routine coagulation assays plasma stability – in the wake of the new European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) biological variability database
- Improving HCV diagnosis following a false-negative anti-HCV result