Diverse associations observed between pregnancy complications and RBC or plasma folates determined by an in-house developed LC-MS/MS method

Zhengwen Xu; Youran Li; Ying Liu; Shengmin Liu; Lin Zhang; Jing Wang; Shaofei Su; Lin Liu; Lanlan Meng; Hongyuan Zhu; Jingru Sun; Lijun Shao; Lin Li; Yanhong Zhai; Guanghui Li; Zheng Cao

doi:10.1080/07853890.2023.2265381

Diverse associations observed between pregnancy complications and RBC or plasma folates determined by an in-house developed LC-MS/MS method

Ann Med. 2023;55(2):2265381. doi: 10.1080/07853890.2023.2265381. Epub 2023 Oct 12.

Authors

Zhengwen Xu^{1

2}, Youran Li^{1

2}, Ying Liu^{1

2}, Shengmin Liu³, Lin Zhang⁴, Jing Wang⁴, Shaofei Su⁵, Lin Liu^{1

2}, Lanlan Meng^{1

2}, Hongyuan Zhu^{1

2}, Jingru Sun³, Lijun Shao³, Lin Li³, Yanhong Zhai^{1

2}, Guanghui Li⁶, Zheng Cao^{1

2}

Affiliations

¹ Department of Laboratory Medicine, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, PR China.
² Center of Clinical Mass Spectrometry, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, PR China.
³ Health Biotech Co. Ltd, Beijing, PR China.
⁴ Department of Internal Medicine, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, PR China.
⁵ Central Laboratory, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, PR China.
⁶ Department of Obstetrics, Beijing Obstetrics and Gynecology Hospital, Division of Endocrinology and Metabolism, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, PR China.

Abstract

Background: As folates are essential for embryonic development and growth, it is necessary to accurately determine the levels of folates in plasma and red blood cells (RBCs) for clinical intervention. The aims of this study were to develop and validate a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for quantitation of folates in plasma and RBCs and to examine the association between plasma and RBC folate concentrations and gestational diabetes mellitus (GDM), gestational hypertension (GH) and preeclampsia (PE).

Methods: With the in-house developed LC-MS/MS, a retrospective cross-sectional study was conducted. The healthy pregnant women of first- (n = 147), second- (n = 84) and third-trimester (n = 141) or the women diagnosed with GDM (n = 84), GH (n = 58) or PE (n = 23), that were aged between 22 and 46 years old and registered at our institute, were subjected for measurement of folic acid (FA) and 5-methyltetrahydrofolate (5-MTHF), followed by appropriate statistical association analysis.

Results: The assay for simultaneous quantitation of FA and 5-MTHF in plasma and RBCs was linear, stable, with imprecision less than 15% and recoveries within ±10%. The lower limits of quantification for FA and 5-MTHF measurement in whole blood were 0.57 and 1.09 nmol/L, and in plasma were 0.5 and 1 nmol/L, respectively. In the association analysis, the patients with lower RBC folate level (<906 nmol/L) presented higher risks of PE development (OR 4.861 [95% CI 1.411-16.505]) by logistic regression and restricted cubic spline (RCS) regression in a nonlinear fashion. In addition, higher level of plasma folates in pregnancy was significantly associated with GH risk but may be protective for the development of GDM.

Conclusions: The in-house developed LC-MS/MS method for folates and metabolites in plasma or RBC showed satisfactory analytical performance for clinical application. Further, the levels of folates and metabolites were diversely associated with GDM, GH and PE development.

Keywords: Folate; LC-MS/MS; RBC; gestational diabetes mellitus; gestational hypertension; plasma; preeclampsia.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Chromatography, Liquid
Cross-Sectional Studies
Erythrocytes / chemistry
Female
Folic Acid / analysis
Humans
Middle Aged
Pre-Eclampsia*
Pregnancy
Retrospective Studies
Tandem Mass Spectrometry* / methods
Young Adult

Substances

Folic Acid

Grants and funding

This work was supported by the Training Fund for Open Projects at Clinical Institutes and Departments of Capital Medical University (CCMU2022ZKYXZ006), the Beijing Municipal Administration of Hospitals Incubating Program (No. PX2022058) and High-level Construction Project of Public Health Technical Personnel in Beijing Municipal Health System (No. Lingjunrencai-02-02). The funding bodies did not take part in the design of the study, the collection, analysis and interpretation of the data, or manuscript writing.