Potential of first trimester plasma lipidome in high-risk pregnancy groups

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Abstract

Objective: To evaluate the relationship between plasma lipids, changes in their concentration during early pregnancy, and the risk of preeclampsia (PE) in pregnant women at a high risk for placenta-mediated complications.

Materials and methods: This prospective case-control study included 66 pregnant women, including a group at high risk for placenta-associated complications based on medical history and first trimester screening (n=38) and a control group (n=28). Lipid extracts of blood plasma from the first trimester of pregnancy were analyzed using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Lipids were identified using Lipid Match R-script by accurate mass using the Lipid Maps database and characteristic tandem mass spectra (MS/MS). Based on lipids identified as having a statistically significant correlation with clinical data (Spearman's criterion), a model of projections to latent structures was constructed using two predictive axes. From lipids with a variable projection value greater than 1 in the model, those with which the model based on logistic regression had the lowest Akaike information criterion and coefficients that were significantly different from zero were selected.

Results: Correlation analysis according to high-risk groups identified 48 lipids, for which the level of correlation with at least one clinical parameter was average or above average (R>0.6), belonging to the classes of phosphatidylcholines, phosphatidylinositols, sphingomyelins, and triglycerides. Two logistic regression models were constructed to identify patients at high risk for PE by plasma lipid levels in the first trimester of pregnancy with optimal sensitivity and specificity of 0.91 and 0.91 for the positive ion regimen (phosphatidylethanolamine PE 16:0_22:6 and phosphatidylcholine PC 18:0_18:1) and optimal sensitivity and specificity of 0.82 and 0.96 for the negative ion mode (sphingomyelins SM d24:0/18:1 and SM d22:1/20:4). Survival function analysis yielded a relative risk for the group defined as high-risk using the model based on lipid profile in the positive ion mode of 33.5 with CI 4.7–241, and a relative risk for the PE screening outcome of 2.67 with CI 0.74–9.64.

Conclusion: Changes in the first-trimester plasma lipid spectrum, mainly phosphatidylcholines, lysophosphatidylcholines, phosphatidylethanolamine, triglycerides, and sphingomyelins, are associated with the risk of PE in the high-risk group. This allows us to propose logistic regression models based on first-trimester plasma marker lipid levels as a refinement after the first-trimester screening. In the future, the data obtained may contribute to the improvement of preventive measures for placenta-associated disorders and the timely monitoring of their development.

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About the authors

Ekaterina A. Minaeva

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of the Russian Federation

Author for correspondence.
Email: minaevakatya93@yandex.ru
ORCID iD: 0000-0001-8555-6670

post-graduate student, 1st Obstetric Department of Pregnancy Pathology

Russian Federation, Moscow

Natalia L. Starodubtseva

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of the Russian Federation

Email: n_starodubtseva@oparina4.ru
ORCID iD: 0000-0001-6650-5915

PhD (Bio.), Head of the Laboratory of Clinical Proteomics

Russian Federation, Moscow

Roman G. Shmakov

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of the Russian Federation

Email: r_shmakov@oparina4.ru
ORCID iD: 0000-0002-2206-1002

Dr. Med. Sci., Professor, Professor of the Russian Academy of Sciences, Director of the Institute of Obstetrics

Russian Federation, Moscow

Vitaliy V. Chagovets

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of the Russian Federation

Email: vvchagovets@gmail.com

PhD, Head of the Laboratory of Metabolomics and Bioinformatics

Russian Federation, Moscow

Alisa O. Tokareva

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of the Russian Federation

Email: a_tokareva@oparina4.ru

PhD, specialist at the Laboratory of Clinical Proteomics

Russian Federation, Moscow

Anastasia V. Novoselova

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of the Russian Federation

Email: a_novoselova@oparina4.ru

Junior Researcher at the Laboratory of Metabolomics and Bioinformatics

Russian Federation, Moscow

Evgeny N. Kukaev

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of the Russian Federation; V.L. Talrose Institute for Energy Problems of Chemical Physics at N.N. Semenov Federal Research Center for Chemical Physics Russian Academy of Sciences

Email: e_kukaev@oparina4.ru

PhD, Senior Researcher at the Laboratory of Clinical Proteomics

Russian Federation, Moscow; Moscow

Vladimir E. Frankevich

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of the Russian Federation; Siberian State Medical University, Ministry of Health of the Russian Federation

Email: v_vfrankevich@oparina4.ru
ORCID iD: 0000-0002-9780-4579

Dr. Sci. (Physico-Mathematical), Deputy Director of the Institute of Translational Medicine

Russian Federation, Moscow; Tomsk

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Supplementary files

Supplementary Files
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1. JATS XML
2. Fig. 1. Correlation matrix of the most characteristic lipids with clinical parameters

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3. Fig. 2. Graph of PLS model accounts in the positive ion mode (a) and in the negative ion mode (b)

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4. Fig. 3. Plots of OPLS model accounts for discrimination of PE cases in the positive ion mode (a), in the negative ion mode (b)

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5. Fig. 4. Operating curve (ROC) and area under the operating curve (AUC) for positive ion mode (a) and negative ion mode (b)

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6. Fig. 5. "Survival curves" for groups: a) high and low risk of PE, defined using a model based on lipids taken in positive ion/negative ion mode); b) formed on the basis of screening results, with the value of the log-rank test criterion indicated

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