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Plasma trimethylamine N-oxide metabolites in the second trimester predict the risk of hypertensive disorders of pregnancy: a nested case-control study

Hypertension Research volume 47, pages 778–789 (2024)Cite this article

Abstract

The relationship between gut microbiota products trimethylamine oxide (TMAO) and related metabolites including betaine, choline and L-carnitine and hypertensive disorders of pregnancy (HDP) is unclear. In order to examine whether plasma TMAO and related metabolites predict the risk of HDP, a nested case-control study was conducted in Chinese women based on a prospective cohort including 9447 participants. 387 pairs of pregnant women (n = 774) were matched and their plasma TMAO, betaine, choline, and L-carnitine at 16–20 gestational weeks were measured by liquid chromatography–mass spectrometry. Odds ratio (OR) and the 95% confidence interval (95% CI) were calculated using the conditional logistic regression, to examine the association between TMAO metabolites and HDP. The findings showed that higher plasma betaine (≥24.94 μmol/L) was associated with a decreased risk of HDP and its subtype gestational hypertension (GH), with adjusted ORs of 0.404 (95% CI: 0.226–0.721) and 0.293 (95% CI: 0.134–0.642), respectively. Higher betaine/choline ratio (>2.64) was associated with a lower risk of HDP and its subtype preeclampsia or chronic hypertension with superimposed preeclampsia (PE/CH-PE), with adjusted ORs of 0.554 (95% CI: 0.354–0.866) and 0.226 (95% CI: 0.080–0.634). Moreover, compared with traditional factors (TFs) model, the TMAO metabolites+ TFs model had a higher predictive ability for PE/CH-PE (all indexes P values < 0.0001). Therefore, it suggests that the detection of plasma betaine and choline in the early second trimester of pregnancy can better assess the risk of HDP.

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Data described in the manuscript, code book, and analytic code will be made available upon request pending approval by the authors.

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Acknowledgements

We gratefully acknowledge the cooperation and participation of the members of this study. We especially thank the clinical staff at all participating hospitals for their support and contribution to this project.

Funding

This study was supported by grants from the National Natural Science Foundation of China (NO. 81903384), Natural Science Foundation of Jiangsu Province (NO. BK20181438), the Scientific Research Project of Suzhou Gusu Health Fostering Talents Plan (NO. GSWS2021066), the Science, Education and Health of Suzhou Youth Science and Technology Project (NO. KJXW2020073), the Maternal and Child Health Project of Jiangsu Province (NO. F202027, F201830), and the Suzhou Municipal Science and Technology Bureau (NO. SKY2023036, SKY2023041, and SS202009).

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  1. These authors contributed equally: He Xu, Pei Feng.

Authors and Affiliations

  1. Department of Epidemiology and Biostatistics, School of Public Health, Suzhou Medical College of Soochow University, Suzhou, 215123, China

    He Xu, Yexiu Sun, Di Wu, Dandan Wang, Hao Peng & Hongmei Li

  2. Department of Community Health Care, Kunshan Maternity and Children’s Health Care Hospital, Kunshan, China

    Pei Feng

  3. Department of Maternal and Child Health, Suzhou Industrial Park Center for Disease Control and Prevention, Suzhou, China

    Lei Wu

  4. MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou, 215123, China

    Hao Peng & Hongmei Li

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Xu, H., Feng, P., Sun, Y. et al. Plasma trimethylamine N-oxide metabolites in the second trimester predict the risk of hypertensive disorders of pregnancy: a nested case-control study. Hypertens Res 47, 778–789 (2024). https://doi.org/10.1038/s41440-023-01563-w

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