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

Hypertens Res. 2024 Mar;47(3):778-789. doi: 10.1038/s41440-023-01563-w. Epub 2024 Jan 4.

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.

Keywords: Betaine; Choline; Hypertensive disorders of pregnancy; L-carnitine; Trimethylamine oxide.

MeSH terms

  • Betaine / metabolism
  • Carnitine / metabolism
  • Case-Control Studies
  • Choline / metabolism
  • Female
  • Humans
  • Hypertension, Pregnancy-Induced*
  • Methylamines*
  • Pre-Eclampsia*
  • Pregnancy
  • Pregnancy Trimester, Second
  • Prospective Studies

Substances

  • Betaine
  • trimethyloxamine
  • Choline
  • Carnitine
  • Methylamines