Associations of trimethylamine N-oxide and its precursors with hypertensive disorders of pregnancy, its subtypes and blood pressure in the offspring: findings from the Shanghai Birth Cohort

BACKGROUND: Trimethylamine N-oxide (TMAO) and its precursors (choline, betaine, and carnitine) have been associated with hypertension in nonpregnant adults, yet limited research exists on their relationship with hypertensive disorders of pregnancy (HDP). Additionally, no prior studies have investigated whether TMAO and its precursors influence offspring blood pressure (BP). OBJECTIVES: This study aims to examine the associations of TMAO and its precursors during early pregnancy with the risk of HDP and its subtypes (gestational hypertension (GH), preeclampsia (PE) and eclampsia) and BP in four-year-old children within the Shanghai Birth Cohort. STUDY DESIGN: Plasma TMAO and its precursors were measured at 10-12 gestational weeks via liquid chromatography-mass spectrometry. Logistic regression was employed to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs) to evaluate their associations with HDP and its subtypes, while linear regressions examined their relationships with childhood systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP). RESULTS: The study involved 1985 pregnant women and 803 four-year-old children. TMAO levels in the second quartile are linked to an increased risk of HDP (OR = 1.49, 95% CI: 1.03-2.16) and GH (OR = 1.57, 95% CI: 1.06-2.33) compared to the lowest quartile. The ORs for the highest quartile of betaine, compared with the lowest quartile, are 0.64 (95% CI: 0.44-0.93) for HDP risk and 0.61 (95% CI: 0.41-0.90) for GH risk, respectively. In the highest quartile of carnitine compared to the lowest quartile, carnitine level is negatively associated with the incidence of PE and eclampsia (OR = 0.32, 95% CI: 0.12-0.84), and positively associated with the incidence of GH (OR = 1.58, 95% CI: 1.06-2.36). Additionally, maternal carnitine positively correlated with child SBP (β = 0.13 mmHg, 95% CI: 0.01-0.24) and MAP (β = 0.10 mmHg, 95% CI: 0.01-0.19). CONCLUSIONS: Elevated level of TMAO is associated with an increased risk of HDP, while higher betaine levels exhibit a protective effect. Carnitine is positively associated with the risk of GH. These findings suggest that TMAO and its precursors may serve as potential biomarkers for early HDP identification and prevention. However, future well-designed studies are needed to further investigate the associations of TMAO and its precursors with HDP, its subtypes, and offspring BP.