Trimethylamine N-Oxide and Its Precursors Are Associated with Gestational Diabetes Mellitus and Pre-Eclampsia in the Boston Birth Cohort

Abstract

Background Trimethylamine N-oxide (TMAO) and its precursors choline, betaine, and carnitine have been associated with cardiometabolic disease in non-pregnant adults. However, studies examining TMAO and its precursors in relation to cardiometabolic conditions during pregnancy are lacking. Objective The primary objective was to estimate the association of TMAO and its precursors in maternal and cord plasma with gestational diabetes mellitus (GDM) and pre-eclampsia (PE) among women in the Boston Birth Cohort. A secondary objective was to determine whether associations vary by race/ethnicity. Design Odds ratios for each outcome according to tertiles and to a standard deviation increment of TMAO, choline, betaine, and carnitine were estimated using logistic regression. Final models were adjusted for covariates. Results Among 1496 women, 115 women had GDM and 159 had PE during the index pregnancy. Inter-metabolite correlations of TMAO and its precursors were stronger within cord plasma (r = 0.38-0.87) than within maternal plasma (r = 0.08-0.62). Maternal TMAO was associated with higher odds of GDM (3rd vs. 1st tertile OR = 1.75; 95% CI 1.04, 2.94), while maternal choline, betaine, and carnitine were not associated with GDM. Maternal TMAO and choline were not associated with PE, while carnitine was associated with higher (OR = 1.86; 95% CI 1.18, 2.94) and betaine with lower odds of PE (OR = 0.37; 95% CI 0.23, 0.59). In cord plasma, TMAO was not associated with GDM or PE, but choline, betaine, and carnitine were associated with higher odds of PE (OR = 3.11; 95% CI 1.62, 5.96; OR = 2.65; 95% CI 1.42, 4.93; OR = 2.56; 95% CI 1.39, 4.69; respectively). Cord choline was associated with lower odds of GDM (OR = 0.52; 95% CI 0.27, 0.99), while other cord metabolites were not significantly associated with GDM. Associations did not vary by race/ethnicity. Conclusions TMAO and its precursors, were associated with GDM and PE, but the associations differed based on metabolite medium (maternal vs. cord plasma). ClinicalTrials.gov identifier: NCT03228875

Contractile effect of trimethylamine and trimethylamine‐n‐oxide on isolated human umbilical arteries

“…31 Furthermore, Barziyal et al found that the cord blood concentration of TMAO was higher in gestational diabetes mellitus (GDM) patients (2.8 μM) compared to healthy controls (1.4 μM). 32 TMAO plasma levels were not linked to GDM or preeclampsia in cord plasma, but higher odds of preeclampsia were associated with its precursors, betaine, and carnitine, according to the study by McArthur et al 13 Although research on TMA and TMAO levels in cord blood is limited, there is a growing body of literature investigating their plasma levels in patients with various diseases. Plasma levels of TMAO in healthy adults range from 0.5 μM to approximately 5 μM.…”

“…27,28 TMAO was associated with pregnancy induced diseases such as gestational diabetes and preeclampsia in recent studies. 13,29 Chen et al were examined the role of TMAO on endothelial dysfunction and hypertension in a rat model of preeclampsia (reduced uterine perfusion pressure model). 30 They reported that increased TMAO plasma levels, contribute to endothelial dysfunction and hypertension by promoting vascular inflammation and oxidative stress in preeclampsia rat model.…”

“…TMAO was associated with pregnancy induced diseases such as gestational diabetes and preeclampsia in recent studies 13,29 . Chen et al were examined the role of TMAO on endothelial dysfunction and hypertension in a rat model of preeclampsia (reduced uterine perfusion pressure model) 30 .…”

“…12 In addition, TMAO and its precursors were associated with pregnancy-related diseases such as gestational diabetes and preeclampsia in recent studies. [13][14][15] Although there are studies in the literature showing the relationship of TMAO with cardiovascular and metabolic diseases, the related mechanisms have not been fully elucidated. TMAO has been associated with endothelial dysfunction and inflammation in in vitro cell culture studies and in experimental animal studies.…”

“…In a meta‐analysis study ( n = 11 750) examining the relationship between CVDs and TMAO, an increase in TMAO concentration was associated with an increase in serious cardiovascular events 12 . In addition, TMAO and its precursors were associated with pregnancy‐related diseases such as gestational diabetes and preeclampsia in recent studies 13–15 …”