Abstract
BackgroundPreeclampsia and preterm delivery (PTD) are believed to affect women’s long-term health including cardiovascular disease (CVD), but the biological underpinnings are largely unknown. We aimed to test whether maternal postpartum metabolomic profiles, especially CVD-related metabolites, varied according to PTD subtypes with and without preeclampsia, in a US urban, low-income multi-ethnic population.MethodsThis study, from the Boston Birth Cohort, included 980 women with term delivery, 79 with medically indicated PTD (mPTD) and preeclampsia, 52 with mPTD only, and 219 with spontaneous PTD (sPTD). Metabolomic profiling in postpartum plasma was conducted by liquid chromatography-mass spectrometry. Linear regression models were used to assess the associations of each metabolite with mPTD with preeclampsia, mPTD only, and sPTD, respectively, adjusting for pertinent covariates. Weighted gene coexpression network analysis was applied to investigate interconnected metabolites associated with the PTD/preeclampsia subgroups. Bonferroni correction was applied to account for multiple testing.ResultsA total of 380 known metabolites were analyzed. Compared to term controls, women with mPTD and preeclampsia showed a significant increase in 36 metabolites, mainly representing acylcarnitines and multiple classes of lipids (diacylglycerols, triacylglycerols, phosphocholines, and lysophosphocholines), as well as a decrease in 11 metabolites including nucleotides, steroids, and cholesteryl esters (CEs) (P < 1.3 × 10−4). Alterations of diacylglycerols, triacylglycerols, and CEs in women with mPTD and preeclampsia remained significant when compared to women with mPTD only. In contrast, the metabolite differences between women with mPTD only and term controls were only seen in phosphatidylethanolamine class. Women with sPTD had significantly different levels of 16 metabolites mainly in amino acid, nucleotide, and steroid classes compared to term controls, of which, anthranilic acid, bilirubin, and steroids also had shared associations in women with mPTD and preeclampsia.ConclusionIn this sample of US high-risk women, PTD/preeclampsia subgroups each showed some unique and shared associations with maternal postpartum plasma metabolites, including those known to be predictors of future CVD. These findings, if validated, may provide new insight into metabolomic alterations underlying clinically observed PTD/preeclampsia subgroups and implications for women’s future cardiometabolic health.
Highlights
Preeclampsia and preterm delivery (PTD) are believed to affect women’s long-term health including cardiovascular disease (CVD), but the biological underpinnings are largely unknown
We aimed to identify both shared and divergent metabolomic patterns for different PTD subtypes with and without preeclampsia, and further to test whether such PTD/preeclampsia-associated metabolomic patterns may vary by maternal characteristics such as ethnicity and parity
Metabolomic differences were modest in women with medically indicated PTD (mPTD) only, who had lower levels of 4 PEs (C32:1, C34:2, C36:2, and C36:4) than term controls
Summary
Preeclampsia and preterm delivery (PTD) are believed to affect women’s long-term health including cardiovascular disease (CVD), but the biological underpinnings are largely unknown. Pregnancy complications and PTD are associated with risk of having the same conditions in subsequent pregnancies, and lead to an increased long-term risk of adverse health outcomes, including cardiovascular diseases (CVDs) [1,2,3,4], the leading causes of death for women in the USA [5]. PTD is heterogeneous, with a variety of different PTD subtypes (i.e., spontaneous vs medically indicated PTD), with and without preeclampsia, which may affect CVD risk through different pathways.
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