Urinary metabolic variation analysis during pregnancy and application in Gestational Diabetes Mellitus and spontaneous abortion biomarker discovery

Abstract

Pregnancy is associated with the onset of many adaptation processes that are likely to change over the course of gestation. Understanding normal metabolites’ variation with pregnancy progression is crucial for gaining insights of the key nutrients for normal fetal growth, and for comparative research of pregnancy-related complications. This work presents liquid chromatography-mass spectrum-based urine metabolomics study of 50 health pregnant women at three time points during pregnancy. The influence of maternal physiological factors, including age, BMI, parity and gravity to urine metabolome was explored. Additionally, urine metabolomics was applied for early prediction of two pregnancy complications, gestational diabetes mellitus and spontaneous abortion. Our results suggested that during normal pregnancy progression, pathways of steroid hormone biosynthesis and tyrosine metabolism were significantly regulated. BMI is a factor that should be considered during cross-section analysis. Application analysis discovered potential biomarkers for GDM in the first trimester with AUC of 0.89, and potential biomarkers for SA in the first trimester with AUC of 0.90. In conclusion, our study indicated that urine metabolome could reflect variations during pregnancy progression, and has potential value for pregnancy complications early prediction. The clinical trial number for this study is NCT03246295.

Longitudinal metabolic and gut bacterial profiling of pregnant women with previous bariatric surgery

“…Pregnancy has been shown to induce substantial time-dependent alterations in physiology and metabolism 53 54 under the constantly changing physiological demand as the mother responds to the needs of the growing fetus. Nevertheless, the systematic effect of BS on the metabolic profiles is superimposed on the changing metabolic landscape and can be clearly observed in the metabolic phenotypes.…”

The threshold effect of factors associated with spontaneous abortion in human-assisted reproductive technology

“…With increasing age, the number and quality of oocytes significantly reduces, the number of mitochondria reduces, there is a significant decrease in ATP content in the cytoplasm, and the proportion of abnormal embryo chromosome structure increases. Spontaneous abortion is closely related to embryo chromosomal abnormalities 18 , 19 , some studies have shown that chromosomal abnormalities are the most common cause of spontaneous abortion, and 45% to 70% of SABs are caused by chromosomal and genetic abnormalities 20 , 21 . Another study showed that pregnant women ≥ 35 years of age who had a spontaneous abortion in patients receiving ART was significantly higher than that of women < 35 years of age, and the proportion of autosomal triploid abnormalities was the highest 22 .…”

Machine learning approaches to predict gestational age in normal and complicated pregnancies via urinary metabolomics analysis

“…This is a challenging attempt to predict gestational age in normal and complicated pregnancies by means of urinary metabolomics. Although a few studies have analyzed urinary metabolites in pregnant women, fewer than 50 metabolites were analyzed in each of those studies 16 – 18 .…”

“…This cluster included pyrimidines (e.g., cytosine, thymine, and uracil) and hydrophilic basic amino acids (e.g., histidine and lysine). Only a few previous studies have described the roles of, or changes in, these metabolites during pregnancy 18 , 25 . Furthermore, enrichment analysis of metabolites selected by the predictive model revealed significant enrichment of metabolites related to vitamins in cluster 3.…”