Association of Elevated Maternal Serum Total Bile Acids With Low Birth Weight and Intrauterine Fetal Growth Restriction

Song, Fuzhen; Chen, Yuanyuan; Chen, Lei; Li, Huan; Cheng, Xiajin; Wu, Wei

doi:10.1001/jamanetworkopen.2021.17409

Cited by 22 publications

(16 citation statements)

References 51 publications

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“…(3) BW was positively correlated with bile acid. (Song et al, 2021) also found the same results. Bile acids, an essential metabolic molecule for dietary lipids and the absorption and metabolism of lipid-soluble vitamins, can bind to receptors (FXR and TGR5) to stimulate GLP-1 and PYY secretion (Sonne et al, 2014;Xie et al, 2021), affecting energy intake and absorption.…”

Section: Discussionsupporting

confidence: 70%

Association of Differential Metabolites With Small Intestinal Microflora and Maternal Outcomes in Subclinical Hypothyroidism During Pregnancy

Cai

et al. 2022

Front. Cell. Infect. Microbiol.

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ObjectiveTo investigate the association of differential metabolites with small intestinal microflora and maternal outcomes in subclinical hypothyroidism (SCH) during pregnancy.MethodsThe plasma of pregnant women in the SCH group and control group was analyzed by liquid chromatography-mass spectrometry (LC-MS), obtaining differential metabolites. Then, methane and hydrogen breath tests were performed in both groups, and basic clinical data and maternal outcome information were collected. Finally, differential metabolites were analyzed for small intestinal bacterial overgrowth (SIBO) and pregnancy outcomes using Spearman correlation analysis.Results(1) Multivariate statistics: There were 564 different metabolites in positive ion mode and 226 different metabolites in negative ion mode. (2) The positive rate of the methane hydrogen breath test in the SCH group was higher than that in the control group (p<0.05). (3) KEGG pathway analysis revealed that differential metabolites were mainly involved in bile secretion, cholesterol metabolism, and other pathways. (4) Serum cholesterol (TC) and triglyceride (TG) levels and hypertensive disorder complicating pregnancy (HDCP) were higher in the SCH group (p<0.05), and newborn birth weight (BW) was lower than that in the control group (p<0.05). (5) SIBO was negatively correlated with glycocholic acid and BW, and positively correlated with TC. Glycocholic acid was negatively correlated with TG but positively correlated with BW. TG was positively correlated with HDCP.ConclusionDifferential metabolites in the SCH group during pregnancy were disordered with small intestinal bacteria, which may affect pregnancy outcomes, and bile acids and cholesterol may be potential biomarkers for studying their mechanism of action.

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Section: Discussionsupporting

confidence: 70%

Association of Differential Metabolites With Small Intestinal Microflora and Maternal Outcomes in Subclinical Hypothyroidism During Pregnancy

Cai

et al. 2022

Front. Cell. Infect. Microbiol.

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“…ICP is typically a mild disease for the mother, whereas may lead to serious effects on the fetus, by increasing risks of fetal distress, premature delivery, small for gestational age, and stillbirth (Ovadia et al, 2019; Wikstrom Shemer et al, 2013). Our previous study also showed that the risks of low birth weight and intrauterine growth restriction were higher in women with high TBA than women with low TBA (Song et al, 2021). Thus, there is thought to be more severe injury to the placental‐fetal side than to the maternal side.…”

Section: Discussionmentioning

confidence: 70%

Autophagic flux inhibition, apoptosis, and mitochondrial dysfunction in bile acids‐induced impairment of human placental trophoblast

Yang

Zhou

et al. 2022

Journal Cellular Physiology

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Intrahepatic cholestasis of pregnancy (ICP) is a common pregnancy‐specific disease, characterized by increased bile acid levels and adverse fetal outcomes. We previously reported excessive bile acids led to dysfunction of placental trophoblasts in ICP. However, the detailed mechanism is still unclear. Autophagy is fundamental process for protecting cell survival against adverse conditions. Here, we evaluated the effect of increased concentration of bile acids on autophagy in trophoblasts in vitro and in vivo. First, we demonstrated that the autophagy substrate p62/sequestosome‐1 was accumulated in placental tissues from patients with ICP and in human trophoblasts treated with hydrophobic bile acids, including chenodeoxycholic acid and deoxycholic acid. Furthermore, we found that treatment with hydrophobic bile acids impaired autophagic flux in both time‐ and concentration‐dependent manners, by suppressing the AMP‐activated protein kinase/unc‐51‐like kinase 1 autophagic signaling pathway. Notably, trophoblasts were prone to apoptotic cell death upon starvation along with bile‐acids treatment in vitro or in an ICP mouse model in vivo. Additionally, we revealed mitochondrial dysfunction was the predominant biological process in excessive bile acids induced trophoblast impairment under starvation by proteomic assay. Collectively, our study proposed a complex interaction of excessive bile acids induced autophagic flux, mitochondrial dysfunction, and cellular apoptosis in placental trophoblasts may play a critical role in the pathogenesis of ICP.

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“…Next, we tested the relationship between serum TBA and the severity of PE. Based on a previous report 24 , we categorized TBA levels into 4 groups. As shown in Table 2, higher serum TBA levels were associated with increased severity of PE.…”

Section: Resultsmentioning

confidence: 99%

“…A recent study in China reported increased TBA levels with a decrease in birth weight 39 . Song and coworkers also found that serum TBA levels in all ranges were associated with the risk of IUGR and that HDP had an additive effect on the association 24 . Consistent with these studies, our data show that the maternal TBA level was negatively associated with birth weight and positively associated with the risk of LBW and IUGR.…”

Section: Commentmentioning

confidence: 92%

The association of serum total bile acid with new-onset hypertension during pregnancy

Deng

Zhang

et al. 2022

Preprint

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Background: There has been considerable interest in the interrelationship between the liver and hypertension. The relationship between serum total bile acid (TBA) and hypertension has been reported. Moreover, intrahepatic cholestasis of pregnancy was correlated to gestation hypertension. However, the association between maternal serum TBA level in the normal range and new-onset hypertension disorders during pregnancy remains unclear. To evaluate the relationship between maternal serum TBA level in the normal range and the risk, disease severity and adverse pregnancy outcomes of new-onset hypertension during pregnancy.Method: Using the electronic medical records on all pregnant women from the Department of Obstetrics and Gynecology, Third Affiliated Hospital of Guangzhou Medical University, between 2014 and 2020, we conducted a retrospective cohort study of 2581 singleton pregnant women with maternal serum TBA levels in the normal range. Patients were grouped into the non-hypertension during pregnancy (1071), gestational hypertension (480) and preeclampsia (1030) groups. Result: We found that maternal serum TBA levels were significantly higher in the preeclampsia and gestational hypertension groups than in the non-hypertension group (p<0.01). Multiple logistic regression analysis showed that TBA level was independently and significantly associated with preeclampsia and gestational hypertension (odds ratio: 1.37, 95% confidence interval [CI]: 1.27-1.48, p=0.001, odds ratio: 1.34, 95% confidence interval [CI]: 1.24-1.46, p=0.005, respectively). Moreover, elevated TBA level was positively associated with the risk of severe PE and negatively with mild PE (p<0.01). In addition, maternal serum TBA levels were negatively related to birth weight (p < 0.001).Conclusions: These results suggest that maternal serum TBA in the normal range also might be a valuable biomarker for disease severity in preeclampsia and gestational hypertension. Additionally, our results also indicate associations of serum total bile acid levels in the normal range with an increased risk of intrauterine growth restriction and low birth weight among offspring. These results suggest that TBA could serve as a prognostic biomarker for new-onset hypertension during pregnancy.

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Association of Elevated Maternal Serum Total Bile Acids With Low Birth Weight and Intrauterine Fetal Growth Restriction

Cited by 22 publications

References 51 publications

Association of Differential Metabolites With Small Intestinal Microflora and Maternal Outcomes in Subclinical Hypothyroidism During Pregnancy

Association of Differential Metabolites With Small Intestinal Microflora and Maternal Outcomes in Subclinical Hypothyroidism During Pregnancy

Autophagic flux inhibition, apoptosis, and mitochondrial dysfunction in bile acids‐induced impairment of human placental trophoblast

The association of serum total bile acid with new-onset hypertension during pregnancy

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