Maternal blood EBF1-based microRNA transcripts as biomarkers for detecting risk of spontaneous preterm birth: a nested case-control study

Author(s):  
Guoli Zhou ◽  
Claudia Holzman ◽  
Yujing J. Heng ◽  
Mark Kibschull ◽  
Stephen J. Lye
2019 ◽  
Author(s):  
Xing Chen ◽  
Ning Huang ◽  
Chaoqun Liu ◽  
Yue Chen ◽  
Lulu Huang ◽  
...  

Abstract Background: Gut microbiota has been proven to disease susceptibility and may lead to increased risk of preterm birth. To date, the link of gut microbial-related metabolite trimethylamine-N-oxide (TMAO), L-carnitine, and betaine, with spontaneous preterm birth (sPTB) has not been established. This study aimed to investigate the association of TMAO, L-carnitine and betaine, with sPTB risk. Methods: A nested case-control study was designed including 129 sPTB cases and 258 controls based on Guangxi Birth Cohort Study. TMAO, L-carnitine, and betaine level in maternal serum were determined by liquid chromatography with mass spectrometry. Conditional logistic regression analyses were used to examine the association between maternal serum metabolites and sPTB. Stratified analyses were further conducted according to BMI and preterm prelabor rupture of membranes. Spline analyses were performed to explore the dose-response relationship between the metabolites and sPTB.Results: Statistically significant association with decreased sPTB risk was observed for the highest L-carnitine (OR: 0.47; 95% CI: 0.23, 0.95). In risk analyses stratified by BMI, similar results were observed in normal weight gravida (BMI: 18.5~23.9 kg/cm2). The significant subtype-specific association with TMAO (OR: 0.43; 95% CI: 0.20, 0.93) and L-carnitine (OR: 0.45; 95% CI: 0.21, 0.97) were observed for preterm labor but not PPROM. Spline regression analysis indicated non-linear associations with TMAO and sPTB risk (P for nonlinearity: 0.057). Significant associations of TMAO with sPTB were observed in normal weight gravida (P = 0.028) and preterm labor subtype (P = 0.025). No statistically significant associations with sPTB risk were observed for betaine (P > 0.05).Conclusions: TMAO and L-carnitine levels in maternal serum are inversely linked with sPTB risk. Discovery of the association between gut-microbiota initiated TMAO metabolism and sPTB may open new avenues for diagnose and therapy.


2021 ◽  
Vol 9 ◽  
Author(s):  
Dongni Huang ◽  
Zheng Liu ◽  
Xiyao Liu ◽  
Yuxiang Bai ◽  
Mengshi Wu ◽  
...  

Spontaneous preterm birth (sPTB) is the leading cause of infant morbidity and mortality worldwide. Deficiency of effective predict methods is an urgent problem that needs to be solved. Numbers of researchers spare no efforts to investigate differential indicators. To evaluate the value of the differential indicators, a prospective nested case-control study was carried out. Among an overall cohort of 1,050 pregnancies, 20 sPTB pregnancies, and 20 full-term pregnancies were enrolled in this study. Participants were followed-up until labor. The psychological profile was evaluated utilizing the Zung Self-Rating Depression Scale at 11–14 weeks. Stress-related biomarker-cortisol and metabolites were detected by Electrochemiluminescence Immunoassay (ECLIA) and Gas Chromatography-Mass Spectrometry (GC-MS) in serum samples during pregnancy, respectively. The expression level of cortisol was up-regulated in serum and the score of the Zung Self-Rating Depression Scale was significantly higher in the sPTB group when compared to the control group. Note that, 29 metabolomics were differentially expressed between the sPTB group and the control group. The scores of the Zung Self-Rating Depression Scale, the level of cortisol, Eicosane, methyltetradecanoate, and stearic acid in serum were selected to establish the model with lasso logistic regression. Validation of the model yielded an optimum corrected AUC value of 89.5%, 95% CI: 0.8006–0.9889 with a sensitivity of 100.0%, and specificity of 78.9%. In conclusion, this study establishes a prediction model of sPTB with five variables, which may predict sPTB more accurately and sensitively in the second trimester.


Cytokine ◽  
2019 ◽  
Vol 117 ◽  
pp. 91-97 ◽  
Author(s):  
Lulu Huang ◽  
Qingzhi Hou ◽  
Yaling Huang ◽  
Juan Ye ◽  
Shengzhu Huang ◽  
...  

2021 ◽  
Author(s):  
Laura Goodfellow ◽  
Marijn C. Verwijs ◽  
Angharad Care ◽  
Andrew Sharp ◽  
Jelena Ivandic ◽  
...  

AbstractObjectiveTo assess the association between vaginal microbiome (VMB) composition and recurrent early spontaneous preterm birth (sPTB)/preterm prelabour rupture of membranes (PPROM).DesignNested case-control study.SettingUK tertiary referral hospital.SampleHigh-risk women with previous sPTB/PPROM <34+0 weeks gestation who had a recurrence (n=22) or delivered at ≥37+0 weeks without PPROM (n=87).MethodsVaginal swabs collected between 15-22 weeks gestation were analysed by 16S rRNA gene sequencing and 16S quantitative PCR.Main outcome measureRecurrent early sPTB/PPROM.Results28/109 high-risk women had anaerobic vaginal dysbiosis, with the remainder dominated by lactobacilli (L. iners 36/109, L. crispatus 23/109, or other 22/109). VMB type, diversity, and stability were not associated with recurrence. Women with a recurrence, compared to those without, had a higher median vaginal bacterial load (8.64 vs. 7.89 log10 cells/μl, adjusted odds ratio (aOR)=1.90, 95% confidence interval (CI)=1.01-3.56, p=0.047) and estimated Lactobacillus concentration (8.59 vs. 7.48 log10 cells/μl, aOR=2.35, CI=1.20-4.61, p=0.013). A higher recurrence risk was associated with higher median bacterial loads for each VMB type after stratification, although statistical significance was reached only for L. iners-domination (aOR=3.44, CI=1.06-11.15, p=0.040). Women with anaerobic dysbiosis or L. iners-domination had a higher median vaginal bacterial load than women with a VMB dominated by L. crispatus or other lactobacilli (8.54, 7.96, 7.63, and 7.53 log10 cells/μl, respectively).ConclusionsVaginal bacterial load is associated with early sPTB/PPROM recurrence. Domination by lactobacilli other than L. iners may protect women from developing high bacterial loads. Future PTB studies should quantify vaginal bacteria and yeasts.FundingWellbeing of Women, London, UKTweetable abstractIncreased vaginal bacterial load in the second trimester may be associated with recurrent early spontaneous preterm birth.


Author(s):  
Guoli Zhou ◽  
Thu V Duong ◽  
Eric P Kasten ◽  
Hanne M Hoffmann

Abstract Previous studies have observed an association between maternal circadian rhythm disruption and preterm birth (PTB). However, the underlying molecular mechanisms and the potential of circadian clock genes to serve as predictors of PTB remain unexplored. We examined the association of 10 core circadian transcripts in maternal blood with spontaneous PTB (sPTB) vs term births using a nested case–control study design. We used a public gene expression dataset (GSE59491), which was nested within the All Our Babies (AOB) study cohort in Canada. Maternal blood was sampled in trimesters 2–3 from women with sPTB (n = 51) and term births (n = 106), matched for 5 demographic variables. In 2nd trimester maternal blood, only CLOCK and CRY2 transcripts were significantly lower in sPTB vs term (p = 0.02 ~ 0.03, FDR &lt; 0.20). A change of PER3 mRNA from trimesters 2 to 3 was significantly associated with sPTB (decline in sPTB, p = 0.02, FDR &lt; 0.20). When CLOCK and CRY2 were modeled together in 2nd trimester blood, the odds ratio of being in the low level of both circadian gene transcripts was greater in sPTB vs term (OR = 4.86, 95%CI = (1.75,13.51), p &lt; 0.01). Using GSVA and Pearson correlation, we identified 98 common pathways that were negatively or positively correlated with CLOCK and CRY2 expression (all p &lt; 0.05, FDR &lt; 0.10). The top three identified pathways were amyotrophic lateral sclerosis, degradation of extracellular matrix, and inwardly rectifying potassium channels. These three processes have previously been shown to be involved in neuron death, parturition, and uterine excitability during pregnancy, respectively.


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