scholarly journals Vaginal Microbiota and Cytokine Levels Predict Preterm Delivery in Asian Women

Author(s):  
Manoj Kumar ◽  
Selvasankar Murugesan ◽  
Parul Singh ◽  
Marwa Saadaoui ◽  
Duaa Ahmed Elhag ◽  
...  

Preterm birth (PTB) is the most common cause of neonatal morbidity and mortality worldwide. Approximately half of PTBs is linked with microbial etiologies, including pathologic changes to the vaginal microbiota, which vary according to ethnicity. Globally more than 50% of PTBs occur in Asia, but studies of the vaginal microbiome and its association with pregnancy outcomes in Asian women are lacking. This study aimed to longitudinally analyzed the vaginal microbiome and cytokine environment of 18 Karen and Burman pregnant women who delivered preterm and 36 matched controls delivering at full term. Using 16S ribosomal RNA gene sequencing we identified a predictive vaginal microbiota signature for PTB that was detectable as early as the first trimester of pregnancy, characterized by higher levels of Prevotella buccalis, and lower levels of Lactobacillus crispatus and Finegoldia, accompanied by decreased levels of cytokines including IFNγ, IL-4, and TNFα. Differences in the vaginal microbial diversity and local vaginal immune environment were associated with greater risk of preterm birth. Our findings highlight new opportunities to predict PTB in Asian women in low-resource settings who are at highest risk of adverse outcomes from unexpected PTB, as well as in Burman/Karen ethnic minority groups in high-resource regions.

2020 ◽  
Author(s):  
Manoj Kumar ◽  
Selvasankar Murugesan ◽  
Parul Singh ◽  
Marwa Saadaoui ◽  
Duaa Ahmed Elhag ◽  
...  

Abstract Background: Preterm birth (PTB) is the most common cause of neonatal morbidity and mortality worldwide. Approximately half of PTBs are linked with microbial etiologies, including pathologic changes to the vaginal microbiota, which vary according to ethnicity. Globally more than 50% of PTBs occur in Asia, but studies of the vaginal microbiome and its association with pregnancy outcomes in Asian women are lacking. This study aimed to characterize the vaginal microbiome and cytokine environment of 18 Karen and Burman pregnant women who delivered preterm and 36 matched controls delivering at full term. Results: Using 16S ribosomal RNA gene sequencing we identified a predictive vaginal microbiota signature for PTB that was detectable as early as the first trimester of pregnancy, characterized by higher levels of Prevotella buccalis , and lower levels of Lactobacillus crispatus and Finegoldia , accompanied by decreased levels of cytokines including IFNγ, IL-4 and TNFα. Conclusion: Our findings highlight new opportunities to predict PTB in Asian women in low-resource settings who are at highest risk of adverse outcomes from unexpected PTB, as well as in Burman/Karen ethnic minority groups in high-resource regions.


2017 ◽  
Vol 114 (37) ◽  
pp. 9966-9971 ◽  
Author(s):  
Benjamin J. Callahan ◽  
Daniel B. DiGiulio ◽  
Daniela S. Aliaga Goltsman ◽  
Christine L. Sun ◽  
Elizabeth K. Costello ◽  
...  

Preterm birth (PTB) is the leading cause of neonatal morbidity and mortality. Previous studies have suggested that the maternal vaginal microbiota contributes to the pathophysiology of PTB, but conflicting results in recent years have raised doubts. We conducted a study of PTB compared with term birth in two cohorts of pregnant women: one predominantly Caucasian (n = 39) at low risk for PTB, the second predominantly African American and at high-risk (n = 96). We profiled the taxonomic composition of 2,179 vaginal swabs collected prospectively and weekly during gestation using 16S rRNA gene sequencing. Previously proposed associations between PTB and lower Lactobacillus and higher Gardnerella abundances replicated in the low-risk cohort, but not in the high-risk cohort. High-resolution bioinformatics enabled taxonomic assignment to the species and subspecies levels, revealing that Lactobacillus crispatus was associated with low risk of PTB in both cohorts, while Lactobacillus iners was not, and that a subspecies clade of Gardnerella vaginalis explained the genus association with PTB. Patterns of cooccurrence between L. crispatus and Gardnerella were highly exclusive, while Gardnerella and L. iners often coexisted at high frequencies. We argue that the vaginal microbiota is better represented by the quantitative frequencies of these key taxa than by classifying communities into five community state types. Our findings extend and corroborate the association between the vaginal microbiota and PTB, demonstrate the benefits of high-resolution statistical bioinformatics in clinical microbiome studies, and suggest that previous conflicting results may reflect the different risk profile of women of black race.


Author(s):  
Kristin C. Darwin ◽  
Jerome J. Federspiel ◽  
Brittany L. Schuh ◽  
Ahmet A. Baschat ◽  
Arthur J. Vaught

Objective The aim of the study is to compare maternal and neonatal outcomes among patients who are normotensive, hypertensive by Stage I American College of Cardiology-American Heart Association (ACC-AHA) criteria, and hypertensive by American College of Obstetricians and Gynecologists (ACOG) criteria. Study Design Secondary analysis of a prospective first trimester cohort study between 2007 and 2010 at three institutions in Baltimore, MD, was conducted. Blood pressure at 11 to 14 weeks' gestation was classified as (1) normotensive (systolic blood pressure [SBP] <130 mm Hg and diastolic blood pressure [DBP] <80 mm Hg); (2) hypertensive by Stage I ACC-AHA criteria (SBP 130–139 mm Hg or DBP 80–89 mm Hg); or (3) hypertensive by ACOG criteria (SBP ≥140 mm Hg or DBP ≥90 mm Hg). Primary outcomes included preeclampsia, small for gestational age (SGA) neonate, and preterm birth. Results Among 3,422 women enrolled, 2,976 with delivery data from singleton pregnancies of nonanomalous fetuses were included. In total, 20.2% met hypertension criteria (Stage I ACC-AHA n = 254, 8.5%; ACOG n = 347, 11.7%). The Stage I ACC-AHA group's risk for developing preeclampsia was threefold higher than the normotensive group (adjusted relative risk [aRR] 3.70, 95% confidence interval [CI] 2.40–5.70). The Stage I ACC-AHA group had lower preeclampsia risk than the ACOG group but the difference was not significant (aRR 0.87, 95% CI 0.55–1.37). The Stage I ACC-AHA group was more likely than the normotensive group to deliver preterm (aRR 1.44, 95% CI 1.02–2.01) and deliver an SGA neonate (aRR 1.51, 95% CI 1.07–2.12). The Stage I ACC-AHA group was less likely to deliver preterm compared with the ACOG group (aRR 0.65, 95% CI 0.45–0.93), but differences in SGA were not significant (aRR 1.31, 95% CI 0.84–2.03). Conclusion Pregnant patients with Stage I ACC-AHA hypertension in the first trimester had higher rates of preeclampsia, preterm birth, and SGA neonates compared with normotensive women. Adverse maternal and neonatal outcomes were numerically lower in the Stage I ACC-AHA group compared with the ACOG group, but these comparisons only reached statistical significance for preterm birth. Optimal pregnancy management for first trimester Stage I ACC-AHA hypertension requires active study. Key Points


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Soegaard ◽  
F Skjoth ◽  
P B Nielsen ◽  
J Beyer-Westendorf ◽  
T B Larsen

Abstract Background Anticoagulation is essential to prevent recurrent venous thromboembolism (VTE) during pregnancy in women with a history of preconception VTE. However, information on the safety of anticoagulant drugs in this setting is limited. Purpose To investigate the risk of maternal and foetal adverse outcomes associated with anticoagulant exposure during pregnancy. Methods Nationwide cohort of all pregnant women in Denmark with preconception VTE, 2000–2017. We linked individual-level data from nationwide registries on anticoagulant exposure, maternal and foetal outcomes. Results Among 5,099 pregnancies in 3,246 women with preconception VTE (mean age 31 years, 41% nulliparous), 36.4% were exposed to anticoagulants during first trimester (66.4% low-molecular-weight heparin (LMWH), 31.9% VKA, and 1.8% NOAC (Table). No maternal deaths occurred. Maternal outcomes were comparable among LMWH and unexposed women, whereas recurrent VTE and foetal loss was more prevalent in VKA and NOAC exposed women. Foetal risk was lowest in unexposed and LMWH exposed, whereas preterm birth was prevalent in VKA and NOAC exposed. Table 1. Maternal and foetal outcomes in pregnant women with preconception VTE according to first trimester anticoagulant exposure Maternal outcomes No anticoagulants LMWH VKA NOAC Total pregnancies/singleton foetuses, N 3,244/2,722 1231/1,124 591/442 33 /26 Recurrent VTE, % (N) 2.7 (89) 3.3 (41) 6.4 (38) – (<5) Antenatal bleeding, % (N) 2.3 (73) 2.7 (33) 1.5 (9) 0 Preeclampsia, % (N) 3.0 (98) 2.1 (26) 4.4 (26) – (<5) Foetal loss, % (N) 13.4 (436) 6.6 (81) 22.2 (131) 21.2 (7) Foetal outcomes in live singleton births, except stillbirth   Stillbirth, % (N) 0.6 (17) 0.6 (7) – (<5) 0   Mean gestational age, days/birthweight, gram 246/3,458 246/3,471 238/3,212 243/3,138   Preterm birth (<37 weeks), % (N) 41.1 (1,111) 38.3 (428) 63.2 (277) 57.7 (15)   Very preterm birth (<28 weeks), % (N) 0.9 (24) 1.3 (14) 2.7 (12) 0   Small for gestational age, % (N) 4.2 (109) 4.5 (49) 4.8 (20) – (<5)   Mean 5-minute Apgar score, (sd) 9.8 (0.8) 9.8 (0.7) 9.8 (1.0) 9.7 (1.0)   Congenital defects 8.4 (226) 9.0 (100) 10.0 (44) – (<5) Counts are supressed in cells with <5 observations to prevent disclosure of potentially identifiable information. Conclusion Our findings are reassuring and in support of the recommendation of LMWH for pregnant women with prior VTE. Few women were exposed to NOAC during pregnancy, and the safety of NOACs cannot be substantiated with the current level of evidence. Acknowledgement/Funding The Obel Family Foundation partly funded this research by an unrestricted grant.


2020 ◽  
Vol 42 (4) ◽  
pp. 487-499 ◽  
Author(s):  
Erna Bayar ◽  
Phillip R. Bennett ◽  
Denise Chan ◽  
Lynne Sykes ◽  
David A. MacIntyre

Abstract Preterm birth is a global health concern and continues to contribute to substantial neonatal morbidity and mortality despite advances in obstetric and neonatal care. The underlying aetiology is multi-factorial and remains incompletely understood. In this review, the complex interplay between the vaginal microbiome in pregnancy and its association with preterm birth is discussed in depth. Advances in the study of bacteriology and an improved understanding of the human microbiome have seen an improved awareness of the vaginal microbiota in both health and in disease.


2021 ◽  
Vol 10 (21) ◽  
pp. 5088
Author(s):  
Julja Burchard ◽  
Ashoka D. Polpitiya ◽  
Angela C. Fox ◽  
Todd L. Randolph ◽  
Tracey C. Fleischer ◽  
...  

Preterm births are the leading cause of neonatal death in the United States. Previously, a spontaneous preterm birth (sPTB) predictor based on the ratio of two proteins, IBP4/SHBG, was validated as a predictor of sPTB in the Proteomic Assessment of Preterm Risk (PAPR) study. In particular, a proteomic biomarker threshold of −1.37, corresponding to a ~two-fold increase or ~15% risk of sPTB, significantly stratified earlier deliveries. Guidelines for molecular tests advise replication in a second independent study. Here we tested whether the significant association between proteomic biomarker scores above the threshold and sPTB, and associated adverse outcomes, was replicated in a second independent study, the Multicenter Assessment of a Spontaneous Preterm Birth Risk Predictor (TREETOP). The threshold significantly stratified subjects in PAPR and TREETOP for sPTB (p = 0.041, p = 0.041, respectively). Application of the threshold in a Kaplan–Meier analysis demonstrated significant stratification in each study, respectively, for gestational age at birth (p < 001, p = 0.0016) and rate of hospital discharge for both neonate (p < 0.001, p = 0.005) and mother (p < 0.001, p < 0.001). Above the threshold, severe neonatal morbidity/mortality and mortality alone were 2.2 (p = 0.0083,) and 7.4-fold higher (p = 0.018), respectively, in both studies combined. Thus, higher predictor scores were associated with multiple adverse pregnancy outcomes.


Life ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1229
Author(s):  
Mahima Sharma ◽  
Chitrakshi Chopra ◽  
Malvika Mehta ◽  
Varun Sharma ◽  
Sharada Mallubhotla ◽  
...  

Background: There is a unique microbial community in the female lower genital tract known as the vaginal microbiota, which varies in composition and density and provides significant benefits during pregnancy, reproductive cyclicity, healthy newborn delivery, protection from preterm birth, infections such as UTIs, bacterial vaginosis, and so on, and improves the efficacy of treatments for vaginal cancers. Methods: It is necessary to know how the vaginal microbiome is composed in order to make an accurate diagnosis of the diseases listed above. A microbiome’s members are difficult to classify, and the way microbial communities function and influence host–pathogen interactions are difficult to understand. More and more metagenomic studies are able to unravel such complexities due to advances in high-throughput sequencing and bioinformatics. When it comes to vaginal microbiota research, we’ll be looking at the use of modern techniques and strategies that can be used to investigate variations in vaginal microbiota in order to detect diseases earlier, better treat vaginal disorders, and boost women’s health. Discussion: The discussed techniques and strategies may improve the treatment of vaginal disorders and may be beneficial for women’s overall health.


2021 ◽  
Author(s):  
William F Kindschuh ◽  
Federico Baldini ◽  
Martin C Liu ◽  
Kristen D Gerson ◽  
Jingqui Liao ◽  
...  

Spontaneous preterm birth (sPTB) is a leading cause of maternal and neonatal morbidity and mortality, yet both its prevention and early risk stratification are limited. The vaginal microbiome has been associated with PTB risk, possibly via metabolic or other interactions with its host. Here, we performed untargeted metabolomics on 232 vaginal samples, in which we have previously profiled the microbiota using 16S rRNA gene sequencing. Samples were collected at 20-24 weeks of gestation from women with singleton pregnancies, of which 80 delivered spontaneously before 37 weeks of gestation. We find that the vaginal metabolome correlates with the microbiome and separates into six clusters, three of which are associated with spontaneous preterm birth (sPTB) in Black women. Furthermore, while we identify five metabolites that associate with sPTB, another five associate with sPTB only when stratifying by race. We identify multiple microbial correlations with metabolites associated with sPTB, including intriguing correlations between vaginal bacteria that are considered sub-optimal and metabolites that were enriched in women who delivered at term. We propose that several sPTB-associated metabolites may be exogenous, and investigate another using metabolic models. Notably, we use machine learning models to predict sPTB risk using metabolite levels, weeks to months in advance, with high accuracy. We show that these predictions are more accurate than microbiome-based and maternal covariates-based models. Altogether, our results demonstrate the potential of vaginal metabolites as early biomarkers of sPTB and highlight exogenous exposures as potential risk factors for prematurity.


Author(s):  
Monika Kushwaha ◽  
Sanjeev Narang

Background: This study is cross-sectional, observational and comparative study, at Index Medical College, Hospital & Research Centre, Indore, Madhya Pradesh from July 2017 to July 2019 with sample size 100 placentae. Method: The placenta received was evaluated blinded of maternal pregnancy outcome. The pattern of morphology was evaluated both qualitatively (type of lesion) and quantitatively (number of lesions). Result: In Present study 79% of the deliveries were term deliveries and 21% were preterm deliveries. On placental macroscopy, placenta weight was significantly low among the neonates of preterm deliveries (370.00±60.49) as compared to term deliveries (440.89±55.22). Preterm placenta had higher number of abnormal placental lesion compared to term pregnancies. Conclusion: The uteroplacental insufficiency defined as placental infarct, fibrosis of chorionic villi, thickening of blood vessels, and poor vascularity of chorionic villi. Placental histopathological lesions are strongly associated with maternal under perfusion and uteroplacental insufficiency. These are the reasons for preterm birth. Thus, knowledge of the etiological factor can be use to reduce maternal and neonatal morbidity and mortility. Keywords: Placenta, Term & Preterm.


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