410: A vital statistics study of birth weight centile and fetal death risk (original) (raw)
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Journal of Obstetrics and Gynaecology Research, 2021
Aim. To examine whether there are differences in the vaginal microbiome of women who miscarry compared to those who have normal pregnancy outcomes. Methods. Prospective observational study conducted at the Canberra Hospital, Australia with 24 participant women in the first trimester of pregnancy. The vaginal microbiomes of the 24 women were characterised using sequencing analysis of the V4 region of the16S rRNA gene employing an Illumina MiSeq instrument with QIAGEN reagents. Vaginal microbiome data were correlated with pregnancy clinical metadata. Results. Ordination plots showed differences in the composition of microbiomes of women who miscarried and controls. In nulliparous women, Lactobacillus crispatus was the dominant bacterium in 50% of women. Lactobacillus iners was the dominant bacterium in 50% of women with a history of prior miscarriage and a miscarriage in the study compared to 15% (p=0.011) in those with no history of miscarriage and no miscarriage in the study. There were significant differences in the number of OTU and the richness of the microbiomes of women who miscarried compared to those who delivered at term. Eight taxa were found in different relative abundances in both groups of women. Conclusions. The study indicated that the composition of the vaginal microbiome varies with pregnancy history. Also, there was a significant difference in the vaginal microbiomes between women who suffered miscarriage and those who continued to term delivery both in the overall microbiome populations and in the abundances of individual taxa.
Questioning the fetal microbiome illustrates pitfalls of low-biomass microbial studies
Nature, 2023
Whether the human fetus and the prenatal intrauterine environment (amniotic fluid, placenta) are stably colonized by microbes in a healthy pregnancy remains the subject of debate. Here, we evaluate recent studies that characterized microbial populations in human fetuses from the perspectives of reproductive biology, microbiology, bioinformatics, immunology, clinical microbiology, and gnotobiology, and assess possible mechanisms by which the fetus might interact with microbes. Our analysis indicates that the detected microbial signals are likely the result of contamination during the clinical procedures to obtain fetal samples, DNA extraction, and DNA sequencing. Further, the existence of live and replicating microbial populations in healthy fetal tissues is not compatible with fundamental concepts of immunology, clinical microbiology, and the derivation of germ-free mammals. These conclusions are important to our understanding of human immune development and also illustrate common pitfalls in the microbial analyses of many other low-biomass environments. The pursuit of a "fetal microbiome" serves as a cautionary example of the challenges of sequence-based microbiome studies when biomass is low or absent and emphasizes the need for a trans-disciplinary approach that goes beyond contamination controls, also incorporating biological, ecological, and mechanistic concepts.
Vaginal Microbiome in Pregnant Women with and without Short Cervix
Nutrients
Cervical shortening is a recognised risk factor for pre-term birth. The vaginal microbiome plays an essential role in pregnancy and in maternal and foetal outcomes. We studied the vaginal microbiome in 68 women with singleton gestation and a cervical length ≤25 mm and in 29 pregnant women with a cervix >25 mm in the second or early third trimester. Illumina protocol 16S Metagenomic Sequencing Library Preparation was used to detail amplified 16SrRNA gene. Statistical analyses were performed in R environment. Firmicutes was the phylum most represented in all pregnant women. The mean relative abundance of Proteobacteria and Actinobacteriota was higher in women with a short cervix. Bacterial abundance was higher in women with a normal length cervix compared to the group of women with a short cervix. Nonetheless, a significant enrichment in bacterial taxa poorly represented in vaginal microbiome was observed in the group of women with a short cervix. Staphylococcus and Pseudomonas, ta...
First-trimester vaginal microbiome diversity: A potential indicator of preterm delivery risk
Scientific Reports
Preterm birth is a leading cause of global neonate mortality. Hospitalization costs associated with preterm deliveries present a huge economic burden. Existing physical/biochemical markers for predicting preterm birth risk are mostly suited for application at mid/late pregnancy stages, thereby leaving very short time (between diagnosis and delivery) for adopting appropriate intervention strategies. Recent studies indicating correlations between pre/full-term delivery and the composition of vaginal microbiota in pregnant women have opened new diagnostic possibilities. In this study, we performed a thorough meta-analysis of vaginal microbiome datasets to evaluate the utility of popular diversity and inequality measures for predicting, at an early stage, the risk of preterm delivery. Results indicate significant differences (in diversity measures) between 'first-trimester' vaginal microbiomes obtained from women with term and preterm outcomes, indicating the potential diagnostic utility of these measures. In this context, we introduce a novel diversity metric that has significantly better diagnostic ability as compared to established diversity measures. The metric enables 'early' and highly accurate prediction of preterm delivery outcomes, and can potentially be deployed in clinical settings for preterm birth risk-assessment. Our findings have potentially far reaching implications in the fight against neonatal deaths due to preterm birth. Technological advances in medical diagnostics and therapeutics in the last decade have greatly reduced the burden of several life-threatening diseases affecting young children 1. The Millennium Development Goals (MDG) report released by UN in 2015 indicates significant reduction in the incidence rates of malaria, tuberculosis, measles, and AIDS in the last 15 years 2. However, amidst these encouraging signs of improvement, the report highlights that a majority of deaths in children (under 5) occur within the first 28 days of life (i.e. the neonatal period). Complications arising due to preterm births are indicated as the single largest contributor to neonatal deaths 3,4. Surprisingly, in comparison to the decrease in incidence rates of other diseases across the globe, the rate of preterm births has remained more or less constant, irrespective of a country's economic status. For instance, in 2014, the rate of preterm births in US stood at 9.6%, which is quite comparable to the rate (~12%) tracked in countries from the developing world (Brazil, India, and Nigeria) 5. Overall, these trends highlight the urgent need for greater international attention on developing improved methods for diagnosis, prevention, and management of preterm births. The entire cascade of patho-physiologic events that cause a preterm delivery (PTD) is not completely understood till date. Genetic predisposition, maternal risk factors (e.g., age, smoking, alcohol intake, reproductive history), urinary tract infections, intrauterine infections, etc., are typically associated with increased PTD risk. Given the variety of predisposing factors that contribute to an increased PTD risk 6,7 , there exist intervention approaches that can potentially promote a healthy full-term gestation outcome 8,9. However, the success of these intervention approaches is dependent on identification of high-risk subjects as early as possible during pregnancy 3. Given this context, diagnostic markers (physical and/or biochemical) that can accurately indicate, at an early stage of pregnancy, the possibility of progression towards a preterm delivery outcome assume a lot of significance 10,11. Figure 1 provides an overview of approaches (and few commercial in vitro diagnostic offerings) used for determining PTD risk. Given below is a summary of various methods depicted in Fig. 1. Briefly, general factors considered for 'risk scoring' include ethnicity, socioeconomic status, periodontal health, blood pressure, weight, diabetes, smoking, alcohol consumption, inter-pregnancy duration, etc. 10,12-14 .
American Journal of Obstetrics and Gynecology, 2013
Ͼ13 wks gestation, lethal fetal anomaly, contraindication to labour. Delivery planned between 375/7 to 386/7 weeks by CS or inducing labour. Primary composite outcome: perinatal/neonatal mortality and/or serious neonatal morbidity. 2800 patients required to detect reduction of primary outcome from 4% to 2%. power 80%, 2-sided, ␣ error of 0.05. A logistic model was used with generalized estimating equations to account for correlation between babies from the same pregnancy. RESULTS: 2804 women randomized from 26 countries. 1398 to planned CS vs.1406 to planned VB. There was no significant difference between treatment groups. Fifty seven babies of 2781(2.05%) experienced the primary outcome in planned CS vs.52 of 2782 (1.87%) in planned VB (OR1.098,CI 0.726-1.663,p ϭ 0.6569). There was no significant interaction between treatment group and parity, GA at randomization, mother's age, presentation of twin B, Chorionicity, and country's PNMR.Twin B more likely to experience the primary outcome (ORϭ1.895,CI:1.329-2.703, pϭ0.0003). The interaction between treatment group and birth order was not significant (OR;Aϭ1.239; OR;Bϭ1.030, pϭ0.6125). 89 9% of the women who planned CS delivered both babies by CS. 60.45% in planned VB delivered at least twin A vaginally. 4% of women in planned VB group delivered twin B by CS following VB of twin A. Women in the planned CS delivered earlier but had no increase in maternal mortality or morbidity compared to planned VB. CONCLUSION: Planned CS in twins at 32-38 week does not decrease (or increase) perinatal/neonatal death or serious neonatal morbidity vs planned VB when the first twin is cephalic.
Journal of Clinical Medicine, 2020
The vaginal microbiota plays a critical role in pregnancy. Bacteria from Lactobacillus spp. are thought to maintain immune homeostasis and modulate the inflammatory responses against pathogens implicated in cervical shortening, one of the risk factors for spontaneous preterm birth. We studied vaginal microbiota in 46 pregnant women of predominantly Caucasian ethnicity diagnosed with short cervix (<25 mm), and identified microbial communities associated with extreme cervical shortening (≤10 mm). Vaginal microbiota was defined by 16S rRNA gene sequencing and clustered into community state types (CSTs), based on dominance or depletion of Lactobacillus spp. No correlation between CSTs distribution and maternal age or gestational age was revealed. CST-IV, dominated by aerobic and anaerobic bacteria different than Lactobacilli, was associated with extreme cervical shortening (odds ratio (OR) = 15.0, 95% confidence interval (CI) = 1.56–14.21; p = 0.019). CST-III (L. iners-dominated) was...
MBio, 2019
In many impoverished regions of the world, it may not be possible to assess two major risk factors for preterm birth: a short cervical length and the depletion of vaginal lactobacilli. We determined whether measuring specific compounds in vaginal fluid might be a simple, noninvasive, and cost-effective way to predict the bacteria that dominate the vaginal microbiome and indicate the presence of a shortened cervix (Ͻ25 mm). Vaginal fluid samples were prospectively collected from midtrimester pregnant women, and the concentrations of D-and L-lactic acid, tissue inhibitor of matrix metalloproteinases TIMP-1 and TIMP-2, matrix metalloproteinases MMP-2 and MMP-8, the 70-kDa heat shock protein, a2 isoform of vacuolar ATPase, and sequestrome-1 were quantified by an enzyme-linked immunosorbent assay (ELISA). The compositions of vaginal microbiomes were assessed by analysis of the V1-V3 regions of 16S rRNA genes, while cervical length was determined by transvaginal ultrasonography. The vaginal microbiomes could be clustered into five community state types (CSTs), four of which were dominated by a single Lactobacillus species. The dominance of Lactobacillus crispatus or Lactobacillus jensenii in the vaginal microbiome predicted the level of D-lactic acid present. Several of the biomarkers, especially TIMP-1, in combination with the subject's age and race, were significantly associated with cervical length. Using piecewise structural equation modeling, we established a causal network that links CST to cervical length via biomarkers. We concluded that measuring levels of TIMP-1 and D-lactic acid in vaginal secretions might be a straightforward way to assess the risk for preterm birth due to a short cervix and microbiome composition. IMPORTANCE Premature birth and its complications are the largest contributors to infant death in the United States and globally. A short cervical length and the depletion of Lactobacillus species are known risk factors for preterm birth. However, in many resource-poor areas of the world, the technology to test for their occurrence is unavailable, and pregnant women with these risk factors are neither identified nor treated. In this study, we used path analysis to gain an unprecedented understanding of interactions between vaginal microbiome composition, the concentrations of
The Perinatal Microbiome and Pregnancy: Moving Beyond the Vaginal Microbiome
Cold Spring Harbor Perspectives in Medicine, 2015
The human microbiome, the collective genome of the microbial community that is on and within us, has recently been mapped. The initial characterization of healthy subjects has provided investigators with a reference population for interrogating the microbiome in metabolic, intestinal, and reproductive health and disease states. Although it is known that bacteria can colonize the vagina, recent metagenomic studies have shown that the vaginal microbiome varies among reproductive age women. Similarly, the richness and diversity of intestinal microbiota also naturally fluctuate among gravidae in both human and nonhuman primates, as well as mice. Moreover, recent evidence suggests that microbiome niches in pregnancy are not limited to maternal body sites, as the placenta appears to harbor a low biomass microbiome that is presumptively established in early pregnancy and varies in association with a remote history of maternal antenatal infection as well as preterm birth. In this article, we will provide a brief overview on metagenomics science as a means to investigate the microbiome, observations pertaining to both variation and the presumptive potential role of a varied microbiome during pregnancy, and how future studies of the microbiome in pregnancy may lend to a better understanding of human biology, reproductive health, and parturition. C ompleted in 2012, the Human Microbiome Project (HMP) characterized the microbiome composition of multiple body sites in healthy individuals of different ethnicities located in two separate cities (
From Short- to Long-Term Effects of C-Section Delivery on Microbiome Establishment and Host Health
Microorganisms, 2021
The establishment of gut microbiota has been proven to be impacted by several factors during pregnancy, delivery, and neonate periods. The body of evidence describing C-section delivery (CSD) as one of the most disruptive events during early life has expanded in recent years, concluding that CSD results in a drastic change in microbiota establishment patterns. When comparing the gut microbiota composition of CSD babies with vaginally delivered (VD) babies, the former show a microbiome that closely resembles that found in the environment and the mother’s skin, while VD babies show a microbiome more similar to the vaginal microbiome. Although these alterations of normal gut microbiota establishment tend to disappear during the first months of life, they still affect host health in the mid–long term since CSD has been correlated with a higher risk of early life infections and non-transmissible diseases, such as inflammatory diseases, allergies, and metabolic diseases. In recent years, ...