Project description:Pregnancy loss is often caused by chromosomal abnormalities of the conceptus. The prevalence of these abnormalities and the allocation of (ab)normal cells in embryonic and placental lineages during intrauterine development remain elusive. We analyzed 1,745 spontaneous pregnancy losses and found that roughly half (50.4%) of the products of conception (POC) were karyotypically abnormal, with maternal and paternal age independently contributing to the increased genomic aberration rate in pregnancy loss. We applied genome haplarithmisis to a subset of 94 pregnancy losses with normal parental and POC karyotypes. Genotyping of parental DNA as well as POC extraembryonic mesoderm and chorionic villi DNA, representing embryonic and trophoblastic tissues, enabled characterization of the genomic landscape of both lineages. Of these pregnancy losses, 35.1% had chromosomal aberrations not previously detected by karyotyping, increasing the rate of aberrations of pregnancy losses to 67.8% by extrapolation. In contrast to viable pregnancies where mosaic chromosomal abnormalities are often restricted to chorionic villi, such as confined placental mosaicism, we found a higher degree of mosaic chromosomal imbalances in extraembryonic mesoderm rather than chorionic villi in pregnancy losses. Our results stress the importance of scrutinizing the full allelic architecture of genomic abnormalities in pregnancy loss to improve clinical management and basic research of this devastating condition.
Project description:Extensive genome analysis of pregnancy loss products by genome haplarithmisis. Pregnancy loss (PL) is the primary pregnancy complication, mostly caused by chromosomal abnormalities of the conceptus. However, the nature and prevalence of these abnormalities and the allocation of (ab)normal cells in embryonic and placental compartments during intrauterine development remains elusive. We analyzed 1,745 spontaneous PLs and found that ~50% were karyotypically normal. We applied genome haplarithmisis to 91 PL families with normal karyotypes, following whole-genome genotypes of the parents as well as of the extraembryonic mesoderm (EM) and chorionic villi (CV), representing embryonic and placental cells, of the product of conception (POC), which allowed characterizing genomic landscape of both lineages. 36.4% of these PLs have chromosomal aberrations not previously detected by karyotyping. In contrast to viable pregnancies where mosaic chromosomal abnormalities are often restricted to the CV, we find that in spontaneous abortions, the situation is reversed with a higher degree of mosaic chromosomal imbalances in EM rather than CV.
Project description:Extensive genome analysis of pregnancy loss products by genome haplarithmisis. Pregnancy loss (PL) is the primary pregnancy complication, mostly caused by chromosomal abnormalities of the conceptus. However, the nature and prevalence of these abnormalities and the allocation of (ab)normal cells in embryonic and placental compartments during intrauterine development remains elusive. We analyzed 1,745 spontaneous PLs and found that ~50% were karyotypically normal. We applied genome haplarithmisis to 91 PL families with normal karyotypes, following whole-genome genotypes of the parents as well as of the extraembryonic mesoderm (EM) and chorionic villi (CV), representing embryonic and placental cells, of the product of conception (POC), which allowed characterizing genomic landscape of both lineages. 36.4% of these PLs have chromosomal aberrations not previously detected by karyotyping. In contrast to viable pregnancies where mosaic chromosomal abnormalities are often restricted to the CV, we find that in spontaneous abortions, the situation is reversed with a higher degree of mosaic chromosomal imbalances in EM rather than CV.
Project description:Adverse obstetric outcomes, such as preeclampsia, preterm birth, gestational diabetes, and fetal growth restriction, are poorly predicted by maternal history and risk factors alone, especially in nulliparae. The ability to predict these outcomes from the first trimester would allow for the early initiation of prophylactic therapies, institution of an appropriate model and location of care, and recruitment of a truly "high risk" population to clinical trials of interventions to prevent or ameliorate these conditions. To this end, development of adequately sensitive and specific predictive tests for these outcomes has become a significant focus of perinatal research. This paper reviews the biomarkers involved in these multiparametric tests and also outlines the performance of these tests and issues regarding their introduction into clinical practice.
Project description:Capturing a paradoxical embolism in real-time has been a challenge in recent literature. We present the unique case of a 33-year-old, G3P2 female at 8 weeks gestation presenting with dyspnea. An active thrombus through an undiagnosed patent foramen ovale was found requiring emergent surgical intervention with a positive outcome. The presence of a deep vein thrombosis, inferior vena caval thrombus, patent foramen ovale, and pulmonary artery thrombi was contemporarily documented. To our knowledge, there is minimal literature with this presentation.
Project description:BackgroundPregnancy loss prediction based on routinely measured ultrasound characteristics is generally aimed toward distinguishing nonviability. Physicians also use ultrasound indicators for patient counseling, and in some cases to decide upon the frequency of follow-up sonograms. To improve clinical utility, allocation of cut-points should be based on clinical data for multiple sonographic characteristics, be specific to gestational week, and be determined by methods that optimize prediction.ObjectivesTo identify routinely measured features of the early first trimester ultrasound and the gestational age-specific cut-points that are most predictive of pregnancy loss.Materials and methodsThis was a secondary analysis of 617 pregnant women enrolled in the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial; all women had 1-2 previous pregnancy losses and no documented infertility. Each participant had a single ultrasound with a detectable fetal heartbeat between 6 weeks 0 days and 8 weeks 6 days. Cut-points for low fetal heart rate and small crown-rump length were separately defined for gestational weeks 6, 7, and 8 to optimize prediction. Identity and log-binomial regression models were used to estimate absolute and relative risks, respectively, and 95% confidence intervals between jointly categorized low fetal heart rate, small crown-rump length, and clinical pregnancy loss. Adjusted models accounted for gestational age at ultrasound in weeks. Missing data were addressed using multiple imputation.ResultsA total of 64 women experienced a clinical pregnancy loss following the first ultrasound (10.4%), 7 were lost to follow-up (1.1%), and 546 women (88.5%) had a live birth. Low fetal heart rate and small crown-rump length (≤122, 123, and 158 bpm; ≤6.0, 8.5, and 10.9 mm for gestational weeks 6, 7, and 8, respectively) were independent predictors of clinical pregnancy loss, with greatest risks observed for pregnancies having both characteristics (relative risk, 2.08; 95% confidence interval, 1.24-2.91). The combination of low fetal heart rate and small crown-rump length was linked to a 16% (95% confidence interval, 9.1-23%) adjusted absolute increase in risk of subsequent loss, from 5.0% (95% confidence interval, 1.5-8.5%) to 21% (95% confidence interval, 15-27%). Abnormal yolk sac diameter or the presence of a subchorionic hemmhorage did not improve prediction of clinical pregnancy loss.ConclusionIdentified cut-points can be used by physicians for patient counseling, and in some cases to decide upon the frequency of follow-up sonograms. The specified criteria should not be used to diagnose nonviability.
Project description:Our objective was to prospectively validate the use of gestational sac (GS), yolk sac (YS) diameter, crown-rump length (CRL), and embryonal heart rate (HR) dimensions to identify early pregnancy loss. This was a prospective cohort study of first trimester pregnancies. GS and YS diameter, CRL, and HR measurements were serially obtained in singleton and twin pregnancies from 6 through 10 weeks' gestation. Non-parametric tests and logistic regression models were used for comparisons of distributions and testing of associations. A total of 252 patients were included, of which 199 were singleton pregnancies, 51 were twins, and 2 were triplets (304 total fetuses). Fifty-two patients had 61 losses. We built nomograms with the changes of the parameters evaluated in ongoing, as well as in pregnancy loss. In the pregnancies which failed, all the parameters showed significant changes, with different temporal onsets: GS and YS were the first to become abnormal, deviating from normality as early as 6 weeks' gestation (OR 0.01, 95% CI 0.0-0.09, and OR 3.36, 95% CI 1.53-7.34, respectively), followed by changes in HR, and CRL, which became evident at 7 and 8 weeks (OR 0.96, 95% CI 0.92-1.0, and OR 0.59, 95% CI 0.48-0.73, respectively). Our observations showed that, after 5 complete weeks' gestation, a small GS and a large YS reliably predicted pregnancy loss. The YS reliably identified the occurrence of a miscarriage at least 7 days prior its occurrence. CRL and HR became abnormal at a later time in pregnancy and closer to the event. These findings have important implications for patient counseling and care planning, as well as a potential bearing on cost effectiveness within early pregnancy care.
Project description:During pregnancy, the vaginal microbiome plays an important role in both maternal and neonatal health outcomes. Throughout pregnancy, the vaginal microbial composition undergoes significant changes, including a decrease in overall diversity and enrichment with Lactobacillus spp. In turn, the modifications in the microbial profiles are associated with shifts in the composition of vaginal metabolites. In this study, we characterized the vaginal metabolic profiles throughout pregnancy at two different gestational ages, correlating them with a microscopic evaluation of the vaginal bacterial composition. A total of 67 Caucasian pregnant women presenting to the Family Advisory Health Centres of Ravenna (Italy) were enrolled and a vaginal swab was collected at gestational ages 9-13 weeks (first trimester) and 20-24 weeks (second trimester). The composition of the vaginal microbiome was assessed by Nugent score and women were divided in 'H' (normal lactobacilli-dominated microbiota), 'I' (intermediate microbiota), and 'BV' (bacterial vaginosis) groups. Starting from the cell-free supernatants of the vaginal swabs, a metabolomic analysis was performed by means of a 1H-NMR spectroscopy. From the first to the second trimester, a greater number of women showed a normal lactobacilli-dominated microbiota, with a reduction of cases of dysbiosis. These microbial shifts were associated with profound changes in the vaginal metabolic profiles. Over the weeks, a significant reduction in the levels of BV-associated metabolites (e.g. acetate, propionate, tyramine, methylamine, putrescine) was observed. At the same time, the vaginal metabolome was characterized by higher concentrations of lactate and of several amino acids (e.g. tryptophan, threonine, isoleucine, leucine), typically found in healthy vaginal conditions. Over time, the vaginal metabolome became less diverse and more homogeneous: in the second trimester, women with BV showed metabolic profiles more similar to the healthy/intermediate groups, compared to the first trimester. Our data could help unravel the role of vaginal metabolites in the pathophysiology of pregnancy.