The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study found strong associations between higher levels of maternal glucose at 24-32 weeks, within what is currently considered normoglycemia and adverse pregnancy outcomes. Our aim was to evaluate the associations between first-trimester fasting plasma glucose level and adverse pregnancy outcomes.

Chorionic villus sampling (CVS), routinely used for prenatal diagnosis of cytogenetic disorders, also possesses great potential for the study of placentation. To better understand villus biology, human placentation, and how these relate to pregnancy outcomes, we examined the morphology and transcriptomes of villi obtained via CVS from 10 to 14 weeks of pregnancy and correlated these with pregnancy attributes and clinical outcomes. First, we established a morphological scoring system based on three main villus features: branching, budding and vascularization. We then tested whether morphology scores were predictive of pregnancy attributes and clinical outcomes. Finally, we used RNA sequencing to assess the transcriptional basis of villus morphology and tested the hypothesis that gene expression may predict pregnancy outcomes. We demonstrate that villus morphology varies tremendously between patients, irrespective of gestational age, and that transcriptional differences are highly predictive of villus morphology. We show that pre-eclampsia markers are associated with villi with low morphology scores. Additionally, we identify SVEP1 as a possible biomarker for defining gestational age. Overall, chorionic villi in the first trimester remain one of the few means to correlate placental function with pregnancy outcome and these samples are a valuable and increasingly rare resource.

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. In this study, we analyzed 1,745 spontaneous pregnancy losses and found that roughly half (50.4%) of the products of conception (POCs) were karyotypically abnormal, with maternal and paternal age independently contributing to the increased genomic aberration rate. 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 extra-embryonic 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 extra-embryonic mesoderm rather than chorionic villi. 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.

No abstract available

Background. Bedside sonography performed by emergency physicians is frequently utilized for real-time clinical decision-making in the emergency department (ED) setting. This includes the sonographic evaluation of pain or bleeding in the first trimester of pregnancy. The detection of intrauterine pregnancy (IUP) or life-threatening conditions, including ectopic pregnancy, is critical. Objectives. This paper will review several important pearls and avoidable pitfalls of this diagnostic modality by brief presentation of illustrative cases followed by discussion of key principles. Case Reports. Three patients evaluated in the ED for bleeding or pain occurring during the first trimester of pregnancy will be presented. Conclusions. When conducting emergency bedside ultrasound for the evaluation of first trimester pregnancy, it is important to avoid common pitfalls that can place your patient at risk.

During pregnancy, maternal metabolism undergoes substantial changes to support the developing fetus. Such changes are finely regulated by different mechanisms carried out by effectors such as microRNAs (miRNAs). These small non-coding RNAs regulate numerous biological functions, mostly through post-transcriptional repression of gene expression. miRNAs are also secreted in circulation by numerous organs, such as the placenta. However, the complete plasmatic microtranscriptome of pregnant women has still not been fully described, although some miRNA clusters from the chromosome 14 (C14MC) and the chromosome 19 (C19MC and miR-371-3 cluster) have been proposed as being specific to pregnancy. Our aims were thus to describe the plasma microtranscriptome during the first trimester of pregnancy, by assessing the differences with non-pregnant women, and how it varies between the 4th and the 16th week of pregnancy.

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.

Most pregnancy complications originate with early placentation. MicroRNAs (miRNAs) may play an important role in placentation and function as biomarkers of future pregnancy complications. We summarized from the literature all first trimester circulating miRNAs associated with pregnancy complications of placental origin and further identified the miRNAs which have the most evidence as potential early biomarkers for pregnancy complications. We conducted a systematic review following PRISMA reporting guidelines (PROSPERO CRD42020183421). We identified all first trimester serum or plasma miRNAs associated with a pregnancy complication of placental origin (preeclampsia, intrauterine growth restriction (IUGR), gestational hypertension, preterm delivery) and the number of times those miRNAs were identified, as a measure of replication. Twenty-one studies examined 118 unique miRNAs, and 87 were associated with at least one pregnancy complication; preeclampsia was the most common. Seven miRNAs were significantly associated with a pregnancy complication in at least two studies: miR-125b, miR-518b, miR-628-3p, miR-365a-3p, miR-520h, miR-374a-5p, miR-191-5p. Few miRNAs were associated with more than one pregnancy complication: miR-518b and miR-520h with preeclampsia and gestational hypertension, miR-374a-5p and miR-191-5p with preterm birth and preeclampsia. Our systematic review suggests seven miRNAs as potential biomarkers of pregnancy complications. These complications are thought to originate with early placental defects and these miRNAs may also be biomarkers of placental pathology. First-trimester biomarkers of pregnancy complications can facilitate early detection and interventions.

In this study we researched for the first trimester pregnancy measurements by transabdominal and transvaginal ultrasound: gestational sac volume (GSV), embryo volume (EV), placenta volume (PV), yolk sac volume (YSV) and crown rump lengh (CRL) in predicting pregnancy outcome. Our goals was to demonstrate the ability of the first trimester ultrasound in identifying patients at high risk for abortion, intrauterine growth restriction (IUGR) and low birth weight.

In this study, we investigated the associations of maternal dietary iron intake during the first trimester of pregnancy and pregnancy outcomes and related complications in pregnant women of Isfahan, Iran. In this prospective study, 812 healthy first-trimester singleton pregnant women were selected randomly from 20 various health centers across Isfahan city during 2015-2016. The maternal dietary iron classified into 2 groups, including heme and non-heme iron. Factors including pre-eclampsia, gestational hypertension, gestational diabetes mellitus, intrauterine growth restriction (IUGR), and nausea and vomiting in pregnancy considered as the pregnancy-related complications. Infant's birth weight, birth height, and birth head circumference were also determined as the pregnancy-outcomes. There was a significant association between total iron consumption and infant head circumference (p = 0.01). Total maternal iron (the sum of heme and non-heme iron) was negatively associated with both infant's birth height (p = 0.006) and birth weight (p = 0.02). Non-heme iron consumption is positively associated with high-risk of IUGR (p = 0.004). Heme intake was associated with an increased risk of maternal fasting blood sugar (FBS) (p = 0.04). Higher heme, non-heme, and total iron intake were associated with lower risk of pre-eclampsia (heme: crude p = 0.05; non-heme iron: adjusted p = 0.02; total iron: adjusted p = 0.05). Maternal total iron intake was directly associated with infant head circumference, whereas, negatively associated with both birth weight and birth height. High non-heme iron intake may increase the risk of IUGR, and a high intake of heme iron may increase FBS.

Threatened miscarriage is the most common gynecological emergency, occurring in about 20% of pregnant women. Approximately one in four of these patients go on to have spontaneous miscarriage and the etiology of miscarriage still remains elusive. In a bid to identify possible biomarkers and novel treatment targets, many studies have been undertaken to elucidate the pathways that lead to a miscarriage. Luteal phase deficiency has been shown to contribute to miscarriages, and the measurement of serum progesterone as a prognostic marker and the prescription of progesterone supplementation has been proposed as possible diagnostic and treatment methods. However, luteal phase deficiency only accounts for 35% of miscarriages. In order to understand the other causes of spontaneous miscarriage and possible novel urine biomarkers for miscarriage, we looked at the changes in urinary metabolites in women with threatened miscarriage. To this end, we performed a case-control study of eighty patients who presented with threatened miscarriage between 6 and 10 weeks gestation. Urine metabolomics analyses of forty patients with spontaneous miscarriages and forty patients with ongoing pregnancies at 16 weeks gestation point to an impaired placental mitochondrial β-oxidation of fatty acids as the possible cause of spontaneous miscarriage. This study also highlighted the potential of urine metabolites as a non-invasive screening tool for the risk stratification of women presenting with threatened miscarriage.

Autophagy is a degradation process that acts in response to environmental stressors. Recently, autophagy has been detected in normal term, preeclamptic and intrauterine growth-restricted placentas. The object of this work was to investigate the presence of autophagy in first trimester voluntary interruption of pregnancy placental villi by the expression of autophagy-related proteins, light chain 3 (LC3), and Beclin-1. In first trimester placental villi laser scanning confocal microscopy (LSCM) analysis revealed LC3 and Beclin-1 immunoreactivity prevalently located in villous cytotrophoblasts. Using LSCM, LC3, and Beclin-1 were localized to the cytoplasm of the trophoblast layer in human full-term placentas. Beclin-1 expression and LC3 activation were confirmed by western blotting. These data emphasize that autophagy activation is different among cytotrophoblasts and syncytiotrophoblasts depending on the gestational age and thus we speculate that autophagy might play a prosurvival role throughout human pregnancy.

First trimester miscarriage is a major concern in IVF-ET treatments, accounting for one out of nine clinical pregnancies and for up to one out of three recognized pregnancies. To develop a machine learning classifier for predicting the risk of cleavage-stage embryos to undergo first trimester miscarriage based on time-lapse images of preimplantation development.

This study was designed to review the screening performance of combined test at the Ewha Womans University Mokdong hospital.

Abortion is an important problem in obstetrics throughout the world. The common and standard method for pregnancy termination at first trimester is surgery (curettage). Nowadays, an effective method of pregnancy termination at first trimester is medical treatments. The aim of this study is to compare misoprostol alone or in combination with methotrexate for pregnancy termination at first trimester. This study is a randomized clinical trial. A total of 200 pregnant women at first trimester were randomizedly divided into two groups for termination of pregnancy. The first group received 800 μg vaginal misoprostol. If conceptus residual remained, the same dose of misoprostol was repeated. The second group received 50 mg/m² intramuscular methotrexate, and then 800 μg vaginal misoprostol was administered after 72 h. If conceptus residual remained, the same dose of misoprostol was repeated after 24 h. Abdominal ultrasonography was performed at seventh day for both groups. Should conceptus residual remained or if pregnancy continued, curettage was performed. The results were analyzed statistically in terms of chi-square, and student's t-test, using the SPSS software. A P-value equal or smaller than 0.05, was considered statistically significant. In this study, 83% of the first group and 81% of the second group had successful abortion. There was a significant correlation between the dose of misoprostol and abortion (P = 0.001) and between type of pregnancy and need for curettage (P < 0.000) in both groups, but there was no significant correlation between gestational age and the numberof doses administered (P = 0.932).In conclusion it seems that pregnancy termination by misoprostol alone or in combination with methotrexate is a safe and cost-effective method.

The outbreak of the Zika Virus (ZIKV) and its association with fetal abnormalities have raised worldwide concern. However, the cellular tropism and the mechanisms of ZIKV transmission to the fetus during early pregnancy are still largely unknown. Therefore, we ex vivo modeled the ZIKV transmission at the maternal-fetal interface using organ culture from first trimester pregnancy samples. Here, we provide evidence that ZIKV strain circulating in Brazil infects and damages tissue architecture of the maternal decidua basalis, the fetal placenta and umbilical cord. We also show that ZIKV replicates differentially in a wide range of maternal and fetal cells, including decidual fibroblasts and macrophages, trophoblasts, Hofbauer cells as well as umbilical cord mesenchymal stem cells. The striking cellular tropism of ZIKV and its cytopathic-induced tissue injury during the first trimester of pregnancy could provide an explanation for the irreversible congenital damages.

Periodontal diseases (gingivitis and periodontitis) are chronic non-communicable inflammatory diseases. The risk of developing gingivitis and periodontitis increases during pregnancy. Also, periodontitis increases the risk of developing adverse pregnancy outcomes such as preterm birth and preeclampsia. Early diagnosis of adverse pregnancy outcomes is essential and periodontitis could be an early sign to take into consideration.

Embryonic chromosomal abnormality is one of the significant causative factors of early pregnancy loss. Our goal was to evaluate the clinical utility of next-generation sequencing (NGS) technology in identifying chromosomal anomalies associated with first-trimester pregnancy loss. In addition, we attempted to provide fertility guidance to couples anticipating a successful pregnancy. A total of 1,010 miscarriage specimens were collected between March 2016 and January 2019 from women who suffered first-trimester pregnancy loss. Total DNA was isolated from products of conception, and NGS analysis was carried out. We detected a total of 634 cases of chromosomal variants. Among the 634 cases, 462 (72.9%) displayed numerical variants including 383 (60.4%) aneuploidies, 44 (6.9%) polyploidies, and 34 (5.5%) mosaicisms. The other 172 (27.1%) cases showed structural variants including 19 (3.0%) benign copy number variations (CNVs), 52 (8.2%) pathogenic CNVs, and 101 (16%) variants of unknown significance (VOUS) CNVs. When maternal age was ≥ 35 years, the sporadic abortion (SA) group showed an increased frequency of chromosomal variants in comparison with the recurrent miscarriage (RM) group (90/121 vs. 64/104). It was evident that the groups with advanced maternal age had a sharply increased frequency of aneuploidy, whatever the frequency of pregnancy loss (71/121 vs. 155/432, 49/104 vs. 108/349). Our data suggest that NGS could be used for the successful detection of genetic anomalies in pregnancy loss. We recommend that fetal chromosome analysis be offered routinely for all pregnancy losses, regardless of their frequency.

Human placenta releases specific nanovesicles (i.e. exosomes) into the maternal circulation during pregnancy, however, the presence of placenta-derived exosomes in maternal blood during early pregnancy remains to be established. The aim of this study was to characterise gestational age related changes in the concentration of placenta-derived exosomes during the first trimester of pregnancy (i.e. from 6 to 12 weeks) in plasma from women with normal pregnancies.

In the 2016 Zika virus (ZIKV) pandemic, a previously unrecognized risk of birth defects surfaced in babies whose mothers were infected with Asian-lineage ZIKV during pregnancy. Less is known about the impacts of gestational African-lineage ZIKV infections. Given high human immunodeficiency virus (HIV) burdens in regions where African-lineage ZIKV circulates, we evaluated whether pregnant rhesus macaques infected with simian immunodeficiency virus (SIV) have a higher risk of African-lineage ZIKV-associated birth defects. Remarkably, in both SIV+ and SIV- animals, ZIKV infection early in the first trimester caused a high incidence (78%) of spontaneous pregnancy loss within 20 days. These findings suggest a significant risk for early pregnancy loss associated with African-lineage ZIKV infection and provide the first consistent ZIKV-associated phenotype in macaques for testing medical countermeasures.