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Epigenetics Dec 2023Most pregnancy complications originate with early placentation. MicroRNAs (miRNAs) may play an important role in placentation and function as biomarkers of future...
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.
Topics: Pregnancy; Humans; Infant, Newborn; Female; Pregnancy Trimester, First; Pre-Eclampsia; Hypertension, Pregnancy-Induced; Circulating MicroRNA; Placenta; Premature Birth; DNA Methylation; MicroRNAs; Pregnancy Complications; Placentation; Biomarkers
PubMed: 36503407
DOI: 10.1080/15592294.2022.2152615 -
International Journal of Molecular... Apr 2024Preeclampsia, a serious complication of pregnancy, involves intricate molecular and cellular mechanisms. Fetal microchimerism, where fetal cells persist within maternal... (Review)
Review
Preeclampsia, a serious complication of pregnancy, involves intricate molecular and cellular mechanisms. Fetal microchimerism, where fetal cells persist within maternal tissues and in circulation, acts as a mechanistic link between placental dysfunction and maternal complications in the two-stage model of preeclampsia. Hormones, complements, and cytokines play pivotal roles in the pathophysiology, influencing immune responses, arterial remodeling, and endothelial function. Also, soluble HLA-G, involved in maternal-fetal immune tolerance, is reduced in preeclampsia. Hypoxia-inducible factor 1-alpha (Hif-α) dysregulation leads to placental abnormalities and preeclampsia-like symptoms. Alterations in matrix metalloproteinases (MMPs), endothelins (ETs), chemokines, and cytokines contribute to defective trophoblast invasion, endothelial dysfunction, and inflammation. Preeclampsia's genetic complexity includes circRNAs, miRNAs, and lncRNAs. CircRNA_06354 is linked to early-onset preeclampsia by influencing trophoblast invasion via the hsa-miR-92a-3p/VEGF-A pathway. The dysregulation of C19MC, especially miR-519d and miR-517-5p, affects trophoblast function. Additionally, lncRNAs like IGFBP1 and EGFR-AS1, along with protein-coding genes, impact trophoblast regulation and angiogenesis, influencing both preeclampsia and fetal growth. Besides aberrations in CD31+ cells, other potential biomarkers such as MMPs, soluble HLA-G, and hCG hold promise for predicting preeclampsia and its complications. Therapeutic interventions targeting factors such as peroxisome PPAR-γ and endothelin receptors show potential in mitigating preeclampsia-related complications. In conclusion, preeclampsia is a complex disorder with a multifactorial etiology and pathogenesis. Fetal microchimerism, hormones, complements, and cytokines contribute to placental and endothelial dysfunction with inflammation. Identifying novel biomarkers and therapeutic targets offers promise for early diagnosis and effective management, ultimately reducing maternal and fetal morbidity and mortality. However, further research is warranted to translate these findings into clinical practice and enhance outcomes for at-risk women.
Topics: Female; Humans; Pregnancy; Biomarkers; Hormones; MicroRNAs; Placenta; Pre-Eclampsia; Trophoblasts
PubMed: 38674114
DOI: 10.3390/ijms25084532 -
Schizophrenia Research Dec 2023Schizophrenia is a severe mental illness that affects a significant proportion of the global population, particularly those of childbearing age. Several studies have... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Schizophrenia is a severe mental illness that affects a significant proportion of the global population, particularly those of childbearing age. Several studies have attempted to find an association between schizophrenia and obstetric complications, with varying results.
OBJECTIVE
The primary objective of this systematic review and meta-analyses was to summarize the relationship between maternal schizophrenia and perinatal pregnancy outcomes.
DATA SOURCES
PubMed, Web of Science and Ovid EMBASE were searched from January 2001 to September 2022 using keywords related to pregnancy, women, schizophrenia.
STUDY SELECTION
A total of 23 independent studies across 21,253 individuals with schizophrenia were identified and included in the analysis.
DATA EXTRACTION
The following data were extracted: author, year of publication, country/continent of data collection, study design, demographic characteristics, diagnoses criteria, related complications. Data were analyzed using random-effects pairwise meta-analysis and were reported as prevalence and odd ratios (OR). Statistical heterogeneity was quantified with the I statistic.
RESULTS
The prevalence of adverse perinatal pregnancy outcomes was represented in descending order: cesarean section (26.0 %); labor induction (24.0 %); small for gestational age (10.5 %); gestational diabetes mellitus (9.2 %); preterm birth (9.1 %); low birth weight (7.8 %); preterm rupture of membranes (6.1 %); 1-Minute Apgar Score < 7 (5.6 %); large for gestational age (5.5 %); birth defect (5.4 %); antepartum hemorrhage (4.4 %);preeclampsia/eclampsia (4.8 %); postpartum hemorrhage (3.9 %); 5-Minute Apgar Score < 7 (3.6 %); gestational hypertension (3.3 %); placental abruption (1.0 %); placenta previa (0.6 %); thromboembolic disease (0.4 %); neonatal mortality (0.3 %) (P ≤ 0.05). There was a higher risk of adverse outcomes including gestational diabetes mellitus, preeclampsia/eclampsia, placental abruption, thromboembolic disease, preterm birth, birth defect, 1-Minute Apgar score < 7, small for gestational age, low birth weight and neonatal mortality compared with non-schizophrenia population (P ≤ 0.05).
CONCLUSIONS
Women with schizophrenia are at higher risk of adverse perinatal pregnancy outcomes. It is imperative that research efforts continue to focus on the reproductive safety of women with schizophrenia during their childbearing years.
Topics: Pregnancy; Female; Infant, Newborn; Humans; Pregnancy Outcome; Premature Birth; Diabetes, Gestational; Abruptio Placentae; Cesarean Section; Pre-Eclampsia; Eclampsia; Schizophrenia; Placenta
PubMed: 37979419
DOI: 10.1016/j.schres.2023.11.001 -
Indian Journal of Pediatrics Dec 2023India contributes the highest absolute number of stillbirths in the world. This systematic review and meta-analysis was conducted to synthesize the burden, timing and... (Meta-Analysis)
Meta-Analysis Review
India contributes the highest absolute number of stillbirths in the world. This systematic review and meta-analysis was conducted to synthesize the burden, timing and causes of stillbirths in India. Forty-nine reports from 46 studies conducted in 21 Indian states and Union Territories were included. It was found that there was no uniformity/standardization in the definition of stillbirths and in the classification system used to assign the cause. The share of antepartum stillbirths was estimated to be two-third while remaining were intrapartum stillbirths. Maternal conditions and fetal causes were found to be the leading cause of stillbirth in India. The maternal condition was assigned as the commonest cause (25%) followed by fetal (14%), placental cause (13%), congenital malformation (6%) and intrapartum complications (4%). Approximately 20% of the stillbirths were assigned as unknown or unexplained. This review demonstrates that there is a paucity of quality stillbirth data in India. Other than the state level differences in stillbirth rates, no other data is available on inequities in stillbirths in India. There is an urgent need for strengthening availability and quality of stillbirth data in India on both stillbirth rates as well as the causes. There is a need to conduct additional research to know the timing of the stillbirths, causes of death and actual burden. India needs to strengthen stillbirth audits along with registry to find out the modifiable factors and delays for making country specific preventive strategies. The policy makers, academic community and researchers need to work together to ensure accelerated and equitable reduction in stillbirths in India.
Topics: Humans; Female; Pregnancy; Stillbirth; Placenta; Risk Factors; Prenatal Care; India
PubMed: 37556034
DOI: 10.1007/s12098-023-04749-9 -
Journal of Extracellular Vesicles Nov 2023Extracellular vesicles (EVs) play a crucial role in pregnancy, revealed by the presence of placental-derived EVs in maternal blood, their in vitro functionality, and... (Review)
Review
Extracellular vesicles (EVs) play a crucial role in pregnancy, revealed by the presence of placental-derived EVs in maternal blood, their in vitro functionality, and their altered cargo in pregnancy pathologies. These EVs are thought to be involved in the development of pregnancy pathologies, such as pre-eclampsia, pre-term birth, and fetal growth restriction, and have been suggested as a source of biomarkers for gestational diseases. However, to accurately interpret their function and biomarker potential, it is necessary to critically evaluate the EV isolation and characterization methodologies used in pregnant cohorts. In this systematic scoping review, we collated the results from 152 studies that have investigated EVs in the blood of pregnant women, and provide a detailed analysis of the EV isolation and characterization methodologies used. Our findings indicate an overall increase in EV concentrations in pregnant compared to non-pregnant individuals, an increased EV count as gestation progresses, and an increased EV count in some pregnancy pathologies. We highlight the need for improved standardization of methodology, greater focus on gestational changes in EV concentrations, and further investigations into the functionality of EVs. Our review suggests that EVs hold great promise as diagnostic and translational tools for gestational diseases. However, to fully realize their potential, it is crucial to improve the standardization and reliability of EV isolation and characterization methodologies, and to gain a better understanding of their functional roles in pregnancy pathologies.
Topics: Pregnancy; Female; Humans; Extracellular Vesicles; Placenta; Reproducibility of Results; Pre-Eclampsia
PubMed: 37974377
DOI: 10.1002/jev2.12377 -
Journal of Obstetrics and Gynaecology... Nov 2023Planned hysterectomy at the time of cesarean delivery may be reasonable in cases other than placenta accreta spectrum disorders. Our objective was to synthesize the... (Review)
Review
OBJECTIVE
Planned hysterectomy at the time of cesarean delivery may be reasonable in cases other than placenta accreta spectrum disorders. Our objective was to synthesize the published literature on the indications and outcomes for planned cesarean hysterectomy.
DATA SOURCES
We performed a systematic review of published literature from the following databases from inception (1946) to June 2021: MEDLINE, PubMed, EMBASE, Cochrane CENTRAL, DARE, and clinicaltrials.gov.
STUDY SELECTION
We included all study designs where subjects underwent planned cesarean delivery with simultaneous hysterectomy. Emergency procedures and those performed for placenta accreta spectrum disorders were excluded.
DATA EXTRACTION AND SYNTHESIS
The primary outcome was surgical indication, though other surgical outcomes were evaluated when data permitted. Quantitative analysis was limited to studies published in 1990 or later. Risk of bias was assessed using an adaptation of the ROBINS-I tool.
CONCLUSION
The most common indication for planned cesarean hysterectomy was malignancy, with cervical cancer being the most frequent. Other indications included permanent contraception, uterine fibroids, menstrual disorders, and chronic pelvic pain. Common complications included bleeding, infection, and ileus. The surgical skill for cesarean hysterectomy continues to be relevant in contemporary obstetrical practice for reproductive malignancy and several benign indications. Although the data indicate relatively safe outcomes, these studies show significant publication bias and, therefore, further systematic study of this procedure is justified.
PROSPERO REGISTRATION NUMBER
CRD42021260545, registered June 16, 2021.
Topics: Pregnancy; Female; Humans; Placenta Accreta; Retrospective Studies; Risk Factors; Hysterectomy; Neoplasms
PubMed: 37380105
DOI: 10.1016/j.jogc.2023.04.025 -
Arthroscopy : the Journal of... Aug 2023To summarize the available evidence regarding the clinical application of placenta-derived products to treat knee osteoarthritis (OA), underlining the differences... (Review)
Review
PURPOSE
To summarize the available evidence regarding the clinical application of placenta-derived products to treat knee osteoarthritis (OA), underlining the differences existing among products, their preparation methods, and the clinical results reported so far.
METHODS
A research on PubMed, Cochrane, and Google Scholar databases was performed. The following inclusion criteria for relevant articles were used: (1) randomized controlled trials (RCTs), prospective and retrospective studies, on humans; (2) written in English; (3) published in indexed journals in the last 10 years (2011-2022); and (4) dealing with the use of placenta-derived products for the treatment of knee OA. Exclusion criteria were articles written in other languages; animals or in vitro trials; reviews; and trials analyzing other applications of placenta-derived products not related to knee OA.
RESULTS
In total, 16 studies were included in the present systematic review. Five studies investigated placenta-derived products as an augmentation during surgical procedures, whereas 11 studies were focused on the injective approach only. Of these, only 4 were RCTs and were all from the injective approach group. Potential risk of bias was carried out using Cochrane Risk of Bias 2 tool for RCTs and a modified Coleman approach for nonrandomized studies, revealing for both an overall insufficient quality. Clinical outcomes reveal excellent safety profile and notable efficacy, despite the different types of products used and different administration methods adopted.
CONCLUSIONS
Placental products showed a good safety profile and overall satisfactory outcomes for the treatment of knee OA.
LEVEL OF EVIDENCE
Level IV, systematic review of Level II, III and IV studies.
Topics: Humans; Osteoarthritis, Knee; Injections, Intra-Articular
PubMed: 37116549
DOI: 10.1016/j.arthro.2023.03.033 -
Human Reproduction Update Mar 2024With increasing significance of developmental programming effects associated with placental dysfunction, more investigations are devoted to improving the...
BACKGROUND
With increasing significance of developmental programming effects associated with placental dysfunction, more investigations are devoted to improving the characterization and understanding of placental signatures in health and disease. The placenta is a transitory but dynamic organ adapting to the shifting demands of fetal development and available resources of the maternal supply throughout pregnancy. Trophoblasts (cytotrophoblasts, syncytiotrophoblasts, and extravillous trophoblasts) are placental-specific cell types responsible for the main placental exchanges and adaptations. Transcriptomic studies with single-cell resolution have led to advances in understanding the placenta's role in health and disease. These studies, however, often show discrepancies in characterization of the different placental cell types.
OBJECTIVE AND RATIONALE
We aim to review the knowledge regarding placental structure and function gained from the use of single-cell RNA sequencing (scRNAseq), followed by comparing cell-type-specific genes, highlighting their similarities and differences. Moreover, we intend to identify consensus marker genes for the various trophoblast cell types across studies. Finally, we will discuss the contributions and potential applications of scRNAseq in studying pregnancy-related diseases.
SEARCH METHODS
We conducted a comprehensive systematic literature review to identify different cell types and their functions at the human maternal-fetal interface, focusing on all original scRNAseq studies on placentas published before March 2023 and published reviews (total of 28 studies identified) using PubMed search. Our approach involved curating cell types and subtypes that had previously been defined using scRNAseq and comparing the genes used as markers or identified as potential new markers. Next, we reanalyzed expression matrices from the six available scRNAseq raw datasets with cell annotations (four from first trimester and two at term), using Wilcoxon rank-sum tests to compare gene expression among studies and annotate trophoblast cell markers in both first trimester and term placentas. Furthermore, we integrated scRNAseq raw data available from 18 healthy first trimester and nine term placentas, and performed clustering and differential gene expression analysis. We further compared markers obtained with the analysis of annotated and raw datasets with the literature to obtain a common signature gene list for major placental cell types.
OUTCOMES
Variations in the sampling site, gestational age, fetal sex, and subsequent sequencing and analysis methods were observed between the studies. Although their proportions varied, the three trophoblast types were consistently identified across all scRNAseq studies, unlike other non-trophoblast cell types. Notably, no marker genes were shared by all studies for any of the investigated cell types. Moreover, most of the newly defined markers in one study were not observed in other studies. These discrepancies were confirmed by our analysis on trophoblast cell types, where hundreds of potential marker genes were identified in each study but with little overlap across studies. From 35 461 and 23 378 cells of high quality in the first trimester and term placentas, respectively, we obtained major placental cell types, including perivascular cells that previously had not been identified in the first trimester. Importantly, our meta-analysis provides marker genes for major placental cell types based on our extensive curation.
WIDER IMPLICATIONS
This review and meta-analysis emphasizes the need for establishing a consensus for annotating placental cell types from scRNAseq data. The marker genes identified here can be deployed for defining human placental cell types, thereby facilitating and improving the reproducibility of trophoblast cell annotation.
PubMed: 38478759
DOI: 10.1093/humupd/dmae006 -
American Journal of Obstetrics and... Feb 2024This study aimed to evaluate the association between human chorionic gonadotropin and adverse pregnancy outcomes. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This study aimed to evaluate the association between human chorionic gonadotropin and adverse pregnancy outcomes.
DATA SOURCES
Medline, Embase, PubMed, and Cochrane were searched in November 2021 using Medical Subject Headings (MeSH) and relevant key words.
STUDY ELIGIBILITY CRITERIA
This analysis included published full-text studies of pregnant women with serum human chorionic gonadotropin testing between 8 and 28 weeks of gestation, investigating fetal outcomes (fetal death in utero, small for gestational age, preterm birth) or maternal factors (hypertension in pregnancy: preeclampsia, pregnancy-induced hypertension, placental abruption, HELLP syndrome, gestational diabetes mellitus).
METHODS
Studies were extracted using REDCap software. The Newcastle-Ottawa scale was used to assess for risk of bias. Final meta-analyses underwent further quality assessment using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) method.
RESULTS
A total of 185 studies were included in the final review, including the outcomes of fetal death in utero (45), small for gestational age (79), preterm delivery (62), hypertension in pregnancy (107), gestational diabetes mellitus (29), placental abruption (17), and HELLP syndrome (2). Data were analyzed separately on the basis of categorical measurement of human chorionic gonadotropin and human chorionic gonadotropin measured on a continuous scale. Eligible studies underwent meta-analysis to generate a pooled odds ratio (categorical human chorionic gonadotropin level) or difference in medians (human chorionic gonadotropin continuous scale) between outcome groups. First-trimester low human chorionic gonadotropin levels were associated with preeclampsia and fetal death in utero, whereas high human chorionic gonadotropin levels were associated with preeclampsia. Second-trimester high human chorionic gonadotropin levels were associated with fetal death in utero and preeclampsia.
CONCLUSION
Human chorionic gonadotropin levels are associated with placenta-mediated adverse pregnancy outcomes. Both high and low human chorionic gonadotropin levels in the first trimester of pregnancy can be early warning signs of adverse outcomes. Further analysis of human chorionic gonadotropin subtypes and pregnancy outcomes is required to determine the diagnostic utility of these findings in reference to specific cutoff values.
Topics: Pregnancy; Humans; Female; Infant, Newborn; Pre-Eclampsia; Abruptio Placentae; Diabetes, Gestational; HELLP Syndrome; Placenta; Premature Birth; Biomarkers; Chorionic Gonadotropin; Pregnancy Outcome; Hypertension, Pregnancy-Induced; Fetal Death
PubMed: 37572838
DOI: 10.1016/j.ajog.2023.08.007 -
Clinical Infectious Diseases : An... Jan 2024Tularemia is caused by the gram-negative bacterium Francisella tularensis. Although rare, tularemia during pregnancy has been associated with pregnancy complications;...
BACKGROUND
Tularemia is caused by the gram-negative bacterium Francisella tularensis. Although rare, tularemia during pregnancy has been associated with pregnancy complications; data on efficacy of recommended antimicrobials for treatment are limited. We performed a systematic literature review to characterize clinical manifestations of tularemia during pregnancy and examine maternal, fetal, and neonatal outcomes with and without antimicrobial treatment.
METHODS
We searched 9 databases, including Medline, Embase, Global Health, and PubMed Central, using terms related to tularemia and pregnancy. Articles reporting cases of tularemia with ≥1 maternal or fetal outcome were included.
RESULTS
Of 5891 articles identified, 30 articles describing 52 cases of tularemia in pregnant patients met inclusion criteria. Cases were reported from 9 countries, and oropharyngeal and ulceroglandular tularemia were the most common presenting forms. A plurality (46%) of infections occurred in the second trimester. Six complications were observed: lymph node aspiration, lymph node excision, maternal bleeding, spontaneous abortion, intrauterine fetal demise, and preterm birth. No deaths among mothers were reported. Of 28 patients who received antimicrobial treatment, 1 pregnancy loss and 1 fetal death were reported. Among 24 untreated patients, 1 pregnancy loss and 3 fetal deaths were reported, including one where F. tularensis was detected in placental and fetal tissues.
CONCLUSIONS
Pregnancy loss and other complications have been reported among cases of tularemia during pregnancy. However, risk of adverse outcomes may be lower when antimicrobials known to be effective are used. Without treatment, transplacental transmission appears possible. These data underscore the importance of prompt recognition and treatment of tularemia during pregnancy.
Topics: Humans; Female; Infant, Newborn; Pregnancy; Tularemia; Premature Birth; Placenta; Francisella tularensis; Abortion, Spontaneous; Anti-Infective Agents
PubMed: 38294114
DOI: 10.1093/cid/ciad686