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International Journal of Molecular... Jun 2024The placenta plays a key role in several adverse obstetrical outcomes, such as preeclampsia, intrauterine growth restriction and gestational diabetes mellitus. The early... (Review)
Review
The placenta plays a key role in several adverse obstetrical outcomes, such as preeclampsia, intrauterine growth restriction and gestational diabetes mellitus. The early identification of at-risk pregnancies could significantly improve the management, therapy and prognosis of these pregnancies, especially if these at-risk pregnancies are identified in the first trimester. The aim of this review was to summarize the possible biomarkers that can be used to diagnose early placental dysfunction and, consequently, at-risk pregnancies. We divided the biomarkers into proteins and non-proteins. Among the protein biomarkers, some are already used in clinical practice, such as the sFLT1/PLGF ratio or PAPP-A; others are not yet validated, such as HTRA1, Gal-3 and CD93. In the literature, many studies analyzed the role of several protein biomarkers, but their results are contrasting. On the other hand, some non-protein biomarkers, such as miR-125b, miR-518b and miR-628-3p, seem to be linked to an increased risk of complicated pregnancy. Thus, a first trimester heterogeneous biomarkers panel containing protein and non-protein biomarkers may be more appropriate to identify and discriminate several complications that can affect pregnancies.
Topics: Humans; Pregnancy; Female; Biomarkers; Pregnancy Trimester, First; Placenta; Pregnancy Outcome; Pre-Eclampsia; MicroRNAs; Pregnancy-Associated Plasma Protein-A; Diabetes, Gestational
PubMed: 38892323
DOI: 10.3390/ijms25116136 -
BMJ Open Jun 2024Preterm pre-eclampsia is a leading cause of maternal morbidity and mortality. The Pre-eclampsia Intervention 2 (PI 2) trial suggested that metformin sustained release...
INTRODUCTION
Preterm pre-eclampsia is a leading cause of maternal morbidity and mortality. The Pre-eclampsia Intervention 2 (PI 2) trial suggested that metformin sustained release (XR) may prolong gestation by a week in pregnant women undergoing expectant management (7.6 days, geometric mean ratio 1.39, 95% CI 0.99 to 1.95; p=0.057). These findings should be confirmed with a larger sample size, and we need to know if such a prolongation improves neonatal outcome. Here, we describe the protocol for such a follow-up trial.
METHODS
The PI 3 trial is a phase III, intention-to-treat, double-blind, placebo-controlled randomised clinical trial to assess if metformin XR can prolong gestation and improve neonatal outcomes in women undergoing expectant management for preterm pre-eclampsia. We will recruit women who are between 26+0 and 31+6 weeks pregnant. Women will be randomised to receive either 3 g metformin XR or an identical placebo in divided daily doses. The primary outcome is prolongation of pregnancy. Secondary outcomes are neonatal birth weight and length of neonatal care admission (an indicator of neonatal health at birth). All other outcomes will be exploratory. We will record tolerability and adverse events. We plan a sample size of 500 participants to be powered for the primary and secondary outcomes.
ETHICS AND DISSEMINATION
PI 3 has ethical approval (Health Research Ethics Committee 2, Stellenbosch University, Protocol number M21/03/007, Project ID 21639, Federal Wide Assurance Number 00001372, Institutional Review Board Number IRB0005239), and is registered with the Pan African Clinical Trial Registry (PACTR202104532026017) and the South African Medicine Control Council (20211211). Data will be presented at international conferences and published in peer-reviewed journals.
TRIAL REGISTRATION NUMBER
PACTR202104532026017).
Topics: Humans; Pregnancy; Female; Metformin; Pre-Eclampsia; Double-Blind Method; South Africa; Hypoglycemic Agents; Infant, Newborn; Randomized Controlled Trials as Topic; Adult; Pregnancy Outcome
PubMed: 38890136
DOI: 10.1136/bmjopen-2023-082880 -
BMJ Case Reports Jun 2024Eclampsia spectrum disorders are a set of serious complications of pregnancy that commonly present after 20 weeks of gestation. There is an association between molar...
Eclampsia spectrum disorders are a set of serious complications of pregnancy that commonly present after 20 weeks of gestation. There is an association between molar pregnancy, a gestational trophoblastic disease resulting from abnormal fertilisation and gametogenesis, and eclampsia spectrum disorders which can result in manifestation of pre-eclamptic symptomatology earlier than 20 weeks of gestation. We report a case of a gravida 1 para 0 in her mid 20s at 16-weeks gestation presenting with partial hydatidiform mole who developed eclampsia, haemolysis, elevated liver enzymes and low platelets syndrome and posterior reversible encephalopathy syndrome. Ultrasound findings were consistent with molar pregnancy and pathology confirmed partial molar pregnancy with triploid 69, XYY karyotype. This case highlights the early onset potential of eclampsia spectrum disorders in molar pregnancies while suggesting screening such patients for hypertensive disorders.
Topics: Humans; Female; Hydatidiform Mole; Pregnancy; HELLP Syndrome; Eclampsia; Adult; Uterine Neoplasms; Posterior Leukoencephalopathy Syndrome
PubMed: 38890113
DOI: 10.1136/bcr-2023-258188 -
IMeta Apr 2024Numerous studies have demonstrated the pivotal roles of intestinal microbiota in many physiopathological processes through complex interactions with the host. As a... (Review)
Review
Numerous studies have demonstrated the pivotal roles of intestinal microbiota in many physiopathological processes through complex interactions with the host. As a unique period in a woman's lifespan, pregnancy is characterized by changes in hormones, immunity, and metabolism. The gut microbiota also changes during this period and plays a crucial role in maintaining a healthy pregnancy. Consequently, anomalies in the composition and function of the gut microbiota, namely, gut microbiota dysbiosis, can predispose individuals to various pregnancy complications, posing substantial risks to both maternal and neonatal health. However, there are still many controversies in this field, such as "sterile womb" versus "in utero colonization." Therefore, a thorough understanding of the roles and mechanisms of gut microbiota in pregnancy and its complications is essential to safeguard the health of both mother and child. This review provides a comprehensive overview of the changes in gut microbiota during pregnancy, its abnormalities in common pregnancy complications, and potential etiological implications. It also explores the potential of gut microbiota in diagnosing and treating pregnancy complications and examines the possibility of gut-derived bacteria residing in the uterus/placenta. Our aim is to expand knowledge in maternal and infant health from the gut microbiota perspective, aiding in developing new preventive and therapeutic strategies for pregnancy complications based on intestinal microecology.
PubMed: 38882493
DOI: 10.1002/imt2.167 -
Cureus Jun 2024Advances in assisted reproductive technologies have enabled postmenopausal women to achieve pregnancy beyond their reproductive lifespan. Although rare, these...
Advances in assisted reproductive technologies have enabled postmenopausal women to achieve pregnancy beyond their reproductive lifespan. Although rare, these pregnancies are challenging and require a multidisciplinary approach due to the higher prevalence of medical comorbidities in this population. The placenta accreta spectrum is characterized by an abnormal invasion of chorionic villi into the myometrium. Risk factors associated with the placenta accreta spectrum include prior uterine surgeries, advanced maternal age, multiparity, in vitro fertilization, and placenta previa. We present a case of a 59-year-old postmenopausal woman with chronic hypertension, stage II chronic kidney injury, and superimposed pre-eclampsia who underwent cesarean delivery complicated by suspected focal placenta accreta. Histopathological examination revealed significant deviations from normative placental architecture, emphasizing the invasion of the villi. Further, congested blood vessels and the presence of inflammatory cells, along with heightened collagen deposition, suggest an underlying pathological process affecting placental health. These findings underscore a perturbation of placental homeostasis, emphasizing the necessity for further investigation into the mechanisms contributing to placental pathology in postmenopausal pregnancies.
PubMed: 38882221
DOI: 10.7759/cureus.62332 -
PeerJ 2024COVID-19 is an infectious pathology that shows vascular changes during pregnancy, as well as in the placentas. The main objectives of this study were to estimate the...
BACKGROUND
COVID-19 is an infectious pathology that shows vascular changes during pregnancy, as well as in the placentas. The main objectives of this study were to estimate the prevalence and the risk factors for preeclampsia in hospitalized pregnant women with COVID-19. As well as comparing maternal and perinatal outcomes in hospitalized pregnant women with COVID-19 and preeclampsia with those without preeclampsia.
METHODS
Prospective cohort study of 100 hospitalized pregnant women from two tertiary hospitals, diagnosed with COVID-19, and divided into two groups: PE+ group (pregnant women with COVID-19 and preeclampsia) and PE- group (pregnant women with COVID-19 without preeclampsia). These pregnant women had prevalence, risk factors, maternal and perinatal data analyzed.
RESULTS
The prevalence of preeclampsia was 11%. Severe COVID-19 was the main risk factor for preeclampsia (OR = 8.18 [CI 1.53-43.52]), as well as fetal growth restriction was the main perinatal outcome (OR = 8.90 [CI 1.52-38.4]). Comorbidities were more frequent in the PE+ group (63.6% 31.5%, = 0.03), as well as prematurity (81.8% 41.6%, = 0.02), low birth weight (63.6% 24.7%, = 0.01), and the need for neonatal intensive care admission of the newborn (63.6% 27.0%, = 0.03). Pregnant women with PE had twice as long a length of stay in the intensive care unit (RR = 2.35 [CI 1.34-4.14]). Although maternal mortality was more frequent among pregnant women with PE, it was not statistically significant.
CONCLUSIONS
Prevalence of preeclampsia in hospitalized pregnant women with COVID-19 was 11%. Severe COVID-19 was the main risk factor for preeclampsia and associated comorbidities increased the risk for developing preeclampsia. Long length of stay in the intensive care unit was the main maternal outcome and fetal growth restriction was the main perinatal outcome of preeclampsia.
Topics: Humans; Pregnancy; Female; Pre-Eclampsia; COVID-19; Brazil; Prospective Studies; Adult; Tertiary Care Centers; Pregnancy Complications, Infectious; Risk Factors; Pregnancy Outcome; Prevalence; SARS-CoV-2; Infant, Newborn; Fetal Growth Retardation; Comorbidity
PubMed: 38881857
DOI: 10.7717/peerj.17481 -
Metabolomics : Official Journal of the... Jun 2024Preeclampsia is a pregnancy-specific clinical syndrome and can be subdivided into early-onset preeclampsia (EOPE) and late-onset preeclampsia (LOPE) according to the...
BACKGROUND
Preeclampsia is a pregnancy-specific clinical syndrome and can be subdivided into early-onset preeclampsia (EOPE) and late-onset preeclampsia (LOPE) according to the gestational age of delivery. Patients with preeclampsia have aberrant lipid metabolism. This study aims to compare serum lipid profiles of normal pregnant women with EOPE or LOPE and screening potential biomarkers to diagnose EOPE or LOPE.
METHODS
Twenty normal pregnant controls (NC), 19 EOPE, and 19 LOPE were recruited in this study. Untargeted lipidomics based on ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to compare their serum lipid profiles.
RESULTS
The lipid metabolism profiles significantly differ among the NC, EOPE, and LOPE. Compared to the NC, there were 256 and 275 distinct lipids in the EOPE and LOPE, respectively. Furthermore, there were 42 different lipids between the LOPE and EOPE, of which eight were significantly associated with fetal birth weight and maternal urine protein. The five lipids that both differed in the EOPE and LOPE were DGTS (16:3/16:3), LPC (20:3), LPC (22:6), LPE (22:6), PC (18:5e/4:0), and a combination of them were a potential biomarker for predicting EOPE or LOPE. The receiver operating characteristic analysis revealed that the diagnostic power of the combination for distinguishing the EOPE from the NC and for distinguishing the LOPE from the NC can reach 1.000 and 0.992, respectively. The association between the lipid modules and clinical characteristics of EOPE and LOPE was investigated by the weighted gene co-expression network analysis (WGCNA). The results demonstrated that the main different metabolism pathway between the EOPE and LOPE was enriched in glycerophospholipid metabolism.
CONCLUSIONS
Lipid metabolism disorders may be a potential mechanism of the pathogenesis of preeclampsia. Lipid metabolites have the potential to serve as biomarkers in patients with EOPE or LOPE. Furthermore, lipid metabolites correlate with clinical severity indicators for patients with EOPE and LOPE, including fetal birth weight and maternal urine protein levels.
Topics: Humans; Pregnancy; Female; Pre-Eclampsia; Lipidomics; Adult; Biomarkers; Lipids; Tandem Mass Spectrometry; Lipid Metabolism; Chromatography, High Pressure Liquid; Gestational Age
PubMed: 38879866
DOI: 10.1007/s11306-024-02134-x -
Current Problems in Cardiology Jun 2024. The long-term impact of gestational complications on cardiovascular outcomes in women remains a subject of debate. (Review)
Review
BACKGROUND
. The long-term impact of gestational complications on cardiovascular outcomes in women remains a subject of debate.
AIM
To assess the 5-year risk of cardiovascular events and all-cause mortality in women with gestational diabetes and hypertension.
METHODS
Retrospective study utilising an health research network(TriNetX). The primary outcome was the composite risk of a cardiovascular event within 5 years with secondary outcomes being its components (all-cause death, acute heart failure, myocardial infarction, ischaemic stroke). Women were categorised into 8 different groups based on the ICD-codes for pregnancy related complications recorded 9 months before the delivery:1) gestational diabetes,2) gestational hypertension,3) gestational diabetes with gestational hypertension,4) gestational diabetes with gestational hypertension without pre-eclampsia or eclampsia,5) gestational diabetes with pre-eclampsia or eclampsia,6) gestational hypertension without pre-eclampsia or eclampsia,7) pre-eclampsia or eclampsia,and 8) no gestational complications. Cox-regression analyses were used to produce hazard ratios (HRs) and 95 % confidence intervals (CI) before and after propensity score matching (PSM).
RESULTS
We identified, 24,402 women with gestational diabetes and gestational hypertension and 920,478 without gestational complications. After PSM, compared to women without pregnancy complications, women with gestational diabetes and gestational hypertension had a higher 5-year risk of composite outcome(HR 2.25,95 %CI 2.02-2.51), all-cause death(HR 1.64,95 %CI 1.31-2.06), acute heart failure(HR 2.06,95 %CI 1.69-2.52), myocardial infarction(HR 2.46,95 %CI 1.93-3.14), and ischemic stroke(HR 2.37,95 %CI 2.06-2.74). Women who experienced pre-eclampsia or eclampsia showed the highest risk of primary and secondary outcomes.
CONCLUSIONS
Gestational complications are associated with worse long-term cardiovascular outcomes. There is a clear call to action required to improve the longitudinal management of gestational complications to improve women's long-term health.
PubMed: 38876163
DOI: 10.1016/j.cpcardiol.2024.102698 -
Frontiers in Immunology 2024Preeclampsia/eclampsia (PE), a critical complication during pregnancy, has been suggested to correlate with immune cell phenotypes and levels of circulating inflammatory...
OBJECTIVES
Preeclampsia/eclampsia (PE), a critical complication during pregnancy, has been suggested to correlate with immune cell phenotypes and levels of circulating inflammatory proteins. Our study aimed to employ a two-sample mendelian randomization (MR) analysis to assess the potential causal effects of immune cell phenotypes and circulating inflammatory proteins on the onset of PE.
METHODS
We utilized summary-level data from genome-wide association studies (GWAS). This included statistics for 371 immune cell phenotypes from 3,757 individuals in the Sardinian founder population, and data on 91 circulating inflammatory proteins from 14,824 European ancestry participants. Additionally, genetic associations related to PE were extracted from the FinnGen consortium, involving 1,413 cases and 287,137 controls. We applied inverse variance weighting (IVW) and supplementary methods like MR-Egger, weighted median, and weighted mode to comprehensively assess potential causal links.
RESULTS
Our analysis revealed significant causal associations of several immune cells type and inflammatory proteins with PE. Out of the immune cell phenotypes analyzed, six immune phenotypes emerged as significant risk factors (0.01), mainly include CD4 on activated and secreting CD4 regulatory T cells, CD28 on CD39+ CD4+ T cells, CD127- CD8+ T cell absolute cell (AC) counts, HLA DR on HLA DR+ CD8+ T cell, CD66b on CD66b++ myeloid cells, and HLA DR on dendritic cells. And ten were identified as protective factors (0.01). Such as CD45 on CD33br HLA DR+ CD14-, CD33+ HLA DR+ AC, CD33+ HLA DR+ CD14- AC, CD33+ HLA DR+ CD14dim AC, CD27 on CD24+ CD27+ B cell, CD20- CD38- %B cell, IgD- CD24- %B cell CD80 on plasmacytoid DC, CD25 on CD4+ T cell, and CD25 on activated & secreting CD4 regulatory T cell. Furthermore, among the inflammatory proteins studied, five showed a significant association with PE, with three offering protective effects mainly include that C-X-C motif chemokine 1, tumor necrosis factor ligand superfamily member 14, and C-C motif chemokine 19 and two exacerbating PE risk such as STAM-binding domain and Interleukin-6 (p <0.05).
CONCLUSIONS
Our study highlights the pivotal roles played by diverse immune cell phenotypes and circulating inflammatory proteins in the pathophysiology of PE. These findings illuminate the underlying genetic mechanisms, emphasizing the criticality of immune regulation during pregnancy. Such insights could pave the way for novel intervention strategies in managing PE, potentially enhancing maternal and neonatal health outcomes.
Topics: Humans; Female; Pre-Eclampsia; Pregnancy; Genome-Wide Association Study; Genetic Predisposition to Disease; Mendelian Randomization Analysis; Phenotype; Polymorphism, Single Nucleotide; Biomarkers; Adult; Inflammation
PubMed: 38873604
DOI: 10.3389/fimmu.2024.1389843 -
Chronic Diseases and Translational... Jun 2024Growth differentiation factor-15 (GDF-15) is a stress response protein and is related to cardiovascular diseases (CVD). This study aimed to investigate the association...
BACKGROUND
Growth differentiation factor-15 (GDF-15) is a stress response protein and is related to cardiovascular diseases (CVD). This study aimed to investigate the association between GDF-15 and pre-eclampsia (PE).
METHOD
The study involved 299 pregnant women, out of which 236 had normal pregnancies, while 63 participants had PE. Maternal serum levels of GDF-15 were measured by using enzyme-linked immunosorbent assay kits and then translated into multiple of median (MOM) to avoid the influence of gestational week at blood sampling. Logistic models were performed to estimate the association between GDF-15 MOM and PE, presenting as odd ratios (ORs) and 95% confidence intervals (CIs).
RESULTS
MOM of GDF-15 in PE participants was higher compared with controls (1.588 vs. 1.000, < 0.001). In the logistic model, pregnant women with higher MOM of GDF-15 (>1) had a 4.74-fold (95% CI = 2.23-10.08, < 0.001) increased risk of PE, adjusted by age, preconceptional body mass index, gravidity, and parity.
CONCLUSIONS
These results demonstrated that higher levels of serum GDF-15 were associated with PE. GDF-15 may serve as a biomarker for diagnosing PE.
PubMed: 38872765
DOI: 10.1002/cdt3.126