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1.
Sci Rep ; 12(1): 4109, 2022 03 08.
Article in English | MEDLINE | ID: covidwho-1735290

ABSTRACT

Preeclampsia and cardiovascular disease (CVD) share multiple features and risk factors. Circulating angiotensin-converting enzyme 2 (ACE2) is increased in CVD and mediates SARS-CoV-2 entry into host cells, causing COVID-19 infection. The role of ACE2 in preeclampsia pathophysiology is unknown. We hypothesized that circulating ACE2 is increased in mid-pregnancy in women later developing preeclampsia. We included 296 women later developing preeclampsia (cases) and 333 women with a continuous healthy pregnancy (controls). Circulating ACE2 was measured with an immunoassay based on proximity extension assay technology, with levels being expressed as relative quantification on a log2 scale. Median (interquartile range) ACE2 levels were higher in cases than in controls; 3.84 (3.50-4.24) vs. 3.72 (3.45-4.04), p = 0.002. Adjusted logistic regression models showed a 60% increased risk for later development of preeclampsia with one unit elevation of ACE2 (adjusted odds ratio (aOR) 1.60, 95% confidence intervals (CI) 1.17-2.18). Preterm preeclampsia (diagnosis before 37 gestational weeks, n = 97) seemed to have a stronger ACE2 association than term preeclampsia, n = 199 (aORs, 95% Cis 2.14, 1.15-3.96 and 1.52, 1.04-2.23, respectively). Circulating ACE2 is increased at mid-pregnancy in women later developing preeclampsia, particularly preterm preeclampsia. Thus, our finding indicates a partly shared pathophysiological pathway between preeclampsia and CVD.


Subject(s)
Angiotensin-Converting Enzyme 2/blood , Pre-Eclampsia/diagnosis , Adult , Body Mass Index , Cardiovascular Diseases/complications , Cardiovascular Diseases/pathology , Case-Control Studies , Female , Gestational Age , Hospitals, University , Humans , Logistic Models , Odds Ratio , Pre-Eclampsia/pathology , Pregnancy , Risk Factors , Sweden
2.
Am J Obstet Gynecol ; 226(2S): S844-S866, 2022 02.
Article in English | MEDLINE | ID: covidwho-1705227

ABSTRACT

Preeclampsia is one of the "great obstetrical syndromes" in which multiple and sometimes overlapping pathologic processes activate a common pathway consisting of endothelial cell activation, intravascular inflammation, and syncytiotrophoblast stress. This article reviews the potential etiologies of preeclampsia. The role of uteroplacental ischemia is well-established on the basis of a solid body of clinical and experimental evidence. A causal role for microorganisms has gained recognition through the realization that periodontal disease and maternal gut dysbiosis are linked to atherosclerosis, thus possibly to a subset of patients with preeclampsia. The recent reports indicating that SARS-CoV-2 infection might be causally linked to preeclampsia are reviewed along with the potential mechanisms involved. Particular etiologic factors, such as the breakdown of maternal-fetal immune tolerance (thought to account for the excess of preeclampsia in primipaternity and egg donation), may operate, in part, through uteroplacental ischemia, whereas other factors such as placental aging may operate largely through syncytiotrophoblast stress. This article also examines the association between gestational diabetes mellitus and maternal obesity with preeclampsia. The role of autoimmunity, fetal diseases, and endocrine disorders is discussed. A greater understanding of the etiologic factors of preeclampsia is essential to improve treatment and prevention.


Subject(s)
Pre-Eclampsia/etiology , Pre-Eclampsia/physiopathology , Female , Humans , Pregnancy
3.
Nurs Womens Health ; 26(2): 152-160, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1693059

ABSTRACT

Preeclampsia is a condition of pregnancy that is associated with high morbidity and mortality rates. Individuals diagnosed with preeclampsia have an increased chance of developing depression during pregnancy and in the postpartum period. This ultimately increases the risk for negative physical and emotional outcomes. A review of the etiology, pathophysiology, symptomatology, and risk factors for preeclampsia and depression, as well as the impact of COVID-19, can improve outcomes by helping nurses provide evidence-based holistic care. This article focuses on providing enhanced knowledge to help nurses identify the psychosocial aspects of preeclampsia and advocate for appropriate mental health assessment and intervention for affected individuals.


Subject(s)
COVID-19 , Depression, Postpartum , Pre-Eclampsia , COVID-19/complications , Depression/complications , Female , Humans , Postpartum Period , Pre-Eclampsia/psychology , Pregnancy
5.
Biochim Biophys Acta Mol Basis Dis ; 1868(3): 166321, 2022 03 01.
Article in English | MEDLINE | ID: covidwho-1670191

ABSTRACT

SARS-CoV-2 causes coronavirus disease 2019 (COVID-19) also in pregnant women. Infection in pregnancy leads to maternal and placental functional alterations. Pregnant women with vascular defects such as preeclampsia show high susceptibility to SARS-CoV-2 infection by undefined mechanisms. Pregnant women infected with SARS-CoV-2 show higher rates of preterm birth and caesarean delivery, and their placentas show signs of vasculopathy and inflammation. It is still unclear whether the foetus is affected by the maternal infection with this virus and whether maternal infection associates with postnatal affections. The SARS-CoV-2 infection causes oxidative stress and activation of the immune system leading to cytokine storm and next tissue damage as seen in the lung. The angiotensin-converting-enzyme 2 expression is determinant for these alterations in the lung. Since this enzyme is expressed in the human placenta, SARS-CoV-2 could infect the placenta tissue, although reported to be of low frequency compared with maternal lung tissue. Early-onset preeclampsia (eoPE) shows higher expression of ADAM17 (a disintegrin and metalloproteinase 17) causing an imbalanced renin-angiotensin system and endothelial dysfunction. A similar mechanism seems to potentially account for SARS-CoV-2 infection. This review highlights the potentially common characteristics of pregnant women with eoPE with those with COVID-19. A better understanding of the mechanisms of SARS-CoV-2 infection and its impact on the placenta function is determinant since eoPE/COVID-19 association may result in maternal metabolic alterations that might lead to a potential worsening of the foetal programming of diseases in the neonate, young, and adult.


Subject(s)
COVID-19/physiopathology , COVID-19/virology , Oxidative Stress/physiology , Pre-Eclampsia/physiopathology , Pre-Eclampsia/virology , Animals , Female , Humans , Pregnancy , SARS-CoV-2/pathogenicity
6.
Cell Rep Med ; 3(1): 100490, 2022 01 18.
Article in English | MEDLINE | ID: covidwho-1665525

ABSTRACT

Neurofilament light (NFL) is a promising circulating biomarker in preeclampsia and COVID-19, even without evident neurological complications. Several pathways might contribute to the elevated serum NFL levels seen in both pathologies. Future studies will determine whether NFL is a long COVID marker and delineate NFL's role in COVID-19-associated preeclampsia.


Subject(s)
COVID-19/blood , COVID-19/epidemiology , Neurofilament Proteins/blood , Pre-Eclampsia/blood , Pre-Eclampsia/epidemiology , SARS-CoV-2 , Biomarkers/blood , COVID-19/virology , Comorbidity , Female , Humans , Incidence , Pregnancy
7.
Ceska Gynekol ; 86(6): 410-413, 2021.
Article in English | MEDLINE | ID: covidwho-1638650

ABSTRACT

OBJECTIVE: To summarize information about possible effects of covid-19 on intrauterine fetal death and present three cases of intrauterine fetal death in women with recent covid-19 infection. METHODS: Review of available information about pregnancy with covid-19 and comparison with own observation of cases during spring 2021. CONCLUSION: Covid-19 influences risk of intrauterine fetal death, preeclampsia/eclampsia or HELLP syndrome. Coagulation changes and drop of platelets is considered as one of the causes of intrauterine fetal death due to fetal vascular malperfusion.


Subject(s)
COVID-19 , HELLP Syndrome , Pre-Eclampsia , Female , Fetal Death/etiology , Humans , Pregnancy , Risk Factors , SARS-CoV-2
10.
Front Immunol ; 12: 775168, 2021.
Article in English | MEDLINE | ID: covidwho-1555043

ABSTRACT

COVID-19 is characterized by virus-induced injury leading to multi-organ failure, together with inflammatory reaction, endothelial cell (EC) injury, and prothrombotic coagulopathy with thrombotic events. Complement system (C) via its cross-talk with the contact and coagulation systems contributes significantly to the severity and pathological consequences due to SARS-CoV-2 infection. These immunopathological mechanisms overlap in COVID-19 and pre-eclampsia (PE). Thus, mothers contracting SARS-CoV-2 infection during pregnancy are more vulnerable to developing PE. SARS-CoV-2 infection of ECs, via its receptor ACE2 and co-receptor TMPRSS2, can provoke endothelial dysfunction and disruption of vascular integrity, causing hyperinflammation and hypercoagulability. This is aggravated by bradykinin increase due to inhibition of ACE2 activity by the virus. C is important for the progression of normal pregnancy, and its dysregulation can impact in the form of PE-like syndrome as a consequence of SARS-CoV-2 infection. Thus, there is also an overlap between treatment regimens of COVID-19 and PE. C inhibitors, especially those targeting C3 or MASP-2, are exciting options for treating COVID-19 and consequent PE. In this review, we examine the role of C, contact and coagulation systems as well as endothelial hyperactivation with respect to SARS-CoV-2 infection during pregnancy and likely development of PE.


Subject(s)
COVID-19/immunology , Complement System Proteins/immunology , Pre-Eclampsia/immunology , Pregnancy Complications, Infectious/immunology , COVID-19/drug therapy , COVID-19/physiopathology , Complement Inactivator Proteins/therapeutic use , Endothelium/immunology , Female , Humans , Pre-Eclampsia/physiopathology , Pre-Eclampsia/prevention & control , Pregnancy , Pregnancy Complications, Infectious/drug therapy , Pregnancy Complications, Infectious/physiopathology , SARS-CoV-2 , Thrombosis/immunology
11.
PLoS Med ; 18(11): e1003857, 2021 11.
Article in English | MEDLINE | ID: covidwho-1542163

ABSTRACT

BACKGROUND: To the best of our knowledge, no study has exhaustively evaluated the association between maternal morbidities and Coronavirus Disease 2019 (COVID-19) during the first wave of the pandemic in pregnant women. We investigated, in natural conceptions and assisted reproductive technique (ART) pregnancies, whether maternal morbidities were more frequent in pregnant women with COVID-19 diagnosis compared to pregnant women without COVID-19 diagnosis during the first wave of the COVID-19 pandemic. METHODS AND FINDINGS: We conducted a retrospective analysis of prospectively collected data in a national cohort of all hospitalizations for births ≥22 weeks of gestation in France from January to June 2020 using the French national hospitalization database (PMSI). Pregnant women with COVID-19 were identified if they had been recorded in the database using the ICD-10 (International Classification of Disease) code for presence of a hospitalization for COVID-19. A total of 244,645 births were included, of which 874 (0.36%) in the COVID-19 group. Maternal morbidities and adverse obstetrical outcomes among those with or without COVID-19 were analyzed with a multivariable logistic regression model adjusted on patient characteristics. Among pregnant women, older age (31.1 (±5.9) years old versus 30.5 (±5.4) years old, respectively, p < 0.001), obesity (0.7% versus 0.3%, respectively, p < 0.001), multiple pregnancy (0.7% versus 0.4%, respectively, p < 0.001), and history of hypertension (0.9% versus 0.3%, respectively, p < 0.001) were more frequent with COVID-19 diagnosis. Active smoking (0.2% versus 0.4%, respectively, p < 0.001) and primiparity (0.3% versus 0.4%, respectively, p < 0.03) were less frequent with COVID-19 diagnosis. Frequency of ART conception was not different between those with and without COVID-19 diagnosis (p = 0.28). When compared to the non-COVID-19 group, women in the COVID-19 group had a higher frequency of admission to ICU (5.9% versus 0.1%, p < 0.001), mortality (0.2% versus 0.005%, p < 0.001), preeclampsia/eclampsia (4.8% versus 2.2%, p < 0.001), gestational hypertension (2.3% versus 1.3%, p < 0.03), postpartum hemorrhage (10.0% versus 5.7%, p < 0.001), preterm birth at <37 weeks of gestation (16.7% versus 7.1%, p < 0.001), <32 weeks of gestation (2.2% versus 0.8%, p < 0.001), <28 weeks of gestation (2.4% versus 0.8%, p < 0.001), induced preterm birth (5.4% versus 1.4%, p < 0.001), spontaneous preterm birth (11.3% versus 5.7%, p < 0.001), fetal distress (33.0% versus 26.0%, p < 0.001), and cesarean section (33.0% versus 20.2%, p < 0.001). Rates of pregnancy terminations ≥22 weeks of gestation, stillbirths, gestational diabetes, placenta praevia, and placenta abruption were not significantly different between the COVID-19 and non-COVID-19 groups. The number of venous thromboembolic events was too low to perform statistical analysis. A limitation of this study relies in the possibility that asymptomatic infected women were not systematically detected. CONCLUSIONS: We observed an increased frequency of pregnant women with maternal morbidities and diagnosis of COVID-19 compared to pregnant women without COVID-19. It appears essential to be aware of this, notably in populations at known risk of developing a more severe form of infection or obstetrical morbidities and in order for obstetrical units to better inform pregnant women and provide the best care. Although causality cannot be determined from these associations, these results may be in line with recent recommendations in favor of vaccination for pregnant women.


Subject(s)
COVID-19/epidemiology , Cesarean Section/statistics & numerical data , Pandemics , Pregnancy Complications/epidemiology , Pregnancy Outcome , Premature Birth/epidemiology , Adult , Diabetes, Gestational/epidemiology , Female , Fetal Distress/epidemiology , France/epidemiology , Humans , Hypertension, Pregnancy-Induced/epidemiology , Infant, Newborn , Intensive Care Units , Logistic Models , Maternal Mortality , Obesity/epidemiology , Postpartum Hemorrhage/epidemiology , Pre-Eclampsia/epidemiology , Pregnancy , Pregnant Women , Retrospective Studies , SARS-CoV-2
12.
Am J Physiol Regul Integr Comp Physiol ; 321(6): R833-R843, 2021 12 01.
Article in English | MEDLINE | ID: covidwho-1541942

ABSTRACT

Angiotensin-converting enzyme 2 (ACE2) is a membrane-bound protein containing 805 amino acids. ACE2 shows approximately 42% sequence similarity to somatic ACE but has different biochemical activities. The key role of ACE2 is to catalyze the vasoconstrictor peptide angiotensin (ANG) II to Ang-(1-7), thus regulating the two major counterbalancing pathways of the renin-angiotensin system (RAS). In this way, ACE2 plays a protective role in end-organ damage by protecting tissues from the proinflammatory actions of ANG II. The circulating RAS is activated in normal pregnancy and is essential for maintaining fluid and electrolyte homeostasis and blood pressure. Renin-angiotensin systems are also found in the conceptus. In this review, we summarize the current knowledge on the regulation and function of circulating and uteroplacental ACE2 in uncomplicated and complicated pregnancies, including those affected by preeclampsia and fetal growth restriction. Since ACE2 is the receptor for SARS-CoV-2, and COVID-19 in pregnancy is associated with more severe disease and increased risk of abnormal pregnancy outcomes, we also discuss the role of ACE2 in mediating some of these adverse consequences. We propose that dysregulation of ACE2 plays a critical role in the development of preeclampsia, fetal growth restriction, and COVID-19-associated pregnancy pathologies and suggest that human recombinant soluble ACE2 could be a novel therapeutic to treat and/or prevent these pregnancy complications.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , Placenta/enzymology , Pregnancy Complications/enzymology , Renin-Angiotensin System , Uterus/enzymology , Angiotensin-Converting Enzyme 2/therapeutic use , Animals , Blood Pressure , COVID-19/enzymology , COVID-19/physiopathology , COVID-19/virology , Female , Fetal Growth Retardation/enzymology , Fetal Growth Retardation/physiopathology , Humans , Inflammation Mediators/metabolism , Placenta/physiopathology , Pre-Eclampsia/enzymology , Pre-Eclampsia/physiopathology , Pregnancy , Pregnancy Complications/drug therapy , Pregnancy Complications/physiopathology , Pregnancy Complications, Infectious/enzymology , Pregnancy Complications, Infectious/physiopathology , Pregnancy Complications, Infectious/virology , SARS-CoV-2/pathogenicity , Uterus/physiopathology , Water-Electrolyte Balance
16.
Ultrasound Obstet Gynecol ; 59(2): 146-152, 2022 02.
Article in English | MEDLINE | ID: covidwho-1509199
17.
Am J Obstet Gynecol ; 226(2): 177-186, 2022 02.
Article in English | MEDLINE | ID: covidwho-1482415

ABSTRACT

Physiological, mechanical, and immunologic alterations in pregnancy could potentially affect the susceptibility to and the severity of COVID-19 during pregnancy. Owing to the lack of comparable incidence data and the challenges with disentangling differences in the susceptibility from different exposure risks, the data are insufficient to determine whether pregnancy increases the susceptibility to SARS-CoV-2 infection. The data support pregnancy as a risk factor for severe disease associated with COVID-19; some of the best evidence comes from the United States Centers for Disease Control and Prevention COVID-19 surveillance system, which reported that pregnant persons were more likely to be admitted to an intensive care unit, require invasive ventilation, require extracorporeal membrane oxygenation, and die than nonpregnant women of reproductive age. Although the intrauterine transmission of SARS-CoV-2 has been documented, it appears to be rare. It is possibly related to low levels of SARS-CoV-2 viremia and the decreased coexpression of angiotensin-converting enzyme 2 and transmembrane serine protease 2 needed for SARS-CoV-2 entry into cells in the placenta. Evidence is accumulating that SARS-CoV-2 infection during pregnancy is associated with a number of adverse pregnancy outcomes including preeclampsia, preterm birth, and stillbirth, especially among pregnant persons with severe COVID-19 disease. In addition to the direct impact of COVID-19 on pregnancy outcomes, there is evidence that the pandemic and its effects on healthcare systems have had adverse effects such as increased stillbirths and maternal deaths on the pregnancy outcomes. These trends may represent widening disparities and an alarming reversal of recent improvements in maternal and infant health. All the 3 COVID-19 vaccines currently available in the United States can be administered to pregnant or lactating persons, with no preference for the vaccine type. Although the safety data in pregnancy are rapidly accumulating and no safety signals in pregnancy have been detected, additional information about the birth outcomes, particularly among persons vaccinated earlier in pregnancy, are needed.


Subject(s)
COVID-19 Vaccines/therapeutic use , COVID-19/epidemiology , Pre-Eclampsia/epidemiology , Pregnancy Complications, Infectious/epidemiology , Premature Birth/epidemiology , Stillbirth/epidemiology , COVID-19/physiopathology , COVID-19/prevention & control , COVID-19/therapy , Disease Susceptibility , Female , Healthcare Disparities , Humans , Infectious Disease Transmission, Vertical , Pregnancy , Pregnancy Complications, Infectious/physiopathology , Pregnancy Complications, Infectious/prevention & control , Pregnancy Complications, Infectious/therapy , Risk Factors , SARS-CoV-2 , Severity of Illness Index
18.
Curationis ; 44(1): e1-e8, 2021 Sep 21.
Article in English | MEDLINE | ID: covidwho-1478192

ABSTRACT

BACKGROUND: Preeclampsia is one of the causes of maternal deaths and is also responsible for complications such as premature births worldwide. In South Africa, hypertensive disorders cause 14% of all maternal deaths. Evidence indicates that it may be beneficial to empower women to monitor their blood pressure (BP) in the comfort of their homes. OBJECTIVES: The purpose of this study was to explore and describe preeclampsia patients' knowledge and attitudes towards the self-monitoring of their BP. METHOD: An exploratory, descriptive and contextual qualitative research study was conducted. Fourteen preeclampsia patients were purposively sampled and participated in the study. In-depth semi-structured interviews were used to collect data. Data were analysed using the thematic analytic approach. RESULTS: The knowledge and attitudes towards the self-monitoring of blood pressure (SMBP) were explored. Four themes emerged, namely understanding of hypertension disorders during pregnancy, openness on self-monitoring at home, its hindrances and benefits. The participants portrayed limited understanding and knowledge of preeclampsia, yet they had positive attitudes towards monitoring BP themselves and were open and willing to do self-monitoring at home. CONCLUSION: The use of SMBP may relieve overcrowding in public healthcare institutions. Encouraging patients to participate in self-monitoring could promote active participation and a positive outlook on their pregnancies. The unavailability and unaffordability of the equipment may pose a challenge to women with a low socioeconomic status.


Subject(s)
Hypertension , Pre-Eclampsia , Attitude , Blood Pressure , Female , Humans , Pregnancy , Qualitative Research
19.
J Obstet Gynaecol Can ; 44(2): 193-195, 2022 02.
Article in English | MEDLINE | ID: covidwho-1458741

ABSTRACT

BACKGROUND: Hypertension, proteinuria, and hepatic dysfunction have been described as manifestations of coronavirus disease 2019 (COVID-19) and are generally accepted as poor prognostic factors. However, these same findings can also occur in pregnant women with preeclampsia, thus creating a diagnostic challenge. CASE: We report a case of COVID-19 infection in an otherwise healthy pregnant patient with secondary hypertension, proteinuria, and significant hepatic dysfunction. Maternal placental growth factor (PlGF) testing was used to rule out preeclampsia. The patient received supportive care and improved significantly. She went on to have a spontaneous vaginal term delivery of a healthy male baby. CONCLUSION: COVID-19 infection in pregnancy may present as preeclampsia-like syndrome. PlGF testing can be used to differentiate preeclampsia from COVID-19 and facilitate appropriate management.


Subject(s)
COVID-19 , Pre-Eclampsia , Biomarkers , Female , Humans , Male , Placenta Growth Factor , Pre-Eclampsia/diagnosis , Pregnancy , SARS-CoV-2 , Vascular Endothelial Growth Factor Receptor-1
20.
PLoS One ; 16(3): e0247782, 2021.
Article in English | MEDLINE | ID: covidwho-1456064

ABSTRACT

OBJECTIVE: To evaluate the effect of aspirin dose on the incidence of all gestational age preeclampsia and preterm preeclampsia. DATA SOURCES: Electronic databases (Cochrane, PubMed, Scopus, ClinicalTrials.gov and the Web of Science) were searched for articles published between January 1985 and March 2019 with no language restrictions. METHODS: We followed the PRIMSA guidelines and utilized Covidence software. Articles were screened by 2 independent reviewers, with discrepancies settled by an independent 3rd party. Study selection criteria were randomized trials comparing aspirin for prevention of all gestational age and preterm preeclampsia to placebo or no antiplatelet treatment in women aged 15-55 years with moderate or high-risk factors according to the list of risk factors from American College of Obstetricians and Gynecologists and United States Preventive Services Task Force guidelines. The quality of trials was assessed using the Cochrane risk of bias tool. The data were pooled using a random-effects meta-analysis comparing aspirin at doses of <81, 81, 100, and 150 mg. Pre-specified outcomes were all gestational age and preterm preeclampsia. RESULTS: Of 1,609 articles screened, 23 randomized trials, which included 32,370 women, fulfilled the inclusion criteria. In preterm preeclampsia, women assigned at random to 150 mg experienced a significant 62% reduction in risk of preterm preeclampsia (RR = 0.38; 95% CI: 0.20-0.72; P = 0.011). Aspirin doses <150 mg produced no significant reductions. The number needed to treat with 150 mg of aspirin was 39 (95% CI: 23-100). There was a maximum 30% reduction in risk of all gestational age preeclampsia at all aspirin doses. CONCLUSIONS: In this meta-analysis, based on indirect comparisons, aspirin at a dose greater than the current, recommended 81 mg was associated with the highest reduction in preterm preeclampsia. Our meta-analysis is limited due to the deficiency of homogeneous high evidence data available in the literature to date; however, it may be prudent for clinicians to consider that the optimal aspirin dose may be higher than the current guidelines advise. Future research to compare the efficacy aspirin doses greater than 81 mg is recommended. STUDY REGISTRATION: PROSPERO, CRD42019127951 (University of York, UK; http://www.crd.york.ac.uk/PROSPERO/).


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Aspirin/administration & dosage , Pre-Eclampsia/epidemiology , Pre-Eclampsia/prevention & control , Adolescent , Adult , Dose-Response Relationship, Drug , Female , Humans , Incidence , Middle Aged , Pregnancy , Risk Factors , Young Adult
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