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BJOG : An International Journal of... Nov 2023The objective of the study was to investigate the role of genetic variants in complement proteins in pre-eclampsia.
OBJECTIVE
The objective of the study was to investigate the role of genetic variants in complement proteins in pre-eclampsia.
DESIGN
In a case-control study involving 609 cases and 2092 controls, five rare variants in complement factor H (CFH) were identified in women with severe and complicated pre-eclampsia. No variants were identified in controls.
SETTING
Pre-eclampsia is a leading cause of maternal and fetal morbidity and mortality. Immune maladaptation, in particular, complement activation that disrupts maternal-fetal tolerance leading to placental dysfunction and endothelial injury, has been proposed as a pathogenetic mechanism, but this remains unproven.
POPULATION
We genotyped 609 pre-eclampsia cases and 2092 controls from FINNPEC and the national FINRISK cohorts.
METHODS
Complement-based functional and structural assays were conducted in vitro to define the significance of these five missense variants and each compared with wild type.
MAIN OUTCOME MEASURES
Secretion, expression and ability to regulate complement activation were assessed for factor H proteins harbouring the mutations.
RESULTS
We identified five heterozygous rare variants in complement factor H (L3V, R127H, R166Q, C1077S and N1176K) in seven women with severe pre-eclampsia. These variants were not identified in controls. Variants C1077S and N1176K were novel. Antigenic, functional and structural analyses established that four (R127H, R166Q, C1077S and N1176K) were deleterious. Variants R127H and C1077S were synthesised, but not secreted. Variants R166Q and N1176K were secreted normally but showed reduced binding to C3b and consequently defective complement regulatory activity. No defect was identified for L3V.
CONCLUSIONS
These results suggest that complement dysregulation due to mutations in complement factor H is among the pathophysiological mechanisms underlying severe pre-eclampsia.
Topics: Humans; Pregnancy; Female; Complement Factor H; Case-Control Studies; Placenta; Pre-Eclampsia; Genotype
PubMed: 37156755
DOI: 10.1111/1471-0528.17529 -
The Journal of Clinical Endocrinology... Feb 2024Cardiovascular disease (CVD) is the leading cause of death among women. Adverse pregnancy outcomes (APOs) are cardiovascular risk factors that are unique to women and... (Review)
Review
Cardiovascular disease (CVD) is the leading cause of death among women. Adverse pregnancy outcomes (APOs) are cardiovascular risk factors that are unique to women and include gestational diabetes (GDM) and preeclampsia. While these risk factors emerge during the reproductive years and allow for early risk reduction counseling, they are often overlooked and not elicited by providers. This mini-review focuses primarily on GDM and preeclampsia, their relationship with CVD, mechanisms by which these conditions lead to CVD, and management, pharmacological and nonpharmacological, for the clinician who is caring for a woman with a history of an APO.
Topics: Pregnancy; Female; Humans; Pregnancy Outcome; Cardiovascular Diseases; Pre-Eclampsia; Diabetes, Gestational; Risk Factors
PubMed: 37933906
DOI: 10.1210/clinem/dgad600 -
Acta Paediatrica (Oslo, Norway : 1992) Mar 2024There has been limited research about the associations between pre-eclampsia and neonatal complications in relation to gestational age. This register-based study aimed...
AIM
There has been limited research about the associations between pre-eclampsia and neonatal complications in relation to gestational age. This register-based study aimed to address that gap in our knowledge.
METHODS
We used Swedish Medical Birth Register to carry out a population-based study on primiparas with singleton pregnancies from 1999 to 2017. Descriptive statistics and logistic regressions were used to study the associations between pre-eclampsia and neonatal complications in different gestational ages. The data is presented as adjusted odds ratios (aORs) with 95% CI.
RESULTS
The study comprised 805 591 primiparas: 2.9% had mild to moderate pre-eclampsia and 1.4% had severe pre-eclampsia. Neonates born to women with pre-eclampsia had increased risks of several complications compared to those born to mothers without pre-eclampsia. After adjustment for confounding variables, the risk of being small for gestational age (aOR 5.3, CI: 5.1-5.5) and needing resuscitation (aOR 2.6, CI: 2.4-2.7) were increased. The risk of a low Apgar score and convulsions/hypoxic ischemic encephalopathy was increased at 32-41 weeks of gestation. Moreover, the overall risk of sepsis (aOR 1.9. CI: 1.8-2.1) and perinatal death (aOR 1.2, CI: 1.1-1.5) was also increased.
CONCLUSION
Compared with infants of mothers without pre-eclampsia, those exposed to pre-eclampsia had higher risks of all the studied neonatal complications.
Topics: Pregnancy; Infant, Newborn; Infant; Female; Humans; Pre-Eclampsia; Gestational Age; Perinatal Death; Infant, Small for Gestational Age; Mothers; Infant, Newborn, Diseases
PubMed: 38140818
DOI: 10.1111/apa.17080 -
Journal of Reproductive Immunology Jun 2024Pre-eclampsia (PE) is a hypertension condition that occurs exclusively during pregnancy and has the potential to impact nearly all organ systems. It is estimated to... (Review)
Review
Pre-eclampsia (PE) is a hypertension condition that occurs exclusively during pregnancy and has the potential to impact nearly all organ systems. It is estimated to complicate approximately 2-8% of pregnancies worldwide. PE is a prominent medical disorder that poses a significant risk to pregnant mothers and their infants. This review commences by giving the most up-to- date concepts about the pathophysiology of PE. The condition involves atypical infiltration of trophoblast cells into the spiral arteries of the decidua and myometrium, resulting in an insufficient establishment of proper blood flow between the uterus and placenta. The aberrant activation of natural killer (NK) cells in both the peripheral blood and the decidua has been identified as one of the contributing factors to the development of PE. The strong evidence for the genetic etiology of PE is provided by the association between maternal killer cell immunoglobulin-like receptor (KIR) and Human Leukocyte Antigen (HLA-C) in trophoblast cells. Recent observations provide evidence that changes in the expression of anti-angiogenic factors in the placenta are the underlying cause of the clinical symptoms associated with the condition. This review also provides a comprehensive overview of the latest advancements in understanding the underlying causes of PE. It specifically highlights the emergence of new diagnostic biomarkers and their potential implications for therapeutic interventions in managing this medical condition.
Topics: Humans; Pre-Eclampsia; Pregnancy; Female; Biomarkers; Killer Cells, Natural; Trophoblasts; Receptors, KIR; Placenta; HLA-C Antigens; Animals; Decidua
PubMed: 38555746
DOI: 10.1016/j.jri.2024.104236 -
European Heart Journal. Quality of Care... Jan 2024There is a need for further studies on the cardiovascular risk of women experiencing pre-eclampsia (PE). (Meta-Analysis)
Meta-Analysis
BACKGROUND/INTRODUCTION
There is a need for further studies on the cardiovascular risk of women experiencing pre-eclampsia (PE).
PURPOSE
To update the literature regarding the association between a history of PE and subsequent cardiovascular diseases, including cardiovascular death, coronary heart diseases, heart failure, and stroke, focusing on the trend in the effect size (ES) estimates over time.
METHODS AND RESULTS
Following PRISMA guidelines, from inception to May 2023, we performed a systematic review of PubMed, MEDLINE, Scopus, and EMBASE. Randomized, cohort, or case-control studies in English were included if fulfiling the following criteria:(i) The association between PE and subsequent cardiovascular disease was adjusted for clinically relevant variables, (ii) the presence of a control group, and (iii) at least 1 year of follow-up. Pooled adjusted ESs and 95% confidence intervals (CIs) were used as effect estimates and calculated with a random-effect model. Twenty-two studies met the inclusion criteria. PE was associated with a higher risk of cardiovascular death (ES 2.08, 95% CI 1.70-2.54, I2 56%, P < 0.00001), coronary artery diseases (ES 2.04, 95% CI 1.76-2.38, I2 87%, P < 0.00001), heart failure (ES 2.47, 95% CI 1.89-3.22, I2 83%, P < 0.00001), and stroke (ES 1.75, 95% CI 1.52-2.02, I2 72%, P < 0.00001) after adjusting for potential confounders. This risk is evident in the first 1-to-3 years of follow-up and remains significant until 39 years of follow-up.
CONCLUSIONS
Compared to women who experienced a normal pregnancy, those suffering from PE have about double the risk of lifetime cardiovascular disease.
Topics: Pregnancy; Female; Humans; Cardiovascular Diseases; Pre-Eclampsia; Risk Factors; Coronary Artery Disease; Heart Failure; Heart Disease Risk Factors; Stroke
PubMed: 37974053
DOI: 10.1093/ehjqcco/qcad065 -
International Journal of Gynaecology... Oct 2023Protein neutrophil gelatinase-associated lipocalin (NGAL) has been associated with kidney injury and inflammatory conditions. In particular, several studies have found... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Protein neutrophil gelatinase-associated lipocalin (NGAL) has been associated with kidney injury and inflammatory conditions. In particular, several studies have found an association between maternal blood and urine levels and the development of pre-eclampsia.
OBJECTIVES
To examine whether maternal blood and urine levels of NGAL are good predictors of pre-eclampsia.
SEARCH STRATEGY
The authors searched MEDLINE databases via PubMed, Embase, Scopus, Scielo, Google Scholar, PROSPERO International Prospective Register of Systematic Reviews, and the Cochrane Central Register of Controlled Trials.
SELECTION CRITERIA
The authors included case-control observational clinical studies comparing protein levels of NGAL in serum and urine in women with pre-eclampsia with uncomplicated pregnancies. Only studies where the collection of blood or urine was peformed before the occurrence of pre-eclampsia were selected.
DATA COLLECTION AND ANALYSIS
The primary outcome was the difference in NGAL levels in blood or urine between women with and without pre-eclampsia.
RESULTS
Seven studies in total were included: five studies measuring NGAL in blood and two in urine. Regarding the serum studies, 315 patients were included as cases and 540 as controls. Higher NGAL in maternal blood during all three trimesters together was associated with pre-eclampsia; the standardized mean difference was 1.15 ng/mL (95% confidence interval, 0.92-1.39; P < 0.01). Regarding the urine studies, 39 patients were included as cases and 220 as controls. There was no statistically significant difference between patients with pre-eclampsia and controls regarding urine NGAL.
CONCLUSIONS
NGAL in maternal blood is higher in patients who later develop pre-eclampsia compared with controls and could be used as a potential predicting test in the routine clinical setting.
Topics: Pregnancy; Humans; Female; Lipocalin-2; Pre-Eclampsia; Biomarkers; Acute Kidney Injury; Kidney
PubMed: 37040030
DOI: 10.1002/ijgo.14777 -
JNMA; Journal of the Nepal Medical... Nov 2023Pre-eclampsia is a pregnancy-related hypertensive disorder with maternal and neonatal complications. Many studies are done regarding the prevalence of pre-eclampsia in...
INTRODUCTION
Pre-eclampsia is a pregnancy-related hypertensive disorder with maternal and neonatal complications. Many studies are done regarding the prevalence of pre-eclampsia in Nepal but ascertaining the maternal risk factors and fetal outcomes are important. The aim of this study was to find out the prevalence of pre-eclampsia among pregnant women admitted to the Department of Obstetrics and Gynaecology of a tertiary care centre.
METHODS
A descriptive cross-sectional study was conducted among pregnant women admitted to the Department of Obstetrics and Gynaecology of a tertiary care hospital from 13 July 2023 to 29 September 2023 after obtaining ethical approval from the Institutional Review Committee. Convenience sampling method was used. Point estimate was calculated at a 95% Confidence Interval.
RESULTS
Among 5065 patient, pre-eclampsia was seen in 44 (0.87%) (0.61-1.13, 95% Confidence Interval). A total of 16 (36.36%) cases of pre-eclampsia were in the age group 25-29 years and 30 (68.18%) of them were nulliparous. A total of 38 (86.36%) of the newborns of the pre-eclamptic cases had low birth weight. The APGAR score of newborns at the 1 minute after birth was 26 (59.09%) followed by the newborns who needed re-evaluation 16 (36.36%). The APGAR score recorded at 5 minutes showed maximum newborns with normal APGAR score 40 (90.90%).
CONCLUSIONS
The prevalence of pre-eclampsia among pregnant women was found to be lower than other studies done in similar settings.
KEYWORDS
maternity; Nepal; pre-eclampsia; prevalence.
Topics: Pregnancy; Female; Infant, Newborn; Humans; Adult; Pre-Eclampsia; Pregnant Women; Tertiary Care Centers; Gynecology; Cross-Sectional Studies
PubMed: 38289744
DOI: 10.31729/jnma.8265 -
The Indian Journal of Medical Research Oct 2023Pre-eclampsia (PE), a multifactorial de novo hypertensive pregnancy disorder, is one of the leading causes of foeto-maternal morbidity and mortality. Currently,... (Review)
Review
Pre-eclampsia (PE), a multifactorial de novo hypertensive pregnancy disorder, is one of the leading causes of foeto-maternal morbidity and mortality. Currently, antihypertensive drugs are the first-line therapy for PE and evidence suggests that low-dose aspirin initiated early in high risk pregnancies may reduce the risk of development or severity of PE. However, an early prediction of this disorder remains an unmet clinical challenge. Several potential serum biomarkers associated with maternal immunoregulation and placental angiogenesis have been evaluated but are ineffective and inconsistent for early prediction. Although placental biomarkers would be more specific and sensitive in predicting the risk of PE, accessing the placenta during pregnancy is not feasible. Circulating placental exosomes (pEXO), originating from foeto-maternal interface, are being evaluated as the placenta's surrogate and the best source of non-invasive placental biomarkers. pEXO appear in the maternal circulation starting from six weeks of gestation and its dynamic biological cargo across pregnancy is associated with successful pregnancy outcomes. Therefore, monitoring changes in pEXO expression profiles could provide new insights into the prediction, diagnosis and treatment of PE. This narrative review comprehensively summarizes the available literature on the candidate predictive circulating biomarkers evaluated for PE to date. In particular, the review elucidates the current knowledge of distinct molecular signatures emanating from pEXO in pre-eclamptic women to support the discovery of novel early predictive biomarkers for effective intervention and management of the disease.
Topics: Pregnancy; Female; Humans; Placenta; Pre-Eclampsia; Exosomes; Pregnancy Outcome; Biomarkers; Hypertension
PubMed: 37987999
DOI: 10.4103/ijmr.ijmr_2143_22 -
International Journal of Gynaecology... Jan 2024To discuss the points that still challenge low- and middle-income countries (LMICs) and strategies that have been studied to help them overcome these issues. (Review)
Review
OBJECTIVE
To discuss the points that still challenge low- and middle-income countries (LMICs) and strategies that have been studied to help them overcome these issues.
METHODS
Narrative review addressing 20 years of articles concerning pre-eclampsia morbidity and mortality in LMICs. We summarized evidence-based strategies to overcome the challenges in order to reduce the pre-eclampsia impact on perinatal outcomes.
RESULTS
Pre-eclampsia is the first or second leading cause in the ranking of avoidable causes of maternal death, and approximately 16% of all maternal deaths are attributable to eclampsia and pre-eclampsia. Considering the social and economic contexts, it represents a major public health concern, and prevention and early detection of pre-eclampsia seem to be a major challenge. Reducing maternal mortality related to hypertensive disturbances depends on public policies to manage these preventable conditions. Early and continuous recognition of signs of severity related to hypertensive disorders during pregnancy and childbirth, self-monitoring of symptoms and blood pressure, as well as preventive approaches such as aspirin and calcium, and magnesium sulfate, are lifesaving procedures that have not yet reached a universal scale.
CONCLUSION
This review provides a vision of relevant points to support pregnant women in overcoming the constraints to healthcare access in LMICs, and strategies that can be applied in primary prenatal care units.
Topics: Pregnancy; Female; Humans; Pre-Eclampsia; Developing Countries; Eclampsia; Parturition; Hypertension
PubMed: 37329226
DOI: 10.1002/ijgo.14913 -
Journal of Human Hypertension Aug 2023Higher blood pressure prior to pregnancy is associated with increased risk of placental abruption, hypertension and preeclampsia, preterm delivery and fetal growth... (Review)
Review
Higher blood pressure prior to pregnancy is associated with increased risk of placental abruption, hypertension and preeclampsia, preterm delivery and fetal growth restriction. These conditions are jointly termed placental syndromes as they are characterised by impaired placentation and early placental vascularization. Placental syndromes are associated with an increased maternal risk of progression to hypertension and cardiovascular disease (CVD) in later life. Women affected by both a clinical placental syndrome and with evidence of placental maternal vascular malperfusion (MVM) have a particularly high risk of hypertension and CVD. Yet whether placental impairment and clinical syndromes are causes or consequences of higher blood pressure in women remains unclear. In this review, we address the relationship between blood pressure and maternal health in pregnancy. We conclude that there is a pressing need for studies with a range of detailed measures of cardiac and vascular structure and function taken before, during and after pregnancy to solve the 'chicken and egg' puzzle of women's blood pressure and pregnancy health, and to inform effective precision medicine prevention and treatment of both placental syndromes and chronic hypertension in women.
Topics: Pregnancy; Female; Humans; Placenta; Syndrome; Hypertension; Pre-Eclampsia; Cardiovascular Diseases; Placentation
PubMed: 36702879
DOI: 10.1038/s41371-023-00802-4