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American Family Physician Mar 2024Hypertensive disorders of pregnancy are a major contributor to maternal morbidity and mortality in the United States and include chronic and gestational hypertension,...
Hypertensive disorders of pregnancy are a major contributor to maternal morbidity and mortality in the United States and include chronic and gestational hypertension, preeclampsia, HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome, eclampsia, and chronic hypertension with superimposed preeclampsia. For patients with chronic hypertension, oral antihypertensive therapy should be initiated or titrated at a blood pressure threshold of 140/90 mm Hg or greater. Gestational hypertension and preeclampsia without severe features can be managed with blood pressure monitoring, laboratory testing for disease progression, antenatal testing for fetal well-being, and delivery at 37 weeks' gestation. The use of antihypertensive drugs to control nonsevere hypertension in the setting of gestational hypertension and preeclampsia does not improve outcomes and is not recommended. Antihypertensive therapy should be initiated expeditiously for acute-onset severe hypertension to prevent hemorrhagic stroke. Preeclampsia with severe features requires immediate stabilization and inpatient treatment with magnesium sulfate for seizure prophylaxis and antenatal corticosteroids (if preterm). Patients in the preterm period should receive antenatal corticosteroids without delaying delivery to complete courses. Hypertensive disorders of pregnancy can worsen or initially present after delivery and account for up to 44% of pregnancy-related deaths in the first six days postpartum. Patients should be monitored closely in the early postpartum period. Hypertensive disorders of pregnancy are linked to poor long-term maternal and fetal outcomes, including increased maternal lifetime risk of cardiovascular disease. Daily low-dose aspirin therapy starting at 12 to 16 weeks' gestation is safe and effective for reducing the risk of preeclampsia for patients with risk factors.
Topics: Infant, Newborn; Pregnancy; Humans; Female; Pre-Eclampsia; Hypertension, Pregnancy-Induced; Antihypertensive Agents; Hypertension; Blood Pressure; Adrenal Cortex Hormones
PubMed: 38574215
DOI: No ID Found -
BJOG : An International Journal of... Jun 2024To explore whether the association between polycystic ovary syndrome (PCOS) and pre-eclampsia depends on treated clinical hyperandrogenism and whether PCOS is associated...
OBJECTIVE
To explore whether the association between polycystic ovary syndrome (PCOS) and pre-eclampsia depends on treated clinical hyperandrogenism and whether PCOS is associated with different subtypes of pre-eclampsia.
DESIGN
Nationwide register-based cohort study.
SETTING
Sweden.
POPULATION
Nulliparous women with PCOS (n = 22 947) and non-PCOS controls (n = 115 272) giving singleton birth at ≥22 gestational weeks during 1997-2015. Treated clinical hyperandrogenism was defined as filled prescriptions of anti-androgenic drugs during 2005-2017 (n = 2301 among PCOS women).
METHODS
The risk of pre-eclampsia was estimated with conditional logistic regression, expressed as adjusted odds ratio (OR) with 95% confidence interval (CI). Adjustments were performed individually for confounders and predictors.
MAIN OUTCOME MEASURES
Overall pre-eclampsia. Early/late (delivery <34/≥34 weeks) pre-eclampsia. Pre-eclampsia with or without a small-for-gestational-age (SGA) infant.
RESULTS
Compared with controls, women with PCOS had a 29% increased risk of pre-eclampsia (predictor adjusted OR 1.29, 95% CI 1.20-1.39), with similar risk estimates for PCOS women with and without treated clinical hyperandrogenism. The association between PCOS and early pre-eclampsia seemed stronger than its association with late pre-eclampsia (predictor adjusted OR 1.64 (95% CI 1.33-2.02) and 1.26 (95% CI 1.17-1.37). Additionally, the association seemed slightly stronger between PCOS and pre-eclampsia in women with an SGA infant than without.
CONCLUSIONS
Women with PCOS face an increased risk for pre-eclampsia, especially early pre-eclampsia and pre-eclampsia with an SGA infant. We were unable to determine on the basis of available data, whether hyperandrogenism is associated with pre-eclampsia.
Topics: Humans; Female; Polycystic Ovary Syndrome; Pre-Eclampsia; Pregnancy; Adult; Sweden; Registries; Hyperandrogenism; Risk Factors; Infant, Small for Gestational Age; Cohort Studies; Case-Control Studies; Infant, Newborn; Young Adult
PubMed: 38082470
DOI: 10.1111/1471-0528.17734 -
Best Practice & Research. Clinical... Jun 2024Preeclampsia/eclampsia was first described 2000 years ago. Concepts guiding diagnosis have changed over time making longitudinal studies challenging. Similarly, concepts... (Review)
Review
Preeclampsia/eclampsia was first described 2000 years ago. Concepts guiding diagnosis have changed over time making longitudinal studies challenging. Similarly, concepts of pathophysiology have evolved from eclampsia as a pregnancy seizure disorder to preeclampsia as a hypertensive and renal disorder to our current concept of a preeclampsia as a pregnancy specific, multisystemic inflammatory disorder. Although preeclampsia is pregnancy specific and many pathophysiologic findings begin to resolve with delivery, its impact extends beyond pregnancy. The risk of cardiovascular and neurological disease is increased after pregnancy in women who have had preeclampsia. The disorder is not a disease, but a syndrome and emerging data indicate multiple pathways to the syndrome. It is likely that our failure to have a major impact on prediction and prevention despite a large increase in understanding is due to the existence of multiple subtypes of preeclampsia. This concept should guide future research.
Topics: Humans; Female; Pregnancy; Pre-Eclampsia; Risk Factors; Eclampsia
PubMed: 38490067
DOI: 10.1016/j.bpobgyn.2024.102480 -
Best Practice & Research. Clinical... Feb 2024Preeclampsia is a major cause of maternal and perinatal morbidity and mortality. It is important to identify women who are at high risk of developing this disorder in... (Review)
Review
Preeclampsia is a major cause of maternal and perinatal morbidity and mortality. It is important to identify women who are at high risk of developing this disorder in their first trimester of pregnancy to allow timely therapeutic intervention. The use of low-dose aspirin initiated before 16 weeks of gestation can significantly reduce the rate of preterm preeclampsia by 62 %. Effective screening recommended by the Fetal Medicine Foundation (FMF) consists of a combination of maternal risk factors, mean arterial pressure, uterine artery pulsatility index (UtA-PI) and placental growth factor (PLGF). The current model has detection rates of 90 %, 75 %, and 41 % for early, preterm, and term preeclampsia, respectively at 10 % false-positive rate. Similar risk assessment can be performed during the second trimester in all pregnant women irrespective of first trimester screening results. The use of PLGF, UtA-PI, sFlt-1 combined with other investigative tools are part of risk assessment.
Topics: Infant, Newborn; Pregnancy; Female; Humans; Pre-Eclampsia; Placenta Growth Factor; Gestational Age; Pregnancy Trimester, First; Aspirin; Biomarkers; Uterine Artery
PubMed: 38056380
DOI: 10.1016/j.bpobgyn.2023.102436 -
BJOG : An International Journal of... Mar 2024To report the predictive performance for preterm birth (PTB) of the Fetal Medicine Foundation (FMF) triple test and National Institute for health and Care Excellence...
OBJECTIVE
To report the predictive performance for preterm birth (PTB) of the Fetal Medicine Foundation (FMF) triple test and National Institute for health and Care Excellence (NICE) guidelines used to screen for pre-eclampsia and examine the impact of aspirin in the prevention of PTB.
DESIGN
Secondary analysis of data from the SPREE study and the ASPRE trial.
SETTING
Multicentre studies.
POPULATION
In SPREE, women with singleton pregnancies had screening for preterm pre-eclampsia at 11-13 weeks of gestation by the FMF method and NICE guidelines. There were 16 451 pregnancies that resulted in delivery at ≥24 weeks of gestation and these data were used to derive the predictive performance for PTB of the two methods of screening. The results from the ASPRE trial were used to examine the effect of aspirin in the prevention of PTB in the population from SPREE.
METHODS
Comparison of performance of FMF method and NICE guidelines for pre-eclampsia in the prediction of PTB and use of aspirin in prevention of PTB.
MAIN OUTCOME MEASURE
Spontaneous PTB (sPTB), iatrogenic PTB for pre-eclampsia (iPTB-PE) and iatrogenic PTB for reasons other than pre-eclampsia (iPTB-noPE).
RESULTS
Estimated incidence rates of sPTB, iPTB-PE and iPTB-noPE were 3.4%, 0.8% and 1.6%, respectively. The corresponding detection rates were 17%, 82% and 25% for the triple test and 12%, 39% and 19% for NICE guidelines, using the same overall screen positive rate of 10.2%. The estimated proportions prevented by aspirin were 14%, 65% and 0%, respectively.
CONCLUSION
Prediction of sPTB and iPTB-noPE by the triple test was poor and poorer by the NICE guidelines. Neither sPTB nor iPTB-noPE was reduced substantially by aspirin.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Aspirin; Biomarkers; Iatrogenic Disease; Placenta Growth Factor; Pre-Eclampsia; Pregnancy Trimester, First; Premature Birth; Uterine Artery; Clinical Trials as Topic
PubMed: 37749709
DOI: 10.1111/1471-0528.17673 -
BJOG : An International Journal of... Jan 2024Investigate cost-effectiveness of first trimester pre-eclampsia screening using the Fetal Medicine Foundation (FMF) algorithm and targeted aspirin prophylaxis in... (Observational Study)
Observational Study
OBJECTIVE
Investigate cost-effectiveness of first trimester pre-eclampsia screening using the Fetal Medicine Foundation (FMF) algorithm and targeted aspirin prophylaxis in comparison with standard care.
DESIGN
Retrospective observational study.
SETTING
London tertiary hospital.
POPULATION
5957 pregnancies screened for pre-eclampsia using the National Institute for Health and Care Excellence (NICE) method.
METHODS
Differences in pregnancy outcomes between those who developed pre-eclampsia, term pre-eclampsia and preterm pre-eclampsia were compared by the Kruskal-Wallis and Chi-square tests. The FMF algorithm was applied retrospectively to the cohort. A decision analytic model was used to estimate costs and outcomes for pregnancies screened using NICE and those screened using the FMF algorithm. The decision point probabilities were calculated using the included cohort.
MAIN OUTCOME MEASURES
Incremental healthcare costs and QALY gained per pregnancy screened.
RESULTS
Of 5957 pregnancies, 12.8% and 15.9% were screen-positive for development of pre-eclampsia using the NICE and FMF methods, respectively. Of those who were screen-positive by NICE recommendations, aspirin was not prescribed in 25%. Across the three groups, namely, pregnancies without pre-eclampsia, term pre-eclampsia and preterm pre-eclampsia there was a statistically significant trend in rates of emergency caesarean (respectively 21%, 43% and 71.4%; P < 0.001), admission to neonatal intensive care unit (NICU) (5.9%, 9.4%, 41%; P < 0.001) and length of stay in NICU. The FMF algorithm was associated with seven fewer cases of preterm pre-eclampsia, cost saving of £9.06 and QALY gain of 0.00006/pregnancy screened.
CONCLUSIONS
Using a conservative approach, application of the FMF algorithm achieved clinical benefit and an economic cost saving.
Topics: Pregnancy; Female; Infant, Newborn; Humans; Aspirin; Pregnancy Trimester, First; Pre-Eclampsia; Cohort Studies; Retrospective Studies; Cost-Benefit Analysis
PubMed: 37431533
DOI: 10.1111/1471-0528.17598 -
Lancet (London, England) Jul 2023Pre-eclampsia is a leading cause of maternal and perinatal mortality. Evidence regarding interventions in a low-income or middle-income setting is scarce. We aimed to... (Randomized Controlled Trial)
Randomized Controlled Trial
Planned delivery or expectant management for late preterm pre-eclampsia in low-income and middle-income countries (CRADLE-4): a multicentre, open-label, randomised controlled trial.
BACKGROUND
Pre-eclampsia is a leading cause of maternal and perinatal mortality. Evidence regarding interventions in a low-income or middle-income setting is scarce. We aimed to evaluate whether planned delivery between 34 and 36 weeks' gestation can reduce maternal mortality and morbidity without increasing perinatal complications in India and Zambia.
METHODS
In this parallel-group, multicentre, open-label, randomised controlled trial, we compared planned delivery versus expectant management in women with pre-eclampsia from 34 to 36 weeks' gestation. Participants were recruited from nine hospitals and referral facilities in India and Zambia and randomly assigned to planned delivery or expectant management in a 1:1 ratio by a secure web-based randomisation facility hosted by MedSciNet. Randomisation was stratified by centre and minimised by parity, single-fetus pregnancy or multi-fetal pregnancy, and gestational age. The primary maternal outcome was a composite of maternal mortality or morbidity with a superiority hypothesis. The primary perinatal outcome was a composite of one or more of: stillbirth, neonatal death, or neonatal unit admission of more than 48 h with a non-inferiority hypothesis (margin of 10% difference). Analyses were by intention to treat, with an additional per-protocol analysis for the perinatal outcome. The trial was prospectively registered with ISRCTN, 10672137. The trial is closed to recruitment and all follow-up has been completed.
FINDINGS
Between Dec 19, 2019, and March 31, 2022, 565 women were enrolled. 284 women (282 women and 301 babies analysed) were allocated to planned delivery and 281 women (280 women and 300 babies analysed) were allocated to expectant management. The incidence of the primary maternal outcome was not significantly different in the planned delivery group (154 [55%]) compared with the expectant management group (168 [60%]; adjusted risk ratio [RR] 0·91, 95% CI 0·79 to 1·05). The incidence of the primary perinatal outcome by intention to treat was non-inferior in the planned delivery group (58 [19%]) compared with the expectant management group (67 [22%]; adjusted risk difference -3·39%, 90% CI -8·67 to 1·90; non-inferiority p<0·0001). The results from the per-protocol analysis were similar. There was a significant reduction in severe maternal hypertension (adjusted RR 0·83, 95% CI 0·70 to 0·99) and stillbirth (0·25, 0·07 to 0·87) associated with planned delivery. There were 12 serious adverse events in the planned delivery group and 21 in the expectant management group.
INTERPRETATION
Clinicians can safely offer planned delivery to women with late preterm pre-eclampsia, in a low-income or middle-income country. Planned delivery reduces stillbirth, with no increase in neonatal unit admissions or neonatal morbidity and reduces the risk of severe maternal hypertension. Planned delivery from 34 weeks' gestation should therefore be considered as an intervention to reduce pre-eclampsia associated mortality and morbidity in these settings.
FUNDING
UK Medical Research Council and Indian Department of Biotechnology.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Pre-Eclampsia; Stillbirth; Watchful Waiting; Developing Countries; Premature Birth; Perinatal Death; Hypertension
PubMed: 37393919
DOI: 10.1016/S0140-6736(23)00688-8 -
Critical Care Nursing QuarterlyHypertension has been shown to have long-term cardiovascular effects if left untreated. Hypertension also has been shown to affect women during pregnancy, which can be...
Hypertension has been shown to have long-term cardiovascular effects if left untreated. Hypertension also has been shown to affect women during pregnancy, which can be detrimental not only to the patient but also to the fetus. Early identification and treatment are paramount to prevent adverse outcomes. This article details the epidemiology, clinical presentation, diagnosis, and treatment of essential hypertension in women, gestational hypertension, preeclampsia, and eclampsia.
Topics: Pregnancy; Female; Humans; Hypertension; Pre-Eclampsia; Hypertension, Pregnancy-Induced
PubMed: 37684733
DOI: 10.1097/CNQ.0000000000000480 -
Postgraduate Medical Journal Aug 2023Observational studies have shown an association between age at menarche (AAM) and the risk of gynecological diseases. However, the causality cannot be determined due to...
BACKGROUND
Observational studies have shown an association between age at menarche (AAM) and the risk of gynecological diseases. However, the causality cannot be determined due to residual confounding.
METHODS
We conducted a Mendelian randomization (MR) study to evaluate the causal effect of AAM on several gynecological diseases, including endometriosis, female infertility, pre-eclampsia or eclampsia, uterine fibroids, breast cancer, ovarian cancer, and endometrial cancer. Single nucleotide polymorphisms were used as genetic instruments. The inverse variance weighted method was used as the primary approach and several other MR models were conducted for comparison. Cochran's Q test, Egger's intercept test, and leave-one-out analysis were conducted for sensitivity analysis. Radial MR analysis was conducted when detecting the existence of heterogeneity.
RESULTS
After Bonferroni correction and thorough sensitivity analysis, we observed a robust causal effect of AAM on endometrial cancer (odds ratio: 0.80; 95% confidence interval: 0.72-0.89; P = 4.61 × 10-5) and breast cancer (odds ratio: 0.94; 95% confidence interval: 0.90-0.98; P = .003). Sensitivity analysis found little evidence of horizontal pleiotropy. The inverse variance weighted method also detected weak evidence of associations of AAM with endometriosis and pre-eclampsia or eclampsia.
CONCLUSIONS
This MR study demonstrated a causal effect of AAM on gynecological diseases, especially for breast cancer and endometrial cancer, which indicates AAM might be a promising index to use for disease screening and prevention in clinical practice. Key messages What is already known on this topic - Observational studies have reported associations between age at menarche (AAM) and a variety of gynecological diseases but the causality has not been determined. What this study adds - This Mendelian randomization study demonstrated that AAM causally affects the risk of breast cancer and endometrial cancer. How this study might affect research, practice, or policy - The findings of our study imply that AAM could be a candidate marker for early screening of populations at higher risk of breast cancer and endometrial cancer.
Topics: Pregnancy; Humans; Female; Endometriosis; Eclampsia; Menarche; Mendelian Randomization Analysis; Pre-Eclampsia; Breast Neoplasms; Endometrial Neoplasms; Outcome Assessment, Health Care; Genome-Wide Association Study
PubMed: 37302123
DOI: 10.1093/postmj/qgad023 -
International Journal of Molecular... Aug 2023Endometrial decidualization is a uterine process essential for spiral artery remodeling, embryo implantation, and trophoblast invasion. Defects in endometrial... (Review)
Review
Endometrial decidualization is a uterine process essential for spiral artery remodeling, embryo implantation, and trophoblast invasion. Defects in endometrial decidualization and spiral artery remodeling are important contributing factors in preeclampsia, a major disorder in pregnancy. Atrial natriuretic peptide (ANP) is a cardiac hormone that regulates blood volume and pressure. ANP is also generated in non-cardiac tissues, such as the uterus and placenta. In recent human genome-wide association studies, multiple loci with genes involved in natriuretic peptide signaling are associated with gestational hypertension and preeclampsia. In cellular experiments and mouse models, uterine ANP has been shown to stimulate endometrial decidualization, increase TNF-related apoptosis-inducing ligand expression and secretion, and enhance apoptosis in arterial smooth muscle cells and endothelial cells. In placental trophoblasts, ANP stimulates adenosine 5'-monophosphate-activated protein kinase and the mammalian target of rapamycin complex 1 signaling, leading to autophagy inhibition and protein kinase N3 upregulation, thereby increasing trophoblast invasiveness. ANP deficiency impairs endometrial decidualization and spiral artery remodeling, causing a preeclampsia-like phenotype in mice. These findings indicate the importance of natriuretic peptide signaling in pregnancy. This review discusses the role of ANP in uterine biology and potential implications of impaired ANP signaling in preeclampsia.
Topics: Humans; Animals; Signal Transduction; Natriuretic Peptides; Pre-Eclampsia; Uterus; Hypertension, Pregnancy-Induced; Placenta; Serine Endopeptidases
PubMed: 37569683
DOI: 10.3390/ijms241512309