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BMC Pregnancy and Childbirth May 2024Preeclampsia (PE), an obstetric disorder, remains one of the leading causes of maternal and infant mortality worldwide. In individuals with PE, the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Preeclampsia (PE), an obstetric disorder, remains one of the leading causes of maternal and infant mortality worldwide. In individuals with PE, the coagulation-fibrinolytic system is believed to be among the most significantly impacted systems due to maternal inflammatory responses and immune dysfunction. Therefore, this systematic review and meta-analysis aimed to assess the association of prothrombin time (PT), thrombin time (TT) and activated partial thromboplastin time (APTT) levels with preeclampsia.
METHODS
This systematic review and meta-analysis was conducted in accordance with the PRISMA guidelines. Articles relevant to the study, published from July 26, 2013, to July 26, 2023, were systematically searched across various databases including PubMed, Scopus, Embase, and Hinari. The methodological quality of the articles was evaluated using the Joanna Briggs Institute critical appraisal checklist. Utilizing Stata version 14.0, a random-effects model was employed to estimate the pooled standardized mean difference (SMD) along with the respective 95% CIs. The I statistics and Cochrane Q test were utilized to assess heterogeneity, while subgroup analyses were performed to explore its sources. Furthermore, Egger's regression test and funnel plot were employed to assess publication bias among the included studies.
RESULTS
A total of 30 articles, involving 5,964 individuals (2,883 with PE and 3,081 as normotensive pregnant mothers), were included in this study. The overall pooled SMD for PT, APTT, and TT between PE and normotensive pregnant mothers were 0.97 (95% CI: 0.65-1.29, p < 0.001), 1.05 (95% CI: 0.74-1.36, p < 0.001), and 0.30 (95% CI: -0.08-0.69, p = 0.11), respectively. The pooled SMD indicates a significant increase in PT and APTT levels among PE patients compared to normotensive pregnant mothers, while the increase in TT levels among PE patients was not statistically significant.
CONCLUSIONS
The meta-analysis underscores the association between PE and prolonged PT and APTT. This suggests that evaluating coagulation parameters like PT, APTT, and TT in pregnant women could offer easily accessible and cost-effective clinical indicators for assessing PE. However, multicenter longitudinal studies are needed to evaluate their effectiveness across various gestational weeks of pregnancy.
Topics: Humans; Pregnancy; Female; Pre-Eclampsia; Partial Thromboplastin Time; Prothrombin Time; Thrombin Time; Blood Coagulation
PubMed: 38741046
DOI: 10.1186/s12884-024-06543-7 -
Journal of Psychosomatic Obstetrics and... Dec 2024To assess the impact of low-dose aspirin (LDA) on obstetrical outcomes through a meta-analysis of placebo-controlled randomized controlled trials (RCTs). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To assess the impact of low-dose aspirin (LDA) on obstetrical outcomes through a meta-analysis of placebo-controlled randomized controlled trials (RCTs).
METHODS
A systematic search of the PubMed, Cochrane Library, Web of Science and Embase databases from inception to January 2024 was conducted to identify studies exploring the role of aspirin on pregnancy, reporting obstetrical-related outcomes, including preterm birth (PTB, gestational age <37 weeks), small for gestational age (SGA), low birth weight (LBW, birthweight < 2500g), perinatal death (PND), admission to the neonatal intensive care unit (NICU), 5-min Apgar score < 7 and placental abruption. Relative risks (RRs) were estimated for the combined outcomes. Subgroup analyses were performed by risk for preeclampsia (PE), LDA dosage (<100 mg vs. ≥100 mg) and timing of onset (≤20 weeks vs. >20 weeks).
RESULTS
Forty-seven studies involving 59,124 participants were included. Compared with placebo, LDA had a more significant effect on low-risk events such as SGA, PTB and LBW. Specifically, LDA significantly reduced the risk of SGA (RR = 0.91, 95% CI: 0.87-0.95), PTB (RR = 0.93, 95% CI: 0.89-0.97) and LBW (RR = 0.94, 95% CI: 0.89-0.99). For high-risk events, LDA significantly lowered the risk of NICU admission (RR = 0.93, 95% CI: 0.87-0.99). On the other hand, LDA can significantly increase the risk of placental abruption (RR = 1.72, 95% CI: 1.23-2.43). Subgroup analyses showed that LDA significantly reduced the risk of SGA (RR = 0.86, 95% CI: 0.77-0.97), PTB (RR = 0.93, 95% CI: 0.88-0.98) and PND (RR = 0.65, 95% CI: 0.48-0.88) in pregnant women at high risk of PE, whereas in healthy pregnant women LDA did not significantly improve obstetrical outcomes, but instead significantly increased the risk of placental abruption (RR = 5.56, 95% CI: 1.92-16.11). In pregnant women at high risk of PE, LDA administered at doses ≥100 mg significantly reduced the risk of SGA (RR = 0.77, 95% CI: 0.66-0.91) and PTB (RR = 0.56, 95% CI: 0.32-0.97), but did not have a statistically significant effect on reducing the risk of NICU, PND and LBW. LDA started at ≤20 weeks significantly reduced the risk of SGA (RR = 0.76, 95% CI: 0.65-0.89) and PTB (RR = 0.56, 95% CI: 0.32-0.97).
CONCLUSIONS
To sum up, LDA significantly improved neonatal outcomes in pregnant women at high risk of PE without elevating the risk of placental abruption. These findings support LDA's clinical application in pregnant women, although further research is needed to refine dosage and timing recommendations.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Abruptio Placentae; Aspirin; Infant, Low Birth Weight; Infant, Small for Gestational Age; Pre-Eclampsia; Pregnancy Outcome; Premature Birth; Randomized Controlled Trials as Topic
PubMed: 38712869
DOI: 10.1080/0167482X.2024.2344079 -
PloS One 2024Women at increased risk of developing pre-eclampsia are advised to take a daily low-dose of aspirin from 12 weeks of pregnancy to reduce their risks. Despite the... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Women at increased risk of developing pre-eclampsia are advised to take a daily low-dose of aspirin from 12 weeks of pregnancy to reduce their risks. Despite the well-established prophylactic effect of aspirin, adherence to this therapy is low. This systematic review aimed to summarise evidence on the barriers and facilitators of adherence to low-dose aspirin to inform intervention development to support decision making and persistence with aspirin use for pre-eclampsia prevention.
MATERIALS AND METHODS
A systematic review and meta-synthesis of qualitative research was co-produced by representatives from charities, and public, clinical and academic members. Eight electronic databases (MEDLINE, PsycINFO, CINAHL, Web of Science, Scopus, EMBASE, Prospero, OpenGrey), archives of charities and professional organisations were searched (between October and November 2023 and re-run in August 2023) using predefined search terms. Studies containing qualitative components related to barriers and facilitators of adherence to low-dose aspirin during pregnancy were included. Quality assessment was performed using the Critical Appraisal Skills Programme checklist for qualitative research. A combination of the COM-B framework with phases of adherence process as defined by international taxonomy was used as the coding framework. Co-production activities were facilitated by use of 'Zoom' and 'Linoit'.
RESULTS
From a total of 3377 papers identified through our searches, five published studies and one dissertation met our inclusion criteria. Studies were published from 2019 to 2022 covering research conducted in the USA, Canada, UK, Netherlands and Australia. Barriers and facilitators to adherence were mapped to six categories of the COM-B for three phases of adherence: initiation, implementation, and discontinuation. The discontinuation phase of adherence was only mentioned by one author. Four key themes were identified relating to pregnancy: 'Insufficient knowledge', 'Necessity concerns balance', 'Access to medicine', 'Social influences', and 'Lack of Habit'.
CONCLUSIONS
The COM-B framework allowed for detailed mapping of key factors shaping different phases of adherence in behavioural change terms and now provides a solid foundation for the development of a behavioural intervention. Although potential intervention elements could be suggested based on the results of this synthesis, additional co-production work is needed to define elements and plan for the delivery of the future intervention.
TRIAL REGISTRATION
PROSPERO CRD42022359718. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022359718.
Topics: Aspirin; Humans; Pregnancy; Female; Medication Adherence; Pre-Eclampsia; Qualitative Research
PubMed: 38701053
DOI: 10.1371/journal.pone.0302720 -
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 -
Frontiers in Medicine 2024Meta-analysis focusing on the role of first-trimester neutrophil-to-lymphocyte ratio (NLR) in the prediction of preeclampsia.
OBJECTIVE
Meta-analysis focusing on the role of first-trimester neutrophil-to-lymphocyte ratio (NLR) in the prediction of preeclampsia.
DATA SOURCES
PubMed, Scopus, Web of Science, Cochrane Library, and Embase databases were queried from inception up to December 31, 2022.
STUDY ELIGIBILITY CRITERIA
The study included all types of original research that was conducted in humans and values of NLR were measured during the first trimester, among patients who later developed preeclampsia, compared to the values of control groups.
STUDY APPRAISAL AND SYNTHESIS METHODS
Two reviewers independently performed data abstraction and quality appraisal, and disagreements were resolved by consensus and, if necessary, by the opinion of a third reviewer. During the analysis, PRISMA and MOOSE guidelines were followed. All statistical analyses were made with .
RESULTS
For the research on the predictive role of NLR values in the first trimester for preeclampsia, a total of 6 studies were selected for analysis, covering 2,469 patients. The meta-analysis revealed a 95% confidence interval (CI) for the effect size of 0.641 to 1.523, with a prediction interval of 0.027 to 2.137.
CONCLUSION
Based on the analysis, NLR is a promising biochemical marker for future pieces of research that try to find new screening methods for first-trimester preeclampsia. We encourage other researchers to examine NLR's predictive value combined with other markers in preeclampsia screening, this way being able to find new and affordable protocols for first-trimester preeclampsia screening.
SYSTEMATIC REVIEW REGISTRATION
identifier CRD42023392663.
PubMed: 38633299
DOI: 10.3389/fmed.2024.1336764 -
Open Heart Apr 2024The primary concern for women who have experienced peripartum cardiomyopathy (PPCM) is the safety of a subsequent pregnancy (SSP). To maximie decision-making, facilitate... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The primary concern for women who have experienced peripartum cardiomyopathy (PPCM) is the safety of a subsequent pregnancy (SSP). To maximie decision-making, facilitate effective patient counselling, and ultimately improve maternal and fetal outcomes as a whole, it is critical to comprehend the outcomes of SSP in women who have previously experienced PPCM. This study aimed to evaluate the outcomes of SSP in women with PPCM.
METHODS
Three databases (PubMed, Scopus, and ScienceDirect) were used to identify relevant studies prior to 17 October 2023. A total of 662 studies were reviewed. Following the abstract and full-text screenings, 18 observational studies were included, out of which 2 were deemed suitable for inclusion in this meta-analysis. The quality assessment was conducted using the Newcastle-Ottawa Scale.
RESULTS
This study has a total of 487 SSPs. Although recovered left ventricular (LV) function before entering SSP has the potential to be a beneficial prognostic factor, recovered LV function still has a substantial risk of relapse. The mortality rate of PPCM in an SSP ranged from 0% to 55.5%. Persistent LV dysfunction was significantly associated with an increased mortality rate (OR 13.17; 95% CI 1.54 to 112.28; p=0.02) and lower LV ejection fraction (MD -12.88; 95% CI -21.67 to -4.09; p=0.004). Diastolic and right ventricular functions remained unchanged before SSP and at follow-up. The majority of the SSP was observed alongside hypertension, while pre-eclampsia emerged as the predominant hypertensive complication in most studies.
CONCLUSION
SSP increases the risk of relapse and mortality in women with a previous history of PPCM. Persistent LV dysfunction prior to the SSP has a higher mortality risk compared with recovered LV function. SSP was also associated with the worsening of LV echocardiography parameters.
Topics: Pregnancy; Humans; Female; Peripartum Period; Cardiomyopathies; Ventricular Function, Left; Ventricular Dysfunction, Left; Recurrence; Observational Studies as Topic
PubMed: 38569669
DOI: 10.1136/openhrt-2024-002626 -
Journal of Clinical Medicine Mar 2024: The objective was to assess the association between early HbA1c levels and pregnancy complications and whether this relationship is affected when HbA1c thresholds are... (Review)
Review
: The objective was to assess the association between early HbA1c levels and pregnancy complications and whether this relationship is affected when HbA1c thresholds are greater than or less than 39 mmol/mol (5.7%). : Electronic searches of the MEDLINE and EMBASE databases up to October 2022 were conducted. We included retrospective and prospective observational studies. The inclusion criteria were as follows: HbA1c measurements taken at <20 weeks' gestation, singleton pregnancy, and no pre-existing diabetes mellitus. : We assessed the certainty of the evidence with the GRADE system. We determined the proportion of patients in each group who met the criteria for obstetrical outcomes and pooled data into two subgroups according to the HbA1c threshold: <39 mmol/mol or >39 mmol/mol (5.7%). Sixteen studies with a total of 43,627 women were included. An association between elevated early HbA1c levels and pre-eclampsia, large for gestational age (LGA), macrosomia, and preterm delivery (RR 2.02, 95% CI 1.53-2.66; RR 1.38, 95% CI 1.15-1.66; RR 1.40, 95% CI 1.07-1.83; and RR 1.67, 95% CI 1.39-2.0, respectively) was shown, with a moderate-high grade of certainty. According to the subgroup analysis of all studies, LGA, pre-eclampsia, and labour induction were associated with elevated HbA1c levels only in studies using an HbA1c threshold >39 mmol/mol (5.7%). The association between HbA1c levels and premature birth was statistically significant in studies using both higher and lower HbA1c thresholds. : Women with high early HbA1c levels below the range of diabetes presented an increased risk of pregnancy complications such as macrosomia, LGA, and pre-eclampsia. An early HbA1c threshold of >39 mmol/mol (5.7%) showed the strongest association with pregnancy complications.
PubMed: 38541957
DOI: 10.3390/jcm13061732 -
PloS One 2024Despite conflicting findings in the current literature regarding the correlation between contraceptives and maternal health consequences, statistical analyses indicate... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Despite conflicting findings in the current literature regarding the correlation between contraceptives and maternal health consequences, statistical analyses indicate that family planning may decrease the occurrence of such outcomes. Consequently, it is crucial to assess the capability of family planning to mitigate adverse maternal health outcomes.
OBJECTIVES
This review investigates the effects of modern contraceptive use on maternal health.
SEARCH METHODS
This systematic review is registered on Prospero (CRD42022332783). We searched numerous databases with an upper date limit of February 2022 and no geographical boundaries.
SELECTION CRITERIA
We included observational studies, including cross-sectional, cohort, case-control studies, and non-RCT with a comparison group. We excluded systematic reviews, scoping reviews, narrative reviews, and meta-analyses from the body of this review.
MAIN RESULTS
The review included nineteen studies, with five studies reporting a reduction in maternal mortality linked to increased access to family planning resources and contraceptive use. Another three studies examined the impact of contraception on the risk of preeclampsia and our analysis found that preeclampsia risk was lower by approximately 6% among contraceptive users (95% CI 0.82-1.13) compared to non-users. Two studies assessed the effect of hormonal contraceptives on postpartum glucose tolerance and found that low-androgen contraception was associated with a reduced risk of gestational diabetes (OR 0.84, 95% CI 0.58-1.22), while DMPA injection was possibly linked to a higher risk of falling glucose status postpartum (OR 1.42, 95% CI 0.85-2.36). Two studies evaluated high-risk pregnancies and births in contraceptive users versus non-users, with the risk ratio being 30% lower among contraceptive users of any form (95% CI 0.61, 0.80). None of these results were statistically significant except the latter. In terms of adverse maternal health outcomes, certain contraceptives were found to be associated with ectopic pregnancy and pregnancy-related venous thromboembolism through additional analysis.
Topics: Pregnancy; Humans; Female; Family Planning Services; Pre-Eclampsia; Cross-Sectional Studies; Contraception; Contraceptives, Oral, Hormonal; Glucose
PubMed: 38498424
DOI: 10.1371/journal.pone.0294475 -
MedRxiv : the Preprint Server For... Mar 2024In this study the presence of uterine fibroids was significantly associated with an increased risk of development of hypertensive disorders of pregnancy even when...
CAPSULE
In this study the presence of uterine fibroids was significantly associated with an increased risk of development of hypertensive disorders of pregnancy even when accounting for age and BMI in meta-regression. This finding has potential implications for risk stratification and monitoring for hypertension during pregnancy in this population.
OBJECTIVE
To examine the association between uterine fibroids and the development of hypertensive disorders in pregnancy.
DATA SOURCES
Cochrane, Embase, PubMed, MEDLINE, Scopus, and Web of Science databases were searched from inception through April 2023.
STUDY SELECTION AND SYNTHESIS
Cohort, case-control, or case series studies including uterine fibroid status and hypertensive disorders of pregnancy status were included. The comparison group was pregnant women without uterine fibroids. Inverse-variance weighted random effects models were used to pool RR and OR estimates separately. Age and BMI were explored as potential sources of heterogeneity using inverse-variance weighted meta-regression.
MAIN OUTCOMES
Hypertensive disorders of pregnancy (HDP) defined as gestational hypertension, pre-eclampsia, eclampsia, superimposed preeclampsia, or hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome.
RESULTS
A total of 17 studies were included (Total N=1,374,395 participants, N=64,968 with uterine fibroids). Thirteen studies were retrospective cohorts and four were case-control studies. Women with uterine fibroids had a significantly higher risk of hypertensive disorders in pregnancy compared to women without uterine fibroids with RR 1.74 (95% CI 1.33-2.27, p<0.01), and OR 2.87 (95% CI 1.38-5.97, p<0.01), in cohort studies and case-control studies, respectively. In meta-regression analyses, age did not significantly change the positive association between uterine fibroids and hypertensive disorders in pregnancy.
CONCLUSION
Uterine fibroids were associated with an increased risk of hypertensive disorders of pregnancy when all available literature was synthesized, including when shared risk factors are examined in meta-regression analyses.
RELEVANCE
If confirmed in future studies, investigations into the mechanisms of this association are needed as this finding potentially has implications for risk stratification and monitoring for hypertensive disorders of pregnancy in this population.
TRIAL REGISTRATION
PROSPERO, ID # 331528.
PubMed: 38496589
DOI: 10.1101/2024.03.05.24303824 -
Hypertension in Pregnancy Dec 2024Preeclampsia (PE) is a pregnancy disorder that represents a major cause of maternal and perinatal morbidity and mortality. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Preeclampsia (PE) is a pregnancy disorder that represents a major cause of maternal and perinatal morbidity and mortality.
METHODS
This network meta-analysis was registered with PROSPERO. We searched the PubMed, ClinicalTrials.gov. and Embase databases for studies published from inception to the 31 of March 2023. RevMan5.3 software provided by the Cochrane Collaboration was used for direct meta-analysis (DMA) statistical analysis. Funnel maps, network meta-analysis (NMA), the surface under the cumulative ranking curve (SUCRA) to rank the different interventions and publication bias were generated by STATA 17.0 software.
RESULTS
We included eight randomized controlled trials (RCTs) involving a total of 1192 women with PE; two studies were of high quality and six were of moderate quality. Eight interventions were addressed in the NMA. In the DMA, we found that blood pressure in the Ketanserin group were significantly higher than those in the Nicardipine group. NMA showed that blood pressure in the Dihydralazine group was significantly higher than that in the Methyldopa, Labetalol, Nicardipine and Diltiazem groups. And the blood pressure in the Labetalol group was significantly lower than that in the Nicardipine group. SUCRA values showed that Diltiazem was more effective in lowering blood pressure than other drugs looked at in this study.
CONCLUSION
According to the eight RCTs included in this study, Diltiazem was the most effective in reducing blood pressure in PE patients; Labetalol and Nicardipine also had good effects. Diltiazem is preferred for the treatment of patients with severe PE and high blood pressure.
Topics: Pregnancy; Female; Humans; Antihypertensive Agents; Labetalol; Pre-Eclampsia; Diltiazem; Nicardipine; Network Meta-Analysis
PubMed: 38488570
DOI: 10.1080/10641955.2024.2329068