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Obstetrics and Gynecology Jul 2024
Topics: Humans; Pre-Eclampsia; Female; Pregnancy; Biomarkers
PubMed: 38949551
DOI: 10.1097/AOG.0000000000005626 -
Obstetrics and Gynecology Jul 2024To evaluate maternal and neonatal outcomes by type of antihypertensive used in participants of the CHAP (Chronic Hypertension in Pregnancy) trial. (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
OBJECTIVE
To evaluate maternal and neonatal outcomes by type of antihypertensive used in participants of the CHAP (Chronic Hypertension in Pregnancy) trial.
METHODS
We conducted a planned secondary analysis of CHAP, an open-label, multicenter, randomized trial of antihypertensive treatment compared with standard care (no treatment unless severe hypertension developed) in pregnant patients with mild chronic hypertension (blood pressure 140-159/90-104 mm Hg before 20 weeks of gestation) and singleton pregnancies. We performed three comparisons based on medications prescribed at enrollment: labetalol compared with standard care, nifedipine compared with standard care, and labetalol compared with nifedipine. Although active compared with standard care groups were randomized, medication assignment within the active treatment group was not random but based on clinician or patient preference. The primary outcome was the occurrence of superimposed preeclampsia with severe features, preterm birth before 35 weeks of gestation, placental abruption, or fetal or neonatal death. The key secondary outcome was small for gestational age (SGA) neonates. We also compared medication adverse effects between groups. Relative risks (RRs) and 95% CIs were estimated with log binomial regression to adjust for confounding.
RESULTS
Of 2,292 participants analyzed, 720 (31.4%) received labetalol, 417 (18.2%) received nifedipine, and 1,155 (50.4%) received no treatment. The mean gestational age at enrollment was 10.5±3.7 weeks; nearly half of participants (47.5%) identified as non-Hispanic Black; and 44.5% used aspirin. The primary outcome occurred in 217 (30.1%), 130 (31.2%), and 427 (37.0%) in the labetalol, nifedipine, and standard care groups, respectively. Risk of the primary outcome was lower among those receiving treatment (labetalol use vs standard adjusted RR 0.82, 95% CI, 0.72-0.94; nifedipine use vs standard adjusted RR 0.84, 95% CI, 0.71-0.99), but there was no significant difference in risk when labetalol was compared with nifedipine (adjusted RR 0.98, 95% CI, 0.82-1.18). There were no significant differences in SGA or serious adverse events between participants receiving labetalol and those receiving nifedipine.
CONCLUSION
No significant differences in predetermined maternal or neonatal outcomes were detected on the basis of the use of labetalol or nifedipine for treatment of chronic hypertension in pregnancy.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov, NCT02299414.
Topics: Humans; Pregnancy; Female; Labetalol; Nifedipine; Antihypertensive Agents; Adult; Pregnancy Outcome; Hypertension; Infant, Newborn; Pregnancy Complications, Cardiovascular; Hypertension, Pregnancy-Induced; Administration, Oral; Infant, Small for Gestational Age; Pre-Eclampsia; Chronic Disease
PubMed: 38949541
DOI: 10.1097/AOG.0000000000005613 -
Sichuan Da Xue Xue Bao. Yi Xue Ban =... May 2024Obstetric antiphospholipid syndrome (OAPS) is an autoimmune disorder associated with various pathological pregnancies, such as recurrent miscarriage, stillbirth, severe... (Review)
Review
Obstetric antiphospholipid syndrome (OAPS) is an autoimmune disorder associated with various pathological pregnancies, such as recurrent miscarriage, stillbirth, severe pre-eclampsia and severe placental insufficiency. The persistent presence of antiphospholipid antibodies (aPLs) is the most important laboratory characteristic of OAPS. OAPS severely affects the reproductive health of women of childbearing age in China. Reports indicate that approximately 9.6% stillbirths, 11.5% severe pre-eclampsia, and 54% recurrent miscarriages are associated with OAPS or aPLs. However, the pathogenesis of OAPS remains unclear. Previously, thrombosis at the maternal-fetal interface (MFI) was considered the main mechanism of OAPS-related pathological pregnancies. Consequently, the use of low molecular weight heparin and aspirin throughout pregnancy was recommended to improve outcomes in OAPS patient. In recent years, many studies have found that thrombosis in MFI is uncommon, but various inflammatory factors are significantly increased in the MFI of OAPS patients. Based on these findings, some clinicians have started using anti-inflammatory treatments for OAPS, which have preliminarily improved the pregnancy outcomes. Nevertheless, there is no consensus on these second-line treatments of OAPS. Another troubling issue is the clinical diagnosis of OAPS. Similar to other autoimmune diseases, there are only classification criteria for OAPS, and clinical diagnosis of OAPS depends on the clinicians' experience. The present classification criteria of OAPS were established for clinical and basic research purposes, not for patient clinical management. In clinical practice, many patients with both positive aPLs and pathological pregnancy histories do not meet the strict OAPS criteria. This has led to widespread issues of incorrect diagnosis and treatment. Timely and accurate diagnosis of OAPS is crucial for effective treatment. In this article, we reviewed the epidemiological research progress on OAPS and summarized its classification principles, including: 1) the persistent presence of aPLs in circulation; 2) manifestations of OAPS, excluding other possible causes. For the first point, accurate assessment of aPLs is crucial; for the latter, previous studies regarded only placenta-related pregnancy complications as characteristic manifestations of OAPS. However, recent studies have indicated that adverse pregnancy outcomes related to trophoblast damage, such as recurrent miscarriage and stillbirth, also need to be considered in OAPS. We also discussed several key issues in the diagnosis and treatment of OAPS. First, we addressed the definition of non-standard OAPS and offered our opinion on defining non-standard OAPS within the framework of the 2023 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) APS criteria. Then, we discussed the advantages and disadvantages of different aPL testing methods, emphasizing that harmonizing results across platforms and establishing specific reference values are keys to resolving controversies in aPL testing results. We also introduced the application of non-criteria aPLs, especially anti-phosphatidylserine/prothrombin antibody (aPS/PT) and anti-β2 glycoprotein Ⅰ domain Ⅰ antibody (aβ2GPⅠDⅠ). Additionally, we discussed aPL-based OAPS risk classification strategies. Finally, we proposed potential treatment methods for refractory OAPS. The goal is to provide a reference for the clinical management of OAPS.
Topics: Humans; Antiphospholipid Syndrome; Pregnancy; Female; Pregnancy Complications; Abortion, Habitual; Antibodies, Antiphospholipid; Heparin, Low-Molecular-Weight; Aspirin; Pre-Eclampsia
PubMed: 38948301
DOI: 10.12182/20240560104 -
Sichuan Da Xue Xue Bao. Yi Xue Ban =... May 2024Some epidemiological studies have shown that pregnant women who develop preeclampsia (PE) have elevated levels of testosterone in their maternal plasma compared to women...
OBJECTIVE
Some epidemiological studies have shown that pregnant women who develop preeclampsia (PE) have elevated levels of testosterone in their maternal plasma compared to women with normal blood pressure during pregnancy, revealing a potential association between hyperandrogenism in women and PE. To explore the causal relationship between hyperandrogenism and PE, this study selected total testosterone (TT), bioavailable testosterone (BIOT), and sex hormone binding globulin (SHBG) as exposure factors and PE and chronic hypertension with superimposed PE as disease outcomes. Two-sample Mendelian randomization (MR) analyses were used to genetically dissect the causal relationships between the three exposure factors (TT, BIOT, and SHBG) and the outcomes of PE and chronic hypertension with superimposed PE.
METHODS
Two independent genome-wide association study (GWAS) databases were used for the two-sample MR analysis. In the GWAS data of female participants from the UK Biobank cohort, single nucleotide polymorphisms (SNPs) associated with TT, BIOT, and SHBG were analyzed, involving 230454, 188507, and 188908 samples, respectively. GWAS data on PE and chronic hypertension with superimposed PE from the Finnish database were used to calculate SNP, involving 3556 PE cases and 114735 controls, as well as 38 cases of chronic hypertension with superimposed PE and 114735 controls. To meet the assumptions of instrumental relevance and independence in MR analysis, SNPs associated with exposure were identified at the genome-wide level (<5.0×10), and those in linkage disequilibrium interference were excluded based on clustering thresholds of <0.001 and an allele distance greater than 10000 kb. Known confounding factors, including previous PE, chronic kidney disease, chronic hypertension, diabetes, systemic lupus erythematosus, or antiphospholipid syndrome, were also identified and the relevant SNPs were removed. Finally, we extracted the outcome data based on the exposure-related SNPs in the outcome GWAS, integrating exposure and outcome data, and removing palindromic sequences. Five genetic causal analysis methods, including inverse variance-weighted method (IVW), MR-Egger regression, weighted median method, simple mode method, and weighted mode method, were used to infer causal relationships. In the IVW, it was assumed that the selected SNPs satisfied the three assumptions and provided the most ideal estimate of the effect. IVW was consequently used as the primary analysis method in this study. Considering the potential heterogeneity among the instrumental variables, random-effects IVW was used for MR analysis. The results were interpreted using odds ratios (OR) and the corresponding 95% confidence interval (CI) to explain the impact of exposure factors on PE and chronic hypertension with superimposed PE. If the CI did not include 1 and had a value less than 0.05, the difference was considered statistically significant. Sensitivity analysis was conducted to assess heterogeneity and pleiotropy. Heterogeneity was examined using Cochran's test, and pleiotropy was assessed using MR-Egger intercept analysis. Additionally, leave-one-out analysis was conducted to examine whether individual SNPs were driving the causal associations. To further validate the findings, MR analyses were performed using the same methods and outcome variables, but with different exposure factors, including waist-to-hip ratio adjusted for BMI (WHRadjBMI) and 25-hydroxyvitamin D levels, with MR results for WHRadjBMI and PE serving as the positive controls and MR results for 25-hydroxyvitamin D levels and PE as the negative controls.
RESULTS
According to the criteria for selecting genetic instrumental variables, 186, 127, and 262 SNPs were identified as genetic instrumental variables significantly associated with testosterone indicators TT, BIOT, and SHBG. MR analysis did not find a causal relationship between the TT, BIOT, and SHBG levels and the risk of developing PE and chronic hypertension with superimposed PE. The IVW method predicted that genetically predicted TT (OR [95% CI]=1.018 [0.897-1.156], =0.78), BIOT (OR [95% CI]=1.11 [0.874-1.408], =0.392), and SHBG (OR [95% CI]=0.855 [0.659-1.109], =0.239) were not associated with PE. Similarly, genetically predicted TT (OR [95% CI]=1.222 [0.548-2.722], =0.624), BIOT (OR [95% CI]=1.066 [0.242-4.695], =0.933), and SHBG (OR [95% CI]=0.529 [0.119-2.343], =0.402) were not significantly associated with chronic hypertension with superimposed PE. Additionally, MR analysis using the MR-Egger method, weighted median method, simple mode method, and weighted mode method yielded consistent results, indicating no significant causal relationship between elevated testosterone levels and PE or chronic hypertension with superimposed PE. Heterogeneity was observed for SHBG in the analysis with PE (Cochran's test, =0.01), and pleiotropy was detected for BIOT in the analysis with PE (MR-Egger intercept analysis, =0.014), suggesting that the instrumental variables did not affect PE through BIOT. Other instrumental variables did not show significant heterogeneity or pleiotropy. Leave-one-out analysis confirmed that the results of the MR analysis were not driven by individual instrumental variables. Consistent with previous MR studies, the results of the control MR analyses using WHRadjBMI and 25-hydroxyvitamin D levels supported the accuracy of the MR analysis approach and the methods used in this study.
CONCLUSION
The MR analysis results suggest that current genetic evidence does not support a causal relationship between TT, BIOT, and SHBG levels and the development of PE and chronic hypertension with superimposed PE. This study suggests that elevated testosterone may be a risk factor for PE but not a direct cause.
Topics: Humans; Female; Polymorphism, Single Nucleotide; Pregnancy; Pre-Eclampsia; Genome-Wide Association Study; Hyperandrogenism; Sex Hormone-Binding Globulin; Mendelian Randomization Analysis; Testosterone; Hypertension
PubMed: 38948277
DOI: 10.12182/20240560106 -
Cureus May 2024Pheochromocytoma, a rare but potentially serious condition, poses challenges in timely identification, especially during pregnancy due to misconceptions about...
Pheochromocytoma, a rare but potentially serious condition, poses challenges in timely identification, especially during pregnancy due to misconceptions about pregnancy-related hypertension causes. However, paroxysmal symptoms heighten diagnostic suspicion. The diagnosis relies on biochemical confirmation of catecholamine hypersecretion followed by imaging for tumor localization. When diagnosed at or after 24 weeks, alpha-adrenoceptor blockers are recommended during pregnancy to manage catecholamine excess, delaying tumor removal until viability or post-delivery. The rarity of this condition during pregnancy, coupled with diagnostic and management challenges, underscores its importance for obstetric professionals in addressing hypertensive control, delivery timing, and surgical intervention.
PubMed: 38947606
DOI: 10.7759/cureus.61286 -
Research Square Jun 2024Little research has examined early life risk for symptoms of cognitive disengagement syndrome (CDS) despite a well-established literature regarding co-occurring outcomes...
BACKGROUND
Little research has examined early life risk for symptoms of cognitive disengagement syndrome (CDS) despite a well-established literature regarding co-occurring outcomes (e.g., attention-deficit/hyperactivity disorder). The current study estimated bivariate associations between early life risk factors and CDS in a large and representative sample of U.S. children.
METHODS
We conducted secondary analyses of baseline data from the Adolescent Brain Cognitive Development (ABCD) study (N = 8,096 children, 9-10 years old). Birthing parents reported early life risk factors on a developmental history questionnaire, including parental, prenatal, delivery and birth, and developmental milestone information. They also completed the Child Behavior Checklist, which includes a CDS subscale that was dichotomized to estimate the odds of elevated CDS symptoms (i.e., score > 70) in children related to risk indices.
RESULTS
We observed significantly elevated odds of CDS related to parental risk factors (i.e., unplanned pregnancy, pregnancy awareness after 6 weeks, teenage parenthood), birthing parent illnesses in pregnancy (i.e., severe nausea, proteinuria, pre-eclampsia/toxemia, severe anemia, urinary tract infection), pregnancy complications (i.e., bleeding), prenatal substance exposures (i.e., prescription medication, tobacco, illicit drugs), delivery and birth risk factors (i.e., child blue at delivery, child not breathing, jaundice, incubation after delivery), and late motor and speech milestones in children.
CONCLUSIONS
Several early-life risk factors were associated with elevated odds of CDS at ages 9-10 years; study design prevents the determination of causality. Further investigation is warranted regarding early life origins of CDS with priority given to risk indices that have upstream commonalities (i.e., that restrict fetal growth, nutrients, and oxygen).
PubMed: 38947040
DOI: 10.21203/rs.3.rs-4468007/v1 -
Zhonghua Yi Xue Yi Chuan Xue Za Zhi =... Jul 2024To assess the association of -c.108C>T and c.192Q>R polymorphisms of paraoxonase 1 (PON1) gene with preeclampsia (PE) and the influence of genotypes on the metabolic and...
OBJECTIVE
To assess the association of -c.108C>T and c.192Q>R polymorphisms of paraoxonase 1 (PON1) gene with preeclampsia (PE) and the influence of genotypes on the metabolic and oxidative stress indexes among Chinese women.
METHODS
This case-control study has included 334 patients with PE and 1337 healthy pregnant women. The -c.108C>T and c.192Q>R genotypes were determined by PCR and restriction fragment length polymorphism method. Metabolic and oxidative stress parameters were also analyzed.
RESULTS
No statistical difference in the genotypic and allelic frequencies for the -c.108C>T and c.192Q>R polymorphisms of the PON1 gene was found between the PE patients and the healthy controls (P > 0.05). Nevertheless, the 192Q-108T haplotype of these polymorphisms was associated with an increased risk of PE (P = 0.007). Total antioxidant capacity (TAC) and atherosderosis index were higher in patients with the -108TT genotype compared with those with a CT genotype (P < 0.05); whilst total oxidant status was lower in patients with a CT genotype compared with those with a CC genotype (P = 0.036). Malondialdehyde level was higher in patients with a 192RR genotype compared with those with a QQ genotype (P = 0.019). TAC level was higher in patients with a RR genotype compared with those with a QR genotype (P = 0.015).
CONCLUSION
The 192Q-108T haplotype of the PON1 gene is associated with the risk for PE. These polymorphisms may be associated with abnormal lipid metabolism and oxidative stress among Chinese PE patients.
Topics: Humans; Aryldialkylphosphatase; Female; Pregnancy; Pre-Eclampsia; Adult; Asian People; Case-Control Studies; Genotype; Gene Frequency; Polymorphism, Single Nucleotide; Genetic Predisposition to Disease; China; Oxidative Stress; Young Adult; East Asian People
PubMed: 38946375
DOI: 10.3760/cma.j.cn511374-20230515-00287 -
Mymensingh Medical Journal : MMJ Jul 2024The spectrum of indications for primary caesarean section changes with advancing parity. As parity advances more cesarean section are done for maternal rather than fetal... (Observational Study)
Observational Study
The spectrum of indications for primary caesarean section changes with advancing parity. As parity advances more cesarean section are done for maternal rather than fetal indications. The objective of this study was to determine the indications and complications of caesarean section in multiparous women with history of previous vaginal delivery. This cross-sectional descriptive observational study was conducted in Mymensingh Medical College Hospital from January 2019 to June 2019 among 100 purposively selected multiparous women who underwent primary caesarean section. A well-designed, semi-structured questionnaire was used to collect data by face-to-face interview, clinical examinations and laboratory investigations. Data analysis was conducted in SPSS 20.0 version. Majority (74.0%) of the women in this study were in the age group 21-30 years with mean age of 26.3±5.76 years. Majority of the patients were of second gravida (42.0%) followed by third gravida (33.0%). The highest gravida in this study was 6th. Most of the patients were of para 1(44.0%). Highest para in this study was para 5. The most common indication of caesarean section in this study was foetal distress (26.0%). The next common indications were cephalo-pelvic disproportion (22.0%), antepartum haemorrhage (13.0%), mal-presentaion or mal-position (16.0%). Other causes were PROM (8.0%), prolonged labour (6.0%), cord prolapse (2.0%), post-dated pregnancy (4.0%), severe pre-eclampsia (2.0%) and secondary subfertility (1.0%). There was no case of maternal mortality in this study but 15 mothers suffered from various post-operative complications like wound infection (4.0%), UTI (4.0%), puerperal pyrexia (3.0%), postpartum haemorrhage (3.0%) and paralytic ileus (1.0%). Among the babies delivered 97 were live births. Among the 97 live births 11(11.34%) were preterm babies. Among the babies delivered majority (85.0%) was with good APGAR score (7-10). In conclusion it can say that a multiparous women in labour requires the same attention as that of primigravida. A parous women needs good obstetric care to improve maternal and neonatal outcome and still keeping caesarean section to a lower rate.
Topics: Humans; Female; Adult; Cesarean Section; Pregnancy; Cross-Sectional Studies; Parity; Postoperative Complications; Tertiary Care Centers; Young Adult; Fetal Distress; Cephalopelvic Disproportion
PubMed: 38944712
DOI: No ID Found -
American Heart Journal Jun 2024Hypertensive disorders of pregnancy (HDP) are associated with increased long-term risk for cardiometabolic risk factors (chronic hypertension [HTN], obesity, diabetes)...
BACKGROUND
Hypertensive disorders of pregnancy (HDP) are associated with increased long-term risk for cardiometabolic risk factors (chronic hypertension [HTN], obesity, diabetes) and heart failure. Exercise capacity is a known predictor of heart failure in patients with normal resting cardiac filling pressures. In this prospective observational cohort study, we sought to identify predictors of reduced postpartum exercise capacity in participants with normotensive vs. preeclamptic pregnancies.
METHODS
Preeclampsia (PreE) and normotensive subjects were enrolled to undergo bedside echocardiography within 48 hours of delivery, and rest/exercise echocardiography 12 weeks postpartum.
RESULTS
Recruited subjects (n=68) were grouped according to their blood pressure as: a) normotensive pregnancy n=15; b) PreE with normotensive postpartum (PreE-Resolved, n=36); c) PreE with persistent postpartum HTN (PreE-HTN, n=17). At enrollment, a significantly higher percentage of subjects in the PreE-HTN group were Black. Compared to normotensive and PreE-Resolved subjects, those with PreE-HTN demonstrated higher resting systolic blood pressure (SBP, 112 [normotensive] vs 112 [PreE-Resolved] vs 134 [PreE-HTN], p<0.001) and diastolic blood pressure (DBP, 70.0 vs 72.5 vs 85.0, p<0.001), and significantly less postpartum weight loss (9.6% vs 13.6% vs 3.8%, p<0.001). Following Bruce protocol stress testing, PreE-HTN subjects demonstrated achieved significantly lower exercise duration (10.4 vs 10.2 vs 7.9 minutes, p = 0.001). Subjects with PreE-HTN also demonstrated evidence of exercise-induced diastolic dysfunction as assessed by peak exercise lateral e' (18.0 vs 18.0 vs 13.5, p=0.045) and peak exercise tricuspid regurgitation velocity (TR Vm, 2.4 vs 3.0 vs 3.1, p = 0.045). Exercise duration was negatively associated with gravidity (R=-0.27, p=0.029) and postpartum LV mass index (R=-0.45, p<0.001), resting average E/e' (R=-0.51, p<0.001), BMI (R=-0.6, p<0.001) and resting SBP (R=-0.51, p<0.001).
CONCLUSIONS
Postpartum exercise stress testing capacity is related to readily available clinical markers including pregnancy factors, echocardiographic parameters and unresolved cardiometabolic risk factors.
PubMed: 38944263
DOI: 10.1016/j.ahj.2024.06.002 -
Reproductive Biomedicine Online May 2024The pathophysiology of endometriosis remains unclear. Retrograde menstruation could be a phenomenon that initiates the process, but it may not explain the entire...
The pathophysiology of endometriosis remains unclear. Retrograde menstruation could be a phenomenon that initiates the process, but it may not explain the entire pathophysiology of endometriosis. Current evidence suggests that endometriosis is a type of chronic inflammatory disease. Many conditions that affect the vascular endothelium, including atherosclerosis, cardiovascular disease and pre-eclampsia, have been shown to be associated with endometriosis. Evidence to date suggests a complex interaction in endometriosis between angiogenesis, hormones and immunological changes stemming from chronic inflammation, with the inflammatory cells releasing cytokines and chemokines including tumour necrosis factor-α (TNF-α). Indeed, TNF-α is considered to be one of the possible markers of endometriosis in the blood, endometrium or menstrual blood. We emphasize the importance of pursuing research for novel and safer anti-inflammatory and immunomodulatory drugs that can be used by patients with endometriosis on a long-term basis.
PubMed: 38943810
DOI: 10.1016/j.rbmo.2024.104292