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Reproductive Sciences (Thousand Oaks,... Jun 2024Polycystic ovary syndrome (PCOS) is an endocrine disorder that primarily affects women of reproductive age. It is recognized as the leading cause of infertility due to... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Polycystic ovary syndrome (PCOS) is an endocrine disorder that primarily affects women of reproductive age. It is recognized as the leading cause of infertility due to anovulation. This research aims to evaluate the diagnostic potential of oxidative stress biomarkers, including advanced oxidation protein products (AOPP), malondialdehyde (MDA), uric acid (UA), and nitric oxide (NO), in identifying PCOS.
METHODS
A literature search was conducted in the EMBASE, PubMed, Cochrane Library, and Scopus databases. The standardized mean difference (SMD) and 95% confidence interval (CI) were employed to assess the correlation between free radical product and PCOS. Moreover, the presence of heterogeneity among the studies was assessed utilizing the I statistic and Cochran Q test. The methodological rigor of the incorporated studies was assessed through the application of the Newcastle-Ottawa Scale. Furthermore, the presence of publication bias was determined via Begg and Egger tests.
RESULTS
This meta-analysis reviewed 38 observational studies, including 17,845 women. The results revealed a significant association between PCOS in women and alterations in free radical levels. The study revealed that the PCOS group had significantly higher levels of AOPP (SMD = 3.193; 95% CI, 2.86 to 3.25), UA (SMD = 0.68; 95% CI, 0.24 to 1.13), and MDA (SMD = 1.16; 95% CI, 0.77 to 1.56) compared to the healthy control group. Furthermore, the analysis found a significantly lower level of NO (SMD = (- 0.59); 95% CI, - 1.15 to - 0.03) in the PCOS patient.
CONCLUSION
Screening of specific biomarkers associated with free radical products could provide valuable benefits in the prognosis and diagnosis of PCOS.
Topics: Polycystic Ovary Syndrome; Humans; Female; Biomarkers; Oxidative Stress; Free Radicals; Uric Acid; Nitric Oxide; Advanced Oxidation Protein Products; Malondialdehyde
PubMed: 38212583
DOI: 10.1007/s43032-023-01447-x -
Blood Advances Feb 2024Advancements in orally bioavailable iron chelators and MRI methods have improved life expectancy and reproductive potential in thalassemia major (TM) and thalassemia... (Meta-Analysis)
Meta-Analysis
Advancements in orally bioavailable iron chelators and MRI methods have improved life expectancy and reproductive potential in thalassemia major (TM) and thalassemia intermedia (TI). Pregnancy is associated with adverse maternal and neonatal outcomes, frequency of which has not been well delineated. This systematic review aims to provide risk estimates of maternal and fetal outcomes in TM and TI and explore pregnancy's impact on iron homeostasis. Fifteen studies (429 participants, 684 pregnancies) were included. Meta-analysis revealed a higher thrombosis risk in TI (3.7%) compared to TM (0.92%), unchanged from prepregnancy. Heart failure risks in the earlier years appeared similar (TM 1.6% vs TI 1.1%), and maternal mortality in TM was 3.7%, but with current management, these risks are rare. Gestational diabetes and pre-eclampsia occurred in 3.9% and 11.3% of TM pregnancies, respectively. Caesarean section rates were 83.9% in TM and 67% in TI. No significant difference in stillbirth, small for gestational age neonates, or preterm birth incidence between TM and TI was observed. In TM pregnancies, red cell requirements significantly increased (from 102 to 139 ml/kg/year, P = 0.001), and 70% of TI pregnancies required blood transfusions. As expected, increased transfusion alongside chelation cessation led to a significant increase in serum ferritin during pregnancy (TM by 1005 ng/mL; TI by 332 ng/mL, P < 0.0001). Deterioration in iron status was further reflected by an increase in liver iron concentration (from 4.6 to 11.9 mg/g dry weight, P < 0.0001), and myocardial T2-star (T2∗) magnetic resonance imaging decreased (from 36.2 ± 2.5 ms to 31.1 ms) during pregnancy. These findings emphasize the elevated maternal risk of iron-related cardiomyopathy during pregnancy and labor, stressing the importance of cardiac monitoring and postpartum chelation therapy resumption.
Topics: Humans; Infant, Newborn; Pregnancy; Female; beta-Thalassemia; Iron; Pregnancy Outcome; Cesarean Section; Premature Birth
PubMed: 38181780
DOI: 10.1182/bloodadvances.2023011636 -
Journal of Reproduction & Infertility 2023Cell-free fetal DNA (cffDNA) is a novel screening method for fetal aneuploidy that facilitated non-invasive prenatal testing (NIPT) through analysis of cffDNA in... (Review)
Review
BACKGROUND
Cell-free fetal DNA (cffDNA) is a novel screening method for fetal aneuploidy that facilitated non-invasive prenatal testing (NIPT) through analysis of cffDNA in maternal plasma. However, despite increased sensitivity, it has a number of limitations that may complicate of its results interpretation. Therefore, elucidating factors affecting fetal fraction, as a critical limitation, guides its clinical application.
METHODS
In this report, systematic search was carried out through PubMed, Web of Science, and Scopus databases until February 11, 2022 by using keywords consist of "noninvasive prenatal screening", "NIPT", "noninvasive prenatal", "cell free DNA" and "fetal fraction". The articles were screened for eligibility criteria before data extraction.
RESULTS
A total of 39 eligible studies, most published between 2010 and 2020, were included. Based on the results of studies, a negative correlation between maternal age and BMI/body weight with fetal fraction was found. Furthermore, LDL, cholesterol, triglyceride level, metformin, heparin and enoxaparin therapy, hemoglobin-related hemoglobinopathies, and physical activity showed to have negative associations. Interestingly, it seems the ethnicity of patients from South and East Asia has a correlation with fetal fraction compared to Caucasians. Positive correlation was observed between gestational age, free β-hCG, PAPP-A, living in high altitude, and twin pregnancy.
CONCLUSION
Considering each factor, there was significant inconsistency and controversy regarding their impact on outcomes. Indeed, multiple factors can influence the accuracy of NIPS results, and it is worth noting that the impact of these factors may vary depending on the individual's ethnic background. Therefore, it is important to recognize that NIPS remains a screening test, and comprehensive pre- and post-NIPS counseling should be conducted as part of standard clinical practice.
PubMed: 38164433
DOI: 10.18502/jri.v24i4.14149 -
American Journal of Medical Genetics.... May 2024RASopathies are a group of malformation syndromes known to lead to nonimmune hydrops fetalis (NIHF) in severe presentations. Pathogenic variants can be de novo or... (Meta-Analysis)
Meta-Analysis Review
RASopathies are a group of malformation syndromes known to lead to nonimmune hydrops fetalis (NIHF) in severe presentations. Pathogenic variants can be de novo or parentally inherited. Despite being a known frequent presentation, the fraction of monogenic NIHF cases due to RASopathies is limited in the literature. Also, the specific parental contribution of RASopathies to NIHF is not well described. Our objective was to review pooled exome sequencing (ES) diagnostic yield of RASopathies for NIHF and to determine the parental contribution of RASopathy to NIHF. We performed a systematic review of prenatal ES studies from January 1, 2000 to August 1, 2022. Thirty-six studies met inclusion criteria. Cases with RASopathy gene variants were reviewed. NIHF cases were further classified as isolated or non-isolated. Thirty-six ES studies including 46 pregnancies with NIHF and a diagnosed RASopathy were reviewed. Forty-four diagnostic variants and 2 variants of uncertain significance in 12 RASopathy genes were identified. Expanding on what was previously published, a total of 506 NIHF cases were extracted with 191 cases yielding a positive diagnosis by ES. The overall rate of RASopathy diagnosis in clinically diagnosed NIHF cases was 9% (44/506). The rate of RASopathy diagnosis among NIHF cases with positive genetic diagnosis by ES was 23% (44/191). Of the 46 cases identified, 13 (28%) variants were parentally inherited; specifically, 5/13 (38%) maternal, 3/13 (23%) paternal, 2/13 (15%) biparental, and 3/13 (23%) unspecified. Majority of NIHF cases 29/46 (63%) were isolated. Among NIHF cases with positive ES diagnoses, RASopathy diagnostic yield by ES was 23%. NIHF secondary to RASopathies was parentally inherited in 28% of cases. Most cases of NIHF due to RASopathy were isolated, with no prenatal detection of associated anomalies.
Topics: Pregnancy; Male; Female; Humans; Hydrops Fetalis; Exome Sequencing; Fathers
PubMed: 38156365
DOI: 10.1002/ajmg.a.63494 -
Medicina (Kaunas, Lithuania) Dec 2023: Pain management poses a significant challenge for patients experiencing vaso-occlusive crisis (VOC) in sickle cell disease (SCD). While opioid therapy is highly...
: Pain management poses a significant challenge for patients experiencing vaso-occlusive crisis (VOC) in sickle cell disease (SCD). While opioid therapy is highly effective, its efficacy can be impeded by undesirable side effects. Local regional anesthesia (LRA), involving the deposition of a perineural anesthetic, provides a nociceptive blockade, local vasodilation and reduces the inflammatory response. However, the effectiveness of this therapeutic approach for VOC in SCD patients has been rarely reported up to now. The objective of this study was to assess the effectiveness of a single-shot local regional anesthesia (LRA) in reducing pain and consequently enhancing the management of severe vaso-occlusive crisis (VOC) in adults with sickle cell disease (SCD) unresponsive to conventional analgesic therapy. : We first collected consecutive episodes of VOC in critical care (ICU and emergency room) for six months in 2022 in a French University hospital with a large population of sickle cell patients in the West Indies population. We also performed a systematic review of the use of LRA in SCD. The primary outcome was defined using a numeric pain score (NPS) and/or percentage of change in opioid use. : We enrolled nine SCD adults (28 years old, 4 females) for ten episodes of VOC in whom LRA was used for pain management. Opioid reduction within the first 24 h post block was -75% (50 to 96%). Similarly, the NPS decreased from 9/10 pre-block to 0-1/10 post-block. Five studies, including one case series with three patients and four case reports, employed peripheral nerve blocks for regional anesthesia. In general, local regional anesthesia (LRA) exhibited a reduction in pain and symptoms, along with a decrease in opioid consumption post-procedure. : LRA improves pain scores, reduces opioid consumption in SCD patients with refractory pain, and may mitigate opioid-related side effects while facilitating the transition to oral analgesics. Furthermore, LRA is a safe and effective procedure.
Topics: Adult; Female; Humans; Pain Management; Retrospective Studies; Analgesics, Opioid; Volatile Organic Compounds; Pain; Analgesics; Anemia, Sickle Cell
PubMed: 38138299
DOI: 10.3390/medicina59122196 -
European Journal of Haematology Mar 2024Hydroxyurea reduces the frequency of vaso-occlusive complications, increases hemoglobin, and decreases mortality in sickle cell disease (SCD). Although current... (Meta-Analysis)
Meta-Analysis
Hydroxyurea reduces the frequency of vaso-occlusive complications, increases hemoglobin, and decreases mortality in sickle cell disease (SCD). Although current guidelines recommend escalation to maximum tolerated dose (MTD), the use of fixed low-dose hydroxyurea is common in low-resource countries. We conducted a systematic review and meta-analysis to evaluate the efficacy of escalated doses versus fixed low-dose of hydroxyurea in adults with SCD. Nine studies were included in the quantitative synthesis, four evaluating fixed low-dose and five evaluating escalated doses of hydroxyurea. Average daily doses of hydroxyurea in the fixed low-dose and escalated dose studies were ~10 and 22 mg/kg, respectively. There was no difference in the estimate of vaso-occlusive crisis rate between escalated and fixed low-dose studies (p = .73). The mean difference in hemoglobin from baseline to follow-up was greater for fixed low-dose than escalated dose studies (1.07 g/dL vs. 0.54 g/dL, p = .01). No difference was seen in the mean estimate of fetal hemoglobin. Despite limited eligible studies and substantial heterogeneity of effect between the studies for several outcomes, there appears to be clinical equipoise regarding the most appropriate hydroxyurea dosing regimen in adults with SCD. Controlled studies of hydroxyurea at MTD versus fixed low-dose in adults with SCD are required.
Topics: Adult; Humans; Hydroxyurea; Antisickling Agents; Anemia, Sickle Cell; Fetal Hemoglobin; Hemoglobins
PubMed: 38019026
DOI: 10.1111/ejh.14138 -
Journal of Health Care For the Poor and... 2023People of African descent and those identifying as Black and/or Latino experience a disproportionate burden of sickle cell disease (SCD), a chronic, serious blood...
People of African descent and those identifying as Black and/or Latino experience a disproportionate burden of sickle cell disease (SCD), a chronic, serious blood condition. Caregivers of children with chronic medical conditions report worse mental health than others. Disease-associated stressors can affect caregivers of children with SCD. We conducted a systematic review to summarize the prevalence of mental health symptoms in caregivers of children with SCD and to see if symptoms were associated with the child's SCD. This review is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. We searched PubMed, PsycINFO, and Embase, identifying 1,322 records of which 40 met criteria for inclusion in this review. Findings suggest caregivers experience mental health problems, and poorer mental health was associated with worse child SCD-related outcomes and treatment adherence. Efforts should be made to routinely screen SCD caregiver mental health and to refer accordingly.
Topics: Adolescent; Child; Humans; Anemia, Sickle Cell; Caregivers; Mental Health; Treatment Adherence and Compliance
PubMed: 38015138
DOI: No ID Found -
Presse Medicale (Paris, France : 1983) Dec 2023Neurovascular disease such as symptomatic stroke, silent brain infarcts and vascular cognitive impairment are common complications of sickle cell disease (SCD) that can... (Meta-Analysis)
Meta-Analysis
Neurovascular disease such as symptomatic stroke, silent brain infarcts and vascular cognitive impairment are common complications of sickle cell disease (SCD) that can have devastating consequences on quality of life, employment, and social functioning. Early recognition of neurovascular disease is a prerequisite for the timely optimization of medical care and to connect patients to adaptive resources. While cognitive impairment has been well described in children, currently available data are limited in adults. As a result, guidance on the optimal cognitive screening strategies in adults is scarce. We conducted a systematic review to identify the different screening tools that have been evaluated in SCD. A meta-analysis was performed to estimate the prevalence of suspected cognitive impairment in this population. In this qualitative synthesis, we present 8 studies that evaluated 6 different screening tools. Patient characteristics that impacted on cognitive screening performance included age, education level, and a prior history of stroke. We report a pooled prevalence of 38% [14-62%] of suspected cognitive impairment. We discuss the relative benefits and limitations of the different screening tools to help clinicians select an adapted approach tailored to their specific patients' needs. Further studies are needed to establish and validate cognitive screening strategies in patients with diverse cultural and educational backgrounds.
Topics: Child; Adult; Humans; Quality of Life; Anemia, Sickle Cell; Cognitive Dysfunction; Stroke; Educational Status
PubMed: 37979834
DOI: 10.1016/j.lpm.2023.104207 -
Prenatal Diagnosis Dec 2023To investigate the maternal and fetal safety of In utero stem cell transplantation (IUSCT).
OBJECTIVE
To investigate the maternal and fetal safety of In utero stem cell transplantation (IUSCT).
METHODS
Medline®, Embase and Cochrane library (1967-2023) search for publications reporting IUSCT in humans. Two reviewers independently screened abstracts and full-text papers.
RESULTS
Sixty six transplantation procedures in 52 fetuses were performed for haemoglobinopathies (n = 14), red cell/bleeding disorders (n = 4), immunodeficiencies (n = 15), storage disorders (n = 7), osteogenesis imperfecta (n = 2) and healthy fetuses (n = 10). The average gestational age was 18.9 weeks; of procedures reporting the injection route, cells were delivered by intraperitoneal (n = 37), intravenous (n = 19), or intracardiac (n = 4) injection or a combination (n = 3); most fetuses received one injection (n = 41). Haematopoietic (n = 40) or mesenchymal (n = 12) stem cells were delivered. The cell dose was inconsistently reported (range 1.8-3.3 × 10 cells total (n = 27); 2.7-5.0 × 10 /kg estimated fetal weight (n = 17)). The acute fetal procedural complication rate was 4.5% (3/66); the acute fetal mortality rate was 3.0% (2/66). Neonatal survival was 69.2% (36/52). Immediate maternal and pregnancy outcomes were reported in only 30.8% (16/52) and 44.2% (23/52) of cases respectively. Four fetal/pregnancy outcomes would also classify as ≥ Grade 2 maternal adverse events.
CONCLUSIONS
Short-, medium-, and long-term maternal and fetal adverse events should be reported in all IUSCT studies.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Infant; Pregnancy Outcome; Prenatal Care; Fetus; Gestational Age
PubMed: 37975679
DOI: 10.1002/pd.6459 -
The Cochrane Database of Systematic... Nov 2023Beta-thalassaemia is an inherited blood disorder that reduces the production of haemoglobin. The most severe form requires recurrent blood transfusions, which can lead... (Review)
Review
BACKGROUND
Beta-thalassaemia is an inherited blood disorder that reduces the production of haemoglobin. The most severe form requires recurrent blood transfusions, which can lead to iron overload. Cardiovascular dysfunction caused by iron overload is the leading cause of morbidity and mortality in people with transfusion-dependent beta-thalassaemia. Iron chelation therapy has reduced the severity of systemic iron overload, but removal of iron from the myocardium requires a very proactive preventive strategy. There is evidence that calcium channel blockers may reduce myocardial iron deposition. This is an update of a Cochrane Review first published in 2018.
OBJECTIVES
To assess the effects of calcium channel blockers plus standard iron chelation therapy, compared with standard iron chelation therapy (alone or with a placebo), on cardiomyopathy due to iron overload in people with transfusion-dependent beta thalassaemia.
SEARCH METHODS
We searched the Cochrane Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books, to 13 January 2022. We also searched ongoing trials databases and the reference lists of relevant articles and reviews.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) of calcium channel blockers combined with standard chelation therapy versus standard chelation therapy alone or combined with placebo in people with transfusion-dependent beta thalassaemia.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. We used GRADE to assess certainty of evidence.
MAIN RESULTS
We included six RCTs (five parallel-group trials and one cross-over trial) with 253 participants; there were 126 participants in the amlodipine arms and 127 in the control arms. The certainty of the evidence was low for most outcomes at 12 months; the evidence for liver iron concentration was of moderate certainty, and the evidence for adverse events was of very low certainty. Amlodipine plus standard iron chelation compared with standard iron chelation (alone or with placebo) may have little or no effect on cardiac T2* values at 12 months (mean difference (MD) 1.30 ms, 95% confidence interval (CI) -0.53 to 3.14; 4 trials, 191 participants; low-certainty evidence) and left ventricular ejection fraction (LVEF) at 12 months (MD 0.81%, 95% CI -0.92% to 2.54%; 3 trials, 136 participants; low-certainty evidence). Amlodipine plus standard iron chelation compared with standard iron chelation (alone or with placebo) may reduce myocardial iron concentration (MIC) after 12 months (MD -0.27 mg/g, 95% CI -0.46 to -0.08; 3 trials, 138 participants; low-certainty evidence). The results of our analysis suggest that amlodipine has little or no effect on heart T2*, MIC, or LVEF after six months, but the evidence is very uncertain. Amlodipine plus standard iron chelation compared with standard iron chelation (alone or with placebo) may increase liver T2* values after 12 months (MD 1.48 ms, 95% CI 0.27 to 2.69; 3 trials, 127 participants; low-certainty evidence), but may have little or no effect on serum ferritin at 12 months (MD 0.07 μg/mL, 95% CI -0.20 to 0.35; 4 trials, 187 participants; low-certainty evidence), and probably has little or no effect on liver iron concentration (LIC) after 12 months (MD -0.86 mg/g, 95% CI -4.39 to 2.66; 2 trials, 123 participants; moderate-certainty evidence). The results of our analysis suggest that amlodipine has little or no effect on serum ferritin, liver T2* values, or LIC after six months, but the evidence is very uncertain. The included trials did not report any serious adverse events at six or 12 months of intervention. The studies did report mild adverse effects such as oedema, dizziness, mild cutaneous allergy, joint swelling, and mild gastrointestinal symptoms. Amlodipine may be associated with a higher risk of oedema (risk ratio (RR) 5.54, 95% CI 1.24 to 24.76; 4 trials, 167 participants; very low-certainty evidence). We found no difference between the groups in the occurrence of other adverse events, but the evidence was very uncertain. No trials reported mortality, cardiac function assessments other than echocardiographic estimation of LVEF, electrocardiographic abnormalities, quality of life, compliance with treatment, or cost of interventions.
AUTHORS' CONCLUSIONS
The available evidence suggests that calcium channel blockers may reduce MIC and may increase liver T2* values in people with transfusion-dependent beta thalassaemia. Longer-term multicentre RCTs are needed to assess the efficacy and safety of calcium channel blockers for myocardial iron overload, especially in younger children. Future trials should also investigate the role of baseline MIC in the response to calcium channel blockers, and include a cost-effectiveness analysis.
Topics: Child; Humans; beta-Thalassemia; Calcium Channel Blockers; Iron Overload; Iron; Cardiomyopathies; Amlodipine; Iron Chelating Agents; Ferritins; Edema
PubMed: 37975597
DOI: 10.1002/14651858.CD011626.pub3