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Hemoglobin Nov 2020Thalassemia is a genetic mutation of the α- or β-globin chains that lead to defective erythropoiesis. This study aimed to collect evidences from all published studies... (Meta-Analysis)
Meta-Analysis
Thalassemia is a genetic mutation of the α- or β-globin chains that lead to defective erythropoiesis. This study aimed to collect evidences from all published studies that investigated the clinical effectiveness of calcium channel blockers (CCBs) in conjunction with chelation therapy for reducing iron overload in patients with thalassemia. A systematic search was conducted in PubMed, Institute for Scientific Information (ISI) Web of Science, Scopus, Cochrane Central Register of Controlled Trials, and Virtual Health Library. Original studies reporting the use of CCBs in patients with thalassemia were included for meta-analysis. A total of five randomized studies including 210 patients were included with a follow-up period of 3-12 months. There was no significant difference between amlodipine and control groups in increasing the heart T2* magnetic resonance imaging (MRI) [mean difference (MD) 95% confidence interval (95% CI) = -1.9 (-4.4 to 0.5), = 0.119] or reducing the liver iron concentration [MD 95% CI = -0.046 (-0.325 to 0.2), = 0.746]. Although there were no serious adverse events reported in the included trials, further studies are recommended to strengthen our findings.
Topics: Amlodipine; Biomarkers; Calcium Channel Blockers; Chelation Therapy; Drug Therapy, Combination; Humans; Iron Chelating Agents; Iron Overload; Magnetic Resonance Imaging; Randomized Controlled Trials as Topic; Treatment Outcome; beta-Thalassemia
PubMed: 33430665
DOI: 10.1080/03630269.2020.1853561 -
Genetics in Medicine : Official Journal... Jan 2021Hydrops fetalis (HF), accumulation of fluid in two or more fetal compartments, is life-threatening to the fetus. Genetic etiologies include many chromosomal and...
Hydrops fetalis (HF), accumulation of fluid in two or more fetal compartments, is life-threatening to the fetus. Genetic etiologies include many chromosomal and monogenic disorders. Despite this, the clinical workup typically evaluates limited genetic targets. To support broader molecular testing of pregnancies with HF, we cataloged the spectrum of monogenic disorders associated with nonimmune hydrops fetalis (NIHF). We performed a systematic literature review under PROSPERO tag CRD42018099495 of cases reporting NIHF meeting strict phenotypic criteria and well-defined genetic diagnosis. We ranked the evidence per gene based on number of reported cases, phenotype, and molecular/biochemical diagnosis. We identified 131 genes with strong evidence for an association with NIHF and 46 genes with emerging evidence spanning the spectrum of multisystem syndromes, cardiac disorders, hematologic disorders, and metabolic disorders. Several genes previously implicated with NIHF did not have any reported cases in the literature with both fetal hydrops and molecular diagnosis. Many genes with strong evidence for association with NIHF would not be detected using current sequencing panels. Nonimmune HF has many possible monogenic etiologies, several with treatment implications, but current diagnostic approaches are not exhaustive. Studies are needed to assess if broad sequencing approaches like exome sequencing are useful in clinical management of HF.
Topics: Female; Fetus; Humans; Hydrops Fetalis; Pregnancy; Prenatal Care; Exome Sequencing
PubMed: 33082562
DOI: 10.1038/s41436-020-00967-0 -
The Cochrane Database of Systematic... Aug 2019Thalassaemia is a quantitative abnormality of haemoglobin caused by mutations in genes controlling production of alpha or beta globins. Abnormally unpaired globin chains...
BACKGROUND
Thalassaemia is a quantitative abnormality of haemoglobin caused by mutations in genes controlling production of alpha or beta globins. Abnormally unpaired globin chains cause haemolytic anaemia by causing membrane damage and cell death within organ systems and destruction of erythroid precursors in the bone marrow. The life-long management of the general health effects of thalassaemia in affected individuals is a highly challenging issue in and of itself; and failure to deal with dental and orthodontic complications in people with thalassaemia exacerbates the public health, financial and personal burden posed by the condition. There exists a lack of evidence-based guidelines for care-seekers and providers to best deal with such dental and orthodontic complications in thalassaemia, which this review seeks to address.
OBJECTIVES
The main objective of this review was to assess different methods to treat dental and orthodontic complications in people with thalassaemia.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We searched the reference lists of relevant articles and reviews.Date of last search: 01 August 2019.We also searched nine online databases (PubMed, Google Scholar, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Literature in the Health Sciences in Latin America and the Caribbean database, African Index Medicus, Index Medicus for South East Asia Region, Index Medicus for the Eastern Mediterranean Region, Indexing of Indian Medical Journals). We searched the reference lists of relevant articles and reviews and contacted haematologists, experts in fields of dentistry, organizations, pharmaceutical companies and researchers working in this field.Date of last search: 22 July 2019.
SELECTION CRITERIA
We searched for published or unpublished randomised controlled trials for treatment of dental and orthodontic complications in individuals diagnosed with thalassaemia, irrespective of phenotype, severity, age, gender and ethnic origin.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened 35,202 titles from search results. We identified four unique randomised controlled trials, of which one seemed potentially relevant. Based on closer inspection, the trial was found not to be eligible for inclusion.
MAIN RESULTS
We did not find any relevant trials for inclusion in the review.
AUTHORS' CONCLUSIONS
We were unable to draw any conclusions due to the lack of available data and trials. This review highlights the need for conducting and appropriate reporting, of high-quality randomised controlled trials investigating the effectiveness of various treatment modalities for dental and orthodontic complications in people with thalassaemia.
Topics: Humans; Malocclusion; Randomized Controlled Trials as Topic; Thalassemia; Tooth Diseases
PubMed: 31425614
DOI: 10.1002/14651858.CD012969.pub2 -
Nonimmune hydrops fetalis and congenital disorders of glycosylation: A systematic literature review.Journal of Inherited Metabolic Disease Mar 2020Numerous etiologies may lead to nonimmune hydrops fetalis (NIHF) including congenital disorders of glycosylation (CDG). Recognition of CDG in NIHF is challenging. This...
Numerous etiologies may lead to nonimmune hydrops fetalis (NIHF) including congenital disorders of glycosylation (CDG). Recognition of CDG in NIHF is challenging. This study reviews prenatal and neonatal characteristics of CDG presenting with NIHF. A systematic literature search was performed. Thirteen articles met the inclusion criteria. Twenty-one cases with NIHF associated with a CDG were reported. There were 17 live births, three pregnancy terminations, and one fetal demise. Timing of CDG diagnosis was reported mostly postnatally (90%; 10/11). Postnatal genetic testing was reported in 18 patients; three patients were diagnosed by isoelectric focusing of serum transferrin that showed a type 1 pattern. The genes reported for CDG with NIHF for 15 distinct families include: PMM2 in 47% (7/15), ALG9 in 20% (3/15), ALG8 in 13% (2/15), ALG1 in 7% (1/15), MGAT2 in 7% (1/15), and COG6 7% (1/15). In our review, 81% (17/21) reported facial dysmorphism, 52% (11/21) reported CNS abnormalities, most commonly cerebellar atrophy (64%; 7/11), and 38% (8/21) reported cardiovascular abnormalities, most commonly hypertrophic cardiomyopathy (63%; 5/8). Among live births, 71% (12/17) infants died at a median age of 34 days (range 1-185). Thrombocytopenia was reported in 53% (9/17) patients. Of those who survived past the neonatal period, 80% (4/5) had significant reported developmental delays. CDG should be on the differential diagnosis of NIHF in the presence of cerebellar atrophy, hypertrophic cardiomyopathy, or thrombocytopenia. Our review highlights the poor prognosis in infants with NIHF due to CDG and demonstrates the importance of identifying these disorders prenatally to guide providers in their counseling with families regarding pregnancy management. SYNOPSIS: Poor prognosis in fetuses and infants with nonimmune hydrops fetalis due to congenital disorders of glycosylation highlights the importance of prenatal diagnosis of this disorder.
Topics: Congenital Disorders of Glycosylation; Female; Fetal Death; Glycosylation; Humans; Hydrops Fetalis; Infant, Newborn; Phosphotransferases (Phosphomutases); Pregnancy; Prenatal Diagnosis
PubMed: 31420886
DOI: 10.1002/jimd.12162 -
Ultrasound in Obstetrics & Gynecology :... Apr 2020To report the perinatal outcome of singleton pregnancies complicated by placental chorioangioma diagnosed on prenatal ultrasound. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To report the perinatal outcome of singleton pregnancies complicated by placental chorioangioma diagnosed on prenatal ultrasound.
METHODS
MEDLINE, EMBASE, CINAHL and ClinicalTrials.gov databases were searched for studies reporting the outcome of pregnancies complicated by placental chorioangioma. Inclusion criteria were singleton pregnancy diagnosed with placental chorioangioma on prenatal ultrasound, with no other associated structural anomaly. The primary outcome was perinatal mortality. Secondary outcomes included associated non-structural anomalies detected on prenatal ultrasound (including fetal hydrops, anemia, polyhydramnios, signs of hyperdynamic circulation and small-for-gestational-age (SGA) fetus), SGA at birth, composite neonatal morbidity and preterm birth. Outcome was assessed separately in pregnancies undergoing and those not undergoing fetal therapy. Subanalyses were performed according to the presence of hydrops and the size of the tumor in all pregnancies diagnosed with chorioangioma. Random-effects meta-analyses of proportions were used to analyze the data.
RESULTS
Twenty-eight studies (161 pregnancies) were included. In pregnancies complicated by chorioangioma that did not undergo intervention, intrauterine death occurred in 8.2% (95% CI, 3.8-15.0%), while neonatal death and perinatal death occurred in 3.8% (95% CI, 1.0-8.1%) and 11.1% (95% CI, 5.0-19.4%), respectively. SGA at birth was present in 24.0% (95% CI, 13.5-36.5%) of cases, while preterm birth < 37 weeks complicated 34.1% (95% CI, 21.1-48.3%) of pregnancies. Composite neonatal morbidity occurred in 12.0% (95% CI, 4.5-22.3%) of cases. On ultrasound, signs of fetal hyperdynamic circulation were present in 21.0% (95% CI, 9.6-35.3%) of cases, while peak systolic velocity in the fetal middle cerebral artery was increased in 20.6% (95% CI, 10.9-32.3%). Subanalysis according to the size of chorioangioma, including both pregnancies that did and those that did not undergo intervention, showed a progressive increase in the occurrence of most of the outcomes explored with increasing size of the tumor. Furthermore, the prevalence of adverse perinatal outcome was high in pregnancies complicated by chorioangioma presenting with fetal hydrops. There was no randomized controlled trial comparing intervention vs expectant management in pregnancies complicated by chorioangioma with signs of fetal compromise (hydrops or hyperdynamic circulation). Overall, perinatal mortality occurred in 31.2% (95% CI, 18.1-46.1%) of fetuses undergoing in-utero therapy, and 57.3% (95% CI, 39.2-74.4%) had resolution of hydrops or hyperdynamic circulation after treatment.
CONCLUSIONS
Placental chorioangioma is associated with adverse perinatal outcome. The size of the mass and presence of fetal hydrops are likely to be the main determinants of perinatal outcome in affected pregnancies. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.
Topics: Adult; Female; Hemangioma; Humans; Hydrops Fetalis; Infant, Newborn; Perinatal Death; Perinatal Mortality; Placenta Diseases; Pregnancy; Pregnancy Complications, Neoplastic; Pregnancy Outcome; Ultrasonography, Prenatal
PubMed: 31034661
DOI: 10.1002/uog.20304 -
Hematology (Amsterdam, Netherlands) Dec 2019Beta-thalassemias are a group of recessively autosomal inherited disorders of hemoglobin synthesis, which, due to mutations of the beta-globin gene, lead to various...
OBJECTIVES
Beta-thalassemias are a group of recessively autosomal inherited disorders of hemoglobin synthesis, which, due to mutations of the beta-globin gene, lead to various degrees of defective beta-chain production, an imbalance in alpha/beta-globin chain synthesis, ineffective erythropoiesis, and anemia. Improved survival in thalassemic patients has led to the emergence of previously unrecognized complications, such as renal disease.
METHODS
A comprehensive literature review through PubMed was undertaken to summarize the published evidence on the epidemiology and pathophysiology of renal disease in thalassemia. Literature sources published in English since 1990 were searched, using the terms beta-thalassemia, renal disease.
RESULTS
Renal disease is considered to be the 4th cause of morbidity among patients with transfusion dependent thalassemia. Chronic anemia, hypoxia and iron overload are the main mechanisms implicated in development of renal injury, whereas several studies also suggested a contributive role of iron chelators.
DISCUSSION AND CONCLUSION
Kidney disease may develop through progressive renal tubular and glomerular damage; thus, its early recognition is important in order to prevent and/or reverse deterioration. This review will provide an insight on the involved mechanisms implicated in kidney disease in thalassemic patients and will discuss the updates on diagnosis and prevention of renal complications in thalassemia.
Topics: Female; Humans; Hypoxia; Iron Overload; Kidney Diseases; Male; beta-Thalassemia
PubMed: 30947625
DOI: 10.1080/16078454.2019.1599096 -
Journal of Clinical Virology : the... May 2019Human parvovirus B19 (B19) is widespread infection in humans, yet the impact on adverse pregnancy outcomes is controversial. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Human parvovirus B19 (B19) is widespread infection in humans, yet the impact on adverse pregnancy outcomes is controversial.
OBJECTIVE
to evaluate the impact of B19 infection during pregnancy on adverse pregnancy outcome, and investigated the incidence of fetal loss and fetal hydrops after maternal B19 infection during pregnancy.
STUDY DESIGN
A systematic literature search was performed using Embase, Medline, PubMed, Web of science, and the Cochrane Library database for relevant publications up to 10 August 2018. Cohort studies and case-control studies were included in analyses.
RESULTS
In total, 36 eligible studies were included. Of these, 18 studies reported the risk of maternal B19 infection during pregnancy on fetal loss and 20 studies reported the incidence of fetal loss or fetal hydrops after maternal B19 infection. Collectively, the results indicated that maternal B19 infection increased the risk of fetal loss, spontaneous abortion, and stillbirth with ORs of 2.68 (95% CI: 2.02-3.55), 2.42 (95% CI: 1.76-3.33), and 3.53 (95% CI: 1.91-6.54), respectively, when compared with uninfected pregnant women. In addition, the incidence of fetal loss and fetal hydrops in B19 infected pregnant women was 7.6% (95% CI: 5.5-9.5) and 9.3% (95% CI: 5.6-13.0), respectively.
CONCLUSIONS
maternal parvovirus B19 infection during pregnancy increased the risk of fetal loss, spontaneous abortion, and stillbirth. A high incidence of fetal loss and fetal hydrops was observed in pregnant women with parvovirus B19 infection.
Topics: Abortion, Spontaneous; Female; Fetal Death; Humans; Hydrops Fetalis; Parvoviridae Infections; Parvovirus B19, Human; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Outcome; Risk Factors; Stillbirth
PubMed: 30897374
DOI: 10.1016/j.jcv.2019.03.004 -
Ultrasound in Obstetrics & Gynecology :... Nov 2018To explore the outcome of fetuses affected by congenital parvovirus B19 (PB19) infection, with or without signs of hydrops on ultrasound. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To explore the outcome of fetuses affected by congenital parvovirus B19 (PB19) infection, with or without signs of hydrops on ultrasound.
METHODS
PubMed, EMBASE and CINAHL databases were searched for studies reporting on prenatal diagnosis and outcome of fetal PB19 infection. The outcomes explored were miscarriage, perinatal death (PND), intrauterine death, neonatal death, spontaneous resolution of hydrops or fetal anemia, need for intrauterine transfusion (IUT), resolution of hydrops or anemia after transfusion, fetal loss following transfusion, abnormal brain scan after birth and abnormal neurodevelopmental outcome. Outcomes were reported according to the presence or absence of signs of hydrops on ultrasound. A subgroup analysis was performed including hydropic and non-hydropic fetuses diagnosed at < 20 weeks and ≥ 20 weeks of gestation. Meta-analyses of proportions and meta-analyses using individual-data random-effects logistic regression were performed to analyze the data.
RESULTS
Thirty-five observational studies were included, involving 611 fetuses affected by PB19 infection. The risks of miscarriage (odds ratio (OR), 11.5; 95% CI, 2.7-49.7) and PND (OR, 4.2; 95% CI, 1.6-11.0) were higher in fetuses with PB19 infection presenting, compared with those not presenting, signs of hydrops on ultrasound. In fetuses affected by hydrops, spontaneous resolution of the infection, defined as disappearance of hydrops without need for IUT, occurred in 5.2% (95% CI, 2.5-8.8%) of cases whereas, in the group of fetuses not affected by hydrops, infection resolved in 49.6% (95% CI, 20.7-78.6%) of cases. IUT was performed in 78.7% (95% CI, 66.4-88.8%) of hydropic and in 29.6% (95% CI, 6.0-61.6%) of non-hydropic fetuses affected by congenital PB19 infection and resolution of the infection after IUT occurred in 55.1% (95% CI, 34.0-75.3%) and in 100% (95% CI, 57.3-100%) of cases, respectively. The risk of fetal loss after IUT was higher in fetuses affected compared with those not affected by hydrops (OR, 9.8; 95% CI, 2.8-34.6). The prevalence of abnormal brain imaging was 9.8% (95% CI, 2.5-21.0%) in fetuses affected and 0.0% (95% CI, 0.0-7.0%) in those not affected by hydrops, whilst the corresponding figures for abnormal neurodevelopmental outcome were 9.5% (95% CI, 2.6-20.2) and 0.0% (95% CI, 0.0-7.5), respectively; however, statistical power to assess these outcomes was inadequate due to the small number of included cases.
CONCLUSIONS
Hydrops is the main determinant of mortality and adverse perinatal outcome in fetuses with PB19 infection. Perinatal outcome in non-hydropic fetuses is generally favorable. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.
Topics: Erythema Infectiosum; Female; Fetal Death; Gestational Age; Humans; Hydrops Fetalis; Parvovirus B19, Human; Pregnancy; Pregnancy Complications, Infectious; Prenatal Diagnosis
PubMed: 29785793
DOI: 10.1002/uog.19092 -
Clinical Infectious Diseases : An... Feb 2018Artemisinin derivatives are widely used antimalarial drugs. There is some evidence from in vitro, animal and clinical studies that hemoglobinopathies may alter their...
Artemisinin derivatives are widely used antimalarial drugs. There is some evidence from in vitro, animal and clinical studies that hemoglobinopathies may alter their disposition and antimalarial activity. This review assesses relevant data in α-thalassemia, sickle cell disease (SCD), β-thalassemia and hemoglobin E. There is no convincing evidence that the disposition of artemisinin drugs is affected by hemoglobinopathies. Although in vitro studies indicate that Plasmodium falciparum cultured in thalassemic erythrocytes is relatively resistant to the artemisinin derivatives, mean 50% inhibitory concentrations (IC50s) are much lower than in vivo plasma concentrations after recommended treatment doses. Since IC50s are not increased in P. falciparum cultures using SCD erythrocytes, delayed post-treatment parasite clearance in SCD may reflect hyposplenism. As there have been no clinical studies suggesting that hemoglobinopathies significantly attenuate the efficacy of artemisinin combination therapy (ACT) in uncomplicated malaria, recommended artemisinin doses as part of ACT remain appropriate in this patient group.
Topics: Antimalarials; Artemisinins; Hemoglobinopathies; Humans; Malaria, Falciparum
PubMed: 29370347
DOI: 10.1093/cid/cix785 -
The Journal of Maternal-fetal &... Jun 2019To explore the effect of maternal fluorinated steroid therapy on fetuses affected by immune-mediated complete atrio-ventricular block (CAVB) in utero. (Meta-Analysis)
Meta-Analysis
INTRODUCTION
To explore the effect of maternal fluorinated steroid therapy on fetuses affected by immune-mediated complete atrio-ventricular block (CAVB) in utero.
MATERIAL AND METHODS
Pubmed, Embase, Cinahl, and ClinicalTrials.gov databases were searched. Only studies reporting the outcome of fetuses with immune CAVB diagnosed on prenatal ultrasound without any cardiac malformations and treated with fluorinated steroids compared to those not treated were included. The primary outcome observed was the regression of CAVB; secondary outcomes were need for pacemaker insertion, overall mortality, defined as the occurrence of either intrauterine (IUD) or neonatal (NND) death, IUD, NND, termination of pregnancy (TOP). Furthermore, we assessed the occurrence of all these outcomes in hydropic fetuses compared to those without hydrops at diagnosis. Meta-analyses of proportions using random effect model and meta-analyses using individual data random-effect logistic regression were used to combine data.
RESULTS
Eight studies (162 fetuses) were included. The rate of regression was 3.0% (95%CI 0.2-9.1) in fetuses treated and 4.3% (95%CI 0.4-11.8) in those not treated, with no difference between the two groups (odds ratio (OR): 0.9, 95%CI 0.1-15.1). Pacemaker at birth was required in 71.5% (95%CI 56.0-84.7) of fetuses-treated and 57.8% (95%CI 40.3-74.3) of those not treated (OR: 9, 95%CI 0.4-3.4). There was no difference in the overall mortality rate (OR: 0.5, 95%CI 0.9-2.7) between the two groups; in hydropic fetuses, mortality occurred in 76.2% (95%CI 48.0-95.5) of the treated and in 23.8% (95%CI 1.2-62.3) of the untreated group, while in those without hydrops the corresponding figures were 8.9% (95%CI 2.0-20.3) and 12% (95%CI 8.7-42.2), respectively. Improvement or resolution of hydrops during pregnancy occurred in 76.2% (95%CI 48.0-95.5) of cases treated and in 23.3% (95%CI 1.2-62.3) of those nontreated with fluorinated steroids.
CONCLUSIONS
The findings from this systematic review do not suggest a potential positive contribution of antenatal steroid therapy in improving the outcome of fetuses with immune CAVB.
Topics: Atrioventricular Block; Female; Humans; Hydrops Fetalis; Pregnancy; Steroids, Fluorinated
PubMed: 29251180
DOI: 10.1080/14767058.2017.1419182