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Blood Sep 2020Congenital dyserythropoietic anemias (CDAs) are a heterogeneous group of inherited anemias that affect the normal differentiation-proliferation pathways of the erythroid... (Review)
Review
Congenital dyserythropoietic anemias (CDAs) are a heterogeneous group of inherited anemias that affect the normal differentiation-proliferation pathways of the erythroid lineage. They belong to the wide group of ineffective erythropoiesis conditions that mainly result in monolinear cytopenia. CDAs are classified into the 3 major types (I, II, III), plus the transcription factor-related CDAs, and the CDA variants, on the basis of the distinctive morphological, clinical, and genetic features. Next-generation sequencing has revolutionized the field of diagnosis of and research into CDAs, with reduced time to diagnosis, and ameliorated differential diagnosis in terms of identification of new causative/modifier genes and polygenic conditions. The main improvements regarding CDAs have been in the study of iron metabolism in CDAII. The erythroblast-derived hormone erythroferrone specifically inhibits hepcidin production, and its role in the mediation of hepatic iron overload has been dissected out. We discuss here the most recent advances in this field regarding the molecular genetics and pathogenic mechanisms of CDAs, through an analysis of the clinical and molecular classifications, and the complications and clinical management of patients. We summarize also the main cellular and animal models developed to date and the possible future therapies.
Topics: Anemia, Dyserythropoietic, Congenital; Animals; Blood Transfusion; Diagnosis, Differential; Disease Models, Animal; Genetic Heterogeneity; Glycoproteins; Hematopoietic Stem Cell Transplantation; Hepcidins; High-Throughput Nucleotide Sequencing; Humans; Hydrops Fetalis; Iron Overload; Kruppel-Like Transcription Factors; Mice; Mice, Knockout; Microtubule-Associated Proteins; Molecular Diagnostic Techniques; Nuclear Proteins; Peptide Hormones; Vesicular Transport Proteins; Zebrafish
PubMed: 32702750
DOI: 10.1182/blood.2019000948 -
The New England Journal of Medicine Oct 2020The cause of most fetal anomalies is not determined prenatally. Exome sequencing has transformed genetic diagnosis after birth, but its usefulness for prenatal diagnosis...
BACKGROUND
The cause of most fetal anomalies is not determined prenatally. Exome sequencing has transformed genetic diagnosis after birth, but its usefulness for prenatal diagnosis is still emerging. Nonimmune hydrops fetalis (NIHF), a fetal abnormality that is often lethal, has numerous genetic causes; the extent to which exome sequencing can aid in its diagnosis is unclear.
METHODS
We evaluated a series of 127 consecutive unexplained cases of NIHF that were defined by the presence of fetal ascites, pleural or pericardial effusions, skin edema, cystic hygroma, increased nuchal translucency, or a combination of these conditions. The primary outcome was the diagnostic yield of exome sequencing for detecting genetic variants that were classified as either pathogenic or likely pathogenic according to the criteria of the American College of Medical Genetics and Genomics. Secondary outcomes were the percentage of cases associated with specific genetic disorders and the proportion of variants that were inherited.
RESULTS
In 37 of the 127 cases (29%), we identified diagnostic genetic variants, including those for disorders affecting the RAS-MAPK cell-signaling pathway (known as RASopathies) (30% of the genetic diagnoses); inborn errors of metabolism and musculoskeletal disorders (11% each); lymphatic, neurodevelopmental, cardiovascular, and hematologic disorders (8% each); and others. Prognoses ranged from a relatively mild outcome to death during the perinatal period. Overall, 68% of the cases (25 of 37) with diagnostic variants were autosomal dominant (of which 12% were inherited and 88% were de novo), 27% (10 of 37) were autosomal recessive (of which 95% were inherited and 5% were de novo), 1 was inherited X-linked recessive, and 1 was of uncertain inheritance. We identified potentially diagnostic variants in an additional 12 cases.
CONCLUSIONS
In this large case series of 127 fetuses with unexplained NIHF, we identified a diagnostic genetic variant in approximately one third of the cases. (Funded by the UCSF Center for Maternal-Fetal Precision Medicine and others; ClinicalTrials.gov number, NCT03412760.).
Topics: Female; Genetic Variation; Humans; Hydrops Fetalis; Pregnancy; Prenatal Diagnosis; Prognosis; Exome Sequencing
PubMed: 33027564
DOI: 10.1056/NEJMoa2023643 -
Ugeskrift For Laeger Oct 2022Congenital hydrops fetalis describes an abnormal accumulation of fluid in two or more compartments in a fetus. The disease is categorized based on the aetiology: immune-... (Review)
Review
Congenital hydrops fetalis describes an abnormal accumulation of fluid in two or more compartments in a fetus. The disease is categorized based on the aetiology: immune- and non-immune hydrops fetalis. Today, the non-immune form is the most common. Once born, the child is initially handled symptomatically and will often need intensive care and treatment. Even though approximately one in five cases is still idiopathic, genetic diagnostic tools have become increasingly important in the diagnostic process. The prognosis depends on the aetiology and the gestational age when diagnosed and at birth, as argued in this review.
Topics: Infant, Newborn; Female; Child; Humans; Hydrops Fetalis; Gestational Age; Prognosis
PubMed: 36331166
DOI: No ID Found -
Hemolytic disease of the fetus and newborn: systematic literature review of the antenatal landscape.BMC Pregnancy and Childbirth Jan 2023Prevention of pregnancy-related alloimmunization and the management of hemolytic disease of the fetus and newborn (HDFN) has significantly improved over the past...
BACKGROUND
Prevention of pregnancy-related alloimmunization and the management of hemolytic disease of the fetus and newborn (HDFN) has significantly improved over the past decades. Considering improvements in HDFN care, the objectives of this systematic literature review were to assess the prenatal treatment landscape and outcomes of Rh(D)- and K-mediated HDFN in mothers and fetuses, to identify the burden of disease, to identify evidence gaps in the literature, and to provide recommendations for future research.
METHODS
We performed a systematic search on MEDLINE, EMBASE and clinicaltrials.gov. Observational studies, trials, modelling studies, systematic reviews of cohort studies, and case reports and series of women and/or their fetus with HDFN caused by Rhesus (Rh)D or Kell alloimmunization. Extracted data included prevalence; treatment patterns; clinical outcomes; treatment efficacy; and mortality.
RESULTS
We identified 2,541 articles. After excluding 2,482 articles and adding 1 article from screening systematic reviews, 60 articles were selected. Most abstracted data were from case reports and case series. Prevalence was 0.047% and 0.006% for Rh(D)- and K-mediated HDFN, respectively. Most commonly reported antenatal treatment was intrauterine transfusion (IUT; median frequency [interquartile range]: 13.0% [7.2-66.0]). Average gestational age at first IUT ranged between 25 and 27 weeks. weeks. This timing is early and carries risks, which were observed in outcomes associated with IUTs. The rate of hydrops fetalis among pregnancies with Rh(D)-mediated HDFN treated with IUT was 14.8% (range, 0-50%) and 39.2% in K-mediated HDFN. Overall mean ± SD fetal mortality rate that was found to be 19.8%±29.4% across 19 studies. Mean gestational age at birth ranged between 34 and 36 weeks.
CONCLUSION
These findings corroborate the rareness of HDFN and frequently needed intrauterine transfusion with inherent risks, and most births occur at a late preterm gestational age. We identified several evidence gaps providing opportunities for future studies.
Topics: Female; Humans; Pregnancy; Erythroblastosis, Fetal; Hydrops Fetalis; Hemolysis; Blood Transfusion, Intrauterine; Fetus
PubMed: 36611144
DOI: 10.1186/s12884-022-05329-z -
Pediatrics and Neonatology Apr 2014
Topics: Humans; Hydrops Fetalis; Infant, Newborn
PubMed: 24345792
DOI: 10.1016/j.pedneo.2013.10.005 -
Journal of Medical Genetics Feb 1992Seventy-two fetuses or neonates with non-immune hydrops were examined between 1983 and 1988. The commonest association was chromosome abnormality; 11 fetuses had a 45,X... (Comparative Study)
Comparative Study Review
Seventy-two fetuses or neonates with non-immune hydrops were examined between 1983 and 1988. The commonest association was chromosome abnormality; 11 fetuses had a 45,X karyotype and 11 autosomal trisomy. Chromosome abnormality was suspected in a further 20 on necropsy findings but chromosome culture was not possible or unsuccessful. In 11 cases there was histological evidence of infection; seven babies had major structural anomalies and six affected fetuses were twins. In six (8%) the cause of hydrops was not determined compared with eight (16%) of cases examined between 1976 and 1982. Hydrops was diagnosed more frequently while the fetus was alive, before 20 weeks' gestation, and associated with chromosome anomaly than found previously.
Topics: Chromosome Aberrations; Diseases in Twins; Female; Gestational Age; Humans; Hydrops Fetalis; Infections; Pregnancy; Prenatal Diagnosis; Viscera
PubMed: 1613772
DOI: 10.1136/jmg.29.2.91 -
The Turkish Journal of Pediatrics 2019Yuan SM, Lin H. Fetal intrapericardial teratomas. Turk J Pediatr 2019; 61: 153-158. Fetal intrapericardial teratomas are rare and benign. However, they can be... (Review)
Review
Yuan SM, Lin H. Fetal intrapericardial teratomas. Turk J Pediatr 2019; 61: 153-158. Fetal intrapericardial teratomas are rare and benign. However, they can be life-threatening owing to the complicated massive pericardial effusions, tamponade, or cardiorespiratory distress. The purpose of this review is to give an overview on clinical features, management and prognoses of fetal intrapericardial teratomas. The materials of this study were based on a comprehensive literature retrieval of fetal intrapericardial teratomas published in the past two decades. It was noteworthy that fetal pericardial/pleural effusions or ascites were detected since 19-week gestation, and tumors could be found since 21-week gestation. A growing trend of tumors was observed in more than half of the cases. Prenatal centesis and postnatal tumor resection were required in most of the cases. Fetoneonatal deaths (including fetal demise, termination of pregnancy and neonatal death) occurred in one-third of the cases. The neonatal survival rate was 59.4%. Symptomatic fetuses usually required perinatal maneuvers, such as pericardiocentesis, or thoraco-/ pericardio-amniotic shunt in order to improve fetal hemodynamic status and prolong the pregnancy for lung maturity. Open fetal surgery and ex utero intrapartum treatment (EXIT) procedure can be considered, however, impact of EXIT procedure on later delivery remains uncertain. Postnatal operation is a curative and symptom-relieving method for those cases with prenatally diagnosed intrapericardial teratomas. As a result, the fetoneonatal outcomes are somewhat promising.
Topics: Abortion, Induced; Female; Fetal Death; Fetal Heart; Heart Neoplasms; Humans; Hydrops Fetalis; Infant, Newborn; Paracentesis; Pericardial Effusion; Perinatal Death; Pregnancy; Prenatal Diagnosis; Teratoma
PubMed: 31951327
DOI: 10.24953/turkjped.2019.02.001 -
Hellenic Journal of Cardiology : HJC =... 2019Fetal arrhythmias warrant sophisticated surveillance and management, especially for the high-risk pregnancies. Clinically, fetal arrhythmias can be categorized into 3... (Review)
Review
Fetal arrhythmias warrant sophisticated surveillance and management, especially for the high-risk pregnancies. Clinically, fetal arrhythmias can be categorized into 3 types: premature contractions, tachyarrhythmias, and bradyarrhythmias. Fetal arrhythmias include electrocardiography, cardiotocography, echocardiography and magnetocardiography. Oxygen saturation monitoring can be an effective way of fetal surveillance for congenital complete AV block or SVT during labor. Genetic surveillance of fetal arrhythmias may facilitate the understanding of the mechanisms of the arrhythmias and provide theoretical basis for diagnosis and treatment. For fetal benign arrhythmias, usually no treatment but a close follow-up is need, while persistant fetal arrhythmias with congestive heart dysfunction or hydrops fetalis, intrauterine or postnatal treatments are required. The prognoses of fetal arrhythmias depend on the type and severity of fetal arrhythmias and the associated fetal conditions. Responses of fetal arrhythmias to individual treatments and clinical schemes are heterogeneous, and the prognoses are poor particularly under such circumstances.
Topics: Arrhythmias, Cardiac; Bradycardia; Cardiotocography; Echocardiography; Electrocardiography; Female; Fetal Diseases; Fetal Therapies; Fetus; Heart Failure; Humans; Hydrops Fetalis; Magnetocardiography; Pregnancy; Prenatal Care; Prognosis; Tachycardia; Watchful Waiting
PubMed: 30576831
DOI: 10.1016/j.hjc.2018.12.003 -
Current Biology : CB Apr 2017Parpaite and Coste introduce Piezo channels and their role in mechanotransduction.
Parpaite and Coste introduce Piezo channels and their role in mechanotransduction.
Topics: Anemia, Hemolytic, Congenital; Animals; Craniofacial Abnormalities; Humans; Hydrops Fetalis; Ion Channels; Lymphangiectasis, Intestinal; Lymphedema; Mammals; Mechanotransduction, Cellular; Mutation
PubMed: 28376327
DOI: 10.1016/j.cub.2017.01.048 -
Journal of Ultrasound in Medicine :... May 2018Polyhydramnios and placentomegaly are commonly observed in nonimmune hydrops fetalis (NIHF); however, whether their ultrasonographic identification is relevant for...
OBJECTIVES
Polyhydramnios and placentomegaly are commonly observed in nonimmune hydrops fetalis (NIHF); however, whether their ultrasonographic identification is relevant for prognosis is controversial. We evaluated outcomes of fetal or neonatal death and preterm birth (PTB) in cases of NIHF alone and in those with polyhydramnios and/or placentomegaly (P/PM).
METHODS
We conducted a retrospective cohort of singletons with NIHF evaluated between 1994 and 2013. Nonimmune hydrops fetalis was defined as 2 or more abnormal fluid collections, including ascites, pericardial effusion, pleural effusion, and skin edema. Primary outcomes were intrauterine fetal demise (IUFD) and neonatal death. Secondary outcomes were PTB (<37, < 34, and <28 weeks) and spontaneous PTB. Outcomes were compared between cases of NIHF alone and NIHF with P/PM.
RESULTS
A total of 153 cases were included; 21% (32 of 153) had NIHF alone, and 79% (121 of 153) had NIHF with P/PM. There was no significant difference in neonatal death (38.1% versus 43.0%; P = .809) between the groups. Intrauterine fetal demise was seen more frequently in NIHF alone (34.4% versus 17.4%; P = .049). Nonimmune hydrops fetalis-with-P/PM cases were more likely to deliver before 37 weeks (80.0% versus 57.1%; P = .045) and before 34 weeks (60.0% versus 28.6%; P = .015) and to have spontaneous PTB (64.4% versus 33.3%; P = .042). Adjusted odds ratios accounting for the etiology of NIHF supported these findings, with the exception of IUFD.
CONCLUSIONS
Compared to NIHF alone, pregnancies with NIHF and P/PM had a lower risk of IUFD and were at increased risk of PTB (<37 and <34 weeks) and spontaneous PTB. This information may help providers in counseling patients with NIHF and supports the need for close antenatal surveillance.
Topics: Adolescent; Adult; California; Causality; Comorbidity; Female; Fetal Death; Humans; Hydrops Fetalis; Infant; Infant Death; Infant, Newborn; Middle Aged; Placenta; Placenta Diseases; Polyhydramnios; Pregnancy; Premature Birth; Retrospective Studies; Ultrasonography, Prenatal; Young Adult
PubMed: 29076544
DOI: 10.1002/jum.14462