Cases Of Nonimmune Hydrops Fetalis Research Articles

English

Hydrops fetalis is a serious fetal condition characterized by abnormal accumulation of fluid in fetal soft tissues and serous cavities. There are two types of hydrop fetalis:Immune hydrops fetalis (IHF). Non-immune hydrops fetalis (NIHF). We report a case of NIHF delivered by a 18 year old primi gravida. A single female fetus 27 weeks 5 days of gestational age was delivered by caesarean section. The mother was blood group A positive. She went for regular antenatal check-up. Ultrasound at 24 weeks revealed cystic hygroma with hydrops fetalis, severe oligohydramnios and intra-uterine fetal death. On examination, the neonate was a female and grossly oedematous. She showed scalp and body wall edema including limbs edema and ascites. Radiograph of the fetus was taken and fetus was dissected to rule out anomalies in internal organs.

Parvovirus infection: an immunohistochemical study using fetal and placental tissue.

Parvovirus B19 infection causes 5% to 15% of cases of nonimmune hydrops fetalis. The aim of our study was to evaluate the use of immunohistochemistry in diagnosing parvovirus infection in fetal and placental tissue during routine fetal and perinatal autopsies. Histology slides of 20 cases of confirmed parvovirus infection were reviewed, and immunohistochemistry was applied to selected blocks of fetal and placental tissue. Immunohistochemistry was positive in all 20 cases, and histologic viral inclusions were seen in 19 cases. Immunohistochemical staining was closely correlated with histology and was more sensitive than histology in detecting virally infected cells, especially in autolyzed tissue. All cases also had confirmatory evidence of parvovirus infection by polymerase chain reaction of fetal liver and positive maternal serology, where it was available. We conclude that parvovirus immunohistochemistry is a reliable method for diagnosing parvovirus infection, especially in autolyzed tissue where histologic assessment may be suboptimal.

Non-immune hydrops fetalis

Non-immune hydrops fetalis (NIHF) refers to hydrops in the absence of maternal circulating red-cell antibodies, and constitutes up to 90% of all described hydrops fetalis cases. One-third of hydropic fetuses are discovered incidentally during prenatal sonography in the first or second trimester of gestation. Although hydrops is a fetal condition, in many cases there are associated maternal findings, such as preeclampsia, polyhydramnios, and mirror syndrome (generalized maternal edema, that ‘mirrors’ the edema of the hydropic fetus and placenta). NIHF should be seen as a symptom or clinical phenotype rather than as a disorder, and considered as a non-specific, end-stage status of a wide variety of disorders. Numerous disorders including fetal disorders, maternal diseases (e.g., severe maternal anemia, diabetes and maternal indomethacin use) and placental/cord abnormalities have been associated with NIHF. Despite extensive investigations, the etiology on NIHF may remain unknown in 15% to 25% of patients, even after an autopsy has been performed. Chromosomal abnormalities are the cause of NIHF in 25-70% of the cases. Therefore, fetal or neonatal chromosome analysis is indicated in all cases of NIHF. Abnormalities of the cardiovascular system are responsible for as many as 40% of cases of NIHF. Thoracic abnormalities increase intrathoracic pressure and can obstruct venous return to the heart, leading to peripheral venous congestion, or they may obstruct the lymphatic duct, resulting in lymphedema. Fetal anemia accounts for 10-27% of hydrops. To evaluate the risk of fetal anemia, Doppler measurement of the middle cerebral artery peak systolic velocity should be performed in all hydropic fetuses after 16 weeks of gestation. Parvovirus B19 is the most common infectious agent associated with hydrops. Even in persistent severe anemia, the prognosis is generally good if the fetus is supported by intrauterine fetal transfusions. The development of hydrops in fetuses with a TORCH infection is a poor prognostic indicator. Although hypoproteinemia is frequently proposed as one of the causes of hydrops fetalis, recent studies show that hypoalbuminemia is unlikely to cause the initial development of hydrops. However, it seems to occur as a secondary effect in the cascade of hydrops, and might be the trigger for mild hydrops to evolve into severe hydrops. In addition, not all infants with hypoproteinemia become hydropic, and hydrops fetalis is uncommon in congenital nephrotic syndrome and congenital analbuminemia. In the pathogenesis, inherited metabolic disorders, especially lysosomal storage diseases, are more common than previously thought. Inherited metabolic disorders must be always thought when investigating cases of recurrent NIHF in the same family. It is very important to examine the placenta carefully in cases where hydrops or ascites are present at birth or detected by ultrasound, especially in the transient form. Even if a family does not agree to autopsy, placental examination may be done. Proceedings of the 10 th International Workshop on Neonatology · Cagliari (Italy) · October 22 nd -25 th , 2014 · The last ten years, the next ten years in Neonatology Guest Editors: Vassilios Fanos, Michele Mussap, Gavino Faa, Apostolos Papageorgiou

Association of Nonimmune Hydrops Fetalis With Familial Hemophagocytic Lymphohistiocytosis in Identical Twin Neonates With Perforin His222Arg (c665A>G) Mutation

This is the first study demonstrating that nonimmune hydrops fetalis (NIHF) in identical twin neonates is associated with biallelic gene defect causing familial hemophagocytic lymphohistiocytosis. Preterm male twins (31(4/7) wk) with NIHF and hepatosplenomegaly gradually developed pancytopenia, hyperferritinemia, hyponatremia, hypoalbuminemia, and elevated alanine aminotransferase, aspartate aminotransferase, bilirubin, and lactate dehydrogenase levels. Suspected sepsis led to antibiotic therapy. Upon detection of hemophagocytosis in bone marrow, multiorgan failure and pulmonary bleeding led to death. Homozygous His222Arg (c665A>G) mutation was identified in Perforin. Familial hemophagocytic lymphohistiocytosis should be considered in first days of NIHF cases to have chance for HLH-2004 therapy. Missense mutations of Perforin codon His222 may lead to intrauterine presentation.

Non-immune hydrops fetalis caused by herpes simplex virus type 2 in the setting of recurrent maternal infection

We report a case of non-immune hydrops fetalis (NIHF) caused by herpes simplex virus type 2 (HSV-2) in an infant whose mother had recurrent HSV-2 infection. In spite of prematurity, severe disseminated infection and hydrops, the infant survived and was neurologically intact. HSV-2-induced NIHF is extremely rare, particularly in the setting of recurrent maternal infection, and this case is, to our knowledge, the first report of a surviving infant. HSV-2 should be considered in the differential diagnosis of NIHF and early initiation of empiric acyclovir therapy is recommended in this setting, pending the results of virologic diagnostic tests.

Nonimmune hydrops fetalis in a children’s hospital: a six-year series

We aimed to study the profile of nonimmune hydrops fetalis (NIHF) in the local population and identify its outcomes and causes. We carried out a retrospective review of the medical records in KK Women's and Children's hospital, a single tertiary referral centre, for pregnancies with an antenatal diagnosis of NIHF in the six-year period from 1 January 2005 to 31 December 2010. A total of 29 cases of NIHF were identified; 19 (66%) cases underwent karyotype evaluation, 17 (59%) underwent intrauterine infection screening, and all underwent antenatal thalassaemia screening. The median gestational age at diagnosis was 27 (range 12-37) weeks, median gestational age at birth was 33 (range 27-37) weeks, and median birth weight of live births was 2,480 (range 1,230-3,900) g. The aetiologies for NIHF were identified in 20 (69%) cases, which included cardiac anomalies (n = 5), haematological problems (n = 4), congenital tumours (n = 4), genetic/metabolic disorders (n = 4) and cystic hygromas (n = 3). The cause of NIHF was not identified in the remaining 9 (31%) cases. There were 19 live births - 8 (42%) survived and 11 (58%) died in the neonatal period - and one stillbirth. Nine women opted for medical termination of pregnancy following the diagnosis of NIHF. It is important to thoroughly investigate all cases of NIHF and identify its causes in order to provide appropriate antenatal and postnatal counselling. In our series, almost one-third of NIHF cases had no identified aetiology. The neonatal mortality rate was approximately 58%.

Non‐immune hydrops fetalis: A prospective study of 53 cases

Non-immune hydrops fetalis (NIHF) is a symptom caused by a heterogeneous group of conditions. Diagnostic investigations may constitute a real challenge. This study aimed to evaluate prospectively and systematically a series of NIHF cases using a research protocol expanded for studying inborn errors of metabolism (IEM) during 2 years-2010 and 2011. We also reviewed the frequency of IEM among the NIHF reported in literature. A clinical or etiopathogenic diagnosis was reached in 46 (86.8%) of the 53 studied cases. The main diagnostic groups were chromosomal anomalies (28.3%), syndromic (18.9%), isolated cardiovascular anomaly (7.5%) and congenital infection (7.5%). Metabolic causes were found in 5.7%, all lysosomal storage disorders (LSD). In seven (13.2%), no diagnosis was found in part because of incomplete evaluation. The hydrops was identified prenatally in 90.5% of cases. In 5.7% a spontaneous and complete resolution of the hydrops occurred during pregnancy. Overall mortality was 75.5%. The IEM frequency in the present study (5.7%) was higher than that usually reported. We suggest performing studies directed to IEMs if the more common causes are excluded.

Neonatal Bartter syndrome and unilateral ectopic renal cyst as new renal causes of hydrops fetalis: two case reports and review of the literature

Non-immune hydrops fetalis (NIHF) is a challenging entity as it represents the end stage of several different disorders. Renal and genitourinary causes of NIHF are rare and include congenital renal malformations, tumors and ureter-urethra disorders. Herein, two NIHF cases with different renal causes were presented. The first case that had antenatal NIHF was diagnosed neonatal Bartter syndrome. The second case of NIHF with antenatal large cyst in the surrenal gland area required surgery and ectopic renal cyst was diagnosed. To our best of knowledge, these are the first reports of NIHF associated with neonatal Bartter syndrome and ectopic renal cyst in neonates. Although it may be coincidental, these cases suggest that both neonatal Bartter syndrome and unilateral ectopic renal cyst may cause NIHF development in neonates by several different mechanisms. Therefore, these two rare entities should be suspected in cases of NIHF with similar findings.

A Case of Non-Immune Hydrops Fetalis Caused by Wolf-Parkinson-White Syndrome

Hydrops fetalis is a nonspecific clinical condition characterized by an accumulation of fluid in at least two fetal compartments or edema. In the past, most of the cases of hydrops were caused by erythroblastosis fetalis related to Rh alloimmunisation, while today most of them were induced by non-immune conditions. The incidence of non-immune hydrops fetalis is 1:830-4600 per live births. Non-immune hydrops fetalis is mostly associated with chromosomal disorders, cardiac malformations, arrhythmias, and TORCH infections. Despite advances in medicine, the mortality of non-immune hydrops fetalis is still high. In this report, an infant with non-immune hydrops fetalis born at 28th week of gestational age by caeseran section due to hydrops and fetal distress and previously considered to be congenital nephrotic syndrome because of hypoalbuminemia and massive proteinuria, but diagnosed to be Wolf-Parkinson-White Syndrome is presented with literature highlights.

Hidrops fetalis no immune: A propósito de un caso

Presentamos un caso de hidrops fetalis no inmune por trisomía del par 21, diagnosticado a las 31 semanas de gestación. Mediante cordocentesis y estudio cromosómico de linfocitos se llegó al diagnóstico etiológico de síndrome Down. La paciente reingresó a los 6 días del procedimiento con diagnóstico de óbito fetal, produciéndose el parto vaginal electivo al siguiente día. La importancia de este trabajo radica en destacar la factibilidad del diagnóstico citogenético antenatal en nuestro medio mediante técnicas invasivas.

A Case of Nonimmune Hydrops Fetalis Caused by Homozygous α-Thalassemia

Hydrops fetalis is a serious condition which indicates poor prognosis for the affected fetus. Although the incidence of isoimmune hydrops fetalis has decreased markedly, nonimmune hydrops fetalis cases have been more frequently reported. Nonimmune-mediated hydrops can be caused by hemoglobinopathies. In this report we present a case of nonimmune hydrops fetalis caused by homozygous α-thalassemia. Because of the high incidence of the disease in our country, α-thalassemia should be investigated in all cases with nonimmune hydrops fetalis. Conflict of interest:None declared.

A Case of Non-Immune Hydrops Fetalis due to Umbilical Venous Malformation and Noonan Syndrome

Anomalies of the fetal venous system are rare. Major portion of fetal venous anomalies are malformation of umbilical vein and ductus venosus. Abnormal umbilico-systemic shunt, bypassing the ductus venosus makes direct connection between the high-pressure umbilical system and the low-pressure systemic system. And it makes adverse to the fetal hemodynamics. Fetal hemodynamic distress may induce fetal growth retardation, hepatomegaly, cardiomegaly, hydrops fetalis and fetal death. We report a case of non-immune hydrops fetalis which was associated with abnormal umbilical vein pathway. Our patient had bifurcated umbilical veins. Main branch of umbilical vein was drained directly to the left internal iliac vein and another branch was drained to the portal vein. After birth, extrahepatic shunt through main branch of umbilical vein that bypassed the portal system was persisted and thrombocytopenia was combined due to consumption in thrombus of a dilated anomalous umbilical vein. Later this case was diagnosed as Noonan syndrome with a genetic testing.

Non-immune hydrops: Qatar experience

Objective: To describe the presenting signs, diagnostic findings, and outcomes of 64 cases of non-immune hydrops fetalis (NIHF) cases seen in Women’s Hospital, Qatar during the years 2003–2011. Method: A retrospective chart review of patients with signs suggesting of NIHF was done. A detailed scan was performed and karyotyping and detailed investigations were offered. Results: Average maternal age at diagnosis was 31 years. Fifty-six percent of the patients were diagnosed during the 2nd trimester. Most common presenting signs were: ascites, pleural effusion, scalp edema, skin edema, pericardial effusion, generalize edema and cystic hygroma. Two patients were positive for PV B19 infection. Fetal karyotyping performed in 78% of the patients showed abnormal chromosomes in 9 cases. Three patients showed fetal anemia with abnormal peak systolic velocity of the medial cerebral artery (MCA-PSV). Seventeen (27%) fetuses survived the perinatal period with live births occurring between gestational ages 30–41 weeks. Ten (59%) of the 17 babies survived post delivery (6 months post survival data). Major identifiable abnormalities that might have caused symptoms of hydrops were cardiac (23.43%), and chromosomal (14%). Conclusion: Non-immune hydrops fetalis is a complex problem. Establishment of a clear procedure for the follow up of such patients is extremely important.

Fast protocol for the diagnosis of lysosomal diseases in nonimmune hydrops fetalis

Nonimmune hydrops fetalis (NIHF) is defined by the excessive fluid accumulation in more than one foetal compartments and body cavities because of nonimmune reasons. It has been described that 14 lysosomal diseases may be causative of NIHF. The aim of this study was to design a fast protocol to investigate the most frequent lysosomal diseases that are reported that may cause NIHF. We analysed the glycosaminoglycans excretion in the amniotic fluid supernatant and four different lysosomal enzymatic activities in the amniotic cultured cells of the different NIHF amniotic fluids we received. We investigated 30 NIHF cases, using this fast protocol. We detected two cases of NIHF because of lysosomal diseases, which represent 6.6%. We diagnosed one case of mucopolysaccharidosis type VII and one case of Gaucher disease. The fast protocol we designed analyses seven of the most frequent lysosomal pathologies that have been described that may cause NIHF, with only five different determinations, which make the analysis of NIHF fast, cost-effective and without need of too much amniotic fluid. We believe this protocol may be useful for the analysis of lysosomal diseases in NIHF.

Adverse reproductive outcome induced by Parvovirus B19 and TORCH infections in women with high-risk pregnancy

The frequency of fetopathogenic viruses and Toxoplasma gondii infections in the TORCH group (Toxoplasma gondii, rubella virus, cytomegalovirus (CMV), herpes simplex virus) together with Parvovirus B19 (B19) in pregnant women with bad obstetric history (BOH) and/or concurrent pregnancy complications was investigated. Sixty women (20-35 years) with BOH and/or antecedent pregnancy complications were studied. Twenty-nine healthy pregnant women matched for age, parity and gestational age served as controls. Sera were analyzed for IgM antibodies for B19 and TORCH agents by ELISA. Cord blood and 33 placental tissues from six malformed newborns were tested for B19 DNA by PCR. Out of 60 high-risk pregnant women, 47 (78%) had BOH while 23 (38.3%) had underlying complications including polyhydramnios (n=10), oligohydramnios (n=6) and intrauterine growth restriction (n=7). Adverse outcomes occurred in 36 (60%) high-risk cases. All 16 cases with polyhydramnios/oligohydramnios resulted in preterm stillbirths while the remaining 20 cases resulted in seven abortions, six newborns with congenital malformations, four full-term stillbirths and three cases of non-immune hydrops fetalis (NIHF). IgM positivity to T. gondii, rubella, cytomegalovirus, herpes simplex virus and B19 virus was 8.3%, 15%, 30%, 3.3% and 13.6% respectively. B19 infection caused NIHF in three cases and cardiac anomaly in one. All placental tissues and cord blood were negative for B19 DNA. None of the controls had IgM antibodies to any pathogen. Women with BOH and/or pregnancy complications had a high frequency of TORCH and parvovirus B19 infections causing fetal wastage, IUGR, NIHF and congenital malformations.

Short-term and long-term outcomes of 214 cases of non-immune hydrops fetalis

Despite advances in diagnosis and management, non-immune hydrops fetalis (NIHF) has a high mortality rate. Perinatal survival depends on the underlying disorder and the gestational age at diagnosis. As prognostic information is limited, this study acquired data regarding the neurological development of perinatal survivors. We performed a retrospective chart review of 214 cases in which NIHF was diagnosed antenatally. We recorded maternal demographic characteristics and interventions and their effectiveness, as well as the short-term outcome (survival) and long-term outcome including developmental quotients. Among the affected fetuses, 91 (42.5%) survived the perinatal period. Fetuses with chylothorax, chyloascites, or meconium peritonitis, and those in whom therapy was effective, had high survival rates irrespective of the type of intrauterine intervention. The subsequent intact survival rate was 28/56 (50.0%), with intact defined as ratio of the number of infants with normal development to the number of all infants followed. In contrast to the perinatal survival rate, the intact survival rate decreased as gestational age at diagnosis advanced. These findings suggest that the long-term intact survival rate depends on the underlying cause of NIHF. Additionally, while survival was improved with intensive perinatal care during the perinatal period, aggressive perinatal intervention was not a prognostic factor for neurological outcome.

Should PMM2-deficiency (CDG Ia) be searched in every case of unexplained hydrops fetalis?

Hydrops fetalis (HF) is characterized by an accumulation of fluid in the extracellular compartments and in body cavities. Non-immune HF (NIHF) is caused by a wide variety of disorders and overall, 20–25% of NIHF remain unexplained. Inborn errors of metabolism, mostly lysosomal storage diseases have been estimated to account for 1–2% of cases, leading to HF by anemia or liver failure. Very few cases of NIHF and Congenital Disorder of Glycosylation (CDG) have been reported. We present here a case of recurrence of HF in a non-related couple in which the diagnosis of CDG type I was suspected at fetal pathological examination then confirmed at the enzymatic and molecular levels, as well as on a characteristic CDG I serum transferrin profile at 30weeks of gestation. We also provide a systematic review of reported cases with CDG type I and NIHF reported thus far. When NIHF remains unexplained despite exhaustive obstetrical screening, analysis of PMM activity in the parents' leucocytes is possible and might be performed easily during pregnancy. The accurate diagnosis is important in terms of counseling during pregnancy or later, in order to allow an early molecular prenatal diagnosis for the following pregnancies.

Identifying the etiologic role of Parvovirus B19 in non-immune hydrops fetalis by histopathology, immunohistochemistry and nucleic acid testing: a retrospective study

Abstract Intrauterine Parvovirus B19 infections may cause fetal anemia, non-immune hydrops fetalis or abortion. This study focuses on the pathogenic role of Parvovirus B19 in non-immune hydrops fetalis at Hacettepe University, a major reference hospital in Turkey. Twenty-two cases of non-immune hydrops fetalis were retrospectively selected out of a total of 431 hydrops fetalis specimens from the Department of Pathology archieves. Paraffine embedded tissue sections from placental and liver tissues from each case were evaluated by histopathology, immunohistochemistry, nested PCR and commercial quantitative Real-time PCR. Viral DNA was detected in placental tissues by Real-time PCR in 2 cases (2/22, 9.1%) where histopathology also revealed changes suggestive of Parvovirus B19 infection. No significant histopathologic changes were observed for the remaining sections. Nested PCR that targets the VP1 region of the viral genome and immunohistochemistry for viral capsid antigens were negative for all cases. As a result, Parvovirus B19 is identified as the etiologic agent for the development of non-immune hydrops fetalis for 9.1% of the cases in Hacettepe University, Turkey. Real-time PCR is observed to be an effective diagnostic tool for nucleic acid detection from paraffine embedded tissues. Part of this study was presented as a poster at XIIIth International Congress of Virology, San Francisco, USA (Abstract V-572).

Transplacental Digitalization for Nonimmune Hydrops Fetalis Caused by Isolated Noncompaction of the Ventricular Myocardium

Noncompaction of the ventricular myocardium (NCVM) is a rare form of cardiomyopathy with a poor prognosis, and it is characterized by prominent trabeculations and deep intertrabecular recesses. This disease is speculated to occur because of arrest of the normal myocardial development process during early embryogenesis. In symptomatic infants, cardiac transplantation may be the only current curative option. Although NCVM is a congenital disorder, there are only a few previous reports on its status during fetal life. Here we report a case of nonimmune hydrops fetalis caused by this rare disease; in this case, digoxin administration to the mother could improve the fetal hemodynamics, and evaluation of the circulatory state of the fetus by using the preload index of the inferior vena cava (PLI) was proven to be sensitive and useful.

Detection of parvovirus B19 infection in formalin-fixed and paraffin-embedded placenta and fetal tissues

Parvovirus B19 infection was first discovered in 1975 and it is implicated in fetal death from hydrops fetalis the world over. Diagnosis is usually made through histological identification of the intranuclear inclusion in placenta and fetal organs. However, these cells may be scarce or uncharacteristic, making definitive diagnosis difficult. We analyzed histologically placentas and fetal organs from 34 cases of non-immune hydrops fetalis, stained with Hematoxylin and Eosin (HE) and submitted to immunohistochemistry and polymerase chain reaction (PCR). Of 34 tissue samples, two (5.9%) presented typical intranuclear inclusion in circulating normoblasts seen in Hematoxylin and Eosin stained sections, confirmed by immunohistochemistry and PCR. However, PCR of fetal organs was negative in one case in which the placenta PCR was positive. We concluded that parvovirus B19 infection frequency is similar to the literature and that immunohistochemistry was the best detection method. It is highly specific and sensitive, preserves the morphology and reveals a larger number of positive cells than does HE with the advantage of showing cytoplasmic and nuclear positivity, making it more reliable. Although PCR is more specific and sensitive in fresh or ideally fixed material it is not so in formalin-fixed paraffin-embedded tissues, frequently the only one available in such cases.