Etiology and perinatal outcomes between early and late-onset nonimmune hydrops fetalis

SUMMARY OBJECTIVE: We aimed to compare the etiology and perinatal outcomes of non-immune hydrops fetalis diagnosed early- and late-onset at our hospital. METHODS: The records of the patients who applied to our department were reviewed, and we reached 42 non-immune hydrops fetalis cases retrospectively and examined the medical records. Hydrops diagnosis week, birth week, accompanying anomalies, and perinatal outcomes were compared as ≤12 weeks (early-onset) and >12 weeks (late-onset). RESULTS: The prevalence of non-immune hydrops fetalis was 0.05%, and the median week of diagnosis for hydrops was 18 weeks. Consanguinity (16.7%) was found in seven pregnancies, and the other seven patients (16.7%) had a history of hydrops in previous pregnancies. Anomalies of the skeletal system, central nervous system, and gastrointestinal tract accounted for 66.7% of ≤12 weeks in non-immune hydrops fetalis cases. Cardiac abnormalities were more common (26.7%) in patients at > 12 weeks (p=0.078). A statistically significant difference was found between the distribution of week of birth and week of diagnosis (p=0.029). Notably, 66.7% of patients diagnosed before week 12 and 23.3% of patients diagnosed after week 12 delivered their babies before week 24. Spontaneous intrauterine death occurred before week 12 in 45.5% (n=5) of non-immune hydrops fetalis and after week 12 in 39.1% (n=9) of non-immune hydrops fetalis. Notably, 69.2% (n=9) of the patients who had prenatal invasive testing resulted in normal karyotype. CONCLUSION: In this study, most of the fetuses diagnosed with early-onset non-immune hydrops fetalis were born in the first 24 weeks. Additionally, live birth rates and cardiac anomalies were observed to be higher in late-onset non-immune hydrops fetalis.

Non-immune hydrops fetalis: a case series

Hydrops fetalis is a clinical condition characterized by pathological fluid accumulation in soft tissues and serous cavities of the fetus like peritoneal cavity, pleural cavity, pericardial space, and body wall edema. Hydrops fetalis is broadly classified into Immune Hydrops Fetalis (IHF) and Non-Immune Hydrops Fetalis (NIHF). Incidence of immune hydrops fetalis due to Erythroblastosis fetalis secondary to Rh Iso-immunisation has drastically reduced due to widespread use of anti-D immunoglobulin. In the last few decades, the majority of cases are identified as non-immune hydrops. It is important to determine the cause of the hydrops fetalis in order to administer optimal management of the neonate at birth. Despite recent advances the mortality of non-immune hydrops is still high. Authors report here six cases of non-immune hydrops fetalis encountered at our tertiary care hospital over last three years.

Genetic analysis of a family with recurrent hydrops fetalis and dilated cardiomyopathy / 中华医学遗传学杂志

Objective@#To carry out genetic testing for a family with two pregnancies affected with hydrops fetalis and dilated cardiomyopathy (DCM) of the fetus.@*Methods@#DNA was extracted from fetal tissue as well as peripheral blood samples from the couple. Single nucleotide polymorphism array (SNP array) and next-generation sequencing (NGS) were carried out to screen potential mutation. Suspected mutation was validated with PCR and Sanger sequencing.@*Results@#The manifestation of fetal echocardiography was consistent with DCM. No obvious abnormality was found by SNP array analysis. A hemizygous c. 481G>A (p.G161R) mutation of the TAZ gene was detected in the male fetus by NGS and confirmed by Sanger sequencing. The mutation was inherited from his mother.@*Conclusion@#Barth syndrome due to the c. 481G>A mutation of the TAZ gene probably underlies the recurrent hydrops fetalis and fetal DCM in this family.

Estudo da etiopatogenia da hidropisia fetal não-imune a partir de uma série de casos utilizando um protocolo de investigação ampliado / Study of etiopathogenesis of non-immune hydrops fetalis from a series of cases using an expanded investigation protocol

A hidropisia fetal não-imune (HFNI) é causada por um grupo heterogêneo de condições e atualmente corresponde à maior parte dos casos de hidropisia fetal. Em função da ampla diversidade etiopatogênica, a investigação dos casos de HFNI constitui um desafio diagnóstico. Esse estudo teve como objetivo a avaliação prospectiva e sistemática de uma série de casos de HFNI a partir de um protocolo de investigação ampliado, que incluiu a pesquisa de doenças metabólicas. O presente estudo também incluiu a revisão dos casos de HFNI registrados previamente pelo Programa de Genética Perinatal na maternidade da Unicamp. Durante aproximadamente dois anos (2010-2012), foram identificados 53 casos de HFNI. Nesse período, ocorreram 6.129 nascimentos na maternidade local, com registro de HFNI em 37 recém-nascidos, conferindo uma prevalência de 60 por 10.000 nascimentos, valor maior do que o observado no período anterior ao estudo (1987 a 2009). Para o restante da análise, quatro casos foram excluídos devido à impossibilidade de estudá-los adequadamente. A maioria dos hidrópicos nasceu pré-termo (43 - 73,5%). Houve registro de 23 nativivos (47%), 10 óbitos no período neonatal e 26 óbitos durante a gestação (53%), resultado em uma mortalidade geral (pré-natal e neonatal) de 73,4%. A hidropisia foi identificada no pré-natal na maioria dos casos (44 - 89,8%) e, apesar da condição ser comumente associada a mau prognóstico, em três pacientes (6,1%) houve resolução completa e espontânea da hidropisia durante a gestação. Os principais grupos diagnósticos encontrados foram: anomalias cromossômicas (17 casos - 34,7%), quadros sindrômicos (16,4% - oito casos), cardiopatias e infecções congênitas (8,2% - quatro casos cada). Os erros inatos do metabolismo (EIM) corresponderam a 6,1% da amostra (três casos de doenças de depósito lisossômico). Três casos (6,1%) foram classificados como idiopáticos.

Non-immune hydrops fetalis (NIHF) is caused by a hetereogenous group of conditions, currently accounting for the most cases of hydrops fetalis. Because of the wide etiopathogenic diversity, the investigation of NIHF cases constitutes a real diagnostic challenge. This study aimed to evaluate prospectively and systematically a series of NIHF cases from an expanded research protocol including the investigation of metabolic diseases. The present study also aimed to revise the NIHF cases previously recorded by Perinatal Genetics Program (PGP) in the maternity hospital of Unicamp. During approximately two years (2010-2012), 53 cases were identified. In this period, among 6,129 births that occurred in our hospital, NIHF was identified in 37 newborns, given a birth prevalence of 60 per 10,000, higher than that was observed in the previous period - 23:10,000 (1987-2009). For purpose of all other analysis, four of the 53 cases evaluated had to be excluded due to inability to assess them correctly. Most hydropic individuals were born preterm (43 - 73.5%). Twenty-three patients (47%) were live births, 10 of them died before hospital discharge; and 26 (53%) died in the prenatal period, given an overall mortality of 73.4%. The hydrops were identified in prenatal period in most cases (44 - 89.8%), and despite being commonly associated with poor prognosis, three cases (6.1%) had complete and spontaneous resolution of hydrops during pregnancy. The main diagnostic groups were chromosomal abnormalities (17 - 34.7%), syndromic (8 - 16.4%), isolated heart defects (4 - 8.2%), and congenital infections (4 - 8.2%). Inborn errors of metabolism (IEM) occurred in three cases (6.1%), all represented by lysosomal storage diseases. Three cases (6.1%) were classified as idiopathic.

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

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.

Amniotic fluid amino acid levels in non-immune hydrops fetalis: a case-control study

In a prospective case-control study, we compared the amniotic fluid amino acid levels in non-immune hydrops fetalis (NIHF) and normal fetuses. Eighty fetuses underwent amniocentesis for different reasons at the prenatal diagnosis unit of the Department of Obstetrics and Gynecology, Faculty of Medicine, Dicle University. Forty of these fetuses were diagnosed with NIHF. The study included 40 women each in the NIHF (mean age: 27.69 ± 4.56 years) and control (27.52 ± 5.49 years) groups, who had abnormal double- or triple-screening test values with normal fetuses with gestational ages of 23.26 ± 1.98 and 23.68 ± 1.49 weeks at the time of sample collection, respectively. Amniotic fluid amino acid concentrations (intra-assay variation: 2.26-7.85 percent; interassay variation: 3.45-8.22 percent) were measured using EZ:faast kits (EZ:faast GC/FID free (physiological) amino acid kit; Phenomenex, USA) by gas chromatography. The standard for quantitation was a mixture of free amino acids from Phenomenex. The levels of 21 amino acids were measured. The mean phosphoserine and serine levels were significantly lower in the NIHF group, while the taurine, α-aminoadipic acid (aaa), glycine, cysteine, NH4, and arginine (Arg) levels were significantly higher compared to control. Significant risk variables for the NIHF group and odds coefficients were obtained using a binary logistic regression method. The respective odds ratios and 95 percent confidence intervals for the risk variables phosphoserine, taurine, aaa, Arg, and NH4 were 3.31 (1.84-5.97), 2.45 (1.56-3.86), 1.78 (1.18-2.68), 2.18 (1.56-3.04), and 2.41 (1.66-3.49), respectively. The significant difference between NIHF and control fetuses suggests that the amniotic fluid levels of some amino acids may be useful for the diagnosis of NIHF.

A Case of Non-immune Hydrops Fetalis due to Congenital Syphilis

Congenital syphilis is a rare cause of non-immune hydrops fetalis. We cared for a neonate with hydrops fetalis who was delivered by emergency Cesarean section due to prolonged fetal bradycardia and ascites at 34 weeks of gestation. He had anemia, purpura, and hepatosplenomegaly, and the serologic tests revealed congenital syphilis (high titers of serum VDRL and TPHA, and a positive serum FTA-ABS IgM). He survived after aspiration of ascitic fluid, ventilator care, and intravenous penicillin therapy. We report a case of non-immune hydrops fetalis due to congenital syphilis with a brief review of literature.

A Case of Non-immune Hydrops Fetalis due to Intraperitoneal Hemangioma

Hydrops describes the infant who has generalized edema due to accumulation of excess fluid. In severe case, massive edema with ascites and pleural and pericardial effusions are commonly combined. The main etiology of hydrops fetalis has been changed from immune type which is caused by fetomaternal blood group incompatibility to nonimmune type. Although cardiovascular diseases are the most common (23% to 38%) causes for nonimmune hydrops fetalis, fetal tumors still compromise 5% to 7% of the diseases. We report a case of nonimmune hydrops fetalis due to intraperitoneal hemangioma. The newborn infant was managed surgically and had excellent outcome.

A Case of Nonimmune Hydrops Fetalis due to Placental Chorioangioma

Fetal hydrops describes the infant who has generalized edema due to accumulation of exess fluid, in serious case, ascites and pleural and pericardial effusions are commonly combined. The chorioangioma is considered the most common primary tumor of the placenta, which is about 1% of all pregnancy. However, the majority of the cases are asymptomatic but larger ones, usually more than 5cm in diameter, are commonly associated with maternal and fetal complications. We report a case of nonimmune hydrops fetalis due to large chorioangioma with associated polyhydramnios. The newborn infant was managed conservatively and had excellent outcome.

A Case of Nonimmune Hydrops Fetalis due to Placental Chorioangioma

Fetal hydrops describes the infant who has generalized edema due to accumulation of exess fluid, in serious case, ascites and pleural and pericardial effusions are commonly combined. The chorioangioma is considered the most common primary tumor of the placenta, which is about 1% of all pregnancy. However, the majority of the cases are asymptomatic but larger ones, usually more than 5cm in diameter, are commonly associated with maternal and fetal complications. We report a case of nonimmune hydrops fetalis due to large chorioangioma with associated polyhydramnios. The newborn infant was managed conservatively and had excellent outcome.