Nonimmunologic hydrops fetalis--a review of 31 cases

Non-immunologic hydrops fetalis-a review of 31 cases: 31 Patients with non-immunologic hydrops fetalis (NIHF) seen between 1984 and 1987 are described. 13 infants survived. The infants with major congenital malformations and connatal infections died. In 8 of the patients who died a cause for NIHF could not be identified. 10 of the survivors presented chylous ascites and/or chylothorax without major congenital anomalies. 2 infants had fetal tachyarrhythmia and 1 patient showed severe anemia due to fetomaternal hemorrhage.     

Investigation of Nonimmune Hydrops Fetalis: Multidisciplinary Studies Are Necessary for Diagnosis—Review of 94 Cases

This review of 94 cases of nonimmune hydrops fetalis (NIHF) over a 10-year period was undertaken to evaluate the frequency of this pathology among fetal and infant deaths and to determine the most common likely etiologies in a northeastern region of France. NIHF represented 6% of the fetal deaths examined in our laboratory. The combination of findings from morphologic examination of the placenta and fetus with the results of microbiological and cytogenetic investigations (conventional cytogenetic study, fluorescent in situ hybridization [FISH], or DNA ploidy image analysis) led to an etiologic diagnosis for NIHF in two-thirds of the cases and suggested a diagnosis in an additional 23% of cases. The most common causes of NIHF were chromosome abnormalities (33%), infections (16%), and cardiac pathology (13.8%). The detection of a cause for NIHF is important for genetic counseling and management of subsequent pregnancies. Our experience suggests that a diagnosis is possible in a large majority of NIHF when obstetricians and pathologists carefully coordinate the management of prenatal and postnatal investigations and when new techniques, such as molecular biology and DNA quantification, are used. Received January 12, 1998; accepted October 14, 1998.     

非免疫性胎儿水肿新生儿的临床特征及预后分析

目的 分析非免疫性胎儿水肿（NIHF）新生儿的临床特征、病因及转归情况。方法 回顾性分析23例NIHF新生儿的临床资料及转归。结果 23例NIHF患儿中,早产儿18例（78%）,足月儿5例（22%）;出生窒息12例（52%）,其中重度窒息6例。NIHF病因包括双胎输血综合征（TTTS）8例（35%）,心血管畸形3例（13%）,微小病毒B19感染3例（13%）,先天性乳糜胸2例（9%）,Turner综合征1例（4%）,柯萨奇病毒感染1例（4%）,病因不明5例（22%）。临床治愈13例（57%）,死亡10例,新生儿期病死率为43%。死亡组中早产儿、新生儿窒息、5分钟Apgar评分<8分及心力衰竭比例（分别为100%、100%、60%、60%）明显高于存活组（分别为62%、15%、8%、8%）（P < 0.05）。结论 NIHF新生儿易发生出生窒息;胎龄越小、窒息程度越重、合并心力衰竭者新生儿期死亡风险越大。TTTS中受血儿是NIHF的主要病因。     

Non-immunologic hydrops fetalis (NIHF)--case report of double partial trisomy 15q and 17q resulting from familial translocation 15/17 and cytogenetic findings in 50 cases with hydrops fetalis

We report the first case of non-immune hydrops fetalis (NIHF) with trisomy 15q11/17q22.5 resulting from a familial translocation 15/17. Furthermore the cytogenetic findings of 50 cases with hydrops fetalis are presented. Of the 30 cytogenetic analyzable cases 7 showed chromosomal abnormalities (4x45,X; 2x47,XY,+21; 1x47,XY,+13). In every case of NIHF a chromosomal analysis should be performed if possible from different tissues.     

Intrauterine treatment on non-immune hydrops fetalis.

In 51 cases with non-immunologic hydrops fetalis (NIHF), perinatal management was performed based on our protocol. Twenty-two cases were treated by albumin and/or packed red cell (PRC) injection into the fetal abdominal cavity, and 9 cases by transplacental digitalization. Among the cases treated by albumin and/or PRC injection, 6 of 8 cases without pleural effusion recovered in utero, and all 6 cases are alive. However, of 14 cases with pleural effusion, none recovered in utero, and only one case is alive. Of 9 cases treated by transplacental digitalization, 2 cases recovered in utero, and only one case is alive. All fetuses with congenital heart anomaly died. This evidence indicates that albumin and/or PRC injection into the fetal abdominal cavity is an effective procedure for in utero treatment of NIHF without pleural effusion, but suggests that in NIHF resulting from either congenital heart anomaly and/or heart failure, the survival rate may not be increased by transplacental digitalization.     

Fetal case of congenital cystic adenomatoid malformation of the lung: fetal therapy and a review of the published reports in Japan

We herein report a case of type I congenital cystic adenomatoid malformation of the lung (CCAML) with non-immune hydrops fetalis (NIHF), a mediastinal shift and polyhydramnios diagnosed at 24 weeks' gestation by ultrasonography. The fetus was treated with a cyst-amniotic shunt at 29 weeks' gestation. Following a postnatal whole resection of the right lung, postpneumonectomy syndrome appeared and, as a result, the infant died 13 months after delivery due to respiratory failure. Only 19 cases demonstrating CCAML associated with NIHF have been reported previously in Japan. Four cases showed a spontaneous resolution of NIHF, while 5 cases with type I CCAML, which all underwent fetal intervention, demonstrated an excellent outcome.     

Nonimmune Hydrops Fetalis in the Liveborn: Series of 32 Autopsies

Nonimmune hydrops fetalis (NIHF) or generalized soft tissue edema and cavity effusions may be due to cardiovascular diseases, congenital infections, genitourinary malformations, thoracic masses, placental conditions, chromosomal abnormalities, and idiopathic. We report 32 cases of NIHF from among 429 neonates who underwent autopsies (incidence 7.45%). Sixteen cases (50%) had cardiovascular disease; all were due to low output cardiac failure; 7 had structural congenital heart disease. Three of the children with congenital heart disease also had chromosomal abnormalities: 2 had trisomy 18 and 1 had Noonan syndrome. Among myocardial conditions were five subjects with cardiomyopathies (1 of each of the following types): oncocytic, dilated, endocardial fibroelastosis, cardiac glycogenosis, and carnitine deficiency; 3 had myocarditis, and 1 had cardiac rhabdomyomas. Congenital infections were due to cytomegalovirus in 3 cases, bacteria in 2, and parvovirus in 1. The mechanism of NIHF in these cases might be a combination of decreased myocardial contractility due to myocarditis and fetal anemia. Genitourinary diseases were present in 5 newborns: Two had congenital nephrotic syndrome, 1 had VACTER association, 1 had prune-belly syndrome, and 1 had urogenital sinus malformation. Intrathoracic lesions were found in 2 babies (pulmonary sequestration and diaphragmatic hernia). One twin died of volume overload due to twin transfusion syndrome. Only 2 newborns were classified as idiopathic. Our study shows that cardiovascular diseases that lead to heart failure or impaired venous return are more common in the liveborn (50%), whereas congenital infections are more common in the stillborn with NIHF.     

Spondylocostal dysostosis

Spondylocostal dysostosis is a rare condition characterized by short stature due to a short trunk, multiple morphological abnormalities of the vertebras and ribs due to malsegmentation of the axial skeleton. Radiological features include reduced number of vertebrae and ribs, hemivertebrae, fused or sagitally cleft vertebrae or multiple rib fusions. Three distict clinical entities are described. We report nine cases of this syndrome, seven were infants and presented with an abnormal shape of the thorax. Two of them had a maningocoele, and one succumbed to the CNS anomalies on the third day of life. The other two cases were two and eight years of age. Cardiac lesion was detected in one case and renal malformations in three cases. Reduction in the rib number was present in all cases, and rib fusion in seven cases. Thoracic vertebral dysegmentation was noted in all, lumbar in three and cervical in one case. This is the first large series from India. No clear single etiology was established.     

Value of Autopsy in Nonimmune Hydrops Fetalis: Series of 51 Stillborn Fetuses

Nonimmune hydrops fetalis (NIHF) is used to describe fetuses and newborns with generalized edema and cavity effusions. It is helpful to alert physicians about the presence of anemia, heart failure, and/or hypoproteinemia, but this diagnosis is frequently overlooked. We reviewed the autopsy files from 1990 to 2000, selected all cases with NIHF including clinical information (with maternal laboratory tests and ultrasound), and classified patients by etiology. Among 840 stillborn autopsies during the 11-year period, we found 51 with NIHF (6.07%). The clinical summary had mentioned hydrops in 14 patients and the etiology in another 7 by fetal ultrasonography, but without addressing the possibility of hydrops. In the remaining 30 cases neither hydrops nor an etiology was mentioned. Other pertinent diagnoses were maternal diabetes mellitus (4), congenital heart disease (3), and cystic hygroma (2). The following diagnoses were made in one instance each: cardiac tumor, twin transfusion syndrome, congenital adenomatoid malformation, syphilis, Turner syndrome, and cerebral arteriovenous malformation. Postmortem and placental examination confirmed the following etiologies: congenital infections (17); placental pathology significant enough to explain NIHF (10); cardiovascular diseases (8) (further classified as congenital heart disease [3], rhabdomyoma [1], and vascular malformations [4]); chromosomal abnormalities (6); uncontrolled maternal diabetes (4); intrathoracic lesions (2); prune-belly syndrome (2); and idiopathic NIHF (2). Only 3.9% of the cases studied had no identifiable etiology. The cause of hydrops was confirmed by autopsy in 47 fetuses (92%), which further supports the importance of performing an autopsy. Thirty-two cases (62.74%) had placental abnormalities helpful to the etiology (parvovirus, syphilis, Turner's syndrome, etc.). In 20 instances, the clinical summary had no mention of either hydrops or any of the diseases leading to it. The autopsy in conjunction with placental examination and fetal ultrasound represent the best combination to determine the etiology of NIHF among stillborn fetuses.     

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.     

Long-term outcome of 51 liveborn neonates with non-immune hydrops fetalis

To search for an efficient method of management of non-immune hydrops fetalis (NIHF), the clinical outcome of 51 newborns with NIHF was retrospectively assessed in a single centre. As the short-term outcome, the mortality rate was mainly dependent on the causes of NIHF and the presence of pleural effusion. The survival rate of the patients with pleural effusion (7/28; 25%) was significantly lower than that of those without it (14/23; 61%) (p < 0.02). All 7 survivors with pleural effusion were diagnosed antenatally after 29 weeks of gestation and were delivered after 31 weeks of gestation. With respect to the long-term outcome, 13 (68.4%) of 19 patients who survived beyond 1 y of age showed normal development, 2 mild developmental delay at 1 y of age and 1 mental retardation at 8 y of age, while 3 (15.8%) had severe psychomotor retardation with marked growth failure. Two of these three patients were born as very-low-birthweight infants. The follow-up results indicate that pleural drainage in utero and prevention of premature delivery should be proposed to improve the outcome of NIHF patients.     

The diagnosis and treatment of the nonimmune hydrops fetalis

Fetal hydrops is associated with two distinct pathophysiologic situations. The isoimmune hydrops fetalis is a well understood disorder, and as the result of medical advances and prophylactic therapy its frequency is diminishing. The nonimmune hydrops fetalis is a poorly understood disease with a bad prognosis. The two disorders can be differentiated with the indirect Coombs test. In both cases the ultrasound examination plays an important role in the diagnosis, prognosis and management. Examination of the fetal blood sample gives recently a possibility to approach the disease. In NIHF the examination of fetal blood sample would give a relatively quick and effective diagnosis but its value for the treatment is limited. Although with the present technology it is impossible to diagnose all cases of NIHF, the early recognizing, the careful and step by step investigation, the active perinatologic management mostly can show the etiology and can help the perinatal team at the treatment of the disease.     

Pulmonary vascular sling: Report of seven cases and review of the literature

Summary A total of 130 cases of pulmonary vascular sling, including seven new cases in our collection, were studied. The sex distribution was 60% male and 40% female. The age at presentation was in the first year of life in 90% of cases. Barium-esophagraphy showing anterior indentation was diagnostic in most of the cases. Bronchoscopy and tracheobronchography were useful in detecting associated tracheobronchial anomalies preoperatively. The analysis of 68 autopsied cases revealed associated tracheobronchial anomalies in 40% of the cases. Anomalies of the tracheobronchial tree took three major forms: abnormal distribution of cartilage in the walls of the trachea and major bronchi, intrinsic stenosis, and abnormal branching, the latter being that ofbronchus suis. Acquired changes secondary in the sling resulted in compression of the major respiratory pathway by the anomalous left pulmonary artery. Major associated cardiovascular anomalies were present in 30% of the cases. These were represented by ventricular septal defect, atrial septal defect, patent ductus arteriosus, tetralogy of Fallot, common ventricle, and coarctation of the aorta.     

IMMUNOHISTOCHEMICAL DISTRIBUTION OF VASCULAR ENDOTHELIAL GROW TH FACTOR IN THE HUMAN PLACENTA ASSOCIATED HYDROPS FETALIS WITH

The purpose of this study was to determine the distribution and the expression of vascular endothelial growth factor VEGF in human placentas obtained from 22 cases of nonimmunologic hydrops fetalis NIHF , ranging from 25 to 41 weeks of gestation, as compared with those in 75 normal placentas. The terminal villi were examined immunohistochemically using rabbit anti-human VEGF immunoglobulin G. The expression of VEGF in the terminal villi was assessed by the ratio of the VEGF-positive area to the capillary area. Among the 22 placentas, 18 placentas were hydropic and appeared to be histologically immature, and the other 4 placentas, whose fetuses eventually recovered before their deliveries, were nonhydropic. In both the HF and normal placentas, syncytiotrophoblasts expressed VEGF in the villi throughout gestation. VEGF was also expressed by stromal cells in the terminal villi of normal placentas in only the first trimester, whereas its expression continued until the term of pregnancy in 12 of 18 HF placentas. The ratio of the VEGF-positive area to the capillary area was significantly higher in the terminal villi of all hydropic HF placentas than in those of the normal placentas but was entirely the same in the four nonhydropic placentas as in the normal control placentas. These results suggest that the persistent expression of VEGF by stromal cells in the hydropic villi of NIHF, in addition to the VEGF expression by syncytioptrophoblasts, seems to be a reaction to poor villous vascular development and to participate in the regulatory mechanisms of vascular function including angiogenesis and permeability.     

Embryonic holoprosencephaly: pathology and phenotypic variability

Holoprosencephaly (HPE) is one of the major brain anomalies caused by the failure of cleavage of the prosencephalon during the early stage of development. Over 200 cases of HPE in the Kyoto Collection of Human Embryos were observed grossly and histologically, with special emphasis on the anomalies of the brain, face and eye. The facial anomalies of HPE human embryos after Carnegie stage (CS) 18 could be classified into cyclopia, synophthalmia, ethmocephaly, cebocephaly, and premaxillary agenesis, similarly as the classical classification for postnatal cases. On the other hand, HPE embryos at CS 13-17 showed some characteristic facies which are different from those in older embryos. In the present paper, pathology and phenotypic variability in HPE embryos were discussed from the embryopathological point of view. Recently, the molecular mechanism of HPE has been clarified by the techniques of gene manipulation, and various HPE genes have been identified by gene analysis of familial HPE cases. HPE is one of the major CNS anomalies which have been extensively studied and provides a clue to the mechanisms of normal and abnormal development of craniofacial structures.     

Minor congenital anomalies and ataxic cerebral palsy.

The incidence of minor congenital anomalies was examined in 36 patients with ataxic cerebral palsy, in unaffected family members, and in 100 unrelated control subjects. None of the control subjects or family members had more than four anomalies, and 25 of 36 (69%) of the patients had more than four. The distribution of anomalies differed considerably, with 60% of the index cases having seven or more, and 94% of the controls having three or less. The number occurring in the patients was significantly more than in their relatives. Of the 25 patients with more than four anomalies, 16 (64%) had undergone potentially adverse perinatal or early postnatal events. Thus minor congenital anomalies were considerably more frequent in those with ataxic cerebral palsy than in related or unrelated control subjects. These anomalies may be markers of early prenatal factors that contributed to the adverse outcome either directly or by predisposing to perinatal difficulties.     

CHARGE-Association with Pulmonary Stenosis

CHARGE-association was proposed by Pagon et al. (1) as an acronym for a malformation syndrome including Coloboma, Heart disease, Atresia choanae, Retarded growth and development and/or CNS anomalies, Genital anomalies and/or hypogonadism and Ear anomalies and/or deafness. More than 60 cases have been reported with four or more of the seven defects (2). Associated anomalies may appear but many of the features are midline facial or central nervous system defects. At least two separate genetic forms may exist even if sporadic cases are most frequent. This report concerns a boy with heart defects not previously described in the complete CHARGE-association.     

Hydrops Fetalis Caused by Fetal Kasabach-Merritt Syndrome

There have been only 2 previous reports of nonimmunologic hydrops fetalis (NIHF) caused by fetal Kasabach-Merritt syndrome, both of which were pathological studies. This is the first clinical case report of NIHF due to fetal Kasabach-Merritt syndrome that was prenatally diagnosed by sonography, computerized tomography, and percutaneous umbilical blood sampling.     

Autopsies of sudden infant death syndrome—classification and epidemiology

An enquiry into sudden infant death syndrome (SIDS) in 1987 furnished us with detailed epidemiological data for 281 cases that underwent a thorough post-mortem examination. This analysis uses these data to evaluate the role the autopsy plays in explaining sudden death. The cases were classified into three diagnostic groups: explained causes of death (group 1), unexplained deaths with anomalies (group 2), and no anomaly (group 3). These 281 cases show the three essential features that characterize SIDS: over-representation of males, increased deaths during the second and third months of life, and increased deaths during winter. The autopsy examination revealed that many of these deaths had a medical explanation. Almost half were assigned to group 1. At the time of autopsy, no precise pathology could be diagnosed for 147 deaths; of these, 140 showed histological anomalies. There were only seven sudden deaths for which no abnormal sign was evident at the autopsy. These results are compared with those of similar studies and discussed in connection with three factors: the initial selection of cases, the nature and degree of the investigations, and the possible interpretations of the symptoms uncovered.     

Hepatic cysts and hyperechogenicities: Perinatal assessment and unifying theory on their origin

The authors report their experience with the perinatal diagnosis of six cases of hepatic cyst and six of liver hyperchogenicities. The in utero diagnosis of hepatic cysts was difficult when the cysts were large or subhepatic. A precise diagnosis was sometimes achieved only after surgery. Small intraparenchymal cysts tended to regress spontaneously. Liver hyperechogenicities were diffuse or localized. They were unrelated to liver infection, tumors, meconium peritonitis or biliary tract anomaly. Both entities could be related to vascular disruption phenomenon (VDP) in which structural anomalies result from damage to normal development of embryonic or fetal vessels with anomalies of perfusion to the developing organs. The consequences of VDP to the liver are variable depending on the time and duration of the phenomenon. Localized infarct or ischemia can fibrose or calcify leading to segmental hyperechogenicities. Necrosis with tissue reabsorption can be the origin of some (sub)hepatic cysts. When such anomalies are detected there should be a careful study of the placentation, and a search for potential associated anomalies should be undertaken.