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。     

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.     

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.     

Nonimmune hydrops fetalis: report of 22 cases including three siblings.

Twenty-two cases of nonimmune hydrops fetalis (NIHF) seen over a three-year period are described. Eight cases were associated with major congenital anomalies, seven cases with minor anomalies or other disease entities, and seven idiopathic cases. The overall mortality rate was 50%, greatest in those cases complicated by major anomalies. The clinical problems commonly encountered in management of these patients are reviewed, and include prenatal detection, perinatal asphyxia, disseminated intravascular coagulopathy, fluid and electrolyte imbalance, and respiratory difficulty. A review of the literature for those entities found in association with NIHF is also included. The case studies of three consecutive siblings with NIHF born to the same parents are briefly analyzed.     

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.     

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.     

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.     

Congenital chylothorax with hydrops: postnatal care and outcome following antenatal diagnosis

We consecutively managed 25 cases of fetal chylothorax with hydrops (pleuroamniotic shunting in 20/25 cases). Three of the 16 liveborn infants died before day 5 from malformations (n = 1) or complications of antenatal origin (n = 2). Eleven of the 13 survivors were treated in our unit. Four infants whose chylothorax had resolved before birth following antenatal shunting were delivered at term, and had no respiratory disease. Seven infants, whose chylothorax persisted, were delivered prematurely and required intensive respiratory care (with mechanical ventilation for a median duration of 34 days). The 11 infants were maintained on total parenteral nutrition for a median duration of 31 days. They were discharged home after complete clinical recovery at a median age of 64 days. Antenatal pleuroamniotic shunting may improve the prognosis of congenital chylothorax with hydrops. Chylothorax persisting at birth resolves progressively with medical management. Congenital chylothorax, critical care, non-immunologic fetal hydrops, pleuroamnotic shunting, preterm newborn     

Congenital chylothorax: lymphopenia and high risk of neonatal infections

AIM: To describe the clinical course of patients with congenital chylothorax focusing on infectious complications. Congenital chylothorax is a common manifestation of non-immune hydrops fetalis (NIHF). The drainage of chyle leads to loss of cellular and plasmatic factors that influence the patient's immune response and increase the risk of infections. METHODS: In a retrospective analysis of 24 preterm infants with NIHF treated between 1998 and 2002, congenital chylothorax was diagnosed in 7 patients. RESULTS: All 7 patients were treated conservatively with pleural drainage over a median period of 22 d (range 10-36 d). Lymphopenia was found in all patients (median of minimal lymphocyte counts 285/microl, range 80-770). The nadir was on day 5 (2-6 d). Lymphopenia lasted for 12 d median (range 4-39 d) and was significantly correlated with the duration of lymph drainage (p = 0.001). Cell-surface analysis of peripheral blood lymphocytes was performed in two patients. Both patients had a decreased number of total T cells. Four out of seven (57%) patients developed nosocomial infections. This incidence of nosocomial infections in patients with congenital chylothorax is about three times higher than that in other neonatal patients. None of the children suffered from fungal or viral infection. Although there was a very high incidence of infections, no correlation between lymphopenia and the occurrence of infections could be shown. CONCLUSION: Drainage of congenital chylothorax results in the loss of lymphocytes and bears a high risk of infections.     

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.     

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.     

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.     

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.     

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.     

Tachyarrhythmia, cardiac rhabdomyomata and fetal hydrops in a premature infant with tuberous sclerosis

An hydropic infant was delivered at 32 weeks gestation by emergency Caesarean section for acute polyhydramnios. A diagnosis of cardiac rhabdomyomata was made on echocardiography. The baby survived 10 days, during which time repeated episodes of supraventricular tachycardia occurred. She eventually died of cardiac failure following an episode of septicaemia, convulsions and aspiration pneumonia. Necropsy showed multiple cardiac rhabdomyomata and numerous cerebral germinal layer and periventricular white matter nodules. This case stresses the importance of clinical investigations and perinatal necropsy in non-immune hydrops fetalis (NIHF) in determining the causes of clinical presentation and the underlying pathology.     

THE RE-EMERGENCE OF EARLY CONGENITAL SYPHILIS

Ten infants with early congenital syphilis are presented. Hepatosplenomegaly is a marked feature in all the infants. The majority of them were of low birth weight. Syphilitic pemphigus was present in 5, and hydrops fe talis in 4. Five infants survived, including one witn hydrops fetalis. Early diagnosis and intensive therapy are necessary for survival. A high index of swpicion is required for early and more frequent diagnosis of this condition.     

Nonimmune hydrops fetalis part II: does etiology influence mortality?

Hydrops fetalis is a condition in which there is an excess of total body fluid, primarily within the fetal interstitial spaces. Etymologically, hydrops fetalis is a Latin term meaning "edema of the fetus." In addition to generalized edema, the fetus has at least one of the following: ascites, pericardial effusion, pleural effusion(s), and an abnormally thick (>6 cm) placenta. Hydrops is classified as nonimmune hydrops fetalis (NIHF) when it occurs without evidence of isoimmunization.     

Nonimmunologic hydrops fetalis: a clinicopathological study of 50 autopsy cases

Fifty cases of nonimmunologic hydrops fetalis found in Japanese infants are reported. Nonimmunologic hydrops fetalis is associated with various pathological conditions, twin transfusion syndrome including acardiac monsters, fetal heart diseases, congenital cystic adenomatoid malformation, pulmonary sequestration, pulmonary lymphangiectasia, intrauterine infections such as cytomegalovirus infection and neonatal hepatitis, congenital neuroblastoma, Kasabach-Merritt syndrome, cystic hygroma, and chromosomal aberrations. The mechanism of hydrops fetalis found in these conditions is discussed from various viewpoints. Despite a careful examination, no causative conditions were found in 14 cases. The placenta showed a proliferation of Hofbauer cells that were strongly positive for immunoreactive alpha 1-antichymotrypsin and there were other common findings such as edema of terminal villi and fibrin thrombi.     

CONGENITAL PARVOVIRUS INFECTION

Congenital parvovirus infection was diagnosed in two liveborn premature infants born at 24 and 35 weeks of gestational age. The illnesses were associated with placentomegaly, petechial rash, edema, hepatomegaly, anemia and thrombocytopenia, respiratory insufficiency, and death at 5 and 6 days of age. The syndromes exhibited by these cases shared common but nonspecific features with other life-threatening congenital infections. Serological studies in one case supported the diagnosis of parvoviral infection. Postmortem examination of both revealed nuclear inclusions in erythroid precursor cells characteristic of parvovirus infection. Use of the polymerase chain reaction confirmed the presence of parvovirus DNA in one of the cases. Intrauterine parvovirus B19 infection is most commonly associated with hydrops fetalis, "transient" hydrops, or a favorable outcome in infants found to be viremic after birth. These and previously reported examples of congenital B19 disease exemplify an exceptional form of human parvovirus infection.     

Maternal cell microchimerism in newborn tissues

OBJECTIVES: On the basis of reports of maternal cells being detected in the umbilical cord blood of newborn infants, we tested the hypothesis that maternal cells can migrate out of the circulation into newborn tissues. STUDY DESIGN: We studied autopsy material from 4 newborn infants who never received a blood transfusion and died during the first week of life. The study subjects' diagnoses were trisomy 21 with nonimmune hydrops, 46, XY, 4q+ with multiple congenital anomalies, Potter syndrome, and congenital ichthyosis. Fluorescence in situ hybridization analysis with X and Y chromosome-specific probes was performed on sections of paraffin-embedded tissue, including liver, spleen, thymus, thyroid, and skin. RESULTS: Female cells, as defined by the presence of intact nuclei with two X chromosome signals, were detected in multiple tissue types from all 4 male neonates. The number of female cells varied from 3 to 45 per slide. CONCLUSIONS: Maternal cells enter the fetal circulation and are capable of migration to fetal and neonatal organs. This is of importance with regard to potential consequences of umbilical cord blood transplantation and postnatal development of autoimmune disease.