Pediatric and Developmental Pathology 5, 365–374, 2002 DOI: 10.1007/s10024-001-0260-6 © 2002 Society for Pediatric Pathology
Value of Autopsy in Nonimmune Hydrops Fetalis: Series of 51 Stillborn Fetuses MARIA M. RODRı´GUEZ,1* FERNANDO CHAVES,1 RITA L. ROMAGUERA,1 PETER L. FERRER,2 CLAUDIA DE LA GUARDIA,1 AND JOCELYN H. BRUCE1 1
Department of Pathology, Division of Pediatric Pathology, University of Miami/Jackson Memorial Hospital, Holtz Center 2142, 1611 NW 12th Avenue, Miami, FL 33136, USA 2 Departments of Pediatrics, Radiology, and Obstetrics, Division of Pediatric Cardiology, University of Miami/Jackson Memorial Hospital, Miami, FL, USA Received November 26, 2001; accepted March 17, 2002; published online May 21, 2002.
ABSTRACT 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 Subscribers can view Figures 1– 4 in this article in color at http://link.springer-ny.com/link/service/journals/10024/contents/01/0260/ paper/index.html *Corresponding author, e-mail:
[email protected]
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. Key words: autopsies, fetal edema, fetal hydrops, nonimmune hydrops fetalis, placenta, stillborn
INTRODUCTION Nonimmune hydrops fetalis (NIHF) is a specific name given to a syndrome characterized by generalized soft tissue edema and cavity effusions in fetuses and affected newborns. It is also usually associated with an enlarged placenta and the presence of nucleated red blood cells in fetal vessels.
NIHF usually carries a poor prognosis with an overall survival rate of less than 10% [1]. The distinction between immune and nonimmune hydrops fetalis was made by Dr. Edith Potter in her classic article published in 1943 [2]. She observed several important details: in pregnancies leading to erythroblastosis fetalis (immune hydrops), 90% of the mothers were Rh negative and all except one ended in the delivery of infants with fatal erythroblastosis; and in the nonimmune group, all mothers were Rh positive and primigravidas. All of these mothers in the nonimmune group who carried future pregnancies were able to give birth to normal, living children. More than half a century after the recognition of this condition as a separate entity, the prenatal diagnosis of NIHF by the obstetrician is still not always made and the identification of the etiology remains elusive for both obstetricians and pathologists. The systematic utilization of obstetric ultrasound in pregnancy has resulted in early and more frequent detection of hydrops fetalis. The routine use of fetal echocardiography enables the detection of a number of fetuses in whom the hydrops is secondary to congestive heart failure in utero. The purpose of this investigation was to review NIHF autopsy material from our institution, using a systematic approach that we propose to reduce the number of cases in which the cause of the hydrops fetalis cannot be determined.
METHODS The stillborn autopsy files from our institution were reviewed for the 11-year period from January 1, 1990 to December 31, 2000. We selected all cases of NIHF, using the following criteria: generalized soft tissue edema, presence of nucleated red blood cells in fetal vessels (autopsy organs and/or placenta), and presence of fluid in at least one of pleural, pericardial, or peritoneal cavities. We checked the clinical summaries from these 51 autopsies and recorded the number that had included the clinical impression of NIHF. The clinical information was also reviewed to determine if the mother had prenatal care and how early and consistently she had been followed during pregnancy. Laboratory data including maternal hemoglobin, hematocrit, white blood cell count, blood group, Rh status, antibody screening test, rapid plasma reagin (RPR), and glu-
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cose levels were recorded. Patients with positive antibody screening test were excluded. The autopsies with NIHF were then divided into several categories, including congenital infections, placental lesions, structural and functional cardiovascular diseases producing low- and high-output congestive heart failure, chromosomal abnormalities, maternal diabetes, intrathoracic lesions, genitourinary malformations, and idiopathic hydrops fetalis. The cases of congenital-specific infections were included only if the diagnosis was confirmed. Diagnosis of syphilis was made when the mother had a reactive RPR and positive Steiner stain for spirochetes in tissues. Congenital cytomegalovirus (CMV) infection was diagnosed primarily by the presence of cytomegalic cells in fetal tissues and then confirmed with nuclear staining by immunohistochemistry (see below). Herpes simplex virus (HSV) was suspected grossly when multifocal areas of necrosis were present on the hepatic surface, and confirmed histologically by the presence of necrosis, multinucleated cells with amphophilic intranuclear inclusions, and nuclear staining for HSV by immunohistochemistry (see below). The diagnosis of parvovirus B-19 was suspected by the classical histology of inclusions in nucleated red blood cells on hematoxylin and eosin–stained sections and was confirmed by immunoperoxidase stain for this virus (see below). All immunoperoxidase reagents used were from Dako (Carpinteria, CA). The slides were cut at 3 mm and deparaffinized. Endogenous peroxidase activity was blocked by incubation in 6% hydrogen peroxide for 5 min, and the sections were incubated for 30 min in a humidity chamber. The dilutions used were as follows: for CMV, 1:1000; for HSV, 1:50; and for parvovirus, 1:1000. Positive and negative controls were run with the specimens. Only cases with nuclear stains were considered positive. We took blood and/or pulmonary bacterial cultures in all autopsies in which there was a suspicion of a bacterial infection. We also performed Brown and Brenn stains for bacteria in autopsy and/or placental tissues when evidence of acute inflammation was found in the placenta and pulmonary sections.
The category of placental pathology included fetomaternal transfusion, twin transfusion syndrome, umbilical vein thrombosis, and mineralization of trophoblastic basement membrane, which has been associated with hydrops and hydramnios in the past [3]. Fetomaternal transfusion was suspected with paleness of the fetal skin and internal organs, and was confirmed by means of a modified Kleihauer-Betke test in maternal blood [4]. Twin transfusion syndrome was diagnosed when one twin was pale and the other was plethoric, the placenta was monochorionic with vascular communication, and the internal organs were pale and plethoric, respectively. Umbilical vein thrombosis was suspected upon inspection of the umbilical cord and was confirmed by microscopic examination of hematoxylin and eosin and phosphotungstic acid hematoxylin (PTAH) staining the fibrin layer. Cases were classified as structural cardiovascular disease when a severe congenital heart disease or a cardiac tumor was found at autopsy to be associated with cardiomegaly. These structural cardiovascular diseases lead to low-output heart failure. Other cases with hemangiomas or arteriovenous malformations were classified as functional cardiovascular diseases conducive to high-output congestive heart failure. The vascular malformations were studied by elastic van Gieson stain to differentiate between arteriovenous malformations and hemangiomas. Most of these cases with structural cardiovascular diseases leading to lowand high-output heart failure were studied prenatally, including some by fetal echocardiography. Analysis of these cases was aided by the close communication between the pediatric pathologists, the pediatric cardiologist performing fetal echocardiography, and members of the Division of MaternalFetal Medicine. Chromosomal abnormalities were suspected when phenotypic features such as cystic hygroma in a hydropic female fetus were present, and were confirmed by chromosomal analysis. Karyotypes were performed only in patients with dysmorphic features. Under the category of intrathoracic lesions we included hydropic fetuses with either congenital cystic adenomatoid malformation of the lung, recently renamed by Dr. Stocker as congenital pul-
monary airway malformation (CPAM) [5], and/or pulmonary sequestration, producing mediastinal deviation and NIHF. Prune-belly syndrome was diagnosed if a massively distended urinary bladder was found as a minimum criterium. Patients who did not meet any of these criteria were classified as idiopathic hydrops fetalis.
RESULTS Out of 840 stillborn autopsies performed during the 11-year period, 51 cases met the criteria for NIHF, representing 6.07%. Our results concur with a larger series of NIHF in France [6]. The range of gestational age was 20 – 41 weeks, with a mean of 29.3 weeks. Our series does not include fetuses younger than 20 weeks, because by Florida Law these fetuses are considered abortions and are therefore surgical specimens. Among these 51 autopsies, the clinical summary mentioned the diagnosis of NIHF in 14 instances (27.4%). Of these patients, the following etiologies were determined in 7 (13.7%) by means of fetal ultrasound: cystic hygroma (2), cerebral hemangioma (1), arteriovenous malformation (1), congenital heart disease (2), and cardiac tumor (1). Although other clinical summaries did not mention NIHF, important diagnostic information was noted, such as congenital heart disease, maternal diabetes mellitus, twin transfusion syndrome, congenital adenomatoid malformation, congenital syphilis, and Turner syndrome. The 51 cases were assigned different categories, according to the etiology obtained or confirmed by the autopsy, as follows: congenital infections, placental causes, structural and functional cardiovascular diseases (low and high output), maternal diabetes, chromosomal abnormalities, intrathoracic lesions, prune-belly syndrome, and idiopathic (see Table 1). Congenital infections represented the largest group and were found in 17 patients (33.3%). These infections were confirmed to be of bacterial, HSV (Fig. 1A, B), parvovirus B-19 (Fig. 1C), syphilis (Fig. 1D), and CMV origin. (A color version of all figures is available online.) The placenta was a useful tool for determining etiology, since 10 patients (19.6%) demonstrated placental pathology significant enough to explain the poor pregnancy outcome and the etiolAUTOPSY
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Table 1. Distribution of patients with nonimmune hydrops fetalis by etiology No. of cases (%)
Etiology Congenital infections Syphilis
7 (13.7)
Parvovirus
4 (7.8)
Bacterial
3 (5.9)
HSV
2 (3.9)
CMV
1 (2)
Placental Twin transfusion syndrome
5 (9.8)
Fetomaternal transfusion
2 (3.9)
Umbilical vein thrombosis
1 (2)
Mineralization of trophoblastic basement membrane
2 (3.9)
Structural and functional cardiovascular diseases Low output Endocardial cushion defect
1 (2)
Cardiac rhabdomyoma
1 (2)
Pulmonary atresia
1 (2)
Hypoplastic left heart syndrome
1 (2)
High output Hemangioma
2 (3.9)
Arteriovenous malformation
1 (2)
Intestinal angiodysplasia
1 (2)
Chromosomal abnormalities Turner syndromea
5 (9.8)
Partial mole
1 (2)
Maternal diabetes
4 (7.8)
Intrathoracic lesions Congenital pulmonary airway malformation
1 (2)
Pulmonary sequestration
1b (2)
Genitourinary Prune-belly syndrome
2 (3.9)
Idiopathic
2 (3.9)
Total
51 (100)
HSV, herpes simplex virus; CMV, cytomegalovirus. a Coexistent with congenital heart disease. b Coexistent with congenital pulmonary airway malformation (CPAM), also known as congenital cystic adenomatoid malformation (CCAM).
ogy of NIHF. In addition, 32 patients (63%) who were categorized as having an etiology other than placental pathology also had an abnormal placenta along with congenital syphilis, parvovirus, chromosomal abnormalities, etc. The most common
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placental abnormality was the presence of nucleated red blood cells within fetal vessels. Many of the placentas were larger than age-matched controls (43.13%). In general terms, when fetal weight was increased, placental weight was also increased. We did not find any chorangioma in our series to explain the etiology of NIHF. We classified the fetuses with primary congestive heart failure as having either structural or functional cardiovascular disease and then subdivided the disease further as being of low- or highoutput failure (see Discussion). Among the structural cardiovascular diseases, we found three patients with severe congenital heart disease and one with a cardiac rhabdomyoma replacing ⬎ 50% of the myocardium and producing subaortic stenosis. The latter patient had cerebral lesions seen only in tuberous sclerosis. In the group of patients with congenital heart disease, one was diagnosed prenatally at 27 weeks of gestation as having pulmonary atresia, ventricular septal defect, and absent ductus arteriosus; there was severe ventricular hypertrophy with hypokinetic ventricles, and associated tricuspid insufficiency. There were four cases of functional cardiovascular disease: two of these were secondary to hemangiomas, one was due to an arteriovenous malformation of the brain and neck, and the other was intestinal angiodysplasia. These patients had markedly increased cardiac preload, secondary cardiomegaly (functional cardiomyopathy), and signs of high-output congestive heart failure. One of the fetuses had a cerebral cavernous hemangioma with abundant nucleated red blood cells inside the tortuous and dilated blood vessels. This fetus also had hydranencephaly that was probably due to the compression by the massive hemangioma during early gestation. Another fetus had a ruptured hepatic cavernous hemangioma. Although he was hydropic, we believe the cause of death was exsanguination, since 70 ml of blood was found in the peritoneum (Fig. 2A, B). The possibility that part of this fluid volume came from a previous peritoneal effusion could not be completely ruled out; however, the color and consistency was that of pure blood. The third patient in this category had been studied prenatally and had a large arteriovenous malformation of the circle of Willis extending to the neck. His fetal echocardio-
Figure 1. Congenital infections. A: Liver from a 22week-old male fetus with congenital herpes simplex virus infection demonstrating multifocal areas of necrosis on the surface; some of them are dot-like, but others are confluent and larger. B: Microscopic hematoxylin and eosin–stained section of the same liver shown in A (⫻20). Note that the necrosis is more pronounced in the right lower corner. There is also extensive extramedullary he-
matopoiesis. C: Chronic villitis from a patient with parvovirus infection (hematoxylin and eosin). There is margination of the chromatin toward the periphery of nucleated red blood cells in fetal vessels (⫻20). D: Necrotizing funisitis in a patient with congenital syphilis. The umbilical vessel walls are thickened and opaque and surrounded by a pale gray rim of necrosis.
gram showed dilated superior vena cava, right atrial and ventricular enlargement, increased cardiothoracic ratio, and increased flow velocity at the main pulmonary artery and aorta, with a dilated carotid artery. Only mild pericardial effusion was present at the time of the study. The autopsy confirmed the massive cardiomegaly due mainly to dilated right cavities and the extremely dilated internal and external jugular veins and superior vena cava (Fig. 2C, D). The macerated male fetus with intestinal angiodysplasia had anasarca confirmed prenatally by ultrasound. This fetus had pleural catheter placement in utero at 25 weeks to drain the pleural effusions, but the fluid reappeared rapidly. Among cases with chromosomal abnormalities, we found five fetuses with Turner syndrome
and one severely dysmorphic fetus (Fig. 3A) whose placenta had all the gross and microscopic features of a partial mole (Fig. 3B). This macerated fetus was a cyclops with a superiorly placed proboscis. Chromosomal analysis was attempted; however, the cells failed to grow because of the severity of maceration. In spite of the relatively high frequency of maternal diabetes in our population, only four hydropic fetuses were delivered to diabetic mothers, representing 7.8% of this series. All these mothers had poor glucose control during pregnancy. None of the fetuses whose autopsies revealed a diaphragmatic hernia had hydrops fetalis. We did find one patient with coexistence of pulmonary sequestration and congenital pulmonary airway malformation (CPAM), better known as congenital cystic AUTOPSY
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Figure 2. Functional cardiovascular disease leading to high-output congestive heart failure. A: Hydropic fetus delivered at 34 weeks of gestation. Notice the facial edema and distended abdomen. B: Large ruptured, hepatic, cavernous hemangioma with 70 ml of blood in the peritoneal cavity and a large blood clot over the left hepatic lobe. C: This stillborn macerated male fetus has a cervical mass and distended thorax and abdomen. He
had been followed prenatally by fetal echocardiography and was diagnosed with cardiomegaly with dilated right cavities due to cervical and cerebral vascular malformation. D: The autopsy confirmed the prenatal findings of arteriovenous malformation. Depicted here is a massively dilated heart and pulmonary hypoplasia due to large bilateral pleural and peritoneal effusions.
adenomatoid malformation (CCAM) type 2 (Fig. 4), and another with an isolated CPAM type 2. Both of them had mediastinal deviation and NIHF. Prune-belly syndrome is a relatively uncommon cause of NIHF, because the edema and dis-
tension are usually confined to the abdomen. In our series we found two fetuses with massive distension of the urinary bladder and generalized edema. One was a female without renal anomaly and the other had ambiguous external genitalia,
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Figure 3. Suspected chromosomal abnormality. A: This macerated cyclops has a centrally located eye with a superiorly placed proboscis and microstoma. There is generalized edema and large pleural and peritoneal effu-
sions. B: The placenta associated with this fetus demonstrated a combination of hydropic and more normal-looking chorionic villi, as usually seen in partial hydatidiform moles.
but had a bicornuate uterus and a vagina, in addition to severe bilateral hydronephrosis, a vesicovaginal fistula, and multicystic dysplastic kidneys. There were two hydropic fetuses (3.9%) in which the cause of the hydrops fetalis could not be determined; therefore they were classified as idiopathic. One of these fetuses, delivered at 23 weeks, had 90 ml of amber fluid in the peritoneum, 5 and 10 ml in the pleural cavities, and 4 ml in the pericardium. A retroplacental hematoma was found. To the best of our knowledge, this placental pathology has not been associated with the development of NIHF. We could neither prove nor exclude the possibility of fetal blood contributing to the development of the retroplacental hematoma as the reason for fetal anemia leading to NIHF. Another fetus was delivered at 36 weeks with effusions in pleural, peritoneal, and pericardial cavities, and
had severe cardiomegaly with a heart weight of 41 g (normal: 13.9 ⫾ 5.8 g). No valvular anomalies were detected. It is possible that a primary cardiomyopathy was responsible for the generalized edema.
DISCUSSION The number of autopsies (including those of stillborn fetuses) has steadily declined at most institutions over the last 20 years. The reasons for the decrease are believed to be multifactorial. First, the development of high-resolution imaging techniques has allowed clinicians to diagnose abnormalities with more precision, so they do not feel the need for autopsy as in the past. Second, clinicians fear possible litigation if an unsuspected diagnosis of a potentially treatable condition is uncovered by the autopsy. Finally, there is an AUTOPSY
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Figure 4. Intrathoracic lesions. A: This preterm female fetus was delivered at 31 weeks gestation with generalized edema and large pleural and peritoneal effusions. B: The autopsy reveals a large bilobed extralobar pulmonary sequestration.
apparent lack of interest among pathologists to perform a task that will not be reimbursed by any medical insurance. In using autopsy to analyze hydrops in stillborn fetuses our data show no identifiable cause for hydrops in only 3.9% of cases. This finding supports the claim that autopsy, especially when accompanied by placental examination, continues to be the most complete procedure to determine the cause of death and the possible etiology of NIHF. Of the 51 autopsies we performed, only 14 stillborn fetuses (27.4%) had the clinical diagnosis of NIHF and the reports of 7 (13.7%) additional fetuses mentioned the etiology without linking it to hydrops (see Results), even though this series came from a tertiary care center with an active Division of Maternal-Fetal Medicine, including fetal ultrasound and echocardiography.
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The higher the awareness of obstetricians of the fetal signs and symptoms of NIHF, the higher the probability of making a positive impact on perinatal outcome in other pregnancies. Mothers with syphilis and bacterial infections can be treated with antibiotics if they go to a prenatal clinic early and consistently. Maternal glucose levels can be controlled during pregnancy in known diabetic mothers. In cases of a previous chromosomal abnormality, early chorionic villous sampling, amniocentesis, or triple screening are indicated and fetal ultrasound could be performed if there is a history of a previous hydropic fetus with a congenital heart disease, a congenital pulmonary airway malformation (CPAM), also known as adenomatoid malformation, or a hemangioma. In our study, the cause of death and possible etiology of NIHF were determined in more than 90% of
cases. In other series, the etiology of hydrops was identified in approximately 50% of patients without autopsy and in about 80% after postmortem examination [7,8]. In patients with NIHF, we use a systematic approach: we review the medical record and get a laboratory printout prior to autopsy performance to check for abnormal laboratory tests (RPR, CMV, HSV, bacterial cultures, glucose level, etc.). This approach is extremely helpful in cases of congenital syphilis and maternal diabetes. We also look for fetal ultrasound results and maintain close communication with members of the Maternal-Fetal Division and Pediatric Cardiology, as well as personnel at the Cytogenetics Laboratory. It is our experience that, in most cases, the karyotype is not ready at the time of the autopsy. However, if amniocentesis was not performed, we send a sterile skin sample to the Cytogenetics Laboratory. We always include the placenta as part of the autopsy report. While doing the autopsy, it is critical to pay special attention to features such as an extremely pale fetus, because the NIHF may be due to fetomaternal transfusion and it is critical to obtain a maternal blood sample for the Kleihauer-Betke test in a timely manner. Postmortem viral and bacterial cultures will help to establish the cause in a number of instances. The heart should be carefully dissected to rule out congenital heart disease. It is important to remember that premature closure of foramen ovale or ductus arteriosus can produce NIHF and intrauterine fetal demise. Other lesions such as congenital adenomatoid malformation, arteriovenous malformation, large hemangiomas, cystic hygromas, cardiac tumors, teratomas, and prunebelly syndrome are easier to detect during dissection. Microscopic examination is helpful to confirm congenital infections such as syphilis, parvovirus, HSV, and CMV, etc. After the initial histologic examination with hematoxylin and eosin–stained slides, we request immunohistochemical analysis to confirm the diagnosis. Microscopic examination can be helpful to more precisely diagnose arteriovenous malformations, angiodysplasias, lymphangiomas, and hemangiomas. In twin pregnancies, it is critical to check for the size and color discrepancies between twins and to look for vascular anastomosis in the placenta. We conclude
that NIHF is idiopathic only when this systematic approach fails to reveal any etiology. Analysis of the placentas was helpful in supporting the diagnosis of congenital syphilis in all our patients. They were large; some had chronic villitis, relative villous immaturity and fibrosis, and one of them had necrotizing funisitis with barberpole macroscopic configuration of the umbilical cord. Although these features are not pathognomonic, they have been described in the past in syphilitic placentitis [9]. The category of structural and functional cardiovascular diseases includes patients with congenital heart disease, cardiac rhabdomyomas, arrhythmias, hemangiomas, angiodysplasias, sacrococcygeal teratomas, and arteriovenous malformations, etc. The reason for this classification in lieu of the more traditional heart failure characterization is that, in our viewpoint, the mechanism of heart failure as an explanation for NIHF is not restricted to fetuses with structural and functional cardiovascular diseases. Congestive heart failure occurs in both the recipient and the donor in the twin transfusion syndrome. Cases with parvovirus infection are associated with severe anemia and/or myocarditis. CPAM and extralobar pulmonary sequestration may produce not only mediastinal shift and pulmonary hypoplasia but also cardiovascular compromise, including venous and cardiac compression. The degree of myocardial involvement in our patient with cardiac rhabdomyoma associated with tuberous sclerosis precluded any early intervention. This type of massive tumor is rare and it was the only death in a series of 11 cases of cardiac rhabdomyomas diagnosed prenatally in our institution [10]. In the group of fetuses with maternal diabetes, poor glucose control was a factor in all four mothers. In a study series of placentas from normoglycemic diabetic and hyperglycemic diabetic mothers, it was found that normoglycemia reduces placental maturation disorders, perinatal mortality, and morbidity [11]. Among intrathoracic lesions, we found one patient with coexistence of an extralobar pulmonary sequestration and CPAM (CCAM) type 2. It is possible that at least one of our cases with idiopathic NIHF was related to fetal cardiac arrhythAUTOPSY
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mias, because cardiomegaly was demonstrated on autopsy. In our experience with clinical cases followed by fetal echocardiography, hydrops fetalis occurred almost exclusively in cases of sustained supraventricular tachyarrhythmias. The median gestational age of hydropic and nonhydropic fetuses was 33 weeks [12]. This report underscores the need for combining and correlating autopsy with placental examination to determine potential causes of death among stillborn fetuses, particularly those with suspected NIHF. REFERENCES
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