Nonimmune Hydrops Fetalis in the Liveborn: Series of 32 Autopsies

Nonimmune Hydrops Fetalis in theLiveborn: Series of 32 Autopsies

MAR�A M. RODR�GUEZ,1* JOCELYN H. BRUCE,1 XAVIER F. JIM�NEZ,1

RITA L. ROMAGUERA,1 EDUARDO BANCALARI,2 OTTO L. GARC�A,3 AND PETER L. FERRER3

1Department of Pathology, Division of Pediatric Pathology, University of Miami, Jackson Memorial Medical Center,1611 NW 12 Avenue, Miami, FL 33136, USA2Department of Pediatrics, Division of Neonatology, University of Miami, Jackson Memorial Medical Center,1611 NW 12 Avenue, Miami, FL 33136, USA3Department of Pediatrics, Division of Pediatric Cardiology, University of Miami, Jackson Memorial Medical Center,1611 NW 12 Avenue, Miami, FL 33136, USA

Received August 6, 2004; accepted February 18, 2005; published online July 14, 2005.

ABSTRACTNonimmune hydrops fetalis (NIHF) or generalized soft

tissue edema and cavity effusions may be due to car-

diovascular diseases, congenital infections, genitouri-

nary 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 cardio-

myopathies (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 parvo-

virus 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 congen-

ital 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 dis-

eases that lead to heart failure or impaired venous re-

turn are more common in the liveborn (50%), whereas

congenital infections are more common in the stillborn

with NIHF.

Key words: anemia, cardiac failure, congenital infec-

tions, edema, hydrops fetalis, neonate

INTRODUCTIONFor many years obstetricians and midwives had

noticed a subset of babies born with generalized

soft tissue edema and a high mortality rate. John

William Ballantyne, a British gynecologist, in 1892

described a triad of maternal edema, fetal hy-

drops, and placentomegaly. Half a century after

the original description, Potter published an arti-

cle recognizing a group of fetuses that had uni-

versal edema unassociated with erythroblastosis

fetalis [1]. The condition was named nonimmune

hydrops fetalis (NIHF) to emphasize the different

etiology of the anasarca.

NIHF is associated with generalized soft tis-

sue edema and cavity effusions at birth and usu-

ally carries a poor prognosis. Predisposing factors*Corresponding author, e-mail: [email protected]

Pediatric and Developmental Pathology 8, 369–378, 2005

DOI: 10.1007/s10024-005-8089-z

ª 2005 Society for Pediatric Pathology

are fetal anemia, hypoproteinemia, cardiac fail-

ure, and conditions leading to mediastinal shifting

and venous compression.

Review articles and large series have been

published in the past 2 decades [2–4]. Among the

major causes of NIHF are cardiovascular diseases

leading to low and high output heart failure, pla-

cental anomalies, chromosomal abnormalities,

thoracic masses, anemia, intrauterine infections,

renal malformations, and metabolic conditions [5].

The systematic utilization of obstetric ultra-

sound in pregnancy has resulted in early and more

frequent detection of hydrops fetalis, and routine

use of fetal echocardiography enables the detec-

tion of a number of fetuses with hydrops fetalis

secondary to congestive heart failure in utero.

We recently published an autopsy series of 51

stillborn fetuses with NIHF and concluded that

congenital infections and placental problems are

the most common causes of NIHF in stillborns [6].

To further understand the causative factors and

pathogenetic mechanisms of NIHF in a different

population, we extended our analysis and studied

32 cases of liveborn babies with NIHF.

The purpose of this study was to determine

whether the etiology is different in the newborn

and to alert obstetricians, neonatologists, and

pediatric cardiologists about the possibility of

early intervention to improve the neonatal out-

come in children with NIHF.

METHODSThe neonatology database from our hospital was

searched for total number of neonates admitted to

the neonatal intensive care unit and total number

of deaths for the 14-year period from January 1990

to December 2003.

The autopsy files from pathology were re-

viewed by searching for liveborn neonates with the

diagnosis of NIHF during the same period. Cases

were selected according to the following criteria:

generalized soft tissue edema and presence of fluid

in at least 1 of the pericardial, pleural, and peri-

toneal cavities. Clinical summaries from these

autopsies, in addition to chest radiographs, elec-

trocardiograms, and echocardiograms were re-

viewed to determine how many had a clinical

diagnosis of NIHF. We analyzed laboratory data

including hemoglobin, hematocrit, blood group,

white blood cell count, rapid plasma reagin, blood

cultures, and immunoglobulin M antibodies for

specific infections when available. Autopsy proto-

cols and microscopic slides were reviewed and

cases were divided into categories such as car-

diovascular, infections, thoracic lesions, genito-

urinary, and placental. Cases not included in any

of these categories were labeled as idiopathic.

Blood and/or pulmonary bacterial and viral

cultures were performed on all autopsies when

infection was suspected. Brown and Brenn stains

for bacteria were done in autopsy and/or placental

tissues when evidence of acute inflammation was

found in the placenta and pulmonary sections.

Cases were categorized as congenital viral infec-

tions if they had histologic findings, positive cul-

tures, and immunohistochemical confirmation.

Very small tissue fragments were fixed in glutar-

aldehyde for possible electron microscopic exam-

ination.

Cardiovascular disease was diagnosed when

a severe congenital heart disease (CHD) or mor-

phologic evidence of cardiac abnormality was

found at autopsy to be associated with cardio-

megaly. For classification purposes cardiovascular

diseases were classified as CHDs, cardiomyopa-

thies, myocarditis, and cardiac tumors. Most of

these cases with structural cardiovascular diseases

were studied prenatally, including some by fetal

echocardiography.

If cardiomegaly was detected by ultrasonog-

raphy or autopsy, a portion of myocardium was

frozen for possible metabolic studies. All hearts

with CHD were dissected by a pediatric cardiolo-

gist (O.L.G.) and 1 of the pediatric pathologists.

Results were correlated with echocardiographic

findings. Chromosomal abnormalities were sus-

pected when phenotypic features such as cystic

hygroma, overlapping of the fingers, and/or dys-

morphic features were present. These were con-

firmed by chromosomal analysis.

The placentas were examined, whenever

available, by searching for edema, vascular anas-

tomoses in twin placentas, chorangiomas, presence

of nucleated red blood cells in fetal vessels, inflam-

mation, mineralization of the trophoblastic base-

ment membrane, and trophoblastic inclusions.

Because the reasons leading to NIHF are so

diverse, we recommend using a protocol for

370 M. M. RODRIGUEZ ET AL.

autopsies of stillborn fetuses or newborn babies

with NIHF (Table 1). Previous autopsy protocols

have been published [7,8] and they can be ex-

tremely useful. Knisely [8] recommended per-

forming full body radiographs of hydropic fetuses

even if a skeletal dysplasia is not considered. We

only radiograph those fetuses with grossly recog-

nizable abnormalities. Our approach to the hy-

dropic stillborn fetuses and liveborn babies is the

same according to the protocol.

RESULTSFrom 1990 to 2003, 14,949 neonates were admit-

ted to neonatal intensive care unit and 747 died

(118 were non-neonatal deaths). The mortality

rate was 4.99%. We performed 429 neonatal

autopsies with an autopsy rate of 57% and iden-

tified 32 cases of NIHF (7.45%). Placenta was

available for study in 18 cases (56%), because

some of these subjects had been delivered in other

hospitals and then transported to our center due

to a serious prognosis. Placental findings included

large, friable placentas with relative villous

immaturity and edema. Most of these placentas

had nucleated red blood cells in fetal vessels, a

microscopic feature associated with fetal anemia,

intrauterine hypoxia, or chronic infection. Some

had focal mineralization of the trophoblastic

basement membrane, villous edema, and fibrosis;

chronic villitis was found in 3 placentas, 2 of them

in neonates born with congenital cytomegalovirus

(CMV). These chorionic villi contained not only

lymphocytes but also plasma cells, a finding that

in our experience may be seen in TORCH infec-

tions.

Gestational age ranged from 27 to 40 weeks,

with survival periods ranging from 10 min to 120

days. There were 20 males and 12 females, with a

male:female ratio of 1.66:1.

Sixteen cases (50%) had clinical or patho-

logic evidence of cardiovascular disease, and all

cases were due to low output cardiac failure.

Among these 16 cases, 7 neonates had structural

CHD (Table 2). Three of the children with CHD

had chromosomal abnormalities: 2 had trisomy 18

and 1 had Noonan syndrome.

Nine additional children presented with

myocardial conditions (Table 3). Five newborns

had cardiomyopathy: 1 had the dilated type, 1 had

carnitine deficiency (Fig. 1A–C), 1 had cardiac

glycogenosis type IX due to isolated cardiac

phosphorylase kinase deficiency (Fig. 1D–F), 1

had oncocytic cardiomyopathy (Fig. 2C,D), and 1

presented with primary endocardial fibroelastosis.

A newborn male with carnitine deficiency

also had a living brother with cardiomyopathy due

to carnitine deficiency. Our subject was born pre-

term at 29 weeks of gestation after an emergent

cesarean section because of fetal tachycardia. He

died of a combination of cardiac failure and pul-

monary hypoplasia. The autopsy revealed a car-

diomyopathy with cardiomegaly (17 g, 7.2 ± 2.7 g)

and endocardial fibroelastosis as usually found in

carnitine deficiency [9]. Frozen cardiac tissue

confirmed low levels of total and free carnitine and

total acylcarnitine.

Table 1 Autopsy protocol for patients with nonimmune hydrops fetalis

1 Before autopsy: read clinical information, talk to clinicians

2 Examine placenta: it is usually large, pale and edematous; look for chorangiomas and vascular anastomosesin twins

3 External examination; if pale infant or fetus, ask for maternal blood to rule out fetal-maternal transfusion andother causes of fetal anemia (parvovirus, twin transfusion syndrome, congenital infections, etc.); photographbody and face (frontal and lateral views)

4 Place sterile skin in RPMI for cytogenetics

5 Internal examination: measure pleural, pericardial, and peritoneal effusions; look for hepatic hemangiomas,pulmonary sequestration, diaphragmatic hernias, or congenital pulmonary airway malformation

6 Keep heart and lungs together to look for vascular anomalies, e.g., total pulmonary venous return and aberrantvessels feeding a pulmonary sequestration; use heart dissection to check for valvular or myocardial disease

7 Take bacterial and viral cultures

8 Freeze myocardium and liver for possible metabolic studies

9 Fix 1 mm3 of myocardium and liver in Karnovsky medium for possible electron microscopic analysis

NIHF IN THE NEONATE 371

Table 2 Patients with nonimmune hydrops fetalis associated with congenital heart disease

Patient no. Congenital heart disease Associated conditions

1 VSD bicuspid AV and PV, coarctation of the aorta Trisomy 18

2 VSD bicuspid AV and PV, aneurysm of ductus arteriosus Trisomy 18

3 ASD dysplastic TV and MV Noonan syndrome

4 ECD dysplastic MV

5 MV insuciency: EFE

6 VSD, TV stenosis, and hypoplastic aorta

7 HLHS (MV atresia and hypoplastic aorta)

ASD, atrial septal defect; AV, aortic valve; ECD, endocardial cushion defect; EFE, endoeardial fibroelastosis; HLHS, hypoplastic left heart syndrome;MV, mitral valve; PV, pulmonary valve; TV, tricuspid valve; VSD, ventricular septal defect.

Table 3 Distribution of 32 patients with nonimmune hydrops fetalis by etiology

Etiology No. of cases %

Cardiovascular 16 50

Structural congenital heart disease with valvular involvement* 7 21.88

Cardiomyopathies

Dilated 1 3.12

Oncocytic 1 3.12

Cardiac glycogenosis 1 3.12

Carnitine deficiency 1 3.12

Endocardial fibroelastosis 1 3.12

Myocarditis 3 9.38

Cardiac tumors (rhabdomyomas) 1 3.12

Congenital infections 6 18.75

Cytomegalovirus 3 9.38

Bacterial 2 6.25

Parvovirus� 1 3.12

Genitourinary 5 15.62

Congenital nephrotic syndrome� 2 6.25

Prune-belly syndrome 1 3.12

Urogenital sinus malformation 1 3.12

VACTER association 1 3.12

Intrathoracic lesions 2 6.25

Pulmonary sequestration + CPAM§ 1 3.12

Diaphragmatic hernia 1 3.12

Placental: twin transfusion syndrome# 1 3.12

Idiopathic 2 6.25

Total 32 100

* There were 2 neonates with trisomy 18 and 1 with Noonan syndrome and pulmonary lymphangiectasis.�This patient had a systemic infection including myocarditis.�One of these 2 children also had a repaired total anomalous pulmonary venous return, a focal cytomegalov infection in the kidney, and a superiorvena cava thrombus

§ Congenital pulmonary airway malformation, also known as congenital adenomatoid malformation type 2.

# This was the recipient twin; therefore, the mechanism for nonimmune hydrops fetalis is volume overload.


The neonate with cardiac glycogenosis was

previously reported [10]. The autopsy confirmed a

severe cardiomyopathy and cardiomegaly due to

biventricular wall thickening. Microscopically, the

myocardial cells had very clear cytoplasm, with

strongly positive periodic acid-Schiff staining that

disappeared after diastase digestion (Fig. 1D–F).

Myocardial glycogen content was markedly high

and PhK assay levels were extremely low. Three

patients developed myocarditis (Fig. 2A,B), and 1

neonate had several cardiac rhabdomyomas.

Congenital infections were found in 6

additional cases: 2 due to bacterial infections

(Clostridium perfringens and Escherichia coli,

respectively), 3 infected with CMV, and 1 with

congenital parvovirus involving the placenta,

heart, thymus, pancreas, spleen, lung, and liver

that was confirmed by immunohistochemistry

(Fig. 3).

Intrathoracic lesions were present in 2 ba-

bies: 1 presented with a pulmonary sequestration

accompanied by a congenital pulmonary airway

malformation (Fig. 4) and the other with a left-

sided diaphragmatic hernia. The neonate with a

left-sided pulmonary sequestration and congenital

pulmonary airway malformation was born by

Figure 1. Primary cardiovascular conditions that leadto cardiomyopathy and severe congestive heart failuredue to storage diseases. A. Globoid heart with a whitish(milky) discoloration of the endocardium as seen inendocardial fibroelastosis. B. Microscopic section of theheart displays a thickened endocardium and vacuoliza-tion of subendocardial myocardium suggestive of car-nitine deficiency (hematoxylin and eosin, originalmagnification 20·). C. Trichrome-stained section fromthe same heart enhances the myocardial thickening

(original magnification 20·). D. Cross-section from theheart of 1 subject with cardiac glycogenosis due tophosphorylase kinase deficiency. Left ventricular thick-ness was 1.4 cm without counting the papillary muscles.E. Periodic acid-Schiff (PAS) stain demonstrates abun-dant PAS-positive material within myocardium (originalmagnification 20·). F. PAS after diastase digestion. Allmyocardial fibers are extremely pale because the gly-cogen was digested by diastase.


cesarean section at 32 weeks because a fetal

ultrasound showed polyhydramnios, pulmonary

sequestration and NIHF. The subject developed a

tension hydrothorax and a large peritoneal effu-

sion with associated respiratory distress. The in-

fant died 2 days after birth despite ventilatory

Figure 2. Primary cardiovascular conditions. A. Myo-cardium demonstrates necrosis and dystrophic calcifi-cations (arrow) as seen in intrauterine myocarditis(hematoxylin and eosin, original magnification 20·). B.Myocardial fibrosis indicates longstanding myocarditis(trichrome stain, original magnification 20·). C. Heart

from a subject with oncocytic cardiomyopathy. There isfocal yellow discoloration of endocardium under thetricuspid valve. D. In the same heart shown in C, there ispaleness of subendocardial myocardium (hematoxylinand eosin, original magnification 10·).

Figure 3. Infectious etiology. A. Horizontal section ofthe liver from a subject with congenital parvovirusinfection. Several petechial hemorrhages are foundscattered through the hepatic parenchyma. B. Liversection demonstrates virally infected cells with periph-

eral margination of the chromatin (hematoxylin andeosin, original magnification 20·). C. Liver from thesame patient with immunohistochemistry for parvovirus(original magnification 20·). There is brown nuclearstaining of numerous cells.


support. The mechanism for hydrops fetalis in this

patient seems to be a combination of shunt via the

large feeding vessel exiting directly from the aorta

and venous compression by the large intrathoracic

mass.

Genitourinary diseases were confirmed in 5

newborns. Two had congenital nephrotic syn-

drome due to diffuse mesangial sclerosis, 1 had

VACTER association, 1 had prune-belly syndrome,

and 1 had urogenital sinus malformation. How-

ever, 1 subject with congenital nephrotic syn-

drome also had total anomalous pulmonary

venous return (repaired 2 weeks after birth). The

subject also developed a superior vena cava

thrombus secondary to a subclavian line and a

documented focal CMV infection in the kidney;

therefore, the pathophysiology of the NIHF is

multifactorial (Fig. 5).

One newborn was the recipient of a twin

transfusion syndrome and the cause was classified

as a placental condition due to the presence of

vascular anastomosis; nevertheless, the mecha-

nism is volume overload that induced congestive

heart failure.

Only 2 neonates were classified as idiopathic.

One had histologic features suggestive of a lyso-

somal storage disease with Alcian blue–positive

macrophages in the lungs and spleen, but the

specific enzymatic defect could not be proved. The

other subject had polyhydramnios, fetal pleural

effusions, and hydrops fetalis by prenatal ultra-

sound. It was decided to deliver the baby at 27

weeks of gestation by cesarean section to imme-

diately perform a thoracocentesis and to prevent

further development of pulmonary hypoplasia.

The neonate had a generalized subcutaneous

edema, with bilateral pleural and peritoneal effu-

sions. Laboratory tests confirmed a moderate

anemia. He died 3 h after birth due to respiratory

insufficiency.

Figure 4. Intrathoracic masses leading to venous com-pression. A. Posterior view of organ block demonstratesa large left thoracic mass (large arrow) composed ofpulmonary parenchyma outside the normal pleuralinvestment of the lung and not connected to the tra-cheobronchial tree. The malformation is connected to alarge feeding artery exiting the aorta (small arrow),

which is typically seen in extralobar pulmonary seques-tration. B. Bronchiole-like structures diagnostic of con-genital pulmonary airway malformation type 2(hematoxylin and eosin, original magnification 20·).The coexistence of these 2 lesions is seen in 50% of casesof extralobar sequestration.


The correct etiology was suspected by the

neonatologists, obstetricians, and/or pediatric

cardiologists in 25 (78%) of these neonates, and

autopsy confirmed or detected the etiology in 5

additional subjects (15.6%).

Taking into account that the mechanism for

hydrops in the recipient of the twin transfusion

syndrome was volume overload and cardiac failure

and that in pulmonary sequestration the patho-

physiology was venous compression and a large

artery exiting directly from the aorta and acting as

a large patent ductus arteriosus, it is reasonable to

assume that cardiovascular problems were the

leading problem or an important contributory

factor in 19 of 32 subjects (59%) and were the most

common cause of NIHF in this series.

DISCUSSIONNumerous pathologic conditions related to fetal,

placental, and maternal diseases have been asso-

ciated with NIHF and the pathogenetic mecha-

nisms that cause fetal edema seem to be

congestive heart failure, systemic venous hyper-

tension, decreased oncotic pressure, nonimmune

anemia, and fetal circulatory obstruction [3].

The mechanism of edema in patients with

CHD is heart failure. Endomyocardial conditions

can produce intracardiac hemodynamic dysfunc-

tion with a variable degree of heart failure, as seen

in our cases with cardiac rhabdomyoma, storage

diseases, myocarditis, cardiomyopathies, and

endocardial fibroelastosis. Similar cases causing

hydrops fetalis have been well documented in the

literature [9–13].

One neonate in our series had clinical mani-

festations of cardiomyopathy associated with

cardiac arrhythmias of unknown etiology and the

autopsy revealed a myocarditis. However, heart

failure in some cases may be due to mechanisms

not readily established by histopathologic studies,

such as supraventricular tachycardias, atrial flut-

ter, or ventricular tachycardias [14,15]. In these

cases, systemic venous hypertension produces an

impaired ventricular filling that is related to short

diastole and, if prolonged, eventually induces a

secondary cardiomyopathy.

Although there is a higher incidence of con-

genital defects of the left heart and great vessels

than of right-sided lesions [16], a malformation of

the right heart, in particular tricuspid insuffi-

ciency, is more prone to cause generalized edema

in the fetus [17], showing right heart failure as the

common pathogenetic pathway in cases of NIHF.

It is conceivable that increased systemic venous

pressure might be brought about by obstruction to

right heart output.

Although the reported frequency of chromo-

somal abnormalities in hydrops (10%) would

Figure 5. MultifactorialNIHF. A. Infant withsevere subcutaneousedema. B. Section of thesuperior vena cava showsorganized thrombus(hematoxylin and eosin,original magnification10·). C. Kidneydemonstrates diffusemesangial sclerosis(hematoxylin and eosin,original magnification20·). D. Typicalcytomegalic inclusion ina renal tubule(hematoxylin and eosin,original magnification20·).


indicate that chromosomal analysis should be a

routine part of the investigation of hydrops [2],

there appears to be no clear pathogenesis for hy-

drops in chromosomally abnormal fetuses that

have no cardiovascular abnormality or cystic hy-

gromas. In our series, the 2 neonates identified

with trisomy 18 and the 1 neonate with Noonan

syndrome also had CHD. Nevertheless, karyotype

should be performed as part of the study of hy-

dropic infants to exclude the possibility of mosai-

cism or any other chromosomal abnormality.

Congenital infections can be bacterial and

viral. The possibility of fetal shock and anemia

needs to be considered. The mechanism for the

development of NIHF in children with congenital

parvovirus seems to be a combination of myo-

carditis that produces heart failure and fetal ane-

mia. In a review article, Machin [2] found only a

4% rate of infections; most infections could not be

further classified because the diagnosis was made

by histologic evidence only. Among the classifi-

able infections, CMV represented the largest

group.

Intrathoracic masses that produce hydrops

may be due to a considerable increase in intra-

thoracic pressure that ultimately exceeds systemic

venous pressure. Space-occupying lesions within

the thorax, as in our 2 infants with pulmonary

sequestration and diaphragmatic hernia, support

the concept of impaired venous return as a path-

ogenetic mechanism of hydrops fetalis.

Patients with chondrodysplasia may be born

with hydrops due to a small thoracic cavity [2].

However, we found no subject with skeletal dys-

plasia associated with NIHF in the stillborn [6] or

liveborn series.

When comparing this series with our previ-

ously reported stillborn series [6], cardiovascular

diseases were found to be more common in the

liveborn (50% vs. 14%). Although congenital

infections represented the largest group in the

stillborn series (34%), these infections represented

only 19% in the present series. No subjects with

high output failure (hemangiomas and atrioven-

tricular malformations) were found among the

liveborn. Only 1 newborn with twin transfusion

syndrome was documented in this series; the

mechanism for hydrops in this case was volume

overload leading to heart failure.

In conclusion, our comparative series of 51

stillborn fetuses and 32 liveborn infants show that

placental problems, which account for 20% of the

causes of NIHF in stillborns, are not as frequent in

neonatal NIHF, where structural and/or functional

cardiac dysfunction is the predominant abnor-

mality. Neonates suspected to have NIHF ought to

be investigated for possible causes of cardiovas-

cular failure because more than 50% of cases of

neonatal hydrops fetalis appear to be due to this

pathogenetic mechanism.

A close interaction among pediatric cardiolo-

gists, neonatologists, and pathologists is extremely

helpful to better guide patients� management and,

in case of death, a more precise autopsy approach. A

very detailed autopsy allows a better understanding

of the anatomy, histopathology, metabolism, he-

modynamics, and pathophysiology of the fetus and

the neonate and helps further clarify the etiology

and possible therapy of NIHF.

ACKNOWL EDGMEN T S

We thank Beatriz Varela for technical assistance

in preparing the composite photographs.

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Nonimmune Hydrops Fetalis in the Liveborn: Series of 32 Autopsies

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