Hydrops fetalis

Lamiaa Mohsen
 Hydrop fetalis
• Hydrops fetalis is a condition in the fetus
characterized by an abnormal collection of fluid with
at least  two of the following:
– Edema
(fluid beneath the skin, more than 5 mm).
– Ascites
(fluid in abdomen)
– Pleural effusion
 (fluid in the pleural cavity, the fluid-filled space that
surrounds the lungs)
– Pericardial effusion
(fluid in the pericardial sac, covering  that surrounds the
heart)
 Hydrop fetalis
• Hydrops fetalis is typically diagnosed during
ultrasound evaluation for other  complaints
– Fetal tachycardia
– Large fordate
– Decreased fetal movement
– Abnormal serum screening
– Antenatal hemorrhage
 Etiology
• Hydrops fetalis is found in about 1 per 2,000
births and is categorized as :
– Immune hydrops
– Nonimmune hydrops
 Immune hydrops
• Accounts for 10-20%of cases
• Maternal antibodies against red-cells of the fetus
cross the placenta and coat fetal red cells which are
then destroyed (hemolysis) in the fetal spleen.
• The severe anemia leads to
• High-output congestive heart failure.
• Increased red blood cell production by the spleen and liver
leads to hepatic circulatory obstruction (portal
hypertension)
 Immune hydrops
• Anti-D, anti-E, and antibodies directed against other
Rh antigens comprise the majority of antibodies
responsible for hemolytic disease of the newborn .
• However, there are numerous, less commonly
encountered, antibodies such as anti-K (Kell), anti-Fya
(Duffy) , and anti-Jka (Kidd)  that may also cause hemolytic
disease of the newborn.
 Non-immune hydrops
• Accounts for 80 -90% of cases
• Any other cause besides immune.
• In general nonimmune hydrops (NIH) is
caused by a failure of the interstitial fluid (the
liquid between the cells of the body) to return
into the venous system .
 Non-immune hydrops
• This may due to:
– Cardiac failure
(High output failure from anemia,  sacrococcygeal
teratoma, fetal adrenal neuroblastoma, etc.)
– Impaired venous return
(Metabolic disorders)
– Obstruction to normal lymphatic flow
(Thoracic malformations)
– Increased capillary permeability
– Decreased colloidal osmotic pressure
(Congential nephrosis)
 Causes
• Causes can be grouped in 6 broad categories:
– Cardiovascular
– genetic abnormalities
– intrathoracic malformations
– hematological disorders
– infectious conditions
– idiopathic forms
 Cardiac causes
• Structural anomalies
– Abnormalities of left ventricular outflow
• Aortic valvular stenosis
• Aortic valvular atresia
• Coarctation of the aorta
• Aortico-left ventricular tunnel
• Atrioventricular canal
• Left ventricular aneurysm
• Truncus arteriosus
• Hypoplastic left heart
• Spongiosum heart
• Endocardial fibroelastosis
 Cardiac causes
• Structural anomalies (cont.)
– Abnormalities of right ventricular outflow
• Pulmonary valvular atresia or insufficiency
• Ebstein anomaly
 Cardiac causes
• Structural anomalies (cont.)
– Other vascular malformations
• Arteriovenous malformations
• Diffuse hemangiomatosis
• Placental hemangioma
• Umbilical cord hemangioma
• Hepatic hemangioendothelioma
• Abdominal hemangioma
• Pulmonary arteriovenous fistula
• Cervical hemangioendothelioma
• Paratracheal hemangioma
• Cutaneous cavernous hemangioma
• Arteriovenous malformations of the brain
 Cardiac causes
• Nonstructural anomalies
– Obstruction of venous return
• Superior or inferior vena cava occlusion
• Absent ductus venosus
• Umbilical cord torsion or varix
• Intrathoracic or abdominal tumors or masses
• Disorders of lymphatic drainage
 Cardiac causes
• Nonstructural anomalies (cont.)
– Supraventricular tachycardia
– Congenital heart block
– Prenatal closure of the foramen ovale or ductus
arteriosus
– Myocarditis
– Idiopathic arterial calcification or hypercalcemia
– Intrapericardial teratoma
 Hematologic causes
• Isoimmunization (hemolytic disease of the
newborn, erythroblastosis)
– Rh (most commonly D; also C, c, E, e)
– Kell (K, k, Kp, Js[B])
– ABO
– MNSs (M, to date)
– Duffy (Fyb )
 Hematologic causes
• Other hemolytic disorders
– Glucose phosphate isomerase deficiency
(autosomal recessive)
– Pyruvate kinase deficiency (autosomal recessive)
– G-6-PD deficiency (X-linked dominant)
 Hematologic causes
• Disorders of red cell production
– Congenital dyserythropoietic anemia types I and II (autosomal
dominant)
– Diamond-Blackfan syndrome (autosomal dominant)
– Lethal hereditary spherocytosis (spectrin synthesis defects)
(autosomal recessive)
– Congenital erythropoietic porphyria (Günther disease)
(autosomal recessive)
– Leukemia (usually associated with Down or Noonan syndrome)
– Alpha-thalassemia (Bart hemoglobinopathy)
– Parvovirus B19 (B19V)
 Hematologic causes
• Fetal hemorrhage
– Intracranial or intraventricular
– Hepatic laceration or subcapsular
– Placental subchorial
– Tumors (especially sacrococcygeal teratoma)
– Fetomaternal hemorrhage
– Twin-to-twin transfusion
– Isoimmune fetal thrombocytopenia
 Infectious causes
• B19V
• Cytomegalovirus (CMV)
• Syphilis
• Herpes simplex
• Toxoplasmosis
• Hepatitis B
• Adenovirus
• Ureaplasma urealyticum
• Coxsackievirus type B
• Listeria monocytogenes
• Enterovirus10
• Lymphocytic choriomeningitis virus (LCMV)11
 Inborn errors of metabolism
– Glycogen-storage disease, type IV
– Lysosomal storage diseases
• Gaucher disease, type II (glucocerebroside deficiency)
• Morquio disease (mucopolysaccharidosis, type IV-A)
• Hurler syndrome (mucopolysaccharidosis, type 1H; alpha1–iduronidase
deficiency)
• Sly syndrome (mucopolysaccharidosis, type VII; beta-glucuronidase
deficiency
• Farber disease (disseminated lipogranulomatosis)
• GM1 gangliosidosis, type I (beta-galactosidase deficiency)
• Mucolipidosis I
• I-cell disease (mucolipidosis II)
• Niemann-Pick disease, type C
 Inborn errors of metabolism
– Salla disease (infantile sialic acid storage disorder
[ISSD] or sialic acid storage disease,
neuroaminidase deficiency)
– Hypothyroidism and hyperthyroidism
– Carnitine deficiency
 Genetic syndromes
– Achondrogenesis, type IB (Parenti-Fraccaro syndrome)
– Achondrogenesis, type II (Langer-Saldino syndrome)
– Arthrogryposis multiplex congenita, Toriello-Bauserman type
– Arthrogryposis multiplex congenita, with congenital muscular
dystrophy
– Beemer-Langer (familial short-rib syndrome)
– Blomstrand chondrodysplasia
– Caffey disease (infantile cortical hyperostosis; uncertain inheritance)
– Coffin-Lowry syndrome (X-linked dominant)
– Cumming syndrome
– Eagle-Barrett syndrome (prune-belly syndrome; since 97% males,
probably X-linked)
 Genetic syndromes
– Familial perinatal hemochromatosis
– Fraser syndrome
– Fryns syndrome
– Greenberg dysplasia
– Lethal congenital contracture syndrome
– Lethal multiple pterygium syndrome (excess of males, so probably X-
linked)
– Lethal short-limbed dwarfism
– McKusick-Kaufman syndrome
– Myotonic dystrophy (autosomal dominant)
– Nemaline myopathy with fetal akinesia sequence
– Noonan syndrome (autosomal dominant with variable penetrance)
 Genetic syndromes
– Perlman/familial nephroblastomatosis syndrome (inheritance
uncertain)
– Simpson-Golabi-Behmel syndrome (X-linked [Xp22 or Xp26])
– Sjögren syndrome A (uncertain inheritance)
– Smith-Lemli-Opitz syndrome
– Tuberous sclerosis (autosomal dominant)
– Yellow nail dystrophy with lymphedema syndrome (autosomal
dominant
 Chromosomal syndromes
– Beckwith-Wiedemann syndrome (trisomy 11p15)
– Cri-du-chat syndrome (chromosomes 4 and 5)
– Dehydrated hereditary stomatocytosis (16q23-qter)
– Opitz G syndrome (5p duplication)
– Pallister-Killian syndrome (isochrome 12p mosaicism)
– Trisomy 10, mosaic
– Trisomy 13
– Trisomy 15
– Trisomy 18
– Trisomy 21 (Down syndrome)
– Turner syndrome (45, X)
 Tumor or mass causes
• Intrathoracic tumors or masses
– Pericardial teratoma
– Rhabdomyoma
– Mediastinal teratoma
– Cervical vascular hamartoma
– Pulmonary fibrosarcoma
– Leiomyosarcoma
– Pulmonary mesenchymal malformation
– Lymphangiectasia
 Tumor or mass causes
• Intrathoracic tumors or masses (cont.)
– Bronchopulmonary sequestration
– Cystic adenomatoid malformation of the lung
– Upper airway atresia or obstruction (laryngeal or
tracheal)
– Diaphragmatic hernia
– Eventration of the diaphragm
 Tumor or mass causes
• Abdominal tumors or masses
– Metabolic nephroma
– Polycystic kidneys
– Neuroblastoma
– Hepatic mesenchymal hamartoma
– Hepatoblastoma
– Ovarian cyst
 Tumor or mass causes
• Other conditions
– Placental choriocarcinoma
– Placental chorangioma
– Cystic hygroma
– Intussusception
– Meconium peritonitis
– Intracranial teratoma
– Sacrococcygeal teratoma
 Pathophysiology
• In immune hydrops, excessive and prolonged
hemolysis causes anemia, which in turn
stimulates marked marrow erythroid
hyperplasia
• It also stimulates extramedullary
hematopoiesis in the spleen and liver with
eventual hepatic dysfunction
 Pathophysiology
• The precise pathophysiology of hydrops
remains unknown
• Theories includes
– Heart failure form profound anemia and hypoxia
– Portal hypertension due to hepatic parenchymal
disruption caused by extramedullary hemopoiesis
– Decreased colloid oncotic pressure resulting from
liver dysfunction and hypopreteinemia
 Pathophysiology
• The degree and duration of anemia is the major
factor causing and influencing the severity of
ascites
• Secondary factors include hypoproteinemia
caused by liver dysfunction and capillary
endothelial leakage resulting from tissue
hypoxia, both of these lead to protein loss and
decreased colloid oncotic pressure
 Pathophysiology
Severe anemia

Hepatic extramedullary hematopoeisis

Decreased production of plasma proteins

Decreased plasma COP

 Pathophysiology
Congestive heart failure

Increased central venous pressure

Increased capillary hydrostatic pressure

Pathophysiology
Severe tissue hypoxia

Endothelial cell damage

Capillary leak of fluid & protein

Decreased Increased
COP CVP

Increased
fluid efflux
from intravascular
space

Capillary
leak
 Pathophysiology
• There may be cardiac enlargement and
pulmonary hemmorrhage
• Fluid collects in the fetal thorax, abdominal
cavity, or skin
• The placenta is markedly edematous, enlarge,
and boggy. It contains large, prominent
cotyledons and edematous villi
 Pathophysiology
• Pleural effusions may be so severe as to
restrict lung development, which causes
pulmonary compromise after birth
• Ascites, hepatomegaly, and splenomegaly
may lead to severe labor dystocia
• Severe hydropic changes are easily seen with
sonography
 Pathophysiology
• Fetuses with hydrops may die in utero from
profound anemia and circulatory failure
• One sign of severe anemia and impending
death is the sinusoidal fetal heart rate pattern
• Hydrops placental changes leading to
placentomegaly can cause preeclampsia
 Pathophysiology
• The liveborn hydropic infant appears pale,
edematous, and limp at birth and usually
requires resuscitation
• The spleen and liver are enlarged, and there
may be widespread ecchymosis or scattered
petechiae
• Dyspnea and circulatory collapse are common
Non-immune Hydrops Fetalis
Placenta of Hydropic Pregnancy

Placenta of Normal Pregnancy

 Associated complication
• Polyhydramnios
• Placenta abruption
• Uterine atony
• Pre-mature labour
• Hydropic, theickened placenta (> 6 cm)
• Retained placenta
• Preeclapsia
 Associated complication
• In an attempt to compensate for the fetal hypoxia,
placenta increases in size and sometimes also
penetrate deeper into the myometrium. Thus causes
the morbid adherence of placenta and can cause the
problems for third stage of labor necessitating the
manual removal of Placenta.
 Associated complication
• Mirror syndrome
• The mother develops preeclampsia along with
severe edema that is similar to that of the fetus
• Caused by vascular changes in the swollen,
hydropic placenta, this likely related to
antiangiopenic factors produced by
hyperplacentosis
 History
• A history suggesting the presence of any of the
following factors should trigger an extensive
diagnostic study for hydrops fetalis:
• Maternal history
– Rh negative (d;d) blood type
– Known presence of isoimmune blood group
antibodies
– Prior administration of blood products
– Risks of illicit drug use
 History
• Maternal history (cont.)
– Collagen-vascular disease
– Thyroid disease or diabetes
– Organ transplant (liver, kidney)
– Blunt abdominal trauma (abuse, auto accident)
– Coagulopathy
– Use of indomethacin, sodium diclofenac, or
potentially teratogenic drugs during pregnancy
– Younger (<16 y) or older (>35 y) maternal age
 History
• Maternal history (cont.)
– Risk factors for sexually transmitted diseases
– Hemoglobinopathy (especially with Asian or
Mediterranean ethnicity)
– Occupational exposure to infants or young
children
– Pet cat
– Current or recent community epidemic of viral
illness
 History
• Family history
– Jaundice in other family members or in previous
child
– Family history of twinning (specifically,
monozygotic)
– Family history of genetic disorders, chromosomal
abnormalities, or metabolic diseases
– Congenital malformation in previous child
– Previous fetal death
 Physical
• The presence of any of the following maternal
or fetal physical findings should prompt
further diagnostic evaluation:
– Twinning
– Hydramnios
– Exanthem or other evidence of intercurrent viral
illness
– Herpetic lesion or chancre
– Decrease in fetal movements
 History
• Family history (cont.)
– Hydramnios in earlier pregnancies
– Prior hydrops fetalis
– Previous fetomaternal transfusion
– Congenital heart disease in previous child
 Laboratory Studies
• Diagnostic studies may be considered best by
temporal grouping (ie, fetal, maternal,
placental, neonatal, postmortem).
• Assessments generally proceed from low-risk
noninvasive tests to higher-risk invasive
techniques as required for precise and
complete diagnosis to properly manage the
individual pregnancy.
 Maternal laboratory studies
• Assessment of maternal blood type (red cells)
and antibody screen (identification, and
quantitation when indicated, of maternal
plasma antibodies)
• Qualitative and quantitative estimates of the
proportion of red cells containing fetal
hemoglobin in the maternal circulation
 Maternal laboratory studies
• The search for maternal-fetal infection
– Syphilis serology
• Antibody screens for common fetal infections
– toxoplasmosis, other infections, rubella, CMV
infection, and herpes simplex [TORCH]
• Hemoglobin electrophoresis for alpha-
thalassemia heterozygosity
 Maternal laboratory studies
• Maternal serum screening tests
– AFP levels
– Unconjugated estriol (uE3)
– Human chorionic gonadotropin levels
– inhibin-A levels
– Maternal serum IgG placental alkaline
phosphatase levels
 Laboratory Studies
• Ultrasound - a diagnostic imaging technique
which uses high-frequency sound waves and a
computer to create images of blood vessels,
tissues, and organs. Ultrasounds are used to
view internal organs as they function, and to
assess blood flow through various vessels.
 Laboratory Studies
• Level II sonogram with Doppler measurement of
the peak systolic velocity (PSV)  in the fetal
middle cerebral artery (MCA) to assess for fetal
anemia. If there is evidence for anemia or
equivocal result obtain:
• Maternal blood counts and hemoglobin electrophoresis
(with hemoglobin DNA analysis), Kleihauer-Betke stain,
glucose 6-phosphate dehydrohgenase deficiency screen.
• Maternal TORCH titers, RPR, listeria, parvovirus B19,
coxsackie, adenovirus, and varicella IgG and IgM, as
indicated.
 Laboratory Studies
• Fetal echocardiogram
– Consider fetal heart rate monitoring for 12 to 24
hours if fetal arrhythmia is suspected.
• Amniocentesis for fetal karyotype and PCR
(polymerase chain reaction) for infections
• Fetal percutaneous blood sampling for same and
in addition fetal liver function; and metabolic
testing if indicated.
 Laboratory Studies
• In the presence of a family history of an
inheritable metabolic disorder or recurrent
nonimmune hydrops test for :
• Storage disorders such as Gaucher’s, gangliosidosis,
sialidosis, beta-glucuronidase deficiency, and
mucopolysaccharidosis
– Enzyme analysis and carrier testing in parents and/or analysis
of fetal or neonatal blood or urine.
– Histological examination of fetal tissues.
• Maternal thyroid antibodies
 Normal
four
Chamber
Cardiac
View
 Pericardial Effusion

Heart
Body wall
edema in a
hydropic
fetus
www.thefetus.net Fetal Ascites
Fetal Ascites
 Fetal Ascites

© www.thefetus.net
©
©
©
Hydrocele can
be an early
manifestation
in hydrops
Soft Tissue
shadow and
pleural
effusion in
hydropic
neonate
 Treatment
Cause Treatment

Fetal anemia Fetal blood sampling followed by in utero

transfusion
Fetal Arrhythmia Medications such as digoxin, sotalol,
propanolol , flecainide, amiodarone

Intrinsic thoracic malformations Thoracentesis or thoracoamniotic shunt

for pleural effusions in select cases

Twin to twin transfusion Fetoscopic laser ablation of

communicating vessels
Syphilis Penicillin
 Treatment
• Transplacental drug therapy
– Drugs are given to the mother and are passed to the
fetus through the placenta
– The main conditions which respond to this approach
are fetal dysrrhythmias (SVT)
– Once the type of dysrrhythmia is identified, anti-
arrhythmic agent is given to the mother, with careful
monitoring of her ECG & blood levels.
– Drugs: Digoxin, Verapamil, Amiadarone, Flecanide.
– Careful Maternal & Fetal Monitoring is Essential
 Treatment
• Direct fetal drug therapy
– Maternal administration of drugs may be
ineffective due to:
• Maternal Metabolism
• Maternal Side Effects
• Variable Passage Across Placenta
– Routes for direct fetal drug therapy:
• Intraperitoneal
• Intramuscular
• Intravascular
 Treatment
• Invasive Procedures
– Blood / Albumin Transfusion to Fetus
• Intraperitoneal
• Intravenous
– Umbilical Vein
– Hepatic Vein
 Treatment
• Invasive Procedures
– Drainage Procedures:
• Large Pleural Effusions
• Ascities
• All invasive procedures carry an inherent
increased risk of fetal demise or pre-mature
labor.
 Counseling
• Long term prognosis depends on underlying
cause and severity of the heart failure.
• If the cause of NIH cannot be determined, the
perinatal mortality is approximately 50%
• Prognosis is much poorer if diagnosed at less
than 24 weeks , pleural effusion is present,  or
structural abnormalities are present .
– Pulmonary hypoplasia is a common cause of death in
neonates with plerual effusions.
– Fetal hydrops associated with a structural heart
defect is associated with an almost 100% mortality
rate.
 Counseling
• If early in pregnancy (less than 24 weeks)  with
no treatable cause the option of termination
may be a consideration.
• Recurrence is uncommon unless related to
blood group incompatibility (isoimmunization)
or inheritable disorder.
 Antepartum
• Follow up of the fetus will depend on the
gestational age of the fetus,  and the mother's
wishes regarding intervention.
• If treatment has been successful or hydrops is
resolving spontaneously, the fetus may be
followed with repeat sonograms every 1 to 2
weeks and antenatal testing.
– Patients treated for immune hydrops are usually 
delivered at  37 weeks' or when fetal lung maturity
has been confirmed.
 Antepartum
• Consultation with the neonatologist may help
to decide when it is appropriate to  proceed
with preterm delivery for possible postnatal
treatment .
• The mother should be evaluated frequently
for signs of "mirror" syndrome.
 Delivery
• The fetus should be delivered at tertiary care
center with neonatologists and other
appropriate specialists.
• There is no evidence that delivery by cesarean
section has a marked effect on outcome.
• Cord blood should be obtained at delivery for
hemoglobin concentration and direct Coombs
testing
 Delivery
• A postmortem evaluation should be
performed in all cases of hydrops that result in
neonatal death. One study showed that a
combined approach of a thorough antenatal
assessment and autopsy may be more likely to
determine the cause of non-immune hydrops .
A hydropic neonate under extensive
Thank you for your attention