perinatology.com
   Hydrops Fetalis

Presentation

Hydrops fetalis is typically diagnosed during ultrasound evaluation for other  complaints such as :

• Polyhydramnios
• Size greater than dates
• Fetal tachycardia
• Decreased fetal movement
• Abnormal serum screening
• Antenatal hemorrhage

Causes

Hydrops fetalis is found in about 1 per 2,000 births and is categorized as immune or 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)
• 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.

Nonimmune 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 .

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)

Normal return of of interstitial fluid to veins though lymphatic system (high pressure to low pressure)
Blood capillaries		Interstitial Fluid		Lymph  capillaries and veins		Large Veins
Mechanisms that may cause increased interstitial fluid
Increased capillary permeability OR  Decreased colloidal osmotic pressure				Lymph  capillaries and veins		Large Veins
Blood capillaries				Obstruction to lymph flow		Large Veins
Blood capillaries				Lymph  capillaries and veins		Impaired venous return OR Cardiac failure

Some conditions may involve more than one mechanism . For example, parvovirus may cause cardiomyopathy and anemia from marrow suppression.

• Conditions Associated with NIH
  (This list is not exhaustive)

 
• Cardiac
  • Cardiomyopathy, Ebstein's anomaly, pulmonary atresia, coarctation of the aorta, hypoplastic left heart, complete AV canal, left sided obstructive lesions, premature closure of the foramen ovale
  • Intracardiac tumors (tuberous sclerosis)
  • Cardiac arrhythmia
    • SVT, flutter, heart block, WPW syndrome
• Chromosomal /Genetic Syndromes
  • T13, T18, T21, XO (Turners syndrome) , Noonan syndrome , multiple pterygium syndrome, Pena-Shokeir, arthrogryposis
• Fetal Anemia
  • Alpha (α) thalassemia, parvovirus, fetal hemorrhage, G-6-PD deficiency
• Infection
  • Parvovirus, CMV, syphilis, coxsackie virus, rubella, toxoplasmosis, herpes,varicella, adenovirus, enterovirus, influenza, listeria
• Thoracic Abnormalities
  • Congenital cystic adenomatoid malformation (CCAM) , chylothorax, diaphragmatic hernia, mediastinal tumor, skeletal dysplasias
• Twinnning
  • Twin to twin transfusion Severe anemia in the donor twin or high-output failure in the recipient
• Tumors
  • Fetal sacrococcygeal teratoma, hemangiomas (Hepatic, Klippel-Trenaunay syndrome), fetal adrenal neuroblastoma, placental tumors (chorioangioma)
    
• Miscellaneous
  •  Cystic hygromas, inheritable disorders of metabolism (lysosomal storage diseases) ,maternal thyroid disease, congenital nephrotic syndrome.

Evaluation

• Obtain maternal history (including pedigree)
• Evaluate for immune hydrops
  • Obtain maternal indirect Coombs test to screen for antibodies associated with blood group incompatibility.
• Evaluate for nonimmune hydrops
  • 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.
  • 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 OR fetal percutaneous blood sampling for same and in addition fetal liver function; and metabolic testing if indicated.
  • 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

Treatment

Maternal complications
 

The mother may develop edema , hypertension, and proteinuria during conservative management of hydrops a condition known as Mirror syndrome (also known as  pseudotoxemia or Ballantyne syndrome) . Symptoms may persist after delivery.

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.
• 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.
• 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.