Sandbox:Ezici

Historical Perspective

Hydrops fetalis was first discovered by Dr. John William Ballantyne, a Scottish physician and obstetrician, in 1892.

Classification

Hydrops Fetalis may be classified into two groups based on the presence or absence of rhesus iso-immunization:

• Immune Hydrops Fetalis
• Non-Immune Hydrops Fetalis (NIHF)

Pathophysiology

• It is thought that hydrops fetalis is caused by conditions with either increased rate of fluid transudation from the vascular compartment or decreased lymphatic return to the circulation.
• This is shown to be originated from developmental defects in microcirculation and lymphatic system, respectively.
• The potential causes may be immune or non-immune, and they often result in anemia and further hypoxia.
• The sympathetic system becomes activated due to hypoxia, and it causes blood redistribution with decreased blood flow to the liver and kidneys.
• Decreased blood flow to the liver and kidneys, results in decreased albumin, increased ADH, and increased activity of RAAS.
• Following these changes, the central venous pressure increases, which further results in decreased lymphatic return.
• As a result, hydrops fetalis (the accumulation of fluid, or edema, in at least two fetal compartments) occurs.
• The pathophysiology of non-immune causes also depend on the underlying conditions, include:
  • Decreased ventricular filling during diastole (i.e. tachyarrhythmias)
  • Increased central venous pressure due to the increased right heart pressure (i.e. cardiac tumors and subendocardial fibroelastosis)
  • Obstruction of lymphatic drainage due to a mass (i.e. cystic hygroma)

Causes

Hydrops Fetalis is caused by either immune or non-immune conditions.

• Immune hydrops fetalis
  • Antibodies may occur due to the exposure of non-self RBC antigens during the previous pregnancy or transfusion.
  • In the next pregnancy, these antibodies may attack the fetal erythrocytes if the fetus has that antigen.
  • Following the red blood cell destruction, hemolytic disease of the fetus and newborn (HDFN) may occur with a wide range of clinical outcome from only mild anemia to high output heart failure and hydrops fetalis.
    • Rh disease is the major cause for immune-mediated hydrops fetalis; however, owing to preventative methods developed in the 1970s, the incidence of Rh disease has markedly declined.
    • Rh disease can be prevented by administration of anti-D IgG (Rho (D) Immune Globulin) injections to RhD-negative mothers during pregnancy and/or within 72 hours of the delivery.
• Non-immune hydrops fetalis (NIHF)
  • Currently, with the decreased prevelance of Rh disease, non-immune causes are responsible for up to 90% of cases.
  • The most common causes of non-immune hydrops fetalis are hematologic diseases, and chromosomal abnormalities, followed by lymphatic anomalies, and cardiovascular diseases. Causes of NIHF include:
    • Structural cardiac malformations (especially hypoplastic left heart, endocardial cushion defect)
    • Arrhythmias
    • Congenital lymphatic dysplasia
    • Chromosomal abnormalities (Turner Syndrome, trisomy 13, trisomy 18, trisomy 21)
    • Alpha-thalassemia
    • Fetomaternal transfusion
    • Infections (Parvo-B19, CMV, Adenovirus, Enterovirus)
    • Twin to twin transfusion syndrome (both donor and recipient fetus)
    • Congenital cystic adenomatoid malformation
    • Diaphragmatic hernia
    • Extrapulmonary sequestration
    • Hydrothorax
    • Chylothorax
    • Noonan Syndrome
    • Urethral Obstruction
    • Prune belly syndrome
    • Lysosomal storage disease
    • Vascular tumors
    • Teratoma
    • Leukemia
    • Hepatic tumors
    • Neuroblastoma
    • Meconium peritonitis
    • Gastrointestinal obstructions

Epidemiology and Demographics

• In developed countries, the incidence of non-immune hydrops fetalis (NIHF) is 25-79 per 100.000 live born infants worldwide.
• The median gestational age (GA) at diagnosis of NIHF is 23 weeks.
• Gestational age is predictive of mortality, as preterm infants with this condition are more likely to die.
• The case-fatality rate of NIHF is ranged from 43.2% to 78.2%.