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 to 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 of 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 the 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 prevalence 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 (Parvovirus-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 diseases
    • 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%.

Risk Factors

• According to the U.S. Preventive Services Task Force (USPSTF), screening for Rh(D) incompatibility by Rh(D) blood typing and antibody testing are strongly recommended for all pregnant women during their first visit for pregnancy-related care.
• The USPSTF recommends repeated Rh(D) antibody testing for all unsensitized Rh(D)-negative women at 24 to 28 weeks gestation, unless the biological father is known to be Rh(D) negative.