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 cardiovascular diseases, chromosomal abnormalities, lymphatic anomalies, and hematologic 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
  • Approximately 20% of the NIHF cases are idiopathic.

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.

Risk Factors

• Maternal risk factors in the development of non-immune hydrops fetalis (NIHF) include multiple gestation, preexisting maternal diabetes, mental illness, illicit drug use, and preeclampsia.

Screening

• 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.

Natural History and Prognosis

• Prognosis is generally poor, and the mortality rate of patients with non-immune hydrops fetalis (NIHF) is approximately 43.2% at 1 year of age.
• Deaths usually occur in the neonatal period.
• The cause of deaths after the neonatal period are usually underlying disease rather than hydrops fetalis itself.
• Gestational age is predictive of mortality, as preterm infants with this condition are more likely to die.
• The presence of either large birth weight, polyhydramnious, or prematurity are associated with a particularly poor prognosis among patients.

Diagnosis

Ultrasound

• Hydrops fetalis can be diagnosed and monitored by ultrasound scans.
• An official diagnosis is made by identifying excess serous fluid in at least one space (ascites, pleural effusion, of pericardial effusion) accompanied by skin edema (greater than 5 mm thick).
• A diagnosis can also be made by identifying excess serous fluid in two potential spaces without accompanying edema.
• Prenatal ultrasound scanning enables early recognition of hydrops fetalis and has been enhanced with the introduction of MCA Doppler.

Laboratory Findings

• Hydrops Fetalis may be caused by maternal TORCH infections, and parvovirus B19 infection, therefore, antibodies against these infections should be checked.
• Sjögren syndrome may cause hydrops fetalis with complete heart blocks and bradyarrhythmias, therefore, Anti-SS-A/SS-B antibodies should be considered in suspected cases.
• An elevated concentration of alpha-fetoprotein (AFP) may suggest fetomaternal hemorrhage, which may result in hydrops fetalis.
• Immune hydrops fetalis can be detected by direct and indirect coombs test.
• Thyroid hormone levels, complete blood count, and metabolic panel also should be checked in the neonatal period.

Other Diagnostic Studies

• Other diagnostic studies for hydrops fetalis include chorionic villous sampling (CVS), which may demonstrate chromosomal abnormalities or Hb Barts disease.

Treatment

• The treatment depends on the cause and stage of the pregnancy.
  • Severely anemic fetuses, including those with Rh disease and alpha thalassemia major, can be treated with blood transfusions while still in the womb. This treatment increases the chance that the fetus will survive until birth.
  • Therapy for cardiac tachyarrhythmia, supraventricular tachycardia, atrial flutter, or atrial fibrillation etiologies are maternal transplacental administration of antiarrhythmic medication(s). This type of treatment is recommended unless the fetus is close to term.
  • Therapy for Fetal anemia caused by a parvovirus infection or fetomaternal hemorrhage is fetal blood sampling followed by intrauterine transfusion. This treatment at an advanced gestational age poses risks and should not be performed if the risks associated with delivery are considered to be less than those associated with the procedure.
  • Fetal hydrothorax, chylothorax, or large pleural effusion associated with bronchopulmonary sequestration should be treated using a fetal needle drainage of effusion or placement of thoracoamniotic shunt. This procedure can be performed prior to delivery if gestational age is advanced.
  • Hydrops Fetalis resulting from fetal CPAM can be treated using either a fetal needle drainage of effusion or placement of thoracoamniotic shunt or a maternal administration of corticosteroids, betamethasone 12.5 mg IM q24 h × 2 doses or dexamethasone 6.25 mg IM q12 h × 4 doses.
  • Therapy for hydrops fetalis derived from TTTS or TAPS requires laser ablation of placental anastomoses or selective termination.
  • Therapy for hydrops fetalis derived from TRAPS requires percutaneous radio frequency ablation.