In the event of a pregnancy where the fetus has the Rh-D blood antigen and the mother does not, the mothers immune system will respond to the red blood cells as foreign and create antibodies against the Rh-D antigen on the fetal blood cells. Rh disease develops in the event of a second pregnancy where the mothers immune system launches an attack, via IgG, against the infants Rh-D positive blood cells. The immune response results in hemolysis of fetal red blood cells causing severe anemia.Hemolysis caused by the Rh incompatibility, causes extramedullary hematopoiesis in the fetal liver and bone marrow. The push to make more erythroblasts to help compensate with the hemolysis over works the liver causing hepatomegaly. The resulting liver dysfunction decreases albumin output which in turn decreases oncotic pressure. Consequentially, the decrease in pressure results in overall peripheral edema and ascites.Rh disease is currently an uncommon cause of immune-mediated hydrops fetalis. Due 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. However, a small percentage of pregnant mothers are still susceptible to Rh disease even after receiving anti-D IgG (Rho(D) Immune Globulin). Non-immune pathophysiology
Severe anemia leads to hyperdynamic circulation, which means high-output cardiac failure causes the blood to circulate rapidly. The excessive pumping of blood causes the left side of the heart to fail leading to pulmonary edema.
The build up of fluid in the lungs increases the pressure in the lungs leading to vasoconstriction. The coupled vasoconstriction and pulmonary hypertension causes the right side of the heart to fail which in turn, increases the venous hydrostatic pressure in the body. The summation of these effects ultimately leads to peripheral edema and ascites. All in all, the left side failure of the heart will lead to pulmonary edema whereas right side failure will lead to peripheral edema and ascites. The non-immune form of hydrops fetalis has many causes including:
Iron deficiency anemia
Paroxysmal supraventricular tachycardia resulting in heart failure
Deficiency of the enzyme beta-glucuronidase. This enzyme deficiency is the cause of the lysosomal storage disease called mucopolysaccharidosis type VII. Congenital disorders of glycosylation
Parvovirus B19 (fifth disease) infection of the pregnant woman (most common cause)
Cytomegalovirus in mother
Congenital pulmonary airway malformation (formerly called congenital cystic adenomatoid malformation)
Maternal syphilis and maternal diabetes mellitus
Alpha-thalassemia can also cause hydrops fetalis when all four of the genetic loci for α globin are deleted or affected by mutation. This is termed Hb Barts (consists of y-4 tetramers). Uncommonly, Niemann-Pick disease Type C (NPC) and Gaucher disease type 2 can present with hydrops fetalis. Turner syndrome
Tumors, the most common type of fetal tumor being teratoma, particularly a sacrococcygeal teratoma.