Fig. 7.27 Hydropsfetalis.(A)Generalizedaccumulationoffluidinthefetus.(B)Fluidaccumulationparticularlyprominentinthesofttissuesoftheneck.Thisconditionhasbeentermedcystic hygroma. Cystichygromasarecharacteristicallyseenwith,butnotlimitedto,constitutionalchromosomalanomaliessuchas45,Xkaryotypes.(Courtesy of Dr. Beverly Rogers,Department of Pathology,University of Texas Southwestern Medical Center,Dallas,Texas.) http://ebooksmedicine.net
Immune hydrops results from an antibody-induced hemolytic disease in the newborn that is caused by blood group incompatibility between mother and fetus. Such an incompatibility occurs when the fetus inherits red cell antigenic determinants from the father that are foreign to the mother. The most common antigens to result in clinically significant hemolysis are the Rh and ABO blood group antigens. Of the numerous antigens included in the Rh system, only the D antigen is a major cause of Rh incompatibility. Fetal red cells may reach the maternal circulation during the last trimester of pregnancy, when the cytotrophoblast is no longer present as a barrier, or during childbirth itself (fetomaternal bleed). The mother then becomes sensitized to the foreign antigen and produces antibodies that, in future pregnancies, can freely traverse the placenta to the fetus, in which they cause red cell destruction. With initiation of immune hemolysis, progressive anemia in the fetus leads to tissue ischemia, intrauterine cardiac failure, and peripheral pooling of fluid (edema). As discussed later, cardiac failure may be the final pathway by which edema occurs in many cases of nonimmune hydrops as well.
Several factors influence the immune response to Rh-positive fetal red cells that reach the maternal circulation:
Concurrent ABO incompatibility protects the mother against Rh immunization, because the fetal red cells are promptly coated by isohemagglutinins (preformed anti-A or anti-B antibodies) and removed from the maternal circulation.
The antibody response depends on the dose of immunizing antigen, so hemolytic disease develops only when the mother has experienced a significant transplacental bleed (more than 1 mL of Rh-positive red cells).
The isotype of the antibody is important, because immunoglobulin G (IgG) (but not IgM) antibodies can cross the placenta. The initial exposure to Rh antigen evokes the formation of IgM antibodies, so Rh disease is very uncommon with the first pregnancy. Subsequent exposure during the second or third pregnancy generally leads to a brisk IgG antibody response.
Appreciation of the role of previous sensitization in the pathogenesis of Rh-hemolytic disease of the newborn has led to its therapeutic control. Currently, Rh-negative mothers are given Rh immune globulin (RhIg) at 28 weeks and within 72 hours after delivery of an Rh-positive baby. The RhIg masks the antigenic sites on the fetal red cells that may have leaked into the maternal circulation during childbirth, thus preventing long-lasting sensitization to Rh antigens.