Introduction:
The Rh-factor (rhesus factor) is a surface antigen on the red blood cells. It was first discovered on the red blood cells of the rhesus monkey, and it is named so. Several antigens (more than 50) are included in the Rh blood group. However, the D antigen is the most common, and its high immunogenicity is mainly responsible for Rh disease. Based on the presence and absence of D-antigens on the surface of red blood cells, a person can be Rh-positive and Rh-negative, respectively.
When an Rh-negative mother gives birth to an Rh-positive child, it results in hemolytic disease, and the newborn will show a broad range of symptoms. Early diagnosis of the condition and appropriate prophylaxis is crucial to prevent the risk of neonatal mortality. This article will outline the pathophysiology, diagnosis, and management of Rh-hemolytic disease in newborns and the role of medical professionals from multiple disciplines in managing the disease and improving health outcomes worldwide.
What Is Rh Incompatibility?
Rh incompatibility, otherwise known as Rh-hemolytic disease, is a condition that arises when an Rh-negative mother is exposed to Rh-positive blood. Rh-positive blood contains D antigen on the red blood cell surface, whereas it is absent in the case of Rh-negative blood. The exposure will trigger the production of antibodies against the D antigen in the Rh-negative mother, a process referred to as isoimmunization. Once sensitized, the antibodies against the D antigen will remain in the maternal blood throughout their life. The antibodies can move freely across the placenta during subsequent pregnancies to reach fetal circulation. However, suppose the carrying fetus is Rh-positive. In that case, the D-antibodies will form a complex with fetal D antigen, destroying fetal red blood cells and causing hemolytic anemia in newborns, referred to as erythroblastosis fetalis. The extent and severity of the disease depend upon the number of D-antibodies, the gestation period, and the enzymatic activity of the child.
Underdiagnosis often leads to a high mortality rate in the neonatal period of almost 24 %. The best method of preventing such a situation is universal screening and administering Rh antibodies as a prophylactic measure to reduce neonatal mortality significantly.
What Are the Causes of Rh-Hemolytic Disease in Newborns?
Rh incompatibility occurs due to two main reasons, which are
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Exposure of Rh-Negative Maternal Blood to Rh-Positive Fetal Blood:
Exposure of fetal blood to maternal blood may occur through bleeding during pregnancy, secondary to normal childbearing, accidental or induced abortions, invasive procedures like (amniocentesis, cordocentesis, chorionic villous sampling), cesarian delivery, ectopic pregnancy (baby grows outside the uterus) or trauma.
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Errors in blood transfusion, like, transfusing Rh-positive blood into Rh-negative women during a case of emergency:
Once the formation of antibodies against the D-antigen sensitizes the female, future pregnancies are risky. Rh-incompatibility develops in the fetus if the child happens to be Rh-positive. It results in hemolytic disease in the newborn. The antibodies against the D antigen will cross the placenta and reach the fetal blood causing severe anemia and hyperbilirubinemia (increased bilirubin in the blood) in the fetus leading to neurological damage and death.
What Is the Pathophysiology of Rh-Hemolytic Disease?
The production of antibodies against the D antigen in the maternal blood depends upon several factors.
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The volume of blood lost in trauma during pregnancy.
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The extent of the immune response produced by the mother.
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Presence of ABO incompatibility concurrently (occurs when the baby's blood group is A or B and the mother's blood group is O).
When the Rh-positive fetal blood crosses the placental barrier, which separates the maternal-fetal blood circulation and reaches the maternal blood, the mother's immune system considers the fetal blood as a foreign body. It produces an immune response by initially producing IgM antibodies.
In the first pregnancy, when the initial blood exposure occurs, no specific symptoms are seen in the fetus because the IgM antibodies cannot cross the placental barrier. However, subsequent exposure in the following pregnancy will produce IgG antibodies against the D antigen. It can easily cross the placental barrier to reach fetal circulation and binds with the D antigen on the surface of fetal red blood cells. The formation of an antigen-antibody complex in the fetus will activate an immune response in the fetal body which attacks the red blood cells and produce a large quantity of bilirubin in fetal circulation. While the fetus is inside the uterus, the excess bilirubin is removed from the fetal body with the help of maternal enzymes. Once the baby is born, early removal of excess bilirubin will not be possible because of the insufficiency of specific enzymes. The newborns will be presented with jaundice (high bilirubin level in the blood), kernicterus (brain damage caused by a high bilirubin level), and severe hemolytic anemia.
How Is Rh-Incompatibility Evaluated?
The United States preventive services task force recommends evaluating the Rh-blood type of every pregnant woman. If a woman is Rh-negative, the presence of antibodies against the D antigen in their blood should be determined. An antibody titer test is performed. If the maternal anti-D-antibody titers are greater than 1:16, amniocentesis should be performed early to determine the Rh status of the baby.
In case of emergencies, when a patient comes for delivery without prior blood investigations, the blood sample from the umbilical cord is taken for fetal blood analysis. Based on the analysis, the need for early exchange transfusion is evaluated. Pelvic ultrasound imaging will show signs of fetal soft tissue edema, ascites, scalp edema, etc. In cases of severely affected babies, cardiomegaly and hepatomegaly are observed.
How Is Rh-Hemolytic Disease in Newborns Managed?
The most effective prophylactic measure for Rh-incompatibility is the Rh-immunoglobulin introduced five decades ago. A significant decrease in disease incidence and associated mortality has been observed after using prophylactic immunoglobulin.
Jaundice is treated using phototherapy. Depending on the severity of hemolytic anemia of the fetus, in-utero blood transfusions are performed.
Conclusion:
From the above article, it is clear that with appropriate awareness and availability of prophylactic measures, it is possible to limit the global crisis associated with Rh-incompatibility leading to increased incidence of neonatal mortality. However, lack of awareness is the stigma that leads to the global burden of Rh-hemolytic disease leading to fetal demise. A multidisciplinary approach toward identifying and preventing the disease will lead to a better tomorrow.
