The Rhesus (Rh) factor is a protein found on the surface of red blood cells; its presence determines Rh status. If the protein is present, the individual is Rh-positive (about 85% of the population). The absence of the protein means the individual is Rh-negative. While Rh status is not inherently problematic, it is a serious consideration for blood transfusions, where incompatible blood can trigger a severe immune reaction. The factor’s most recognized impact occurs during pregnancy when an Rh-negative mother carries an Rh-positive fetus. This article explains the genetics of the Rh factor, the risks of Rh incompatibility, and preventative medical measures.
The Genetics of Rh Status
The Rh factor is determined by the RHD gene, which produces the D antigen protein on the red blood cell surface. Rh status is inherited from parents, separate from the ABO blood type, following a simple dominant and recessive model. The presence of the D antigen is the dominant trait.
An Rh-positive person has at least one copy of the dominant D allele, meaning the D antigen is expressed. This can be two dominant alleles or one dominant and one recessive allele. Conversely, an individual must inherit two copies of the recessive d allele, one from each parent, to be Rh-negative. The recessive d allele corresponds to a lack or deletion of the RHD gene, resulting in no D antigen production.
Two Rh-positive parents can potentially have an Rh-negative child if both are heterozygous (carrying one dominant D and one recessive d allele). An Rh-negative parent only carries d alleles and can only pass the recessive trait. Therefore, an Rh-negative mother can only carry an Rh-positive fetus if the biological father is Rh-positive.
Understanding Rh Incompatibility in Pregnancy
Rh incompatibility, often called Rh disease, occurs when an Rh-negative mother carries an Rh-positive fetus. The mother’s immune system recognizes the fetal Rh-positive red blood cells as foreign invaders because they carry the D antigen that her own cells lack. The mother’s body mounts an immune defense against these foreign antigens.
Sensitization is the initial event where the mother’s immune system is exposed to the fetal red blood cells. This exposure most commonly happens during childbirth when the placenta detaches and fetal blood mixes with maternal circulation. Exposure can also occur during procedures like amniocentesis, miscarriage, ectopic pregnancy, or abdominal trauma.
Upon initial exposure, the mother’s B cells produce immunoglobulin G (IgG) antibodies against the D antigen. Since this process takes time, the first pregnancy involving an Rh-positive fetus is usually unaffected. Once sensitized, the mother’s immune system retains a memory of the D antigen, and these anti-D IgG antibodies persist in her bloodstream.
In any subsequent pregnancy with an Rh-positive fetus, these pre-existing antibodies pose a severe risk. The small IgG antibodies cross the placental barrier and enter the fetal bloodstream. Once there, they attach to and destroy the Rh-positive red blood cells, a process called hemolysis. This condition is known as Hemolytic Disease of the Fetus and Newborn (HDFN), which leads to fetal anemia.
The destruction of red blood cells forces the fetus to rapidly produce new ones, potentially causing an enlarged liver and spleen. Severe anemia can progress to hydrops fetalis, characterized by widespread swelling and organ failure. After birth, the rapid breakdown of red blood cells causes high bilirubin levels and severe jaundice. If left untreated, this jaundice can lead to kernicterus, a type of brain damage.
Protecting Against Rh Incompatibility
Modern prenatal care has made Rh incompatibility largely preventable, dramatically reducing the incidence of HDFN. The process starts with routine blood typing and antibody screening of all pregnant individuals during their first prenatal visit. This screening, often called the indirect Coombs test, determines the mother’s Rh status and checks for pre-existing anti-D antibodies, which indicate prior sensitization.
If an Rh-negative individual has not developed anti-D antibodies, the preventative treatment is Rh immune globulin, commonly known as RhoGAM. RhoGAM is a plasma-derived medication containing passive anti-D antibodies. The injection is given to the mother and works by intercepting and destroying any Rh-positive fetal red blood cells that may have entered the maternal circulation.
This preventative action removes the foreign D antigens before they can trigger the mother’s self-generated, long-lasting immune response. Routine RhoGAM administration typically occurs around 28 weeks of gestation, a period associated with minor fetomaternal bleeding risk. An additional dose is administered to the Rh-negative mother within 72 hours after delivery, but only if the newborn is confirmed to be Rh-positive.
RhoGAM is also administered after any event that could cause fetal and maternal blood to mix, such as miscarriage, abortion, or invasive prenatal testing. This targeted use of Rh immune globulin has been highly effective, decreasing the risk of Rh sensitization from approximately 16% to less than 1%. The treatment prevents the creation of the mother’s own anti-D antibodies, protecting current and future Rh-positive fetuses from HDFN.