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Understanding rhesus disease of the fetus

Understanding rhesus disease of the fetus

Fetuses with a positive blood group, conceived by mothers with a negative blood group are at risk of developing rhesus disease

Rhesus disease can occur only when a mother with a negative blood group conceives a baby with a positive blood group

Blood groups are among the several attributes passed on from parents to the offspring and governed by the genes inherited from each parent. The antigens (protein structures) found on the surface of red blood cells help determine the blood group. The rhesus D (RhD) antigen determines the negative/positive classification. Having a negative blood group doesn’t have any health implications apart from a complication that could arise during pregnancy — rhesus disease or hemolytic disease, which has fatal consequences on the fetus.

There are eight blood groups: A+, B+, AB+, O+, A-, B-, AB-, and O-. The A, B, and AB blood groups contain A, B and AB antigens respectively, while the O blood group lacks both. Then comes the negative/positive classification. “This is determined by the presence of the rhesus D antigen,” shares Dr Gayathri D Kamath, senior consultant, obstetrics and gynecology, Fortis Hospitals, Bengaluru. “If you have RhD antigen on the surface of the RBCs, the blood group is positive. When the RhD antigen is absent, the blood group is negative.”

Causes of rhesus disease of the newborn

“Rhesus disease is also known as Rh incompatibility disease,” says Dr Divya Kumaraswamy, consultant, obstetrics and gynecology, Aster RV Hospital, Bengaluru. “When a mother with an Rh- blood group and partner with Rh+ blood group conceive a baby with an Rh+ blood group, there is a risk that the fetus [with positive blood group conceived in subsequent pregnancies] can suffer from rhesus disease. This is because mixing of maternal blood with the fetal blood during pregnancy or delivery will lead to the production of antibodies against the Rh antigen.”

Rhesus disease can occur only when a mother with a negative blood group conceives a baby with a positive blood group and not the other way around.

How blood mixes and causes rhesus disease

While the blood (of mother and fetus) gets mixed during the first delivery, there are other reasons why rhesus disease can occur, too.

“In a pregnant woman, the placenta acts as a barrier to prevent the mixing of maternal and fetal blood,” explains Dr Kamath. “In spite of it, certain events like trauma, bleeding or surgical procedures can cause fetal blood to enter the maternal blood circulation.”

If the mother’s blood group is negative, lacking the Rh antigen and the fetal blood with an RhD antigen enters the maternal circulation, the mother’s immune system recognizes it to be a foreign particle and triggers an immune response. This results in the production of antibodies against the RhD+ blood group, which is called Rh sensitization.

Effect of rhesus disease on the fetus

For the antibodies to be formed after the mixture of blood (Rh sensitization), it takes between 5 to 15 weeks. Thus, it’s fairly uncommon for the first baby to be affected.

“With Rh sensitization, the mother has already developed antibodies against the Rh antigen. Thus, if the subsequent babies are Rh+, these antibodies in the maternal blood pass through the placenta,” explains Dr Kamath. “They attack the fetal red blood cells, resulting in a drop of hemoglobin, causing anemia. As anemia worsens, it causes the heart to pump faster and results in cardiac failure and death of the fetus — miscarriage or stillbirth.”

In some cases, kernicterus, a form of brain damage caused by very high levels of bilirubin, is also seen.

Dr Kamath, however, remembers a case where an expecting mother in her first pregnancy was already Rh-sensitized. She had not had a miscarriage previously, so she was unaware of the exact cause. The baby, who was anemic, was given intrauterine blood transfusions. Eventually, she delivered a healthy baby.

Prevention and treatment of rhesus disease

In order to safeguard the baby from rhesus disease, it is essential to prevent the mixing of blood, along with other measures. Pregnant mothers with a negative blood group and a partner with a positive blood group should perform an indirect Coombs test to detect antibodies in the maternal blood. “If the test is negative, it implies that there are no antibodies in the maternal circulation. So, anti-D injection should be given around 28 weeks of pregnancy,” informs Dr Kamath. “These injections contain readymade antibodies, which act like blockers and combine with the Rh antigen of the fetal blood cells that have entered the mother’s circulation. Then the immune system of the mother will not recognize the foreign body; hence, it won’t produce antibodies against it.”

Dr Kumaraswamy adds, “The injection can also be administered within 72 hours of the delivery of the first Rh+ baby to prevent the development of rhesus disease in further pregnancies.”

Regular monitoring of the fetus with antenatal ultrasound and checking bilirubin levels in amniotic fluid helps detect the disease early. Further, a baby affected with rhesus disease can be treated with phototherapy and exchange transfusion during the neonatal period.


  • Rhesus disease is seen in fetuses conceived by mothers with a negative blood group and partners with a positive blood group.
  • In such cases, fetal blood entering maternal blood circulation can lead to the formation of antibodies against the positive blood group.
  • These antibodies can cross the placenta and attack the red blood cells of the fetus, resulting in anemia, jaundice,  kernicterus or even stillbirth.
  • Anti-D injection administered during 28-32 weeks of pregnancy or within 72 hours post-delivery can help prevent rhesus disease in subsequent pregnancies.

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