Non-invasive determination of fetal Rhesus factor in pregnant women

In which cases may it be necessary to determine the Rhesus factor of the unborn child?

What is Rhesus factor?

Rhesus factor is genetically inherited from the mother and the father. It refers to the presence or absence of a specific protein on the surface of the red blood cells. The Rhesus factor gene has two alleles: Rh positive (Rh+) when a specific protein is present on the surface of the red blood cells and Rh negative (Rh-) when a specific protein is absent from the surface of the red blood cells. Rh+ blood and Rh- blood are incompatible. It is important to know your Rh factor in blood transfusion cases, as transfusion of incompatible blood causes pathological blood clotting, which is unacceptable for the body. Furthermore, all pregnant women need to know their Rh factor, and Rh- women also must know their partner’s Rh factor. It is usually determined when the woman gets registered for prenatal care. If the pregnant woman is Rh- and the father of the unborn child is Rh+, there is a probability of 50% that the child may inherit the positive Rh factor from the father. Such couples are also at risk of fetal and neonatal haemolytic disease development and they require early determination of the fetal Rh factor to elaborate futher clinical tactics. Approximately 85% of all women and men are Rh positive, while the rest are Rh negative. In this case, there is a probability of approximately 13% that the couple facing the aforementioned risk will be formed.

What is Rhesus incompatibility?

In this case (Rh- mother/Rh+ fetus), there is a Rhesus conflict or Rhesus factor incompatibility between maternal and fetal blood which may lead to sensitization or immunization of the mother’s body (as is in the case of vaccination) against the Rh+ blood. If the child’s Rh+ blood gets into the mother’s blood during pregnancy or childbirth, a Rhesus conflict occurs: the mother’s body will start making anti-Rh antibodies. If sensitization occurs in the first pregnancy, fetal haemolytic disease may develop, and clinical manifestations of Rh incompatibility become more severe in each subsequent pregnancy (the fetus suffers more). Until recently, non-invasive determination of fetal Rh factor was not available and Rh negative pregnant women were regularly tested for antibodies in the blood. If antibodies are detected, it means that the sensitization has occurred and special treatment has to be used.

Why is Rhesus factor conflict dangerous?

The antibodies produced in the mother’s body during sensitization are able to disrupt the child’s red blood cells. This, in turn, may cause fetal haemolytic disease or haemolytic disease of the newborn (after birth), which in some cases may be a child’s life-threatening condition that requires supervision by a professional obstetrician and a potential invasive manipulation – a blood transfusion to the fetus.

When does Rh sensitization occur?

• If an Rh- woman has ever received a transfusion of Rh+ blood
• During a natural birth or a C-section (if the fetus is Rh+)
• In case of termination of pregnancy (if the fetus was Rh+) or spontaneous abortion. An Rh- woman is strongly recommended to keep her first pregnancy.
• In case of termination, the woman must be given an injection of anti-D immunoglobulin
• Manual separation of the placenta after delivery increases the possibility for the red blood cells from the baby to leak into the woman’s bloodstream
• If the mother injures her abdomen during pregnancy
• If an invasive procedure has been necessary during pregnancy (such as amniocentesis, chorionic villus sampling and cordocentesis)
• In case of an ectopic pregnancy
• In case of threatened termination of pregnancy when there is spotting
• In case of external rotation of the fetus in a breech presentation

All of the above cases require supervision by a specialist.

Forms of haemolytic disease of the newborn:

Substances released from the red blood cells that have been broken down (such as bilirubin) get into the blood plasma, which leads to further pathological reactions, the mildest of which is manifested as newborn anaemia. The newborn is pale because of reduced haemoglobin and red blood cell count. Transfusion of antibody-free blood on day 1 or 2 after birth can quickly improve the condition. A more severe form of haemolytic disease of the newborn is manifested as jaundice, which usually develops in the first day after birth and continues to intensify. As the condition progresses, the newborn becomes languid, sucks poorly and may develop convulsions due to bilirubin-induced CNS injury. This condition cannot be left without special supervision and a set of corrective actions. General fetal edema is the most severe form of the disease, in which case the child dies in the first hours after birth.

Is there a solution?

The Genetic centre iVF Riga offers non-invasive determination of Rh factor, which is an absolutely safe procedure for both the fetus and the pregnant woman. Venous blood is taken from the pregnant woman in order to extract the so-called circulating fetal DNA which appears in maternal circulation starting from approximately the 10thgestational week. Pregnancy progresses and this DNA concentration in maternal blood increases. This is why this analysis is recommended to make from 18th until 22th week of pregnancy, when the concentration is sufficient for a convincing result. During the molecular testing of the fetal DNA, genes are identified that encode or determine the physical manifestations of the Rh factor (whether a specific protein will be present on the surface of the red blood cells of the fetus). If it is determined that the fetal Rh factor is negative as is the mother’s Rh factor, an Rh conflict cannot develop and pregnancy is monitored as usual. In contrast, if the fetal Rh factor is positive, the further continuation of pregnancy will be monitored by an experienced OB/GYN who will also monitor the course of pregnancy and prescribe the required steps where necessary.

Paternal RHD zygosity test

Rhesus factor (Rh) is a protein located on the surface of red blood cells (erythrocytes) in the majority of the population. These people are called Rh positive (Rh+). If these proteins are absent on the surface of red blood cells, the person is Rh-negative (Rh-). The gene that is responsible for the Rh factor is genetically inherited from both parents. Rhesus-negative individuals inherit both from the mother and from the father a negative, or “-” allele (“–“). Rhesus-positive carry at least one “+” Rh gene: “++” or “+ -“. Rh incompatibility can occur if Rh-negative (“–“) woman is waiting for Rh-positive child. In this case, the immunoglobulin injection at the 28th week of pregnancy and after the birth of a child is recommended for the prevention of Rh incompatibility.

• If the partner is Rh-, Rh incompatibility does not occur, since all children of this pair will also be Rh-.
• If the partner is Rh+, Paternal RHD zygosity determination is necessary to find out the genetic status of the Rh+ partner ( “++” or “+ -“).
• If the partner is Rh+(“++”, homozygous), all the descendants of this pair will be Rh+ and during each pregnancy Rh-immunoglobulin prophylaxis is indicated.
• If the partner is Rh+ (“+ -“, heterozygous), 50% of the descendant of this pair will have Rh- blood group, at which immunoprophylaxis is not needed, but in 50% of cases the expected child will be Rh+, and then an immunoglobulin injection will be required. In such cases, it is recommended to check the Rh factor of the expected child during each subsequent pregnancy in order to make a decision about the need for immunoprophylaxis.