Maternal-fetal Rhesus conflict: probability, when it occurs, what is dangerous, what to do

Part of the humoral immunity of the body is the system of blood antigens. Thus, on the plasma membranes of erythrocytes there are glycoprotein corpuscular antigens, among almost fifty of which the rhesus conflict during pregnancy is most often caused by agglutinogen D or the rhesus factor (Rh).

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Epidemiology

It is believed that no more than 15% of the European population has a negative Rh factor, that is, approximately every tenth expectant mother is Rh-.

Among the Basques of Spain, the prevalence of Rh negative blood reaches 35%; among Africans - 4%; among residents of Middle Asia - 2-4%; among the population of Southeast Asia and the Asia-Pacific region - less than 1%.

According to official data, Ph- is determined in 16-17% of whites, 7-8% of African Americans, 2-3% of American Indians in the USA. At the same time, as experts from the American Pregnancy Association claim, Rh-incompatible pregnancies, leading to isoimmunization (alloimmunization) and Rh-conflict, make up almost 20% of all gestations in the country. In 13 out of a hundred marriages, children are born to Rh- mothers from Rh+ fathers; one in a thousand babies is born with fetal hemolytic disease.

In Europe, approximately 13% of newborns are at risk of Rh incompatibility and half of them have complications, but with preventive treatment this number does not exceed 1%.

The risk of a conflict in the ABO blood group during pregnancy is estimated differently in different sources: from 2% to 16%.

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Causes Rh conflict

The conditions for the occurrence of Rh incompatibility between mother and fetus, that is, the causes of Rh conflict during pregnancy, are associated with the fact that the pregnant woman has a negative Rh blood type (Rh-), while the future child, like the father, has a positive Rh blood type (Rh+).

Although the majority of the population is Rh+, some people simply lack this highly immunogenic agglutinogen D (cluster of differentiation CD240D) in their blood. This is a recessive trait that is inherited with the d-allele of the RHD gene, which codes for the RhD transmembrane protein of red blood cells.

The presence of D-antigen in the blood of the future child causes incompatibility between the fetus and mother – Rhesus conflict. The inheritance of the Rhesus factor of the blood by the child and the probability of Rhesus conflict are more clearly presented in the table:

Mother's Rh factor	Father's Rh factor	Rh factor of the child	Probability of Rhesus conflict
Ph+	Ph+	Ph+ (75%) or Ph- (25%)	Absent
Ph-	Ph+	In 50% of pregnancies Ph+, in 50% Ph-	50%
Ph+	Ph-	Ph+ or Ph-	Absent
Ph-	Ph-	In 100% of pregnancies Ph-	Absent

The Rh factor is one of the most important factors for the ABO blood group and is of primary importance not only in obstetrics. Rh conflict may occur during blood transfusion: when a patient with Rh- is transfused with donor blood with Rh+. This leads to the production of antibodies to red blood cell antigens and forms an increased reactivity of humoral immunity (sensitization), which, during subsequent transfusion of blood plasma, provokes agglutination of red blood cells and is fraught with hemotransfusion shock.

In addition, incompatibility may arise as a conflict in the ABO blood group. This system of erythrocyte antigens takes into account the presence of antibodies, which are endogenous alloagglutinins: G-globulin antigens A (α-agglutinin) or B (β-agglutinin). They can be produced during any pregnancy, including the first. Unlike the formation of Rh antibodies in a Rhesus conflict, they do not need a stimulus from a second conflict pregnancy, i.e. a sensitization factor for the body.

This table of ABO blood groups gives an idea of the inheritance of a child's blood group and the combinations of mother's and father's blood groups that cause incompatibility between mother and fetus. Let us recall that the zero blood group (0) corresponds to the traditional I group, A - II, B - III and AB - IV.

Mother's blood type	Father's blood type	Blood type of the child	Probability of conflict
0	0	0	Absent
A	0	A or 0	Absent
IN	0	B or 0	Absent
AB	0	A or B	Absent
0	A	0 or A	No more than 50%
A	A	0 or A	Absent
IN	A	0, A, B or AB	No more than 50%
AB	A	A, B or AB	Absent
0	IN	0 or B	No more than 50%
A	IN	0, A, B or AB	No more than 50%
IN	IN	0 or B	Absent
AB	IN	0, B or AB	Absent
0	AB	A or B	Tall
A	AB	A, B or AB	No more than 50%
IN	AB	A, B or AB	No more than 50%
AB	AB	A, B or AB	Absent

Moreover, it turns out that up to 30% of patients with a negative Rh do not show any signs of iso-serological incompatibility, even when a significant volume of Rh-positive blood enters their bloodstream.

The risk of Rh sensitization after the first pregnancy is reduced by simultaneous incompatibility of the ABO blood group (by almost 5%), which, as hematologists suggest, may be the result of rapid utilization of incompatible red blood cells and subsequent weakening of the overall effect on the D antigen.

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Risk factors

In addition to the mother's own negative Rh factor and the fetus's positive Rh factor, as well as her zero blood group and the father's blood groups A or B, obstetricians and gynecologists name such risk factors for the development of sensitization and subsequent occurrence of Rh conflict as previous miscarriages, ectopic (extrauterine) or frozen pregnancy; Rh conflict developing after an abortion, after placental abruption; Rh conflict after childbirth, as well as after delivery by cesarean section; after invasive prenatal diagnostic procedures (puncture of the amniotic sac and collection of amniotic fluid for examination, etc.).

There is a significant risk of Rh-conflict if the pregnant woman has a history of transfusion of Rh+ blood plasma, as well as blunt abdominal trauma (severe bruises).

According to clinical observations, amniotic intrauterine hemorrhages are observed in 15-50% of pregnancies, and their frequency increases as the pregnancy progresses and in most cases occurs during childbirth.

The situation is complicated by the significant volume of transplacental hemorrhage and the very high degree of immunoreactivity of the mother.

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Pathogenesis

Blood with Rh+ from the circulatory system of the embryo and fetus can enter the bloodstream of the mother who has Rh-, which doctors call transplacental passage of embryonic erythrocytes. And the pathogenesis of the Rh conflict is that the absence of D-antigen in the mother's blood causes a reaction to its presence in the blood of the future child similar to an allergic reaction - with sensitization and the formation of RhD IgG antibodies.

The main immunoglobulin in Rh conflict is IgG, which accounts for almost 80% of all isotypes of serum antibodies that provide a secondary immune response. And the higher the density and antigenic determinant of the D-antigen on the surface of fetal erythrocytes, the more pronounced the reaction of the maternal immune system - isoimmunization (isoserological incompatibility or alloimmunization). Also read the article - Rh sensitization during pregnancy

During the current and all subsequent pregnancies, antibodies are able to penetrate into the fetus's blood, and if their level is high enough, antigen-antibody complexes with Rh-positive embryonic erythrocytes are formed, and hemolysis (destruction) of erythrocytes in the child's blood occurs. The fetus develops fetal hemolytic anemia with Rh-conflict.

At the same time, Rh conflict during the first pregnancy is usually not a threat, and the difference in the Rh factors of the parents does not cause problems for the child's health. Immunologists explain this by the fact that when carrying the first child, the body of the expectant mother simply does not have time to produce the corresponding antibodies (remember the physiological immunosuppression inherent in the period of pregnancy). However, this can only happen if the pregnant woman's medical history did not include certain circumstances (which ones are in the Risk Factors section).

In most cases, a Rh conflict occurs during the second pregnancy, a Rh conflict during the third pregnancy, etc. This is associated with the fact that isoimmunization occurs over time: the blood of a woman with Rh- already produces enough antibodies that can attack the child's red blood cells. And each time the problems can be more serious. The risk increases with multiple pregnancy, when a Rh conflict develops during a twin pregnancy - if the father's Rh+ is inherited.

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Symptoms Rh conflict

It should be noted right away that the symptoms of Rh-conflict in a pregnant woman are absent, that is, isoimmunization in the expectant mother does not manifest itself in any way, and her Rh-incompatibility with the fetus does not reveal itself in any way. And the course of pregnancy with Rh-conflict in physiological terms is practically no different from how gestation proceeds in women with Rh+. The hormonal background changes characteristic of the period of bearing a child also occur, toxicosis with Rh-conflict or swelling of soft tissues do not become stronger, etc.

But pregnancy management with Rh-conflict requires from the obstetrician-gynecologist not only high professionalism, but also maximum attention to the condition of the expectant mother and strict compliance with all medical prescriptions by the pregnant woman, in particular, timely blood tests. Since the only objective evidence of a brewing problem is increased antibodies with Rh-conflict, which begin to be produced in the body of the expectant mother to the D-antigen in the blood of the fetus (see below - section Diagnosis of Rh-conflict during pregnancy).

Rhesus conflict in early pregnancy (starting from 6-8 weeks) is possible, since the production of blood in the fetus begins approximately three weeks after implantation of the embryo in the uterus, and the Rh antigen is identified on the membranes of red blood cells at an early stage, 40 days after conception.

As a rule, the initial response to the RhD IgG antigen is slow, sometimes it occurs after five to six months. In this case, the Rh conflict is diagnosed in the late stages of pregnancy. But in subsequent pregnancies, the effect of maternal antigens on fetal erythrocytes begins 4-8 weeks earlier.

Also, a competent specialist will definitely have concerns about the development of a Rh conflict at the end of the second trimester due to polyhydramnios (increased volume of amniotic fluid), which is characteristic of Rh sensitization of the fetus and the development of fetal erythroblastosis.

Usually, childbirth with Rh-conflict (in the absence of contraindications caused by other pathologies) occurs naturally. However, if the child's condition is severe, a planned cesarean section is prescribed for Rh-conflict (at 37 weeks). But in both cases, breastfeeding with Rh-conflict is prohibited.

The first signs of the development of Rh-conflict in the fetus can be determined by ultrasound examination of the condition of such internal organs as the spleen, liver, heart (they will be enlarged). The placenta may also be thicker, and fluid accumulation in the abdominal cavity of the fetus is visualized on ultrasound.

Complications and consequences

Of course, the most negative and life-threatening consequences and complications of Rh-conflict during pregnancy are experienced by the child’s body.

The consequences for the child (both during intrauterine development, neonatal and infancy) are manifested in IgG-mediated hematological disorders:

• hemolytic disease of the newborn or fetal erythroblastosis (P55 according to ICD-10);
• Rh isoimmunization of the fetus and newborn (P55.0 according to ICD-10);
• ABO isoimmunization of the fetus and newborn (P55.1 according to ICD-10).

Anemia develops with Rh-conflict, cardiac insufficiency and dropsy - with edema of the subcutaneous tissues of the fetus's head, soft tissues of the body, with pleural and pericardial effusions and ascites. In severe cases, hemolysis can lead to extramedullary hematopoiesis and reticuloendothelial clearance of embryonic erythrocytes - with hepatosplenomegaly and decreased liver function (reduced production of blood proteins).

A slightly elevated level of bilirubin in the serum is manifested by the development of jaundice in newborns with Rh-conflict, but the levels of bilirubin (a pigment of red blood cells, a product of their hemolysis) should be constantly monitored.

Significantly elevated bilirubin in newborns with Rh-conflict can lead to nuclear jaundice (P57.0 according to ICD-10), which manifests itself not only as yellowing of the skin and sclera, muscle rigidity, convulsions, feeding difficulties, etc.

Unconjugated hyperbilirubinemia during the neonatal period can lead to brain damage and partial dysfunction. This is due to the neurotoxic effect of high concentrations of bilirubin in the blood on the gray matter of the brain. The damage can be either minor or fatal, leading to a lethal outcome.

Rhesus conflict during pregnancy has consequences for the mother. Firstly, the production of RhD IgG antibodies continues throughout life and has a negative effect on all subsequent pregnancies - if the future child has a positive Rhesus factor. And this threatens a more severe course of fetal erythroblastosis of the fetus and newborn.

Secondly, due to fetal edema in the first months of pregnancy, miscarriage often occurs due to Rh-conflict. And intrauterine fetal death - frozen pregnancy due to Rh-conflict - is noted by obstetricians in 8-10% of cases.

By the way, it is possible to perform IVF in case of Rh-conflict, however, when pregnancy occurs, the same problems may arise as with natural conception.

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Diagnostics Rh conflict

The blood group and Rh factor test is taken once – at the first visit to the antenatal clinic regarding pregnancy. If the woman’s Rh is negative, the child’s father should also take a blood test and accurately determine the Rh.

Diagnosis of Rhesus conflict during pregnancy is carried out on the basis of numerous laboratory tests of the blood of the expectant mother.

Blood tests for Rh incompatibility are the Coombs antiglobulin test, which is performed on the pregnant woman's venous blood; this test detects the mother's serum antibodies to the fetal D-antigen, and its positive result is a sign of their Rh incompatibility. And in newborns with Rh incompatibility, this test is performed immediately after birth to detect hemolytic anemia.

At what week do you take tests for Rh-conflict? At the first visit to the obstetrician-gynecologist, pregnant women with Rh- are put on special records and receive a referral for a blood test for antibodies in case of Rh-conflict. It is supposed to be taken at 7-8 weeks.

By regularly determining titers in case of Rh conflict, the doctor monitors the development of Rh sensitization and its intensity. If the initial result is negative (the analysis did not show the presence of IgG-anti-D antibodies), then a repeat test should be done at the 20th week of pregnancy. During the next 10 weeks, titers are determined every four weeks; from the 30th to the 36th week – once every two weeks; during the last month – weekly.

Below is a table of RhD IgG antibody titers for Rhesus conflict (with standard interpretation of the indicators):

1:4	Rhesus sensitization of the pregnant woman is determined
Above 1:8	Increasing the level of Rh sensitization without requiring invasive diagnostic intervention
1:16	Increased risk to fetal life; amniotic fluid testing (amniocentesis) is necessary
1:32	Development of intrauterine hemolysis and fetal hydrops, high risk of fetal death; amniocentesis and cord blood analysis for bilirubin are required
1:64 and above	Doppler flow monitoring of the fetal middle intracranial artery is required; termination of pregnancy or early delivery may be necessary

Cord blood analysis is performed to determine the fetus's blood type and Rh factor; hematocrit; levels of hemoglobin, bilirubin, and ferritin in its blood, as well as the amount of albumin, reticulocytes, platelets, and neutrophils. It may be necessary to analyze the amniotic fluid for bilirubin content.

Instrumental diagnostics include Dopplerography, Doppler blood flow velocity (in the heart, umbilical and intracranial arteries of the fetus); CTG (cardiotocography) is performed to assess the work of the fetal heart.

From the 18th week, they begin to do ultrasounds for Rh-conflict - at least five to six times, and more if necessary, in order to monitor the condition of the fetus, not to miss its deterioration (increased swelling) and to avoid such a measure as premature termination of pregnancy - abortion for Rh-conflict.

More information in the material - Rhesus conflict during pregnancy - Diagnostics

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Treatment Rh conflict

What does treatment of Rh-conflict during pregnancy mean? These are measures aimed at preventing the consequences of Rh-incompatibility in the mother and the development of hemolytic disease in the fetus.

Sensitization in the mother and the production of antibodies due to Rh conflict can be stopped by the introduction of human Rh immunoglobulin – RhO(D). This is a specially created immunoglobulin for the prevention of Rh conflict, consisting of IgG antibodies of human blood plasma and capable of penetrating the placenta. The mechanism of action is to block the human immune system from recognizing this Rh antigen.

Trade names of this drug: RhoGAM, KamRho, Rhophylac (R), Partobulin SDF, Resonativ, Gamulin Rh, HypRho-D, etc. It is administered intramuscularly – 300 mcg; the duration of action of a single dose is 2-4 weeks. The drug is usually prescribed from the 26th to 28th week at regular intervals throughout the second half of pregnancy, as well as during the first three days after delivery. Possible side effects include pain at the injection site, allergic reactions, fever, headache, decreased levels of red blood cells in the blood.

Prevention of Rhesus conflict during pregnancy in a hospital is carried out in cases where examination has shown an increase in antibody titers and it is necessary to cleanse the mother's blood of them, that is, to carry out plasmapheresis for Rhesus conflict.

In addition, in the clinic, intrauterine blood transfusion is performed to the fetus in case of Rh conflict, which is a replacement hematotransfusion through the umbilical vein and has been considered the method of choice in obstetric practice for the past three decades. The period of implementation is from the 22nd to the 34th week of pregnancy.

Treatment of hemolytic disease in newborns begins immediately after birth. Read more about this - Hemolytic disease of the newborn

Prevention

Today, the prevention of Rh conflict that occurs during pregnancy consists of the use of the same immunoglobulin RhO(D).

Some may think that this is a vaccination or a shot against Rh-conflict during pregnancy. But this is not the case. This immunoglobulin is prescribed to prevent an immune response to Rh-positive blood in people with Rh-negative blood. The drug can also be used to treat immune thrombocytopenic purpura.

Immunoglobulin is administered to women with Rh- immediately after an abortion, miscarriage, ectopic pregnancy and any other manipulations in one way or another related to conception and the threat of isoimmunization. Its effect is limited to 4-6 weeks.

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Forecast

Despite all the achievements of modern medicine, a 100% positive prognosis for the birth of healthy children in couples in which the woman has a negative Rh blood type and the man has a positive Rh blood type is impossible. After all, the Rh conflict is a consequence of the reaction of the blood's immune system, and erythrocytes not only carry oxygen to tissues, remove carbon dioxide from them, provide adenosine triphosphate (ATP) for all biochemical processes in the body, but also exhibit immunomodulatory activity.

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