Fetal maternal hemorrhage is the loss of fetal blood cells into the maternal circulation. Small insignificant hemorrhage of fetal blood into the maternal circulation occurs in nearly all pregnancies. The term fetal maternal hemorrhage signifies a significant amount of bleeding of fetal blood in maternal circulation. In some cases, the hemorrhage is large enough to compromise the fetus, resulting in fetal death, stillbirth, or a severely anemic infant.
Fetal maternal hemorrhage is said to be responsible for nearly 14% of unexplained fetal deaths and 3% of all fetal deaths.
Pathophysiology of Fetal Maternal Hemorrhage
A membrane in the placenta made of two layers, the syncytiotrophoblast and the cytotrophoblast acts as placental barrier and avoids direct contact between fetal and maternal circulation.
Any malfunction or break in this barrier leads to fetal maternal hemorrhage. Hemorrhage occurs from the fetus to the maternal circulation because placental blood vessels have higher blood pressure.
It is estimated that less than 1 mL of fetal blood is lost to the maternal circulation during routine deliveries.
Causes of increased fetal-maternal haemorrhage are
- Trauma- maternal falls and motor vehicle accidents
- Placental abruption
- Obstetric procedures
- External cephalic version
- Manual removal of a retained placenta
- Placental anomalies
- Abruptio Placentae
- Monochorionic–monoamnionic twins
- Spontaneous with no cause found.
Up to 30 mL of fetal maternal transfusion may occur without affecting mother or fetus but loss in excess of this may result in significant morbidity and mortality to the fetus.
Amount of blood loss, rate of blood loss and the chronicity of the bleed are important determinant of the severity of feto-maternal hemorrhage.
Feto-maternal hemorrhage can occur as early as 4 weeks of gestation.
Once bleeding starts two things can occur
- ABO incompatibility is present – Maternal clotting system may be activated, limiting the effect of the hemorrhage.
- No ABO incompatibility – clotting is less likely to be activated and the hemorrhage may continue.
If the fetus can compensate for the blood loss, the pregnancy may continue to delivery of an infant with varying degrees of anemia.
Fetus may compensate by [These findings may be noticed on Doppler ultrasound]
- Fetal tachycardia
- Increased cardiac
- Increased flow in the umbilical vessels
[When born, such fetuses may show evidence of increased hemopoetic activity in the neonate’s peripheral blood smear.]
In the setting of uncompensated anemia, the fetus may develop high-output heart failure and hydrops fetalis.
Clinical Presentation of Fetal Maternal Hemorrhage
Recognition of fetal maternal hemorrhage during pregnancy is difficult as the symptoms are nonspecific and subtle like nausea, edema, fever, and chills [like transfusion reaction].
Most of the cases are diagnosed retrospectively after an infant is stillborn.
Neonatal anemia has been reported to be the presenting sign in 35% of cases with shock and circulatory failure in severe cases.
At birth, these infants are often pale with evidence of poor perfusion. Respiratory distress and even general respiratory failure may be seen.
Other feature in infant suggesting feto-maternal hemorrhage are
- Acidosis due to bicarbonate depletion [bicarbonate is stored in RBCs]
- Hydrops fetalis
- Cardiomegaly or hepatomegaly.
- Disseminated intravascular coagulation
- Hypoxic-ischemic encephalopathy, cerebral infarction and periventricular leukomalacia
Diagnosis of Feto-maternal Hemorrhage
When suspected, maternal blood can be checked for the presence of fetal red blood cells.
Kleihauer Betke test or acid elution test s a blood test used to measure the amount of foetal hemoglobin transferred from a fetus to its mother’s bloodstream. It takes advantage of the differential resistance of fetal hemoglobin to acid.
In this test, maternal blood smear is fixed, washed with acid, and then stained. The maternal cells are not stable after the acid treatment and do not take-up the stain, appearing as ghost cells on the slide. The volume of hemorrhage can be calculated by accounting for the percentage of fetal cells present on the slide.
Fetal maternal haemorrhage can also be diagnosed by flow cytometry, using anti fetal hemoglobin antibodies (anti-HbF).
These diagnoses should be considered when an infant is born with
- Isoimmune hemolytic anemia (Rh incompatibility)
- Autoimmune diseases
- Congenital infections that result in bone marrow suppression (TORCH)
- Bacterial sepsis.
- Congenital hypoplastic anemia
- Diamond-Blackfan syndrome
- Congenital leukemia
Very rarely, fetal anemia is recognized before delivery. If the infant is near-term gestation, immediate cesarean delivery is indicated.
But if the fetus is of preterm gestation, in utero transfusion can be considered.
In continued hemorrhage continues, serial transfusions may be indicated.
Child with neonatal anemia should be managed accordingly
If the mother and fetus have Rh incompatibility, sensitization can occur and Rh immune globulin injection is indicated.
- Wylie B J, D’Alton M E. Fetomaternal hemorrhage. Obstet Gynecol. 2010;115(5):1039–1051.
- Dupre A R, Morrison J C, Martin J N Jr, Floyd R C, Blake P G. Clinical application of the Kleihauer-Betke test. J Reprod Med. 1993;38(8):621–624.
- Cardwell M S. Fetomaternal hemorrhage. When to suspect, how to manage. Postgrad Med. 1987;82(5):127–130.
- Catalano P M, Capeless E L. Fetomaternal bleeding as a cause of recurrent fetal morbidity and mortality. Obstet Gynecol. 1990;76(5 Pt 2):972–973.
- Fischer R L, Kuhlman K, Grover J, Montgomery O, Wapner R J. Chronic, massive fetomaternal hemorrhage treated with repeated fetal intravascular transfusions. Am J Obstet Gynecol. 1990;162(1):203–204.
- Davis B H, Olsen S, Bigelow N C, Chen J C. Detection of fetal red cells in fetomaternal hemorrhage using a fetal hemoglobin monoclonal antibody by flow cytometry. Transfusion. 1998;38(8):749–756.