The standard obstetrical nomenclature for designating a pregnant woman’s blood type is the ABO type and either Rh positive or Rh negative. These terms are commonly used to describe a woman who has or does not have the Rh(D) antigen on her red blood cells (RBCs). The Rh blood system consists of numerous other antigens, most commonly C, c, E, e, and G.

Maternal Rh(D) alloimmunization develops as a result of maternal immune system exposure to Rh(D)-positive red blood cells (RBCs). Maternal immunization can occur as a result of transplacental fetomaternal hemorrhage during any pregnancy, injection with needles contaminated by Rh(D)-positive blood, or inadvertent transfusion of Rh(D)-positive blood (including during transplantation).

The pathogenesis of fetal anemia is the same for both major and minor RBC antibodies. The predominant mechanism involves transplacental passage of a maternal IgG antibody directed against a fetal erythrocyte antigen. Red blood cell hemolysis is cell mediated, rather than a complement mediated. In Kell alloimmunization in addition to cell-mediated hemolysis, the erythropoiesis is suppressed at the level of the progenitor cell. Because of this, at the same level of anemia, the fetus with Kell alloimmunization has a lower number of circulating reticulocytes and normoblasts compared with the fetus with Rh(D) alloimmunization [3, 4]. The suppressive effect of anti-Kell antibodies does not extend to fetal granulocyte or megakaryocyte progenitors [5], and hence significant thrombocytopenia is less common than in Rh(D) alloimmunization [6, 7].

The diagnosis of Rh(D) alloimmunization is based upon detection of anti-Rh(D) antibody in maternal serum. In Rh(D)-negative women, the antibody screen may be repeated at 28 weeks of gestation and should be repeated at delivery [8, 9].

A positive anti-D titer means that the fetus is at risk for hemolytic disease, not that it has occurred. Variation in titer results between laboratories is common.

Minor red blood cell (RBC) antibodies, with the exception of Kell sensitization, are rarely present in pregnant women and usually remain at low titer (≤4).

If the critical titer is reached, the fetus should be evaluated for the presence of anemia.

Over the years, various studies state that Doppler assessment of the fetal middle cerebral artery (MCA) peak systolic velocity is the best noninvasive tool for predicting fetal anemia in at-risk pregnancies [10].

Severe fetal anemia can be defined as a hematocrit below 25 % or two standard deviations below the mean hematocrit for the gestational age. Severe fetal anemia is an indication for intervention because it may result in fetal cardiac failure and hydrops.

Intrauterine transfusions (IUTs) are generally done between 18 and 34 weeks. Leukodepleted, irradiated O-negative blood cros-matched to the mother’s blood packed to a hematocrit of 75–85 % is used.

The volume of blood for IUT depends upon the initial fetal hematocrit, size of the fetus, the donor hematocrit, and the target hematocrit to be achieved. There are prescribed formulae and charts to calculate the volume for infusion. After 24 weeks of gestation, a target hematocrit of 40–50 % is preferable. The average neonatal survival rate is 80 % [13]. The loss rate from the procedure is approximately 1–3 % per procedure [14, 15].

The packed cells may be given intraperitoneally or by the intravascular route in the umbilical vein either in the cord or intrahepatically. In hydropic cases, the intravascular route is preferred.

The use of intraperitoneal route is on the decline after direct access to the fetal circulation was possible. IPT is effective in non-hydropic cases and is resorted only if vascular access is not available due to fetal position or there is a need to perform a transfusion prior to 20 weeks. The approximate volume of transfusion is calculated by the formula – (gestational age in weeks – 20 × 10).

Vascular access to the fetus can be achieved through the umbilical vein near the insertion into the placenta, in the free loop of the cord, or through the intrahepatic portal vein. The intrahepatic route is what we prefer and use for almost all our transfusions.

Parvovirus B19 is a small non-enveloped DNA virus that frequently infects humans, with antibodies to B19 found in 30–60% of adults. The incidence of B19 infection during pregnancy is 3.3–3.8% [20, 21, 25, 26].

Most intrauterine parvovirus infections do not have an adverse outcome. Rarely, it can lead to fetal loss and hydrops fetalis.

Pregnant women who are suspected to have parvovirus infection should have serologic testing for IgG and IgM antibodies. A positive parvovirus IgM is consistent with acute infection. If both IgG and IgM are negative, PCR testing of maternal plasma for parvovirus B19 DNA may be more sensitive and should be performed [28].

Circulating IgM antibodies can be detected approximately 10 days after exposure and just prior to the onset of symptoms. They may persist for 3 months or longer [38].

Women diagnosed with acute infection should be monitored for serial ultrasounds to evaluate for fetal hydrops. Fetal anemia is diagnosed noninvasively by measuring the peak systolic velocity (PSV) of the middle cerebral artery (MCA) with Doppler ultrasound. A MCA-PSV value ≥1.5 multiples of the median (MoM) correlates strongly with severe fetal anemia.

When severe anemia is suspected on ultrasound findings, the fetus requires close monitoring, and intrauterine transfusion of RBCs is indicated to prevent fetal death from severe anemia.

Polymerase chain reaction (PCR) testing on amniotic fluid is the method of choice to make the fetal diagnosis.

Intrauterine transfusion of RBCs is indicated to prevent fetal death from severe anemia. Fetal transfusion for hydrops improved the survival rate (82 % vs. 55 % without transfusion) [24, 29, 30].