The process by which fetal Rh+ erythrocytes enter the circulation of an Rh- mother during delivery, causing her to produce IMMUNOGLOBULIN G antibodies, which can cross the placenta and destroy the erythrocytes of Rh- fetuses in subsequent pregnancies
Predisposing factors to FMH
–SAB, TAB, Amniocentesis, abdominal trauma, placenta previa, abruptio placenta, IUFD, multiple pregnancy, manual removal of placenta, cesarean section
Timeline of Rh Isoimmunization/sensitization
Management in Pregnancy
•Initial OB visit - identify Rh negative woman and determine baseline antibody screen
•Postpartum - repeat antibody screen and check newborn blood type
–if baby Rh+, administer full dose RhoGam within 72 hours
–if mother’s antibody screen + and titer >1:4 treat as sensitized
Indications for Additional RhoGam
•Tests for determination of FMH - if suspect it may be greater than the full dose RhoGam will cover, do Kleihauer-Betke test to determine the extent of bleed.
Frequent Signs and Symptoms
Signs during pregnancy:
Signs in a newborn:
The fetus of an Rh-negative (blood type) mother and an Rh-positive father may be Rh-positive. If the father is known to be Rh negative, there is no concern. During delivery, a small amount of the infant's blood is absorbed by the mother through the placenta, stimulating her body to produce antibodies against Rh-positive blood. The antibodies are produced after delivery, so the first infant is not affected. With succeeding pregnancies, the antibodies in the mother's blood can potentially destroy fetal blood cells. With subsequent pregnancy, anti-Ah antibodies cross the placenta and may destroy fetal blood cells. The resulting anemia can be severe enough to cause fetal death. If the fetus survives, antibodies can cross to the baby during birth, causing jaundice and other symptoms shortly after birth.
Risk Increases With
With prompt recognition of the disorder, damage to the infant can be prevented with exchange transfusions. These transfusions are administered directly into fetal circulation by PUBS.
If you are pregnant and have Rh-negative blood type, you will be prescribed an anti-Ah gamma globulin injection (RhoGAM) at 28 weeks and again within 72 hours after delivery or termination of a pregnancy for any reason. You may also have antibody titer drawn during pregnancy to see if you are producing anti-Ah antibodies. You do not need RhoGAM if your fetus is Rh negative.
No restrictions after treatment.
The infant may be breast-fed or bottle-fed normally.
Blood production in the fetus begins at about 3 weeks' and Rh antigen has been identifed in the red cell membrane bas early as 38 days after conception. 
Rh-D Negative Unsensitized Patients
Antibody Sensitized Patient
· However, the management of the Kell-sensitized pregnancy may require more intensive surveillance, since maternal titers and amniotic fluid bilirubin levels do not necessarily correlate with disease severity. May involve marrow suppression.
First Sensitized Pregnancy (no prior severely affected pregnancy).
· If the father is Rh negative (or negative for the atypical antigen) then no further testing is necessary.
· IAT titers of < 1:32 or less are managed noninvasively with repeat antibody titers every 2-4 weeks.
· IAT > 64 amniocentesis q 2 to 3 weeks.
· IAT titers of > 1:32 with pregnancies at greater than 27 week are usually monitored with serial amniocentesis
· If the father is heterozygous (Dd) or his blood is unavailable then PUBS or amniocentesis may be used to determine the fetal Rh (or atypical antigen) status if the IAT titer is > 1:32 or albumin titer > 1:16.
· Fetal DNA testing is available for:
RhD, RhE, Rhc, RhC, and Kell.
· For RhE, Rhe, RhC, Rhc, Kell ,and Cellano (k) the parents' DNA should be tested concurrently (Send 5.0 ml of blood in a lavender-topped tube on each parent. DO NOT FREEZE)
· If the fetus is antigen negative then no further testing is necessary.
· If the fetus is antigen positive then the pregnancy is followed with serial titers and ultrasound as long as titers remain below the "critical" value.
Previously Affected Pregnancy
The risk of RhD alloimmunisation during or immediately after a first pregnancy is about 1.5%. Administration of 100ug (500IU) anti-D at 28 weeks and 34 weeks gestation to women in their first pregnancy can reduce this risk to about 0.2% without, to date, any adverse effects. Although such a policy is unlikely to confer benefit or improve outcome in the present pregnancy, fewer women will have Rhesus D antibodies in their next pregnancy.Adoption of such a policy will need to consider the costs of prophylaxis against the costs of care for women who become sensitised and their affected infants, and local adequacy of supply of anti-D gammaglobulin.
Citation: Crowther CA. Anti-D administration in pregnancy for preventing Rhesus alloimmunisation (Cochrane Review). In: The Cochrane Library, Issue 2, 2004. Chichester, UK: John Wiley & Sons, Ltd.
affected by hemolytic disease secrete abnormally high levels of bilirubin into the
amniotic fluid. The amount of bilirubin can be quantitated by
spectrophotometrically measuring absorbance at the 450-nm wavelength in a
specimen of amniotic fluid that has been shielded from light. Alternatively,
percutaneous umbilical blood sampling (PUBS) may be used to determine all
blood parameters directly.
The Liley Curve [see also below]
· A result in Zone I indicates mild or no disease. Fetuses in zone I are usually followed with amniocentesis every 3 weeks.
· A result in zone II indicates intermediate disease. Fetuses in low Zone II are usually followed by amniocentesis every 1-2 weeks.
· A result above the middle of Zone II may require transfusion or delivery. 
Patients with results in zone I or low zone II can be allowed to proceed to term, at which point labor should be induced. In most cases, patients in the middle of zone II can progress to 36-38 weeks of gestation. Depending on gestational age, patients in zone III should either be delivered or should receive intrauterine fetal transfusion.
Although serial determinations of Delta optical density at 450 nm and PUBs are the most common methods for the evaluation of fetal status, Doppler ultrasonography of the middle cerebral artery has also been used to identify fetuses at risk for moderate to severe hemolytic disease.
Today, the Rh-immunized pregnancy can be evaluated with six complementary modalities:
1. Serial maternal serum antibody titers
2. Middle cerebral artery (MCA) peak systolic velocity
3. AF DNA Rh typing
4. AF OD450 nm
5. Sonographic evaluation
6. Cordocentesis or fetal blood sampling (FBS)
In situations where the maternal antibody titer is very low (such as 1:4), fetal disease is usually mild and the outcome is favorable. In such cases, following maternal antibody titers is all that is necessary to evaluate the pregnancy. If the titer is higher, the outcome is not predictable and MCA peak systolic velocity and amniocentesis with AF OD450 and AF DNA Rh typing may be employed.
When severe EBF is suspected, FBS is necessary to determine the fetal hematocrit and perform a fetal transfusion, if indicated.
The MCA peak systolic velocity provides a non-invasive modality for determining moderate to severe fetal anemia.4 This technique does not differentiate between mild fetal anemia and no anemia. The sensitivity of an increased peak systolic velocity in the MCA for prediction of moderate to severe fetal anemia is 100 percent either in the presence or the absence of hydrops fetalis and the false positive is 12 percent.4 The major advantage of MCA Doppler studies is that they are a non-invasive means of detecting fetal anemia and indicate when a transfusion is necessary
Intravascular Fetal Transfusion
Neither MCA peak systolic velocity or AF OD450 can differentiate between mild disease and no disease in the fetus. Therefore, at the initial amniocentesis, 5 mL of uncentrifuged AF should be sent for DNA Rh typing. Fetal DNA is isolated from the AF, and specific portions of the fetal D (Rho), C, and E genes are amplified with polymerase chain reaction.5,6 The error rate is 1%. If the fetus tests Rh-negative, no further testing is necessary and the patient can receive routine obstetric care, avoiding unnecessary Doppler studies and invasive procedures.7-9 If the fetus is Rh-positive, further evaluations are required with MCA peak systolic velocity and AF OD450 studies
The AF OD450 value in the Rh-immunized patient is an almost ideal test of fetal condition. If the clinician fully understands the physiologic properties of AF and the pathophysiology of Rh disease, virtually no serious fetal deterioration should go undetected.
In normal (Rh-negative) pregnancies, the AF OD450 values rise until 24 weeks, then fall until term. In Rh-positive fetuses at risk of dying in utero, the values are higher and the AF OD450 trends rise.
The timing of the initial amniocentesis depends upon the patient's history and antibody titer. If the patient's antibody titer is just at the critical level and the patient has not had a baby with EBF, the initial amniocentesis can be done at 28 to 29 weeks' gestation. If the titer or the history suggests that the EBF may be more severe, then amniocentesis can be performed earlier. In this way, a fetus that needs an intrauterine transfusion can be identified.
Rh-negative (unaffected) zone: If the AF OD450 value falls in the Rh-negative zone, DNA Rh typing should be performed on the initial amniocentesis. If the fetus is Rh-negative, no further testing is necessary and the fetus can be delivered at term. If the fetus is Rh-positive, amniocentesis and AF OD450s should be repeated in 3 to 4 weeks. The maternal Rh antibody titer should be monitored to detect any increase in titers.
Indeterminate zone: If the AF OD450 falls in the indeterminate zone, DNA Rh typing should be performed on the initial amniocentesis. If the fetus is Rh-negative, no further testing is necessary and the fetus can be delivered at term. If the fetus is Rh-positive, the AF OD450 should be repeated every 2 to 4 weeks. Decreasing trends generally indicate that the fetus is Rh-negative or has mild or moderate disease. Horizontal or rising trends of AF OD450 values indicate that the fetus has severe disease.
Rh-positive (affected) zone: If the AF OD450 value falls in the Rh-positive zone, amniocentesis should be repeated in 1 to 2 weeks. FBS is indicated if the values remain elevated or the trend rises.
Intrauterine death risk zone: If the AF OD450 value falls in the intrauterine death risk zone, FBS is indicated for fetal evaluation, including hematocrit and possible transfusion or delivery, if the fetus is mature.
This four-zone management scheme exposes the Rh-negative fetus to a minimum of invasive procedures. Fetuses with AF OD450 levels in the Rh-positive or intrauterine death risk zones may require early FBS.
Schematic representation of the antigen D on the erythrocyte´s surface. The normal RhD protein is shown (left). Every sphere represents an amino acid. Six extracellular loops of amino acids are shown (light yellow and light grey). Transmembranous protein segments are depicted in reddish. The RhD protein differs from the RhCE protein (not shown) be seven extracellular amino acids only (yellow). All other extracellular amino acids (light yellow and light blue) are identical between the RhD- and RhCE-protein. In the DVI-protein (right), two loops carry the RhCE-specific sequence (light blue) rather than the RhD-specific sequence. Thus, the extracellular parts of the DVI-protein differ from the normal RhD-protein by three amino acids only (blue). Other transmembranous and intracellular differences may, however, also effect the protein configuration and are not shown for simplicity.
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