What are the implications of Rh (Rhesus) negativity in pregnant women, including the risk of sensitization during early spontaneous abortion (miscarriage) and its potential as a cause of early miscarriage?

From the Guidelines

Rh negativity in pregnant women can lead to complications when the baby is Rh positive, and sensitization can occur during early miscarriage, but it's not typically a cause of early miscarriage itself, as evidenced by studies such as 1 and 1. To prevent sensitization, Rh negative women who have experienced a miscarriage should receive RhoGAM (Rh immunoglobulin) within 72 hours, with a recommended dose of 50 mg for early miscarriages before 12 weeks, as stated in 1. Some key points to consider:

• Sensitization happens when an Rh negative woman's immune system is exposed to Rh positive blood cells, typically during delivery, miscarriage, or invasive procedures, causing antibody production, as discussed in 1.
• These antibodies can cross the placenta in future pregnancies and attack an Rh positive baby's red blood cells, leading to hemolytic disease of the newborn, highlighting the importance of prevention, as noted in 1.
• While Rh incompatibility rarely causes first miscarriages, untreated sensitization can affect subsequent pregnancies, emphasizing the need for timely administration of RhoGAM, as recommended in 1 and 1.
• All Rh negative women should receive RhoGAM at 28 weeks of pregnancy and within 72 hours after delivery, miscarriage, or procedures like amniocentesis to prevent these complications, as suggested by 1 and 1. It is essential to prioritize the administration of RhoGAM in Rh negative women, especially in cases where the supply is limited, to minimize the risk of sensitization and its potential consequences on future pregnancies, as highlighted in 1.

From the FDA Drug Label

HyperRHO S/D Full Dose should be administered within 72 hours to all nonimmunized Rho(D) negative women who have undergone spontaneous or induced abortion, following ruptured tubal pregnancy, amniocentesis or abdominal trauma unless the blood group of the fetus or the father is known to be Rho(D) negative. If the fetal blood group cannot be determined, one must assume that it is Rho(D) positive,(2) and HyperRHO S/D Full Dose should be administered to the mother.

A woman can become sensitized to the Rh factor during an early miscarriage.

• Sensitization can occur when an Rh-negative woman is exposed to Rh-positive blood, which can happen during pregnancy, childbirth, or miscarriage.
• The drug label recommends administering Rh immune globulin to nonimmunized Rh-negative women after a spontaneous or induced abortion to prevent isoimmunization. However, the label does not explicitly state that Rh negativity is a cause of early miscarriage 2.

From the Research

Rh Negativity in Pregnant Women

• Rh negativity is a condition where an individual's red blood cells lack the Rh antigen, and it can be a concern during pregnancy if the fetus has the Rh antigen.
• If a Rh-negative woman is pregnant with a Rh-positive fetus, there is a risk of sensitization, which can lead to the production of antibodies against the Rh antigen 3.
• Sensitization can occur during pregnancy, childbirth, or abortion, and it can increase the risk of complications in future pregnancies 4, 5, 6.

Risk of Sensitization during Early Miscarriage

• There is a risk of fetomaternal hemorrhage (FMH) during early miscarriage, which can lead to sensitization in Rh-negative women 3, 5.
• However, the evidence suggests that the risk of sensitization during early miscarriage is low, and the use of Rh immune globulin in this setting is not evidence-based 5.
• One study found that there is minimal evidence to support the use of Rh immune globulin for first trimester spontaneous abortions to prevent maternal sensitization or development of hemolytic disease of the newborn 5.

Causes of Early Miscarriage

• Early miscarriage can be caused by various factors, including chromosomal abnormalities, hormonal imbalances, and uterine abnormalities.
• However, there is no evidence to suggest that Rh negativity is a direct cause of early miscarriage 4, 5, 6.
• Rh immune globulin is administered to Rh-negative women after pregnancy loss or abortion to prevent sensitization, but its use in this setting is based on expert opinion and extrapolation from experience with fetomaternal hemorrhage in late pregnancy 6.

Administration of Rh Immune Globulin

• Rh immune globulin is administered to Rh-negative women after pregnancy loss or abortion to prevent sensitization 3, 4, 6.
• The dosage and timing of Rh immune globulin administration vary depending on the gestational age and the presence of fetomaternal hemorrhage 3.
• The American College of Obstetricians and Gynecologists recommends that Rh immune globulin be administered to Rh-negative women after spontaneous abortion, ectopic pregnancy, or molar pregnancy 3.