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Efficacy Endpoints: Rhesus Rh D alloimmunization at six months in a future pregnancy
Harm Endpoints: Maternal anemia requiring transfusion, renal failure, DIC, death
Narrative: • Alloimmunization, in which a Rh negative mother develops anti-Rh antibodies after being exposed to Rh positive blood during pregnancy or in the immediate intra-partum period, can lead to severe complications in future pregnancies. Rh antibodies are capable of crossing the placenta, entering the fetal circulation, and attacking fetal (Rh-positive) red blood cells. This can lead to massive hemolysis, profound anemia, and high output fetal cardiac failure (hydrops fetalis). Post-partum administration of Rh immunoglobulin prophylaxis has made these immune-mediated complications incredibly rare.
This review included six, randomized-controlled trials involving over 10,000 Rh-negative women without detectable anti-D antibodies who gave birth to Rh positive infants. The studies examined the efficacy of post-partum administration of IgG anti-D antibodies in preventing alloimmunization at six months, and in subsequent pregnancies.
Infusion of anti-D in at risk post-partum women significantly reduced detectable alloimmunization at six months and in future pregnancies. Adverse effects of Rh immunoglobulin, including clinically-significant anemia, renal failure, pulmonary edema, DIC, and death, appear to be exceedingly rare.
Caveats: Decreased rates of detectable anti-Rh antibodies do not directly prove that administration of anti-D immunoglobulin reduces actual neonatal mortality and morbidity. The reduction in alloimmunization, has, however, been widely accepted as a surrogate marker for potential fetal morbidity and mortality. This is supported by population-based studies showing a marked decrease in rhesus disease since the administration of post-partum anti-D immunoglobulin has become common practice. We therefore feel that this surrogate marker has been validated, and that it is a reasonable outcome measure for the efficacy of anti-D immunoglobulin in regions with resources and access to the drug.
As with any review, inference for clinical practice is limited by the quality of the included studies. Here, there was moderate variation in the quality of the included studies in terms of randomization, blinding, placebo control, and documented follow up. One trial, for instance, accounted for 47% of the total weight in the overall meta-analysis, and the combination of these studies found significant heterogeneity in the degree of benefit.
Adverse events from anti-D appear to be rare, and nearly all relevant case reports occur in the treatment of idiopathic thrombocytopenic purpura (ITP), during which doses are typically much higher than those used for postpartum women and many regimens require multiple doses.
Author: Gary Green, MD and Dan Runde, MD
Published/Updated: January 8, 2013
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