RH(D) INCOMPATIBILITY
Evidence Statement
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Updated 10/27/11
Evidence StatementClinical Preventive Service RecommendationsU.S. Preventive Services Task Force RecommendationThe U.S. Preventive Services Task Force (USPSTF) strongly recommends Rh (D) blood typing and antibody testing for all pregnant women during their first visit for pregnancy-related care.1The USPSTF also recommends repeated Rh (D) antibody testing for all unsensitized Rh (D)-negative women between 24 and 28 weeks' gestation, unless the biological father is known to be Rh (D)-negative.1 Evidence Rating: A (Strongly Recommend/Good Evidence) The USPSTF found good evidence that Rh (D) blood typing, anti-Rh (D) antibody testing, and intervention with Rh (D) immunoglobulin, as appropriate, prevents maternal sensitization and improves outcomes for newborns. The benefits substantially outweigh any potential harms.1 B (Recommend/At Least Fair Evidence) The USPSTF found fair evidence that repeated antibody testing for unsensitized Rh (D)-negative women (unless the father is also known to be Rh [D]-negative) and intervention with Rh (D) immunoglobulin, as appropriate, provides additional benefit over a single test at the first prenatal visit in preventing maternal sensitization and improving outcomes for newborns. The benefits of repeated testing substantially outweigh any potential harms.1 The American Academy of Family Physicians (AAFP) concurs with the USPSTF. The Value of PreventionEconomic Burden of Condition/DiseaseNo data exist that estimate the total direct or indirect costs of Rh (D) incompatibility in the United States.The value of life years lost due to fetal loss, stillbirth, neonatal and post-neonatal deaths, and productivity loss associated with disability constitute the major components of the economic burden of Rh (D) incompatibility. Costs would be even higher if the additional medical care costs and productivity losses of working pregnant women are considered. Workplace Burden of Condition/DiseaseIn addition to the incremental medical care utilization costs due to complications from Rh (D) incompatibility, there can be significant productivity losses at the workplace when working parents need to take time off from work to care for short- or long-term health problems of their children.Economic Benefit of Preventive InterventionEarly identification of Rh (D) incompatibility allows clinicians to begin treatment before damage is done to the fetus. This prevents otherwise expensive medical treatment, lifelong disability, and even death.Estimated Cost of Preventive InterventionIn 2004, the private-sector cost of screening for Rh (D) incompatibility averaged $15 per screen; approximately 95% of all paid claims fell within the range of $0 to $38. The cost of immune globulin averaged $111 and approximately 95% of all paid claims fell within the range of $0 to $178.5Estimated Cost of TreatmentNot ProvidedCost-Effectiveness and/or Cost-Benefit Analysis of Preventive InterventionA review undertaken on behalf of the National Institute of Clinical Excellence in the United Kingdom, the governmental unit responsible for producing evidence-based recommendations for the UK, found that routine antenatal anti-D preventive medication (immunoglobulin) provides a cost-effective intervention for preventing the incidence of hemolytic disease of the newborn in pregnancies of Rh (D)-negative women.6Condition / Disease Specific InformationEpidemiology of Condition/DiseaseRh (D) incompatibility refers to a condition that develops when a pregnant women with Rh-negative blood type carries a fetus with an Rh-positive blood type. In reaction to what is perceived to be a foreign substance, the woman's body makes antibodies that attack fetal red blood cells (isoimmunization). Since it takes time to build up antibodies, first pregnancies are typically not affected by Rh incompatibility. However, in subsequent pregnancies, Rh incompatibility may cause destruction of fetal red blood cells (hemolysis), which leads to anemia and an accumulation of bilirubin in the fetus's bloodstream (hyperbilirubinemia) that produces jaundice. Extreme jaundice leads to kernicterus, a form of brain damage associated with cerebral palsy and mental retardation. The hemolytic destruction of red blood cells can also lead to hydrops fetalis, a severe anemia resulting in fetal heart failure, total body swelling, respiratory distress or total circulatory collapse, and often death.3Rh incompatibility occurs in approximately 10% of all pregnancies, depending on the race of the pregnant woman and her fetus. Without treatment, 25% to 30% of these fetuses will show various degrees of hemolytic anemia and hyperbilirubinemia. An additional 20% to 25% will be hydropic and will either die in utero (resulting in a stillbirth) or shortly after birth. Hemolytic disease of the fetus accounts for 4 to 5 deaths per 100,000 births in the United States.3 Condition/Disease Risk FactorsOnly Rh-negative women are at risk of having a baby with Rh disease. If an Rh-negative woman and Rh-positive man conceive an Rh-positive fetus, there is a chance that some of the fetus's Rh-positive red blood cells may enter the woman's blood stream, which stimulates the woman's immune system to produce antibodies against the fetus's Rh-positive cells. The risk of Rh disease becomes greater with each subsequent pregnancy.4Preventive Intervention InformationPreventive Intervention: Purpose of Screening and Preventive MedicationEarly identification of Rh (D) incompatibility allows clinicians to begin treatment before damage is done to the fetus. This prevents otherwise expensive medical treatment, lifelong disability, and even death.Benefits and Risks of InterventionEarly detection of Rh (D)-negative blood type in a pregnant woman is of substantial benefit (when the woman is not yet isoimmunized and the father of the fetus is not known to be Rh (D)-negative) because it makes prevention of isoimmunization possible. Clinicians can administer anti-D immune globulin to Rh (D)-negative pregnant women, thereby preventing the maternal isoimmunization that would adversely affect subsequent pregnancies. This course of treatment prevents isoimmunization in 96% of women at risk.4 Screening and treatment with immunoglobulins have few adverse affects.4Initiation, Cessation, and IntervalThe USPSTF strongly recommends that all pregnant women undergo Rh (D) blood typing and antibody testing at their first prenatal visit. Furthermore, the USPSTF recommends that women known to be Rh (D)-negative and unsensitized undergo a repeat Rh (D) antibody test between 24 and 28 weeks' gestation to determine their degree of sensitivity. This second step is unnecessary if the fetus's father is known to be Rh (D)-negative.A full dose (300mg) of immunoglobulin should be administered to1-2:
Intervention ProcessRh (D) blood typing and antibody testing is conducted via an analysis of the blood. Immunoglobulin is administered to those at risk of Rh disease through an injection.Treatment InformationHealth benefit coverage should include provisions for follow-up and treatment services.Strength of EvidenceThe level of evidence supporting the recommendations contained in this section is described below.Evidence-Based Research: Summary Plan DescriptionCovered Preventive MedicationsImmune globulinInitiation, Cessation, and IntervalImmune globulin is covered as a preventive medication for the following populations (as medically indicated):
CPT Codes
Other Information and ResourcesBusiness Group Resource(s)U.S. National Library of MedicineAuthor(s)Campbell KP, Chattopadhyay S. Rh (D) incompatibility evidence-statement: screening and preventive medication. In: Campbell KP, Lanza A, Dixon R, Chattopadhyay S, Molinari N, Finch RA, editors. A Purchaser's Guide to Clinical Preventive Services: Moving Science into Coverage. Washington, DC: National Business Group on Health; 2006. Updated 2011.References
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