Please note: In 2003, the CTF updated its Grades of Recommendations to include an "I Recommendation" for situations where insufficient evidence exists to allow a recommendation to be made. (Formerly, these situations were captured under a "C Recommendation".) This change is not retroactive, and all "C Recommendations" made prior to 2003 have not been reevaluated in light of the new "I" recommendation grade. For a discussion of these recommendation grades, please link to the 2003 article in the Canadian Medical Association Journal here.
Objective
To make recommendations for screening pregnant women in Canada for
D (Rh) sensitization. This guideline is an update of the 1979 Canadian
Task Force recommendations on blood group incompatibility in pregnancy.
Burden of Suffering
Some degree of fetal-maternal transplacental hemmorhage occurs in 75%
of all pregnancies. This phenomenon is not dangerous to the fetus
unless there is an incompatibility between the mother and her fetus with
respect to the D antigen of the red blood cells. D incompatibility
exists when a D negative woman is pregnant with a d positive fetus, which
occurs in up to 9-10% of pregnancies, depending on race. If no preventive
measures are taken, 0.7-1.8% of women will become isoimmunized antenatally,
developing D antibody through exposure to fetal blood; 8-17% will become
isoimmunized at delivery, 3-6% after spontaneous or therapeutic abortion,
and 2-5% after amniocentesis. Once isoimmunization has occurred,
the severity of fetal hemolysis varies. In 50% of the cases the fetus
is very mildly affected and does not require postpartum treatment.
However, without treatment, 25-30% of these offspring will have some degree
of hemolytic anemia and hyperbilirubinemia, another 20-25% will be hydropic
and many will die either in utero of during the neonatal period.
Options
Screening for D blood type is done using hemagglutination. Detection
of anti-D antibodies in women who have been sensitized to D-positive blood
is by the indirect antiglobulin (Coomb's) test (IGAT).
Prevention includes identification of actual or potential maternal and fetal blood incompatibilities before isoimmunization can occur and treatment with intravenous D immunoglobulin (D Ig) or plasma exchange, when necessary. Treatment can occur during pregnancy or immediately after a pregnancy related event (e.g., delivery, abortion, genetic testing).
Outcomes
Prevention of isoimmunization during pregnancy and delivery; detection
if it has occurred because of transplacental hemorrhage; and fetal anemia,
morbidity, and mortality in utero or during the neonatal period
(hemolytic disease).
Evidence
These recommendations were adapted for the Canadian context from a
report/materials prepared for the 1989 U.S. Preventive Services Task Force.
MEDLINE was searched for 1989 - 1993 using the keywords RH-HR blood group
system, RH Isoimmunization, immunoglobulins, amniocentesis, ultrasound,
blood transfusion intrauterine, erythroblastosis fetalis.
Values
The 13-member Task Force of experts in family medicine, geriatric medicine,
pediatrics, psychiatry and epidemiology used an evidence-based method for
evaluating the effectiveness of preventive health care interventions. Recommendations
were not based on cost-effectiveness of options. Patient preferences were
not discussed.
Background papers providing critical appraisal of the evidence and tentative recommendations prepared by the chapter author were pre-circulated to the members. Evidence for this topic was presented and deliberated upon in 1- to 2-day meetings, 2 to 3 times per year from January 1993 to June 1993. Consensus was reached on final recommendations.
Benefits, Harms, and Costs
Clinical trials done in the 1960s showed that women who received a
full dose of D Ig prophylaxis after delivery did not develop isoimmunization.
Antenatal isoimmunization has been shown to be prevented by D Ig at 28
weeks' gestation in non-randomized controlled trials; this reduces the
incidence of isoimmunization to 0.2% of women at risk. Case series and
non-randomized trials showed that D Ig reduced isoimmunization after amniocentesis
(from 5.2% to 0%) and after termination of pregnancy (from 2.6% to 0.4%).
Postpartum doses of D Ig can be based on the amount of fetal blood estimated to have been transferred during delivery: 300 micrograms of D Ig will prevent sensitization to 30 mL of fetal blood. Combined antenatal and postnatal prophylazis will prevent isoimmunization in 96% of women at risk.
D Ig has few side effects although some fetuses develop weak direct-antiglobulin-positivity after antenatal administration, but resulting anemia and hyperbilirubinemia in the newborn infant are rare.
Ultrasound-guided cordiocentesis can detect fetal hemoglobin and D blood type but complications can occur (2% to 7%) including fetal mortality (0.5% to 1.0%).
Severe fetal anemia can be treated with ultrasound-guided intravascular transfusion at experienced centres with success rates of 62% to 86% for hydropic infants and > 90% success for those without hydrops. After pulmonary maturity has been established, early delivery and exchange transfusion can occur with only 1% mortality risk.
Recommendations
Recommendation grade [A, B, C, D, E] and level of evidence
[I, II-1, II-2, II-3, III] are indicated after each recommendation. Citations
in support of individual recommendations are identified in the guideline
text.
Sponsors
The Canadian Task Force on Preventive Health
Care developed this guideline with funding from Health Canada.
Source Document
Beaulieu M.D. Screening for D (Rh) sensitization in pregnancy. In:
Canadian Task Force on the Periodic Health Examination. Canadian
Guide to Clinical Preventive Health Care. Ottawa: Health Canada,
1994; 116-24.