Intramuscular versus intravenous anti-D for preventing Rhesus alloimmunization during pregnancy

Antibodies to the red cell Rhesus D (RhD) antigen may be produced by a RhD-negative mother if she is carrying a RhD-positive baby. Antibodies form with the entry of fetal blood into the maternal circulation (feto-maternal haemorrhage) at birth or following a procedure (such as amniocentesis). Spontaneous sensitisation occurs antenatally at about 28 to 30 weeks gestation. The maternal condition that results from this is known as RhD alloimmunization or sensitization. The antibodies can cause haemolytic disease in the baby resulting in anaemia, oedema and possible death. While the first baby is usually not harmed, the antibodies (directed against antigens inherited from the father) may cause haemolytic disease in subsequent RhD-positive babies.

Anti-D (anti-D immunoglobulin G) is obtained from human plasma and contains high levels of antibody to the fetal RhD antigens. Following administration to the mother, a positive antibody screen is found as the anti-D crosses the placenta and binds to the fetal red blood cells. Since andi-D is derived from pooled donor plasma, there is a risk of transmission of blood-borne diseases.

Anti-D immunoprophylaxis is recommended for RhD-negative mothers at 28 or 30 weeks of pregnancy and within 72 hours of potential maternal exposure to fetal red cells to prevent the mother developing antibodies during the pregnancy. RhD negative mothers also receive postpartum anti-D after a RhD-positive baby to reduce the risk of sensitization during the next pregnancy. Present routes of administration for this product include intramuscular of intravenous routes. This review aimed to compare the efficacy and effectiveness of intramuscular versus intravenous anti-D in preventing rhesus alloimmunization in RhD-negative pregnant women.

We identified two completed randomized controlled studies, involving 447 RhD-negative women. The findings suggest that intramuscular and intravenous anti-D in the 28th week of pregnancy are equally effective in preventing RhD antibody formation (alloimmunization) during the pregnancy. None of the women developed antibodies against the RhD antigen. The small number of studies, low number of participants and methodological limitations mean that we do not have sufficient information to guide practice. The choice of intramuscular or intravenous route of administration will depend on available preparations, the dose to be administered and the woman's preference.

Authors' conclusions: 

It appears that IM and IV administration of anti-D are equally effective. The number of included studies and the number of participants are not enough to assess whether there are any differences. Anti-D can be administered by IM or IV injection. The choice of IM or IV route of administration will depend on the available preparations, the dose to be administered and also on the patients' preferences. This review found insufficient information upon which to guide practice due to the limited number of included studies, small sample sizes and methodological limitations.

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Background: 

Antibodies to the red cell Rhesus D (RhD) antigen can be produced during pregnancy in a RhD-negative mother carrying a RhD-positive fetus, in particular following feto-maternal haemorrhage at birth or following any procedure that may cause feto-maternal haemorrhage. While the first baby is usually not harmed, these antibodies may cause haemolytic disease of the fetus/newborn (HDFN) in subsequent RhD-positive babies. RhD incompatibility is a major cause of HDFN.

To reduce the risk of HDFN, anti-D is given to RhD-negative mothers at 28 or 30 weeks of pregnancy and within 72 hours of potential maternal exposure to fetal red cells. Anit-D is currently available in both intramuscular (IM) and intravenous (IV) preparations.

Objectives: 

To compare the efficacy and effectiveness of IM versus IV anti-D IgG in preventing RhD alloimmunization in RhD-negative pregnant women.

Search strategy: 

We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 September 2012).

Selection criteria: 

Randomized controlled trials, quasi-randomized trials and cluster-randomized trials comparing IM and IV anti-D for preventing RhD alloimmunization in RhD-negative pregnant women.

Data collection and analysis: 

Two review authors independently assessed trials for inclusion and assessed trial quality. Two review authors extracted data. Data were checked for consistency by both authors.

Main results: 

Two studies involving 447 (with sample sizes 14 and 432) RhD negative women were included. The studies compared IM and IV administration of anti-D prophylaxis. In both studies the women received a 1500 IU (300 microgram) dose of Rhophylac during week 28 of gestation. There was no incidence of RhD alloimmunization in either of the studies, as the sample size was insufficient for meaningful comparison of this uncommon outcome. One of the studies found that the mean anti-D IgG concentrations after IV and IM administration differed up to seven days (36.1 (2.6) ng/mL IV; 19.8 (8.7) ng/mL IM on day seven). However, from two to three weeks post-administration, the concentrations were similar for both routes of administration. None of the women involved in the studies developed antibodies against the RhD antigen.

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