This is the second in a series of linked posts that serve as signposts to resources for those who wish to look at questions relating to anti-D. Following on from the first post in this series, which offered a few resources for gaining a basic understanding of the issues, this post links to and considers the Cochrane reviews of this area.
There are currently five Cochrane reviews that look at elements of the administration of anti-D to women in the childbearing period.
Firstly, Anti-D administration after childbirth for preventing Rhesus alloimmunisation considers the basic intervention of offering anti-D to rhesus negative women who have given birth to a rhesus positive baby. It concludes that, ‘Anti-D, given within 72 hours after childbirth, reduces the risk of RhD alloimmunisation in Rhesus negative women who have given birth to a Rhesus positive infant. However the evidence on the optimal dose is limited’ (Crowther et al 1997). As the reference shows, this review was first published in 1997 and, at the time of posting, the Cochrane collaboration cited the most recent search for studies as being in 2009, but the conclusions were unchanged. In my humble opinion, there is very unlikely to be a significant change to this review in the forseeable future because, although some of the trial methods carry a high chance of bias, the intervention is widely considered to be effective. In addition, it has been many years since the last RCT on this topic and this has now become such a commonplace intervention that it would be considered unethical to ask women to take a chance of being randomised into a group that did not receive anti-D. The results of this review are relatively uncontentious, although we do need to bear in mind the risk of bias and I can also frequently be heard pointing out that, just because something is effective, this doesn’t mean it is necessary for everyone…
Next, we have Anti-D administration in pregnancy for preventing Rhesus alloimmunisation, which considers the administration of antenatal anti-D. This was most recently updated in 2013, with no change to the onclusions, and includes only two trials which were not, in the opinion of the reviewers, of particularly high quality. Analysis of the two included trials showed that there were no significant differences in the rate of immunisation between women who received anti-D at 28 and 34 weeks’ gestation and women who did not. Women who received anti-D were, however, significantly less likely to have a positive Kleihauer test, which indicates the presence of fetal cells in maternal blood. I could write quite a bit about how I struggle to understand how the authors were able to leap from this to the conclusion (supported by some studies of lower quality) that antenatal anti-D is beneficial, but instead, I will simply point out that this is a brilliant illustration – and I do have huge respect for the Cochrane process and its contributors despite having somewhat differing views in some areas – of how there is no such thing as ‘unbiased’, even in relation to respected insitutions such as the Cochrane Collaboration. It is very important for us to remember that two teams of reviewers might easily look at the same studies and/or metaanalysis and come up with quite different interpretations of what this means and what we should take from it. (For a further example of this, in a different topic area, see the current and previous versions of the review of active versus expectant management for women in the third stage of labour.)
Closely linked to this is another recent addition, Intramuscular versus intravenous anti-D for preventing Rhesus alloimmunization during pregnancy. The authors included two studies involving a total of 447 rhesus negative women (with 14 in one study and and 432 in the other). The women had a dose greater than that used in many areas, but this barely matters, because no women in either study became isoimmunised and the authors concluded that ‘the sample size was insufficient for meaningful comparison of this uncommon outcome’ (Okwundu and Afolabi 2013). They concluded with the statement that, ‘it appears that IM and IV administration of anti-D are equally effective’, while also noting in the same paragraph that their review ‘found insufficient information upon which to guide practice due to the limited number of included studies, small sample sizes and methodological limitations’ (Okwundu and Afolabi 2013).
From here on in, the problem of getting enough – and good enough – data to include becomes even greater. Another recently added review is Anti-D administration after spontaneous miscarriage for preventing Rhesus alloimmunisation, published in March 2013. This review included one study involving 48 women and of fairly poor methodological quality. The reviewers concluded that, ‘There are insufficient data available to evaluate the practice of anti-D administration in an unsensitised Rh-negative mother after spontaneous miscarriage. Thus, until high-quality evidence becomes available, the practice of anti-D Immunoglobulin prophylaxis after spontaneous miscarriage for preventing Rh alloimmunisation cannot be generalised and should be based on the standard practice guidelines of each country’ (Karanth et al 2013).
Finally, a review of Antenatal immunoglobulin for fetal red blood cell alloimmunization does exist, but it doesn’t contain any studies! In this, Wong et al (2013) set out to ‘assess the efficacy and safety of the use of intravenous immunoglobulin antenatally to women with severe fetal red blood cell alloimmunization’. This was because intravenous immunoglobulin has been suggested to be a viable and less invasive alternative to intrauterine transfusion. However, although there exist case series ‘suggesting a possible role in delaying the onset of fetal anaemia requiring invasive intrauterine transfusion’, there are no randomised trials that compare intravenous immunoglobulin given antenatally to women with severe fetal red blood cell alloimmunization with other treatments. This reviewers thus found no studies that met their inclusion criteria.
Click here to read part 3 of this series: the other side of the picture.
Read more in my book: Anti-D in Midwifery: panacea or paradox?
Crowther CA, Middleton P. Anti-D administration after childbirth for preventing Rhesus alloimmunisation. Cochrane Database of Systematic Reviews 1997, Issue 2. Art. No.: CD000021. DOI: 10.1002/14651858.CD000021.
Crowther CA, Middleton P, McBain RD. Anti-D administration in pregnancy for preventing Rhesus alloimmunisation. Cochrane Database of Systematic Reviews 2013, Issue 2. Art. No.: CD000020. DOI: 10.1002/14651858.CD000020.pub2.
Karanth L, Jaafar SH, Kanagasabai S, Nair NS, Barua A. Anti-D administration after spontaneous miscarriage for preventing Rhesus alloimmunisation. Cochrane Database of Systematic Reviews 2013, Issue 3. Art. No.: CD009617. DOI: 10.1002/14651858.CD009617.pub2.
Okwundu CI, Afolabi BB. Intramuscular versus intravenous anti-D for preventing Rhesus alloimmunization during pregnancy. Cochrane Database of Systematic Reviews 2013, Issue 1. Art. No.: CD007885. DOI: 10.1002/14651858.CD007885.pub2.
Wong KS, Connan K, Rowlands S, Kornman LH, Savoia HF. Antenatal immunoglobulin for fetal red blood cell alloimmunization. Cochrane Database of Systematic Reviews 2013, Issue 5. Art. No.: CD008267. DOI: 10.1002/14651858.CD008267.pub2.