routine antenatal anti-D
- a review of the evidence
sara wickham
A version of this article was originally published in
MIDIRS Midwifery Digest.
While the postnatal administration of anti-D immunoglobulin to
rhesus negative woman who have given birth to a rhesus positive
baby has been considered by many as an acceptable and
beneficial routine intervention for the last thirty years, the
question of whether it is appropriate to offer routine antenatal
administration of this product has been hotly debated for almost
as long. There is little question that women who experience
potentially sensitising events in pregnancy should be given
appropriate information and offered this as an option. Rather,
the debate concerns the issue of so-called 'silent' feto-maternal
transfusion - the existence (or otherwise) of which phenomena
forms part of the basis for arguments in favour of routine
antenatal prophylaxis.
The debate surrounding the routine administration of anti-D
during pregnancy began in 1969, when Zipursky and Israels
suggested that antenatal anti-D administration may prove to
reduce the rate of sensitisation. Bowman and Pollock (1978)
followed this up with the specific recommendation that anti-D
should be administered to all rhesus negative women at 28
weeks to prevent sensitisation in pregnancy. The debate
continued throughout the 1980s and 1990's, with opinions
divided between those who saw antenatal anti-D as a wholly
beneficial intervention, which would save babies, and those
who urged caution for a variety of reasons. Antenatal anti-D
has been offered routinely in some countries, including the USA
and Germany, for a number of years. Yet Britain's first active
discussion of the debate occurred in 1997, when a consensus
conference decided to recommend routine antenatal administration
in the UK; an issue which is currently being debated on practical,
professional and political levels.
Why Offer Antenatal Anti-D?
Proponents of routine antenatal administration base their arguments
around evidence that suggests that current protocols for the
administration of anti-D do not prevent all cases of isoimmunization.
They feel that routine antenatal administration is the best way forward
in moving closer to one hundred per cent protection from
isoimmunization. For example, Hughes et al (1994) carried out research
in Scotland, and concluded that, in 53 of the 80 babies with rhesus
disease, this had been caused by the failure of the current guidelines
to protect against maternal isoimmunization.
The effectiveness of the antenatal anti-D programme in Derbyshire
- where women having their first baby are already offered antenatal
anti-D at 28 and 34 weeks of pregnancy - was evaluated by
Mayne et al (1997), who showed a fall in the mean overall sensitisation
rate from 1.12 per cent in 1988-91 (before the onset of the antenatal
programme) to 0.28 per cent in 1993-95. Another research study by
McSweeney et al (1998) not only provides evidence in support of
antenatal administration, but also highlights part of the argument
against this. While these researchers estimate that over 80 per cent
of women who became isoimmunized might not have experienced this
had they been offered antenatal anti-D, they also found that professionals
failed to offer anti-D in 48 per cent of cases where women experienced
potential sensitising events in the antenatal period. This is one of the
strongest arguments against the administration of routine antenatal anti-D.
The fact that most of the studies of this nature that are cited in support
of routine antenatal anti-D are retrospective proves problematic.
The use of women's case notes in such research is known to cause
difficulties; many aspects of care are not always well documented by
professionals and this can lead to bias in the results of the study.
For instance, if a clinician had not documented the occurrence of a
potentially sensitising event, or perhaps not even asked the woman
about these, then it would look as if the woman had experienced
silent fetomaternal haemorrhage if she then became isoimmunized.
Much of the evidence cited in this area, although interesting and
useful in other ways, does not look at the effectiveness of antenatal
anti-D in the light of prospective, randomised controlled trials.
Only two antenatal anti-D trials of any real size and quality have
been conducted - although it should be noted that neither of these
was single or double blinded. Lee and Rawlinson (1995) gave
women in the treatment group two doses of 50 micrograms
(250 international units) of anti-D at 28 and 34 weeks, and
showed no statistically significant difference between their
outcomes and women in the group who had not received antenatal
anti-D. However, researchers in Huchet et al's (1987) study gave
a larger dose of anti-D (500 international units) at 28 and 34 weeks
and showed a clear reduction in the incidence of isoimmunization
at between two and twelve months, although no data which considered
subsequent pregnancy in those women were available. In response
to this data, Cochrane reviewers concluded that there was still a
need for consideration of other issues, such as cost and supply
of anti-D (Crowther and Kierse 1999). Of course, we should bear
in mind that, even if we feel that the evidence shows antenatal
anti-D administration to be effective, this does not necessarily
mean it is necessary or beneficial for all women;
this is another issue entirely.
Is there Evidence for Caution?
There are two main arguments against the routine administration
of antenatal anti-D; although cost is a major issue, this will not be
considered here - discussion of this can be found in Wickham (2001).
The first of these arguments concerns the difficulty there exists with
trying to establish how effective antenatal anti-D would be when
there are still questions and problems regarding the current program
of routine postnatal administration and antenatal administration
in response to a potentially sensitising event. Ghosh and Murphy's
(1994) Scottish study showed that just over 30 per cent of women
who had experienced an antenatal sensitising event had not been
offered anti-D. Tovey (1983) showed that 22 per cent of the women
in his study became sensitised as a result of 'failure of administration'
and Howard et al (1997) also propose that closer adherence to the 1991
recommendations might further reduce the incidence of isoimmunization.
Their study found that only 20 per cent of women who had experienced
abdominal trauma had been offered anti-D and only 95
per cent adherence to the recommendations in the
area of postnatal administration.
Clearly, it is not helpful to begin an antenatal programme if a proportion
of the women who are becoming sensitised during pregnancy are
facing this as a result of professional failure to offer anti-D after a
potentially sensitising event. Rather than subjecting all women to
antenatal anti-D because some clinicians fail to offer this to the women
that really need it, we need to consider how this trend can be reversed.
We also need to establish how may women are becoming sensitised
as a result of failure to implement the current guidelines, and not
include these woman in figures which are being used to promote
the uptake of routine antenatal prophylaxis.
It is not just midwifery and obstetric departments which are failing to
offer anti-D. Huggon and Watson (1993) sampled 29 women who
arrived in accident and emergency departments following a threatened
miscarriage. Only eight women were tested to establish their blood
group on admission and none of those women who were rhesus
negative were offered anti-D. Gilling-Smith et al (1997) built on this
small-scale study and researched 88 accident and emergency units,
which treated women who experienced bleeding in early pregnancy.
Seventy seven of these failed to administer anti-D when this was
appropriate, and 37 per cent reported not even having access to
Kleihauer testing to determine whether a woman had experienced
a larger bleed than would be covered by the standard dose.
What are the Risks?
The second argument against routine antenatal anti-D concerns
the potential risks of this, both to the woman and to her unborn baby
(who will not herself benefit from this - anti-D effectively being a
protective measure for her siblings). The fact that there has been no
research investigating the effects of anti-D on the unborn child is one
of the factors of concern to those currently calling for caution (Gaskin
1989, Coombes 1999). Gaskin (1989) cites several potential risk factors
where babies are exposed to anti-D, including immune system
compromise and potential problems during later reproduction for rhesus
negative baby girls exposed to anti-D in utero.
Two further potential risks of antenatal anti-D are discussed in the
medical literature; this does not, however, mean that these are the
only possible risks; there may be others not yet predicted. The first
risk is that of augmentation; or enhanced anti-D immunisation (Urbaniak
1998), where a woman who is given passive anti-D during the antenatal
period could, upon exposure to rhesus positive cells (via transplacental
haemorrhage) mount a primary immune response to these.
The second concern is the effect of passive anti-D on the unborn baby.
There has been no systematic study, which looks at the short and
long-term side effects of anti-D in babies (Urbaniak 1998). Although
Gaskin's (1989) evidence concerning immune system compromise
seems to have been ignored, other risks to the baby have been
discussed in the literature. Some of these concern the fact that
about ten per cent of the anti-D given to the mother will cross the
placenta to the baby (Hughes-Jones et al 1971, Urbaniak 1998).
Studies have shown that this causes a proportion of babies to test
positive for antiglobulins (via a direct Coombs test) after they are
born (Tovey et al 1983, Bowman and Pollock 1978, Herman et al 1984).
The few studies which have looked at this have suggested that,
while babies may suffer some anaemia, this does not require
treatment in the immediate postnatal period.
Although Romm (1999) points out that the manufacturers of anti-D
clearly state that this should not be given to babies, no-one has
considered the question of whether there are long term consequences
of this. It should be remembered that unborn babies will also be
exposed to the risks which women face, such as that of virus
transmission (Wickham 2000). This can only be exacerbated
by the fact that the optimal dose of antenatal anti-D is not
known; women and babies may be exposed to more of
this product than they need.
Debating the Issues
In 1997, a Consensus Conference was held so that a group of
experts could determine national recommendations for antenatal
anti-D administration. These experts gathered to assess the evidence,
including many of the studies here and make recommendations
to the Royal College of Obstetricians and Gynaecologists and
the Royal College of Physicians of Edinburgh. This group included
haematologists, obstetricians, general practitioners and even a
medical journalist. Significantly, a number of groups were not
represented; no consumer-focused childbirth organisations or
childbearing women were invited for their opinions, and there was
no clinical midwifery representation on the group. This may seem
undemocratic to some, as it is women who receive the product and
usually midwives who inform them of the issues and administer it.
In relation to current failures of implementation, the conference
noted their concern that; 'there is abundant evidence that the
recommendations are not being fully applied.' (Urbaniak 1998: 1).
They did not, however, feel that this issue warranted further investigation
before making the decision to recommend routine antenatal anti-D.
Another recommendation concerned the suggestion that, 'information
leaflets concerning the recommendations should be given to RhD
negative women and their partners'. This may be an issue which the
midwifery profession needs to debate in relation to informed choice
and the need for balanced information; the vast majority of the information
leaflets currently available - mostly donated by the pharmaceutical
companies producing anti-D - are biased towards women's acceptance
of anti-D rather than the facilitation of informed choice. If more
midwives became involved in the process of writing and evaluating
this kind of information, women may have more of a foundation
upon which to make their choices.
Where do we go from here?
The Royal College of Midwives (RCM 1999) and the UKCC (Coombes
1999) have raised concerns about the guidelines advocating the use
of anti-D in the antenatal period; specifically the lack of testing of the
product for routine use and the lack of sound evidence which suggests
that antenatal administration is beneficial. Coombes (1999) is also among
those who have highlighted the fact that around 40 per cent of the 100,000
or so women who would receive antenatal anti-D each year in the UK
would be carrying rhesus negative babies, and therefore would have
received this unnecessarily. Should paternal blood testing be one of
the options which women should be offered at this time? Women who
are pregnant with their last child are also among those who would not
benefit from antenatal anti-D. Should it become routine practice for
midwives to discuss these issues with women in relation to
their personal need for anti-D?
Many questions remain in this area, which suggest the need for
midwives to become more involved in this debate. Is there enough
sound evidence to support the routine antenatal administration of anti-D,
or should midwives - as women's advocates - be concerned about
this prospect? How can the issues be addressed and the remaining
questions answered in such a way that we know that the options we
are offering women are beneficial rather than harmful and based on
what is truly optimal for those women rather than being deemed
necessary as a result of our own failures in other areas?
More than ever, midwives need to be able to explain and discuss
the evidence with the women who face this decision. Whatever
recommendations are put in place, either locally or nationally,
women have a right to make their own informed choices and
midwives have a duty to enable these choices to be freely made.
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