Low-Dose Aspirin For High-Risk Pregnancy

Doctors have known for many years that the blood clotting systems of some women affected by pre-eclampsia or eclampsia tend to be overactive, making the blood more liable to clot. The specialised clotting cells known as platelets, which circulate in the blood in vast numbers, are particularly affected. The logic of using aspirin to prevent or treat pre-eclampsia is that, if taken in small daily doses, it is known to have a calming effect on platelet activity, so inhibiting the clotting tendency to some.

A number of small medical trials conducted since the mid-1980s have suggested that low-dose aspirin is highly effective in preventing pre-eclampsia, reducing the risk by as much as 70 per cent. However, these trials were too small to produce completely reliable results. So in 1986 the Medical Research Council gave the go-ahead to a massive international trial known as CLASP (1). The results were published (2) in March 1994.

More than 9,000 pregnant women from 16 different countries took part in the trial. All were between 12 and 32 weeks pregnant and considered at high risk of, or with signs of, pre-eclampsia or intrauterine growth retardation (which aspirin was also thought to prevent). Half of these women were treated with 60mg per day of aspirin (one fifth of a normal adult tablet) and the other half took identical looking placebo (dummy) tablets. The trial was a ‘double-bind’ – meaning that neither the women nor their doctors knew who was taking what. The outcomes of the pregnancies of women taking aspirin were then compared to those of the women taking placebo.

The main findings of the CLASP trial were that aspirin:

• reduces the overall risk of developing severe pre-eclampsia by about 12 per cent – a reduction so small in statistical terms that it could have been due to chance. However, when the CLASP results were analysed together with those of all previous trials the combined evidence suggested that the treatment with low-dose → aspirin reduces the risk of severe pre-eclampsia by about one quarter;
• significantly reduces the risk of early-onset pre-eclampsia. Only seven women on aspirin needed delivery before 28 weeks because of pre-eclampsia, compared with 17 on placebo;
• significantly reduces the risk of early-onset pre-eclampsia. Only seven women on aspirin needed delivery before 28 weeks because of pre-eclampsia, compared with 17 on placebo;
• reduces the risk of premature delivery (i.e. before 37 weeks) – by about 14 per cent;
• does not prevent growth retardation in the unborn baby, stillbirth or neonatal death.

Since low-dose aspirin works by subtly reducing the tendency of the blood to clot, the fear has always been that it might increase the risk of bleeding in mother and/or baby either before or after delivery. Happily though, the results of the CLASP trial have largely allayed those fears. Aspirin did not increase the risk of bleeding either in fetuses or in newborn babies and neither did it increase the risk of premature separation (abruption) of the placenta. Although mothers who took aspirin were slightly more likely to need a blood transfusion after delivery than those who took placebo, there was no increased risk of major maternal bleeding either before or after delivery.

It had always been assumed that the dosage of aspirin was too small to harm the development of babies in the womb, and the CLASP trial bore out this theory. The babies of the UK mothers who took part in the trial were followed up for 18 months after the birth, and the data so far suggests no detectable health or developmental differences between babies whose mothers took aspirin and those whose mothers took placebo.

There is no reason to believe that any of the following groups of women stand to benefit from taking low-dose aspirin in pregnancy:

• first-time mothers (unless they are known to be at high risk of early onset pre-eclampsia);
• women with pre-established pre-eclampsia;
• women with a history of late-onset or mild pre-eclampsia.

This treatment should be positively avoided by women who are allergic to aspirin or have a long-term bleeding or platelet disorder. Asthma sufferers should use aspirin with caution because it can sometimes make asthma worse.

The only women for whom the use of low-dose aspirin may be justified are those at especially high risk of developing pre-eclampsia before about 32 weeks. This includes women who have suffered early-onset pre-eclampsia or eclampsia in one or more previous pregnancies. However, aspirin is only likely to prevent half such cases.

Since early-onset pre-eclampsia can appear at any time after 20 weeks of pregnancy, treatment with low-dose aspirin needs to begin before this half-way mark. Most consultants begin the treatment at around 12 weeks of pregnancy, although women with a very bad previous history of pre-eclampsia may be recommended to start the treatment earlier – even before conception. The normal dosage is 75mg – one quarter of a normal adult tablet – taken once daily. The treatment usually stops two weeks before delivery to allow the blood clotting function to return to normal.

If you think you are a candidate for treatment with low-dose aspirin, make an appointment to talk to your consultant in the very early weeks of pregnancy – or even before you conceive. If he or she doesn’t think aspirin therapy is appropriate in your case, make sure you understand why. If you are not satisfied with the decision, ask your GP to refer you elsewhere for a second opinion (3).