The main causes of death within the womb and in the first week of life are foetal growth retardation, in which the foetus develops too slowly; and pre-eclamptic toxaemia, in which the mother develops high blood pressure and kidney damage, leading to convulsions and death if it is not controlled and the pregnancy is not terminated.
Pre-eclampsia and growth retardation have a common origin in the spiral arteries of the placenta through which the foetus receives its oxygen and nutrition. As in the coronary arteries in heart disease, the spiral arteries become narrowed by clots, greatly reducing the flow of blood to the foetus. The rationale for aspirin in such cases is exactly the same as for coronary artery disease.
In 1990 Professor H C S Wallenberg, of Rotterdam, reviewed the results of four trials in 122 women given aspirin for pre-eclampsia. It significantly lowered their high blood pressure, reduced their kidney damage, reduced their need for Caesarean section, and reduced the numbers of births before 37 weeks.
His results led to CLASP - the Collaborative Low Dose aspirin Study in Pregnancy - which compared aspirin 60mg per day with placebo for the prevention and early treatment of pre-eclampsia.
CLASP involved 9,364 women taking this dose of aspirin or placebo from the 12th-13th weeks of pregnancy onwards, 74% of whom were at increased risk of pre-eclampsia and 12% of whom had early signs of pre-eclampsia. Twelve per cent were included because they were at high risk of foetal growth retardation, and 7% already had signs of such retardation.
Although the aspirin treatment was linked in each group with better results than those with placebo, the results were slightly disappointing. aspirin gave a reduction in the odds of occurrence of pre-eclampsia of 13% overall, although it was greater if the treatment was started before the 20th gestational week. As for foetal growth retardation, aspirin treatment reduced it by 20%: there was an 11% reduction in its development when it was used to prevent it. None of these differences was statistically significant.
What was statistically different was a 12% reduction in premature delivery. There was also less pre-eclampsia early in pregnancy: when it did develop on aspirin treatment it developed later, which was safer for both mother and baby. The perinatal mortality (infants dying in the first week of life) in patients given aspirin for pre-eclampsia with and without foetal growth retardation was 5.3%, half that of those given placebo (10.6%). However, aspirin proved to be of no value once pre-eclampsia or foetal growth retardation was established.
There were no differences between the two treatment groups in their side effects: fears that aspirin might cause excess bleeding in pregnancy were dispelled by the trial: the proportion of women with abnormal prenatal, perinatal and postnatal bleeding was the same in the two groups.
Professor Wallenberg explained the relatively low benefits on the fact that the women chosen for the trial were at relatively low risk of developing pre-eclampsia or growth retardation. The doctors doing the trials were so convinced beforehand that the drug worked that they would not put high risk patients into the placebo-controlled trial!
He now advises that pregnant women be told that aspirin has a moderate effect in preventing toxaemia in women at low risk and a marked effect in women at high risk. The latter includes women who have had pre-eclampsia in a previous pregnancy, particularly before the 12th week. They also include women with kidney disease, high blood pressure, systemic lupus erythematosus, or insulin-dependent diabetes, or who have had a sister or mother with pre-eclampsia.