Aspirin did not prevent pre-eclampsia or intrauterine growth retardation
ACP J Club. 1994 Sept-Oct;121:47. doi:10.7326/ACPJC-1994-121-2-047
CLASP (Collaborative Low-dose Aspirin Study in Pregnancy) Collaborative Group. CLASP: a randomised trial of low-dose aspirin for the prevention and treatment of pre-eclampsia among 9364 pregnant women. Lancet. 1994 Mar 12;343:619-29.
To study whether low-dose aspirin given to women at risk effectively reduced the incidence of pre-eclampsia or intrauterine growth retardation (IUGR).
5-year randomized, double-blind, placebo-controlled trial.
213 centers in 16 countries.
9364 women between 12 and 32 weeks gestation who were at risk for pre-eclampsia or IUGR. Women with a history of either condition in previous pregnancies or with chronic hypertension, renal disease, or other risk factors were considered for prophylactic entry. Women with signs or symptoms of IUGR or pre-eclampsia in the current pregnancy were considered for therapeutic entry. Exclusion criteria were clear indication for or against aspirin or a high likelihood of immediate delivery. Post-delivery follow-up was > 99%.
4683 women were randomly allocated to receive coated aspirin, 60 mg/d, and 4681 women were allocated to receive placebo. Medication was started between 12 and 32 weeks gestation and continued until or near delivery. Other aspirin-containing products were discouraged.
Main Outcome Measures
Development of proteinuric pre-eclampsia, duration of pregnancy, crude birth weight, adjusted birth-weight below the 3d centile, stillbirth or neonatal death, IUGR, and maternal and fetal complications.
The groups did not differ for the development of proteinuric pre-eclampsia (6.7% for women taking aspirin vs. 7.6% for women taking placebo) or IUGR (7.7% vs. 8.3%), rate of stillbirth or neonatal death (2.7% vs. 2.8%), maternal hemorrhage, labor or delivery complications, or fetal or neonatal complications including hemorrhage. A trend toward greater birth weight with aspirin was noted (3024 vs. 2991 g; P = 0.05). Women taking aspirin, compared with women taking placebo, had a lower likelihood of preterm delivery (before 37 wk) (19.7% vs. 22.2%; P = 0.003) and a trend toward greater reduction in proteinuric pre-eclampsia the earlier the delivery (P = 0.004).
Routine prophylactic or therapeutic low-dose aspirin was not effective in women at risk for pre-eclampsia or intrauterine growth retardation. Prophylactic treatment may be indicated in women at high risk for early onset pre-eclampsia requiring preterm delivery before or at 32 weeks.
Source of funding: UK Medical Research Council; Clinical Trial Service Unit of Oxford University; Sterling Winthrop; Bayer-Europe; and European Aspirin Foundation.
For article reprint: Dr. C.W.G. Redman, CLASP Coordination Centre, Harkness Building, Radcliffe Infirmary, Oxford OX2 6HE, United Kingdom. FAX 44-865-58-817.
In recent years, the prevention of pre-eclampsia has focused on low-dose aspirin therapy. In 1991, a meta-analysis of 6 trials of women taking low-dose aspirin who were judged to be at high risk for pregnancy-induced hypertension, a subset of which is pre-eclampsia, suggested a 65% reduction in this incidence and a 44% reduction in the incidence of low-birth-weight infants (1). A new meta-analysis, which includes the CLASP report plus 16 published trials of women taking low-dose aspirin who had pre-eclampsia or who were at risk for pre-eclampsia, indicated a 25% reduction in the incidence. In absolute terms, this means that to prevent pre-eclampsia in 1 woman, 56 must be treated. Important inconsistencies, however, exist among these trials.
Why was the benefit of aspirin less apparent in CLASP? In some of the previous trials of women at high risk, the incidence of pre-eclampsia was 17% to 52% in the placebo group (1). This far exceeds the risk of 6% to 8% noted in CLASP, a study which more closely reflects the current population incidence. Perhaps compliance with therapy and follow-up was lower in CLASP, a megatrial compared with the other smaller controlled trials. Also, it may be that the women who were correctly judged by physicians to be at high risk were not offered randomization.
The good news from CLASP and other trials (2) is that aspirin is relatively safe for mother and infant. Although the results of CLASP and the subsequent meta-analysis do not warrant prophylactic use of aspirin for pre-eclampsia prevention, the consistent trend toward prevention of severe, early-onset pre-eclampsia in women who are at high risk deserves further attention. Initial research should be devoted to developing a marker or diagnostic test to reliably identify women at high risk for pre-eclampsia or IUGR in early pregnancy.
Cynthia Morris, PhD, MPH
Oregon Health Sciences University Portland, Oregon, USA