Low-dose aspirin reduces the incidence of preeclampsia in women with multiple gestations and elevated human chorionic gonadotropin

INTRODUCTION: The Maternal Fetal Medicine Units (MFMU) High‐ Risk Aspirin (HRA) study was a randomized placebo‐controlled trial to evaluate the efficacy of low‐dose aspirin (LDA) in reducing the incidence of preeclampsia (PreE) in women at high risk. LDA was ineffective in preventing PreE in this trial, including in women with multiple gestations (MULT). In a previous secondary analysis of this trial, we found that women with MULT and elevated serum human chorionic gonadotropin (hCG) levels had an increased risk of PreE. This study was designed to determine if LDA was effective in preventing PreE in this specific subset of women. METHODS: This is a secondary analysis of the MFMU HRA trial. In this trial, hCG levels were drawn at a mean gestational age of 19.6 weeks. Receiver‐operating characteristic (ROC) curve analysis was used to determine a threshold hCG level that best predicted PreE in women randomized to placebo. For women with hCG levels above this threshold and MULT, the incidence of PreE was compared between women randomized to LDA and those randomized to placebo by odds ratio (OR) and 95% Wald confidence interval (CI). RESULTS: 235 MULT women with complete data were studied. ROC analysis indicated an ideal hCG threshold of 29.96 IU/mL (AUC 0.61, sensitivity 0.68, specificity 0.55). Among MULT women, 114 (48.5%) had an hCG above this threshold; 55 received LDA and 59 placebo. Treatment with LDA was associated with a significant reduction in PreE (OR 0.28, CI 0.08‐0.91). In women with hCG above the threshold, the incidence of PreE was 7.8% in women receiving LDA compared with 28.3% in those receiving placebo. CONCLUSIONS: In women with MULT and elevated hCG levels, LDA treatment was associated with a decreased risk of PreE. This may be an attractive screening strategy based on the easy availability of hCG levels and the high percentage of women with elevated levels that benefit from treatment.