Long-term child outcomes after prenatal aspirin exposure: A 4-year follow-up of a randomized controlled trial (the APRIL study)

Objective: To identify the long-term child outcomes after prenatal aspirin exposure. Methods: This study is a follow-up of a randomized controlled trial (RCT) evaluating low-dose aspirin in the prevention of recurrent spontaneous preterm labor (the APRIL study) comparing aspirin 80 mg daily (n = 194) to placebo (n = 193) in singletons. Children were assessed at 4 years corrected age using the Ages and Stages Questionnaire (third edition, ASQ-3) and the Strengths and Difficulties Questionnaire (SDQ) for (neuro)development and behavioral outcomes, respectively. Data on mortality, general health, growth and a composite of abnormal child outcome or mortality were also collected. Analyses were performed reporting odds ratio (OR) and 95% confidence intervals (CIs). Results: Eight children were deceased until 4 years follow-up (all perinatal deaths; n = 6 in aspirin and n = 2 in the placebo group). We included 231/379 (60.9%) children: 111/231 in the aspirin and 120/231 in the placebo groups. Total ASQ-3 score was higher in the aspirin group (mean 259.3 vs. 248.3, mean difference 10.96, 95% CI: 0.17–21.76). The rate of children with an ASQ-3 score of ≥1SD below the normative data did not differ between groups (35.2% vs. 47.4%; OR 0.60, 95% CI: 0.33–1.09), nor did a score on the SDQ ≥80th centile (18.3% vs. 14.7%; OR 1.30, 95% CI: 0.64–2.66). General health, growth and the composite outcome of abnormal child development or mortality did not significantly differ between groups. Conclusion: We found no harmful effects of daily prenatal exposure to aspirin 80 mg. Our findings contribute to the existing data confirming the safety of low-dose aspirin use in pregnancy.