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.