Prenatal Low-Dose Aspirin and Neurobehavioral Outcomes of Children Born Very Preterm

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Few neuroprotective agents have been identified for the population of very preterm infants at high risk of long-term neurosensory, cognitive, and behavioral disabilities. Treatment of mothers who have high-risk pregnancies with low-dose aspirin (LDA) appears to be well tolerated by the fetus and may produce a moderate reduction in several different risks including preeclampsia, delivery before 37 weeks' gestation, and fetal growth restriction. Little data exist on the long-term effects of aspirin on children born preterm. This observational population-based study investigated the effects of antenatal LDA treatment of high-risk pregnancies on the neurodevelopmental and behavioral abilities of 5-year-olds born before 33 weeks of gestation. Data were obtained from a large cohort study for all infants born before 33 weeks of gestation in 9 regions of France in 1997. The participants were 584 mothers (656 children) with an obstetric history of preeclampsia, fetal growth restriction, or fetal death, or with chronic hypertension, renal, or autoimmune disease. A total of 125 of the 584 mothers (21%) were treated with LDA (LDA group) and 447 were not (no-LDA group). The primary outcome measures were mortality, cerebral damage, and outcome at 5 years of age. Outcomes were measured by a diagnosis of cerebral palsy; assessment of behavioral difficulties using the Strength and Difficulties Questionnaire; and assessment of cognitive outcome using the mental processing composite scale of the Kaufman Assessment Battery for Children, a global IQ-equivalent measure of cognitive ability in 2 dimensions: a sequential score and a simultaneous processing score. LDA had no significant adverse effects on outcomes of fetal/neonatal mortality, cerebral damage, cerebral palsy, or global cognitive impairment at 5 years of age. The rate of simultaneous processing scores of <70 was significantly lower in unadjusted analysis among the LDA group (7%) than in the no-LDA group (19%) (P = 0.04). However, following adjustment for propensity score, prognostic factors, and social class, the association was not significant; the adjusted odds ratio (aOR) was 0.59, with a 95% confidence interval (CI) of 0.17 to 2.06. In the LDA group, a nonsignificant reduction was found in total behavioral difficulties (aOR, 0.44; 95% CI, 0.19–1.02) and hyperactivity (aOR, 0.43; 95% CI, 0.17–1.05). These findings show that antenatal treatment with LDA is not associated with adverse neonatal or long-term outcomes and may be associated with a reduction in neurobehavioral difficulties.