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Published online December 21, 2009
PEDIATRICS Vol. 125 No. 1 January 2010, pp. e29-e34 (doi:10.1542/peds.2009-0994)
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ARTICLE

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

Stéphane Marret, MD, PhDa,b, Laetitia Marchand, PhDc,d, Monique Kaminski, MScc,d, Béatrice Larroque, MD, PhDc,d, Catherine Arnaud, MD, PhDe, Patrick Truffert, MD, PhDf, Gérard Thirez, MD, PhDg, Jeanne Fresson, MD, PhDh, Jean-Christophe Rozé, MD, PhDi, Pierre-Yves Ancel, MD, PhDc,d for the EPIPAGE Study Group

a Department of Neonatal Medicine, Rouen University Hospital, Rouen, France
b Institute for Biomedical Research, Rouen University, Rouen, France
c Epidemiological Research Unit on Perinatal Health and Women's and Children's Health, Villejuif, France
d Pierre and Marie Curie University, Paris, France
e Research Unit on Epidemiology and Public Health, Toulouse, France
f Department of Neonatology, Jeanne de Flandres Hospital, Lille, France
g Paediatric Intensive Care Unit, Saint Jacques Hospital, Besançon, France
h Regional Maternity University Hospital, Nancy, France
i Department of Neonatology, Children's Hospital, Nantes, France

OBJECTIVE: Low-dose aspirin (LDA) given during pregnancy may alter brain development in very preterm infants. We report the short- and long-term outcomes of very preterm infants according to LDA treatment.

PATIENTS AND METHODS: Data were from the Etude Epidemiologique des Petites Ages Gestationnels (EPIPAGE) cohort study, which included all infants born before 33 weeks of gestation in 9 French regions in 1997. This study was restricted to 656 children who were born to 584 women with an obstetric history of placental vascular disease or with chronic hypertension or renal or autoimmune diseases. The main outcome measures were mortality, cerebral lesions, and outcome at 5 years of age, which were measured by a diagnosis of cerebral palsy; behavioral difficulties, which were assessed with the Strength and Difficulties Questionnaire; and cognitive impairment, which was measured by the mental processing composite scale of the Kaufman Assessment Battery for Children (an IQ-equivalent measure of cognitive ability in 2 dimensions: sequential and simultaneous processing scores).

RESULTS: LDA treatment was administered to 125 of 584 (21%) mothers and was not significantly associated with mortality, cerebral lesions, cerebral palsy, or global cognitive impairment of the children at 5 years of age. The proportion of low simultaneous processing scores (<70) was lower in the group with LDA (7% vs 19% without LDA; P = .04). This association was not significant after adjustment for propensity score, prognostic factors, and social class (adjusted odds ratio [aOR]: 0.59 [95% confidence interval (CI): 0.17–2.06]). LDA treatment was associated with a reduction, at the limit of significance, in total behavioral difficulties (aOR: 0.44 [95% CI: 0.19–1.02]) and hyperactivity (aOR: 0.43 [95% CI: 0.17–1.05]).

CONCLUSIONS: LDA was not associated with adverse neonatal or long-term outcomes. Moreover, the results suggest that LDA may be associated with a reduction in neurobehavioral difficulties. More research is needed to assess the effects of aspirin alone or combined with other neuroprotective agents.

Key Words: acetylsalicylic acid • neuroprotection • periventricular leukomalacia • follow-up • neurologic disabilities

Abbreviations: EPIPAGE—Etude Epidemiologique des Petites Ages Gestationnels • SEH—subependymal hemorrhage • IVH—intraventricular hemorrhage • WMI—white matter injury • LDA—low-dose aspirin • MPC—mental processing composite • PS— propensity score • aOR—adjusted odds ratio • CI—confidence interval

Accepted Jul 28, 2009.


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