Preterm infants whose mothers took low-dose aspirin (LDA) exhibit no negative long-term effects and may have fewer neurobehavioral difficulties as children, according to a study published online December 21 in Pediatrics.
“Aspirin is well tolerated by the fetus and seems to produce a moderate reduction of several different risks (preeclampsia, delivery before 37 weeks of gestation, and fetal growth restriction) without increasing infant bleeding,” write Stéphane Marret, MD, PhD, Department of Neonatal Medicine, Rouen University Hospital, Rouen, France, and the Institute for Biomedical Research, Rouen University, Rouen, France, and colleagues. “Nevertheless, the long-term effects of aspirin on preterm children are unknown.”
To determine the effects of LDA on preterm children, researchers studied 656 children born in France in 1997 before 33 weeks’ gestation. Newborn data were gathered from the Etude Epidemiologique des Petites Ages Gestationnels (EPIPAGE) cohort study, which primarily measured mortality and cerebral lesions. Obstetric records confirmed LDA intake. After 5 years, the investigators examined the children for incidence of cerebral palsy, behavioral issues, and cognitive ability.
Researchers concluded there was no significant relationship between LDA and any long-term outcome. Furthermore, they reported an association of LDA with a decrease in behavioral difficulties.
“The cerebral palsy rate at 5 years of age did not differ according to LDA treatment nor did the rate of low MPC [mental processing composite] or low sequential processing scores (<70). The rate of simultaneous processing scores of <70 was significantly lower in the LDA group than in the no-LDA group (7% vs 19%; P = .04), but not after adjustment for PS [propensity score], prognostic factors, and social class (adjusted odds ratio [aOR]: 0.59 [95% confidence interval (CI): 0.17–2.06]),” the study authors write. “Results showed 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]) associated with LDA treatment after adjustment for PS and prognostic factors.”
Vinod Bhutani, MD, FAAP, professor of pediatrics-neonatology, Stanford University School of Medicine, Stanford, California, noted in an interview that further research is needed on more diverse populations and in infants of less than 28 weeks’ gestation. Still, Dr. Bhutani commended the study authors for their “meticulous work” and called the findings a “major contribution.”
“Aspirin has done wonders in heart disease and microvascular disease and this shows it has a potential future for use during pregnancy,” Dr. Bhutani said.
But LuAnn Papile, MD, professor of pediatrics, Baylor College of Medicine, Houston, Texas, found numerous flaws in the study, including low numbers and missing data. According to Dr. Papile, these failings cast doubt on both conclusions that LDA causes no harm and that it may benefit neurologic behavior.
“They only have cognitive scores on 61% and behavioral scores on only 69% of the children. For most follow-up studies, 85% is the cutoff,” Dr. Papile said in an interview. “Their conclusions are truly unwarranted.”
The study authors acknowledged several limitations, including the fact that 25% of the children were not evaluated as 5-year-olds. They also stated that the rate of loss to follow-up was higher in the control group vs the LDA faction, which “may have resulted in an underestimation of neurodevelopmental impairments in the no-LDA group.”
The researchers pointed out that they believe this study is the first to scrutinize the impact of LDA in such a homogeneous newborn population. But they warned against implementation of their findings pending further research.
“However, these results should be interpreted with caution and need to be confirmed,” the study authors write. “Other studies are urgently needed to confirm the clinical potential of aspirin use during pregnancy, because few neuroprotective agents have been identified.”
INSERM (National Institute of Health and Medical Research), the Directorate General for Health of the Ministry for Social Affairs, Merck-Sharp and Dhome-Chibret, Medical Research Foundation, HAS (French National Authority for Health), and the Hospital Program for Clinical Research 2001 (AOMO1117) of the French Ministry of Health supported this study. The study authors have disclosed no relevant financial relationships.