Is intrauterine exposure to acetaminophen associated with emotional and hyperactivity problems during childhood? Findings from the 2004 Pelotas birth cohort

Abstract Background Longitudinal studies have consistently reported that prenatal exposure to acetaminophen can to lead to an increased risk of attention deficit-hyperactivity disorder during childhood. This study aimed to investigate the association between intrauterine exposure to acetaminophen and the presence of emotional and behavioral problems at the ages of 6 and 11 years in a low-middle income country. Methods We performed a prospective longitudinal population-based study using data from the 2004 Pelotas birth cohort. From the 4231 initial cohort participants, 3722 and 3566 children were assessed at 6 and 11 years of age, respectively. The outcomes were assessed using the parent version of Strengths and Difficulties Questionnaire (SDQ). The cut-off points established for the Brazilian population were used to categorize the outcomes. Crude and adjusted odds ratio were obtained through logistic regression. Results Acetaminophen was used by 27.5% (95% confidence interval [CI]: 26.1–28.9) of the mothers at least once during pregnancy. The prevalence of emotional problems at 6 and 11 years was 13.6 and 19.9%, respectively. For hyperactivity problems, prevalence was 13.9 and 16.1%, respectively. Intrauterine exposure to acetaminophen increased the odds of having emotional (odds ratio [OR] = 1.47; 95% CI: 1.07–2.02) and hyperactivity/inattention (OR = 1.42; 95% CI: 1.06–1.92) problems in 6-year-old boys. At the age of 11, a small decrease in the effect was observed for both outcomes after adjustment: OR = 1.31 (95% CI: 0.99–1.73) for emotional problems and OR = 1.25 (95% CI: 0.95–1.65) for hyperactivity/inattention in boys. No association for any phenotypes at both ages was observed for girls. Conclusion The effect of intrauterine exposure to acetaminophen in emotional and hyperactivity symptoms was dependent on sex in a Brazilian cohort. While it seemed to be important for boys, mainly at 6 years of age, for girls, no association was observed.