Prenatal caffeine exposure: association with neurodevelopmental outcomes in 9- to 11-year-old children

Abstract

Background: Despite the widespread use of caffeine including consumption during pregnancy, the effect of prenatal caffeine exposure on child brain development and behavior is unclear. Methods: To address this, we used data from the Adolescent Brain and Cognitive Development Study (n = 11,875 children aged 9–11 years from 22 sites across the United States). We explored the associations between prenatal caffeine exposure and various developmental outcomes including birth outcomes, physical health, behavior problems, cognition, substance use and brain structure in children, and evaluated dose effects. Results: Among 9,978 children (4,745 females) who had valid data for prenatal caffeine exposure and whose mothers did not use drugs of abuse after knowing of pregnancy, 4,170 (41.79%) had no prenatal caffeine exposure, 2,292 (22.97%) had daily, 1,933 (19.37%) had weekly, and 1,583 (15.86%) had less than weekly exposures. Prenatal caffeine exposure including the widely recommended ‘safe’ dose was associated with greater externalizing problems, whereas greater BMI and soda consumption were only observed in children with high dose exposures (3+ per day). Notably, the effect size for association of externalizing problems with prenatal caffeine exposure was comparable with that reported for prenatal alcohol (The American Journal of Psychiatry, 177, 2020 and 1060) and prenatal cannabis (JAMA Psychiatry, 78, 2020 and 64) exposures from previous ABCD publications. Additionally, prenatal caffeine exposure was associated with brain structural changes that included greater posterior and lower frontal cortical thickness and altered parietooccipital sulcal depth. Conclusions: The recommended ‘safe’ dose of caffeine during pregnancy should be carefully studied to assess whether the behavioral and brain correlates observed here are clinically relevant and determine whether it needs adjustment. Because of the high prevalence of caffeine use in the general population, studies on prenatal exposure to drugs of abuse should include prenatal caffeine use as a covariate.