Caffeine exposure in utero is associated with structural brain alterations and deleterious neurocognitive outcomes in 9-10 year old children

Neuropharmacology. 2021 Mar 15;186:108479. doi: 10.1016/j.neuropharm.2021.108479. Epub 2021 Jan 30.


Caffeine, a very widely used and potent neuromodulator, easily crosses the placental barrier, but relatively little is known about the long-term impact of gestational caffeine exposure (GCE) on neurodevelopment. Here, we leverage magnetic resonance imaging (MRI) data, collected from a very large sample of 9157 children, aged 9-10 years, as part of the Adolescent Brain and Cognitive Developmentsm (ABCD ®) study, to investigate brain structural outcomes at 27 major fiber tracts as a function of GCE. Significant relationships between GCE and fractional anisotropy (FA) measures in the inferior fronto-occipito fasciculus and corticospinal tract of the left hemisphere (IFOF-LH; CST-LH) were detected via mixed effects binomial regression. We further investigated the interaction between these fiber tracts, GCE, cognitive measures (working memory, task efficiency), and psychopathology measures (externalization, internalization, somatization, and neurodevelopment). GCE was associated with poorer outcomes on all measures of psychopathology but had negligible effect on cognitive measures. Higher FA values in both fiber tracts were associated with decreased neurodevelopmental problems and improved performance on both cognitive tasks. We also identified a decreased association between FA in the CST-LH and task efficiency in the GCE group. These findings suggest that GCE can lead to future neurodevelopmental complications and that this occurs, in part, through alteration of the microstructure of critical fiber tracts such as the IFOF-LH and CST-LH. These data suggest that current guidelines regarding limiting caffeine intake during pregnancy may require some recalibration.

Keywords: Brain development; Caffeine; Children and adolescents; Diffusion tensor imaging; White matter.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Brain / diagnostic imaging
  • Brain / drug effects*
  • Brain / growth & development*
  • Caffeine / administration & dosage
  • Caffeine / adverse effects*
  • Central Nervous System Stimulants / administration & dosage
  • Central Nervous System Stimulants / adverse effects
  • Child
  • Developmental Disabilities / chemically induced
  • Developmental Disabilities / diagnostic imaging
  • Developmental Disabilities / psychology
  • Female
  • Humans
  • Longitudinal Studies
  • Male
  • Mental Status and Dementia Tests*
  • Neurocognitive Disorders / chemically induced
  • Neurocognitive Disorders / diagnostic imaging
  • Neurocognitive Disorders / psychology
  • Pregnancy
  • Prenatal Exposure Delayed Effects / chemically induced*
  • Prenatal Exposure Delayed Effects / diagnostic imaging
  • Prenatal Exposure Delayed Effects / psychology*


  • Central Nervous System Stimulants
  • Caffeine