In Utero Exposure to Caffeine and Acetaminophen, the Gut Microbiome, and Neurodevelopmental Outcomes: A Prospective Birth Cohort Study

Hannah E. Laue*, Yike Shen, Tessa R. Bloomquist, Haotian Wu, Kasey J.M. Brennan, Raphael Cassoulet, Erin Wilkie, Virginie Gillet, Anne Sandrine Desautels, Nadia Abdelouahab, Jean Philippe Bellenger, Heather H. Burris, Brent A. Coull, Marc G. Weisskopf, Wei Zhang, Larissa Takser, Andrea A. Baccarelli

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Pregnant individuals are exposed to acetaminophen and caffeine, but it is unknown how these exposures interact with the developing gut microbiome. We aimed to determine whether acetaminophen and/or caffeine relate to the childhood gut microbiome and whether features of the gut microbiome alter the relationship between acetaminophen/caffeine and neurodevelopment. Forty-nine and 85 participants provided meconium and stool samples at 6–7, respectively, for exposure and microbiome assessment. Fecal acetaminophen and caffeine concentrations were quantified, and fecal DNA underwent metagenomic sequencing. Caregivers and study staff assessed the participants’ motor and cognitive development using standardized scales. Prenatal exposures had stronger associations with the childhood microbiome than concurrent exposures. Prenatal acetaminophen exposure was associated with a trend of lower gut bacterial diversity in childhood [β = −0.17 Shannon Index, 95% CI: (−0.31, −0.04)] and was marginally associated with differences in the relative abundances of features of the gut microbiome at the phylum (Firmicutes, Actinobacteria) and gene pathway levels. Among the participants with a higher relative abundance of Proteobacteria, prenatal exposure to acetaminophen and caffeine was associated with lower scores on WISC-IV subscales. Acetaminophen during bacterial colonization of the naïve gut is associated with lasting alterations in childhood microbiome composition. Future studies may inform our understanding of downstream health effects.

Original languageEnglish (US)
Article number9357
JournalInternational journal of environmental research and public health
Issue number15
StatePublished - Aug 2022


  • acetaminophen
  • caffeine
  • children’s health
  • microbiome
  • neurodevelopment

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Pollution
  • Health, Toxicology and Mutagenesis


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