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In Utero Exposure to Caffeine and Acetaminophen, the Gut Microbiome, and Neurodevelopmental Outcomes: A Prospective
Hannah E Laue1, Yike Shen2, Tessa R Bloomquist2
1Department of Epidemiology, Geisel School of Medicine, Dartmouth College, Hanover, NH 03755, USA.
Insights
Prenatal acetaminophen exposure may impact a child's gut microbiome, potentially affecting neurodevelopment. This study explored the links between common pregnancy exposures and early childhood gut bacteria composition.
Area of Science:
- Microbiome research
- Developmental neuroscience
- Environmental health
Background:
- Pregnant individuals commonly use acetaminophen and caffeine.
- The impact of these exposures on the developing infant gut microbiome is not well understood.
- Potential links between the gut microbiome and neurodevelopment are an area of active research.
Purpose of the Study:
- To investigate the relationship between prenatal acetaminophen and/or caffeine exposure and the childhood gut microbiome.
- To determine if gut microbiome characteristics modify the association between these exposures and neurodevelopment.
- To assess the long-term effects of early life exposures on gut microbial composition.
Main Methods:
- Collected meconium and stool samples from infants for exposure and microbiome analysis.
- Quantified fecal acetaminophen and caffeine concentrations.
- Performed metagenomic sequencing on fecal DNA.
- Assessed child motor and cognitive development using standardized scales.
Main Results:
- Prenatal exposures showed stronger associations with the childhood microbiome than concurrent exposures.
- Prenatal acetaminophen exposure was linked to a trend of lower gut bacterial diversity (Shannon Index) and altered microbial composition (phyla, gene pathways).
- In children with high Proteobacteria abundance, prenatal acetaminophen and caffeine exposure correlated with lower cognitive scores (WISC-IV subscales).
Conclusions:
- Acetaminophen exposure during early gut colonization is associated with persistent changes in childhood microbiome composition.
- Gut microbiome alterations may mediate the relationship between prenatal exposures and neurodevelopmental outcomes.
- Further research is needed to elucidate the downstream health implications.
Abstract:
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.
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