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Associations between prenatal paracetamol exposure and brain development from ages 4-16: A longitudinal MRI study
Stine Kleppe Krogsrud1, Hedvig Nordeng2, James M Roe3
1Center for Lifespan Changes in Brain and Cognition (LCBC), Department of Psychology, University of Oslo, Norway; School of Health Sciences, Kristiania University of Applied Sciences, Oslo, Norway; Pharmacoepidemiology and Drug Safety Research Group, Department of Pharmacy, University of Oslo, Norway.
Insights
Prenatal paracetamol exposure may be linked to minor differences in fetal brain structure, but it did not affect cognitive abilities like IQ in children. Further research is needed to understand the clinical significance.
Area of Science:
- Neuroscience
- Developmental Pediatrics
- Radiology
Background:
- Concerns exist regarding prenatal paracetamol (acetaminophen) exposure and fetal neurodevelopment.
- Longitudinal data on the impact on brain structure and cognition is limited.
Purpose of the Study:
- To investigate the association between prenatal paracetamol exposure and structural brain development.
- To examine the relationship between prenatal paracetamol exposure and cognitive abilities in children and adolescents.
Main Methods:
- Longitudinal study of 447 children (aged 4.1-16.2 years) using 905 MRI scans.
- Data from The Norwegian Mother, Father and Child Study (MoBa) and Medical Birth Registry of Norway.
- Exposure assessed via maternal self-reported paracetamol use; analyzed using vertex-wise linear mixed effect models.
Main Results:
- Exposed children showed slightly smaller cortical surface area and volume in some brain regions.
- Observed differences were small, with largely overlapping distributions between groups.
- No significant effects of prenatal paracetamol exposure on working memory capacity or IQ scores were found.
Conclusions:
- Prenatal paracetamol exposure may be associated with subtle brain structural variations, particularly with long-term exposure.
- The clinical significance of these minor brain structure differences remains uncertain due to observational design and potential confounding.
- Cognitive outcomes in children appear unaffected by prenatal paracetamol exposure.
Abstract:
Research has raised concerns regarding the potential impact of prenatal paracetamol exposure on fetal neurodevelopment. This is the first longitudinal study to investigate whether such exposure is related to structural brain development and cognitive abilities during childhood and adolescence. The sample includes 447 children aged 4.1-16.2 years with 905 MRI scans. The study is based on The Norwegian Mother, Father and Child Study (MoBa), and uses data from the Medical Birth Registry of Norway. The exposure variable is mothers' self-reported use of paracetamol from prenatal and postnatal questionnaires. Among 447 children (229 girls; mean age 8.38 years), 193 (43.2 %) were prenatally exposed. Days of exposure range from 1 to 128 (mean 8.2). Vertex-wise linear mixed effect models showed that exposed children (n = 193; 393 scans) had slightly smaller cortical surface area and volume in some regions compared to non-exposed children. These results were seemingly driven by long-term exposed children (≥14 days in utero; n = 35; 72 scans, and exposed in all three trimesters, n = 21; 44 scans). However, group differences in brain structure were small with largely overlapping distributions, and the observational design and risk of unmeasured confounding preclude causal inference. Thus, the clinical significance remains uncertain. For cognitive abilities, results were reassuring showing no significant effect of prenatal paracetamol exposure on working memory capacity or IQ scores.
