# Associations between prenatal paracetamol exposure and brain development from ages 4–16: A longitudinal MRI study

## TL;DR

This study finds that prenatal paracetamol exposure may be linked to minor brain structure differences in children but not to cognitive issues like IQ or memory.

## Contribution

This is the first longitudinal MRI study linking prenatal paracetamol exposure to brain development in children.

## Key findings

- Children with prenatal paracetamol exposure had slightly smaller cortical surface area and volume in some brain regions.
- Long-term prenatal exposure was associated with more noticeable brain structure differences.
- No significant effects on IQ or working memory were found in exposed children.

## 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.

•We examined the effect of prenatal paracetamol exposure on brain and cognition.•This is a longitudinal study including children from 4 to 12 years of age.•Children exposed in utero had slightly smaller cortical surface area and volume.•Differences in brain structure were more apparent with long-term prenatal exposure.•No association was found between prenatal exposure and IQ or working memory capacity.

We examined the effect of prenatal paracetamol exposure on brain and cognition.

This is a longitudinal study including children from 4 to 12 years of age.

Children exposed in utero had slightly smaller cortical surface area and volume.

Differences in brain structure were more apparent with long-term prenatal exposure.

No association was found between prenatal exposure and IQ or working memory capacity.