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

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.