Acetaminophen use during pregnancy and offspring attention deficit hyperactivity disorder – a longitudinal sibling control study
Kristin Gustavson,
Eivind Ystrom,
Helga Ask,
Fartein Ask Torvik,
Mady Hornig,
Ezra Susser,
W. Ian Lipkin,
Angela Lupattelli,
Camilla Stoltenberg,
Per Magnus,
Siri Mjaaland,
Ragna Bugge Askeland,
Kjersti Mæhlum Walle,
Michaeline Bresnahan,
Hedvig Nordeng,
Ted Reichborn‐Kjennerud
Affiliations
Kristin Gustavson
Norwegian Institute of Public Health Oslo Norway
Eivind Ystrom
Norwegian Institute of Public Health Oslo Norway
Helga Ask
Norwegian Institute of Public Health Oslo Norway
Fartein Ask Torvik
Department of Psychology University of Oslo Oslo Norway
Mady Hornig
Mailman School of Public Health Columbia University New York NY USA
Ezra Susser
Mailman School of Public Health Columbia University New York NY USA
W. Ian Lipkin
Department of Epidemiology Columbia University Mailman School of Public Health New York NY USA
Angela Lupattelli
Pharmacoepidemiology and Drug Safety Research Group Department of Pharmacy, and PharmaTox Strategic Research Initiative Faculty of Mathematics and Natural Sciences University of Oslo Oslo Norway
Camilla Stoltenberg
Norwegian Institute of Public Health Oslo Norway
Per Magnus
Norwegian Institute of Public Health Oslo Norway
Siri Mjaaland
Norwegian Institute of Public Health Oslo Norway
Ragna Bugge Askeland
Norwegian Institute of Public Health Oslo Norway
Kjersti Mæhlum Walle
Norwegian Institute of Public Health Oslo Norway
Michaeline Bresnahan
Mailman School of Public Health Columbia University New York NY USA
Abstract Background Maternal acetaminophen use during pregnancy is associated with increased risk of ADHD in the child. This could reflect causal influence of acetaminophen on fetal neurodevelopment or could be due to confounding factors. The aim of the current study was to examine unmeasured familial confounding factors of this association. Methods We used data from 26,613 children from 12,902 families participating in the prospective Norwegian Mother, Father, and Child Cohort Study (MoBa). The MoBa was linked to the Norwegian Medical Birth Register and the Norwegian Patient Registry. Siblings discordant for prenatal acetaminophen exposure were compared regarding risk of having an ADHD diagnosis. Results Children exposed to acetaminophen up to 28 days during pregnancy did not have increased risk of receiving an ADHD diagnosis compared to unexposed children. The adjusted Hazard ratio (aHR) was 0.87 (95% C.I. = 0.70‐1.08) for exposure 1 to 7 days, and 1.13 (95% C.I. = 0.82–1.49) for 8–28 days. Long‐term exposure (29 days or more) was associated with a two‐fold increase in risk of ADHD diagnosis (aHR = 2.02, 95% C.I = 1.17–3.25). In the sibling control model, the association between long‐term acetaminophen use and ADHD in the child was aHR = 2.77 (95% C.I. = 1.48–5.05) at the between‐family level, and aHR = 1.06 (95% C.I. = 0.51–2.05) at the within‐family level. Conclusions Both the exposed and the unexposed children of mothers with long‐term use of acetaminophen in one of the pregnancies had increased risk of receiving an ADHD diagnosis. This indicates that the observed association between long‐term acetaminophen use during pregnancy and ADHD in the child may at least partly be confounded by unobserved family factors.
