Acetaminophen Use in Pregnancy and Neurodevelopment: Attention Function and Autism Spectrum Symptoms

Int J Epidemiol. 2016 Dec 1;45(6):1987-1996. doi: 10.1093/ije/dyw115.

Abstract

Background: Acetaminophen is extensively used during pregnancy. But there is a lack of population-representative cohort studies evaluating its effects on a range of neuropsychological and behavioural endpoints. We aimed to assess whether prenatal exposure to acetaminophen is adversely associated with neurodevelopmental outcomes at 1 and 5 years of age.

Methods: This Spanish birth cohort study included 2644 mother-child pairs recruited during pregnancy. The proportion of liveborn participants evaluated at 1 and 5 years was 88.8% and 79.9%, respectively. Use of acetaminophen was evaluated prospectively in two structured interviews. Ever/never use and frequency of use (never, sporadic, persistent) were measured. Main neurodevelopment outcomes were assessed using Childhood Autism Spectrum Test (CAST), Conner's Kiddie Continuous Performance Test (K-CPT) and ADHD-DSM-IV form list. Regression models were adjusted for social determinants and co-morbidities.

Results: Over 40% of mothers reported using acetaminophen. Ever-exposed offspring had higher risks of presenting more hyperactivity/impulsivity symptoms [incidence rate ratio (IRR) = 1.41, 95% confidence interval (CI) 1.01-1.98), K-CPT commission errors (IRR = 1.10, 1.03-1.17), and lower detectability scores (coefficient β = -0.75, -0.13--0.02). CAST scores were increased in ever-exposed males (β = 0.63, 0.09-1.18). Increased effect sizes of risks by frequency of use were observed for hyperactivity/impulsivity symptoms (IRR = 2.01, 0.95-4.24) in all children, K-CPT commission errors (IRR = 1.32, 1.05-1.66) and detectability (β = -0.18, -0.36-0.00) in females, and CAST scores in males (β = 1.91, 0.44-3.38).

Conclusions: Prenatal acetaminophen exposure was associated with a greater number of autism spectrum symptoms in males and showed adverse effects on attention-related outcomes for both genders. These associations seem to be dependent on the frequency of exposure.

Keywords: Acetaminophen; attention function; autism spectrum symptoms; neurodevelopment; paracetamol; pregnancy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetaminophen / adverse effects*
  • Adult
  • Analgesics, Non-Narcotic / adverse effects*
  • Attention
  • Autism Spectrum Disorder / chemically induced*
  • Autism Spectrum Disorder / epidemiology
  • Child Development*
  • Child, Preschool
  • Cohort Studies
  • Diagnostic and Statistical Manual of Mental Disorders
  • Female
  • Humans
  • Impulsive Behavior
  • Male
  • Multivariate Analysis
  • Pregnancy
  • Prenatal Exposure Delayed Effects / chemically induced*
  • Prenatal Exposure Delayed Effects / epidemiology
  • Psychiatric Status Rating Scales
  • Regression Analysis
  • Sex Factors
  • Spain

Substances

  • Analgesics, Non-Narcotic
  • Acetaminophen