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Prenatal paracetamol exposure and neurodevelopmental outcomes in preschool-aged children
Johanne N Trønnes1, Mollie Wood1,2, Angela Lupattelli1
1PharmacoEpidemiology and Drug Safety Research Group, Department of Pharmacy, and PharmaTox Strategic Initiative, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway.
Insights
Prenatal paracetamol exposure, particularly in multiple trimesters, may be linked to behavioral changes in children. However, unmeasured factors could influence these findings, suggesting caution in interpretation.
Area of Science:
- Neurodevelopmental research
- Pediatric health
- Epidemiology
Background:
- Emerging studies suggest a link between prenatal paracetamol (acetaminophen) use and adverse child neurodevelopment.
- Potential confounding factors in previous research may obscure the true association.
Purpose of the Study:
- To investigate the relationship between the duration and timing of prenatal paracetamol exposure and child communication, behavior, and temperament.
- To assess the impact of unmeasured confounding on these associations.
Main Methods:
- Utilized data from the Norwegian Mother and Child Cohort Study (N=32,934).
- Employed linear and generalized linear models with inverse probability weighting and robust standard errors.
- Quantified associations between prenatal paracetamol exposure and various child outcomes.
Main Results:
- Exposure to paracetamol in two trimesters was associated with lower shyness.
- Exposure in three trimesters showed increased risk for internalizing behaviors and borderline externalizing behaviors.
- Sensitivity analyses highlighted the significant role of unmeasured confounding.
Conclusions:
- Short-term or single-trimester prenatal paracetamol use appears to pose minimal risk for the studied outcomes.
- Associations found with multi-trimester exposure require cautious interpretation due to potential confounding.
- Chance or unmeasured confounders remain plausible explanations for observed associations.
Background:
Recent studies have suggested an association between prenatal paracetamol exposure and adverse neurodevelopmental outcomes in children. However, these findings may be confounded by unmeasured factors related to maternal use of paracetamol and child outcomes.
Objective:
To examine the association between duration and timing of prenatal paracetamol exposure on parent-reported communication skills, behaviour, and temperament in preschool-aged children, with focus on the role of unmeasured confounding.
Methods:
We used data from the Norwegian Mother and Child Cohort Study. Linear and generalised linear models with inverse probability weights and robust standard errors were used to quantify the association between prenatal paracetamol exposure and continuous and categorical outcomes.
Results:
Of the 32 934 children included in our study, 8374 (25.4%), 4961 (15.1%), and 1791 (5.4%) were prenatally exposed to paracetamol in one, two, and three trimesters, respectively. Children exposed to paracetamol in two trimesters scored lower on shyness compared with unexposed children (β -0.62, 95% confidence interval [CI] -1.05, -0.19). Children exposed to paracetamol in three trimesters had a moderate increased risk of internalising behaviour problems (relative risk (RR) 1.36, 95% CI 1.02, 1.80) and borderline externalising behaviour problems (RR 1.22, 95% CI 0.93, 1.60) compared with unexposed children. Children exposed to paracetamol in 2nd/3rd trimester scored lower on shyness (β -0.32, 95% CI -0.66, 0.02) compared with unexposed children. Sensitivity analyses indicated that unmeasured confounders play an important role and may potentially bias the effect estimates away from the null.
Conclusions:
Timing of exposure and short-term use of paracetamol during pregnancy do not seem to pose any substantial risk of the outcomes examined. Although we found an association between paracetamol use in multiple trimesters and lower shyness and greater internalising behaviour in preschool-aged children, we cannot rule out chance or unmeasured confounding as possible explanations for these findings.
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