ArticleAmerican journal of epidemiology2019
Use of Negative Control Exposure Analysis to Evaluate Confounding: An Example of Acetaminophen Exposure and Attention-Deficit/Hyperactivity Disorder in Nurses' Health Study II.
Article in American journal of epidemiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
28 citing papers in PubMed, 2 syntheses or guidelines pooled it, 49 citations in OpenAlex.
- Evaluation of the evidence on acetaminophen use and neurodevelopmental disorders using the Navigation Guide methodology.Environmental health : a global access science source · 2025Pooled it
- Pooled it
- Partisan differences in acetaminophen use after revised federal guidance in the United States.Public health · 2026Article
- Paracetamol in Pregnancy: Uncertain Evidence, Certain Consequences.The Medical journal of Australia · 2026Article
- Environmental Chemicals and Maternal Depression During and After Pregnancy: a Scoping Review.Current environmental health reports · 2026Article
- Exposure to Acetaminophen (Paracetamol) during Pregnancy and Childhood Cancer: A Population-Based Cohort Study in Taiwan.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2026Article
- The effects of tv/video viewing hours on later ADHD symptoms: a counterfactual analysis in longitudinal population-representative data.BMC pediatrics · 2025Article
- Paternal and Maternal Exposures to Per- and Polyfluoroalkyl Substances and Child Behavioral Difficulties: A Parental Comparison Study.Environmental science & technology · 2025Article
- Preconception and first trimester exposure to pesticides and associations with stillbirth.American journal of epidemiology · 2025Article
- Neuromodulation for Headache Management in Pregnancy.Current pain and headache reports · 2025Review
- Examining the relationship of acetaminophen use during pregnancy with early language development in children.Pediatric research · 2024Article
- The State of Use and Utility of Negative Controls in Pharmacoepidemiologic Studies.American journal of epidemiology · 2024Review
- Sex-specific neurobehavioral and prefrontal cortex gene expression alterations following developmental acetaminophen exposure in mice.Neurobiology of disease · 2023Article
- The Main Changes in Pregnancy-Therapeutic Approach to Musculoskeletal Pain.Medicina (Kaunas, Lithuania) · 2022Review
- A Systematic Review of the Link Between Autism Spectrum Disorder and Acetaminophen: A Mystery to Resolve.Cureus · 2022Review
- Paracetamol use during pregnancy - a call for precautionary action.Nature reviews. Endocrinology · 2021Review
- Paracetamol (Acetaminophen) and the Developing Brain.International journal of molecular sciences · 2021Review
- Perinatal Acetaminophen Exposure and Childhood Attention-Deficit/Hyperactivity Disorder (ADHD): Exploring the Role of Umbilical Cord Plasma Metabolites in Oxidative Stress Pathways.Brain sciences · 2021Article
- Acetaminophen use during pregnancy and offspring attention deficit hyperactivity disorder - a longitudinal sibling control study.JCPP advances · 2021Article
- Behavioral Problems at Age 11 Years After Prenatal and Postnatal Exposure to Acetaminophen: Parent-Reported and Self-Reported Outcomes.American journal of epidemiology · 2021Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
Frequent maternal use of acetaminophen in pregnancy has been linked to attention-deficit/hyperactivity disorder (ADHD) in children, but concerns regarding uncontrolled confounding remain. In this article, we illustrate use of the negative control exposure (NCE) approach to evaluate uncontrolled confounding bias in observational studies on pregnancy drug safety and explain the causal assumptions behind the method. We conducted an NCE analysis and evaluated the associations between maternal acetaminophen use during different exposure periods and ADHD among 8,856 children born in 1993-2005 to women enrolled in the Nurses' Health Study II cohort. Information on regular maternal acetaminophen use was collected prospectively in biennial questionnaires. A total of 721 children (8.1%) in the cohort had been diagnosed with ADHD as reported by the mothers. Our NCE analysis suggested that only acetaminophen use at the time of pregnancy was associated with childhood ADHD (odds ratio = 1.34, 95% confidence interval: 1.05, 1.72), and the effect estimates for the 2 NCE periods (about 4 years before and 4 years after the pregnancy) were null. Our findings corroborate those of prior reports suggesting that prenatal acetaminophen exposure may influence neurodevelopment. The lack of an association between acetaminophen use in the pre- and postpregnancy exposure periods and ADHD provides assurance that uncontrolled time-invariant factors do not explain this association.
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Registered trials
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