Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstetrique et gynecologie du Canada : JOGC · 2025
The Debate on Acetaminophen Use in Pregnancy and Neurodevelopmental Disorders: Facts or Fiction?
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Pleau Justine, Leal Lisiane F, Sheehy Odile, Bérard Anick
Аннотация
OBJECTIVES: This study aimed to determine if the use of acetaminophen alone and in combination during the second and third trimesters of pregnancy is associated with the risk of attention-deficit/hyperactivity disorder (ADHD) in children, and to evaluate uncertainty from exposure and outcome misclassification.
METHODS: We included all singleton live births from the Quebec Pregnancy Cohort between January 1, 1998, and December 31, 2013. Maternal acetaminophen use was identified through filled prescription data, and children were classified into 3 exposure groups: (1) unexposed, (2) exposed to acetaminophen alone, and (3) exposed to acetaminophen in combination with other medications during the second or third trimester of pregnancy. ADHD was assessed in children aged ≥2 years using a validated algorithm: 2 diagnostic codes, 2 filled prescriptions for ADHD medication, or 1 diagnostic code plus 1 filled prescription. To address potential non-differential exposure and outcome misclassification, we conducted a probabilistic bias analysis using individual-level data, which represents the central contribution of this study.
RESULTS: Among the 182 775 children included, 1.0% were exposed to acetaminophen alone and 2.2% to acetaminophen in combination with other medications. In Cox proportional hazard models, acetaminophen use in combination was associated with increased risk of ADHD (adjusted hazard ratio 1.17; 95% CI 1.06-1.29), while acetaminophen alone showed a weaker association (adjusted hazard ratio 1.09; 95% CI 0.94-1.27). Probabilistic bias analysis demonstrated that these estimates might be biased away from the null.
CONCLUSIONS: Our findings suggest that the observed relationship might be partly explained by exposure and outcome misclassification.
METHODS: We included all singleton live births from the Quebec Pregnancy Cohort between January 1, 1998, and December 31, 2013. Maternal acetaminophen use was identified through filled prescription data, and children were classified into 3 exposure groups: (1) unexposed, (2) exposed to acetaminophen alone, and (3) exposed to acetaminophen in combination with other medications during the second or third trimester of pregnancy. ADHD was assessed in children aged ≥2 years using a validated algorithm: 2 diagnostic codes, 2 filled prescriptions for ADHD medication, or 1 diagnostic code plus 1 filled prescription. To address potential non-differential exposure and outcome misclassification, we conducted a probabilistic bias analysis using individual-level data, which represents the central contribution of this study.
RESULTS: Among the 182 775 children included, 1.0% were exposed to acetaminophen alone and 2.2% to acetaminophen in combination with other medications. In Cox proportional hazard models, acetaminophen use in combination was associated with increased risk of ADHD (adjusted hazard ratio 1.17; 95% CI 1.06-1.29), while acetaminophen alone showed a weaker association (adjusted hazard ratio 1.09; 95% CI 0.94-1.27). Probabilistic bias analysis demonstrated that these estimates might be biased away from the null.
CONCLUSIONS: Our findings suggest that the observed relationship might be partly explained by exposure and outcome misclassification.