Systematic Review and Meta-Analysis: Acetaminophen Use During Pregnancy and the Risk of Neurodevelopmental Disorders in Childhood
Bibliographic record
Abstract
OBJECTIVE: To explore the association between acetaminophen use during pregnancy and the risk of neurodevelopmental disorders (NDDs) in children. METHOD: ) with 95% confidence intervals were calculated in random-effects meta-analysis by type of NDD. We performed sensitivity analysis including a bounding method (E-value) and probabilistic bias analysis. RESULTS: = 1.17, 95% CI = 1.08-1.27). The estimated E-value of 1.61 suggests that the observed association may be partly due to unmeasured confounders. Non-differential exposure misclassification biased results toward the null and differential misclassification potentially biased them away from the null. Similar results were observed when assessing outcome misclassification. Acetaminophen use during pregnancy was not associated with the risk of autism spectrum disorder (ASD) when considering physician-based diagnoses (OR = 1.10, 95% CI = 0.98, 1.24; 2 studies; ASD 69,611, n exposed 222,096, E-value = 1.43). No significant increase in the risk of other NDDs was observed. CONCLUSION: Gestational exposure to acetaminophen was associated with a small increased risk of ADHD, which was attenuated in sensitivity analyses. Further studies are needed to examine this association more robustly. PLAIN LANGUAGE SUMMARY: Concerns have been raised about the possible risk of neurodevelopmental disorders in children exposed to acetaminophen in utero. This study conducted a systematic review and meta-analysis of 16 studies with over 2.5 million participants and found a small increased risk of attention-deficit/hyperactivity disorder (ADHD), though this may be due to unmeasured factors or reporting errors. No increased risk was found for other neurodevelopmental disorders, including autism. Findings suggest cautious interpretation for clinical guidance. STUDY REGISTRATION INFORMATION: Acetaminophen use during pregnancy and the risk of neurodevelopmental disorders (NDDs) in childhood: A Systematic Review and Meta-Analysis Protocol; https://www.crd.york.ac.uk/PROSPERO/view/CRD42024566964; https://osf.io/7rcqe DIVERSITY & INCLUSION STATEMENT: One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. We actively worked to promote sex and gender balance in our author group. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. While citing references scientifically relevant for this work, we also actively worked to promote sex and gender balance in our reference list. While citing references scientifically relevant for this work, we also actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our reference list.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.009 | 0.036 |
| Meta-epidemiology (narrow) | 0.003 | 0.002 |
| Meta-epidemiology (broad) | 0.014 | 0.043 |
| Bibliometrics | 0.004 | 0.005 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.004 | 0.002 |
| Open science | 0.002 | 0.002 |
| Research integrity | 0.003 | 0.003 |
| Insufficient payload (model declined to judge) | 0.004 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".