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The study was conducted in collaboration with the University of California, Los Angeles; University of Massachusetts Lowell; and Harvard T.H. Chan School of Public Health.

The study, published today in BMC Environmental Health, is the first to apply the rigorous Navigation Guide methodology to systematically evaluate the rigor and quality of the scientific literature.

The study was conducted in collaboration with the University of California, Los Angeles; University of Massachusetts Lowell; and Harvard T.H. Chan School of Public Health.

While the study does not show that acetaminophen directly causes neurodevelopmental disorders, the research team’s findings strengthen the evidence for a connection and raise concerns about current clinical practices.

The researchers call for cautious, time-limited use of acetaminophen during pregnancy under medical supervision; updated clinical guidelines to better balance the benefits and risks; and further research to confirm these findings and identify safer alternatives for managing pain and fever in expectant mothers.

So the Navigation Guide is apparently a methodology used to assess and screen for flaws and biases in studies selected for meta analyses, and this is the first time it has been used in a published study.

My guess: it uses AI to screen these studies. Would be interested to see any peer reviewed studies on the Navigation Guide itself.

Evaluation of the evidence on acetaminophen use and neurodevelopmental disorders using the Navigation Guide methodology

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Methods
We applied the Navigation Guide methodology to the scientific literature to comprehensively and objectively examine the association between prenatal acetaminophen exposure and NDDs and related symptomology in offspring. We conducted a systematic PubMed search through February 25, 2025, using predefined inclusion criteria and rated studies based on risk of bias and strength of evidence. Due to substantial heterogeneity, we opted for a qualitative synthesis, consistent with the Navigation Guide’s focus on environmental health evidence.

Results
We identified 46 studies for inclusion in our analysis. Of these, 27 studies reported positive associations (significant links to NDDs), 9 showed null associations (no significant link), and 4 indicated negative associations (protective effects). Higher-quality studies were more likely to show positive associations. Overall, the majority of the studies reported positive associations of prenatal acetaminophen use with ADHD, ASD, or NDDs in offspring, with risk-of-bias and strength-of-evidence ratings informing the overall synthesis.

Conclusions
Our analyses using the Navigation Guide thus support evidence consistent with an association between acetaminophen exposure during pregnancy and increased incidence of NDDs. Appropriate and immediate steps should be taken to advise pregnant women to limit acetaminophen consumption to protect their offspring’s neurodevelopment.

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Summary of assessments
We used the Navigation Guide methodology to rate studies based on several metrics. The risk of bias within each study was assessed using the GRADE approach to grade study characteristics that can introduce systematic errors in the magnitude or direction of the results. We rated each study for risk of bias, including participant recruitment/selection, blinding during the study, exposure assessment methods, outcome assessment methods, methods to address incomplete data, selective outcome reporting, and conflict of interest. We ranked each study on each parameter: 1 indicated low risk of bias, 2 indicated probably low risk of bias, 3 indicated probably high risk of bias, and 4 indicated high risk of bias. We calculated an average bias score for each study. For the ‘blinding during the study’ domain, observational studies were rated as high risk of bias (score of 4) when knowledge of the outcome could influence exposure reporting. For instance, retrospective studies relying on maternal self-reports of acetaminophen use collected after a child’s neurodevelopmental disorder diagnosis were rated high risk due to potential recall bias. Prospective designs or biomarker-based assessments mitigated this bias in higher-quality studies.
Deviations from scoring—such as inconsistencies in study methodology, incomplete data reporting, or challenges in applying bias criteria—were addressed through a structured process. During the study selection and data extraction phase, studies were triaged by title, abstract, and full text; two reviewers (AB and DP) independently assigned a score for each Navigation Guide category. Any deviations, such as studies with atypical designs or potential biases, were flagged for further evaluation. To handle these deviations, we conducted sensitivity analyses to assess their impact on the overall findings. Specifically, we performed two analyses: (1) excluding the lowest-scoring studies to evaluate their influence on the results, and (2) re-weighting confounding domains to address potential bias over- or underestimation.

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… The study, published today in BMC Environmental Health, is the first to apply the rigorous Navigation Guide methodology to systematically evaluate the rigor and quality of the scientific literature. …