Not to mention "The journal is affiliated with the North American Fuzzy Information Processing Society (NAFIPS)" !!

As a post script, I also want to say that I find the “medically necessary” language around APAP use ridiculous and insulting. Do they think pregnant women are taking acetaminophen for fun? Or mistaking the pills for candy?

PPE 2019 study: onlinelibrary.wiley.com/doi/full/10.1111/ppe.12568

IJE 2015 study: academic.oup.com/ije/article/...

You wouldn’t know it from this thread, but other people have opinions about APAP in pregnancy and neurodevelopmental outcomes. @perdamkier.bsky.social in particular has written a lot about the topic, including this piece: onlinelibrary.wiley.com/doi/10.1111/...

...for specific conditions during pregnancy. Active comparator designs would strengthen these types of studies significantly, particularly for conditions where “no treatment” is not a realistic or ethical recommendation.

People taking high doses of APAP for long periods of time aren’t irresponsible, they’re desperate. Most frustratingly, APAP isn’t a particularly good drug for chronic pain conditions. All of which is to say: I think research needs to focus more on comparing clinically meaningful treatments...

And in this small study done in a single hospital in Norway, we saw many women switching from previous migraine treatments to APAP, and reporting high levels of pain not managed by APAP: bmcpregnancychildbirth.biomedcentral.com/articles/10....

But it is critical to understand what is driving high-dose, long-duration APAP use in pregnancy. In this descriptive study of migraine in pregnancy, we saw decreasing use of other drugs and increases in APAP: journals.sagepub.com/doi/10.1177/...

My pet hypothesis, for which I only have indirect evidence, is something like this: I think it is possible that very high doses of APAP over extended periods of time (i.e., 500+mg daily for multiple weeks) could cause neurodevelopmental differences in exposed fetuses.

Why is acetaminophen so hard to study? Reason 4: dose, duration, and timing of use are likely important, which amplifies the measurement problem (Reason 1), makes the confounding problem worse (Reason 2), and is further hampered by the selection problem (Reason 3).

...how do we think about the counterfactual here? The children with prenatal APAP exposure might not have been born, had their parent not used APAP.

Why is acetaminophen so hard to study? Reason 3: studies of neurodevelopment almost always condition on a live birth. But untreated fever in early pregnancy can lead to miscarriage, so...

...much of the use for pain conditions is among people who were managed on a different (more effective) drug before pregnancy and then switched when they became pregnant.

Why is acetaminophen so hard to study? Reason 2: there is a huge range of reasons for using APAP, all of which have different relationships with neurodevelopment. People take APAP for pain and fever, yes, but...

Some studies have used biomarkers (urine, meconium), but APAP is metabolized quickly so these measures are only a snapshot for specific time windows.

Why is acetaminophen so hard to study? Reason 1: it’s hard to measure. Acetaminophen (APAP) is available over the counter and by prescription, alone or in combination with other medications. Studies often rely on parental recall, which varies in accuracy, or prescription fills, which miss OTC use.

I’ve also written a commentary about some of the challenges (posted here by @dremilyrsmith.bsky.social ) bsky.app/profile/drem...

I’ve published 2 papers on acetaminophen in pregnancy and neurodevelopmental outcomes, both as methods supervisor for a doctoral student who was the first author, from the MoBa study. I’ll drop the links at the end of the thread- both are open access either via PMC or the journal website.