Comment by fifteenforty | Hacker News Reader

Comment by fifteenforty | Hacker News Reader

Anaesthesia trainee here (doctor, similar to an anesthesiology resident in US vocabulary)

I've read the actual referenced paper and not the LA times piece.

This type of research is hypothesis generating. As they acknowledge, this shows a correlation, not causation. The big question here is why were these women taking paracetamol/acetaminophen? Was it the drug or the cause of their pain/fever/discomfort that is more relevant to the outcomes observed?

As part of a cohort study, this was just one outcome measured. It is not clear to me whether this was a outcome measure they had intended to analyse from the outset or whether it was post-hoc. This makes a huge difference to the credibility of the finding

With regards to the relative safety of paracetamol and ibuprofen, well, they are totally different drugs. For most healthy, young people, in short courses both will cause little harm, with paracetamol having the edge in safety. Ibuprofen causes significant, undetected kidney and gastrointestinal injury. Paracetamol can cause liver failure, but generally only in overdose, prolonged use or when associated with poor nutritional intake. A healthy person taking the odd dose will not develop liver toxicity. Prolonged administration of ibuprofen will invariably cause damage. For paracetamol it is less clear.

Source: I prescribe and manage these drugs and their side effects daily. Pain management is a core part of my day job.

fifteenforty buries one of the biggest potential issues in his 4th para, so I'm going to highlight it: its not clear if this correlation was found post-hoc or not. If you measure 10 factors and 10 outcomes then you have a potential 100 different correlations. If you assume that any correlation where p<0.05 is significant then you are going to get 5 "significant" correlations just by chance. The summary talks about how they didn't find correlations with acetaminophen before and after pregnancy, so that's 3 distinct factors just there.

> they didn't find correlations with acetaminophen before and after pregnancy, so that's 3 distinct factors just there

No, it's perfectly valid for a drug to only have affect on the growing fetus but where there were not studies proving harm to the child or adult, e.g. Thalidomide.

Also, what they're correlating is memory of paracetamol usage, not actual usage. I'm not sure I remember if I used paracetamol the past 3 months. It may well be that more severe pain (or other) symptoms are more easily remembered, so that their "paracetamol" usage is actually correlated with severity of symptoms, and not entirely with actual usage.

Frankly, I think the summary in that article is a little irresponsible: selling your research a little is normal, but this really asks to be misinterpreted.

Edit, the article summary I'm referring to is:

Children exposed to acetaminophen prenatally are at increased risk of multiple behavioral difficulties, and the associations do not appear to be explained by unmeasured behavioral or social factors linked to acetaminophen use insofar as they are not observed for postnatal or partner’s acetaminophen use. Although these results could have implications for public health advice, further studies are required to replicate the findings and to understand mechanisms.

what they're correlating is memory of paracetamol usage, not actual usage.

According to the article:

"Finally, the authors of the study acted to avoid a common problem with research that links adverse pregnancy outcomes to certain medications: that women whose children have some identifiable problem are more likely to recall taking medications during pregnancy. The current study asked women when they were pregnant about their medication use, and then — seven years after her child’s birth — asked her to assess her child’s emotional and social well-being and report a range of problematic behaviors."

But they asked during pregancy what their medicine use was up to three months ago. For a relatively mundane task like taking paracetamol, I think it's reasonable to question how reliable memory is at that point. Especially since this may be a stressful time with lots of things going on - I can imagine that a pill to make a headache go away is easily forgotten. Or: was that 2 or five months ago?

My reading of the study was that the indication measured was if the mother had remembered taking Acetaminophen and not a direct measure of her actual Tylenol intake. So the study should read "mothers who remembered their drug intake have a slightly elevated risk of attention deficit children."

Good point. It adds yet another layer of uncertainty to the findings.

Supposing this study is further replicated and one wished to avoid paracetamol during pregnancy, what alternatives for pain relief would be recommended?

Well, that depends on your individual attitude to the relative risks of each drug. I realise that answer sounds unhelpful, but the alternatives all have risks. Opioids (and tramadol, a opioid that also has other effects) have been variably associated with birth defects, but the evidence is not conclusive[1].

[1] http://www.ajog.org/article/S0002-9378(10)02524-X/abstract

Given how taxing these types of drugs are, why are opiates not an option for most people? They don't cause any long or short-term damage to organs.

Fears about addiction, and a huge dispute over how well-founded those fears are.

Which is slightly odd, considering we had something like 100 years during which codeine, cocaine, heroin, morphine, and a whole bevy of other currently-scheduled drugs were sold essentially unregulated, over the counter and at every county fair in patent medicines. Surely there must be some data there that some conclusions could be drawn from.

Without careful prescription and monitoring, they are certainly more dangerous than the so-called "simple" analgesics (paracetamol/acetaminophen and the NSAIDs). Each year there are many deaths related to prescription opioids[1] and they do result in long-term damage.

Some commenters here seem to like codeine. It should be considered at least as dangerous as morphine (which it is metabolised to). Depending on your genetic background, you may poorly metabolise codeine (causing it to be ineffective), or you may metabolise codeine too effectively (causing it to cause respiratory depression, low oxygen levels and possibly death). The tide is gradually moving against it[2], but not quickly enough in my opinion.

With all pain, the safest treatments don't involve drugs.

[1] http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6450a3.htm [2] http://www.nps.org.au/publications/health-professional/healt...

This site talks about the problems of opioids for long term pain.

https://rcoa.ac.uk/faculty-of-pain-medicine/opioids-aware

The medical community tends not to talk about addiction, but tolerance.

People prescribed opiates for long term pain develop a tolerance for those opioids, and thus need more to get the same pain relief effect.

Those patients then end up on very high doses of multiple opiates (which is almost certainly causing them harm, and poses significant risk of suicide, or accidental death (of them or people around them)) and still in pain.

People with long term pain deserve better treatment - rapid access to pain management clinics; access to the wide variety of meds combined with psychological therapy and home adaptations. And, yes, opioids if those are the right choice.

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