Thursday, August 11, 2016

Medical Decision Making as a "Patient": Pregnancy Leads to A Trip Down The Rabbit Hole - A Personal Story

My wife is pregnant.  Wanting to be a supportive spouse, I attended the first prenatal visit to see one member of her team of midwives.  (Being a "minimalist" I was, like my wife, fond of the idea of not unnecessarily "medicalizing" the [usually] natural act of labor and birth.)  I realized during that first visit that understanding the intricacies of medical decision making can be a double-edged sword when dealing with practitioners, especially outside of one's specialty.  If ignorance is bliss, 'tis folly to be wise, it is said.  I've come to wonder which is better for you when you get entangled in US healthcare, wisdom or bliss.

During the first visit, we were offered, with an air of agnosticism, a referral for genetic counseling +/- non-invasive prenatal testing (NIPT).  "How accurate is it," I naturally inquired, trying to avoid technical terms such as sensitivity and specificity.  "Something like 99%" came the reply.  So we were given the referral.  But I quickly realized that this was a classic problem of base rates.  The likelihood of a chromosomal abnormality is so low given my wife's age, that even extremely high sensitivities and specificities are inadequate to guide our decision - that is, the test is rendered practically useless because of the low base rates in our case.  And this despite the fact that the sensitivities and specificities of prenatal blood testing are inflated by the way they were derived.  But think of the decision we would have faced had we blindly proceeded with testing without this consideration - given the low base rate, the posterior probability of a chromosomal abnormality such as Down's Syndrome given a "positive" test result would be around 33%.  How would we act on this information?  Is that threshold high enough that we would consider an elective abortion (if we were morally disposed towards that as an option)?  Or would we ignore the information and proceed to term?  And if we were not ethically accepting of elective abortion as a possibility, what other remedy would we have that would justify the information from the testing?  Why would we talk about getting prenatal genetic testing before talking about the choices we may have to face after we receive the results?  Why would not a discussion of remedies, specifically abortion, precede consideration of the testing?  How many couples dive into the rabbit hole only to wonder how they got there and how they can get out?  In this case, we decided that ignorance was indeed bliss, and deferred NIPT.

At that same visit, blood was ordered to be drawn.  I had difficulty understanding why you would need to draw blood from a perfectly healthy woman at 12 weeks gestation.  Blood types and anemia and all that I guessed.  But I was particularly caught by the thyroid testing.  Why are we screening an asymptomatic woman for thyroid disease?  Is that justified by the prior probabilities?  It takes only a google search to learn that ACOG (the American College of Obstetrics and Gynecology) and an endocrine society do not recommend universal testing.  But my questioning why we were doing this was off-putting and frankly unanswerable for the midwife - she was just following the usual routine, whatever her supervisors and mentors had told her to do, without understanding....well without understanding any of this Bayesian mumbo jumbo that I was hinting at.  Alas, thyroid testing, like NIPT, was deferred.  But not for long.

My wife has a sporadic supraventricular tachycardia that affects her while exercising at high altitude.  It causes mild symptoms and usually abates with rest and decent.  She has been meaning to go get a Holter monitor or other testing to confirm that it is AVNRT (atrioventricular nodal reentrant tachycardia which has a probability of 90% or more of being the underlying diagnosis) and then to consider getting it ablated (fixed by burning the short circuit with a heart catheter).  When the midwife learned of this, there was obvious concern and anxiety, and encouragement to see a cardiologist to get it sorted out so they didn't have to worry about it during labor.

I was not a fan of that plan for the same reason I was not a fan of the NIPT - suppose we confirm it is AVNRT, what then?  Are we going to send a pregnant woman for an ablation for a mildly symptomatic disorder that occurs during exercise at altitude to placate the anxieties of the midwife?  And if we're not going to do anything about it, why would we investigate further?  If the probability of a given diagnosis (AVNRT) is 90-95% already, need we know any more to be reasonably confident that we know what we're dealing with?  Does 90% meet or exceed our diagnostic threshold given the options for action at this juncture?

Fan or not, there was a cardiology appointment and thankfully he mostly agreed with me (I was in abstentia) that other than confirming the diagnosis, there was nothing to do during the pregnancy.  But then, out of routine or whatever, he too ordered blood - including that gosh darned TSH.

And, you guessed it.  The TSH is mildly elevated, at 4.5 or so, with a normal T4 (the actual thyroid hormone level.)  Into the rabbit hole we plunge.  The midwife has discovered this result (through the marvels of a highly integrated EMR, Bravo!) and wishes to prescribe a "low dose" of thyroid hormone.  If you google hypothyroidism in pregnancy you will find all sorts of fear-mongering about mental delays and cretins and all sorts of terrifying things.  Isn't it safest to just "replace" the "missing" thyroid hormone with the "low dose" that the midwife wants to use to "normalize" the levels (which in the case of thyroid hormone (T4), the suggested prescription drug, are already normal)?

The quandry we now have is that we have information that we shouldn't have, and it's really not actionable, it just causes anxiety.  While the issue of "subclinical hypothyroidism" in pregnancy is not sorted out, hence the ACOG recommendation to not screen universally, it is said to often "resolve after pregnancy."  So we have mild perturbations in thyroid hormone and THS levels in pregnancy, which spontaneously resolve after pregnancy - sounds like "Pregnant Euthyroid Syndrome" doesn't it?  Who's to know?  All we know is that we have a mildly elevated TSH, and the midwife wants to "treat" to attempt to "normalize" that number, because - well, that's all she knows.

But just how is that going to work?  If my wife's pituitary wanted the T4 to be higher, wouldn't the feedback loop cause the TSH to be higher, thus spurning the T4 higher?  How will the pituitary respond to  the administration of a "small" or subtherapeutic dose of levothyroxine (thyroid hormone)?  Wouldn't this exogenous hormone just interrupt the feedback loop thus leading to further reductions of endogenous thyroid hormone production?  If so, how will a subtherapeutic dose achieve the "normalization" that is sought?  What is the plan for monitoring?  What if "normal" values are not achieved - will the medication be increased?  Withdrawn?  Then what will happen?  Hasn't evolution solved this problem over millions of years, the exceptions being a known disorder of the thyroid such as Hashimoto's or Grave's?

I don't have the answers to these questions, but I know enough to ask them and their corollaries - how do we know that we are doing net benefit here, messing with nature on the basis of the result that we shouldn't have gotten in the first place?  In the absence of empirical data on how to act, my inclination is to ignore the information and not fiddle with the pituitary and the thyroid.  But my poor wife is now torn between her husband, an incisive and curious fellow with just enough knowledge of medical decision making to make him dangerous even outside his specialty, and her well-meaning, if in-over-the-head-a-bit midwife - who ironically was chosen over a conventional OB/GYN based on the presumption of not over-medicalizing the natural process of pregnancy and labor!

Fortunately, none of the decisions we have been forced to face are "Graves" ones and no real harm has been done.  It is just very interesting (and quite concerning also), how little rationality is guiding these routines in medicine, and how incapable the practitioners are of even thinking about whether their routines are rational or of responding to questions about the necessity and utility of the recommended testing and interventions.  And if I'm having a hard time negotiating the system, imagine how difficult it is for the ordinary layperson to avoid iatrogenic cascades.


6 comments:

  1. FWIW, the "average" risk of T21 increases after age 35, and I don't know how old your wife is, but it does occur in younger people. NIPT is lauded for its very high NPV, and I had a positive NIPT at age 33, confirmed by CVS. I knew I would terminate (perhaps different from your scenario), since I am in the medical field and the cardiac abnormalities detected on the subsequent u/s would not have justified carrying to term with all the surgeries that would have been needed--if survived to term at all. I suppose you're not getting the triple tests either? Because, c'mon compared with cfDNA..a composite number of "biomarkers"?? I also contemplated not getting the NIPT for all the reasons you mentioned, statistical probability and "low risk", but in reality am SO happy I did. I got it for all my subsequent pregnancies (well, was considered at risk at that point), but it was very reassuring and the reduced anxiety in subsequent pregancies was very worth it.

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    1. Since she is 28, her risk is on the order of 1/1200, let's round up to 1/1000. We can use my lovely Bayes Theorem calculator on the sidebar of the blog and put in .001 for the prior and I'll go out on a limb and put .999 (or 99.9%) for sensitivity and specificity, along with 1000 for the population size.

      Doing this, we see that the 1/1000 chance is reduced to .000001 with a negative test (the high NPV you referred to), and a positive test makes it 50/50. We also can add up positive tests (2) and negative tests (998) to see what is the probability we will be faced with either of those results. There is a .998% chance we will be delivered a negative result, which is almost the same as the .999% chance that we will have a child without DS WITHOUT TESTING!

      The issue is what you would do with the unlikely positive test. I guess amnio or CVS as you mentioned and all that.

      Consider this - we're both motorcycle riders. So our risk preferences probably don't comport with the average doctor's and nurse's risk preferences.

      I also estimate that in a few years if we're still having kids, we may revisit these numbers, especially in light of any new data or technology.

      Thanks for your comment!

      SKA

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    2. The main point is how educated is your provider which is sad that many patients will never know because they are not as invested in their care (or their wifes care) as are you... as a physician, I know that NIPT is not recommended by ACOG in a low risk patient (ie 28 year old like your wife) due to exactly your point. It is recommended for high risk woman (ie >35 yo, prior child with T21/18/13). many believe the "less specialist" someone is, the less tests they order which is not the case, many specialists, (ie cardiologists and mfm/genetic counselors) would not have made the recommendations of your CNM due to knowledge of other areas. just an observation. Every provider has their strengths, I just think we often do a poor job presenting them to our patients and also our inability to educate patients of our ignorance. Your CNM will likely do great for birthing process but the prenatal nuances are not her strength. Its great that you are there to help your wife, hope all goes well with the pregnancy.

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  2. As a physician, a long-time reader of your blog, and a husband with a pregnant wife, I can say I totally relate. My wife has also been to the cardiologist! It would be funny if it weren't so frustrating and occasionally consequential.

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  3. Much of our population at large is vitamin D deficient. Some say that the majority is insufficient. Pregnant women are more likely to be low on D than the general run, but it's more important for her to be at least sufficient than for the general run. And, afterwards, mother's milk is notoriously low in D. D for two.
    Have you tested for that? It might be more important than the tests that have been done. More important, that is, for your wife than for her midwife.
    What does Bayes say?

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  4. The synthroid was declined and the repeat TSH was normal. Now consider the counterfactual possibilities: synthroid was given and TSH was normal - the desirable result would be attributed to the synthroid; synthroid was given and it threw the feedback loops out of whack - then we'd be running around stressing about it and adjusting doses and chasing our tails.

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