Multiple Miscarriage, MTHFR and Pharmacogenomics: Our Story

… this raises a huge question… How many other drugs are we prescribing to patients, without understanding their genome, that not only won’t help them, but might cause harm?  Pharmacogenomics (the study of how drugs interact with specific genomes) isn’t some nebulous idea that might become useful to medicine in 10+ years time.  Clinicians desperately need to start taking account of patient’s genetics as they prescribe medications right now.  How many adverse drugs events and hospital admissions could be averted by this approach?

 

In a recent post I shared the story of how my wife and I battled through two very difficult pregnancies with severe hyperemesis gravidarum, and how Digital Health Communities (particularly helpher.org) helped us triumph through one of the most difficult times in our lives.

Today I wanted to share the second chapter in this story, which has been hard to write, as it is deeply personal and still a little raw…

 

Following two very difficult pregnancies but two wonderful children (now 8 and 6), my wife and I decided that we were prepared to risk it one more time, and to try for another child, knowing that she would likely suffer from hyperemesis again.  We thought we were ready to deal with whatever was thrown at us.  Little did we know…

In the last two years my wife has suffered five miscarriages.  All have occurred at 6-9 weeks, but it has been a deeply painful time for us.  Miscarriage brings a strange form of grief – in some ways it doesn’t feel like legitimate grief since you don’t know the little person that you’re grieving.  But nevertheless, it is real, and it hurts.  I know that many people reading this will know how it feels.  Early miscarriage is very common, but not something many people feel able to talk about.

As you might imagine, in addition to trying to process what has happened, we’ve also been looking for medical answers.  Why has this been happening?

In looking for answers, both my wife and I have had a number of tests.  One of the tests that my wife had (ordered by her GP) was for her MTHFR gene status.  MTHFR stands for methylene-tetrahydrofolate reductase.  This gene is responsible for creating an enzyme that converts the folate in your diet into the active form that your body needs (5-Methyltetrahydrofolate) – see the diagram below for an explanation of how this works…

 

methylation-cycle

 

An MTHFR genetic test looks for certain variations in the MTHFR gene.  If these variations are present, it reduces that person’s ability to ‘methylate’ folate, i.e. to convert dietary folate or folate supplements into the active form required by the body.  The capacity to ‘methylate’ can be reduced by 30-70%, depending on which variations are present in a person’s genetics.  It turns out that my wife has some of these variations in her genome, affecting her ability to ‘methylate’ folate.

Now, when women are trying to get pregnant, they are strongly advised to take folate supplements, to prevent against conditions occurring in the baby such as spina bifida.  In Australia, folate supplements typically take the form of folic acid, which is a synthesised form (i.e. not a naturally occurring form) of folate.

However, the ability of a woman’s body to convert folate into its active form can vary significantly, depending on MTHFR gene variant status.  In the event that a woman has reduced ability to process folate, this can result in a build up of folate in the blood and cells that has been linked to multiple miscarriage, also known as recurrent pregnancy loss.  To make matters worse, the current clinical guidelines in Australia, in response to recurrent pregnancy loss, are to take higher dosages of folate, which can make the problem worse!

So taking folate, specifically folic acid, can be good or bad, depending on your genome.  In some cases its the right thing to do.  In other cases, it’s causing harm.  And you can’t know which unless you know the MTHFR status of the woman that you are prescribing to.  That’s right.  The blanket advice to all pregnant women to take folic acid can actually cause harm.

In the US, the response has been to prescribe pre-methylated folate, removing the dependence on the woman’s MTHFR status and making the process of taking folate much safer.  Australia has not yet adopted these guidelines.

For me this raises two huge questions:

  1. How many other drugs are we prescribing to patients, without understanding their genome, that not only won’t help them, but might cause harm?  Pharmacogenomics (the study of how drugs interact with specific genomes) isn’t some nebulous idea that might become useful to medicine in 10+ years time.  Clinicians desperately need to start taking account of patient’s genetics as they prescribe medications right now.  How many adverse drugs events and hospital admissions could be averted by this approach?  It could be an amazing lever for health system efficiency, and the cost of genetic testing could easily be recovered through the efficiency savings that i just outlined.  In fact, I foresee a day in the not too distant future when a patient’s genome is front and centre of their health record.
  2. How does medical knowledge about areas such as genetics get distributed to the medical front line?  Our first hand experience has been that many clinicians not only know almost nothing about genetics, but don’t seem interested in considering it.  In fact, my wife’s GP (who ordered the MTHFR test in the first place) recommended that we go and speak to a naturopath, as she didn’t know what to make of the result.  It concerns me that some clinicians are so dismissive of things that they don’t understand, leaving patients to fend for themselves.  You see, we don’t expect doctors to know everything, just to help us navigate the unknown.  Not knowing the answer is not a weakness – just a recognition that the human body is incredibly complex, that medical knowledge is developing at an incredible rate, and that some of the things we used to “know” turn out not to be true…

 

As a result of the MTHFR test, and what we’ve learned subsequently from resources like mthfr.net, my wife is now taking folinic acid (a pre-methylated folate) instead of folic acid.  We’re not there yet, but we’re still hopeful that having another child is a possibility for us…

 

One Response to“Multiple Miscarriage, MTHFR and Pharmacogenomics: Our Story”

  1. Pharm Osazone
    October 16, 2016 at 7:37 am #

    Thank you so much for this piece of genius. You have effectively outlined the basic problems with clinicians today. “Not knowing the answer is not a weakness” should be the right path for medical practitioners to acquire more knowledge in dealing with new and seemingly stubborn cases. May God grant you and your wife a third bundle of joy.

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