The risk of medication during in pregnancy
This week saw an episode of Call the Midwife in which a women who was suffering Hyperemesis Gravidarum was given a drug called Thalidomide. The programme is set in the 1960's and while the women suffering portrayed the horrors of hyperemesis very well, the miraculous cure of the drug was perhaps a little overstated... I don't think even Thalidomide had that much of a wondrous effect on full blown HG! Anyway, that's by the by... We all know the devastating effects Thalidomide caused when taken between days 35-50 of pregnancy. It must be historically one of the most Teratogenic drugs (a medication which causes abnormalities in a developing foetus) ever to have been given in pregnancy and it is thanks to this the danger of using treatments without proper analysis and adequate testing was exposed and no longer happens.als.
The damage Thalidomide caused for the victims at the time is well documented and the history and mechanisms of the drug are understood. There is thankfully support for the people affected by it although there is still a long way to go in getting compensation for everyone affected, particularly in some countries such as Ireland.
However, Thalidomide also, albeit indirectly, damaged another massive group of people and still does. Even today it's legacy results in massive foetal loss and significant morbidity for pregnant women suffering, not just hyperemesis gravidarum but a whole host of medical condition in pregnancy. It reduced illnesses and disease, even life-threatening ones, experienced in pregnancy into states which must be borne regardless of risk to mum and baby.
Fear is the problem. Fear and a lack of understanding of the risks of untreated hyperemesis gravidarum.
Much like the fear of many diseases which are vaccinated against has waned since our children no longer die of them, fear of HG has diminished since the introduction of IV fluids. It's now incredibly rare for women to die from HG, but if Call the Midwife was set in the 1920's the character would simply have died, end of storyline.
Thalidomide was given at a time when people didn't realise that things the mother ingested could have an impact on the foetus. In the same way that pregnant women were regularly x-rayed before we realised the x-rays harmed the foetus (EDIT: See comment below by Margaret O'Hara). And is was normal for women to smoke during pregnancy before we discovered the harm it causes. Eating too much liver can cause problems and regular alcohol consumption is harmful.
We've also discovered that a lot of things are absolutely fine in pregnancy: eating strawberries won't cause birth marks; raising your arms above your head doesn't cause the cord to wrap around the foetus's neck; it's okay to eat peanuts (unless you're allergic obviously)... and you know what? Lots of medications are just fine to take in pregnancy!!!
You see we discover new things all the time thanks to science and research. And ironically, it's thanks to Thalidomide that we now look into whether or not a medication is safe in pregnancy, animal studies are done and data is compiled ensuring detrimental effects would be rapidly picked up... this is the positive legacy of the drug that caused so much harm.
Now I'm not saying all medications are fine... there are a number of medications which are absolutely not okay and can increase the risk of abnormalities (Thalidomide being one of them, it's used to treat a number of conditions worldwide today). But just because one medication that was used for nausea and vomiting in pregnancy caused a problem doesn't mean that ALL anti-emetics cause harm.
What we need is information about the risks so that informed consent can be given for women to make choices. There is already a lot of information available about the common anti-emetics used, just because an individual doctor hasn't hear of it's use doesn't mean it's not common or there isn't evidence of it's safety.
In the last week alone I've had the following comments from women who called the Pregnancy Sickness Support helpline:
“In my last pregnancy, after I got out of hospital, my GP told me that the medication they gave me was harming my baby. He took it me off it. I haven't been to a doctor this time as I'm scared”
“My doctor told me nothing is safe to take”
“I asked about steroids but they said they carry too many risks... what are the risk exactly?”
All of these women were suffering shocking levels of morbidity including significant weight loss, dehydration and malnutrition from months of suffering extreme levels of vomiting and constant vomiting. They were all on the brink of depression, two were considering termination as their jobs and homes were at risk. One was beginning to experience relationship problems and all were experiencing high levels of stress.
You see women do not resort to taking medication in pregnancy lightly. In my, fairly extensive experience, I find women are willing to tolerate extreme levels of sickness, which if they were not pregnant would see them in hospital within 48 hours. Yet because they are pregnant it can be weeks, months or never even, that their doctor treats appropriately.
So lets look at the known risks to the foetus for the following medications:
Cyclizine and Promethazine (Avomine) are first line medications which have been around since the time of the Thalidomide disaster and are part of the same group of medications (H1 receptor antagonist antihistamines) which is the main ingredient in a drug licensed for pregnancy nausea and vomiting in the USA and Canada. There is no evidence they cause any harm to the growing foetus at any point in pregnancy and there is lots of evidence that they do not cause any harm.
The next line of medication is metoclopramide, Prochlorperazine(Stemetil or Buccastem), and domperidone (motilium). Again, these medications have been used since the time of Thalidomide without any evidence of harm caused to the foetus and plenty of evidence that no harm is caused.
Ondansetron (Zofran) has been around for 17 years now so can't really be described as “new and unknown” anymore. Trials of high doses in pregnant animals has shown no problems in the foetus's and a study of over 600,000 pregnancies in Denmark found that ondansetron during pregnancy was not associated with a significantly increased risk of birth defects. Despite strong evidence for it's safety I have recently noticed a number of law firms are looking to make some money claiming ondansetron is associated with an increased risk of heart defects. Ironically, in the long term such a law suit could have the opposite effect and result in the drug being licensed if it's found not to cause any harm.
Finally, the current last line of treatment available in the UK is steroids. Steroids are frequently refused for women with hyperemesis and many women are made to feel ashamed for even asking about them. “Goodness no way! Steroids will harm your baby, why would you want to risk your baby?” was a recent comment one woman received.
Steroids are regularly prescribed in pregnancy for the following conditions, to name but a few:
- Rheumatoid arthritis
- Ulcerative Colitis
- Crohn's disease
- Recurrent miscarriage
Interestingly, women discussing taking steroids for those conditions on online forums talk about how their doctor “persuaded them it was safe” and “explained the risks verses benefits” and “said there were no known risks”. Overwhelmingly the doctors are reassuring about their use. Yet women on hyperemesis forums report “my doctor refused steroids and said my only option is termination” or “I asked about steroids but he said they aren't safe”.
So what are the risks? Well, a few studies have shown a possible increased risk of cleft palette if taken early in pregnancy. By increased risk we are talking an increase from 1 in 700 to 1.3 in 700. More recent studies, such as this one from Denmark, which looked at 51,973 pregnancies in which the mother took steroids in the first trimester and found no increased risk. And while we're talking about cleft palette risk it is worth noting that mothers exposed to highly stressful situations in early pregnancy also carry the same increased risk of cleft palette. Other risks are to do with longer term use throughout the pregnancy, such as gestational diabetes and small for dates baby, both of which are a small risk than the risks associated with untreated hyperemesis in the second and third trimester.
Interestingly the dose required for HG management is generally much less than for those other conditions mentioned above.
So why the difference? Is it ignorance? Prejudice? Fear?
Well it boils down to belief in the condition really doesn't it... the conditions mentioned above are all “real” and exist outside of pregnancy, where are HG is caused by pregnancy and therefore is just a “hormonal woman making a fuss” or something along those lines.
The bit I really don't get is why so many doctors seem to throw the evidence base out of the window as soon a women is pregnant?
Why is it okay to just make stuff up about supposed risks instead of having a look at the evidence?
Since when was termination “safer” for the foetus than taking a medication with a possibletiny increased risk of cleft palette?
These are all questions I'm unfortunately unable to answer, but if you are a healthcare professional who would prefer your patient terminated a wanted baby rather than give her a safe and effective medication perhaps you could explain to me why? Is is fear from the Thalidomide disaster? Is it because you don't think she's really that ill? Is it lack of time to look up the evidence? To be fair it's not hard... it's not like you have to drive to a medical library and trawl through the literature... the information is at your fingertips.
The saddest thing about the episode of Call the Midwife on Sunday was how little we have moved on in terms of treatment and understanding of HG since the 1960's. Women still meet midwives who tell them to “put mind over matter and suck a polo mint” while they are rapidly getting more and more dehydrated. Women are still left until the point of collapse, until their oesophagus is torn to shreds, blood vessels in their face burst, hips covered in bedsores and emaciated bodies too weak to stand. The difference now is that instead of looking at the treatments available and their evidence base for safety and efficiency women are denied them. If that storyline had been set today the character would have been encouraged to terminate the baby, especially given the social situation she was in.
Doctors in the 1960's had to prescribe medication with no knowledge of it's risks, no evidence base behind it. But they don't have to do that now... there is plenty of information widely available, they just have to access it.
I've rather waffled on with this post now... but my point is that Thalidomide did enough damage back in the 60's and I'm sure for those affected it still causes unimaginable misery and frustration that it was ever allowed to happen – but enough is enough. We have to stop letting the legacy of Thalidomide continue to cause harm to mothers and babies. From thousands of foetal deaths to lifelong maternal health complications due to untreated HG, the legacy of fear is rife. They aren't asking for a cure for morning sickness... they are asking for safe treatment for a life threatening complication of pregnancy.
For support, information and full references please refer to the Pregnancy Sickness Supportwebsite.
All treatments are also fully discussed in my book Hyperemesis Gravidarum - The Definitive Guide