Presentation of uncertainty

The context of uncertainties surrounding the newer AEDs required women to make decisions concerning treatment recommendations based on limited or no knowledge of

the teratogenic risks. Two main sources of uncertainty were discussed by women, relating to: the uncertainty of AED effectiveness; and the uncertainties in predicting pregnancy risk as a consequence of in utero exposure to AEDs and/or seizures. The following participant exemplifies the former concept, as she describes her approach to locating evidence as part of her preparations for pregnancy:

FG57: There’s no one in this world that actually knows the answers to everything about epilepsy. There are still people researching it, studying it. We will never know I don’t think. All we can do is just trial and error with medication. (22 year old)

During consultation, discussions of pregnancy risk often highlighted ongoing research emphasising the delays associated with gathering information on adverse events, a point emphasised by one clinician:

127. C: We don’t really know, because the drugs are relatively new and 128. there are not many women who have been exposed to these drugs 129. during pregnancy, because they are relatively new.

[…]

180. C: … it takes decades to find out properly… (OI12; 30 year old).

The lack of research to provide meaningful evidence to direct epilepsy management was illustrated by the following clinician:

296. C: […] we haven’t actually carried 297. out a study where we are looking specifically at the dose. But we do 298. have this gut feeling, or this, I think we feel that it’s dose dependant.

(OI07; 32 year old)

The nature of medical research was also called into question, both in relation to the length of time required to detect rare adverse events, and the ethical limitations on the type of research designs possible:

956. C: […] we can’t really do randomised controlled trials 957. in humans in this subject. And also we need a long time to 958. follow the children (OI23; 30 year old)

The clinician extrapolates the limited evidence on newer AEDs such as levetiracetam (Keppra):

265. C: […] Keppra we don’t know so much about in animal 266. studies; we know that it doesn’t cause problems in the babies of rats 267. and mice, but that does not necessarily mean that it’s going to be a 268. safe drug in adults. (OI02; 22 year old)

Utilizing the UK Epilepsy and Pregnancy Register as a source of reference the clinician extends the account of uncertainty in human testing, and the ever-changing numbers of in utero AED exposures. The clinician provides reassurance about drug safety (by making reference to the human children born to mothers) resulting in the presentation of a kind of ‘pseudo-certainty’ (lines 173 & 180-1), which is used to defend the lack of certainty that problems could still occur:

149. C: […] And the difficulty we’ve got is these other tablets, these newer 150. tablets. We don’t really know for certain where they lie between the 151. tablets that might be very safe and the tablets that are very

152. dangerous. But, what we know so far is that the Keppra tablet seems 153. to be a pretty safe one.

154. P: Right […]

168. C: …These numbers are always changing,

169. but I think there’s about a hundred women so far, who have children 170. only taking Keppra, […]

[…]

173. C: … And so far, none of them, have had any problems… […]

180. C: … it seems to be as far we can tell, a reasonably 181. safe drug, we can’t give you a hundred per cent guarantee…

(OI13; 28 year old)

The difficulty applying population data to predict individual patient risks emphasizes the uncertain outcome of changing treatments:

112: C: […] we could reduce topiramate a bit and 113. see what happens. Or put you on an entirely new drug which is 114. something we wouldn’t do in pregnancy, but you could try and do it 115. now, but, then it is totally unknown territory, you have never used 116. anything other than these two drugs before, and we don’t

117. know if your seizures would be worse or better. (OI14; 27 year old)

The following extract illustrates the uncertainty when extrapolating individual patient risks from epidemiological modelling from trial data on the risk of seizure relapse:

215. C: […] What’s more difficult to

216. predict is whether you fit into that 20% who maybe have an 217. increased risk or not. The fact that you haven’t had any seizures 218. after being on medication, is a potentially good sign, it’s

219. obviously been easy to control and so it’s well controlled.

220. But again, nobody could guarantee that you wouldn’t have a seizure, OI15 (NP, 33 year old)

A further example of uncertainty was raised by women questioning the potential to ‘pass on’ epilepsy. The risk of a child inheriting epilepsy was a subject of discussion for 40 participants, and women raised questions in seven of the observed consultations. The inheritance risk was presented as complex and dependent on a number of factors including, whether one or both parents had epilepsy and the type of epilepsy. Risks were presented by clinicians as uncertain and therefore an unquantifiable risk. However, one woman constructed her personal risk:

FG122: It is a risk that people take, isn’t it. Fifty percent of one parent is epileptic and more so if you have got two parents that are epileptic that the child will be… that’s just like a risk, you know a risk factor that they could be (43 year old, two children)

In the case of participant OI20, she reflected on earlier meetings with clinicians where the provision of information about the life-time prevalence of epilepsy provided reassurance:

OI20: I was talking to the [clinician] and she said everybody has got a 5% chance of getting epilepsy, so I really wouldn’t worry about it. Because I was thinking, oh is my baby going to be born with what I’ve got and she said don’t worry, she said everybody has their risks, so don’t be panicking about this, that and the other, and I was thinking when you put it like that it makes sense though doesn’t it? (30 year old)

The above quote emphasises the search for meaningful risk information – which this patient felt enabled her to interpret the risk as small, and manage her personal worries concerning her future child’s genetic inheritance. Similarly, in the case of FG122, although she had calculated a higher personal inheritance risk, she also drew comfort on the probability that it might not occur suggesting her estimate represented “a risk factor” rather than statement of fact. In contrast, OI13 expressed worries about her ability to cope in response to the clinician emphasising the concept of genetic endowment, implicating the patient as the sole contributor to the risk of her child inheriting epilepsy:

49. C: So, and so there is nobody else in the family with epilepsy? 50. P: No

51. C: And your husband to be does he have epilepsy? 52. P: No

53. C: So it’s just really you, isn’t it? […]

254. C: There might be a slightly increased risk of the baby having epilepsy, 255. but you’ve gone through life pretty well without, with

257. the risks are pretty small, if there is only one of the parents has 258. epilepsy. (OI13)

OI13: Because there’s nobody else in my family at all, that’s got it. So I mean mine must have just been a fluke kind of thing. But that was one of the things when I first started [planning pregnancy]…if there is a child that I will need to give care to, I would just panic … would I be able to give that care or would it affect my health as well kind of thing.

(OI13; 28 year old, future pregnancy intentions)

Women interpreted uncertainties on the part of their clinician as frustrating, highlighting the unpredictable nature of their condition and its management. For individual women, clinicians’ reliance on gut feelings to direct decision-making emphasised the degree of uncertainty, while for other women, interactions with their clinician left them feeling they had no certainties in life, since the clinician was unable to provide the necessary precision, exemplified by the following participant:

OI20: no one has given me a percentage yet … they haven’t got enough information to say it could cause this, this, this, so how do I know? […]

OI20: it just makes me feel like a bad mother …you are just pumping your body full of drugs, which no one can give you a clear answer what its doing. (30 year old, pregnant at time of interview)

The uncertainty surrounding the long-term effects of in utero AED exposure on infant neurodevelopment was also a source of anxiety, sufficient to influence the acceptance of drug withdrawal in preparation for pregnancy. The following participant illustrates an extreme response to the unfolding picture of limited information, in which she considered an uncertain future with potential for “repercussions” such as the discovery of the risk of “learning difficulties” leading to make comparisons with thalidomide:

OI10: … you start thinking oh, and all these things go into your mind and

spinning round a bit, and you think oh, do people know enough about these drugs because obviously they didn’t about that [Thalidomide]. … When I went to see [clinician] and he said about the learning difficulties. I thought ooh… because last year no one knew about that, and then suddenly this year and then you think, in another years time will they be finding more things … you start worrying about all these things that start stacking up a bit, don’t you, and all these possible that don’t show their face now, but in years to come … they could say oh well see all these problems it’s because of that. (30 year old)

The experience of OI10 illustrates an important aspect of clinic communication; where the content of risk information is mainly selected by clinician’s. For some women,the

later discovery of information concerning risks or the extent of uncertainty had influence on their reflections both on their earlier informed decision-making and their doctor-patient relationship, as illustrated by the following discussion of two pregnant women:

FG82: I was really annoyed, because my neurologist, […] I changed medications for my second baby, an he was saying oh, this it’s superb, it’s great, an, I’m sure it is. But then, when I had my 20 week scan, the lady said, “oh, it’s only been out for 7 years”, and for me, that was a step back, because I thought, hang-on a minute, like, he’s pretty confident in it {Yes} but 7 years isn’t a long time {No} To tell if there’s cognitive, you know it’s not a long time, {Yes} an even then, I kind of felt, I’ve been?

FG83: Tricked?

FG82: Because, number one I felt I hadn’t been told everything, until I met [epilepsy nurse specialist] [laugh] and that was really annoying. Because I just, you need to know. (FG82, 37 year old; FG83, 34 year old)