Background

Between 1958 and 1961, Thalidomide was widely prescribed in the UK as a safe, none addictive sedative and tranquiliser. It was manufactured by a German company, Chemie Grünenthal, and distributed in the UK by Distillers Company (Biochemicals) Limited. Despite being marketed as an entirely safe treatment for the discomforts of pregnancy (including morning sickness), Thalidomide caused serious damage to the unborn child when taken during the first trimester. Depending on the timing and level of ingestion, foetal damage typically included:

• Missing, shortened or malformed upper limbs–ranging from complete absence of the arm (upper limb Amelia) with one or more digits attached directly to the shoulder, to short or missing long bones and missing or damaged thumbs and fingers
• Shortened or malformed lower limbs–including short or missing long bones, congenital dislocation of the hip, club foot, and extra toes
• Eye, ear and facial damage–these are the second most common group of birth defects and include missing or damaged ears, narrow ear canals, small or damaged eyes, restricted eye movement and facial palsy
• Malformation of internal organs–such as damage to the heart, urinary and alimentary tracts, and reproductive organs [3].

Together, these birth defects are referred to as Thalidomide Embryopathy or Thalidomide Syndrome.

Thalidomide constituted a major medical safely scandal and has, in Sarah Ferber’s [4] words become “emblematic of the advance then shocked reversal of the optimism of the ‘pharmaceutical revolution’ of the mid twentieth century” (p133). In the UK it prompted extended public campaigns by the Sunday Times newspaper and the parents of UK Thalidomide-damaged children for recognition and compensation. It led to global changes in the way in which drugs are tested and regulated [5], and in the UK to: the establishment of a Royal Commission on Civil Liability and Compensation for Personal Injury; changes to definitions of contempt in civil law cases; and a Law Commission report and legislation on civil liability in ante-natal injury.

A charitable trust—the Thalidomide Children’s Trust (now the Thalidomide Trust–see www.thalidomidetrust.org), was established to oversee compensation payments from Distillers to the families affected by Thalidomide in the UK. Individual payments were determined through assessments of level of impairment, with points being given for different types and severity (totalling from 3.5 to 75 points). The Thalidomide Trust continues to distribute annual payments from the global company Diageo (successor to Distillers) to all UK born Thalidomide survivors. An elected beneficiary National Advisory Council (NAC) advises the Trust. Subsequent campaigns by Thalidomide survivors themselves have focused on the UK Government’s ill-judged licensing of the drug, which had not been adequately tested. In response, in 2010 the Departments of Health (DH) in England, Scotland, Wales and Northern Ireland began paying an annual Health Grant to Thalidomide survivors, in recognition of their growing health and health-related needs. The DH grants, which have been agreed until April 2022, are also administered by the Thalidomide Trust and distributed annually in line with the severity of initial impairment.

Compared to Thalidomide survivors worldwide, UK survivors are relatively unusual in that their families, (and now they themselves) have received compensation payments from childhood. The level of this compensation has increased significantly over the past decade, as a result of both increased payments from Diageo and the DH Grants. This should offer a degree of protection against the disabling consequences of impairments [6]. In other countries compensation arrangements have been much poorer. In Canada for example, when an out of court settlement was reached between Richardson Merrell and 26 families, the company imposed a strict secrecy clause, which resulted in wide disparities in compensation amounts for individuals with similar levels of impairment [5]. In Spain Thalidomide survivors have never received any compensation from the company that made the drug. However, in 2011, after a long campaign by Avite (the Spanish Thalidomide group), the Spanish government did make a small payment to 23 Thalidomide survivors; a fraction of the number believed to have been born in Spain [7].

Ageing with Thalidomide Embryopathy and ageing with disability

The combination of impairments experienced by many Thalidomide survivors (particularly limb difference) is rare, and the historical, social and legal context of their experience is unique. However, because they are such an identifiable group who are ageing together, comparing the similarities and differences between their experiences of ageing with those of other groups with early onset disability may offer new insights into disability and the life-course.

Evidence about the health of Thalidomide survivors as they age is limited [8]. In particular, few studies have explored the interactions between original Thalidomide impairment, newly emerging secondary damage and co-morbidities. There has also been little attempt to understand how changes to impairment impact on the disabling experience. In the 2000s, when Thalidomide survivors reached their 50s, more research into the health of Thalidomide survivors, began to be undertaken. Whilst many studies have a narrow biomedical focus, together they do suggest widespread age-related secondary damage, particularly musculoskeletal problems (often related to overuse of ‘good’ limbs) and common mental health disorders, notably depression and anxiety [9, 10, 11]. These two conditions may of course be related, if emerging musculoskeletal conditions and consequent loss of function (especially difficulties with activities of daily living and/or reduced ability to work) place Thalidomide survivors at greater risk of mental health problems [12].

In the broader field of disability research, the past decade has seen growing interest in the experience of ageing with disability [13, 14], not least because the number of people with from birth or early acquired disabilities who are reaching middle and older age is increasing [15, 16]. Several overarching themes emerge from the current literature. First, people ageing with disability often face particular difficulties such as secondary conditions and overuse syndromes, post onset syndromes (e.g. post-polio syndrome) and a sense of premature ageing. As Molton and Yorkston [16] note, even in conditions which are regarded as ‘static’ (e.g. Cerebral Palsy), peoples’ functional limitations can change across the life course, creating further potential for disability. Moreover, they suggest that “there is now mounting evidence that the cumulative effects of living with a disability condition for many years contribute to premature declines in health” (p291). Secondly, people experiencing the later life effects of early acquired disabilities appear to be more at risk of depression and lower life satisfaction [15,17], although there is evidence that poor overall health, rather than the extent of (original) impairments is more significant in terms of social isolation [13]. Lastly, people growing older with disability often have an elevated risk of acquiring age-related chronic conditions [18, 19], which disability may in turn make more difficult to manage.

Within the disability literature, a few authors [1, 14, 20, 21] have proposed that a life course approach might provide a productive and more holistic framework for thinking about how disability affects people at different points in their lives, including ageing with disability. As Naidoo et al. [14] point out, “age and disability are not defining traits of an individual but overlapping phenomena that occur throughout the span of the life course” (p3). Drawing on the principles of life course theory developed by Elder et al. [22], they suggest that a life course perspective brings to the fore “individual choice and circumstance” and locates them “within larger social and historical context” (p3)

This paper contributes to the literature on ageing with disability by focusing on the experience of UK Thalidomide survivors. It presents evidence that the health problems caused by Thalidomide are not restricted to the well-documented neonatal impairments. On the contrary, it argues that: survivors are encountering significant new Thalidomide-related challenges to their physical and mental health and well-being as they age; that these changes in health are linked to individual choice and circumstance; but also to the social and historical context in which Thalidomide survivors have lived their lives.

Survey respondent characteristics

Here we describe the characteristics of the survey respondents, in order to provide context for the results presented in later sections. In the UK and internationally, limb defects, particularly missing or short arms, are the most commonly recognised feature of Thalidomide damage. However, damage took many forms and varied considerably in severity. The drug was also no respecter of class or culture, so survivors are a widely heterogeneous group. Respondents were evenly split between women and men (174 respectively; three respondent did not give their gender). At the time of the survey, the Trust grouped its beneficiaries in to five impairment bands, with band 1 covering beneficiaries with the least severe impairments and band 5 those with the most severe. Based on these bands, the distribution of the overall severity of their impairments was similar to that of all UK beneficiaries (Fig 1).

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Fig 1. Distributions of survey respondents and all beneficiaries by impairment band.

NOTE: n = 302; it was only possible to identify the impairment band for respondents who gave their names.

https://doi.org/10.1371/journal.pone.0210222.g001

Respondents were asked to describe their original Thalidomide impairments using 25 categories covering limb damage, sensory impairments and internal organ damage, plus a free text box for other damage. For ease of analysis, these were collapsed into eight groupings and their incidence compared (in aggregate form) with data held by the Trust. This enabled us to check that the survey respondents were broadly representative, in terms of the range of impairment, of all UK Thalidomide survivors. For example, the proportions in survey and in the Trust’s data were very similar for respondents with upper limb only damage (survey 58%/Trust 54%), lower limb only damage (survey 5%/Trust 4%), and no limb damage, (survey 12%/Trust 11%). However, there was a difference in the proportion with both upper and lower limb damage (survey 25%/Trust 34%).

However, because the Trust’s information was collected at the time beneficiaries were assessed for their compensation claims i.e. from the 1970’s onwards, the survey also provided a more up to date picture of impairments, particularly damage to internal organs which for many had only come to light later in life as a result of diagnostic scans. This was reflected in survey results. For example, 31% of survey respondents said they had damage to internal organs, whereas the Trust’s data showed just 22% with this type of damage. Thalidomide survivors who were blind or partially sighted appear to be under represented in the survey. This may reflect the method of data collection, although large print version of the questionnaire were available and respondent could choose to complete the survey by telephone. Importantly, the survey confirmed that many Thalidomide survivors have multiple impairments e.g. 73 respondents had upper limb damage and were deaf/partially deaf and 27 respondents had both sight and hearing impairments; and almost all respondents reporting internal organ damage also had other impairment/s.

Almost two thirds of respondents lived with partners/spouses or with a partner/spouse and other family members. Nearly a quarter (76/22%) lived alone (compared to 17% of the general UK population aged 50 to 64 [23]; 10% lived with another family member/s (e.g. parents/sibling). Nine respondents lived at home with full-time paid carers or in residential care. The majority of respondents (304/87%) owned their house or flat, compared to 75% of the general UK population aged 50 to 64 (75%) [24].

Self-reported health problems

The survey asked Thalidomide survivors about additional health problems, over and above their original impairments.

Musculoskeletal problems and pain.

Almost all (93%) reported musculoskeletal problems (pain and/or loss of movement in joints, neck and/or back). Back problems were the most commonly reported musculoskeletal problem, closely followed by shoulder pain/loss of movement and problems with hands (Table 1). In comparison, less than 20% of adults aged 45–64 in the general population report chronic musculoskeletal conditions [25] and only 15% suffer low back pain [26]. The prevalence of musculoskeletal problems, particularly back problems, is therefore higher amongst UK Thalidomide survivors than in the general population, a pattern also found in Swedish Thalidomide survivors [27]. Many survey respondents reported multiple musculoskeletal problems, with a mean of 4.5 problems and over half reporting five or more problems.

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Table 1. Prevalence of musculoskeletal problems.

https://doi.org/10.1371/journal.pone.0210222.t001

Almost half (49%) of respondents reported generalised pain: 26% said this was severe and/or continuous and a further 23% described it as moderate and/or intermittent. Respondents with most severe Thalidomide damage were the most likely to report generalised pain. For some, the cause of the pain was unclear:

“Chronic neuropathic pain in peroneal nerves—both legs, below knee. 5 years. No cause found. Does not respond to treatment/pain management medication.” (Survey ID298)

“I have been suffering with regular bouts of pain in my side. I have had several tests done but I am told there is no conclusive reason for the pain.” (Survey ID104)

Two-thirds (66%) of respondents also reported one or more neurological symptom (e.g. tingling and numbness). Two fifths reported severe tiredness/fatigue; this was more common among respondents in Bands 1 and 2, possibly because they were more likely still to be in paid work and therefore less able to rest.

Multimorbidity.

A high proportion of Thalidomide survivors reported multiple health problems (see Fig 2). Just 3% had no health problem but almost half (46%) reported between four and nine separate problems. Multimorbidity or the presence of multiple diseases in one individual is a growing concern in the UK population as a whole but these results suggest that a higher proportion of Thalidomide survivors are experiencing multimorbidity than would be expected at this point in their life course. For example, in Barnett et al’s [31] study of multimorbidity in Scotland, around a third of patients aged 55 to 59 had two of more morbidities but less than 10% had four or more morbidities. Furthermore, for some Thalidomide survivors the morbidity burden i.e. the overall impact of several conditions on the individual’s “physiologic reserve” and functioning [32] is significant. A comment added by one respondent vividly illustrates this:

“After having operations on both shoulders and left elbow the use of my arms and hand were considerably limited e.g. dressing, washing, cooking, and most basic household chores. Also having a mini stroke has made my balance a bit difficult. And then the cancer came along…” (Survey ID21)

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Fig 2. Proportions of Thalidomide survivors reporting multiple health problems.

https://doi.org/10.1371/journal.pone.0210222.g002

The impact of health problems on paid work

These widespread health problems were reflected in survey respondents’ employment status. Two-fifths (145/41.3%) were now unable to work because of their disability or health problems (Table 2). Previous research suggests that less than 10% of UK Thalidomide survivors have never worked [33]. As in the general population, there were significant differences between men and women: men were more likely to be working full-time; women were more likely to work part-time; and women were also marginally more likely to be unable to work because of their disability or health problems (69 men compared to 76 women).

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Table 2. Work situation.

https://doi.org/10.1371/journal.pone.0210222.t002

The likelihood of not working increased with the severity of impairment: the proportions reporting currently being unable to work increased from 35% of those in Band 1 (least severe) to 75% in Band 5 (most severe); whilst the proportion currently in full-time work decreased from 32% (Band 1) to 8% (Band 5). Moreover, although respondents in impairment bands 1 and 2 were more likely than their peers with more severe impairments to still be in full time work, around a third of them still reported being unable to work because of their disability or health problems. Patterns for those working part-time were less clear.

Comparisons with the general population, and/or with people with disabilities as a whole are difficult, as different sources use different terminology, definitions and age groupings. However, in 2015, 82% of the general population aged 50–54 (78% of women, 86% of men) were in paid work [34] (DWP 2015), suggesting that only 18% of the age group were ‘economically inactive’, compared to 63% of Thalidomide survivors.

In the UK, disabled people may be four times as likely as their non-disabled peers to be unemployed or involuntarily out of work [35]. However, the lifetime economic activity patterns of Thalidomide survivors appear to be somewhat different from those of other disabled people. First, their current employment patterns do not reflect the lower levels of educational achievement which commonly disadvantage disabled people; their educational achievements were broadly similar to those of the general population of a similar age [36]. The proportion of Thalidomide survivors with no qualifications was similar to those of working age disabled people in general. On the other hand, the proportion with degree-level qualifications was higher than working age disabled people in general [37]. Similar educational qualification patterns have been found among German Thalidomide survivors [11]. Secondly, at each level of educational qualification, there was a range of severity and type of impairment (e.g. the 19 respondents with degrees working full time were spread across all five severity bands and most types of impairment). This suggests that whilst respondents’ ability to work was strongly linked to the severity of their impairment, educational qualifications also had an important influence. Thirdly, the survey showed that Thalidomide survivors’ work situation had changed significantly over the last 10 to 15 years. Overall, 207 respondents (59%) reported changes in their work situation since 2000, with most changes taking place in the last five years (Fig 3). This trend has also been seen amongst Thalidomide survivors in Canada and Germany [9, 38].

“Increasingly from 2002 onwards, at which time I was a Director of a limited company working in excess of 50 hours per week. I now struggle to manage 18 hours per week. I have now reached the point where stopping work altogether is imminent.” (Survey ID2)

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Fig 3. Changes in work situation since 2000.

Note: 15 respondents reported more than one change, so appear in more than one category; all had reduced working hours and all but one had changed the type of work they did.

https://doi.org/10.1371/journal.pone.0210222.g003

Less severely impaired respondents (Bands 1 to 3) were more likely to have reduced their working hours or changed the type of work they did. Although greater proportions of more severely impaired beneficiaries (Bands 4 and 5) had stopped working since 2000, this change had also occurred across all impairment bands. For example, over three quarters of respondents in bands 1 to 4 were working prior to 2000. By 2015, less than half of all respondents were working and, moving from band 1 to band 5, there was a gradual fall in the proportions still working.

“2011 I was forced to make a difficult decision to stop working due to continued failing health.” (Survey ID183)

“In 2009 I had to reduce my hours in line with medical advice. In 2010 I had further problems… and in 2011 I was medically retired (not at my request) as my employer had no role for me.” (Survey ID276)

Thalidomide survivors’ health-related quality of life

The SF12 Health Survey was used to measure health related quality of life. SF12 consists of eight scaled sections (General Health; Pain; Physical Functioning; Role Limitation Physical; Mental Health; Role Limitation Emotional; Social Functioning; Vitality), which can be ‘aggregated’ into two domains: physical health related quality of life and mental health related quality of life. Of the 351 survey respondents, 335 returned SF12 questionnaires that were useable for analysis (i.e. no missing data) and for 285 of these we were able to link SF12 scores to level of impairment (as indicated by the number of impairment points the individual had). Fig 4 shows the range of scores for the survey respondents compared to the general population aged 45–54, based on responses to the Central England Healthy Life Survey [39].

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Fig 4. Normalised SF-12 physical and mental health scores for survey group.

https://doi.org/10.1371/journal.pone.0210222.g004

In the physical health domain respondents had a markedly lower average aggregate score than the general population (i.e. a mean of 26.7 compared to 50) indicating that their physical health related quality of life is much poorer. 59.7% (n = 200) of the respondents had a score below 30 i.e. the same as or worse than the 2% of the general population group with the poorest physical health related quality of life, and only 7.5% (n = 25) of the respondents had a score above the average for the general population group.

In the mental health domain the average aggregate score for respondents was 46.5, slightly lower than the general population (score 50). This suggests that on average Thalidomide survivors’ mental health related quality of life is only marginally poorer than their peers in the general population; indeed 40.9% of respondents (n = 137) had a score above the average for the general population. However, 10.7% (n = 36) had a score below 30 i.e. the same as or worse than the 2% of the general population with the poorest mental health related quality of life. Overall men had a higher mean score for physical health (28.6 compared to 24.7) which was significant (t (327) = 2.567, p = 0.01.). Women had a higher mental health score (47.8 compared to 45.1), which was not significant (t (327) = -1.981, p = 0.05).

We also used the SF12 results to examine whether there was any relationship between health-related quality of life and level of impairment. We found that there was a strong negative correlation (r = -.276; p = .000) between lower SF12 physical health scores and severity of impairment i.e. the more severe a respondent’s Thalidomide damage, the poorer their physical health related quality of life was likely to be. In contrast, when we examined the same relationship for mental health related quality of life, we found that the less severe a respondent’s Thalidomide damage, the poorer their mental health related quality of life was likely to be i.e. there was a positive (but weaker) correlation between lower SF12 mental health scores and less severe impairment (r = .148; p = .012).

The responses to the narrative questions in the survey suggested that other factors, in particular being unable to work because of secondary health problems, could be important in explaining variance in both physical and mental health-related quality of life. To examine if this was the case we used hierarchical regression, using three sets of variables: original impairment level (as indicated by the number of impairment points) (step 1); being unable/able to work and qualifications (step 2); and gender and living alone/living with others (step 3). Tables 3 and 4 below show the results for SF12 physical and mental health scores.

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Table 3. Hierarchical Regression results for SF12 Physical.

https://doi.org/10.1371/journal.pone.0210222.t003

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Table 4. Hierarchical Regression results for SF12 mental health.

https://doi.org/10.1371/journal.pone.0210222.t004

The model predicting physical health was significant at: step 1—F (1, 273) = 24.526, p < .001; step 2 –F (3, 271) = 30.337, p < .001; and step 3 –F (5, 269) = 19.396 p < .001. The results for SF12 physical show that together the five variables explained 25% of the variance in physical health related quality of life. However, only three variables make a unique statistically significant contribution (i.e. p = .05 or less)–a higher level of original impairment, being unable to work, and gender (being male), predicted poorer physical health related quality of life, with being unable to work accounting for most of the variance.

The model predicting mental health was sig at: step 1—F (1, 273) = 5.348, p = .021; step 2 –F (3, 271) = 7.514, p < .001; and step 3 –F (5, 269) = 5.080 p < .001. For mental health related quality of life, the five variables explained just 7% of the variance in SF12 mental health scores, with only two variables–lower level of original impairment and being unable to work, making a unique statistically significant contribution to predicting poorer mental health related quality of life.