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Adverse events in childhood and chronic widespread pain in adult life: Results from the 1958 British Birth Cohort Study
PAINÒ 143 (2009) 92–96
www.elsevier.com/locate/pain
Adverse events in childhood and chronic widespread pain in adult life: Results from the 1958 British Birth Cohort Study Gareth T. Jones a,*, Chris Power b, Gary J. Macfarlane a a
Aberdeen Pain Research Collaboration (Epidemiology Group), Institute of Applied Health Sciences, University of Aberdeen, School of Medicine and Dentistry, Polwarth Building, Foresterhill, Aberdeen AB25 2ZD, UK b MRC Centre of Epidemiology for Child Health, Centre for Paediatric Epidemiology and Biostatistics, UCL Institute of Child Health, London, UK
a r t i c l e
i n f o
Article history: Received 11 September 2008 Received in revised form 28 December 2008 Accepted 4 February 2009
Keywords: Chronic widespread pain Childhood adversity Epidemiology
a b s t r a c t Chronic widespread pain (CWP) is a common and frequently disabling condition. Several studies have shown that early life adversity is associated with CWP in later life; however, the majority are retrospective and suffer from potential recall bias. Using data from the 1958 British Birth Cohort Study, the aim of the current study was to examine, prospectively, the relationship between childhood physical and psychological adversity and CWP in adulthood. At 7 yrs data were collected, by parental report, on physically traumatic events (hospitalisation following a road traffic accident, or for surgery); and factors indicating poor social and psychological environment (periods in local authority care, death of a parent; or parental divorce, alcoholism, or financial hardship). CWP was assessed at 45 yrs using self-completion questionnaires. The relationship between childhood events and CWP was examined using Poisson regression. 7571 individuals provided pain data at 45 yrs (71.5%). There was no association between childhood surgery and CWP in adulthood (relative risk: 1.0; 95%CI: 0.9–1.1). However, children who had been hospitalised following a road traffic accident experienced a significant increase in the risk of future CWP (1.5; 1.05–2.1). Children who had resided in institutional care also experienced an increase in the risk of CWP (1.7; 1.3–2.4) as did those who experienced maternal death (2.0; 1.08–3.7) and familial financial hardship (1.6; 1.3–1.9). Further these associations were not explained by adult psychological distress or social class. To prevent long-term consequences of adverse childhood events, future research should study the mechanisms, in particular the biological mechanisms, underlying these relationships. Ó 2009 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
1. Introduction Chronic widespread body pain (CWP) is a common and frequently disabling condition. Prevalence studies have provided remarkably consistent findings across different countries and settings, demonstrating that around 12% of the adult population experience such symptoms at any one time. Prevalence increases with age, to around the sixth decade, and there is an excess prevalence in women [4,7,16,34]. Further, it is the predominant presenting feature of fibromyalgia, which is one of the commonest reasons, internationally, for consultation to a rheumatologist [33]. The aetiology of CWP is multifactorial, and both physical and psychosocial factors play an important role [12]. A number of studies have demonstrated an association between physical trauma and the occurrence of CWP/fibromyalgia [1,5]. However, recent evidence suggests that this may be explained by psychological and psychosocial factors [36,37]. Experiences in early life have also been shown to be important: some have reported that the occur* Corresponding author. Tel.: +44 (0) 1224 552 495; fax: +44 (0) 1224 550 925. E-mail address: [email protected] (G.T. Jones).
rence of multiple common symptoms in childhood (frequent headache, abdominal pain and vomiting) is associated with a 50% increase in the risk of CWP at 45 yrs [19]. This is consistent with other evidence that suggests that those who report common symptoms in childhood experience an increase in the risk of a number of ‘unexplained’ symptoms in adulthood [6,14]. Several authors have also demonstrated that adults with CWP and/or fibromyalgia report an excess of adverse events in childhood. Imbierowicz and Egle found that patients with fibromyalgia had more frequent and/or more severe adversities during childhood compared to patients with chronic pain of nociceptive or neuropathic origin [17], and McBeth and colleagues demonstrated that compared to those with no pain, persons with CWP self-report more hospitalisations, operations, parental loss, and abuse in childhood [26]. However, further examination of objective data (in this case primary care records) revealed evidence of recall bias – those with CWP very accurately recalled these prior events, whereas those free of pain under-reported their true occurrence, thus augmenting the observed relationship. To examine the relationship between early life adverse events and pain in adulthood, in the absence of recall bias, prospective stud-
0304-3959/$36.00 Ó 2009 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.pain.2009.02.003
G.T. Jones et al. / PAINÒ 143 (2009) 92–96
ies are required. However, to date, there are few large-scale longitudinal studies in this field. The aim of the current study was to examine, prospectively, the relationship between physical and psychological adversity in early childhood and CWP in adulthood. 2. Methods The 1958 British Birth Cohort Study (or ‘National Child Development Study’) is a large, ongoing, prospective cohort study of all children born in England, Scotland and Wales in one week in March 1958 [29]. It comprises 17,638 participants who were recruited at birth, supplemented by 920 early migrants, all born in the same week. Participants have been followed up on numerous occasions, and a variety of data have been collected, including information on socioeconomic status, health and development, and familial and education factors. At 7 yrs, parents of participants (most commonly mothers) were interviewed by a Local Authority health visitor, using a structured interview schedule. Data were collected on a variety of adverse childhood events, including on physically traumatic events (hospitalisation following a road traffic accident, surgery, or hospitalisation following an accident at either home or elsewhere); and poor social and psychological environment (periods in local authority care/maternal separation, death of a parent, or parental divorce, alcoholism, or financial hardship). At 45 yrs, 12,069 participants still in contact with the study, and who at 42 yrs had not required a proxy interview, were invited to participate in a biomedical survey. Of these, 10,596 had at least some data on adverse events at 7 yrs, and thus formed the target population for the current study. The survey collected data on a number of health-related factors including the presence of pain. Participants were asked ‘‘During the past month, have you had any ache or pain which has lasted for one day or longer?” Those who answered positively were asked to indicate the location of their pain(s) on a four-view body manikin, and to indicate whether they had been aware of the pain for more than three months. CWP was defined according to the American College of Rheumatology Criteria for the Classification of Fibromyalgia [35] – viz: pain present for three months or longer, both above and below the waist; on both the left and right sides of the body; and in the axial skeleton. 2.1. Analysis The relationship between adverse childhood events and CWP was examined using Poisson regression. Thus, results are expressed as risks ratios (RR) with 95% confidence intervals
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(95%CI), the latter being derived using robust estimates of standard error [11]. Sex, psychological distress, and socioeconomic status were assessed as potential-mediating variables. Psychological distress was measured at age 42 years, using the General Health Questionnaire [10]; each item was scored using the Likert scoring system [9], summed, and divided into tertiles for analysis. Socioeconomic status in adulthood was based on the occupation at age 42 yrs (or at 33 yrs where the former was not available) and, in childhood, based on the paternal occupation at birth, or at age 7 yrs where the data at birth were missing. At both time points it was classified using the Registrar General’s Classification: professional (I); managerial/technical (II); other non-manual (IIInm); skilled manual (IIIm); partly skilled (IV); and unskilled manual (V). To adjust for potential confounding between multiple adverse exposures, a forward stepwise multivariable model was created of all social/psychological adverse events which predicted the outcome at p > 0.20. Variables were included in the final model at p = 0.10 and eliminated at p = 0.15. All analyses were conducted using Stata v10.0 (StataCorp, College Station, Texas). 2.2. Ethical approval Ethical approval for the most recent follow-up (45 yrs) was obtained from the South East, UK, Multi-centre Research Ethics Committee (reference 01/1/44). 3. Results From a total of 9377 participants followed up at age 45 yrs, 7571 provided pain (outcome) data and came from the target sample for the current analysis, giving a response rate of 71.5% (7571/ 10,596). The prevalence of CWP was 12.3%, and there was no difference between men (11.8%) and women (12.7%) (chi2: 1.5; p = 0.22). Reports of a surgical operation in childhood (i.e. before 7 yrs) was fairly common (23%), and most commonly this was for tonsillectomy or adenoidectomy (70%). However, children who underwent surgery were no more likely to report CWP as adults compared to other children (RR: 1.0; 95%CI: 0.9–1.1). Even those who experienced two or more operations as children were at no greater risk of CWP in adulthood (Table 1). Children who had been hospitalised following a road traffic accident experienced a 40% increase in the risk of CWP (1.4; 0.96–1.9), and this relationship remained – augmented slightly – after adjusting for sex, social class and psychological distress (1.5; 1.05–2.1). In contrast, hospitalisation for other reasons
Table 1 Association between childhood physically traumatic adverse events and CPWP at 45 yrs. Exposure
CWP
Total
Risk ratio (95%CI)
Model statistics
Crude
Adjusted*
5715 1560 172
1.0 1.0 (0.8–1.1) 1.1
1.0 1.0 (0.8–1.1) 1.1 (0.7–1.6)
chi2 = 207.95; df = 17; p < 0.001
Hospitalisation following a road traffic accident No 892 (12.2%) Yes 27 (16.6%)
7335 163
1.0 1.4 (0.96–1.9)
1.0 1.5 (1.05–2.0)
chi2 = 213.85; df = 16; p < 0.001
Hospitalisation following an accident at home No 844 (12.4%) Yes 73 (11.0%)
6808 666
1.0 0.9 (0.7–1.1)
1.0 0.9 (0.7–1.1)
chi2 = 211.55; df = 16; p < 0.001
Hospitalisation following an accident (other) No 840 (12.3%) Yes 75 (12.0%)
6838 623
1.0 1.0 (0.8–1.2)
1.0 1.0 (0.8–1.3)
chi2 = 212.03; df = 16; p < 0.001
Surgical operations None 1 P2
*
702 (12.3%) 187 (12.0%) 23 (13.4%)
Adjusted for sex, social class (childhood and adulthood) and psychological distress (adulthood).
G.T. Jones et al. / PAINÒ 143 (2009) 92–96
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(accidents at home/other accidents) was not associated with an increase in risk (Table 1). There was a positive relationship between the length of time a child had been separated from its mother, prior to the age of 7 yrs, 2 and the risk of CWP in adulthood (chitrend : 7.98; p < 0.001). Compared to those who have never experienced separation, those who had been separated for >6 months experienced a 40% increase in the risk of CWP (1.4; 1.02–2.1); an association that remained after adjusting for sex, social class and psychological distress (Table 2). Children who had ever resided in institutional care also experienced an increase in the risk of CWP in later life (1.9; 1.4–2.7); an association that also remained after adjustment for sex, social class and psychological distress (1.7; 1.3–2.4). Further, this variable completely explained the relationship between maternal separation and CWP. No association was found between paternal death, before the age of 7 yrs, and the risk of CWP (0.9; 0.5–1.9). However, maternal death was associated with a doubling in the risk of future symptoms (2.0; 1.08–3.7). Financial family difficulties in childhood were also associated with an increase in the risk of CWP in adulthood, and this relationship remained after adjusting for sex, social class and psychological distress (1.6; 1.3–1.9). Multivariable analysis revealed that, on mutual adjustment, financial difficulties (1.4; 1.2– 1.8), maternal death (2.6; 1.5–4.6) and periods in local authority care (1.6; 1.1–2.2) were all independent predictors of CWP in adulthood.
There are a number of methodological points to consider. Firstly, attrition: of 10,596 individuals with known exposure at 7 yrs, only 7571 provided data on CWP at age 45 yrs (71.5%). Sample attrition would decrease sample size and would increase the likelihood of finding a non-significant result; in the light of some of the current findings, this is important. However, although loss to follow-up will affect the significance of any associations, it should not alter the point estimates. Further, the sample size is still substantial and we calculate that we have 90% power, at the 95% confidence level, to detect a 50% increase in the risk of CWP (should such a relationship exist) associated with any risk factor with a prevalence of 5%. More important is the issue of differential follow-up. Previous work has shown that, while the 45 yr sample remains broadly representative of the surviving cohort [2], follow-up is poorer in the most extreme adversity groups – e.g. persons who resided in local authority care – and this might introduce a bias. However, the effect of this would be to bias our findings towards the null. Childhood events were measured by maternal report. Given familial aggregation of fibromyalgia and depression, it is likely that the mothers of children who went on to develop CWP had higher rates of depression themselves. It is possible, therefore, that these women over reported negative events in their children’s lives, relative to other women, although to explain the current findings, such bias would have to be selective, with an over report of some childhood experiences (e.g. hospitalisation following road traffic accidents), but not others (e.g. surgery). This seems unlikely and, thus, while recall bias cannot be firmly ruled out, we consider it improbable. There will be some measurement error in the potential-mediating variables (social class and psychological distress) as these variables were recorded at 42 yrs, three years prior to the outcome. This problem may be particularly acute for social class, which for some individuals (approximately 12%) was recorded at 33 yrs. However, it is unlikely that the measurement of these variables was sufficiently poor to completely explain the current findings.
4. Discussion We report the results of a longitudinal population-based study to examine the relationship between adult CWP and adverse childhood events. We have shown that physically traumatic events and factors suggesting poor social/psychological environment are associated with long-term increased risk of CWP, and that these associations remain after adjustment for psychological distress and social class.
Table 2 Association between childhood social/psychological adversity and CWP at 45 yrs. Exposure
CWP
Total
Risk ratio (95%CI)
Model statistics
Crude
Adjusted* 1.0 1.0 1.1 1.2 1.4
Maternal separation None <1 wk 1 wk–1 month 1–6 months >6 months
186 265 357 86 30
(11.4%) (11.3%) (12.9%) (14.4%) (16.6%)
1626 2343 2767 596 181
1.0 1.0 1.1 1.3 1.4
Ever in institutional care No Yes
896 (12.1%) 30 (23.3%)
7427 129
1.0 1.9 (1.4–2.7)
1.0 1.7 (1.2–2.3)
chi2 = 227.35; df = 16; p < 0.001
Death of father No Yes
882 (12.3%) 9 (11.3%)
7162 80
1.0 0.9 (0.5–1.7)
1.0 0.9 (0.5–1.6)
chi2 = 197.48; df = 16; p < 0.001
Death of mother No Yes
882 (12.2%) 7 (25.0%)
7230 28
1.0 2.0 (1.08–3.9)
1.0 2.0 (1.08–3.7)
chi2 = 201.35; df = 16; p < 0.001
Family difficulties (divorce/separation/desertion) No 845 (12.2%) Yes 41 (17.2%)
6952 238
1.0 1.4 (1.1–1.9)
1.0 1.3 (0.99–1.7)
chi2 = 202.90; df = 16; p < 0.001
Family difficulties (alcoholism) No 787 (12.1%) Yes 10 (20.8%)
6519 48
1.0 1.7 (0.99–3.0)
1.0 1.3 (0.8–2.4)
chi2 = 171.74; df = 16; p < 0.001
Family difficulties (financial) No Yes
6356 419
1.0 1.8 (1.5–2.2)
1.0 1.6 (1.3–1.9)
chi2 = 212.17; df = 16; p < 0.001
*
737 (11.6%) 89 (21.2%)
(0.8–1.2) (0.96–1.3) (0.99–1.6) (1.02–2.1)
Adjusted for sex, social class (childhood and adulthood) and psychological distress (adulthood).
chi2 = 217.32; df = 19; p < 0.001 (0.9–1.2) (0.96–1.3) (0.9–1.5) (0.9–1.9)
G.T. Jones et al. / PAINÒ 143 (2009) 92–96
We would argue that social class at 33 yrs, while not a perfect measure of social class at 45 yrs, probably contains more signal than noise. Therefore, if the relationship between childhood adversity and CWP was explained by social class, one would expect to see at least some attenuation of risk effects. This was not the case. CWP was assessed at a single point in time, 45 yrs, using a body manikin in a questionnaire survey. From this, we have no data on the composition of the CWP group, in terms of underlying pain problems (e.g. fibromyalgia, versus multiple regional pains, versus multiple injury), nor is it possible to ascertain the duration of symptoms experienced. However, it is probable that a large proportion of the persons would have experienced these symptoms for many years because seldom do they first occur as late as mid-adulthood [25]. Although it is possible that in some subjects, CWP may have originated in childhood, it is unlikely that in these children the maternal report of adverse events was sufficiently augmented as to explain the current findings. This is not the first study to examine the relationship between chronic pain and early adverse experiences. Kopec and Sayre [21] demonstrated an increase in the risk of back pain associated with stressful life events in childhood; and Juang and colleagues found that adolescents with chronic daily headache reported more childhood adversities and, in particular, an excess of physical abuse and parental divorce [20]. However, the majority of previous studies have assessed exposures retrospectively, relying on recall of childhood events and have been shown to be susceptible to recall bias: persons with/without CWP recall prior events with differing degrees of accuracy, leading to spurious estimates of the risk associated with these events [26]. Longitudinally, Raphael and colleagues demonstrated a 20–40% increase in the likelihood of unexplained pain in adulthood associated with childhood victimisation, physical or sexual abuse, or neglect, albeit not statistically significant [30], and Hotopf et al. found that some childhood experiences – maternal ill health – were associated with chest pain at 36 yrs [15]. In the current study, we have focused on events prior to age 7 yrs. It is likely that pain in adulthood is also a function of events later in life. However, by focusing on very early exposures, one decreases the likelihood of observing any effect. The fact that we have observed effects of reasonable magnitude, and of statistical significance, highlights the importance of these exposures. We have shown that children who are hospitalised following a road traffic accident experience a significantly increased risk of CWP nearly 40 yrs subsequently. Whereas other physical exposures – such as surgery, or an accident in the home – are not similarly associated with adult pain. We cannot explain the specificity of this relationship. It may be that (a) in the current study, the trauma involved in the road traffic accident was greater than that in the other accidents; (b) there may be psychological sequelae associated with road traffic accidents that play a role in CWP development, independent of the effects of the physical trauma per se; or (c) that this finding has arisen by chance. It is interesting, however, that these results are consistent with recent studies in adults, which have demonstrated that exposure to a road traffic accidents but not to other physically traumatic events (surgery/accident at work/fracture) is associated with an increase in the risk of CWP in the shortto medium-term [18]. It should be noted, however, that while the magnitude of effect measures is sizeable (risk ratios ranging from 1.5 to 2.0) because these exposures are rare, the population attributable risks are relatively small. In combination, hospitalisation following a road traffic accident, periods in residential care, maternal death, and financial hardship in childhood only account for around 7.5% of all cases of CWP. We provide evidence that children who are exposed to physical and social adversity experience a 50–100% increase in the risk of CWP in adulthood. What could be the likely mechanism of this relationship? Firstly, one must consider confounding. While this
95
cannot be ruled out, the most likely confounders are emotion and distress: these are undoubtedly associated with childhood adverse events and have been demonstrated to be strong predictors of CWP in adulthood [3,23,24]. However, our results are robust to statistical adjustment for General Health Questionnaire score – an instrument demonstrated to be a valid and reliable measure of general psychological distress [32]. Psychosocial or psychological variables may in fact be mediating factors, rather than confounders per se. Either way, however, one would expect statistical adjustment for psychological distress to attenuate the effect of early life adversity. Whereas, no such attenuation is observed. One cannot rule out residual confounding if, for example, the General Health Questionnaire has not fully or adequately captured psychological distress. However, it is unlikely that such an effect would completely negate the observed risk effects. Secondly, the increased risk of CWP in adulthood may be a function of a disadvantageous life trajectory, or that early insults make an individual more susceptible or vulnerable to the effect of risk factors experienced in later life. Exposure to risk events does not follow a random distribution in the population. Thus, disadvantaged children may be more likely to accumulate risks throughout life [31], and it may be one of these later events that act as the final ‘cause’ of CWP. However, our results are altered little by adjustment for adult social class. This suggests that if later life events are responsible for the increase in the risk of CWP, these events are independent of socio-economic status. Finally, early life adverse events may exhibit a long-term biological effect through a number of endocrine pathways. Recent studies suggest an important role of the hypothalamic–pituitary–adrenal (HPA) axis in the onset of CWP [27], and there is some evidence that adverse childhood experiences are associated with HPA axis dysregulation [8,22]. Further, studies in neonates have shown that insults in early life have effects on pain perception that persist well beyond infancy [13], and others have demonstrated, in animal models, that environmental manipulations during development – such as extended periods of maternal separation – can permanently alter HPA axis function, modifying the biological response to stressful stimuli in later life [28]. In summary, we have shown that both physical and social adversity prior to age 7 yrs are associated with an increase in the risk of CWP nearly 40 yrs subsequently. In order to prevent longterm health consequences of adverse childhood events, future research should study the mechanisms, in particular, the biological mechanisms, underlying this relationship. Elucidation of these pathways will need large-scale longitudinal studies using markers of potentially altered biological function.
Acknowledgements We are grateful to the study participants in the birth cohort study. Great Ormond Street Hospital/University College London, Institute of Child Health receives a proportion of funding from the UK Department of Health’s National Institute of Health Research (‘Biomedical Research Centres’ funding). The MRC provides funds for the MRC Centre of Epidemiology for Child Health. None of the authors have any financial or other relationships that might lead to a conflict of interest.
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Adverse events in childhood and chronic widespread pain in adult life: Results from the 1958 British Birth Cohort Study Gareth T. Jones a,*, Chris Power b, Gary J. Macfarlane a a
Aberdeen Pain Research Collaboration (Epidemiology Group), Institute of Applied Health Sciences, University of Aberdeen, School of Medicine and Dentistry, Polwarth Building, Foresterhill, Aberdeen AB25 2ZD, UK b MRC Centre of Epidemiology for Child Health, Centre for Paediatric Epidemiology and Biostatistics, UCL Institute of Child Health, London, UK
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Article history: Received 11 September 2008 Received in revised form 28 December 2008 Accepted 4 February 2009
Keywords: Chronic widespread pain Childhood adversity Epidemiology
a b s t r a c t Chronic widespread pain (CWP) is a common and frequently disabling condition. Several studies have shown that early life adversity is associated with CWP in later life; however, the majority are retrospective and suffer from potential recall bias. Using data from the 1958 British Birth Cohort Study, the aim of the current study was to examine, prospectively, the relationship between childhood physical and psychological adversity and CWP in adulthood. At 7 yrs data were collected, by parental report, on physically traumatic events (hospitalisation following a road traffic accident, or for surgery); and factors indicating poor social and psychological environment (periods in local authority care, death of a parent; or parental divorce, alcoholism, or financial hardship). CWP was assessed at 45 yrs using self-completion questionnaires. The relationship between childhood events and CWP was examined using Poisson regression. 7571 individuals provided pain data at 45 yrs (71.5%). There was no association between childhood surgery and CWP in adulthood (relative risk: 1.0; 95%CI: 0.9–1.1). However, children who had been hospitalised following a road traffic accident experienced a significant increase in the risk of future CWP (1.5; 1.05–2.1). Children who had resided in institutional care also experienced an increase in the risk of CWP (1.7; 1.3–2.4) as did those who experienced maternal death (2.0; 1.08–3.7) and familial financial hardship (1.6; 1.3–1.9). Further these associations were not explained by adult psychological distress or social class. To prevent long-term consequences of adverse childhood events, future research should study the mechanisms, in particular the biological mechanisms, underlying these relationships. Ó 2009 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
1. Introduction Chronic widespread body pain (CWP) is a common and frequently disabling condition. Prevalence studies have provided remarkably consistent findings across different countries and settings, demonstrating that around 12% of the adult population experience such symptoms at any one time. Prevalence increases with age, to around the sixth decade, and there is an excess prevalence in women [4,7,16,34]. Further, it is the predominant presenting feature of fibromyalgia, which is one of the commonest reasons, internationally, for consultation to a rheumatologist [33]. The aetiology of CWP is multifactorial, and both physical and psychosocial factors play an important role [12]. A number of studies have demonstrated an association between physical trauma and the occurrence of CWP/fibromyalgia [1,5]. However, recent evidence suggests that this may be explained by psychological and psychosocial factors [36,37]. Experiences in early life have also been shown to be important: some have reported that the occur* Corresponding author. Tel.: +44 (0) 1224 552 495; fax: +44 (0) 1224 550 925. E-mail address: [email protected] (G.T. Jones).
rence of multiple common symptoms in childhood (frequent headache, abdominal pain and vomiting) is associated with a 50% increase in the risk of CWP at 45 yrs [19]. This is consistent with other evidence that suggests that those who report common symptoms in childhood experience an increase in the risk of a number of ‘unexplained’ symptoms in adulthood [6,14]. Several authors have also demonstrated that adults with CWP and/or fibromyalgia report an excess of adverse events in childhood. Imbierowicz and Egle found that patients with fibromyalgia had more frequent and/or more severe adversities during childhood compared to patients with chronic pain of nociceptive or neuropathic origin [17], and McBeth and colleagues demonstrated that compared to those with no pain, persons with CWP self-report more hospitalisations, operations, parental loss, and abuse in childhood [26]. However, further examination of objective data (in this case primary care records) revealed evidence of recall bias – those with CWP very accurately recalled these prior events, whereas those free of pain under-reported their true occurrence, thus augmenting the observed relationship. To examine the relationship between early life adverse events and pain in adulthood, in the absence of recall bias, prospective stud-
0304-3959/$36.00 Ó 2009 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.pain.2009.02.003
G.T. Jones et al. / PAINÒ 143 (2009) 92–96
ies are required. However, to date, there are few large-scale longitudinal studies in this field. The aim of the current study was to examine, prospectively, the relationship between physical and psychological adversity in early childhood and CWP in adulthood. 2. Methods The 1958 British Birth Cohort Study (or ‘National Child Development Study’) is a large, ongoing, prospective cohort study of all children born in England, Scotland and Wales in one week in March 1958 [29]. It comprises 17,638 participants who were recruited at birth, supplemented by 920 early migrants, all born in the same week. Participants have been followed up on numerous occasions, and a variety of data have been collected, including information on socioeconomic status, health and development, and familial and education factors. At 7 yrs, parents of participants (most commonly mothers) were interviewed by a Local Authority health visitor, using a structured interview schedule. Data were collected on a variety of adverse childhood events, including on physically traumatic events (hospitalisation following a road traffic accident, surgery, or hospitalisation following an accident at either home or elsewhere); and poor social and psychological environment (periods in local authority care/maternal separation, death of a parent, or parental divorce, alcoholism, or financial hardship). At 45 yrs, 12,069 participants still in contact with the study, and who at 42 yrs had not required a proxy interview, were invited to participate in a biomedical survey. Of these, 10,596 had at least some data on adverse events at 7 yrs, and thus formed the target population for the current study. The survey collected data on a number of health-related factors including the presence of pain. Participants were asked ‘‘During the past month, have you had any ache or pain which has lasted for one day or longer?” Those who answered positively were asked to indicate the location of their pain(s) on a four-view body manikin, and to indicate whether they had been aware of the pain for more than three months. CWP was defined according to the American College of Rheumatology Criteria for the Classification of Fibromyalgia [35] – viz: pain present for three months or longer, both above and below the waist; on both the left and right sides of the body; and in the axial skeleton. 2.1. Analysis The relationship between adverse childhood events and CWP was examined using Poisson regression. Thus, results are expressed as risks ratios (RR) with 95% confidence intervals
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(95%CI), the latter being derived using robust estimates of standard error [11]. Sex, psychological distress, and socioeconomic status were assessed as potential-mediating variables. Psychological distress was measured at age 42 years, using the General Health Questionnaire [10]; each item was scored using the Likert scoring system [9], summed, and divided into tertiles for analysis. Socioeconomic status in adulthood was based on the occupation at age 42 yrs (or at 33 yrs where the former was not available) and, in childhood, based on the paternal occupation at birth, or at age 7 yrs where the data at birth were missing. At both time points it was classified using the Registrar General’s Classification: professional (I); managerial/technical (II); other non-manual (IIInm); skilled manual (IIIm); partly skilled (IV); and unskilled manual (V). To adjust for potential confounding between multiple adverse exposures, a forward stepwise multivariable model was created of all social/psychological adverse events which predicted the outcome at p > 0.20. Variables were included in the final model at p = 0.10 and eliminated at p = 0.15. All analyses were conducted using Stata v10.0 (StataCorp, College Station, Texas). 2.2. Ethical approval Ethical approval for the most recent follow-up (45 yrs) was obtained from the South East, UK, Multi-centre Research Ethics Committee (reference 01/1/44). 3. Results From a total of 9377 participants followed up at age 45 yrs, 7571 provided pain (outcome) data and came from the target sample for the current analysis, giving a response rate of 71.5% (7571/ 10,596). The prevalence of CWP was 12.3%, and there was no difference between men (11.8%) and women (12.7%) (chi2: 1.5; p = 0.22). Reports of a surgical operation in childhood (i.e. before 7 yrs) was fairly common (23%), and most commonly this was for tonsillectomy or adenoidectomy (70%). However, children who underwent surgery were no more likely to report CWP as adults compared to other children (RR: 1.0; 95%CI: 0.9–1.1). Even those who experienced two or more operations as children were at no greater risk of CWP in adulthood (Table 1). Children who had been hospitalised following a road traffic accident experienced a 40% increase in the risk of CWP (1.4; 0.96–1.9), and this relationship remained – augmented slightly – after adjusting for sex, social class and psychological distress (1.5; 1.05–2.1). In contrast, hospitalisation for other reasons
Table 1 Association between childhood physically traumatic adverse events and CPWP at 45 yrs. Exposure
CWP
Total
Risk ratio (95%CI)
Model statistics
Crude
Adjusted*
5715 1560 172
1.0 1.0 (0.8–1.1) 1.1
1.0 1.0 (0.8–1.1) 1.1 (0.7–1.6)
chi2 = 207.95; df = 17; p < 0.001
Hospitalisation following a road traffic accident No 892 (12.2%) Yes 27 (16.6%)
7335 163
1.0 1.4 (0.96–1.9)
1.0 1.5 (1.05–2.0)
chi2 = 213.85; df = 16; p < 0.001
Hospitalisation following an accident at home No 844 (12.4%) Yes 73 (11.0%)
6808 666
1.0 0.9 (0.7–1.1)
1.0 0.9 (0.7–1.1)
chi2 = 211.55; df = 16; p < 0.001
Hospitalisation following an accident (other) No 840 (12.3%) Yes 75 (12.0%)
6838 623
1.0 1.0 (0.8–1.2)
1.0 1.0 (0.8–1.3)
chi2 = 212.03; df = 16; p < 0.001
Surgical operations None 1 P2
*
702 (12.3%) 187 (12.0%) 23 (13.4%)
Adjusted for sex, social class (childhood and adulthood) and psychological distress (adulthood).
G.T. Jones et al. / PAINÒ 143 (2009) 92–96
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(accidents at home/other accidents) was not associated with an increase in risk (Table 1). There was a positive relationship between the length of time a child had been separated from its mother, prior to the age of 7 yrs, 2 and the risk of CWP in adulthood (chitrend : 7.98; p < 0.001). Compared to those who have never experienced separation, those who had been separated for >6 months experienced a 40% increase in the risk of CWP (1.4; 1.02–2.1); an association that remained after adjusting for sex, social class and psychological distress (Table 2). Children who had ever resided in institutional care also experienced an increase in the risk of CWP in later life (1.9; 1.4–2.7); an association that also remained after adjustment for sex, social class and psychological distress (1.7; 1.3–2.4). Further, this variable completely explained the relationship between maternal separation and CWP. No association was found between paternal death, before the age of 7 yrs, and the risk of CWP (0.9; 0.5–1.9). However, maternal death was associated with a doubling in the risk of future symptoms (2.0; 1.08–3.7). Financial family difficulties in childhood were also associated with an increase in the risk of CWP in adulthood, and this relationship remained after adjusting for sex, social class and psychological distress (1.6; 1.3–1.9). Multivariable analysis revealed that, on mutual adjustment, financial difficulties (1.4; 1.2– 1.8), maternal death (2.6; 1.5–4.6) and periods in local authority care (1.6; 1.1–2.2) were all independent predictors of CWP in adulthood.
There are a number of methodological points to consider. Firstly, attrition: of 10,596 individuals with known exposure at 7 yrs, only 7571 provided data on CWP at age 45 yrs (71.5%). Sample attrition would decrease sample size and would increase the likelihood of finding a non-significant result; in the light of some of the current findings, this is important. However, although loss to follow-up will affect the significance of any associations, it should not alter the point estimates. Further, the sample size is still substantial and we calculate that we have 90% power, at the 95% confidence level, to detect a 50% increase in the risk of CWP (should such a relationship exist) associated with any risk factor with a prevalence of 5%. More important is the issue of differential follow-up. Previous work has shown that, while the 45 yr sample remains broadly representative of the surviving cohort [2], follow-up is poorer in the most extreme adversity groups – e.g. persons who resided in local authority care – and this might introduce a bias. However, the effect of this would be to bias our findings towards the null. Childhood events were measured by maternal report. Given familial aggregation of fibromyalgia and depression, it is likely that the mothers of children who went on to develop CWP had higher rates of depression themselves. It is possible, therefore, that these women over reported negative events in their children’s lives, relative to other women, although to explain the current findings, such bias would have to be selective, with an over report of some childhood experiences (e.g. hospitalisation following road traffic accidents), but not others (e.g. surgery). This seems unlikely and, thus, while recall bias cannot be firmly ruled out, we consider it improbable. There will be some measurement error in the potential-mediating variables (social class and psychological distress) as these variables were recorded at 42 yrs, three years prior to the outcome. This problem may be particularly acute for social class, which for some individuals (approximately 12%) was recorded at 33 yrs. However, it is unlikely that the measurement of these variables was sufficiently poor to completely explain the current findings.
4. Discussion We report the results of a longitudinal population-based study to examine the relationship between adult CWP and adverse childhood events. We have shown that physically traumatic events and factors suggesting poor social/psychological environment are associated with long-term increased risk of CWP, and that these associations remain after adjustment for psychological distress and social class.
Table 2 Association between childhood social/psychological adversity and CWP at 45 yrs. Exposure
CWP
Total
Risk ratio (95%CI)
Model statistics
Crude
Adjusted* 1.0 1.0 1.1 1.2 1.4
Maternal separation None <1 wk 1 wk–1 month 1–6 months >6 months
186 265 357 86 30
(11.4%) (11.3%) (12.9%) (14.4%) (16.6%)
1626 2343 2767 596 181
1.0 1.0 1.1 1.3 1.4
Ever in institutional care No Yes
896 (12.1%) 30 (23.3%)
7427 129
1.0 1.9 (1.4–2.7)
1.0 1.7 (1.2–2.3)
chi2 = 227.35; df = 16; p < 0.001
Death of father No Yes
882 (12.3%) 9 (11.3%)
7162 80
1.0 0.9 (0.5–1.7)
1.0 0.9 (0.5–1.6)
chi2 = 197.48; df = 16; p < 0.001
Death of mother No Yes
882 (12.2%) 7 (25.0%)
7230 28
1.0 2.0 (1.08–3.9)
1.0 2.0 (1.08–3.7)
chi2 = 201.35; df = 16; p < 0.001
Family difficulties (divorce/separation/desertion) No 845 (12.2%) Yes 41 (17.2%)
6952 238
1.0 1.4 (1.1–1.9)
1.0 1.3 (0.99–1.7)
chi2 = 202.90; df = 16; p < 0.001
Family difficulties (alcoholism) No 787 (12.1%) Yes 10 (20.8%)
6519 48
1.0 1.7 (0.99–3.0)
1.0 1.3 (0.8–2.4)
chi2 = 171.74; df = 16; p < 0.001
Family difficulties (financial) No Yes
6356 419
1.0 1.8 (1.5–2.2)
1.0 1.6 (1.3–1.9)
chi2 = 212.17; df = 16; p < 0.001
*
737 (11.6%) 89 (21.2%)
(0.8–1.2) (0.96–1.3) (0.99–1.6) (1.02–2.1)
Adjusted for sex, social class (childhood and adulthood) and psychological distress (adulthood).
chi2 = 217.32; df = 19; p < 0.001 (0.9–1.2) (0.96–1.3) (0.9–1.5) (0.9–1.9)
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We would argue that social class at 33 yrs, while not a perfect measure of social class at 45 yrs, probably contains more signal than noise. Therefore, if the relationship between childhood adversity and CWP was explained by social class, one would expect to see at least some attenuation of risk effects. This was not the case. CWP was assessed at a single point in time, 45 yrs, using a body manikin in a questionnaire survey. From this, we have no data on the composition of the CWP group, in terms of underlying pain problems (e.g. fibromyalgia, versus multiple regional pains, versus multiple injury), nor is it possible to ascertain the duration of symptoms experienced. However, it is probable that a large proportion of the persons would have experienced these symptoms for many years because seldom do they first occur as late as mid-adulthood [25]. Although it is possible that in some subjects, CWP may have originated in childhood, it is unlikely that in these children the maternal report of adverse events was sufficiently augmented as to explain the current findings. This is not the first study to examine the relationship between chronic pain and early adverse experiences. Kopec and Sayre [21] demonstrated an increase in the risk of back pain associated with stressful life events in childhood; and Juang and colleagues found that adolescents with chronic daily headache reported more childhood adversities and, in particular, an excess of physical abuse and parental divorce [20]. However, the majority of previous studies have assessed exposures retrospectively, relying on recall of childhood events and have been shown to be susceptible to recall bias: persons with/without CWP recall prior events with differing degrees of accuracy, leading to spurious estimates of the risk associated with these events [26]. Longitudinally, Raphael and colleagues demonstrated a 20–40% increase in the likelihood of unexplained pain in adulthood associated with childhood victimisation, physical or sexual abuse, or neglect, albeit not statistically significant [30], and Hotopf et al. found that some childhood experiences – maternal ill health – were associated with chest pain at 36 yrs [15]. In the current study, we have focused on events prior to age 7 yrs. It is likely that pain in adulthood is also a function of events later in life. However, by focusing on very early exposures, one decreases the likelihood of observing any effect. The fact that we have observed effects of reasonable magnitude, and of statistical significance, highlights the importance of these exposures. We have shown that children who are hospitalised following a road traffic accident experience a significantly increased risk of CWP nearly 40 yrs subsequently. Whereas other physical exposures – such as surgery, or an accident in the home – are not similarly associated with adult pain. We cannot explain the specificity of this relationship. It may be that (a) in the current study, the trauma involved in the road traffic accident was greater than that in the other accidents; (b) there may be psychological sequelae associated with road traffic accidents that play a role in CWP development, independent of the effects of the physical trauma per se; or (c) that this finding has arisen by chance. It is interesting, however, that these results are consistent with recent studies in adults, which have demonstrated that exposure to a road traffic accidents but not to other physically traumatic events (surgery/accident at work/fracture) is associated with an increase in the risk of CWP in the shortto medium-term [18]. It should be noted, however, that while the magnitude of effect measures is sizeable (risk ratios ranging from 1.5 to 2.0) because these exposures are rare, the population attributable risks are relatively small. In combination, hospitalisation following a road traffic accident, periods in residential care, maternal death, and financial hardship in childhood only account for around 7.5% of all cases of CWP. We provide evidence that children who are exposed to physical and social adversity experience a 50–100% increase in the risk of CWP in adulthood. What could be the likely mechanism of this relationship? Firstly, one must consider confounding. While this
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cannot be ruled out, the most likely confounders are emotion and distress: these are undoubtedly associated with childhood adverse events and have been demonstrated to be strong predictors of CWP in adulthood [3,23,24]. However, our results are robust to statistical adjustment for General Health Questionnaire score – an instrument demonstrated to be a valid and reliable measure of general psychological distress [32]. Psychosocial or psychological variables may in fact be mediating factors, rather than confounders per se. Either way, however, one would expect statistical adjustment for psychological distress to attenuate the effect of early life adversity. Whereas, no such attenuation is observed. One cannot rule out residual confounding if, for example, the General Health Questionnaire has not fully or adequately captured psychological distress. However, it is unlikely that such an effect would completely negate the observed risk effects. Secondly, the increased risk of CWP in adulthood may be a function of a disadvantageous life trajectory, or that early insults make an individual more susceptible or vulnerable to the effect of risk factors experienced in later life. Exposure to risk events does not follow a random distribution in the population. Thus, disadvantaged children may be more likely to accumulate risks throughout life [31], and it may be one of these later events that act as the final ‘cause’ of CWP. However, our results are altered little by adjustment for adult social class. This suggests that if later life events are responsible for the increase in the risk of CWP, these events are independent of socio-economic status. Finally, early life adverse events may exhibit a long-term biological effect through a number of endocrine pathways. Recent studies suggest an important role of the hypothalamic–pituitary–adrenal (HPA) axis in the onset of CWP [27], and there is some evidence that adverse childhood experiences are associated with HPA axis dysregulation [8,22]. Further, studies in neonates have shown that insults in early life have effects on pain perception that persist well beyond infancy [13], and others have demonstrated, in animal models, that environmental manipulations during development – such as extended periods of maternal separation – can permanently alter HPA axis function, modifying the biological response to stressful stimuli in later life [28]. In summary, we have shown that both physical and social adversity prior to age 7 yrs are associated with an increase in the risk of CWP nearly 40 yrs subsequently. In order to prevent longterm health consequences of adverse childhood events, future research should study the mechanisms, in particular, the biological mechanisms, underlying this relationship. Elucidation of these pathways will need large-scale longitudinal studies using markers of potentially altered biological function.
Acknowledgements We are grateful to the study participants in the birth cohort study. Great Ormond Street Hospital/University College London, Institute of Child Health receives a proportion of funding from the UK Department of Health’s National Institute of Health Research (‘Biomedical Research Centres’ funding). The MRC provides funds for the MRC Centre of Epidemiology for Child Health. None of the authors have any financial or other relationships that might lead to a conflict of interest.
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