Guy's, King's and St Thomas' Schools of Medicine and Dentistry, and the Institute of Psychiatry
Maudsley Hospital, London
Oxford University
Medical Research Council National Survey of Health and Development and Visiting Professor at the Department of Epidemiology and Public Health, University College London Medical School
Guy's, King's and St Thomas' Schools of Medicine and Dentistry, and the Institute of Psychiatry, London
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Correspondence: Dr M. Hotopf, Department of Psychological Medicine, Guy's, King's and St Thomas' Schools of Medicine and Dentistry, and the Institute of Psychiatry, 103 Denmark Hill, London SE5 8AZ. Tel: +44 020 7740 5078; fax: +44 020 7740 5129
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ABSTRACT |
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Aims To test these hypotheses.
Method We used data from the Medical Research Council (MRC) National Survey of Health and Development, a population-based cohort study established in 1946 (n=5362). Subjects were followed from birth in 1946 until 1989 (age 43 years). As outcome, we used operationally defined medically unexplained hospital admissions at age 15-43 years. Exposure variables included childhood illness, and illness in parents during the childhood of the subjects.
Results The risk set (n=4603) comprised individuals still in the Survey at age 15. Ninety-five unexplained hospital admissions were identified. Subjects whose mothers reported below-average health in the father were at increased risk of subsequent unexplained admissions. Below average reported health in the mother was not associated with this increased risk. Defined physical diseases in childhood were not associated, but persistent abdominal pain at age 7-15 years was.
Conclusions Unexplained hospital admissions are associated with certain childhood experiences of illness, but defined physical illness in childhood is not a risk factor.
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INTRODUCTION |
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METHOD |
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Exposures
A range of different variables was collected before the children had
reached 16, and these will form the main exposures for this paper. They are
organised into three main domains: (a) the health of the parents during the
childhood of the subjects; (b) the health of the subjects in childhood; and
(c) the personality or behaviour of the subjects in childhood.
Outcome
At each wave of data-gathering all subjects were asked whether they had
been admitted to hospital since they were last seen by the Survey. For
subjects who had missed the previous wave of data-gathering, the interviewer
was given the date of last contact by the Survey, in order to ensure that
hospital admissions which would have been reported in the previous wave were
recorded. For each admission a questionnaire was sent to the hospital
consultant or medical records administrator, requesting the following details:
diagnosis on admission; investigations performed; diagnosis on discharge; and
treatment given. The physicians or surgeons were encouraged to give full
details of the admission, and often provided discharge summaries or copies of
the case notes. These questionnaires have been put on microfiche. Hence
details of all hospital admissions for the cohort to age 43 years were
available, if needed.
Because medically unexplained admissions to hospital are the focus of this study, and these are not coded separately or given a clearly defined ICD code in the World Health Organization's International Classification of Diseases, two investigators (M.H. and C.W.J.) viewed each microfiche for the entire cohort. They noted any admission which appeared to have been medically unexplained (investigations were negative, or a discharge diagnosis suggested that the cause of the initial complaint was unknown) (269 admissions in 206 survey members). All details of such admissions, including diagnosis on admission, discharge diagnosis, treatments given, investigations performed and any further incidental comments made by the physician, were recorded verbatim in a structured manner. In order to prevent potential bias, gender was disguised where possible (this was impossible when, for example, the chief complaint was gynaecological), and any comments regarding family histories of illness, or illness before the age of 15, were omitted.
Medically unexplained hospital admissions
Medically unexplained admissions were defined as follows.
Four medically qualified investigators (M.H., S.W., C.W.J., and R.M.) determined the likelihood that each admission was medically unexplained using the above definition. The main problem faced in diagnosing medically unexplained admissions was that in many cases there was insufficient evidence to be able to be sure that the admission was truly unexplained. For example, in many cases the initial diagnosis would read abdominal pain, the final diagnosis abdominal pain ?cause and the treatment might have been appendectomy. Such information implies that the patient was admitted with abdominal pain, had an appendectomy, but at discharge the diagnosis remained uncertain. Thus, it implies that the appendix was not inflamed. It seemed very likely that such admissions were unexplained, in the sense that the clinicians had failed to detect a defined underlying cause for the symptoms; however, it was also possible that the presentation was due to a transient undiagnosed infectious illness, which was simply not tested for. In order to avoid misdiagnosing such presentations as medically unexplained, the presence of non-specific indicators of infection or inflammation (such as raised white cell counts, pyrexia, raised ESR) rendered such cases ineligible to qualify as medically unexplained admissions.
Operational criteria
In order to increase the degree of certainty that an admission was
medically unexplained, a four-point scale was devised, with the categories:
not unexplained (meaning the admission did not meet the criteria laid down
above); possibly unexplained; probably unexplained; and definitely
unexplained, as defined below.
Possible. The conditions described above were met, but there was a shortage of desirable information: for example, when the diagnosis on admission was suspected appendicitis, and the diagnosis on discharge was abdominal pain, cause unknown. This diagnosis implied a medically unexplained admission, but further information would have been required to say confidently that there was an absence of defined organic pathology.
Probable. The conditions for medically unexplained admission were met, and there was either more information (suggesting that a reasonable degree of thoroughness was used to investigate the symptoms), or the physician mentioned possible psychosocial reasons for the presentation, or gave a diagnosis which strongly implies medically unexplained symptoms (e.g. irritable bowel syndrome, atypical chest pain, chronic fatigue syndrome).
Definite. The conditions for medically unexplained admission were met, and there was evidence of extensive and thorough investigations which were all given normal or negative results; and the physician mentioned possible psychosocial reasons for the presentation, or gave a diagnosis which strongly implies medically unexplained symptoms (e.g. irritable bowel syndrome, atypical chest pain, fibromyalgia).
The point of these categories was to increase the degree of confidence with which the diagnosis of unexplained symptoms could be made. For some subjects, rich and complete information was available on a variety of investigations, with a clear final diagnosis of a medically unexplained syndrome. These would be designated as definite cases. In others, there was evidence either from the investigations or from the final diagnosis that the symptoms were unexplained; these fell into the probable category. The possible category would include the example of abdominal pain given above: the cause for the presentation was never determined, but there was insufficient evidence to be clear that the presentation was truly medically unexplained.
Two further categories were included: mixed admissions, where there was clear evidence of defined organic pathology but significant psychological overlay was detected; and factitious illness.
The four investigators rated the entire sample. Agreement between the investigators for the categories factitious and mixed was unanimous for the small number (3) of relevant cases. For the remaining admissions the weighted kappa between investigators was 0.65-0.80. Further work has suggested that this approach can be generalised and that psychiatrists achieve acceptable agreement with physicians (Reid et al, 1999).
For the purposes of this article, a medically unexplained admission was diagnosed when at least three of the four investigators thought that the admission was at least probably medically unexplained (n=95 survey members).
Statistical analyses
Statistical analyses were performed using STATA computer software
(StataCorp, 1997). As
medically unexplained hospital admissions could occur at any time between age
15 and age 43, rates of first admissions were analysed. The risk set was
defined as all participants to the study from age 15 onwards
(n=4603). The time from the 15th birthday until first admission for
medically unexplained symptoms was calculated. For those who had not been
admitted to hospital, time from age 15 until the last point of contact with
the survey was calculated. Subjects who dropped out or who died before the
last wave of data-gathering contributed person-years at risk up to the point
of their last contact. For example, if a survey member had completed the
assessment at age 26, but subsequently died aged 31, he or she would
contribute person-years of risk up to the last point of contact with the
survey, and not up to the point of death. The reason for this was that the
outcome depended upon the survey member giving information; this would have
been available up to the age of 26, but not between the ages 26 and 31. Using
these data, rates of admission according to the key exposure variables were
calculated.
Cox's proportional hazards model was used to calculate hazard ratios. These analyses were controlled for gender and father's social class, and were adjusted for sampling weights. Gender-exposure interactions were derived, and where these were statistically significant, results were stratified for gender. Cox's proportional hazard model assumes that relative risk calculated over the period of follow-up is constant. In other words, if the relative risk of developing the outcome is 2, the model assumes that this increased risk among the exposed applies throughout the period of follow-up thus the hazards remain proportional. In order to test this assumption, the results may be represented graphically using Aalen plots. These plot the cumulative rate of the outcome over the duration of the follow-up period according to exposure group. If hazards are proportional, the plot would be expected to diverge at a constant rate. Discontinuities in the rates (for example, points where a relatively steep line for those exposed drops off, and crosses the trajectory of the unexposed) suggest that the proportionality assumption has been broken. Aalen plots are shown here for the main associations we detected.
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RESULTS |
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Table 2 shows the socio-demographic characteristics of individuals with unexplained admissions. The slight excess of females was not statistically significant. There was a clear relationship between medically unexplained symptoms and social class, with higher rates in non-professional classes.
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Relationship between unexplained hospital admissions and family
ill-health
Table 3 shows the
relationships between unexplained hospital admissions and illhealth in the
family during the subject's childhood. Perceived ill-health in the father and
paternal nerves were found to be associated with the outcome.
Figure 1 shows the Aalen plot
for paternal health and Fig. 2 shows the Aalen plot for paternal nerves. These demonstrate that
over the period of follow-up the rates in the three groups remained
approximately proportionate.
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No clear pattern emerged regarding maternal neuroticism; however, this
variable did have a statistically significant interaction term with gender
(2=4.9, 1 d.f., P=0.03).
Table 4 demonstrates the effect
of this interaction: maternal neuroticism was associated with an increased
risk of the outcome in males but not females.
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Relationship between unexplained hospital admissions and childhood
ill-health
Table 5 shows the
relationships between the various measures of childhood ill-health and the
outcome. There was no association between well-defined childhood diseases and
subsequent hospital admissions for medically unexplained symptoms. There was a
strong association between persistent abdominal pain in childhood and the
outcome: children who complained of persistent abdominal pain were over four
times as likely to go on to experience unexplained hospital admissions as
those who did not. Figure 3 shows the Aalen plot for this relationship, which suggests the proportionality
assumption was not broken.
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Because abdominal and pelvic pain were the most common presenting symptoms in the medically unexplained hospital admissions, it was possible that this relationship was simply the result of a continuation of the same symptoms into early adult life. The Aalen plot demonstrates that the increased risk of childhood abdominal pain continues to act throughout adult life. In order to explore this further, the analyses were repeated for two separate groups: those whose admissions were dominated by abdominal or pelvic pain, and those who did not have these symptoms. Surprisingly, childhood abdominal pain was a less powerful predictor of admissions for unexplained abdominal pain or pelvic pain in later life (hazard ratio (HR) 2.8; 0.5-14.7) than for admissions not connected with these symptoms (HR 5.4; 1.5-19.4).
Absence from school was inconsistently associated with the outcome. Before the age of 15 there was no association. However, children whose teachers rated them as frequently absent at age 15 had an increased likelihood of subsequently being admitted to hospital with unexplained symptoms.
Relationship between unexplained hospital admissions and childhood
behaviour and personality
Table 6 shows the
relationships between unexplained admissions and ratings of childhood
behaviour and personality. There was no association with neuroticism on the
Pintner scale, but there was an association with extroversion; extrovert
children were more likely to be admitted for unexplained symptoms. It is
difficult to show a consistent relationship with the teachers' ratings of
behaviour in the children. There were no associations between low energy,
day-dreaming or disobedience, and unexplained hospital admissions. However,
there was a relatively strong association between being a poor worker, and
having poor powers of concentration, and the outcome.
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Individuals who had had a medically unexplained hospital admission as a child were at increased risk of having been admitted to a ward during their adult life (unadjusted odds ratio (OR) 6.9; 95% CI: 4.1-11.5).
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DISCUSSION |
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Shortcomings
It is likely that many more hospital admissions in this sample were
medically unexplained, but we had insufficient details to make the diagnosis
in those cases. Such incomplete ascertainment could lead to bias if the
diagnosis of unexplained admissions was influenced by the exposures under
study. For example, if a childhood history of severe physical illness was
taken into account in the diagnosis, this could lead to an exaggeration of the
relationships detected. This could account for the relationship between
unexplained abdominal pain and later hospital admissions, as consultants might
have been more convinced the symptoms were unexplained, given this history.
However, it seems unlikely that this would influence the relationships between
hospital admissions and parental ill-health. Ascertainment of some of the
childhood risk factors was also incomplete; these factors may have been
non-random, and led to biases which are difficult to predict.
Mechanisms
These findings partially confirm previous reports that exposure to illness
in childhood is a risk factor for subsequent unexplained symptoms. Father's
ill-health appears more important than mother's, and exposure to illness in
the individual in childhood seems to be specific to certain types of
ill-health. Thus, severe chronic physical diseases are not associated with
later unexplained hospital admissions, whereas persistent abdominal pain in
childhood is. This is consistent with the relatively good psychosocial outcome
for the former and the poor psychosocial outcome for the latter, which has
been reported elsewhere (Hotopf et
al, 1998; Pless et
al, 1989). These studies suggest that future interventions
aimed at reducing the longer-term harmful effects of paediatric illness on
psychological health should be targeted at children with unexplained symptoms.
Paediatricians should be reassured that severe chronic diseases have not been
found to be associated with later unexplained symptoms.
The relationship between abdominal pain in childhood and subsequent unexplained hospital admissions was not due to a simple continuation of the symptom in adulthood. Instead, children with persistent abdominal pain appear to go on to develop a range of other symptoms relating to different bodily systems. This concurs with evidence suggesting that medically unexplained syndromes such as irritable bowel syndrome, fibromyalgia and chronic fatigue syndrome all have considerable overlap with one another (Kirmayer et al, 1988; Yunus et al, 1989; Goldenberg et al, 1990; Lane et al, 1991; Hudson et al, 1992; Nooregaard et al, 1993). These appear not to be specific syndromes, but overlapping conditions.
It is unclear how the relationship between paternal ill-health and hospital admissions operates, and why it should be present in the father and not the mother. Unfortunately, there were insufficient details on the exact nature of the fathers' health problems. One intriguing possibility derives from the method of data collection: the father's health status was reported by the mother. Thus, the active ingredient behind this association may be having a parent who identifies and reacts to illness in others in the family. There is some evidence from laboratory studies of social learning that subjects react to pain at a lower threshold when in the presence of a model who cannot tolerate the pain (Craig & Weiss, 1971, 1972). Individuals from families where one parent is distressed by symptoms may, therefore, react to symptoms more readily than those who do not have such experiences. There is some (retrospective) evidence that avoidant illness behaviour (for example, retiring to bed with a headache) is influenced by parental reactions to common illnesses (Turkat & Noskin, 1983). Such parental reactions may also affect illness behaviour in well-defined diseases such as diabetes (Turkat, 1982).
There was a relationship between unexplained hospital admissions and childhood personality; however, this seemed to operate in a different direction to that predicted by our hypothesis. Neuroticism and other internalising traits such as fatigue and day-dreaming were not associated, but extroversion and other similar traits (poor concentration and poor school work) were. This may reflect the nature of the outcome used i.e. actual use made of services in cases of unexplained symptoms. It may be that more introverted individuals have precisely the same rates of unexplained symptoms, but do not contact their doctors or visit accident and emergency departments.
This paper indicates that certain childhood risk factors are associated with later unexplained symptoms leading to hospital admissions. The diagnoses of such unexplained symptoms tend to be diagnoses of exclusion, made following exhaustive investigations. Research such as this may be able to build up a profile of risk factors which allow clinicians to make positive diagnoses of unexplained symptoms.
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Clinical Implications and Limitations |
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LIMITATIONS
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REFERENCES |
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Received for publication June 8, 1999. Revision received September 21, 1999. Accepted for publication September 21, 1999.