facilitate presentation of antigens to immunocompetent
Use of prior vaccinations for the development of new
cells and their activation which could lead to a long-lasting
immune response.
We are grateful to Mrs C White for reviewing the typescript.
References
1 Milliner DS, Shinaberger JH, Shuman P, Coburn JW. Inadvertent
aluminium administration during plasma exchange due to aluminium
contamination of albumin-replacement solutions. N Engl J Med 1985;
312: 165-67.
2 Gupta RK, Relyveld EH, Lindbald EB, Bizzini B, Ben-Efraim S,
Gupta CK. Adjuvants-a balance between toxicity and adjuvancy.
Vaccine 1993; 11: 293-06.
3 Gluck R, Mischler R, Brantschen S, Just M, Althaus B, Cryz SJ Jr.
Immunopotentiating reconstituted influenza virus virosome (IRIV)
vaccine delivery system for immunization against hepatitis A. J Clin
Invest 1992; 90: 2491-95.
4 Herzenberg LA, Tokuhisa T. Epitope specific regulation. J Exp Med
1982; 155: 1730-40.
5 Etlinger HM, Gillessen D, Lahm HW, Matile H, Schonfeld HJ,
Parental neglect during childhood and increased risk of obesity in
young adulthood
Summary
The association of various features of family life with obesity in
childhood is well established, but less is known about the
effect of these influences on the risk of later obesity. In this
prospective, population-based study, we examined the
influence of parental care in childhood on the risk of obesity in
the offspring in young adulthood.
In 1974, 1258 pupils aged 9-10 years were randomly
selected from the third grade of Copenhagen schools.
Information on 987 pupils was obtained from the form
teachers on family structure and the perceived support from
the parents; school medical services reported on the child’s
general hygiene. 756 (86%) of the 881 eligible participants
were followed up 10 years later. The influence of family factors
in childhood on the risk of obesity (body-mass index >95th
centile) in young adulthood was estimated by odds ratios with
control for age and body-mass index in 1974, sex, and social
background. Family structure (biological or other parents and
number of siblings) did not significantly affect the risk of adult
obesity. Parental neglect greatly increased the risk in
comparison with harmonious support (odds ratio 7·1 [95% Cl
2·6-19·3]). Dirty and neglected children had a much greater
risk of adult obesity than averagely groomed children (9·8
[3·5-28·2]). However, being an only child, receiving
overprotective parental support, or being well-groomed had no
effect.
Parental neglect during childhood predicts a great risk of
obesity in young adulthood, independent of age and body-
mass index in childhood, sex, and social background.
Lancet 1994; 343: 324-27
Institute of Preventive Medicine, Copenhagen Health Services,
Kommunehospltalet, DK-1399 Copenhagen (I Lissau PhD,
Prof T I A Sørensen Dr Med Sci); and Department of Paediatrics,
Rigshospitalet, University of Copenhagen (I Lissau), Denmark
Correspondence to: Dr Inge Lissau
324
Trzeciak A.
vaccines. Science 1990; 249: 423-25.
6 Schutze MP, Deriaud E, Przewlocki G, Le Clerc C. Carrier-induced
epitopic suppression is initiated through clonal dominance.J Immunol
1989; 142: 2635-40.
7 André FE, Hepburn A, D’Hondt E. Inactivated candidate vaccines for
hepatitis A. Prog Med Virol 1990; 37: 72-95.
8 Ambrosch F, Wiedermann G, André FE, et al. Comparison of HAV
antibodies induced by vaccination, passive immunization and natural
infection. In: Hollinger FB, Lemon SM, Margolis HS, eds. Viral
hepatitis and liver disease. Baltimore: Williams and Wilkins, 1991:
98-100.
9 Anon. Hepatitis A: a vaccine at last. Lancet 1992; 339: 1198-99.
10 André FE, D’Hondt E, Delem A, Safary A. Clinical assessment of
safety and efficacy of an inactivated hepatitis A vaccine: rationale and
summary of findings. Vaccine 1992; 10 (suppl 1): S160-68.
11 Poovorawan Y, Tieamboonlers A, Chumdermpadetsuk S, Glück R,
Cryz SJ. Control of a hepatitis A outbreak by active immunization of
high-risk susceptibles. J Infect Dis (in press).
12 Gluck R. Towards a universal IRIV traveller vaccine. Third
Conference on International Travel Medicine, April 26-29, 1993. Paris
(abstr). International Society of Travel Medicine, Paris, 1993.
Introduction
Although it is generally accepted that characteristics of
family life are closely linked to the development and
maintenance of obesity in children,l the extent to which
they determine the child’s later propensity to obesity has
not been much investigated.2-4 The possible influence of
family factors5,6 has been debated for several decades.
Bruchmade interesting observations while treating obese
children. She described a prototype of a mother of an obese
child as ambivalent, exerting overprotection and rejection
at the same time. Many obese children were unwanted, only
children, or an afterthought. In a cross-sectional study of
Copenhagen schoolchildren, Quaade8 could not replicate
her findings.
In this 10-year follow-up study of a randomly selected
cohort of 9-10-year-old children,9-11 we examined the
effects of family structure and parents’ care for their
offspring’s well-being during childhood on risk of obesity
in young adulthood.
Subjects and methods
In 1974, a random sample of children, mostly aged 9-10 years, was
drawn from the population of pupils attending the third school
grade in the Copenhagen municipality.12 The sample comprised
1258 children, 25% of the population. The key professionals at
school (the form teacher and the school nurse or doctor) and the
parent or guardian answered questionnaires about the child.
Complete information from school sources was obtained at the first
examination for 987(78%).881 children who were still living on the
island of Sjaelland were followed up 10 years later by a mailed
questionnaire and a subsequent home visit in 1984-85." The
participation rate in follow-up was 86% (756). The 231 children
who were not followed up (106 not available for 10-year follow-up
and 125 non-respondents) showed, as expected, more school
difficulties and health problems, and were of lower social class than
participants."
The form teachers’ questionnaire was completed for 1120
children (89%); it included questions on family structure and an
assessment of the teacher’s perceived support by the parents of
their child (table 1). In Denmark, the form teacher normally has

Table 1: Prevalence of obesity In childhood and young
adulthood In relation to family factors In childhood
daily contact with the pupils and teaches them at least one major
subject, usually for several years. He or she is the person mainly
responsible for contact with parents and coordination of class work.
97% (247) of the form teachers had known the participating pupil
for atleast 6 months.12 The school medical service (59 school
nurses, 16 school medical officers) at the same time, but
independently, answered a questionnaire (for 1100 children [87%])
about the general hygiene of the child (table 1) and reported the
height and weight.
The reported height (without shoes, to the nearest cm) and
weight (naked or in light underwear, to the nearest kg) were those
recorded at the latest examination.12 The age of the child (in
months) at the time of measurement was recorded for all but 11 qf
the participants. In 1984-85, the participants (aged 20-21 years)
were re-examined. Height and weight were obtained by the
questionnaire.9 Body-mass index (weight/height2) was used to
define degree of overweight (90th centile) and obesity (95th
centile). Limits of overweight for male participants were 18.7
kg/m2 at age 9-10 and 25.9 kgfm2 at age 20-21; the limits for females
were 18.9 kg/m2 and 24-2 kg/m2, respectively. The corresponding
cut-offs for obesity were 20-2 kg/m2 and 26-9 kgfm2 for male
participants and 20-1 1 kgfm2 and 26-3 kg/m2 for females.
It has been shown previously that obesity in young adults is
related to parental social factors.9,13 The mother or guardian
reported by mailed questionnaire (for 887 children [71 %]) on her
own and the father’s school education and on householder’s
occupation. We defined low education as 7 years of primary school,
middle as 9 years of school (leaving with a general certificate,
ordinary level), and high as 10-12 years (leaving with secondary
school certificate of education or general certificate of education,
advanced level). Occupational status was classified low for
unskilled manual workers and pensioners; middle for lower-level
salaried employed, non-academic self-employed, and skilled
manual workers; and high for those with academic university
degrees, managing directors, factory owners, and upper-level
salaried employed. Quality of housing was classified according to
the Commission of Dwellings in areas with poor and good houses
(known by postal code for all 1258 children).12 We controlled for
the possible confounding effect of these four social variables by a
confounder score, as well as by the four variables separately.99
Overweight and obesity were used as dependent variables. The
main analysis comprised two steps. In the first step, prevalence of
overweight and obesity in young adulthood was calculated in
relation to family factors in childhood. In the second step, we
carried out logistic regression analysis by maximum likelihood
*With control for body-mass index, age at examination in childhood, sex, and confounder
score.
Table 2: Likelihood of obesity In young adulthood In relation to
family factors
estimation 14 with body-mass index and age at examination in
childhood,15 sex, and the social confounder score as covariates.
95% CI for odds ratios were calculated from the standard errors of
the coefficients. The social confounder score for each individual
was made by a separate logistic regression analysis with overweight
as the dependent variable, and the four social factors as
independent nominal scale variables; a value of zero was assigned to
missing information. Thus, the confounder score is a single
continuous variable that brings together information on the four
social variables.
Results
The prevalence of obesity in childhood and young
adulthood in relation to the family factors in childhood is
shown in table 1. Other results are based on the prospective
analysis of obesity in young adulthood while controlling for
body-mass index in childhood.
Family structure in childhood had no significant effect on
the likelihood of obesity in young adulthood when body-
mass index and age at examination in childhood, sex, and
the social confounder score were included as covariates
(table 2).
By contrast, parental support as perceived by the form
teacher had a highly significant effect on the child’s risk of
obesity in young adulthood (table 2). Children receiving no
support had a significantly higher risk than those raised
with harmonious parental support. Overprotective support
tended to increase the risk of obesity, but the effect was not
significant. General hygiene in childhood also had a highly
significant effect on the risk of obesity in young adulthood.
In comparison with averagely groomed children, those
considered dirty and neglected were 9 8 times more likely to
be obese in young adulthood.
The analysis was repeated in several other ways, with
essentially the same results. We analysed the risk of being
overweight rather than obese (body-mass index above the
90th centile), the risk of becoming obese or overweight
excluding the children already obese (36) or overweight (76)
in childhood, and the risk of being or of becoming obese or
overweight with control for the four social variables
separately and together (instead of using the confounder
score) in the multivariate analysis.
Discussion
Lack of parental care for the offspring’s well-being has a
highly significant association with obesity in young
adulthood: parental neglect during childhood predicts a
325
greatly increased risk of obesity in young adulthood.
Neither overprotective parental support nor family
structure was significantly associated with the risk.
Johnston3concluded after reviewing work published up
to 1985, "Despite 45 years of concentrated research, our
ignorance about childhood obesity is amazing. There are
plenty of correlations and risk ratios, but few in depth
prospective data allow us to disaggregate a condition that
has been a complex and heterogeneous collection of
causes".3This statement still seems to be valid. Our results
are difficult to compare with those of other studies
addressing this problem because of differences in design
(cross-sectional or prospective), setting (general or clinic
population), sample selection (random or non-random), age
group, definition of obesity, control of confounding, and
assessment of family factors.
The advantages and limitations of our study have been
discussed,9,lO but the main point is that the temporal
sequence between assessment of family factors and obesity
is established. The assessment of the family factors was
based on limited information from a mailed questionnaire.
The reliability was checked,12 but the questionnaire was not
directly validated. However, the information was collected
many years before the assessment of obesity in young
adulthood. We believe that no other key professionals know
as much about the parents and the family homes as the form
teachers. In view of the reservations, it is surprising that
parental neglect was such a strong predictor of prospective
obesity. The strength of the association suggests that the
questions used elicit information on a very important
component of the psychosocial influence on obesity. For
screening of individuals at risk it is an obvious advantage
that the risk factors can be easily investigated.
It is likely that perceived lack of parental support and
poor general hygiene are proxy measures of the same aspect
of parental neglect. These assessments were made
independently by two different professionals. Although
there was no significant association with childhood obesity,
the association of the two variables with later obesity was
very strong. These results are consistent with our previous
finding of a more than 4-fold risk of overweight in young
adults whose mothers claimed not to know about the
offspring’s sweet-eating habits as a child; reported actual
sweet-eating habits had less influence.1o
The relation between a mother’s attitude to her child and
obesity in the child was considered by Bruch.7 She
suggested that a mother who does not like her child may
react to this dislike by overprotecting and overfeeding the
child, and thereby induce obesity. We had no information
about whether overprotection and rejection were present at
the same time. Children suffering from parental neglect
seem to be at high risk of obesity in accordance with Bruch’s
findings, but overprotective support, and particularly
being well-groomed or being an only child, did not increase
the risk significantly in our study.
The association between parental neglect and later
obesity is far stronger than those for other psychosocial risk
factors, such as parental education or occupation,9 quality
of dwelling,9 or child’s school performance.15 Future
studies should address the inter-relation between the
psychosocial risk factors in terms of their association with
later obesity.
The mechanisms by which psychosocial factors act are
not known. Dietary habits and physical activity may have
roles, but in studies in the general population, neither have
shown effects on obesity as large as those observed in this
326
study. We suggest that parental neglect may cause a
psychological state that affects energy balance by altering
behaviour (overeating and physical inactivity) or hormone
balances, influencing fat storage (corticosteroids,
catecholamines, or insulin).
A previous adoption study has shown that genetic
relationship can account for the familial resemblance in
obesity in adulthood.16.17 This finding suggests that the
rearing environment, as assessed by degree of obesity of the
family members, has no sustained effect into adulthood.
Other features of family life, unrelated to degree of obesity
in the family, may have roles, however. Whether parental
neglect acts independently of the genetic effect or is a
mediator of it must be addressed in future studies,
including information on degree of obesity of the parents,
which was not available in this study. However, by
controlling for the effect of body-mass index in childhood
we partly addressed this drawback. The parent-offspring
association in body-mass index seems to be fully expressed
by the age of 7.18 Furthermore, the genetic effect observed
in the adoption study produces much smaller odds ratios
(about 2) than those in our study.16
For the prevention of cardiovascular diseases in
adulthood, it is important to begin with preventive
programmes at early school age.19 Garrow20.21 argues that
there is an opportunity to prevent obesity in primary school
children, which may be better than at any other stage in life.
By taking advantage of linear growth, the child can become
thinner simply by keeping the weight constant.
Furthermore, primary school children may be easier to deal
with than teenagers. Thus, modification of pertinent
psychosocial risk factors in early childhood may be worth
while to test in intervention studies. For preventive
purposes, it may also be important to identify children
suffering from parental neglect.
This study was supported by Sygekassernes Helsefond (30-90, 262-90,
247-91, 244-92), the Danish Heart Foundation (Hjerteforeningen), Novo
Nordisk Foundation, and the Danish Medical Research Council
(5.22.99.98).
References
1 Dietz WH. Prevention of childhood obesity. Pediatr Clin North Am
1986; 33: 823-33.
2 Dietz WH, Gortmaker SL. Factors within the physical environment
associated with childhood obesity. Am J Clin Nutr 1984; 39: 619-24.
3 Johnston FE. Health implications of childhood obesity. Ann Intern
Med 1985; 103: 1068-73.
4 Loader P. Childhood obesity: the family perspective. Int J Eating
Disord 1985; 4: 211-25.
5 Kinston W, Loader P, Miller L, Rein L. Interaction in families with
obese children. J Psykosom Res 1988; 32: 513-32.
6 Silverman WK, Israel AC. The development and treatment of
childhood obesity: parental and family factors. Behav Therapist 1987;
10: 197-201.
7 Bruch H. The importance of overweight. New York: WW Norton,
1957.
8 Quaade F. Obese children: anthropology and development.
Copenhagen: Dansk Videnskabs Forlag, 1955.
9 Lissau-Lund-Sørensen I, Sørensen TIA. Prospective study of the
influence of social factors in childhood on risk of overweight in young
adulthood. Int J Obes 1992; 16: 169-75.
10 Lissau I, Breum L, Sørensen TIA. Maternal attitude to sweet eating
habits and risk of overweight in offspring: a ten-year prospective
population study. Int J Obes 1993; 17: 125-29.
11 Lissau I. Tandplejeadfaerd og parodontal sygdom. En 10 års histotisk
prospektiv kohorteundersøgelse. Dissertation. Copenhagen: University
of Copenhagen, 1993.
12 Friis-Hasché E. Skolebørns sundhedstilstand (Thesis). Copenhagen;
Odontologisk boghandels forlag, 1981.
13 Power C, Moynihan C. Social class and changes in weight-for-height
between childhood and early adulthood. Int J Obes 1988; 12: 445-53.
14 SAS Institute. SAS user’s guide: statistics, version 5 edition. Cary,
NC: SAS Institute, 1985.
15 Lissau I, Sørensen TIA. School difficulties in childhood and risk of
overweight and obesity in young adulthood: a ten-year prospective
population study. Int J Obes 1993; 17: 169-75.
16 Stunkard AJ, Sørensen TIA, Hanis C, et al. An adoption study of
human obesity. N Engl J Med 1986; 314: 193-98.
17 Sørensen TIA, Holst C, Stunkard AJ, Skovgaard LT. Correlations of
body mass index of adult adoptees and their biological and adoptive
relatives. Int J Obes 1992; 16: 227-36.
QT dispersion and sudden unexpected death in chronic
heart failure
Summary
Death in chronic heart failure (CHF) can be from progression of
disease or sudden and unexpected. We have attempted to
identify factors that predict sudden death in CHF.
We followed up 44 patients with CHF for 12-50 (mean 36)
months. 4 patients died of non-cardiovascular causes and
were excluded from analysis. There were 7 sudden deaths
(symptoms for less than 1 h in a previously stable patient) and
12 from progressive CHF. Patients who died of progressive CHF
had lower left-ventricular ejection fractions and higher
concentrations of atrial natriuretic factor than the 21
survivors, but there were no differences in these variables
between survivors and those who died suddenly. However, the
sudden death group had significantly (p<0&middot;05) greater
inter-lead variability in the QT interval on the electrocardiogram
(QT dispersion; 98&middot;6 [95% Cl 79&middot;1-118] ms&frac12;) than survivors
(53&middot;1 [41&middot;9-64&middot;3] ms&frac12;) or the group who died from
progressive CHF (66&middot;7 [51&middot;8-81&middot;6] ms&frac12;).
QT dispersion is a marker of myocardial electrical
instability. The association of increased QT dispersion with
sudden death suggests that patients at high risk of such death
could be identified by means of this simple, reproducible test.
This group might benefit from more intensive treatment.
Lancet 1994; 343: 327-29
Introduction
Chronic heart failure (CHF) is the most important public
health problem in cardiovascular medicine. In the
Framingham Heart Study, 2.5 % of people over 45 years old
were affected; median survival time was 3-2 years in men
and 5-4 years in women.’ 50% of deaths in mild CHF and
25% of those in severe CHF are sudden and unexpected.2,3
The distinction between sudden and non-sudden death is
unclear, as are the causes and mechanisms of sudden death.
Many studies have identified risk factors for all deaths in
CHF; low values of left-ventricular ejection fraction,
maximum exercise tolerance, serum sodium, potassium,
and magnesium, and mean arterial pressure all increase the
risk.4-6 Activation of the renin-angiotensin system and the
Department of Clinical Pharmacology, Nlnewells Hospital and
Medical School, Dundee DD1 9SY, UK (C S Barr MRCP, A Naas MB,
M Freeman, C C Lang MRCP, Prof A D Struthers FRCP)
Correspondence to: Dr Craig S Barr
C, Stunkard AJ. Childhood body mass index-
18 S&oslash;rensen TIA, Holst
genetic and familial environmental influences assessed in a longitudinal
adoption study. Int J Obes 1992; 16: 705-14.
19 Hertzel BS, Berenson GS, eds. Cardiovascular risk factors in
childhood: epidemiology and prevention. Amsterdam: Elsevier, 1987.
20 Garrow JS. The management of obesity: another view. Int J Obes 1992;
16 (suppl 2): 59-63.
21 Garrow JS. Management and prevention of obesity in children.
In: obesity and related diseases. Edinburgh: Churchill Livingstone,
1988.
sympathetic nervous system’ are associated with a poor
prognosis. Attempts have been made lately to separate
predictors of death from progressive CHF and predictors of
sudden unexpected death. In one study, an increasing
plasma noradrenaline distinguished patients who died of
progressive CHF from those who died suddenly.8
Prolongation of the QT interval has been found to predict
sudden death in patients with coronary artery disease9
(although not in patients with cardiac dysfunction1O) and
alcoholic cirrhosis,lO,l1 and cardiovascular death in normal,
apparently healthy, individuals in large population
studies.12 Another measure that might be useful in this
context is inter-lead variability in the QT interval
(dispersion). This index reflects regional variation in
ventricular repolarisation,13 which represents an
electrophysiological substrate for arrhythmias.14 Among
patients with acute myocardial infarction, there is increased
dispersion in those who develop ventricular
tachyarrhythmias but not in those without such
complications. is Similarly, QT dispersion is increased in
patients with long QT syndromes who are at high risk of
ventricular arrhythmias.16 Patients with acute myocardial
infarction1S or hypertrophic cardiomyopathy 17 who die
suddenly also have increased QT dispersion. In CHF,
variable electrophysiological properties of the
myocardium, coupled with an already failing heart, might
be associated with alterations in ventricular repolarisation
that could identify patients at risk of sudden death. If this
hypothesis is correct, measurement of QT dispersion might
be a simple non-invasive screening procedure to identify
CHF patients at greater risk of sudden death.
We have prospectively examined haemodynamic,
neurohormonal, and biochemical variables and
retrospectively assessed QT interval measurements in a
cohort of patients with CHF to see which factors predict
sudden unexpected death.
Patients and methods
44 patients of mean age 76 (range 53-85) years, with symptomatic
left-ventricular systolic dysfunction secondary to ischaemic heart
disease (New York Heart Association class III-IV) were followed
up for a mean of 36 (range 12-50) months, and endpoints of
survival, sudden unexpected death, or death from progressive
CHF were assessed. The patients were receiving aspirin, diuretics,
and angiotensin-converting-enzyme (ACE) inhibitors but no other
cardioactive drugs; in particular, none was taking anti-arrhythmic
therapy or drugs that can affect the QT interval. The study was
approved by the Tayside Committee on Medical Research Ethics.
327