ArticlePDF Available

Early Psychosocial Exposures, Hair Cortisol Levels, and Disease Risk

Authors:
  • Commuity medicine

Abstract and Figures

Early psychosocial exposures are increasingly recognized as being crucial to health throughout life. A possible mechanism could be physiologic dysregulation due to stress. Cortisol in hair is a new biomarker assessing long-term hypothalamic-pituitary-adrenal axis activity. The objective was to investigate whether early-life adverse psychosocial circumstances influence infant cortisol levels in hair and health outcomes in children prospectively until age 10. A cohort study in the general community using a questionnaire covering 11 psychosocial items in the family during pregnancy and the cumulative incidence of diagnoses until age 10 years in 1876 children. Cortisol levels in hair were measured by using a radioimmunoassay in those with sufficient hair samples at age 1, yielding a subsample of n = 209. Children with added psychosocial exposures had higher infant cortisol levels in hair (B = 0.40, P < .0001, adjusted for gender and size for gestational age) in a cumulative manner and were significantly more often affected by 12 of the 14 most common childhood diseases, with a general pattern of increasing odds ratios. The findings support the model of physiologic dysregulation as a plausible mechanism by which the duration and number of early detrimental psychosocial exposures determine health outcomes. The model indicates that the multiplicity of adversities should be targeted in future interventions and could help to identify children who are at high risk of poor health. Furthermore, given the prolonged nature of exposure to a stressful social environment, the novel biomarker of cortisol in hair could be of major importance. Copyright © 2015 by the American Academy of Pediatrics.
Content may be subject to copyright.
Early Psychosocial Exposures, Hair
Cortisol Levels, and Disease Risk
Jerker Karlén, MD, PhDa, Johnny Ludvigsson, MD, PhDb, Max Hedmark, MDa, Åshild Faresjö, PhDa,
Elvar Theodorsson, MD, PhDc, Tomas Faresjö, PhDa
abstract BACKGROUND: Early psychosocial exposures are increasingly recognized as being crucial to health
throughout life. A possible mechanism could be physiologic dysregulation due to stress.
Cortisol in hair is a new biomarker assessing long-term hypothalamic-pituitary-adrenal axis
activity. The objective was to investigate whether early-life adverse psychosocial
circumstances inuence infant cortisol levels in hair and health outcomes in children
prospectively until age 10.
METHODS: A cohort study in the general community using a questionnaire covering 11
psychosocial items in the family during pregnancy and the cumulative incidence of diagnoses
until age 10 years in 1876 children. Cortisol levels in hair were measured by using
a radioimmunoassay in those with sufcient hair samples at age 1, yielding a subsample of
n= 209.
RESULTS: Children with added psychosocial exposures had higher infant cortisol levels in hair
(B = 0.40, P,.0001, adjusted for gender and size for gestational age) in a cumulative manner
and were signicantly more often affected by 12 of the 14 most common childhood diseases,
with a general pattern of increasing odds ratios.
CONCLUSIONS: The ndings support the model of physiologic dysregulation as a plausible
mechanism by which the duration and number of early detrimental psychosocial exposures
determine health outcomes. The model indicates that the multiplicity of adversities should be
targeted in future interventions and could help to identify children who are at high risk of
poor health. Furthermore, given the prolonged nature of exposure to a stressful social
environment, the novel biomarker of cortisol in hair could be of major importance.
WHATS KNOWN ON THIS SUBJECT: Early
psychosocial exposures are increasingly
recognized as crucial to health throughout life. A
possible mechanism is physiologic dysregulation
due to stress. Cortisol in hair is a new biomarker
assessing long-term hypothalamic-pituitary-
adrenal axis activity.
WHAT THIS STUDY ADDS: Added early
psychosocial exposures seem to increase infant
long-term hypothalamic-pituitary-adrenal axis
activity and risk of common childhood diseases
in a cumulative manner, supporting the model of
physiologic dysregulation as a plausible
mechanism through which early detrimental
exposures determine health outcomes.
aDivision of Community Medicine, Department of Medicine and Health Sciences, Faculty of Health Sciences, and
Divisions of bPediatrics and cClinical Chemistry, Department of Clinical and Experimental Medicine, Faculty of
Health Sciences, Linköping University, Linköping, Sweden
Dr Karlén conceptualized and designed the study, managed the literature searches, undertook the
statistical analysis and interpretation of data, and wrote the rst draft of the manuscript;
Dr Ludvigsson is founder and project leader of All Babies in Southeast Sweden (ABIS) and organized
collection of material (biological samples and questionnaires), conceptualized and designed the
study, undertook analysis and interpretation of data, and reviewed and revised the manuscript;
Dr Hedmark participated in the concept and design, managed literature searches, undertook the
statistical analysis and interpretation of data, and reviewed and revised the manuscript; Drs A.
Faresjö and Theodorsson participated in the concept and design and analysis and interpretation of
data, undertook and developed the method for hair cortisol analyses, and reviewed and revised the
manuscript; Dr T. Faresjö conceptualized and designed the study, undertook the statistical
analysis and interpretation of data, and reviewed and revised the manuscript; and all authors
approved the nal manuscript as submitted.
www.pediatrics.org/cgi/doi/10.1542/peds.2014-2561
DOI: 10.1542/peds.2014-2561
Accepted for publication Mar 3, 2015
ARTICLE PEDIATRICS Volume 135, number 6, June 2015
at Linkopings Universitetsbibliotek on September 24, 2015pediatrics.aappublications.orgDownloaded from
Early life is increasingly recognized as
crucial to health throughout life.
1,2
Psychosocial circumstances impact
health as early as in childhood, being
associated with, eg, obesity, mental
problems, drug abuse, suicide, and
chronic illness.
3,4
They also act as
a disadvantageous trajectory of adult
health.
5,6
Epidemiologic evidence that
even conditions during fetal
development affect health in
adulthood is particularly
compelling.
7,8
Common childhood
complaints, although not as
thoroughly explored, suggest an
association with, eg, otitis media,
respiratory infections, and
asthma.
911
The actual biological pathways
linking psychosocial environmental
exposures to health disparities
are difcult to uncover, but 1
plausible mechanism is physiologic
dysregulation due to stress.
12
This
dysregulation, in turn, affects other
physiologic functions, such as the
immune system.
13
Some evidence
suggests that even prenatal stress
could shape the development of the
hypothalamic-pituitary-adrenal
(HPA) axis, often measured through
short-term output of the stress
hormone cortisol in saliva,
14,15
as
well as increasing susceptibility to
later psychopathology.
16
Cortisol in hair is a new method that
measures cortisol output over longer
periods of time, because hair grows
1 cm/month and is suggested to be
an assessment of frequent or
prolonged activation of the HPA
axis.
17
There is some evidence for an
association between higher hair
cortisol levels and psychosocial
factors in adults,
18,19
but there have
been only a few studies on child hair
cortisol, although the results point
in the same direction with
a correlation to, eg, parental
education and residence type.
20,21
The aim of this study was to
investigate whether adverse
psychosocial circumstances in the
family during early life alter
long-term HPA axis activity, assessed
through cortisol concentrations in the
hair, and to explore a possible relation
with health outcomes in children
followed prospectively until the age
of 10 years.
METHODS
Participants
All Babies in Southeast Sweden
(ABIS) is a prospective study of
a birth cohort of every child born in
southeastern Sweden between
October 1, 1997, and October 1, 1999
(N=21 700), for which 17 055
parents (78.6%) gave their informed
consent. We selected a subsample of
N= 2447 children, consisting of
every participant living in the 2 cities
of Linköping and Norrköping: these
2 cities are within the same county
council responsible for practically all
health care, operating under the same
clinical practice guidelines, and with
an extensive regional health care
register. We excluded 571 children
due to a lack of complete data on the
independent variable, which left 1876
children (n= 926 girls and n= 950
boys). Cortisol in hair was analyzed in
those with sufcient hair samples
collected at age 1, yielding
a subsample of n= 209 (n= 103 boys
and n= 106 girls). This sample was
stratied according to the
distribution of the vulnerability score
(see below) and gave an oversampled
$3 category (n= 90). The Research
Ethics Committee at the Faculty of
Health Sciences, Linköping University,
Sweden, approved the study.
Psychosocial Vulnerability: A Score
of Risk Factors
The childrens mothers answered
a questionnaire shortly after birth
that contained a broad range of
psychosocial factors. We used the
novel concept of vulnerabilityto
analyze the complex interplay
between these factors.
22
This concept
is a convergence of multiple health-
affecting risk factors that uses
adecit accumulation approach,
which could help identify high-risk
populations and uncover connections
not evident when considering single
risk factors. We included variables in
the existing database associated with
a detrimental impact on health as
suggested in prev ious research. Some
answers were dichotomized: for
example, schooling was simplied
into having an education above
elementary school or not.
Eleven psychosocial items resulted in
the nal composite independent
variable: the psychosocial
vulnerability score. The items were as
follows: fathers highest level of
education elementary school;
mothers highest level of education
elementary school; father
unemployed or on sick leave the year
before pregnancy; mother
unemployed or on sick leave during
pregnancy; living in an apartment,
as opposed to own house; single
mother; parents born abroad;
maternal experienced serious life
event during pregnancy (Have you
been exposed to something which you
perceive as a serious life event during
your pregnancy?); maternal lack of
support (Do you feel your
surroundings give you the support
you and your newborn child need?);
mother not feeling safe (Do you feel
safe and in the circumstances needed
to give you and your newborn child
a good start?); mother worried over
the possibility of child falling ill with
serious disease (How do you usually
feel when you consider the possibility
that your child could fall ill with
a chronic or serious disease in the
future?). For these, a stepwise
6-grade Likert-type scale was applied
between not worried and very
worried, with 4 to 6 being classied
as worried.
Cortisol in Hair: Long-term HPA Axis
Activity
Nurses at the well-baby clinics cut the
childrens hair from the posterior
vertex area of the head at age 1 year,
and the rst 3 cm of outgrowth was
analyzed for cortisol concentrations
PEDIATRICS Volume 135, number 6, June 2015 e1451
at Linkopings Universitetsbibliotek on September 24, 2015pediatrics.aappublications.orgDownloaded from
by using a competitive
radioimmunoassay in methanol
extracts.
18
Hair samples .3 mg were
required to maintain a total interassay
coefcient of variation ,8%.
Health Outcome: Cumulative
Incidence of Diagnoses
International Classication of
Diseases diagnoses (ICD-10) were
derived from the regional health care
register containing data on all health
care visits within the publicly
nanced health care provision, which
represents practically all health care.
There is no evidence of systematic
misclassication in this health care
register.
23
Diagnoses from birth to
February 2008 were recorded on
a case per case basis. Children were
aged 8 to 10 years at follow-up, hence
describing the cumulative incidence
of diagnoses. This follow-up was
almost 100% because dropouts due
to death or moving out of the region
were negligible. In some cases, we
merged closely related diagnoses, eg,
codes J00 through J06 were all
registered in the category J00J06:
acute upper respiratory infections.
Statistical Analyses
We used an independent-samples
ttest when testing the psychosocial
vulnerability score against both hair
cortisol and health outcome. The
score was transformed into
a categorical variable (participants
with $3 psychosocial items were
treated as 1 group due to the small
number of cases, yielding 4 groups:
0 (reference), 1, 2, and $3) when
testing against binary diagnoses.
Regression analysis was used when
adjusting for gender and small for
gestational age (SGA; calculated
according to the National Swedish
Board of Health and Welfare criteria,
2 SDs from the mean depending on
gestational age) against both cortisol
levels and health outcome. The
measured cortisol concentrations
included 2 outliers dened with the
Grubbs test, which were kept in the
analyses. Before the statistical
analysis, all cortisol values were
logarithm transformed due to
positive skewness in the distribution.
RESULTS
Mothersand fathersmean ages
(95% condence intervals [CI]) at the
birth of the child were 30.17
(29.9730.96) and 32.24
(31.9932.48) years, respectively.
There was no difference in cortisol
levels with respect to gender (boys =
2.45 pg/mg and girls = 2.79 pg/mg)
or weight. We found an association
between vulnerability score and
lower birth weight and birth height
for girls. The reference group had
a mean weight of 3570 g, those with
2 items had a mean weight of 3459 g
(P= .023), and those with $3 items
had a mean weight of 3413 g (P= .027).
Children with $3 items were also
shorter at birth than the reference
group (49.8 vs 50.4 cm; P= .035). No
association between cortisol levels
and individual diagnoses was found.
All single vulnerability items
correlated signicantly with the
composite vulnerability score, and
regression analysis could not
distinguish a single item driving the
associations to the different
outcomes.
Psychosocial Vulnerability Score and
Cortisol in Hair
An association was found (r= 0.22,
P= .002) between the vulnerability
score and logarithmized cortisol
concentrations in the hair, as shown
in Fig 1. When adjusting for gender
and SGA, vulnerability was still
signicant. (B = 0.40, P,.0001).
There was also a dose-responselike
increase in cortisol concentrations;
0 items (n= 33) gave a mean of
1.90 pg/mg (95% CI: 0.912.89); 1 item
(n= 46) gave a mean of 2.18 pg/mg
(95% CI: 2.174.16); 2 items (n=27)
gave a mean of 3.17 pg/mg (95% CI:
2.184.16); 3 items (n= 49) gave
a mean of 2.76 pg/mg (95% CI:
2.123.41); 4 items (n= 24) gave
a mean of 2.82 pg/mg (95% CI:
1.993.65); 5 items (n= 10) gave
a mean of 3.86 pg/mg (95% CI:
2.465.26); and 6 items (n= 2) gave
a mean of 7.21 pg/mg (95% CI:
6.887.54). Of the 11 single
dichotomous items, a signicant
difference in mean cortisol values
was found for 2 variables (Table 1).
Also, all but 1 of the items (fathers
occupation), exhibited higher mean
cortisol levels in the exposed group,
although this nding was
nonsignicant.
Psychosocial Vulnerability Score and
Health Outcome
Cumulative incidence was analyzed
for the 14 most common diagnoses,
ranging from 0.81 (acute upper
respiratory infections) to 0.09
(urticaria). Rates below this level
were too low for reliable statistical
analyses. Comparing the mean
vulnerability score in diagnosed
versus undiagnosed groups, it was
signicantly higher for diagnosed
children in 12 out of the
14 International Classication of
Diseases, 10th Revision, groupings.
After adjusting for gender and SGA,
10 diagnoses were still signicant
(B = 1.92, P,.0001) (Table 2).
Gender was also independently
signicant in some cases. Among boys,
acute upper respiratory infections
(P= .002); injury, poisoning, and certain
other consequences of external causes
(P,.0001); and asthma (P= .018)
were signicant. Among girls, urinary
FIGURE 1
Psychosocial vulnerability score and hair cor-
tisol concentration at age 1 year (n= 209).
e1452 KARLÉN et al
at Linkopings Universitetsbibliotek on September 24, 2015pediatrics.aappublications.orgDownloaded from
tract infections were signicant
(P,.0001). Moreover, there was
a correlation with the number of
different diagnoses (r=0.15,
P,.0001). An increase in vulnerability
score was associated with and graded
to a corresponding increase in odds
ratio (OR) for most diagnoses,
although this nding was mostly
signicant among those in the highest
category. One exception was urinary
tract infections, where having some
degree of vulnerability increased all of
the ORs approximately twofold. The
largest increases in ORs, with a more
than twofold increase in the $3
category, were seen among viral
infections of unspecied site, intestinal
infectious disease, and urticaria.
DISCUSSION
The objective of this study was to
investigate whether early-life adverse
psychosocial circumstances inuence
infant hair cortisol levels and affect
health outcomes in children. A
general pattern was seen throughout
the results: added detrimental
exposures resulted in
a corresponding increase in levels of
cortisol in hair and the risk of being
diagnosed with almost all diseases
common in childhood. This pattern
has, to our knowledge, never been
shown before and there are few, if
any, risk indicators that have such
a wide impact on disease risk, which
supports the model of physiologic
dysregulation as a plausible pathway
through which early-life psychosocial
environmental exposures affect
health outcomes.
7,24,25
Furthermore, infant cortisol levels
were signicantly positively
associated with 2 of the 11 single
psychosocial items. In 8 of the
remaining 9 items, mean cortisol
levels were higher in the exposed
group, although not signicantly so.
This nding is in line with the few
studies undertaken on cortisol in hair
in children, in whom higher hair
cortisol levels seem to be linked to
different psychosocial factors.
17,21
The actual pathways linking
psychosocial exposures to altered the
HPA axis activity of the child are not
fully known. A possible mechanism
in the prenatal period could be, eg,
epigenetic modication of DNA,
26
and
early postnatal experiences are
thought to alter the developing brain
circuits controlling the stress
response.
25
Thus, it is not far-fetched
to think that the novel biomarker of
cortisol in hair, which assesses HPA
axis activity over longer periods of
time, could reect the continuous
stress load in the daily social
environment. These ndings t the
accumulation of risk model (allostatic
load) well, stating that health damage
increases with the duration and
number of detrimental
exposures,
1,2,24
as well as suggesting
that these are extra toxic due to the
wear and tear of the body.
12,25
However, no association between
cortisol levels and individual
diagnoses was found, which could be
due to the pathogenesis most often
being multifactorial and probably
dependent on several mechanisms
but also because cortisol in hair is
a novel biomarker that needs to be
developed further, and in this case
was measured in a smaller
TABLE 1 Psychosocial Vulnerability Score, Single Items, and Hair Cortisol Concentration at Age 1
Year
Psychosocial Exposure nCortisol, Mean
(95% CI), log pg/mg
P
a
Vulnerability score (number of single items) 209 2.62 (2.282.96) .002
b
Single items
Mothers marital status
In a relationship 191 2.43 (2.283.00) .733
Single 18 2.64 (1.433.43)
Mothers occupation
Employed 162 2.43 (2.052.82) .041
Unemployed/sick leave 47 3.27 (2.544.00)
Fathers occupation
Employed 193 2.62 (2.273.98) .941
Unemployed/sick leave 16 2.57 (1.393.77)
Residence type
House 73 2.12 (1.502.73) .031
Apartment 136 2.89 (2.493.29)
Fathers educational level
College or university 170 2.47 (2.082.86) .067
High school/9 years 39 3.28 (2.573.99)
Mothers educational level
College or university 182 2.55 (2.172.92) .257
High school/9 years 27 3.13 (2.393.87)
Foreign origin
Neither or 1 parent 191 2.54 (2.192.88) .096
Both parents 18 3.55(2.194.91)
Maternal serious life event
No 174 2.57 (2.202.95) .523
Yes 35 2.88 (2.013.66)
Maternal lack of support
No 208 2.60 (2.252.93)
Yes 1 6.88 ()
Mother feeling safe
c
Yes 204 2.59 (2.252.93)
No 5 4.01 (2.086.93)
Mother worried about child falling ill with serious disease
No 116 2.37 (2.922.82) .099
Yes 93 2.94 (2.433.45)
, not applicable.
a
Mean cortisol in exposed group versus nonexposed group (independent-samples ttest).
b
Pearson correlation, r= 0.22, P= .002.
c
Question was phrased, Do you feel safe and in the circumstances needed to give you and your newborn child a good
start?
PEDIATRICS Volume 135, number 6, June 2015 e1453
at Linkopings Universitetsbibliotek on September 24, 2015pediatrics.aappublications.orgDownloaded from
TABLE 2 Psychosocial Vulnerability Score and Risk of the 14 Most Common Childhood Diagnoses Prospectively Until Age 10 Years
Diagnosis (ICD-10) Number of Psychosocial Items n(%) Diagnosis Risk P
a
P
b
OR 95% CI
Acute upper respiratory infections (J00J06) 0 346 (78) Ref .003 .004
1 603 (79) 1.06 0.801.41
2 368 (83) 1.34 0.961.87
$3 196 (87) 1.83 1.172.86
Otitis media (H65H67) 0 288 (65) Ref .009 .007
1 496 (65) 1.00 0.791.28
2 298 (67) 1.09 0.831.44
$3 172 (76) 1.71 1.192.46
Injury (S00T98) 0 247 (56) Ref .048 .053
1 418 (55) 0.96 0.761.22
2 271 (61) 1.24 0.951.61
$3 138 (62) 1.24 0.901.76
Viral infections of unspecied site (B34) 0 99 (22) Ref ,.0001 ,.0001
1 210 (28) 1.32 1.011.74
2 138 (31) 1.56 1.162.11
$3 85 (38) 2.10 1.482.97
Infections of the skin (L00L08) 0 123 (28) Ref .618
1 205 (27) 0.96 0.741.26
2 126 (28) 1.03 0.771.38
$3 66 (29) 1.07 0.751.53
Other acute lower respiratory infections (J20J22) 0 81 (18) Ref .038 .029
1 133 (18) 0.95 0.701.28
2 92 (21) 1.17 0.841.62
$3 55 (24) 1.44 0.982.12
Conjunctivitis (H10) 0 69 (16) Ref .012 .020
1 137 (18) 1.19 0.871.63
2 89 (20) 1.36 0.961.92
$3 52 (23) 1.62 0.982.12
Dermatitis and eczema (L20L30) 0 65 (15) Ref .001 .032
1 123 (16) 1.12 0.811.55
2 82 (18) 1.31 0.921.88
$3 57 (25) 1.96 1.322.92
Intestinal infectious diseases (A00A09) 0 52 (12) Ref ,.0001 .002
1 102 (13) 1.16 1.182.92
2 74 (17) 1.50 1.343.51
$3 54 (24) 2.36 1.033.25
Urinary tract infections (N30, N34, N39.0) 0 27 (6) Ref .013 .003
1 82 (11) 1.86 1.182.92
2 55 (12) 2.17 1.343.51
$3 24 (11) 1.83 1.033.25
Viral infections characterized by skin and mucous lesion (B00B09) 0 36 (8) Ref .021 .061
1 66 (9) 1.07 0.701.64
2 52 (12) 1.50 0.962.34
$3 28 (12) 1.60 0.952.70
Asthma (J45) 0 32 (7) Ref .006 .004
1 63 (8) 1.16 0.771.80
2 48 (11) 1.55 0.972.48
$3 29 (13) 1.89 1.113.21
Pneumonia (J12J18) 0 40 (9) Ref .160
1 66 (9) 0.96 0.631.44
2 46 (10) 1.16 0.741.81
$3 27 (12) 1.37 0.822.29
Urticaria (L50) 0 29 (7) Ref .002 .016
1 64 (8) 1.31 0.832.06
2 47 (11) 1.69 1.042.73
$3 30 (13) 2.19 1.273.74
N= 1876. ICD-10, International Classication of Diseases, 10th Revision; Ref, reference; , not applicable.
a
Mean vulnerability score in diagnosed versus undiagnosed groups (independent-samples ttest).
b
Adjusted for gender and SGA (binary regression).
e1454 KARLÉN et al
at Linkopings Universitetsbibliotek on September 24, 2015pediatrics.aappublications.orgDownloaded from
subsample. There is also emerging
evidence that exposure to intense
stimuli could actually dampen HPA
axis reactivity in some cases, which
could affect all of the cortisol-related
outcomes in this study, although this
has been shown among adults and
again using methods measuring
short-term activity.
27
There were 2
potential outliers regarding cortisol
levels that were included in the
analyses even though the correlation
coefcient for vulnerability increased
to r= 0.24 when excluded. The reason
for this is that the biological variance
of cortisol seems to be greater at an
early age,
20
so these outliers could
not be considered measurement
errors and excluded due to the risk of
introducing selection bias. Other
possible limitations were related to
the novelty of the biomarker cortisol
in hair: for example, its incorporation
in hair is not fully known and the
effect of the use of cortisone-
containing creams as well as the
inuence of age and gender need
further investigation.
19
However, in
this study, responses to the question
During pregnancy, did you take any
medicine? Cortisone (yes/no)did
not alter the results.
In 12 of the 14 most common
childhood diseases, children
diagnosed with diseases had a higher
vulnerability score than did children
in the undiagnosed groups. There was
also a general pattern of increasing
ORs for every added vulnerability
item, which was statistically
signicant for the most vulnerable
category of children. These results are
in line with earlier ndings
suggesting a relationship between
early psychosocial risk factors and ill
health in childhood,
911
as well as
suggesting a relationship between the
multiplicity of early detrimental
psychosocial factors and disease risk.
Diagnoses are not a measure of actual
disease; however, in Sweden,
children with parents of low
socioeconomic status (SES) are less
likely to see a physician,
28
and thus in
our study, such bias could have made the
association between vulnerability and
disease weaker than it actually is.
Most of the diagnoses that showed
a signicant association were
common infections. There could be an
inference consisting of differences in,
eg, hygiene, siblings, and day care use
that might expose the children in
highly vulnerable families to
pathogens to a greater extent than
was controlled for in this study.
Although, in Sweden, there are only
small differences in type of child care
(which includes free meals) with
respect to, eg, SES, children in
families of low social status attend
day care less often, which is known to
be associated with common infectious
diseases.
28
Families also receive free
or heavily subsidized maternity and
child health care as well as medicines.
Earlier research in adults showed
susceptibility to the common cold
among adults suffering from
psychosocial stress and that the cells
of the immune system are unable to
respond to hormonal control.
29
The concept that the family situation
during pregnancy predicts future
health outcomes for the child due in
part to an alteration in the maturing
HPA axis is intriguing. However, an
obvious weakness in this kind of
research is that the association found
may not equal causal effects.
Although this study had a true
prospective framework, it is not proof
of causality and thus neuroendocrine
programingcould represent the
quality of maternal care that
supposedly remains the same
throughout childhood.
30
It is
probable that family vulnerability
during pregnancy predicts future
vulnerability and that the effects on
health are exerted throughout life.
However, it seems that childhood SES
also acts independently of adult
SES.
24
Another weakness is that the
psychosocial vulnerability score is
a theoretical and multifaceted latent
trait, which makes it difcult to
discern what was actually measured.
It could therefore be argued that
variables that are associated with
diagnoses should be treated as
confounders; however, this possibility
does not take interactions or
potentiating effects into account.
22
Even though the items used were
crude, our hypothesis was articulated
a priori and the general direction of
the outcome suggests that the results
cannot be explained by chance.
Regression analysis could not
distinguish a single item driving the
associations with the different
outcomes, which supports the theory
behind the vulnerability construct,
stating that the accumulation of
adversities also matters.
Furthermore, we only included
participants who had complete
answers for each 1 of the 11 items in
the composite vulnerability variable.
There is possibly an
underrepresentation of individuals in
the higher categories of vulnerability
and the observed associations might
have been even more pronounced if
these children could have been
included.
A general strength is the prospective
design of this study, although some
psychosocial factors studied could be
seen as retrospectively collected
because the mothers recalled them
soon after delivery. Thus, we cannot
rule out possible recall bias from the
mothers. However, the recall accuracy
of the mothers might also be quite
sound, something that has been found
for mothersrecall of the duration of
their breastfeeding dating back over
20 years.
31
Furthermore, another
strength is that the actual number of
diagnoses studied was quite high,
a feature lacking in many former
studies.
24
Although there is a natural
uncertainty that derives from the
novelty of the measures used, the
widespread effect of vulnerability on
the outcomes suggests that the
results are not an effect of chance. As
such, there is a possibility that the
further development of cortisol in
hair and the psychosocial
vulnerability score could make the
PEDIATRICS Volume 135, number 6, June 2015 e1455
at Linkopings Universitetsbibliotek on September 24, 2015pediatrics.aappublications.orgDownloaded from
associations observed even more
pronounced. The cumulative nature
of psychosocial disparities, not only
single risk factors, seems to increase
HPA axis activity as well as risk of
disease. This nding indicates that
interventions should also target the
multiplicity of adversities, as well as
emphasizing the importance of
preventive measures at an early age
of the life course, to decrease both
illness and future cost.
CONCLUSIONS
Children born into families fraught
with multiple adverse psychosocial
exposures seem to have increased
long-term HPA axis activity and are
more likely to be affected by common
childhood diseases in a dose-
responselike manner. This nding
supports the model of physiologic
dysregulation as a plausible
mechanism by which the duration
and number of early detrimental
psychosocial exposures act as
a trajectory to poor health outcomes.
It also indicates that the multiplicity
of psychosocial disparities is of
importance and should be targeted in
future interventions, because it could
help to identify vulnerable children
who are at high risk of poor health.
Moreover, given the prolonged
nature of the exposure to a stressful
social environment, the novel
biomarker of cortisol in hair could be
of major importance in this area of
research.
ACKNOWLEDGMENTS
We thank all of the children, mothers,
and family members participating in
the ABIS (All Babies in Southeast of
Sweden) study, as well as the staff
and nurses working at the well-baby
clinics.
Address correspondence to Jerker Karlén, MD, PhD, Division of Community Medicine, Department of Medicine and Health Sciences, Linköping University, SE-581 83
Linköping, Sweden. E-mail: jerker.karlen@liu.se
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).
Copyright © 2015 by the American Academy of Pediatrics
FINANCIAL DISCLOSURE: The authors have indicated they have no nancial relationships relevant to this article to disclose.
FUNDING: This study was supported in part by The Swedish Child Diabetes Foundation (Barndiabetesfonden), the Research Council of Southeast Sweden (FORSS-
87771, FORSS-36321), the Swedish Medical Research Council (K99-72X-11242-05A), the Wallenberg Foundation (K 98-99D-12813-01A), and the County Council of
Östergötland project grant, Linköping, Sweden.
POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conicts of interest to disclose.
REFERENCES
1. Adler NE, Boyce T, Chesney MA, et al.
Socioeconomic status and health: the
challenge of the gradient. Am Psychol.
1994;49(1):1524
2. Marmot MG, Wilkinson RG, Ovid
Technologies I. Social Determinants of
Health. Oxford, United Kingdom: Oxford
University Press Oxford; 1999
3. Bomela NJ. Social, economic, health and
environmental determinants of child
nutritional status in three Central Asian
Republics. Public Health Nutr. 2009;
12(10):18711877
4. Murasko JE. Socioeconomic status,
height, and obesity in children. Econ
Hum Biol. 2009;7(3):376386
5. Dube SR, Anda RF, Felitti VJ, Chapman
DP, Williamson DF, Giles WH. Childhood
abuse, household dysfunction, and
the risk of attempted suicide
throughout the life span: ndings
from the Adverse Childhood
Experiences Study. JAMA. 2001;
286(24):30893096
6. Smith GD, Hart C, Blane D, Hole D.
Adverse socioeconomic conditions in
childhood and cause specic adult
mortality: prospective observational
study. BMJ. 1998;316(7145):16311635
7. Barker DJ. The fetal origins of coronary
heart disease. Acta Paediatr Suppl. 1997;
422(86):7882
8. Tegethoff M, Greene N, Olsen J, Schaffner
E, Meinlschmidt G. Stress during
pregnancy and offspring pediatric
disease: a national cohort study. Environ
Health Perspect. 2011;119(11):16471652
9. Dowd JB, Aiello AE, Alley DE.
Socioeconomic disparities in the
seroprevalence of cytomegalovirus
infection in the US population:
NHANES III. Epidemiol Infect. 2009;
137(1):5865
10. Paradise JL, Rockette HE, Colborn DK,
et al. Otitis media in 2253 Pittsburgh-
area infants: prevalence and risk factors
during the rst two years of life.
Pediatrics. 1997;99(3):318333
11. Wright RJ, Subramanian SV. Advancing
a multilevel framework for
epidemiologic research on asthma
disparities. Chest. 2007;132(5 suppl):
757S769S
12. McEwen BS, Stellar E. Stress and the
individual: mechanisms leading to
disease. Arch Intern Med. 1993;153(18):
20932101
13. Segerstrom SC, Miller GE. Psychological
stress and the human immune system:
a meta-analytic study of 30 years of
inquiry. Psychol Bull. 2004;130(4):
601630
14. OConnor TG, Ben-Shlomo Y, Heron J,
Golding J, Adams D, Glover V. Prenatal
anxiety predicts individual differences in
cortisol in pre-adolescent children. Biol
Psychiatry. 2005;58(3):211217
15. Tollenaar MS, Beijers R, Jansen J, Riksen-
WalravenJM,deWeerthC.Maternal
prenatal stress and cortisol reactivity to
stressors in human infants. Stress. 2011;
14(1):5365
e1456 KARLÉN et al
at Linkopings Universitetsbibliotek on September 24, 2015pediatrics.aappublications.orgDownloaded from
16. Huizink AC, Mulder EJ, Buitelaar JK.
Prenatal stress and risk for
psychopathology: specic effects or
induction of general susceptibility?
Psychol Bull. 2004;130(1):115142
17. Sauvé B, Koren G, Walsh G, Tokmakejian
S, Van Uum SH. Measurement of cortisol
in human hair as a biomarker of
systemic exposure. Clin Invest Med. 2007;
30(5):E183E191
18. Karlén J, Ludvigsson J, Frostell A,
Theodorsson E, Faresjö T. Cortisol in hair
measured in young adultsa biomarker
of major life stressors? BMC Clin Pathol.
2011;11(1):12
19. Dettenborn L, Tietze A, Kirschbaum C,
Stalder T. The assessment of cortisol in
human hair: associations with
sociodemographic variables and
potential confounders. Stress. 2012;
15(6):578588
20. Karlén J, Frostell A, Theodorsson E,
Faresjö T, Ludvigsson J. Maternal
inuence on child HPA axis:
a prospective study of cortisol levels in
hair. Pediatrics. 2013;132(5). Available at:
www.pediatrics.org/cgi/content/full/132/
5/e1333
21. Vaghri Z, Guhn M, Weinberg J, Grunau RE,
Yu W, Hertzman C. Hair cortisol reects
socio-economic factors and hair zinc in
preschoolers. Psychoneuroendocrinology.
2013;38(3):331340
22. Shi L, Stevens GD, Lebrun LA, Faed P, Tsai
J. Enhancing the measurement of health
disparities for vulnerable populations. J
Public Health Manag Pract. 2008;14
(suppl):S45S52
23. Wiréhn AB, Karlsson HM, Carstensen JM.
Estimating disease prevalence using
a population-based administrative
healthcare database. Scand J Public
Health. 2007;35(4):424431
24. Cohen S, Janicki-Deverts D, Chen E,
Matthews KA. Childhood socioeconomic
status and adult health. Ann N Y Acad
Sci. 2010;1(1186):3755
25. Shonkoff JP, Garner AS; Committee on
Psychosocial Aspects of Child and Family
Health; Committee on Early Childhood,
Adoption, and Dependent Care; Section
on Developmental and Behavioral
Pediatrics. The lifelong effects of early
childhood adversity and toxic stress.
Pediatrics. 2012;129(1). Available at:
www.pediatrics.org/cgi/content/full/129/
1/e232
26. Pembrey M, Saffery R, Bygren LO;
Network in Epigenetic Epidemiology;
Network in Epigenetic Epidemiology.
Human transgenerational responses to
early-life experience: potential impact on
development, health and biomedical
research. J Med Genet. 2014;51(9):
563572
27. Fries E, Hesse J, Hellhammer J,
Hellhammer DH. A new view on
hypocortisolism.
Psychoneuroendocrinology. 2005;30(10):
10101016
28. Hjern A, Haglund B, Rasmussen F, Rosén
M. Socio-economic differences in
daycare arrangements and use of
medical care and antibiotics in Swedish
preschool children. Acta Paediatr. 2000;
89(10):12501256
29. Cohen S, Tyrrell DA, Smith AP.
Psychological stress and susceptibility to
the common cold. N Engl J Med. 1991;
325(9):606612
30. Meaney MJ. Maternal care, gene
expression, and the transmission of
individual differences in stress reactivity
across generations. Annu Rev Neurosci.
2001;24:11611192
31. Natland ST, Andersen LF, Nilsen TI,
Forsmo S, Jacobsen GW. Maternal recall
of breastfeeding duration twenty years
after delivery. BMC Med Res Methodol.
2012;12:179
PEDIATRICS Volume 135, number 6, June 2015 e1457
at Linkopings Universitetsbibliotek on September 24, 2015pediatrics.aappublications.orgDownloaded from
DOI: 10.1542/peds.2014-2561
; originally published online May 4, 2015; 2015;135;e1450Pediatrics and Tomas Faresjö
Jerker Karlén, Johnny Ludvigsson, Max Hedmark, Åshild Faresjö, Elvar Theodorsson
Early Psychosocial Exposures, Hair Cortisol Levels, and Disease Risk
Services
Updated Information &
html
http://pediatrics.aappublications.org/content/135/6/e1450.full.
including high resolution figures, can be found at:
References
html#ref-list-1
http://pediatrics.aappublications.org/content/135/6/e1450.full.
at:
This article cites 30 articles, 6 of which can be accessed free
Subspecialty Collections
ogy_sub
http://pediatrics.aappublications.org/cgi/collection/endocrinol
Endocrinology
ial_issues_sub
http://pediatrics.aappublications.org/cgi/collection/psychosoc
Psychosocial Issues nt:behavioral_issues_sub
http://pediatrics.aappublications.org/cgi/collection/developme
Developmental/Behavioral Issues
the following collection(s):
This article, along with others on similar topics, appears in
Permissions & Licensing
tml
http://pediatrics.aappublications.org/site/misc/Permissions.xh
tables) or in its entirety can be found online at:
Information about reproducing this article in parts (figures,
Reprints http://pediatrics.aappublications.org/site/misc/reprints.xhtml
Information about ordering reprints can be found online:
rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.
Grove Village, Illinois, 60007. Copyright © 2015 by the American Academy of Pediatrics. All
and trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk
publication, it has been published continuously since 1948. PEDIATRICS is owned, published,
PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly
at Linkopings Universitetsbibliotek on September 24, 2015pediatrics.aappublications.orgDownloaded from
DOI: 10.1542/peds.2014-2561
; originally published online May 4, 2015; 2015;135;e1450Pediatrics and Tomas Faresjö
Jerker Karlén, Johnny Ludvigsson, Max Hedmark, Åshild Faresjö, Elvar Theodorsson
Early Psychosocial Exposures, Hair Cortisol Levels, and Disease Risk
http://pediatrics.aappublications.org/content/135/6/e1450.full.html
located on the World Wide Web at:
The online version of this article, along with updated information and services, is
of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.
Boulevard, Elk Grove Village, Illinois, 60007. Copyright © 2015 by the American Academy
published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point
publication, it has been published continuously since 1948. PEDIATRICS is owned,
PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly
at Linkopings Universitetsbibliotek on September 24, 2015pediatrics.aappublications.orgDownloaded from
... In 90 newborn infants, Hoffman et al. (2017) reported no association between maternal education and hair cortisol. Two studies drawn from the same population cohort in Sweden found that maternal education during pregnancy was not associated with children's hair cortisol at 1 year (Karlén et al., 2013(Karlén et al., , 2015. Thirteen further studies examining parental education and hair cortisol in children aged 1-5 years also reported no association (Bryson et al., 2019;Groeneveld et al., 2013;Hinnouho et al., 2019;Kao et al., 2018;Lehto et al., 2018;Liu et al., 2016Liu et al., , 2017Palmer et al., 2013;Pauli-Pott et al., 2017, 2019Rickmeyer et al., 2017;Schloß et al., 2018b;Simmons et al., 2019) Three of these studies drew on the same cohort of German preschool children as the study by Schloß et al. (2018a) described above (Pauli-Pott et al., 2017, 2019Schloß et al., 2018b). ...
... Ling et al. (2019) further found greater food insecurity was associated with higher child hair cortisol in a US cohort of 32 children aged 3-5 years. Karlén et al. (2015) found that children whose mothers were unemployed during pregnancy had higher hair cortisol concentrations at 1 year than those whose mothers were employed. ...
... Rippe et al. (2016) reported a univariable association between single parent status and higher child hair cortisol in 6-year-olds, but this was not observed after accounting for other measures of SES, nor was an association observed in a subsequent Generation R cohort study, which accounted for similar measures in a multivariable analysis (Windhorst et al., 2017). Eight other studies also reported no evidence of association in newborn infants (Hoffman et al., 2017), and child ages ranging from 1 to 6 years (Bryson et al., 2019;Hinnouho et al., 2019;Karlén et al., 2015;Liu et al., 2016Liu et al., , 2017Simmons et al., 2019;Vaghri et al., 2013), in either univariable and multivariable analyses. ...
Article
Psychosocial and socioeconomic adversity in early childhood (termed ‘social adversity’) can have lifelong detrimental effects on health and development. Physiological stress is one proposed mechanism by which social adversity ‘gets under the skin’. There is substantial research interest in whether hair cortisol, a biomarker proposed to measure the cumulative physiological stress response over time, can illustrate this mechanism. As a result, a growing number of studies have tested for associations between indicators of social adversity and child hair cortisol. The aim of this paper is to conduct a comprehensive, systematic review of the evidence for associations between indicators of social adversity and hair cortisol, specifically in young children (birth to 8 years) published any time up to 31 December 2019. The literature search identified 44 published studies that met inclusion criteria. The studies examined associations between one or more indicators of social adversity and child hair cortisol across 35 independent cohorts comprising 8370 children. Indicators of adversity examined in the identified literature included socioeconomic factors (e.g. low parental education, low income and unemployment), psychosocial factors (e.g. parent stress, poor mental health and family violence), and children’s direct exposure to maltreatment, abuse and stressful events. Across all indicators of adversity, a total of 142 associations with hair cortisol were examined. Evidence of associations was limited and inconsistent; 34/142 (24%) showed evidence of a positive association between adversity and higher hair cortisol, 8/142 (6%) showed a negative association, and more than two thirds (100/142, 70%) of all examined associations were null. The collective evidence appears insufficient to conclude that there is a relationship between social adversity and hair cortisol, as a measure of physiological stress response, in young children.
... Transient increased stress either caused by trauma, psychosocial factors, infections etc. can usually be managed by the body [2], while repeated serious stress for instance repeated serious life events such as loss of parents (divorce, death), serious disease in the family [3] or chronic stress contribute to increased morbidity. There is no simple way to determine stress over longer time but in recent years cortisol in hair, reflecting the cortisol concentrations of the body for some months since hair grows ca 1 cm/month [4], has been used as biomarker for long-term stress both in animals [5,6] and in humans [4,7,8]. Recent years, also clinical applications of cortisol measurements have emerged [9] such as biomarker of children's stress at school and also parityrelated variations in cortisol concentrations in hair during pregnancy [10,11]. ...
... Transient increased stress either caused by trauma, psychosocial factors, infections etc. can usually be managed by the body [2], while repeated serious stress for instance repeated serious life events such as loss of parents (divorce, death), serious disease in the family [3] or chronic stress contribute to increased morbidity. There is no simple way to determine stress over longer time but in recent years cortisol in hair, reflecting the cortisol concentrations of the body for some months since hair grows ca 1 cm/month [4], has been used as biomarker for long-term stress both in animals [5,6] and in humans [4,7,8]. Recent years, also clinical applications of cortisol measurements have emerged [9] such as biomarker of children's stress at school and also parityrelated variations in cortisol concentrations in hair during pregnancy [10,11]. ...
Article
Full-text available
Background One of the most important protective health factors for children is breast-feeding, but the mechanisms for this effect are not fully elucidated. Our objective was to assess if the duration of breastfeeding influences cortisol in hair, used as a biomarker for stress in children still at school-age. Methods ABIS (All Babies in Southeast Sweden) is a prospective population-based child cohort study of 17,055 children born Oct 1st1997- Oct 1st 1999, with the aim to study development of immune-mediated diseases. Questionnaires were answered at birth and then at regular follow-ups, and biological samples were collected. As a biomarker of stress, we measured the child’s cortisol in hair collected at 8 years of age, those randomly selected N = 126 children among those with enough hair samples for analyses of hair at 8 years of age. Duration of breastfeeding had been registered as well as psycho-social factors related to breastfeeding and/or stress. Results There was a negative correlation (r = − 0.23, p = 0.01) between total duration of breastfeeding and hair cortisol levels at 8 years of age. In a multivariate analysis this association persisted ( p = 0.01) even when adjusted for other potential intervening factors like age of mother at delivery and early psychosocial vulnerability in the family, an index based on 11 factors (Multivariate model: df = 5, adj R ² = 0.15, F = 5.38, p < 0.01). Conclusion Our results show that longer breastfeeding is associated with lower cortisol levels in the child many years later. These associations should be more elaborated in further studies, and these findings also give some implications for public health. Mothers should be encouraged to breastfeed their children also in the modern society, since breastfeeding promotes health in the child. This information could be given via the obstetric departments and later at the well-baby clinics.
... Specifically, we tested interactions between infant HCC, parent HCC, may be linked to behavioral responses to social stressors in human infants as well. Consistent with prior literature [77], we found that infant and parent HCC were positively correlated. However, our results revealed that infant HCC was uniquely associated with distress vocalizations above and beyond parent HCC, while parent HCC was not associated with either fear behavior. ...
Article
Full-text available
Elevated social fear in infancy poses risk for later social maladjustment and psychopathology. Hair cortisol concentration (HCC), an index of cumulative cortisol exposure, and diurnal salivary cortisol slope, a biomarker of acute stress regulation, have been associated with social fear behaviors in childhood; however, no research has addressed their relations in infancy. Elucidating potential biomarkers of infant social fear behaviors, as well as environmental factors associated with these biomarkers, may grant insights into the ontogeny of fear behaviors that increase risk for internalizing and externalizing psychopathologies later in life. The current study used multiple linear regression to examine if infant HCC, infant diurnal cortisol slope, and income-to-needs ratios (ITN) were differentially associated with observed social fear responses to a Stranger Approach task at 12 months. Using a sample of 90 infants (M age = 12.26m, SD = 0.81m, 50% female), results indicated that increased infant HCC was associated with increased distress vocalizations during the Stranger Approach task, while steeper diurnal cortisol slope was associated with fewer distress vocalizations. Ordinary least squares path analyses did not reveal group differences between economically strained and non-strained infants in how cortisol measures and social fear responses related. Findings underscore very early psychobiological correlates of fearfulness that may increase risk for fear-related disorders and adverse mental health symptomology across childhood.
... While earlier studies have examined salivary cortisol as a marker of physiological stress 24 , hair cortisol concentration have recently gained prominence as a reliable marker of chronic HPA axis activity in children [25][26][27][28][29] . However, the prospective association between hair cortisol levels with later child outcomes has been described in only two studies [30][31][32] , with common childhood diseases, child mental health, and physical and mental well-being being the primary outcome measures. Second, the putative causal mediation role of hair cortisol levels on the association between cumulative adversities and later growth and cognitive outcomes in children has not been investigated so far. ...
Article
Background: Early adversities negatively impact children’s growth and development, putatively mediated by chronic physiological stress resulting from these adverse experiences. We aimed to estimate the associations between prospectively measured cumulative early adversities with growth and cognition outcomes in rural Indian preschool children and to explore if hair cortisol concentration (HCC), a measure of chronic physiological stress, mediated the above association. Methods: Participants were recruited from the SPRING cRCT in rural Haryana, India. Adversities experienced through pregnancy and the first year of life were measured in 1304 children at 12-months. HCC was measured at 12-months in 845 of them. Outcome measures were height-for-age-z-score (HAZ), weight-for-age-z-score (WAZ) and cognition, measured in 1124 children followed up at 3-years. Cognition was measured using a validated tablet-based gamified tool named DEEP. Results: Cumulative adversities at 12-months were inversely associated with all outcomes measures at 3-years. Each unit increase in adversity score led to a decrease of 0·08 units [95% confidence interval (CI):-0·11,-0·06] in DEEP-z-score; 0·12 units [-0·14,-0·09] in HAZ and 0·11 units [-0·13,-0·09] in WAZ. 12-month HCC was inversely associated with DEEP-z-score (-0·09 [-0·16,-0·01]) and HAZ (-0·12 [-0·20,-0·04]), but the association with WAZ was not significant (p = 0·142). HCC marginally mediated the association between cumulative adversities and HAZ (proportion mediated = 0·06, p = 0·014). No evidence of mediation was found for the cognition outcome. Conclusions: Cumulative early adversities and HCC measured at 12-months have persistent negative effects on child growth and cognition at 3-years. The association between adversities and these two child outcomes were differentially mediated by HCC, with no evidence of mediation observed for the cognitive outcome. Future studies should focus on other stress biomarkers, and alternate pathways such as the immune, inflammation and cellular ageing pathways, to unpack key mechanisms underlying the established relationship between early adversities and poor child outcomes.
... The impact of acute and chronic stress exposure on systems that maintain health is well documented in experimental animal and human studies (Calcagni & Elenkov, 2006;Cavigelli & Caruso, 2015;Karlén et al., 2015;Matthews & Gallo, 2011). Although the results from correlational studies in humans on stress exposure and outcomes are relatively robust, there remains substantial heterogeneity and lack of specificity in methodology across studies. ...
Article
Full-text available
Background The science of stress exposure and health in humans has been hampered by differences in operational definitions of exposures and approaches to defining timing, leading to results that lack consistency and specificity. In the present study we aim to empirically derive variability in type, timing and chronicity of stress exposure for Black and White females using prospectively collected data in the Pittsburgh Girls Study (PGS). Methods The PGS is an ongoing 20-year longitudinal, community-based study. In this paper we focused on annual caregiver reports of three domains of stress: subsistence (e.g., resource strain, overcrowding); safety (e.g., community violence, inter-adult aggression), and caregiving (e.g., separation, maternal depression) from early childhood through adolescence. Z-scores were used to conduct a finite mixture model-based latent class trajectory analysis. Model fit was compared using the Akaike Information Criterion (AIC) and Bayesian Information Criterion (BIC). We examined differences in timing and chronicity of stress exposure between Black and White girls. Results Distinct trajectory groups characterized by differential timing and chronicity of stress exposure were observed across all stress domains. Six trajectories characterized subsistence and safety stress, and five characterized caregiving stress. Variability in initial level, chronicity, and magnitude and timing of change was observed within and across domains of stressors. Race differences also varied across the domains: race differences in timing and chronicity were most pronounced for the subsistence and safety domains, whereas Black and White girls had similar levels of exposure to caregiving stress. Conclusions Substantial variability in timing and chronicity was observed within and across stress domains. Modeling specific domains and dimensions of stress exposure is likely important in testing associations between exposure and health; such specificity may lead to more effective deployment of preventive interventions based on stress exposure.
... 7,8 There is also a clear link between psychosocial stressors and obesity, as evidenced by increased cortisol levels among youth with higher levels of central adiposity, which contribute to overall cardiometabolic risk. 9 Together, youth with obesity are at greater risk for reduced HRQOL, and the complications that can arise from having a lower health-related quality of life. ...
Article
Full-text available
Health-related quality of life (HRQOL), a multifaceted construct for understanding health and healthcare outcomes, is comprised of eight domains of well-being and functioning over time and has become an essential factor in assessing outcomes for youth with obesity. For this 12-week family and community-based intervention (ACT; Actively Changing Together), HRQOL was measured before and after the intervention concluded using the obesity-specific HRQOL tool, Sizing Me Up (SMU). This study enrolled 68 youth (10.9 ± 2 years; 54% male; 50% non-Hispanic white). Paired t-tests were used to examine the Sizing Me Up sub-scales: Emotion, Physical, Social Avoidance, Positive Attributes, Teasing, and the total score. A greater change score indicated a larger increase in quality of life sub-scale. Significant improvements from baseline to follow-up were found in the total SMU (mean change = 5.27, SD 10.76, p=0.00) and for the sub-scores of: emotion (mean change = 8.06, SD 16.85, p≤0.00), teasing (mean change = 5.65, SD 16.79, p = 0.01), and social avoidance (mean change = 3.92, SD 11.21, p=0.01). Sizing Me Up provided a clinically meaningful tool for this research study to evaluate obesity-specific health related quality of life among Hispanic and non-Hispanic White youth with obesity. This article is protected by copyright. All rights reserved.
Article
Background: Early adversities negatively impact children’s growth and development, putatively mediated by chronic physiological stress resulting from these adverse experiences. We aimed to estimate the associations between prospectively measured cumulative early adversities with growth and cognition outcomes in rural Indian preschool children and to explore if hair cortisol concentration (HCC), a measure of chronic physiological stress, mediated the above association. Methods: Participants were recruited from the SPRING cRCT in rural Haryana, India. Adversities experienced through pregnancy and the first year of life were measured in 1304 children at 12-months. HCC was measured at 12-months in 845 of them. Outcome measures were height-for-age-z-score (HAZ), weight-for-age-z-score (WAZ) and cognition, measured in 1124 children followed up at 3-years. Cognition was measured using a validated tablet-based gamified tool named DEEP. Results: Cumulative adversities at 12-months were inversely associated with all outcomes measures at 3-years. Each unit increase in adversity score led to a decrease of 0·08 units [95% confidence interval (CI):-0·11,-0·06] in DEEP-z-score; 0·12 units [-0·14,-0·09] in HAZ and 0·11 units [-0·13,-0·09] in WAZ. 12-month HCC was inversely associated with DEEP-z-score (-0·09 [-0·16,-0·01]) and HAZ (-0·12 [-0·20,-0·04]), but the association with WAZ was not significant (p = 0·142). HCC marginally mediated the association between cumulative adversities and HAZ (proportion mediated = 0·06, p = 0·014). No evidence of mediation was found for the cognition outcome. Conclusions: Cumulative early adversities and HCC measured at 12-months have persistent negative effects on child growth and cognition at 3-years. The association between adversities and these two child outcomes were differentially mediated by HCC, with no evidence of mediation observed for the cognitive outcome. Future studies should focus on other stress biomarkers, and alternate pathways such as the immune, inflammation and cellular ageing pathways, to unpack key mechanisms underlying the established relationship between early adversities and poor child outcomes.
Article
Acculturative stress is unique among immigrants and refers to the stress associated with maintaining cultural values and traditions in the host country. Immigrant parents confront psychosocial variables such as acculturative stress, anxiety, and depression that might result in intergenerational negative consequences on their infants. Measurement of hair cortisol concentration (HCC), an outcome of neuroendocrine dysregulation, is one relatively noninvasive approach to gauge stress in infants. No published studies have evaluated associations among parents’ psychosocial variables and infants’ HCC among immigrant families. Therefore, the purpose of this study was to: (1) examine the relationship between maternal and paternal psychosocial stress variables; and (2) examine the association between psychosocial variables of both parents (acculturative stress, anxiety, and depression) and infants’ HCC among immigrant Arab American families. A sample of 31 immigrant Arab American triads (mother–father–infant) was recruited. During one home visit, each parent completed the study questionnaires separately when the baby was 6–24 months old and a hair sample was collected from the infant for HCC. Parents reported significant symptoms of anxiety (33% mothers; 45% fathers) and depression (33% mothers; 35.5% fathers). Paternal acculturative stress, anxiety, and depressive symptoms were significantly correlated to infants’ HCC. Acculturative stress, anxiety, and depressive symptoms were significantly correlated between mother–father dyads. Future research should continue to focus on immigrant families and include both parents to better understand and improve infant health.
Chapter
A third of the general population worldwide has a history of childhood trauma, and it remains a major public health and social welfare problem. Exposure to childhood trauma during development has long-lasting effects on physical and mental health, drug and alcohol use and crime, with high costs for both the individual and the society. Worldwide, up to 20% of children and adolescents experience mental disorders, but early intervention in this age group is largely absent. Psychological and biological mechanisms interact in the association between childhood trauma and poor health outcomes from birth to adult life. In recent years, research and practice on traumatic childhood experiences have shifted from delineating effects of trauma on adulthood health problems to preventing potentially traumatic events in children. This paper aims to summarise the literature on the impact of childhood trauma on mental health and to describe the current evidence base for early interventions focused on preventing and reducing the psychobiological sequelae of childhood trauma. Public health strategies for prevention of childhood trauma include both universal and targeted interventions, ranging from home visiting programmes to parent training programmes, routine screening for adversity in children and caregivers and specialised therapeutic approaches. Childhood is a time of vulnerability but also of opportunity; intervention offered at critically sensitive periods of development may improve the well-being of children throughout their life.
Article
Cortisol (C) and dehydroepiandrosterone (DHEA) are recognized as the main fetal steroids, and they are likely to influence fetal development and have long-term effects on newborn hypothalamic-pituitary-adrenal axis (HPA) function. DHEA is often measured as its sulfates and expressed as DHEA-S. Hair analysis represents a promising methodological approach for the non-invasive measurement of steroids, allowing for a retrospective analysis of the total exposure to steroids over time, and avoiding the influence of acute events or circadian fluctuations. Hair cortisol and DHEA concentrations have been investigated in cows, but no studies have been performed on calves. The object of this study was to evaluate hair cortisol (HC) and hair DHEA-S (HDHEA-S) concentrations in beef calves from birth to six months of age. Hair samples of 12 beef calves (seven males, five females) were firstly collected at birth (T1) and then every three weeks up to six months of age (T2-T10), collecting only the re-growth hair. HC and HDHEA-S were analyzed by radioimmunoassay (RIA). Calves sex, weight and APGAR score were registered immediately after birth. Statistical analysis revealed that both HC and HDHEA-S were influenced by sampling time (P < 0.001). HC concentrations were higher at T1 compared to all subsequent samplings (T2-T10, P < 0.01); HC concentrations were higher at T2 compared to T4-T10 (P < 0.01), while no further changes were detected from T3 onward. Higher HDHEA-S concentrations were registered at T1, T2 and T3 compared to all the other samplings (P < 0.01). No correlation was found between hair concentrations of both steroids and calf sex or birthweight. APGAR score was negatively correlated only with HC at birth (P < 0.05). These data demonstrate that C and DHEA-S are quantifiable in the hair of calves and are influenced by their age. The higher HC detected at birth (T1) probably reflects the high serum C concentrations present late in pregnancy and increased by the fetal HPA axis, by which parturition is initiated in cows. The highest HDHEA-S at birth (T1) in calves indicates that the largest amounts of DHEA and its sulfates are produced during fetal development. Moreover, the findings of higher HC at three weeks after birth and of higher HDHEA-S until six weeks after birth, suggest that C and DHEA secretion continues also beyond birth, and that these steroids could be involved in the events occurring during the challenging first weeks of age in the calf.
Article
Full-text available
It is not known whether psychological stress suppresses host resistance to infection. To investigate this issue, we prospectively studied the relation between psychological stress and the frequency of documented clinical colds among subjects intentionally exposed to respiratory viruses. After completing questionnaires assessing degrees of psychological stress, 394 healthy subjects were given nasal drops containing one of five respiratory viruses (rhinovirus type 2, 9, or 14, respiratory syncytial virus, or coronavirus type 229E), and an additional 26 were given saline nasal drops. The subjects were then quarantined and monitored for the development of evidence of infection and symptoms. Clinical colds were defined as clinical symptoms in the presence of an infection verified by the isolation of virus or by an increase in the virus-specific antibody titer. The rates of both respiratory infection (P less than 0.005) and clinical colds (P less than 0.02) increased in a dose-response manner with increases in the degree of psychological stress. Infection rates ranged from approximately 74 percent to approximately 90 percent, according to levels of psychological stress, and the incidence of clinical colds ranged from approximately 27 percent to 47 percent. These effects were not altered when we controlled for age, sex, education, allergic status, weight, the season, the number of subjects housed together, the infectious status of subjects sharing the same housing, and virus-specific antibody status at base line (before challenge). Moreover, the associations observed were similar for all five challenge viruses. Several potential stress-illness mediators, including smoking, alcohol consumption, exercise, diet, quality of sleep, white-cell counts, and total immunoglobulin levels, did not explain the association between stress and illness. Similarly, controls for personality variables (self-esteem, personal control, and introversion-extraversion) failed to alter our findings. Psychological stress was associated in a dose-response manner with an increased risk of acute infectious respiratory illness, and this risk was attributable to increased rates of infection rather than to an increased frequency of symptoms after infection.
Article
Full-text available
Mammalian experiments provide clear evidence of male line transgenerational effects on health and development from paternal or ancestral early-life exposures such as diet or stress. The few human observational studies to date suggest (male line) transgenerational effects exist that cannot easily be attributed to cultural and/or genetic inheritance. Here we summarise relevant studies, drawing attention to exposure sensitive periods in early life and sex differences in transmission and offspring outcomes. Thus, variation, or changes, in the parental/ancestral environment may influence phenotypic variation for better or worse in the next generation(s), and so contribute to common, non-communicable disease risk including sex differences. We argue that life-course epidemiology should be reframed to include exposures from previous generations, keeping an open mind as to the mechanisms that transmit this information to offspring. Finally, we discuss animal experiments, including the role of epigenetic inheritance and non-coding RNAs, in terms of what lessons can be learnt for designing and interpreting human studies. This review was developed initially as a position paper by the multidisciplinary Network in Epigenetic Epidemiology to encourage transgenerational research in human cohorts.
Article
Full-text available
Objective: To investigate cortisol concentrations in hair as biomarker of prolonged stress in young children and their mothers and the relation to perinatal and sociodemographic factors. Methods: Prospective cohort study of 100 All Babies In Southeast Sweden study participants with repeated measures at 1, 3, 5, and 8 years and their mothers during pregnancy. Prolonged stress levels were assessed through cortisol in hair. A questionnaire covered perinatal and sociodemographic factors during the child's first year of life. Results: Maternal hair cortisol during the second and third trimester and child hair cortisol at year 1 and 3 correlated. Child cortisol in hair levels decreased over time and correlated to each succeeding age, between years 1 and 3 (r = 0.30, P = .002), 3 and 5 (r = 0.39, P < .001), and 5 and 8 (r = 0.44, P < .001). Repeated measures gave a significant linear association over time (P < .001). There was an association between high levels of hair cortisol and birth weight (β = .224, P = .020), nonappropriate size for gestational age (β = .231, P = .017), and living in an apartment compared with a house (β = .200, P = .049). In addition, we found high levels of cortisol in hair related to other factors associated with psychosocial stress exposure. Conclusions: Correlation between hair cortisol levels in mothers and their children suggests a heritable trait or maternal calibration of the child's hypothalamic-pituitary-adrenocortical axis. Cortisol output gradually stabilizes and seems to have a stable trait. Cortisol concentration in hair has the potential to become a biomarker of prolonged stress, especially applicable as a noninvasive method when studying how stress influences children's health.
Article
Full-text available
Socioeconomic status (SES) is consistently associated with health outcomes, yet little is known about the psychosocial and behavioral mechanisms that might explain this association. Researchers usually control for SES rather than examine it. When it is studied, only effects of lower, poverty-level SES are generally examined. However, there is evidence of a graded association with health at all levels of SES, an observation that requires new thought about domains through which SES may exert its health effects. Variables are highlighted that show a graded relationship with both SES and health to provide examples of possible pathways between SES and health end points. Examples are also given of new analytic approaches that can better illuminate the complexities of the SES-health gradient.
Article
Full-text available
Background Studies on the health benefits from breastfeeding often rely on maternal recall of breastfeeding. Although short-term maternal recall has been found to be quite accurate, less is known about long-term accuracy. The objective of this study was to assess the accuracy of long-term maternal recall of breastfeeding duration. Methods In a prospective study of pregnancy and birth outcome, detailed information on breastfeeding during the child’s first year of life was collected from a cohort of Norwegian women who gave birth in 1986–88. Among 374 of the participants, data on breastfeeding initiation and duration were compared to recalled data obtained from mailed questionnaires some 20 years later. Intraclass correlation coefficient (ICC), Bland-Altman plot, and Kappa statistics were used to assess the agreement between the two sources of data. Logistic regression was used to assess predictors of misreporting breastfeeding duration by more than one month. Results Recorded and recalled breastfeeding duration were strongly correlated (ICC=0.82, p < 0.001). Nearly two thirds of women recalled their breastfeeding to within one month. Recall data showed a modest median overestimation of about 2 weeks. There were no apparent systematic discrepancies between the two sources of information, but recall error was predicted by the age when infants were introduced to another kind of milk. Across categories of breastfeeding, the overall weighted Kappa statistic showed an almost perfect agreement (κ = 0.85, 95% confidence interval [CI] 0.82 – 0.88). Conclusion Breastfeeding duration was recalled quite accurately 20 years after mothers gave birth in a population where breastfeeding is common and its duration long.
Article
Full-text available
To inform the future use of hair cortisol measurement, we have investigated influences of potential confounding variables (natural hair colour, frequency of hair washes, age, sex, oral contraceptive (OC) use and smoking status) on hair cortisol levels. The main study sample comprised 360 participants (172 women) covering a wide range of ages (1-91 years; mean = 25.95). In addition, to more closely examine influences of natural hair colour and young age on hair cortisol levels, two additional samples comprising 69 participants with natural blond or dark brown hair (hair colour sample) as well as 28 young children and 34 adults (young age sample) were recruited. Results revealed a lack of an effect for natural hair colour, OC use, and smoking status on hair cortisol levels (all p's >0.10). No influence of frequency of hair washes was seen for proximal hair segments (p = 0.335) but for the third hair segment indicating lower cortisol content (p = 0.008). We found elevated hair cortisol levels in young children and older adults (p < 0.001). Finally, men showed higher hair cortisol levels than women (p = 0.002). The present data indicate that hair cortisol measurement provides a useful tool in stress-related psychobiological research when applied with the consideration of possible confounders including age and sex.
Article
Full-text available
ABSTRACT: Stress as a cause of illness has been firmly established. In public health and stress research a retrospective biomarker of extended stress would be an indispensible aid. The objective of this pilot study was to investigate whether concentrations of cortisol in hair correlate with perceived stress, experiences of serious life events, and perceived health in young adults. Hair samples were cut from the posterior vertex area of (n = 99) university students who also answered a questionnaire covering experiences of serious life events, perceived Stress Scale and perceived health during the last three months. Cortisol was measured using a competitive radioimmunoassay in methanol extracts of hair samples frozen in liquid nitrogen and mechanically pulverised. Mean cortisol levels were significantly related to serious life events (p = 0.045), weakly negatively correlated to perceived stress (p = 0.025, r = -0.061) but nor affected by sex, coloured/permed hair, intake of pharmaceuticals or self-reported health. In a multiple regression model, only the indicator of serious life events had an independent (p = 0.041) explanation of increased levels of cortisol in hair. Out of four outliers with extremely high cortisol levels two could be contacted, both reported serious psychological problems. These findings suggest that measurement of cortisol in hair could serve as a retrospective biomarker of increased cortisol production reflecting exposure to major life stressors and possibly extended psychological illness with important implications for research, clinical practice and public health. Experience of serious life events seems to be more important in raising cortisol levels in hair than perceived stress.
Article
Context Suicide is a leading cause of death in the United States, but identifying persons at risk is difficult. Thus, the US surgeon general has made suicide prevention a national priority. An expanding body of research suggests that childhood trauma and adverse experiences can lead to a variety of negative health outcomes, including attempted suicide among adolescents and adults.Objective To examine the relationship between the risk of suicide attempts and adverse childhood experiences and the number of such experiences (adverse childhood experiences [ACE] score).Design, Setting, and Participants A retrospective cohort study of 17 337 adult health maintenance organization members (54% female; mean [SD] age, 57 [15.3] years) who attended a primary care clinic in San Diego, Calif, within a 3-year period (1995-1997) and completed a survey about childhood abuse and household dysfunction, suicide attempts (including age at first attempt), and multiple other health-related issues.Main Outcome Measure Self-reported suicide attempts, compared by number of adverse childhood experiences, including emotional, physical, and sexual abuse; household substance abuse, mental illness, and incarceration; and parental domestic violence, separation, or divorce.Results The lifetime prevalence of having at least 1 suicide attempt was 3.8%. Adverse childhood experiences in any category increased the risk of attempted suicide 2- to 5-fold. The ACE score had a strong, graded relationship to attempted suicide during childhood/adolescence and adulthood (P<.001). Compared with persons with no such experiences (prevalence of attempted suicide, 1.1%), the adjusted odds ratio of ever attempting suicide among persons with 7 or more experiences (35.2%) was 31.1 (95% confidence interval, 20.6-47.1). Adjustment for illicit drug use, depressed affect, and self-reported alcoholism reduced the strength of the relationship between the ACE score and suicide attempts, suggesting partial mediation of the adverse childhood experience–suicide attempt relationship by these factors. The population-attributable risk fractions for 1 or more experiences were 67%, 64%, and 80% for lifetime, adult, and childhood/adolescent suicide attempts, respectively.Conclusions A powerful graded relationship exists between adverse childhood experiences and risk of attempted suicide throughout the life span. Alcoholism, depressed affect, and illicit drug use, which are strongly associated with such experiences, appear to partially mediate this relationship. Because estimates of the attributable risk fraction caused by these experiences were large, prevention of these experiences and the treatment of persons affected by them may lead to progress in suicide prevention.