Peanut sensitisation and allergy: influence of early life exposure to peanuts
Rachel L. Thompson1, Lisa M. Miles1*, Joanne Lunn1, Graham Devereux2, Rebecca J. Dearman3,
Jessica Strid4and Judith L. Buttriss1
1British Nutrition Foundation, High Holborn House, 52–54 High Holborn, London WC1V 6RQ, UK
2Department of Environmental and Occupational Medicine, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK
3Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, UK
4Peter Gorer Department of Immunobiology, King’s College London School of Medicine at Guy’s Hospital, London SE1 9RT, UK
(Received 2 February 2009 – Revised 15 July 2009 – Accepted 28 September 2009 – First published online 26 January 2010)
The aim of the present systematic review was to evaluate the influence of early life exposure (maternal and childhood) to peanuts and the sub-
sequent development of sensitisation or allergy to peanuts during childhood. Studies were identified using electronic databases and bibliography
searches. Studies that assessed the impact of non-avoidance compared with avoidance or reduced quantities of peanuts or peanut products on either
sensitisation or allergy to peanuts, or both outcomes, were eligible. Six human studies were identified: two randomised controlled trials, two case–
control studies and two cross-sectional studies. In addition, published animal and mechanistic studies, relevant to the question of whether early life
exposure to peanuts affects the subsequent development of peanut sensitisation, were reviewed narratively. Overall, the evidence reviewed was
heterogeneous, and was limited in quality, for example, through lack of adjustment for potentially confounding factors. The nature of the evidence
has therefore hindered the development of definitive conclusions. The systematic review of human studies and narrative expert-led reviews of
animal studies do not provide clear evidence to suggest that either maternal exposure, or early or delayed introduction of peanuts in the diets
of children, has an impact upon subsequent development of sensitisation or allergy to peanuts. Results from some animal studies (and limited
evidence from human subjects) suggest that the dose of peanuts is an important mediator of peanut sensitisation and tolerance; low doses tend
to lead to sensitisation and higher doses tend to lead to tolerance.
Peanut allergy: Diet: Prenatal exposure: Childhood exposure
Onset of peanut allergy typically occurs in childhood, with
70–100%(1)of peanut-allergic children being reported to
react upon their first known dietary exposure to peanuts.
exposure and immunological sensitisation to the allergen,
this suggests that sensitisation has already been acquired,
either in utero, or by unrecognised oral exposure or non-oral
(cutaneous or respiratory) routes. As many as one in fifty-
five children in the UK may currently show evidence of an
allergic reaction to peanuts(2); indeed, peanut allergy is the
most common cause of severe allergic reaction to foods, caus-
ing 30% of all cases of anaphylaxis outside hospital(3). Data
from the Isle of Wight UK Birth Cohort Study suggest a three-
fold rise in the prevalence of peanut sensitisation and allergy
in children born between 1989–90 and 1994–6(4,5). Recent
data from children born in 2001–2 show no further increases
in the prevalence of peanut sensitisation and allergy(6).
In 1998 the UK Government issued precautionary advice
to mothers whose children have a family history of allergic
diseases, that they may wish to avoid peanut consumption
during pregnancy and breast-feeding and avoid giving the
child peanuts and peanut products until the child is 3 years
of age(7). The precautionary advice was based on recommen-
dations from the UK Committee on Toxicity of Chemicals
in Food, Consumer Products and the Environment (COT),
which advises the UK Government. The recommendations
of the COT have since come under scrutiny as further scienti-
fic evidence on the development of peanut allergy and other
food allergies in children has emerged.
The UK Food Standards Agency therefore commissioned a
systematic review of the literature on food allergy published
since 1999, in order to assess the relevant evidence base
since the COT issued its recommendations in 1998. The sys-
tematic review evaluated studies that aimed to investigate
dietary food allergen consumption or avoidance behaviour in
early life and subsequent development of food allergy, with
a particular focus on peanut allergy. The systematic review
covered a wide range of food allergies including cows’
*Corresponding author: Ms Lisa M. Miles, fax þ44 20 7404 6747, email firstname.lastname@example.org
Abbreviations: COT, Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment; RCT, randomised controlled trial.
British Journal of Nutrition (2010), 103, 1278–1286
q The Authors 2010
British Journal of Nutrition
milk, eggs, fish and nuts, as well as peanut allergy. In this
paper, we present the evidence from this systematic review
of literature on early-life patterns of exposure to, and avoid-
ance of, peanut allergens and later development of sensitis-
ation and clinical peanut allergy. The role of maternal and
childhood diets and the subsequent development of sensitis-
ation and allergy to peanuts was investigated using evidence
published since 1998. Non-dietary exposure to peanuts, for
example, cutaneous or environmental exposure, was also
reviewed. The review included both human and animal
studies, and also a review of evidence investigating the
response of cord blood mononuclear cells to allergens in
order to reflect on the concept that intra-uterine immunologi-
cal sensitisation can occur and increases the likelihood of
subsequent atopic disease.
The research questions related to peanut sensitisation and
allergy from human studies are shown below.
Question1. Does maternal
peanuts or peanut products – or avoidance of dietary con-
sumption of peanuts or peanut products – during pregnancy/
lactation have any impact on the subsequent development of
sensitisation, or allergy to peanuts by the child?
Question 2.Does dietary consumption of peanuts or
peanut products – or avoidance of dietary consumption of
peanuts or peanut products in childhood – have any impact
on the subsequent development of sensitisation or allergy to
Question 3. Does non-dietary exposure to peanuts in
childhood, for instance via skin or the respiratory tract, have
any impact on the subsequent development of sensitisation
or allergy to peanuts?
All types of study design were included except case reports
and therapeutic or treatment studies where the aim was to con-
trol allergic symptoms. The comparison of interest in each
study was avoidance or reduced quantities with non-avoidance
of peanuts or peanut products. Both dietary and non-dietary
sources (for example, peanut oil in skin creams) were included
in the systematic review. Excluded were studies reporting diet-
ary intake as nutrients rather than foods and studies on vitamin
and mineral supplements, food preservatives or additives. Out-
comes of interest concerned both sensitisation and allergy.
Measures of sensitisation included peanut-specific skin prick
tests and peanut-specific IgE. Measures of clinical allergy
included a positive food challenge to peanuts (open or blind,
including double-blind placebo-controlled food challenge),
parental reports of suggestive symptoms occurring shortly
after eating peanuts and reports of doctor’s diagnosis of
peanut allergy. Studies with asthma, eczema, atopic dermati-
tis, rhinitis, atopic wheeze, and other respiratory outcomes,
or that did not report specifically on peanut sensitisation or
allergy were excluded.
Question 4.Has the current UK Government guidance on
dietary consumption of peanuts and peanut products had any
impact on sensitisation and allergy rates to peanuts in the UK?
Included were studies that provide information on knowl-
edge of, or adherence to, the 1998 COT recommendations,
as well as information on sensitisation or allergy to peanuts
in the child. Cohort, case–control and cross-sectional studies
assessing the development of sensitisation or clinical peanut
allergy in relation to adherence to COT recommendations
were included. Subjects were women who became pregnant
after June 1998 and infants and children conceived after
June 1998. The exposures included maternal knowledge of
the COT recommendations, and data on dietary and non-
dietary sources of peanuts in the maternal diet and in the
child’s diet up to the age of 3 years. The outcomes of interest
were dietary (maternal and child) intake of peanuts, and
sensitisation to peanuts and peanut allergy in the child
(using the same measures as previously described).
The Cochrane Library (Systematic Reviews and Central Data-
bases), MEDLINE, EMBASE and CAB Abstracts were
searched from 1 January 1999 to 7 March 2008. The search
strategy included both medical subject heading (MeSH)
terms and text terms where possible. A search strategy that
included terms to cover all the research questions for human
studies was developed. Terms for peanuts (Arachis hypogaea,
arachis oil, peanut*) were combined with those for sensitis-
ation and allergy (food hypersensitivity, allerg*, atopy*,
atopic* intolerance, hypersensitivity*). The search was
restricted to papers published in English and to subjects
aged from newborn to 12 years. The reference lists of reviews
and included studies were checked for any further papers.
Abstracts presented at meetings and/or conferences that were
unsupported by a full published paper were not included.
A separate search, on authors of included studies, was con-
ducted to find further articles written by these authors.
No study was excluded on the basis of quality. All titles and
abstracts of papers identified by the searches were assessed for
inclusion by one reviewer. Full copies of papers considered
potentially relevant (not clearly excluded) were obtained.
The full copies of papers were assessed for eligibility indepen-
dently by two reviewers; any disagreement between the
reviewers was resolved by discussion between the reviewers
or by assessment by a third reviewer. Data extraction forms
were developed based upon the checklists developed by the
Scottish Intercollegiate Guidelines Network(8), and included
questions to critically appraise each study. All data extraction
forms were completed independently by two reviewers; any
disagreement between the reviewers regarding relevant data
or quality assessment was resolved by discussion.
Narrative expert-led reviews
Expert-led reviews were conducted of animal studies on
peanut sensitisation or allergy, based on questions 1 to 3.
Studies on animal models were initially identified using the
same search terms, time period and databases as for the
human studies, and then the search was expanded to cover a
broader time period (studies published from 1980 onwards).
The recommendations of the COT issued in 1998 were in
part based on the concept that intra-uterine immunological
sensitisation can occur and increases the likelihood of sub-
sequent atopic disease. This concept was primarily based on
reports of in vitro proliferative and cytokine responses by
Early life determinants of peanut allergy 1279
British Journal of Nutrition
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