Food Allergy & Growth: Identifying At-Risk Children

Clinical Commentary Review
Identifying Children at Risk of Growth and Nutrient
Deficiencies in the Food Allergy Clinic
Carina Venter, PhDa, Rosan Meyer, PhDb,c,d, Maureen Bauer, MDa, J. Andrew Bird, MDe, David M. Fleischer, MDa,
Anna Nowak-Wegrzyn, MD, PhDf,g, Aikaterini Anagnostou, MD, PhDh,i, Brian P. Vickery, MDj,k, Julie Wang, MDl, and
Marion Groetch, MSl Dallas and Houston, Texas; New York, NY; Atlanta, Ga; Aurora, Colo; London and Winchester, United
Kingdom; Leuven, Belgium; and Olsztyn, Poland
BACKGROUND: Food allergies affect growth in children by
decreasing the availability of nutrients through decreased dietary
intake, increased dietary needs, foodemedication interactions,
and psychosocial burden. Guidelines on food allergy management frequently recommend nutrition counseling and growth
monitoring of children with food allergies.
OBJECTIVE: To provide clear guidance for clinicians to identify
children with food allergies who are at nutritional risk and
ensure prompt intervention.
METHODS: We provide a narrative review summarizing
information from national and international guidelines,
retrospective studies, population studies, review articles, case
reports, and case series to identify those with food allergy at
greatest nutritional risk, determine the impact of nutritional
interventions on growth, and develop guidance for risk
reduction in children with food allergies.
RESULTS: Children with food allergies are at increased risk of
nutritional deficiencies and poor growth. Nutritional assessment
and intervention can improve outcomes. Identifying poor
growth is an important step in the nutrition assessment.
Therefore, growth should be assessed at each allergy evaluation.
Interventions to ensure adequate dietary intake for growth
include appropriately prescribed elimination diets, breastfeeding support and assessment, supplemental formula, vitamin
and/or mineral supplementation, appropriate milk substitutes,
and timely introduction of nutrient-dense complementary foods.
a
Council National Peanut Board; receives royalties from UpToDate; and serves as a
consultant for Aquestive, DBV Technologies, Genentech, and Nasus, all of which
are outside the submitted work. institution has received research support from
Aimmune Therapeutics and DBV Technologies; serves as a non-paid member of
the Medical Advisory Board for Food Allergy & Anaphylaxis Connection Team
and the Medical Advisory Council National Peanut Board; receives royalties from
UpToDate; and serves as a consultant for Aquestive, DBV Technologies, Genentech, and Nasus, all of which are outside the submitted work. A. NowakWegrzyn receives research support from NIAID, Alladapt Immunotherapeutics,
Regeneron, DBV, and Siolta Therapeutics; speaking fees from Nestlé, Danone,
and Thermo Fisher; and royalties from UpToDate. She serves as an associate
editor for the Annals of Allergy, Asthma & Immunology, director of the American
Academy of Allergy, Asthma & Immunology board, and the chair of the Medical
Advisory Board of the International FPIES Association. A. Anagnostou reports
institutional grants from FARE, Aimmune Therapeutics, and Novartis; and personal fees from Aimmune, ALK, Novartis, and Genentech. B.P. Vickery reports
grants from Abbott, Alladapt, Genentech, NIH-NIAID, and Siolta; grants and
personal fees from Aimmune, DBV, FARE, Novartis, and Regeneron; personal
fees from AllerGenis, Aravax, Reacta Biosciences, and Sanofi; and stock options
from Moonlight Therapeutics. J. Wang receives research support from the National Institute of Allergy and Infectious Diseases, Aimmune, DBV Technologies,
and Siolta; consultancy fees from ALK Abello and Jubilant HollisterStier; and
royalty payments from UpToDate. M. Groetch receives royalties from UpToDate
and the Academy of Nutrition and Dietetics and consulting fees from Food Allergy Research Education; serves on the Medical Advisory Board of IFPIES, as a
Senior Advisor to FARE, and as a Health Sciences Advisor for APFED; is on the
editorial board of Journal of Food Allergy; and has no commercial interests to
disclose. The other author declares no relevant conflicts of interest.
Received for publication November 27, 2023; revised January 16, 2024; accepted for
publication January 19, 2024.
Available online January 25, 2024.
Corresponding author: Carina Venter, PhD, Section of Pediatric Allergy and
Immunology, Children’s Hospital Colorado, 13123 East 16th Ave, Box B518,
Anschutz Medical Campus, Aurora, CO 80045. E-mail: Carina.Venter@
childrenscolorado.org.
2213-2198
Ó 2024 American Academy of Allergy, Asthma & Immunology
https://doi.org/10.1016/j.jaip.2024.01.027
Section of Pediatric Allergy and Immunology, Children’s Hospital Colorado,
University of Colorado, Aurora, Colo
b
Department of Medicine, Imperial College London, London, United Kingdom
c
Department of Nutrition and Dietetics, University of Winchester, Winchester,
United Kingdom
d
Department of Medicine, KU Leuven, Leuven, Belgium
e
Department of Pediatrics, Division of Allergy and Immunology, UT Southwestern
Medical Center, Dallas, Texas
f
Hassenfeld Children’s Hospital, Department of Pediatrics, NYU Grossman School
of Medicine, New York, NY
g
Department of Pediatrics, Gastroenterology and Nutrition, Collegium Medicum,
University of Warmia and Mazury, Olsztyn, Poland
h
Section of Allergy and Immunology, Baylor College of Medicine, Houston, Texas
i
Section of Allergy and Immunology, Department of Pediatrics, Texas Children’s
Hospital, Houston, Texas
j
Children’s Healthcare of Atlanta, Atlanta, Ga
k
Department of Pediatrics, Emory University, Atlanta, Ga
l
Division of Pediatric Allergy and Immunology, Icahn School of Medicine at Mount
Sinai, New York, NY
Conflicts of interest: C. Venter reports grants from Reckitt Benckiser and personal
fees from Reckitt Benckiser, Nestlé Nutrition Institute, Danone, Abbott Nutrition,
and HAL Allergy outside the submitted work. R. Meyer reports honoraria for
lectures from Nestlé Nutrition Institute, Danone/Nutricia, Abbott Nutrition, and
Reckitt Benckiser; personal consulting fees from Else Nutrition and Abbott
Nutrition; participation as Primary Investigator in a study supported by Danone;
and advisory board member for Nestlé Health Science, all outside the submitted
work. J.A. Bird reports consultancy with AllerGenis, Allergy Therapeutics Ltd,
DBV Technologies, Food Allergy Research & Education (FARE), HAL Allergy,
Genentech, Novartis, and Nutricia; and receives grant funding to his institution
from Aimmune, Astellas, DBV Technologies, FARE, Genentech, NIHeNational
Institute of Allergies and Infectious Diseases (NIAID), Novartis, Siolta, and
Regeneron. He is a non-paid member of the American Academy of Pediatrics
(AAP) Section of Allergy and Immunology Executive Committee, International
FPIES Association medical advisory board, and Texas Department of State Health
Services Stock Epinephrine Advisory Committee and is an independent study
monitor for Vedanta (uncompensated). D.M. Fleischer’s institution has received
research support from Aimmune Therapeutics, ARS Pharmaceuticals, and DBV
Technologies; he serves as a non-paid member of the Medical Advisory Board for
Food Allergy & Anaphylaxis Connection Team and the Medical Advisory
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TABLE I. Practical pointers related to nutritional risk
Abbreviations used
AD- Atopic dermatitis
ARFID- Avoidant restrictive food intake disorder
CM- Cow’s milk
CMA- Cow’s milk allergy
EHF- Extensively hydrolyzed formula
FA- Food allergy
FPIES- Food proteineinduced enterocolitis syndrome
PPI- Proton pump inhibitor
VMS- Vitamin and/or mineral supplementation
Access to foods of appropriate nutritional value is an ongoing
concern.
CONCLUSION: Nutrition intervention or referral to registered
dietitian nutritionists with additional training and/or experience
in food allergy may result in improved growth and nutrition
outcomes. Ó 2024 American Academy of Allergy, Asthma &
Immunology (J Allergy Clin Immunol Pract 2024;12:579-89)
Key words: Food allergy; Malnutrition; Nutrients; Registered
dietitian/nutritionist; Management; Allergist
INTRODUCTION
Many publications have highlighted nutrition and growth
concerns in infants and children with food allergies (FA). The
importance of nutrition counseling and growth assessment is
highlighted in most FA management guidelines.1,2 The
Guidelines for the Diagnosis and Management of Food Allergy in the United States: Summary of the National Institute
of Allergies and Infectious DiseaseseSponsored Expert Panel
Report1 specifically recommends nutritional counseling and
regular growth monitoring for all children with FA (Guideline
23). The European Academy of Allergy and Clinical Immunology Food Allergy and Anaphylaxis Guidelines: Diagnosis
and Management of Food Allergy3 state that the clinical
assessment of patients should include assessing nutritional
status and growth. The newly published Global Allergy and
Asthma European Network guidelines2 concluded that there is
potential for suboptimal nutrition and growth in children with
FA, and it is important that only documented food allergens
be avoided.
Although nutrition counseling by a registered dietitian
nutritionist (RDN) with training and/or experience in managing
FA may be ideal,1-3 clinicians working in the area of FA report a
lack of access to specialist allergy-trained RDNs. Therefore, this
work aims to provide clear guidance for clinicians to identify
children with FA who are at nutritional risk and steps to mitigate
those risks by clinicians who may not have access to allergy
specialist RDNs. When available, prompt referral to a suitably
trained registered or licensed RDNs can be helpful and guidance
on locating a RDN is provided (Table I).
FACTORS THAT MAY CONTRIBUTE TO
NUTRITION RISK
Number of foods avoided and specific FA
Number of FA growth parameters. A systematic review
reported that avoidance of multiple foods, defined as two or more
Factors that may be associated with increased risk
All types of food allergies can increase risk for changes in growth and
nutrient intake, although cow’s milk allergy in infants and young
children poses a particular nutritional risk
Nutritional risk may increase with the number of foods avoided
Cow’s milk allergy
Atopic dermatitis
Eosinophilic esophagitis
Food proteineinduced enterocolitis syndrome
Feeding difficulties
Low food security
Lack of suitable nutritional alternatives may increase risk
Long-term medication use
Additional food restrictions owing to cultural, religious, or personal
choice may increase risk
Factors that may reduce risk or improve nutritional status
Appropriately prescribed elimination diets
Nutrition counseling
Nutrition support and assessment during breast-feeding when maternal
avoidance diet is required
Appropriate choice of supplemental formulas (when formula feeding)
and vitamin mineral supplements, when needed
Nutrition assessment before commencing plant-based beverages
Timely introduction of nutrient-dense complementary foods
Biomarkers for vitamin mineral assessment
Ideally only targeted nutritional biomarkers should be performed,
following from assessment of dietary intake, the foods eliminated,
and growth status.
Core biochemical markers for food allergy include the bone profile with
25[OH] vitamin D, phosphate, iron profile including hemoglobin,
mean corpuscular volume, hematocrit, ferritin, and C-reactive protein
in the presence of failure-to-thrive zinc status.
Other markers including vitamin A, vitamin B12, and folate may be
useful in some patients, depending on the nutrition assessment.
Growth assessment
Weight, length or height, and head circumference (age <2 y) should be
regularly assessed and plotted on the appropriate growth chart.
Online z-score calculator may be used.4
Practical pointers for physicians
Measure height, weight, head circumference (age <2 y) and plot on
growth chart at every appointment to assess growth over time
Timely referral to registered dietitian nutritionist for assessment of
nutrient intake
Timely referral for feeding therapy if concerns for feeding difficulties,
refusal, or aversions
Consider iron studies (including serum ferritin and C-reactive protein),
25[OH] vitamin D, and zinc in children with multiple food
avoidance, picky eating, or food phobia
Find a dietitian who can support your practice
For food allergyetrained dietitians, consult the Food Allergy
Research & Education Web site5 and Find a Nutrition Expert on
eatright.org.6
Many dietitians provide telehealth. Dietitians are nationally
accredited. Some states also have licensure for dietitians. Therefore,
a dietitian can provide telehealth only when licensed in the state
where the patient is located. However, many states do not have
specific licensure restrictions, so any dietitian can provide
telehealth services. If you practice in a state that has licensure
restrictions, a dietitian may be willing to apply for licensure in your
state to support your patients.
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TABLE II. Defining faltering growth and malnutrition (undernutrition)4
Terminology
Faltering growth/failure to thrive
Malnutrition, undernutrition
Wasting
Malnutrition, undernutrition
Stunting
Definition
There is no consensus on the definition, but the most common one used is a
sustained decrease in growth velocity, in which weight for age or
weight for length/height falls by 2 major percentiles over time
e2 to e2.9 z-score weight for height (moderate undernutrition)
e3 and below z-score weight for height (severe undernutrition)
e2 to e2.9 z-score height for age (moderate undernutrition)
e3 and below z-score height for age (severe undernutrition)
Malnutrition
Middle to upper-arm circumference
e2 to e2.9 z-score (moderate undernutrition)
e3 and below z-score (severe undernutrition)
The World Health Organization uses z-scores to define undernutrition as defined here. However, some authors refer to weight for height, weight for age,
and height for age using percentiles. A z-score of 0 refers to the 50th percentile. Percentiles relating to other z-scores depend on the growth chart used.
These z-scores are universally applicable irrespective of the growth chart used.
foods, was associated with reduced longitudinal growth parameters (height and weight) (Table II) in four of six studies identified, irrespective of the type of FA involved.7 A UK growth
survey on children with confirmed FA found that that avoiding
three or more foods affected weight for age, but not the other
growth parameters.8 However, a prospective study in children
with a confirmed noneimmunoglobulin E-mediated food allergy
(IgE-FA), also from the United Kingdom, found that the
number of foods excluded did not affect growth. Nevertheless,
assessing growth is an important aspect of all FA evaluations
(Table I).
Specific FA and growth parameters. Tuokkola et al9
reported on children with any form of allergy to cow’s milk
(CM) and/or wheat, rye, and barley, who were assessed at 1, 3,
and 5 years. They reported that avoiding CM led to lower height
for age z-scores compared with a healthy control group. Medeiros
et al10 reported that in a group of 26 children with any form of
CM allergy (CMA), 11.5% were stunted (Table II), 7.7% were
wasted, and 23% were underweight (e2 z-score weight for age)
compared with 0%, 0%, and 3.3% in the control group,
respectively. In another study that focused on any form of CMA,
height for age was significantly lower in affected children
compared with controls.11,12 In a retrospective study of 9,938
children with an electronic medical record code for FA, those
avoiding CM were significantly shorter and weighed less than a
matched control group without FA.13
Food allergies and nutrient intake
Foods containing the top nine major food allergens are typically high-protein foods providing a range of nutrients
(Table III).14 As nutrient requirements change over the course of
the life span (Table IV), the effect of avoiding certain foods may
also differ across various age groups.15 Data are inconsistent
regarding the consequences of avoiding certain foods on overall
nutrient intake and growth parameters. Some studies indicate a
particular concern relating to CM avoidance in children up to
age 16 years,9,16,17 supported by data that intake of baked CM
products versus complete avoidance16 improves nutritional status. Studies reporting on nutrient intake, in which an RDN and
appropriate nutrition interventions were in place, did not show
an association between food avoidance and nutrient intake.8,18,19
Thus, although it is unclear whether multiple FAs affect
growth, it is shown that avoiding multiple foods will affect
dietary intake in the absence of nutrition intervention. Data
support that CM-avoidant children12,13,16,20 in particular require
dietary guidance to ensure adequate nutrition. The aim is to
prevent nutritional deficiencies and growth impairment
(Table I).
Immunoglobulinemediated FA
Immunoglobulin E-FA has been reported to affect growth in
children. A Finnish study indicated that both height for age and
weight for height were lower in children with IgE-FA (mainly
CMA) compared with controls.21 This was supported by data
from the United States indicating that more children with FA
had lower height for age percentiles than children without FA.22
Other studies indicated low weight for height,23 low weight and
height for age,17 and increased numbers of malnourished23
children with IgE-FA.
NoneIgE mediated FA
Several studies investigated the role of non-IgE mediated FA
on growth. Studies from the United Kingdom reporting on nonIgE mediated FA in children indicated that 9% of children were
stunted, 2.2% were wasted and 2.2% and 10% were overweight
at age less than 5 and greater than 5 years, respectively.8 Another
study from this group, mean age 27 months, with IgE-mediated
FA, noneIgE mediated FA, and mixed IgE-mediated FA, reported that 11.5% were stunted and 3.7% were wasted.24 Vieira
et al25 described that in a cohort of children from Brazil with
gastrointestinal predominant CMA, 23.9% of children were
stunted, 11.3% were wasted, and 15.1% were underweight.
Food proteineinduced enterocolitis syndrome
Children with food proteineinduced enterocolitis syndrome
(FPIES) avoiding three or more foods26 have an increased risk for
food aversion and poor weight gain. Although most children
with FPIES react to a single food, some avoid additional foods
prophylactically27 owing to parental concerns. In a large cohort
of 410 children with FPIES, 69% avoided at least two food
groups because of FPIES.28 The high psychosocial burden28,29
on caregivers can contribute to altered feeding practices, leading to the delayed development of feeding skills and reduced
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TABLE III. Nutrients provided by food containing common food allergens
Nutrients at risk
Eliminated food
Protein
Carbohydrate
Fat
Milk
Egg
Wheat
Soy
Peanuts, tree nuts,
and seeds
Seafood
Peanut
x
x
x
x
x
x
x
x
x
x
x
Fiber
Calcium
Vitamin D
Vitamin B12
x
x
x
x
x
x
x
Iodine
Biotin
Iron
x
x
x
x
Omega -3
fatty acids
x
x
x
x
x
Folate
x
x
x
x
x
x
x
Reprinted with permission from Durban R, et al. Dietary management of food allergy. Immunol Allergy Clin North Am 2021;41:233-70.14
TABLE IV. Changes in food intake nutrient requirements over the life span
Age group
Infants and children
Children
Teenagers
Increased nutritional requirements
Energy, protein, essential fatty
acids,
>6 mo: iron, zinc iodinea
Increased risk
Delayed introduction of foods
Cow’s milk allergy
Multiple food allergies
Family inability to manage food
allergy
Nursery inability to provide
nutritious, safe foods
Feeding difficulties
Energy, protein, essential fatty
acids, iron, calcium
>4 y: zinc
>9 y: iodine
Food aversions/phobia
Family inability to manage food
allergy
Nursery/preschool inability to
provide nutritious, safe foods
Energy, protein, calcium,
phosphorus, magnesium, zinc,
iodine
Females: iron
Longer-term food aversions
Not consuming food allergen that
have been outgrown
Increased requirements with
increased activity (sports)
Family inability to manage food
allergy
School inability to provide
nutritious safe foods
Social events where safe food is
unavailable
aA risk for iodine deficiency has been found specifically in children with cow’s milk allergy.
intake. Indeed, parents of children with FPIES reported greater
feeding difficulty than did those with children with IgE-FA.30
They were also significantly more likely to report adverse
impacts of feeding on the caregiver and family.
Faltering growth can be a feature of chronic FPIES.31
Impaired absorption and excessive gastrointestinal losses can
result from ongoing inflammation. Hematologic and metabolic
disturbances can also be seen in chronic FPIES. The International Consensus Guidelines for the Diagnosis and Management
of Food ProteineInduced Enterocolitis Syndrome32 recommend
guidance during complementary food introduction to ensure
nutritional adequacy. They also strongly recommend consulting
with an RDN to facilitate complementary feeding.
Eosinophilic esophagitis/eosinophilic gastrointestinal
diseases
Growth restriction can be seen in patients with eosinophilic
gastrointestinal diseases, and faltering growth has been reported
in 10% to 24% of patients with EoE.33 Impairments in growth
result from a variety of factors. Recurrent gastrointestinal
symptoms such as pain and vomiting prevent adequate nutritional intake. Eosinophilic esophagitis (EoE) can lead to feeding
dysfunction34,35 because of dysphagia and/or esophageal strictures. Altered feeding behaviors such as EoE symptoms can also
trigger anxiety and/or eating disorders (including food aversions).27,36,37 This may further contribute to nutritional
inadequacy.27 Similar to FPIES, chronic inflammation in itself is
a state that may lead to impairments in growth.38
IS ATOPIC DERMATITIS ASSOCIATED WITH
GROWTH IMPAIRMENT?
Associations between atopic dermatitis (AD) disease severity
and growth have been reported, particularly in younger children.39 A Japanese birth cohort study40 found an association
between impairment in growth parameters (height, weight, and
body mass index) in children who had early-onset persistent AD.
This association may occur for a variety of reasons. Dietary restrictions are often pursued by families of children with AD,41-43
but frequently without physician recommendation or RDN
input.41,44 Unsupervised dietary manipulation can result in the
lower intake of energy, protein, fat, and nutrients, leading to a
negative impact on growth parameters. Children with AD can
have sleep disturbances45 and insufficient sleep.45,46 Atopic
dermatitis has been associated with impaired growth (height).
A mechanism for this is interruption of growth hormone release
owing to poor sleep.47 Early-onset AD is also a risk factor for FA,
so the contribution of FA (or food avoidance) to growth in
children with AD is uncertain.
Severe AD can result in protein loss through the skin, and
there are reports of hypoproteinemia48 as a complication of AD.
Chronic skin inflammation49,50 and superinfection can also
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TABLE V. Avoidant/restrictive food intake disorder criteria56
Criteria
Grade
Significant weight loss (or failure to achieve
expected weight gain or faltering growth in
children)
Significant nutritional deficiency
Dependence on enteral feeding or oral nutritional
supplements
Marked interference with psychosocial
functioning
A1
A2
A3
A4
negatively affect systemic metabolism. Zinc is a cofactor for
enzymes involved in energy metabolism and has a direct impact
on growth through the pituitary growth hormoneeinsulin-like
growth factor-1 axis, which is responsive to zinc status.51
A retrospective study on 189 children with AD, 30% of whom
had concomitant FA, found that 25% of children had low zinc
levels and concomitant severe AD.52 The latter study did not
find an association among FA, the number of foods eliminated,
and low zinc levels, suggesting a different cause for this.
IS FOOD REFUSAL ASSOCIATED WITH FA?
Food refusal is commonly reported in children with FA, ranging
from aversions to breast-feeding or bottle feeding to the refusal of
specific food texture characteristics, and to the more severe spectrum including avoidant restrictive food intake disorder
(ARFID).53 Food refusal increases the risk for both macronutrient
and micronutrient deficiencies,54 and these are more commonly
reported in ARFID.55 This is partly due to Diagnostic and Statistical Manual of Mental Disorders diagnostic criteria (Table V),
including the persistent failure to meet nutritional needs (Table I).
Avoidant restrictive food intake disorder emerged as an eating
disorder only in 2013; it coexists with other medical conditions.57 In the context of FA, case reports of ARFID started to
emerge in EoE58,59 followed by a case series of patients aged
6 months to 18 years who presented to an FA clinic.60 During
the 4-month recruitment period, 54 children were assessed, 34 of
whom met Diagnostic and Statistical Manual of Mental Disorders criteria for A1-A3 and a proposed FAespecific criterion for
A4.60 More research is needed on feeding issues in children along
the spectrum of FA, to prevent food refusal and progression to
ARFID and develop more specific management options.
ARE MEDICATIONS USED IN FA ASSOCIATED
WITH NUTRITIONAL RISK?
Medication use
Medications commonly prescribed for children with FA
include antihistamines, corticosteroids, and epinephrine.2,61 For
FPIES, common drugs include ondansetron,32 and for EoE
treatment they can include proton pump inhibitors (PPIs),
swallowed inhaled corticosteroids, and biologics such as dupilumab.62,63 Other forms of noneIgE mediated FA are treated
according to the presenting symptoms and may include PPIs,
corticosteroids, antihistamines, and immunosuppressive drugs
such as cyclosporine or methotrexate for AD, although their use
is less common since the approval of biologic therapies to treat
moderate to severe AD.64,65
Corticosteroids in children with EoE. Despite concerns
about potential effects on growth, a systematic review
583
concluded that the long-term use of swallowed inhaled corticosteroids was not associated with reduced growth or bone
mineral density.66 Andreae et al67 showed that in a study with
a mean follow-up of 20.4 months in which the longest followup was 68 months (5.7 years), swallowed fluticasone was not
associated with growth impairment. This was also not highlighted as a concern by the Joint Task Force for the American
Academy of Allergy, Asthma & Immunology, the American
College of Allergy, Asthma and Immunology, and the American Gastroenterology Association in the EoE practice
parameter.63 However, a systematic review reported that
inhaled corticosteroids affected growth in children with
persistent asthma, although the drug used and delivery device
may have an impact on the effect seen on growth.68
Proton pump inhibitors. A systematic review on PPI treatment found that the long-term use of PPIs (more than 30
days)69,70 is associated with gut dysbiosis. Proton pump inhibitor
effects on magnesium, calcium, iron, and sodium absorption
need further clarification. Vitamin B12 absorption may be a
particular concern in patients with acid-related diseases, particularly those who already have malnutrition.71 In addition, a
study showed a negative association between chronic PPI use and
bone mineral density classified as either within a year of the
assessment or at the time of assessment.72
ARE SOCIAL DETERMINANTS OF HEALTH
ASSOCIATED WITH NUTRITIONAL RISK IN
CHILDREN WITH FA?
The increasing prevalence of FA has been noted to affect
underresourced marginalized populations disproportionately.73,74 Racial and socioeconomic disparities have similarly
been noted in other aspects of FA care, including prevention,75,76 the presence of an epinephrine autoinjector prescription,77 increased rates of food-induced anaphylaxis,78 and
decreased access to subspeciality care.78,79 Food insecurity is
estimated to occur in 10.5% of US households, with higher
disparities noted in households with children, in Black or
Hispanic individuals, in those below the poverty threshold80
and in households with dietary restrictions such as FA.81
Similarly, because allergen-free foods are significantly more
costly, lower socioeconomic status is associated with limited
access to allergen-free foods,82 because many current federal
nutrition programs do not incorporate the increase in cost for
food-allergic families.83,84
A recent work group report from the American Academy
of Allergy, Asthma & Immunology also indicated that the
COVID-19 pandemic resulted in many more people facing
food insecurity for the first time. The Latinx, Native American,
and Black communities were disproportionately affected according to the survey.85 This disparity in access likely affects
the nutritional status of the child owing to the lack of
affordable, nutritious meals free of specific allergens.80 The lack
of access to allergen-free meals has also been postulated to
contribute to increased rates of accidental ingestions and hospital visits among those of lower socioeconomic status.83 The
literature has demonstrated general nutritional disparities based
on socioeconomic status.86
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WHAT ARE MARKERS FOR NUTRITIONAL RISK
AND ARE THERE SPECIFIC MARKERS FOR
CHILDREN WITH FA THAT DIFFER FROM THOSE
OF THE GENERAL PEDIATRIC POPULATION?
The Child Nutrition Act of 1966 Section 17(b)87 clearly
defines nutritional risk under five broad categories and includes
detectable abnormal biochemical and anthropometrical measures
that affect health and nutritionally related conditions that predispose persons to inadequate nutritional intake: detrimental or
abnormal nutritional conditions detectable by biochemical or
anthropometric measurements; other documented nutritionally
related medical conditions; dietary deficiencies that impair or
endanger health; conditions that directly affect the nutritional
health of a person, such as alcoholism or drug abuse; and conditions that predispose persons to inadequate nutritional patterns
or nutritionally related medical conditions, such as homelessness
and migrancy. Growth in the child with FA can be disrupted by
both physiologic and psychological factors, including the elimination of food allergens, which contribute essential nutrients.
The availability of food alternatives and the psychological
burden, which may lead to disrupted meal patterns, can have a
role in nutrient delivery.21,88 Micronutrient deficiencies are
linked to the elimination of specific foods (ie, CM) but also to a
lack of nutritionally appropriate, allergen-free replacements and
increased nutrient demand. There is increasing evidence indicating that comorbidities and ongoing chronic gut and skin
inflammation affect growth, in particular height.21,39,89
Assessing growth
Ideally, weight, length and height, and head circumference
(age <2 years) measurements are accurately performed with each
allergy evaluation to guide medical and dietary management.90
The frequency of growth assessment may require modification
if faltering growth and/or malnutrition are present91 (Table I).
Although these terms are often used interchangeably, they have
different diagnostic criteria (Table II). Faltering growth is a
decrease in the velocity of weight gain, which results in the child
falling off the expected weight curve on the growth charts, as
described in Table II, whereas malnutrition (or undernutrition)
is primarily defined by a low weight for height (wasting) or a low
height for age (stunting), as defined by the World Health
Organization.92
Micronutrient intake
Micronutrients are important cofactors for growth and general
well-being (Table I). Children with FA have an increased risk for
a variety of vitamin and mineral deficiencies.90 Four studies
assessed nutrient intake compared with a healthy population and
found that vitamins and/or minerals related to bone mineralization (ie, vitamin D, calcium, phosphate) in particular were
lower in children with FA than in children without it.4 Boaventura et al93 assessed the dietary intake of children in Brazil
with CMA versus children without it and found low serum levels
of retinol and vitamin D in 25.9% and 70.3%, respectively, of
children with CMA. Although this study did not assess the blood
serum levels for vitamin D and retinol in the control group, a
comparison with the published Brazilian general pediatric population indicated that vitamin A deficiency (based on retinol
levels) in children aged less than 59 months was 17.9%94 and
vitamin D deficiency in children ages less than 5 years was
4.3%,95 suggesting a higher prevalence of these deficiencies in
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MARCH 2024
children with CMA in Brazil. Calcium intake was significantly
lower in the CMA group. Thomassen et al96 found that 58% of
breast-fed infants with CMA had iodine deficiency, much higher
than that reported in the general population.
The most common vitamin and mineral deficiencies include
vitamin D, calcium, iodine, iron, and zinc, but children with FA
are at risk of developing deficiencies within the whole spectrum
of micronutrients, as well as macronutrients such as essential
fatty acids.96-99 Symptoms and medications need to be taken
into account when considering nutritional biomarkers. In addition, health care professionals should be aware of the sensitivity
and specificity of biomarkers and factors (ie, the acute inflammatory response when a child is unwell, kidney function) that
can influence their accuracy100 (Table I).
WHICH NUTRITION INTERVENTIONS IMPROVE
NUTRITIONAL STATUS IN CHILDREN WITH FA?
Nutrition counseling
Berni Canani et al101 evaluated the impact of nutrition
counseling on children with FA. The authors measured growth,
dietary intake, and biomarkers of nutritional status in children
with FA before and 6 months after nutrition counseling,
including one session of counseling, and compared baseline
measurements with those of children without FA. At baseline,
energy and protein intakes were lower and wasting was more
common (21% vs 3%; P < .001) in children with FA compared
with children without FA. Six months after dietary counseling,
total energy intake in children with FA was comparable to intake
in those without FA at baseline. There was also a significant
increase in iron, fiber, calcium, and zinc intake in children with
FA after 6 months compared with baseline. Table VI lists
alternative or common food sources of important nutrients that
could be affected by elimination diets (Table I).
Referral to an RDN, when available, for a comprehensive
nutrition consultation (Tables VII and VIII) can improve dietary
intake and growth101 and will support caregivers by developing
an individualized plan to ensure the diet is safe and nutritionally
adequate.102
Human milk
Human milk (HM) is the ideal first food for infants. It contains essential nutrients for growth and development and
nonessential components such as IgA and HM oligosaccharides
known to support immune and gut microbial development.103
Both infant and maternal health benefit as a result of breastfeeding. Therefore all health care practitioners should
encourage breast-feeding. The probability of IgE-mediated
allergic reactions to food proteins in HM is low,104 and certain
noneIgE mediated diseases such as FPIES are not commonly
reported in infants exclusively fed HM.32 However, if an infant
has immediate symptoms to HM after maternal ingestion of a
specific food, or if the infant with noneIgE FA is symptomatic
or not growing well, the suspected trigger food should be
removed from the maternal diet for 2 to 4 weeks followed by a
trial of reintroduction to determine whether symptoms recur.
Maternal elimination diets are commonly prescribed for food
proteineinduced allergic proctocolitis whose primary symptom
is hematochezia, although a newer guideline105 suggests a wait
and see approach when hematochezia is of short duration
(<1 month), because it may be self-resolving. The risk of anemia
and poor growth seems to be low in infants with ongoing mild
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585
TABLE VI. Food sources of important nutrients
Nutrient
Allergen
Alternative sources
Protein
Calcium
Milk, egg, fish, peanut, tree nuts, soy
Milk
Meat, poultry, seeds, legumes
Fortified plant-based beverages, calcium-fortified tofu
and other foods
Marine algae oils, refined fish oil supplements and
supplemented foods
Fortified plant-based beverages, salmon, trout, fortified
cereals, mushrooms exposed to ultraviolet light
Iodized salt, seaweed
Beef, poultry, enriched macaroni, long-grain rice, oats,
beans
Beef liver, beef, chicken, potato
Long-chain polyunsaturated fatty acids
Fatty fish
Vitamin D
Cow’s milk and fortified dairy products
Iodine
Selenium
Milk, fish
Brazil nut, fish, egg
Choline
Egg, soy, wheat germ, cod
TABLE VII. Special factors to consider when assessing nutritional
risk
Areas of assessment to consider in breast-fed infant in the presence of poor
growth
Review the adequacy of the maternal diet, especially energy and protein
intake
Increased frequency and duration of infant feedings
Feeding both breasts at each feeding
If long infant sleeping duration, encourage expressing breast milk to
maintain prolactin levels and milk volume
Plan for appropriate introduction of solid foods (timely and nutritionally
dense complementary foods)
Follow country-specific guidance on nutrient intake and
supplementation
Dietary goals when transitioning a child from a suitable formula to a plantbased milk (all goals should be met)
They eat a varied solid food diet with a variety of foods from each food
group (protein foods, grains, and fruit/vegetables in addition to milk
substitute).
They get at least two-thirds of energy from the varied solid food diet.
They consume 16 oz/500 mL milk substitute per day (this includes
human milk, formula, and other dairy substitutes such as yogurt).
They eat age-appropriate textures.
They get enough energy, protein, fat, and micronutrients in the diet from
solid foods and the available milk substitute.
Complementary feeding goals
Begin when the child is developmentally ready to eat, around age 6 mo
(and not before age 4 mo)
For breast-fed infants, nutrients of concern are iron, zinc, and protein.
Recommend infant sources of iron and zinc such as iron-fortified
cereal grains and pureed meats and beans, and recommend infant
sources of protein such as pureed meat, fish, poultry, cooked egg, and
infant-safe forms of nuts, seeds, and legumes
Other nutrients of concern for all infants during complementary feeding
include choline (egg, soy, meat, fish, and potato), potassium (fruits
and vegetables), vitamin D (supplement per country-specific
guidelines), and long-chain polyunsaturated fatty acids (fish and
seeds such as flax and chia)
food proteineinduced allergic proctocolitis when appropriately
managed. Maternal elimination diets may burden the breastfeeding parent and may affect breast-feeding duration and
infant and maternal health. Therefore they should be prescribed
only when necessary.
When breast-fed infants present with FA and maternal elimination diets are required, the maternal diet requires attention. A
maternal diet low in energy and protein may affect HM volume
and subsequently, infant growth.106 Maternal dietary intake of
fatty acids is also a significant determinant of HM fatty acid
levels, including essential long chain polyunsaturated fatty
acids.107-109 Although some studies indicate that certain micronutrients in HM, such as iodine, B vitamins (B1, B2, B6, and
B12), choline, vitamins A, C, and D, and selenium, are affected
by maternal diet,109-113 a 2016 systematic review109 reported
that most evidence of micronutrient content in HM is based on
an indirect association with maternal diet. Specific micronutrient
supplementation to a deficient maternal diet will rapidly replete
deficient maternal stores. However, specialist advice is needed to
choose the correct supplement specific for lactation and further
tailoring may be needed for specific elimination diets
(Table VII).
Supporting breast-feeding and assessing the growth and
nutrient intake of the infant are important steps at each primary
care and allergy and immunology visit. In addition to assessing
for allergic symptoms, a comprehensive breast-feeding assessment
may help to address poor growth in the exclusively breast-fed
infant. Improving growth in the exclusively breast-fed infant
by addressing breast milk production can result in improved
outcomes without the addition of supplemental formula.114
Formula feeding
For children who are formula-fed, improvement in growth
and nutritional status can occur with a change in the approach to
feeding, such as initiating a hypoallergenic formula to substitute
for intact CM-based formula. Improvement in growth and
nutritional status occurs rapidly in infants with chronic FPIES or
enteropathy whose feed is changed to remove the trigger food.32
In a randomized controlled trial comparing an extensively
hydrolyzed formula (EHF)115 with a probiotic supplemented
EHF, infants following a 6-month feeding of either formula had
significant improvement in weight-for-age, length-for-age, and
weight-for-length z-scores as well as restoration of a normal body
mass index. There was no difference in growth parameters between the formulas.116
A 2020 systematic review117 of randomized controlled trials
(15 trials in 18 publications) comparing EHF containing CM
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VENTER ET AL
TABLE VIII. What happens during a comprehensive nutrition
consultation by a registered dietitian?
Assessment
Food- and nutrition-related history
Current food and drink intake
Nutrient intake compared with nutrient needs
Feeding skills
Anthropometrics and growth assessment
Relevant biochemical data, medical tests, and procedures
Relevant clinical history: medical, health, family, and social histories
Nutrition diagnosis and intervention
Identifying nutrition problems (diagnosis) and etiologies
Developing individualized interventions to solve nutrition problems:
food and nutrient delivery, counseling, education, coordination of
care
Developing a plan to meet macronutrient and micronutrient needs
Monitoring
Evaluate progress toward nutrition-related goals
Food allergyespecific dietary counseling and education may include:
Label reading and allergen labeling laws
Understanding cross-contact
Eating away from home
Which foods to avoid
Substitute foods; for instance, may advise on suitable infant formula,
plant-based beverages, and vitamin and mineral supplementation
Eating according to tolerance (ie, discussion about precautionary
advisory labeling)
Information about food allergen doses during and after oral
immunotherapy
proteins with other formulas suggested that all EHF formulas
evaluated were well-tolerated by most children with CMA.
Owing to the limited data available, the authors could not reach
a conclusion about the benefit of one formula over another for
improved growth parameters. They suggested the need
for higher-quality studies to assess the safety and efficacy of EHF
for managing CMA.
Supplemental
formulas
or
micronutrient
supplements
In a prospective observational study, Meyer et al8 recruited
130 children (median age 23.3 months) and prescribed a food
elimination diet (94.8% CM elimination) for the diagnosis of
suspected noneIgE mediated FA. At enrollment, 9% were
stunted and 2.8% were wasted. Participants received elimination
diet advice to address nutritional issues such as protein, energy,
and essential vitamin and mineral intake. There was a statistically
significant improvement in weight for age after the 4-week
elimination diet. Height for age was also improved but did not
reach statistical significance in the short follow up. Three-day
food records indicated that energy in addition to protein
intake, vitamin and/or mineral supplementation (VMS), and
hypoallergenic formula intakes were positively associated with
improved anthropometrics.8 The researchers further evaluated
VMS in 110 children with FA, 32 of whom were taking VMS.
Sixty percent of those who did not take a VMS had a low vitamin
D intake, but low zinc, calcium, and selenium intake were also
common. Of those taking supplements, many were either
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MARCH 2024
undersupplemented or oversupplemented. Children receiving
hypoallergenic formulas were significantly (P ¼ .007) less likely
to be receiving VMS than were those taking over the counter
milk alternatives. The data indicated that even when using a
hypoallergenic formula or taking a VMS, children with FA may
not be meeting nutritional recommendations for specific nutrients, and nutritional assessment should be individualized to
optimize dietary intake (Table III).
To date, no specific guidelines have been published supporting health care professionals in the dietary management of
faltering growth in children with FA. Therefore there has been a
reliance on guidance for the general pediatric population. This
includes the World Health Organization/Food and Agriculture
Organization of the United Nations/United Nations University
guidelines for catch-up growth and guidance for moderately
malnourished children.94,118 The principle for optimal catch-up
growth (defined at 70% lean mass and 30% fat mass) is to ensure
that 8% to 12% of energy comes from protein. It has also been
highlighted that whereas energy and protein consumption are
critical, micronutrients are also essential for growth, including
zinc, potassium, sodium, magnesium, and phosphate, and
micronutrients are essential for the immune system (ie, vitamin
D, vitamin A, folate). Meyer et al38 converted these guidelines in
general pediatrics for clinical practice in FA, which may be useful
for health care professionals working in this field. Therapies
available for the dietary management of faltering growth include
breast-feeding support, manipulation of hypoallergenic formulas,
and sufficient complementary foods.
Complementary foods
Complementary feeding should begin around age 6 months
(and not before age 4 months), once the infant is developmentally ready. They should follow country-specific guidance and
encourage a diversity of foods to meet nutritional needs. For
instance, the Dietary Guidelines for Americans 2020 to 2025119
highlights priority nutrients in this age group. Breast-fed infants
beginning complementary feeding need especially nutrient-rich
foods containing iron, zinc, and protein. Other nutrients of
concern in older infants are vitamin D, choline, and potassium.
Parents should be encouraged to introduce foods from all food
groups that fit within country-specific recommendations, a
family’s food culture, food preferences, and the budget. In the
presence of faltering growth, complementary food (from age 6
months onward) can be useful in optimizing energy, protein, and
micronutrient intake (Table VII).
Cow’s milk allergy and milk substitutes. Children with
CMA should have safe and nutritionally appropriate substitutes.
The use of other mammalian milks (eg, goat, sheep) is not recommended for the management of CMA owing to a high level of
cross-reactivity and nutritional concerns.120 Plant-based beverages are often nutritionally inadequate to support normal growth
and development compared with infant formulas or breast milk.
These beverages are not suitable for children aged less than 1 year
and may not be suitable in children aged 1 to 2 years (Table VII).
Inappropriate milk substitutes can lead to poor growth, severe
growth deficiency disorders, and, in rare cases, kwashiorkor/
marasmus, electrolyte disorders, kidney stones, and severe
nutrient deficiencies including iron deficiency anemia, rickets,
and scurvy.8,121-123
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Plant-based beverages include soy, coconut, almond, rice, oat,
hazelnut, cashew, walnut, pea, sesame, hemp, tiger nut, and quinoa.
These beverages differ in terms of nutritional composition and
characteristics. In general, soy and pea protein beverages contain
protein quantities comparable to those of CM and may contain
comparable calcium and vitamin D when adequately fortified, but
they may be lower in fat and other micronutrients. Most other forms
of plant-based beverages are inappropriate replacements for CM in
toddlers and young children for whom milk remains an important
part of the diet.124 For children aged greater than 1 year, continued
feeding with HM or nutritionally complete substitute formula may
be beneficial, alongside a varied solid food diet, because plant-based
beverages may still be nutritionally inappropriate. The North
American Society for Pediatric Gastroenterology, Hepatology, and
Nutrition124 suggests that when HM or infant or toddler formula
constitutes a substantial source of otherwise absent or reduced nutrients in the child’s restricted diet, plant-based beverages may be
inappropriate. Therefore, the use of plant-based beverages may be
considered only on an individual basis after age 1 year in children
who meet specific dietary goals14 (Table VII). For children who do
not yet meet all of these dietary goals, clinicians may encourage
continued breast-feeding or nutritionally complete formula while
providing nutrition counseling to meet age-appropriate nutrition
goals before transitioning to plant-based beverages (Table VII).
Based on clinical need, these plant-based alternatives may be used in
toddlers aged greater than 2 years who are eating well.125
SUMMARY AND CONCLUSIONS
Food allergies are a growing public health concern that affects
dietary intake. It is important to support nutritional needs and
quality of life in patients with FA. Nutrition care is especially
important for infants and young children because inadequate
nutritional intake can directly affect growth and development.
Clinicians should assess growth in children with FA as indicated
by national guidelines and be aware of the indicators of nutritional risk (Tables I, VII, and VIII). Food allergy teams would
benefit from including an RDN with additional training and/or
experience in managing FA, because the complexity of management is ever-evolving and stretches beyond avoiding the
allergen.126 Further research is needed to determine the impact
of emerging FA therapies on nutritional status.
Acknowledgments
C. Venter, M. Groetch, R. Meyer, and J. Wang initiated the
paper. All authors drafted the first version of different aspects of
the paper. All authors reviewed and commented on various drafts
of the paper.
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