Vitamin D Levels Association with Cow Milk
Allergy Sensitized Based on the SCORAD Index Age Less 1 Year Old at Dr. Zainoel
Abidin Hospital Banda Aceh
Cut Elfira1*, Mulya Safri2,
Darnifayanti3, Sulaiman Yusuf4, TM Thaib5, Anidar6
1,2,3,4,5,6Universitas Syiah Kuala,
Indonesia
Email: si_fira@yahoo.com
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KEYWORDS |
ABSTRACT |
|
Cow's
milk allergy, SCORAD, Vitamin D, 25-hydroxyvitamin D. |
Cow's
milk allergy is an immunologically mediated reaction to cow's milk protein.
Vitamin D plays a crucial role in the immune system, and low blood levels of
vitamin D have been associated with an increased incidence of allergies.
However, findings from various studies remain mixed and sometimes
controversial. This research aimed to investigate the relationship between
vitamin D levels and cow's milk allergy sensitization in infants. A cross-sectional research was conducted involving 34
infants aged less than one year. Allergies were assessed using the SCORAD
index, and vitamin D levels (25(OH)D) were measured for each subject.
Statistical analysis using the Mann-Whitney U test showed significant results
(p<0.05). The mean vitamin D level in the deficiency group was 7.9 ng/mL,
while in the insufficiency group, it was 20.4 ng/mL. Infants with mild SCORAD
predominantly exhibited vitamin D insufficiency (73.5%), while those in the
moderate SCORAD group showed a smaller proportion of insufficiency (11.8%).
Among the participants, 21 infants received exclusive breastfeeding, and 23
received formula milk, with an equal distribution of males and females. This research
highlights that infants with cow's milk allergy and vitamin D insufficiency
or deficiency are at greater risk of heightened allergic sensitization,
emphasizing the potential role of vitamin D status in the diagnosis and
management of allergies. |
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DOI: 10.58860/ijsh.v4i1.275 |
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Corresponding Author: Cut Elfira*
Email: si_fira@yahoo.com
INTRODUCTION
Cow's milk is
the main foreign protein that is often introduced to infants, but it has a high
tendency to cause allergies and is often the first atopic disease observed in
children
The incidence
of cow's milk allergy varies globally. In Western countries, atopic conditions
in children are estimated to affect approximately 30% of the population, with
1.1–5.2% of cases attributed to cow's milk protein allergy. Among infants,
cow's milk allergy affects 2–3%, while 30–45% of atopic dermatitis cases in
children under one year of age are linked to cow's milk allergies. In
Indonesia, the Indonesian Pediatric Society (IDAI) estimates the prevalence of
cow's milk allergy at approximately 2–7.5%. Unique factors in Indonesia, such
as differences in dietary patterns, genetic predispositions, and environmental
influences, may contribute to these figures. However, comprehensive studies
addressing the specific epidemiology and causative factors of cow's milk
allergy in Indonesia are still limited, highlighting a gap in the existing
literature
The clinical
and developmental impacts of avoiding milk or allergenic foods are significant.
Growth disorders are observed in approximately 10% of affected children due to
restricted protein intake, limiting dietary options. Infants with atopic
dermatitis or eczema are often underweight and shorter in stature compared to
healthy peers. These children frequently experience nighttime itching,
shortness of breath, and nasal congestion, resulting in poor sleep quality and
subsequent cognitive and behavioral impairments
In the past
decade, vitamin D deficiency has been increasingly linked to allergic
conditions, including cow's milk allergy
This research
aims to address these gaps by exploring the relationship between low serum
vitamin D levels and the incidence of cow's milk allergy in infants
METHOD
This research
is an observational research with a cross-sectional
design to determine the relationship between vitamin D levels and the incidence
of cow's milk allergy symptoms on the skin based on the SCORAD Index
assessment. The SCORAD Index is a reliable and validated tool commonly used to
assess the severity of atopic dermatitis and other allergic skin conditions.
Its reliability in various populations ensures consistency and accuracy in
evaluating the skin manifestations of cow's milk allergy in this research.
The population
of this research consisted of all patients with cow's milk allergy
sensitization who presented to the pediatric polyclinic or were admitted to the
pediatric ward at Dr. Zainoel Abidin Hospital, Banda Aceh. The sample was
selected using a consecutive sampling technique, where all patients meeting the
inclusion and exclusion criteria during the research period were included. This
approach minimizes selection bias by ensuring that every eligible patient has
an equal chance of being included. However, it is acknowledged that consecutive
sampling may still introduce biases if the population presenting to the
hospital is not representative of the broader population. Efforts to minimize
this potential bias included ensuring a diverse sample by recruiting both
outpatient and inpatient participants
The sample
size in this research was 34 subjects. Inclusion criteria were infants
diagnosed with cow's milk allergy based on the SCORAD Index, aged under 1 year,
with good nutritional status based on the WHO weight-for-length curve, a
history of full-term birth (≥37 weeks of gestation), and families willing
to participate in the research. Exclusion criteria included infants with
impaired kidney function, gastrointestinal issues, liver dysfunction, abnormal
nutritional status based on the WHO curve, or families unwilling to provide
blood samples.
Primary data
were collected through interviews and physical examinations conducted by the
researchers to confirm allergy diagnoses, while secondary data were obtained
through laboratory analysis of vitamin D levels. The independent variable in
this research was infants allergic to cow's milk and aged less than 1 year,
while the dependent variable was vitamin D levels (25(OH)D).
Descriptive
data on subject characteristics were presented as categorical variables (e.g.,
gender, history of atopy, nutritional status, exclusive breastfeeding, or
formula feeding) and numerical variables (e.g., vitamin D levels). Numerical
data were summarized using the mean and standard deviation for normally
distributed data or the median and minimum-maximum range for non-normally
distributed data
RESULT AND DISCUSSION
Thirty
four
subjects who had received this research aged between 1 to 12 months at Dr.
Zainoel Abidin Banda Aceh. The baseline characteristics of the research
subjects are shown in Table 1.
Table
1. Basic Characteristics of Research Samples
|
Characteristics |
Data Distribution (n = 34) |
|
Age (months), median
(min – max) |
5 (1 – 12) |
|
Gender |
|
|
Male |
15 (44.1) |
|
Female |
19 (55.9) |
|
History of Atopy |
|
|
Yes |
34 (100) |
|
No |
0 |
|
Nutritional status |
|
|
Good nutrition |
34 (100) |
|
Malnutrition |
0 |
|
More nutrition |
0 |
|
Diet intake |
|
|
exclusive breastfeeding |
13 (38.2) |
|
Breastmilk + Formula Milk |
12 (35.2) |
|
Formula Milk only |
9 (26.4) |
|
Vitamin D Status |
|
|
Deficiency |
4 (11.8) |
|
Insufficiency |
29 (85.3) |
|
sufficiency |
1 (2.9) |
|
SCORAD Status |
|
|
Mild |
27 (79.4) |
|
Moderate |
7 (20,6) |
The
average age of the subjects involved in this research was 5 months old, with a
female predominance (55.9%). All research subjects had a history of atopy and
showed good nutritional status. Based on the average nutritional intake, there
were 13 subjects who received formula milk and 12 subjects who received breast
milk and formula milk, and a total of 9 subjects who only received formula milk
from birth. Based on vitamin D status, research subjects were dominated by
vitamin D insufficiency, with a percentage of 85.3%, and showed a mild SCORAD
status, with a percentage of 79.4%.
Table 2. Characteristics
of research subjects based on the SCORAD group
|
Characteristics |
SCORAD |
|
|
Mild n = 27 |
Moderate n = 7 |
|
|
Age (months), median
(min-max) |
5 (1 - 21) |
3 (2 – 12) |
|
Gender |
|
|
|
Male |
13 (48.1) |
2 (28.6) |
|
Female |
14 (51.9) |
5 (71.4) |
|
History of Atopy |
|
|
|
Yes |
27 (100) |
7 (100) |
|
Not |
0 |
0 |
|
Nutritional status |
|
|
|
Good nutrition |
27 (100) |
7 (100) |
|
Malnutrition |
0 |
0 |
|
More nutrition |
0 |
0 |
|
Diet intake |
|
|
|
exclusive breastfeeding |
10 (37) |
3 (42.9) |
|
Breastmilk+Formula milk |
17 (63) |
4 (57.1) |
|
Formula milk only |
7 (25.9) |
4 (57.1) |
|
Vitamin D Status |
|
|
|
Deficiency |
1 (3.7) |
3 (42.9) |
|
Insufficiency |
25 (92.6) |
4 (57.1) |
|
sufficiency |
1 (3.7) |
0 |
Table
2 above presents research characteristics data based on clinical features of
atopic dermatitis based on the results of the SCORAD index assessment, 27
patients clinically experienced mild atopic dermatitis, and 7 subjects
experienced moderate degrees; none of the subjects in this research with severe
dermatitis symptoms. All research subjects had a history of atopy and showed
normal nutritional status. Based on nutritional intake, 10 subjects who were
exclusively breastfed experienced milder degrees of allergy, and 19 subjects
who tended to receive formula milk experienced mild symptoms, while subjects
with moderate-grade allergic dermatitis symptoms were dominated by patients
exposed to formula milk. Based on the value of vitamin D In terms of vitamin D
status, Patients with mild SCORAD showed a deficiency distribution of 1 person
(3.7%), insufficiency of 25 people (92.6%), and sufficiency of 1 person (3.7%),
whereas in patients with moderate SCORAD showed a distribution of 3 people
(42.9 %) had a deficiency and 4 people (57,1%) had insufficiency. None of the
subjects with symptoms of moderate-grade dermatitis had vitamin D levels within
the normal range.
Table
3. Characteristics of vitamin D status
|
Characteristics |
Vitamin D Status |
p-value |
||
|
Deficiency (n = 4) |
Insufficiency (n = 29) |
sufficiency (n = 1) |
||
|
Age (months), median
(min-max) |
3.5 (2 – 9) |
5 (1 – 12) |
6 (0) |
0.786 |
|
Gender, n (%) |
|
|
|
0.800 |
|
Male |
2 (50) |
12 (41.4) |
1 (100) |
|
|
Female |
2 (50) |
17 (58.6) |
0 |
|
|
History of Atopy, n
(%) |
|
|
|
- |
|
Yes |
4 (100) |
29 (100) |
1 (100) |
|
|
Not |
0 |
0 |
0 |
|
|
Nutritional Status, n
(%) |
|
|
|
- |
|
Malnutrition |
0 |
0 |
0 |
|
|
Good Nutrition |
4 (100) |
29 (100) |
1 (100) |
|
|
More nutrition |
0 |
0 |
0 |
|
|
Dietary intake, n (%) |
|
|
|
0.084 |
|
Exclusive Breastfeeding, n (%) |
3 (75) |
10 (34.5) |
0 |
|
|
Breastmilk+Formula milk |
1 (25) |
19 (65.5) |
1 (100) |
|
|
Formula Milk only, n (%) |
1(25) |
21(72,4) |
1(0) |
0.048 |
|
Vitamin D level (ng/mL), median (min-max) |
7.9 (7 – 8.5) |
20.4 (11.8 – 29.5) |
39.6 (0) |
- |
Table
3 above presents data on the characteristics of the research, the average age
of patients with cow's milk allergy with vitamin D deficiency and
insufficiency, respectively, is 3.5 months and 5 months. The vitamin D
insufficiency group was dominated by the female sex with a percentage of 58.6%,
while the vitamin D deficiency group showed an equal male and female sex ratio
Table
4. Analysis of the relationship between cow's milk allergy to vitamin D status
|
SCORAD |
Vitamin
D Status |
Total |
p
Nilai value |
||
|
Deficiency |
Insufficiency |
sufficiency |
|||
|
Mild |
1 (2.9) |
25 (73.5) |
1 (2.9) |
27 (79.4) |
0.007 |
|
Modarate |
3 (8.8) |
4 (11.8) |
0 (0) |
7 (20.6) |
|
|
Total |
4
(11.8) |
29
(85.3) |
1
(2.9) |
34
(100) |
|
|
* Mann-Whitney U test |
|||||
Analysis
of the relationship between cow's milk allergy and vitamin D status is
presented in Table 4 above using the alternative Mann-Whitney U test. Patients
with mild SCORAD showed a predominance of vitamin D insufficiency with a
percentage of 73.5%. Similar to the mild SCORAD group, the moderate SCORAD
group showed a predominance of vitamin D insufficiency with a percentage of
11.8%. Statistically, there was a relationship between the incidence of cow's
milk allergy and serum vitamin D status (p < 0.05).
Cow's milk
allergy (CMA) is an immunologically mediated unwanted reaction to cow's milk protein
usually associated with a type I hypersensitivity reaction mediated by IgE
although it can also be mediated by non-IgE mediators or a combination of
both.6,7 Symptoms and signs that appear varied, always preceded by exposure to
cow's milk protein or foods containing cow's milk protein. Can occur quickly
(acute-onset) or delayed onset.
Vitamin D is a
secosteroid that is formed in the skin through the process of photosynthesis by
sunlight. The structure of vitamin D is carried by a steroid compound that has
four rings of a cyclo-pentano-perhydrophenanthrene compound and is a fat-soluble
vitamin prohormone, also known as calciferol
This research
involved 34 infants with a mean age of less than 6 months; a systemic review by
Arne concluded that the greatest incidence of cow's milk allergy is less than 1
year of age by 2 to 3% and will decrease by the age of the children.13 Another
finding by Sardecka et al stated that the risk for cow's milk allergy increases
in the first year of life with a family history of allergies, this is because
in the first year of life, a child's immune system is not fully formed, so it
is very susceptible to exposure to allergens that can trigger allergic
reactions. In another research, the development of allergies in children can be
initiated. As many as 80% of children with eczema symptoms will develop a
recurring atopic dermatitis that occurs in the first year of life, and 73% of
them are caused by an allergy to cow's milk.
A family
history of atopy was found in all 34 samples. The results of this research are
supported by the research of Presscod et al., which explains that parents of
allergy sufferers are the strongest trigger factors for allergy sufferers
because genetic modification and expression will be passed on to children.
Atopy is the tendency of children to become sensitized and produce IgE in
response to allergen exposure. Research by
Vitamin D
levels classified as deficient were 4 subjects (11.8%), with 29 subjects
(85.3%) insufficiency and only 1 subject (2.9%). This is in line with the
research presented by Farjzadeh et al., it was found that the average value of
vitamin D levels in allergic patients was 24.62, which was also below the
normal value according to the category of insufficiency. the average level of
vitamin D, which is classified as normal in patients with milk allergy symptoms
of atopic dermatitis with a value of 48.5.24
The
relationship between vitamin D levels and allergy severity is shown in Table 4,
which was analyzed using the alternative Mann-Whitney U test for parametric
purposes. The aim is to see the relationship between the two. Based on the
comparative test, it was found that there was a significant relationship
between vitamin D levels and the severity of allergy in children with cow's
milk allergy with a p-value <0.05. In this research, it was found that
vitamin D levels were lower in patients who had more severe allergies, as
evidenced by higher SCORAD values. This is supported by several other studies
that assessed the same relationship as the research by
Research in
China showed a significant association between skin allergy and low serum
25(OH)D levels in children. Another research showed an association of vitamin D
deficiency with the severity of atopic dermatitis. The mean serum 25(OH)D level
was higher in children with mild atopic dermatitis than in those with severe
atopic dermatitis
The limitation
of this research is that the method of monitoring infants with cow's milk
allergy uses a cross-sectional research design but has not been able to
describe a causal relationship between vitamin D deficiency and the occurrence
of allergies, so further research is needed in the form of a cohort research.
Steps to enforce cow's milk allergy are carried out by assessing the SCORAD
index, with the results of the research still being subjective
The conclusion
of this research There is a relationship between vitamin D levels and cow's
milk allergy, especially symptoms on the skin based on the SCORAD value.
Subjects with low vitamin D levels had higher SCORAD scores and described a
more severe dermatitis severity. 85.3% of the total sample had vitamin D
insufficiency, and 11.8% of patients had vitamin D deficiency. The average
value for vitamin D deficiency was 7.9 ng/mL, and insufficiency was 20.4 ng/mL.
CONCLUSION
This research
aimed to evaluate the association between vitamin D levels and cow's milk
allergy based on the SCORAD index in infants under one year old. The findings
revealed that low vitamin D levels, both deficiency and insufficiency, were
associated with greater severity of cow's milk allergy. Most research subjects
exhibited vitamin D insufficiency, with a mean level of 20.4 ng/mL, and infants
with lower vitamin D levels experienced more severe atopic dermatitis. The
primary contribution of this research lies in reinforcing the evidence that
vitamin D levels play a crucial role in allergy-related immune responses,
particularly in infants with cow's milk allergy. The research also highlights
the importance of strategies to optimize vitamin D levels, particularly in
at-risk populations, as a potential approach to mitigating allergy severity.
Moreover, this research provides valuable insights into the Indonesian infant
population, contributing to the global understanding of the relationship
between vitamin D status and allergy severity. Future research should focus on
evaluating the effectiveness of vitamin D supplementation in reducing allergy
severity and exploring underlying mechanisms in diverse populations.
REFERENCES
Alhassan Mohammed, H., Mirshafiey, A., Vahedi, H., Hemmasi, G., Moussavi
Nasl Khameneh, A., Parastouei, K., & Saboor‐Yaraghi, A. A. (2017).
Immunoregulation of inflammatory and inhibitory cytokines by vitamin D 3 in
patients with inflammatory bowel diseases. Scandinavian Journal of
Immunology, 85(6), 386–394.
Batmaz, S. B. (2018). Laboratory and severity evaluation of pediatric
atopic dermatitis and moisturizer response in different phenotypes. Allergologia
et Immunopathologia, 46(6), 571–577.
https://doi.org/10.1016/j.aller.2018.03.007
Bulut, M., Ozceker, D., & Tamay, Z. (2020). The relationship
between serum vitamin D levels and childhood atopic dermatitis.
Di, T., & Chen, L. (2021). A narrative review of vitamin D and food
allergy in infants and children. Translational Pediatrics, 10(10),
2614.
Gyure, M. E., Quillin, J. M., Rodríguez, V. M., Markowitz, M. S.,
Corona, R. A., Borzelleca, J. F., Bowen, D. J., Krist, A. H., & Bodurtha,
J. N. (2014). Practical considerations for implementing research recruitment
etiquette. Irb, 36(6), 7.
Hossny, E., Ebisawa, M., El-Gamal, Y., Arasi, S., Dahdah, L., El-Owaidy,
R., Galvan, C. A., Lee, B. W., Levin, M., Martinez, S., Pawankar, R., Tang, M.
L. K., Tham, E. H., & Fiocchi, A. (2019). Challenges of managing food
allergy in the developing world. World Allergy Organization Journal, 12(11),
100089. https://doi.org/10.1016/j.waojou.2019.100089
Jensen, S. A., Fiocchi, A., Baars, T., Jordakieva, G., Nowak-Wegrzyn,
A., Pali-Schöll, I., Passanisi, S., Pranger, C. L., Roth-Walter, F., &
Takkinen, K. (2022). Diagnosis and Rationale for Action against Cow’s Milk
Allergy (DRACMA) Guidelines update-III-Cow’s milk allergens and mechanisms
triggering immune activation. The World Allergy Organization Journal, 15(9).
Li, Z., Celestin, J., & Lockey, R. F. (2016). Pediatric Sleep Apnea
Syndrome: An Update. The Journal of Allergy and Clinical Immunology: In
Practice, 4(5), 852–861. https://doi.org/10.1016/j.jaip.2016.02.022
Mailhot, G., & White, J. H. (2020). Vitamin D and immunity in
infants and children. Nutrients, 12(5), 1233.
Meyer, R., Groetch, M., & Venter, C. (2018). When Should Infants
with Cow’s Milk Protein Allergy Use an Amino Acid Formula? A Practical Guide. The
Journal of Allergy and Clinical Immunology: In Practice, 6(2),
383–399. https://doi.org/10.1016/j.jaip.2017.09.003
Misra, D. P., Zimba, O., & Gasparyan, A. Y.
(2021). Statistical
data presentation: a primer for rheumatology researchers. Rheumatology
International, 41(1), 43–55.
Nowak, S., Wang, H., Schmidt, B., & Jarvinen, K. M. (2021). Vitamin
D and iron status in children with food allergy. Annals of Allergy, Asthma
& Immunology, 127(1), 57–63.
https://doi.org/10.1016/j.anai.2021.02.027
Robinson, K. M. (2023). The Effects of Vitamin D Deficiency and
Endocrine Disruptors on the Development of Human Uterine Leiomyomas (Fibroids)
and Other Female Reproductive Disorders. University of
Bridgeport.
Sanmartin, R., Pardos, C., Doste, D., Aguilera, J.,
Alijarde, R., Jesús Agón‐Banzo, P., García‐Malinis, A. J., Puzo,
J., Hernández‐Martín, Á., & Gilaberte, Y. (2020). The association between
atopic dermatitis and serum 25‐hydroxyvitamin D in children: Influence
of sun exposure, diet, and atopy features—A cross‐sectional research. Pediatric
Dermatology, 37(2), 294–300.
Venter, C., Palumbo, M. P., Sauder, K. A., Glueck, D. H., Liu, A. H.,
Yang, I. V., Ben-Abdallah, M., Fleischer, D. M., & Dabelea, D. (2021).
Incidence and timing of offspring asthma, wheeze, allergic rhinitis, atopic
dermatitis, and food allergy and association with maternal history of asthma
and allergic rhinitis. World Allergy Organization Journal, 14(3),
100526. https://doi.org/10.1016/j.waojou.2021.100526
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