Nahla Ahmed Mohamed¹, Eman Refaat Youness^2*, Marwa Ali Mahmoud², Mina Wassef  Girgiss³, Omaima Mostafa Badran ⁴ and Hanaa Reyad Abdallah⁵

¹Department of Pediatrics, El Galaa Teaching Hospital, General Organization of Teaching Hospitals and Institutes, Cairo, Egypt.

²Medical Biochemistry Department, Medical Research and Clinical Studies Institute, National Research Centre, Cairo, Egypt.

³Medical Research and Clinical Studies Institute, National Research Centre, Cairo, Egypt.

⁴Department of Hepatology &Gastroenterology, Theodor Bilharz Research Institute, ImbabaGiza, Egypt.

⁵Biological Anthropology Department, Medical Research and Clinical Studies Institute– National Research Centre, Cairo, Egypt.

Corresponding Author E-mail: hoctober2000@yahoo.com

Abstract

Helicobacter pylori(H. pylori) infection has been implicated in refractory iron deficiency anemia (IDA) in children, raising concern due to its potential impact on growth and development. We aimed to determine the occurrence of H. pylori infection in children with IDA, its association with refractoriness to oral iron therapy, and its impact on growth.100 children participated in this cross-sectional study aged 4–12 years with IDA who failed to respond to 6 weeks of therapeutic iron supplementation. Participants, recruited from El Galaa Teaching Hospital, underwent full clinical assessment, anthropometry, and laboratory evaluation for IDA indices, H. pylori infection liver and kidney functions.H. pylori infection was detected in 77% of patients. Children who were infected had much lower BMI Z-scores, hematocrit (P = 0.001), hemoglobin (P < 0.001), serum iron (P < 0.001), and ferritin (P = 0.003), and significantly higher TIBC (P < 0.001) than uninfected children. H. pylori infection correlated negatively with BMI Z-score, Hb, Ht, MCV, serum iron, and ferritin (P < 0.05), and positively with TIBC (P < 0.001). Z-scores for height and weight showed no discernible variations.H. pylori infection is strongly relatedto refractory IDA and should be investigated in all affected cases. Although no association with linear growth was observed, H. pylori was negatively linked with nutritional status, reflected by lower BMI Z-scores.

Keywords

Growth impairment; Helicobacter pylori; Interleukin- 6; Iron deficiency anemia; Refractory iron deficiency anemia

Copy the following to cite this article: Mohamed N. A, Youness E. R, Mahmoud M. A, Girgiss M. S, Badran O. M, Abdallah H. R. Prevalence of Helicobacter pylori Infection in a Sample of Egyptian Children with Refractory Iron Deficiency Anemia. Biomed Pharmacol J 2026;19(2).

Copy the following to cite this URL: Mohamed N. A, Youness E. R, Mahmoud M. A, Girgiss M. S, Badran O. M, Abdallah H. R. Prevalence of Helicobacter pylori Infection in a Sample of Egyptian Children with Refractory Iron Deficiency Anemia. Biomed Pharmacol J 2026;19(2). Available from: https://bit.ly/4dARP82

Introduction

Reduced red blood cell count, hematocrit or hemoglobin concentration that is more than two standard deviations below the mean for age and sex is referred to as anemia.¹The most prevalent form of nutritional anemia is iron deficiency anemia (IDA), The pathogenesis of iron deficiency anemia (IDA) results from insufficient iron intake, poor bioavailability, or depleted iron stores, which ultimately lead to inadequate hemoglobin synthesis. These deficiencies contribute to various adverse health outcomes, including immune dysfunction, impaired growth, and cognitive deficits.²

The World Health Organization (WHO) estimates that anemia affects about 25% of the global population about half of the cases caused by iron deficiency anemia (IDA).³IDA is particularly common among high-risk groups such as infants, young children, and women of reproductive age.⁴

The burden is greater in developing countries, where prevalence among preschool children reaches about 39%, compared to 20% in developed regions. This problem persists into later childhood, with high rates reported among school-aged children.⁵

Helicobacter pylori (H. pylori) is a spiral-shaped bacterium that colonizes the human stomach lining. It was first isolated in 1982 by Barry Marshall and Robin Warren.⁶The prevalence of Helicobacter pylori infection in children variable across different countries. In Egypt, a population-based cross-sectional study conducted among asymptomatic schoolchildren reported an overall prevalence of 72.38%. The main risk factors identified were living in overcrowded households and in socially deprived areas. ⁷

Most infected children are asymptomatic, but other H. pylori infected children complaining of many gastrointestinal manifestations such as gastric dyspepsia, nausea and/or vomiting, recurrent unexplained abdominal pain.⁸ In addition to its well-known gastrointestinal effects, H. pylori infection has been associated with a wide range of extra-gastric diseases. These include lymphoma, cardiovascular and dermatological diseases, liver and gallbladder disorders, Iron deficiency anemia, diabetes mellitus, autoimmune diseases, atopy, asthma, neurological and bone disorders, micronutrient deficiencies, growth retardation, and idiopathic thrombocytopenic purpura.⁹

These associations are thought to arise from systemic effects of the infection mediated through hormonal, immunological, and inflammatory pathways, including the release of cytokines and chemokines that extend beyond the gastrointestinal system.¹⁰

Several studies have suggested a link between IDA and infection with H. pylori. This association may be explained by the development of chronic gastritis, which can lead to increased iron loss due to hemorrhagic gastritis, atrophic changes, or even Gastric Cancer. In addition, reduced gastric acidity caused by the infection can impair iron absorption, further contributing to iron deficiency, as well as improvements in unexplained IDA have been observed following successful eradication of the bacterium in both pediatric and adult populations.^11,12

The current workaimed to investigate the occurrence of H. pylori infection and its relation to IDA refractoriness to treatment in a sample of Egyptian children.The present study also assessed the probable relationships amonggrowth retardation, malnutrition andH. pylori infection in children.

Materials and Methods 

Calculation of sample size 

Using the PASS 11^th release, set the power = 0.80 and α = 0.05 and based on preceding studies,a sample size of 100 cases was included in this study. ¹³

Participants and Study design

Thisstudy (cross-sectional)was carried out from July 2024 to September 2024and included 100 childrendiagnosed with IDAwho received iron therapy at the propertherapeutic dose for 6 weeks without any response to oral iron therapy.They were selected from patients followed in the Pediatric Outpatient Clinic of El Galaa Teaching Hospital.

Inclusion criteria

Age: 4–12 years.

Sex: both sexes.

Patients who were diagnosed with IDAand received regular proper therapeutic oral iron therapy for 6 weeks without any improvement in hemoglobin level.

The absence of intestinal parasites, including hookworms, was confirmedvia examination of three consecutive samples of stool.

Exclusion criteria:

Patients with renal impairment, chronic liver disease or malabsorption.

Patients receiving blood transfusion or intake of anticoagulants, salicylates, steroid therapy or non-steroidal anti-inflammatory (NSAID) drugs.

Patients withapparentloss of blood (melena, hematochezia, hematuria, repeated epistaxis or hemoptysis).

Patients with conditions that cause anemia including hematological disorders, malignancy, and connective tissue disease.

Pubertal female patients who had menstruated, had irregular menstruation or prolonged or heavy menstrual periods of > 5 days with alarge quantity of bleeding (changes> 2 napkins/day).

Patients consumed antibiotics or proton-pump inhibitors during the last two weeks prior to joining the study.

Every patient was exposed to the following:

Complete history taking including:

The demographic data includedresidence, ageand sex.

Family history: A History of pylori infection and IDA, GIT ulcers and chronic gastrointestinal diseases (e.g. ulcerative Colitis). Crohn’s disease and inflammatory bowel diseaseoccur in family members.

Past history: Parasitic infection, recurrent post-prandial abdominal pain (location, frequency, duration, character, severity, bleeding, relieving and aggravating factors), drugs, previous diagnostic testing and specific therapy forgastrointestinal diseases, bowel habits,history of nausea or vomiting,appetite nature and any changes in weight.

Clinical examination

A – General examination including the following:

General appearance: lips, skin, and conjunctiva for pallor.

Vital signs: pulse, temperature and blood pressure.

Anthropometric measurements

Anthropometric evaluation was performed, including height and weight,which were measured via standardized equipment. The body mass index (BMI) is calculated by dividing height (in square meters) by weight (in kilograms). The Z scores (standard deviation scores) of weight, height and BMI were calculated via the WHO ANTHRO Plus software.¹⁴

B – Systemic examination including: thechest, heart, abdomen, etc.

Laboratory Investigations:

A DYNACOUNT 3D fully automatic hematology analyzerwas used to produce a complete blood count (CBC).

A Hitachi 704 auto-analyzer and colorimetric enzymatic methods were used to measure serum creatinine, urea, AST, and ALT (Roche Diagnostics, Switzerland).

Iron profile

Iron in the serum was determined via atomic absorption spectrophotometer (Perkin Elmer, Singapore).

Total iron binding capacity (TIBC) was assessed using an enzyme-linked immunosorbent assay (ELISA) (R&D Systems, Minneapolis, MN, USA).

To assess ferritin, the enzyme-linked immunosorbent assay (ELISA) was used (R&D Systems, Minneapolis, MN, USA).

Guaiac fecal occult blood test: This type, sometimes called gFOBT, uses cards to test samples from multiple bowel movements.

Stool sample for pylori antigen: The test was performed on both fresh and frozen samples of stool. When the test could not be performed for one day, the sample was stored at –20°C.

A commercially available enzyme-linked immunosorbent assay (ELISA) from PishtazTeb Diagnostics was used to screen for pylori antigen in feces. The manufacturer’s instructions were followed when doing ELISA.

Ethical approval

The study was conducted in accordance with the Helsinki Declaration and was authorized by the General Organization of Teaching Hospital and Institutes’ ethical committee (No. HG000103). All patients or their legal guardians gave their informed permission.

Statistical analysis

By using IBM SPSS version 27, the data was analyzed using the Statistical Package used for comprehensive statistical analysis, data management, and predictive modeling in the social sciences. For normally distributed data (Gaussian (normal) distribution), the quantitative data are shown as means ± SDs, ranges, and parametric tests; for non-normally distributed data, they are shown as medians and interquartile ranges (IQRs) with non-parametric tests. Qualitative attributes are presented using percentages and numbers. For qualitative data, the Fisher’s exact test and/or chi-square test were used to compare two groups; for quantitative data, the Mann-Whitney test was used as a non-parametric test and an independent t test was used as a parametric test. Correlations were determined via the Spearman correlation test. The p value < 0.05 was considered significant and theconfidence interval was set to 95%,.

Results

One hundred childrenwho were diagnosed with IDAand received regular proper therapeutic oral iron therapy for 6 weeks without any improvement in the hemoglobin levels were involved in this work.

Themean age of the studied patientswas 57 ± 2.47(4.6–12) y. Among them 54 were females (54%), while46 were males (46%).

Regarding the growth assessment of all the studied cases,the median and IQR of the weight Z-scores of our cases was 95 (-1.1–1.2), and that of the height Z-scores was 0.95 (0.1 – 1.6), while the nutritional assessment revealed that the mean ± SD of the BMI Z-scoreswas (- 0.48± 0.81),with a range of (- 2.67 – 1.20).Table (1).

Table 1: Anthropometric characteristics and demographicsofall the patients studied.

Variable		Patients (n=100)
Age (years)	Mean ± SDRange	7.57 ± 2.47
		4.6 – 12
Sex	Females(n, %)Males(n, %)	54 (54%)
		46 (46%)
Weight (Z-score)	Median (IQR)Range	0.95 (-1.1 – 1.2)
		-1.5 – 1.7
Height (Z-score)	Median (IQR)Range	0.95 (0.1 – 1.6)
		-2 – 2.3
BMI(Z-score)	Mean ± SDRange	– 0.48± 0.81
		– 2.67 – 1.20

SD: standard deviation, IQR: interquartile range, BMI: body mass index.

Table 2: Clinical features of all the patients studied.

Variables	Value
General appearance (n, %)
Pallor	32 (32%)
Jaundice	0 (100.0%)
Family history similar condition (n, %)	0 (100.0%)
Family history of chronic GIT disease	0 (100.0%)

With respect to the Clinical featuresof the total studied patients, pallor with observed in 32% of patients without any family history to pylori infection and IDA orFamily history of chronic GIT disease such as Crohn’s disease and inflammatory bowel disease. (Table 2).

Table 3: Laboratory resultsof all the patients studied.

Parameter		Patients (n=100)
Hemoglobin (g/dL)	Mean ± SD	8.23 ± 1.37
	Range	5.8 – 10.4
Hematocrit (%)	Mean ± SD	25.12 ± 2.56
	Range	18 – 28
Mean corpuscular volume (fl)	Mean ± SD	66.92 ± 5.95
	Range	49 – 73
Red cell count (x106/cm3)	Mean ± SD	3.91 ± 0.87
	Range	2.4 – 5.4
Serum iron (mg/dL)	Mean ± SD	34.3 ± 11.24
	Range	18 – 46
Total iron binding capacity (TIBC)(μg/dL)	Mean ± SD	418.69 ± 67.01
	Range	301 – 504
Serum ferritin (ng/mL)	Mean ± SD	14.92 ± 5.77
	Range	4 – 25
AST (IU/L)	Mean ± SD	29.92 ± 4.76
	Range	23 – 44
ALT(IU/L)	Mean ± SD	35.36 ± 3.81
	Range	28 – 42
Urea(mg/dl)	Mean ± SD	27.38 ± 7.13
	Range	18 – 43
Cr(mg/dl)	Mean ± SD	0.7 ± 0.16
	Range	0.5 – 1.1
H. pylori stool antigen	Positive	77 (77%)
	Negative	23 (23%)

With respect to the laboratory findings of the total studied patients, the findings of CBC and iron studies, including low serum ferritin and serum iron and high total iron binding capacity, indicated the persistence of IDA. Liver and renal function tests were within normal values. Helicobacter pylori antigen was positive in 77 % of the patients. (Table 3).

Patients were divided into two groups based on whether or not they had the H. pylori antigen, and they were then compared. There was no discernible difference in age between patients with and without H. pylori infection (p > 0.05). However,a comparison between the two groups according to sex distribution revealed a significant difference (p < 0.001), where the majority of patients with pylori infection were females (70.1%).Females are far more likely than males to develop H. pylori infection, suggesting a clear correlation between sex and the infection. In terms of the physical growth of H. pylori infected children, the mean weight and height Z-scores did not differ significantly fromthose of H. pylori non-infected patients (p = 0.954 & 0.698, respectively). However, regarding the nutritional status of our patients, a comparison of H. pylori-positive andH. pylori-negative patients’ BMI Z scores revealed that there was a significant difference in the infected group (p < 0.001).(Table 4).

Table 4: Comparing patients with and without H. pylori infection based on anthropometric and demographic information

Variable		H. pylori stool antigen		P-value
		-ve	+ve
		N = 23	N = 77
Age (years)	Mean ± SD Range	7.47 ± 2.88 4.6 – 12	7.61 ± 2.36 4.6 – 12	0.819
Sex	Females Males	0 (0%) 23 (100%)	54 (70.1%) 23 (29.9%)	< 0.001
Weight (Z-score)	Median (IQR) Range	-0.9(-1.2 – 1.4) -1.2 – 1.4	1(-1.1 – 1.1) -1.5 – 1.7	0.954
Height (Z-score)	Median (IQR) Range	0.9(-0.5 – 1.6) -0.5 – 2.3	1(0.1 – 1.2) -2 – 2.3	0.698
Height (Z-score)	Median (IQR) Range	0.9(-0.5 – 1.6) -0.5 – 2.3	1(0.1 – 1.2) -2 – 2.3	0.698
BMI Z scores	Mean ± SD Range	0.45±0.54 -0.50 – 1.20	– 0.75±0.66 -2.67 – 0.73	< 0.001

Means ± SDs were compared using the student’s t test; medians (IQRs) were compared using the Kruskal-Wallis test; numbers (%) were compared using the Chi-square test; p < 0.05 = significant; IQR stands for interquartile range; and BMI stands for body mass index.

With respect to laboratory markers, there were significant differences between pylori infected patients and non-infected patients in terms ofhemoglobin levels, hematocrit values, MCVs, serum iron, TIBC, and ferritin serum concentrations (p <0.05). Moreover, no significant differenceswere detected inred cell count or serum alanine transaminase, aspartate transaminase, urea or creatinine levels (p > 0.05)(Table 5).

Table 5: Comparison of laboratory findings in patients with and without H. pylori infection

Variable		H. pylori stool  antigen		P
		Negative	Positive
		N = 23	N = 77
Hb	Mean ± SDRange	9.68 ± 0.688.9 – 10.4	7.8 ± 1.225.8 – 9.3	<0.001
Ht	Mean ± SDRange	26.7 ± 1.2225 – 28	24.65 ± 2.6718 – 28	0.001
MCV	Mean ± SDRange	71.17 ± 1.6769 – 73	65.65 ± 6.1849 – 73	<0.001
RBCs	Mean ± SDRange	3.67 ± 0.822.4 – 5.1	3.98 ± 0.882.6 – 5.4	0.145
Serum iron	Mean ± SDRange	44.78 ± 1.2843 – 46	31.17 ± 11.0018 – 46	<0.001
TIBC	Mean ± SDRange	366 ± 60.6301 – 467	434.43±60.78301 – 504	<0.001
Serum Ferritin	Mean ± SDRange	18 ± 3.9114 – 25	14 ± 5.944 – 25	0.003
AST	Mean ± SDRange	29.43 ± 3.623 – 33	30.06 ± 5.0723 – 44	0.580
ALT	Mean ± SDRange	34.78 ± 3.9228 – 42	35.53 ± 3.7928 – 42	0.411
Urea	Mean ± SDRange	28.09 ± 8.0218 – 43	27.17 ± 6.8918 – 43	0.591
Cr	Mean ± SDRange	0.76 ± 0.170.5 – 1.1	0.69 ± 0.160.5 – 1.1	0.069

Student’s t test, p < 0.05= significant.

Moreover, the findings of our study revealeda significant negative correlation between H. pylori infection and BMI, Z scores, Hb, Ht, MCV, serum ferritin levels and serum iron (p <0.05), whereasTIBCwas significantly positively correlated withH. pylori infection(p < 0.001) (Table 6).

Variable	R	P
Age	0.058	0.568
Z Weight	– 0.006	0.954
Z Height	– 0.039	0.700
Z BMI	– 0.617**	<0.001
Hb	– 0.561**	< 0.001
Ht	– 0.338**	0.001
MCV	– 0.421**	< 0.001
RBCs	0.148	0.141
Serum Iron	– 0.482**	< 0.001
TIBC	0.410**	< 0.001
SerumFerritin	– 0.297**	0.003

Discussion

In cases of refractory IDA, itis recommended to search for H. pylori infection in the pediatric population since low iron status has been associated with H. pylori infection in multiple studies.Harris et al. ¹⁵revealed that hypochlorhydria, inflammation and H. pylori infection, are correlated with IDA in a prospective trial with 123 children.

In this study, we assessedthe prevalence of H. pylori infection among Egyptian pediatric patients diagnosed with IDA refractory to treatment. The major finding of our study was the highpervasivenessof H.pylori infection,which was 77% among patients withIDA. This finding ishigher than the findings of researches carried out by Galal et al¹⁶, Deeb et al¹⁷, Mohammad et al¹⁸and Abdulqawi et al¹⁹ which revealedthe prevalence of H. pylori infection among Egyptian anemic patients (44%,64.6%, 72.4%, and 68%,respectively).

Moreover, in Saudi Arabia, a study conducted by Hasosah et al ²⁰reported that the frequency of H.pylori infection in symptomaticpediatric patients was 49.8%.In another research,Iwańczak et al²¹described a maximalpervasiveness of H. pylori infection in Nigerian (82%), Ethiopian (48%), Bulgarian (61.7%) and Mexicanpatients (43%).

In addition,Bille and Mabeku²²revealed a highpredominance of H. pyloriinfection (80.88%) amonga pediatric populace withIDA in a sub-Saharan setting.

In contrast to our findings, a low pervasiveness of H. pylori infection has beendescribed in researches performed by Abdelaziz et al ^23,Zamani et al ²⁴ andNaous et al²⁵(25%,26%, and 21% respectively). Furthermore, a prospective study conducted on children aged 2–18 years in Turkey reportedthat the occurrenceratio of H. pylori infection was 30.7%.²⁶ Another Polish studyestimated that H. pylorisero-positivitywas 32.0% in children less than 18 years of age.²⁷

The difference in H. pylori infection prevalenceamong various studies may be caused by variations inthe design of the study, methods of H. pylori diagnosis, sample size, exclusion and inclusion criteria, and socioeconomic classes of the target population. ²⁸

The studies that describeda comparatively decreasedincidence of H. pylori infection may be attributed to methods of diagnosisofH. pylori, sincetesting H. pylori stool antigen isan effective, accurateand noninvasive technique, whereasserum antibody testing procedures for H. pylori detection may be concomitant with high false positive results, as they areunable to differentiate between active and past infections.²⁹This could also be elucidated by the spontaneous curability of H. pylori infection due to the use of antibiotics to treat infections other than H. pylori infection in childhood, as a study carried out by Zhou et al³⁰reporteda yearly spontaneous curability rate of 2.9% in children infected withH. pylori. However, theelevated prevalence of H. pylori infection isusually accompanied by numerous risk factors such as a decreased socioeconomic level, overcrowded living environments, low sanitation and an absence of sanitary water and reinfection between family members. ³¹

In 64% to 75% of individuals with both H. pylori infections and IDA, IDA totally disappeared once H. pylori was eliminated, according to Hershko and Camaschella. ³²

No significant difference between the two groups in terms of age was revealed (p = 0.819) with respect to the relation between H. pylori infection and age in the current study, comparing children withH. pylori infection to those without infection Moreover, an insignificant relationship between H. pylori infection and age was found in our cases (p = 0.568).

Galal et al¹⁶revealed thatH. pyloriwas more prevalent with increasing age; pediatric patients over ten years had the greatest rates of H. pylori infection (32.9%), whereas children younger than three years hadthe lowest (13.8%) which in contrast to our results.

Similarly,Hasosah et al²⁰describedthat theH. pylori prevalence was 10.5% in the pediatric population aged less thanthree years; nevertheless, it was 57.7% in patients older than tenyears. This may be attributed to the greater exposureof the pediatric population to the public and outsidecontact, resulting in poornutritional habits such as having street food. In contrast, otherresearchers detected an increase in infectionduring the infantile period because of sharing beds withbrothers or sisters with the infection. ³³

In the present study, comparisonsbetweenH.pylori infected and non-infected children according to sex distribution revealed significant changes (p < 0.01), with the majority of H. pylori infectedchildren being females (70.1%). Thus, there appears to be a very strong relationship between sex and H. pylori infection, with females being significantly more likely to have H. pylori than males.This could be attributed to sex discrimination and extremelyinherent customs, habits and beliefs, as more care is directed towards boys,mainly in a developing nationsuch as Egypt.

In contrast, sex was not detected as a risk factor for infectionwith H. pyloriin children in thestudy by Galal et al.among Egyptian children.¹⁶This was also reportedin Saudi Arabia by Hasosah et al.²⁰

Studies have yielded controversial results concerning the effects of infection with H. pylorion children’s growth, since a number of themhave demonstrated a relationship,³⁴whereas othershave denied this relationship.^35-38

However, a cohort study by Mera et al³⁹confirmed the long-lastingvalue of eliminating H. pyloriin the catch-up of growth in a pediatric populationmonitored for nearly four years.

Yang et al⁴⁰statedthat effective elimination of H. pylori in children accelerates growth and returns acylated ghrelin serum concentrations to normal.

Moreover, a previous study revealed a greater proportion of growth retardationamong pediatric patients withH. pyloriinfection than among healthy children. ⁴¹

In the current study, we also assessed the potential association ofgrowth retardation with H. pylori infection in children. No significant difference in the anthropometric measurements (weight and height Zscores) between theH. pylori positive patientsand H. pylori negative patients(p = 0.954 & 0.698).

Incompatible with our results, research carried out in Egyptexamining the impacts of H. pylori infectionongrowth in the pediatric population,stunted growth was highly prevalentamong the pediatric populationwith H. pylori infection compared with non-infected individuals;the weight-for-age Z scores were significantly lower amongthe pediatric populace withH. pyloriinfection than among those without infection. ¹⁹

Moreover, a meta-analysis performed by Wei et al. revealed a significantincrease in growth retardation in children withH. pylori infection compared with those without infection, as they analyzed 15 observational studies comprising 4199 subjects. A greater rate of growth retardation was detected amongthe H. pyloriinfected pediatric population than among those without infection, especially for height.In addition, there was arelationshipbetweenH. pyloriinfection and retarded growth among the pediatric populationin studiesthat includedH. pyloriwith a prevalence equalto or less than thirty percent or more than thirty percent but not with a prevalence greater than fifty percent. This agrees with our results as the pervasiveness of H. pylori infection was very high in our patients (77%), which was > 50%; thus, we did not detect any correlation of Weight‑for‑Age Z‑score orhight‑for‑Age Z‑score with H. pylori infection in our patients (p = 0.954 & 0.700).⁴²

Additionally, Wei et al ⁴²in their meta-analysis, performed a subgroup analysis and illustrated the associated growth of children withH. pylori infection in Europe, America, and Asia but not in Africa. This finding is also compatible with our results, as we detected non-significant difference in weight or height Z scoresamongstH. pylorinon- infected and infected children who were African.

A possiblejustification for those variations could bevaryingH. pylori prevalence rates,dissimilar environments and nutrition in diverse nations. Additionalinfluences associated with an augmented prevalence of infection with H. pyloriand growth retardation among the pediatric population are connected to low socio-economic levels, which are accompanied byinadequate health care, nutritional deficiencyand deprivedliving circumstances, which can affect outcomes. ^43-46

Additionally, the difference between these studies and our findings may be attributed tothe fact that theimpaired growth of children in these studies was determined by varying guidelines, leading to widepercentile ranges or 1-3 SDs. Furthermore, the differences in age, rate of growth and hormonal concentrations of every sample in the pediatric population might have been important factors in every research. Other possible explanations may be associated with IDA,malnutrition, environmental factors and inter-individual differences. Hence, managing the growth and development of H. pylori infected pediatric populations must consider these wide-ranging influences.

Notably,our results revealed an insignificant association ofH. pyloriinfection with height (p = 0.700).The findings of the currentwork are inconsistent with those described by preceding cross-sectional studies,confirming the negative association of H. pylori infection with linear growth. Large community-based cross-sectional research (n = 3315)in rural Germanyamongthe pediatric population aged five to seven years revealed a significant decreasein height inchildren with H.pyloriinfection compared with those without infection.⁴⁷

An additional studyin Egypt revealeda significantly greater percentage of children with H.pyloriinfectionthan of those free of infection who were under the fifth height-for-age percentile. ¹⁹

In parallel withour results, height was not relatedtoH. pylori infection in research among Alaskan, ³⁶Iranian,³⁷and Australian³⁸pediatric populations.

Regular assessment of anthropometric measurements during childhood and adolescence should be performed. Thus, approaching and evaluating nutritional status non-invasively can assist in monitoringphysical growth. Hence, adjusting the nutritional status entirely, not only height and weight separately, is essential. During achild’s examination, body mass index (BMI) represents one of the mostcommonly utilized measures to assess obesity and malnutrition.⁴⁸ 

With respect to the laboratory data, H. pylori positivepatients had significantly lower Hb, hematocrit, and MCV values (p =0.000, 0.001and0.000, respectively) thanH. pylori negative patients did. We also noted a negative correlation between H. pylori infection and Hb, Ht, MCV, ferritin, and iron serum levels (p < 0.05).

Theconclusions of our workalso coincide with the findings performed byBille &Mabekuthatdescribed a significantly lower Hb concentration (P = 0.01), Ht value (P = 0.04), insignificant MCV (P = 0.13) and low borderline RBC count(P = 0.06) in H. pylori infectedpatients than in non- infectedpatients, as well as a negativerelationshipamongH. pylori infection and Hb level.²² Another study performed by Muhsen et al. reported significantly lower Hb concentrations in H. pylori positive pediatric patients than in the uninfected individuals.⁴⁹However, a meta-analysis of randomized controlled trials of H. pylori elimination by Yuan et al⁵⁰revealed that elimination of H. pylori can increase Hb concentrations.

In the current work, we detected a significant decrease in serum ferritin (p=0.003) and serum iron (p <0.001) and a significant increase in total iron binding capacity (p <0.001) among H.pylori positivepatients compared withH. pylori negativepatients.

These findings agree with thestudythat reported low serum iron and serum ferritin levels and increased serum TIBC levels in H. pylori positive patients with IDA.²²

Study limitations

First, it did not include a normal control group but this could be compensated with that all the parameters included in the laboratory assessment of our cases had normal standards for comparison, and the measures used for the anthropometric assessment were converted into Z scores.

Second, the cross-sectional design of our study prevented us from following up with patients to confirm improvements in IDA and child growth after they were treated with H. pylori therapy in addition to iron administration. Moreover, improving nutrition and the living environment throughout the long-term observation of these children can influence these outcomes.

Third, the sociodemographic factors that are strongly linked to H. pylori infection were not examined. An additional limitation of this study is the restricted generalizability of its findings, as the results and conclusions are based solely on an Egyptian cohort and may not be representative of populations in other geographic or demographic contexts.

Fourth, althoughwe did not performa dietary analysis of our patients to explore whether there was dietary deficiency in the necessary constituents needed for hematopoiesis and whether our patients were receiving their recommended daily allowances, we assessed the nutritional status of our patients via BMI-Z scores.

Conclusion

The current study’s findings point to a substantial correlation between refractory IDA in children and H. pylori infection. Therefore, we recommendthe use of H. pylori detection inroutine work-up protocols for refractory or unexplained IDA management.

WhenH. pylori infection is being diagnosed, immediate eradication of the infection should be started to prevent consequentstrong harmful influences. Moreover, it is essential to create a constant standard classification for growth retardation in children. We recommend that strategies for H. pylori diagnosis and therapy should be prioritized as a public health issue,particularly in developing countriessuch asEgypt. Future studies in children without symptoms are required to address this concern, as successful elimination of H. pyloriduring childhood is essential.

To further explore the effects of H, additional high-quality, well planned controlled clinical trials should be carried out. pylori elimination on IDA and these children’s development.

Acknowledgement

The author would like to thank the General Organization of Teaching Hospital and Institutes for their guidance during the Satellite data procurement.

Funding Sources

The author(s) received no financial support for the research, authorship, and/or publication of this article.

Conflict of Interest

The authors do not have any conflict of interest. 

Data Availability Statement

This statement does not apply to this article.

Ethics Statement

The study was conducted in accordance with the Helsinki Declaration and was authorized by the General Organization of Teaching Hospital and Institutes’ ethical committee (No. HG000103). All patients or their legal guardians gave their informed permission..

Informed Consent Statement

This study did not involve human participants, and therefore, informed consent was not required.

Clinical Trial Registration

This research does not involve any clinical trials.

Permission to reproduce material from other sources

Not Applicable 

Author contributions

• Nahla A. Mohamed: Conceptualization, writing the original draft and approved final draft.
•  Eman Refaat Younessand Marwa A. Mahmoud: laboratory procedures, data analysis and approved final draft.
• Mina Wassef Girgiss:collect the data.
• Omaima Mostafa Badran: Clinical investigations
• Hanaa Reyad Abdallah writing the original draft and approved final draft.

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Abbreviations

AST: Aspartate transaminase

ALT: Alanine transaminase

BMI Z scores: Body Mass Index Standard Deviation Scores

CBC: Complete blood count

BMI: Body mass Index

Cr: creatinine

ELISA:  Enzyme-linked immunosorbent assay

ESPGHAN: European Society for Pediatric Gastroenterology Hepatology and Nutrition

GIT: Gastrointestinal Tract.

1. pylori:Helicobacter pylori

Hb: Hemoglobin

HpSAg:  Helicobacter pylori-specific antigen

Ht: Hematocrit value

ID: Iron deficiency

IDA: Iron deficiency anemia

IL-6: Interleukin- 6

IQR:    inter-quartile range

MCV: Mean Corpuscular Volume

NASPGHAN: North American Society of Pediatric Gastroenterology, Hepatology and Nutrition

RBCs: Red blood cells

SD: Standard deviation

SPSS:  Statistical Package for Social Science

TIBC: Total Iron Binding Capacity

WAZ: Weight‑for‑Age Z‑score

WHO: World Health Organization