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Five- to 7-Year-Old Children With Helicobacter pylori Infection Are Smaller Than Helicobacter-Negative Children: A Cross-Sectional Population-Based Study of 3,315 Children

Richter, T.*; List, S.*; Müller, D. M.*; Deutscher, J.*; Uhlig, H. H.*; Krumbiegel, P.; Herbarth, O.; Gutsmuths, F. J.; Kiess, W.*

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Journal of Pediatric Gastroenterology and Nutrition: October 2001 - Volume 33 - Issue 4 - p 472-475
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Abstract

Chronic gastritis, duodenal and gastric ulcer, and the mucosal-associated lymphoid tissue lymphoma and carcinoma of the stomach are thought to be caused by Helicobacter pylori infection (1). A putative effect of H. pylori infection on growth also has been discussed (2–8). We therefore designed a cross-sectional population-based study to determine the H. pylori prevalence in 5- to 7-year-old children in an area of 657,000 inhabitants and compared the H. pylori status of these children with their standing height and weight.

METHODS

Participants

In a cross-sectional population-based study of 3,837 school beginners for the year 1998, 3,362 (87.6%) could be recruited and investigated for weight, length, and H. pylori status. The children attended schools in two administration districts of the city (n = 2,228) and the rural area outside of Leipzig (n = 1,134). Mean age at the date of investigation was 5.96 years in the city district and 6.29 years in the country district. The age of infected and noninfected groups did not differ (6.15 ± 0.52 vs. 6.07 ± 0.42 years). The number of foreign children in both study groups was 155. Within this group of foreigners, 47 children were non-white. For study reasons, only data from the 3,315 white children were analyzed further. The study was approved by the university ethics commission, and informed consent was obtained in writing from the children's parents in all cases.

Anthropometric Measurements

Measurements of height (all cases as standing height) and weight were performed for all children using mobile routine instruments by members of the Health Administration Office of the city of Leipzig. The means and standard deviations (age range, 5–8 years) of the reference group (9) were transformed into gender-and age-dependent exponential functions. We could thus calculate the standard deviation scores of standing height and weight in relation to age and gender according to tabulated normative data (9).

Urea Breath Test

The stable isotope-based urea breath test was performed as described previously (10). However, we had to consider that the urea breath test can be unreliable for children younger than 7 to 8 years if the children are physically active during test time (11). Therefore, all children were not only fasted overnight but also were without physical activities during test time to avoid fluctuating endogenous ( 12 C) carbon dioxide production that could dilute uncontrollably the 13 C content of the measured gas (11). The 12 C-to- 13 C ratio was then measured in the carbon dioxide of the exhaled air ( 13 C-FANci Analyser; Fischer Analysen Instrumente GmbH, Leipzig, Germany) before and 30 minutes after the intake of 75 mg 13 C labeled urea (lot no. MTI-9912–0116-S2; 13 C isotope ratio, 99.3%; chemical purity, 99.8%; Chemotrade, Leipzig) dissolved in 100 ml orange juice. The differences between the 12 C-to- 13 C ratios in the breath samples before and after urea intake were calculated as delta 13 C over baseline values. Children were regarded as H. pylori positive when the delta over 13 C baseline value was more than 5. The test conditions enabled the use of the breath test also in children younger than 7 years as reported earlier (10,11).

Statistical Analysis

Statistical analysis was performed using the Student t test and the Mann–Whitney U test. Normality distribution (P < 0.05) was tested for by the Kolmogorov-Smirnov test. The SPSS statistical software, version 3.0 (Software Package for the Social Sciences, Chicago, IL), was used.

RESULTS

Height and height standard deviation score values (mean, 0.11 ± 1.14) of all of the 3,315 children as well as of the subgroups were analyzed and shown to be normally distributed. Weight and weight standard deviation score values (mean, 0.57 ± 1.51) were not normally distributed. There were no significant differences between children of the two administration districts. The prevalence of H. pylori infection in boys was 7.2% (95% confidence interval, 5.9–8.5; n = 1,550) and in girls was 6.1% (95% confidence interval, 4.9–7.3; n = 1,552). The H. pylori state of the children was not significantly different between boys and girls of the two administration districts. When weight was adjusted to age, H. pylori-positive children had lower weight than H. pylori-negative children, but none had values lower than the reference population of Prader et al. (9).

H. pylori-positive children were shorter (117.6 ± 5.5 cm vs. 118.9 ± 5.7 cm;P < 0.01). Differences were gender specific. Although H. pylori-positive boys were 2.06 cm smaller than H. pylori-negative boys (117.4 ± 5.6 cm vs. 119.5 ± 5.7 cm;P < 0.001), the difference in girls was not significant (117.9 ± 5.3 cm vs. 118.4 ± 5.7 cm). When height was normalized for age, the differences were more pronounced (Fig. 1A). The mean values of standing height standard deviation scores of H. pylori-negative girls and H. pylori-negative boys are lower than the reference population of Prader et al. (9) (Fig. 2).

FIG. 1.
FIG. 1.:
Box and whisker plots (median, two quartiles between 25th and 75th percentiles and extremes) of the age-and gender-adjusted standing height (A) and weight (B) of 3,315 school beginners of the administration area of Leipzig in relation to Helicobacter pylori testing ( 13 C breath test).
FIG. 2.
FIG. 2.:
Distribution of standing height standard deviation scores (A) and weight standard deviation scores (B) in relation to Helicobacter pylori testing ( 13 C breath test).

Differences between the infected and noninfected children with regard to body weight were not significant (22.1 ± 4.0 kg vs. 22.4 ± 4.0 kg). However, boys with H. pylori infection had a lower weight than noninfected boys (21.6 ± 3.3 kg vs. 22.6 ± 4.0 kg;P < 0.01), but in girls these differences were not observed (22.8 ± 4.6 kg vs. 22.2 ± 4.0 kg). When weight was adjusted to age, H. pylori-positive children had also a lower weight than H. pylori-negative children did. Again, this effect was the result of the lower weight measured in H. pylori-infected boys (Fig. 1B and Table 1). There was no significant difference with regard to body-mass index values between the H. pylori-negative and the H. pylori-positive groups. Because height and weight change in parallel, a difference in body-mass index was unlikely and indeed was not observed (15.9 vs. 16.0).

TABLE 1
TABLE 1:
Body weight (kg), standing height (cm), and age- and sex-adjusted deviation scores (SDs) of Helicobacter pylori –positive and –negative children

The foreign children of nonwhite races had a higher rate of H. pylori infection (P < 0.001) and lower height and weight compared with the study groups, but differences of body weight and height between infected and noninfected children could not be confirmed in this group.

DISCUSSION

A putative influence of H. pylori infection on growth has been suggested by a number of studies. In some of these, serologic methods (3,7) or breath tests (5,12) were used to test for H. pylori infection. Most of these studies were based on a longitudinal study design, included children with an age range of more than 3 years, or both. In our study, a large number of children within a small age range were analyzed using the 13 C urea test in a population-based cross-sectional study. The test system used has been shown to be the most sensitive and specific tool for the noninvasive detection of H. pylori infection (13). In this population (88% of all preschool and school children born in Leipzig in the years 1991–92), a significant difference between the height of H. pylori-positive and that of -negative children was detected. This difference was found using untransformed data as well as age-adjusted values. The differences in body weight were restricted to males and were less pronounced than the effect on height.

In 48 children with short stature aged 5 to 16 years, Sauve-Martin H et al. (14) demonstrated a higher prevalence of H. pylori infection than in children with normal height. However, corrected for socioeconomic status, this difference did not remain significant.

According to the questionnaires answered by the parents of the children, there was no significant difference between H. pylori-positive and H. pylori-negative children with regard to the socioeconomic status of the corresponding families. In a preceding paper, parameters such as sanitary standards of the residence or domestic crowding were shown not to be risk factors for H. pylori transmission in our study population (12).

The gender-specific difference in height of H. pylori-infected versus noninfected children, which was more pronounced in boys, is comparable with that found by other groups (7). This gender difference may be caused by different behavior patterns of boys compared with girls in the investigated age group as well as the result of gender-specific growth phases. In contrast, a longitudinal study showed that growth retardation was more obvious in females than in males (3). We cannot explain the discrepancy between these data and our results.

The observed association of H. pylori infection and lower height may be explained in several ways. H. pylori infection may lead to growth retardation via gastrointestinal (gastritis, gastric acid secretion (15)) and related somatic comorbidity (anemia) (16). However, any chronic infection can be associated with reduced growth. However, it is still premature to recommend a systematic search for H. pylori infection in children with growth retardation, although the findings of a higher rate of H. pylori infections in children with growth retardation have been confirmed by other investigators. For example, growth restriction observed in 37% of children tested positive for H. pylori mat be a result of the chronic infection itself, as Demir et al. (17) stated. In addition or alternatively, children with short stature may become infected by H. pylori at a higher rate and more easily than taller children. H. pylori infection and growth retardation may be caused coincidentally by the same confounding factors, for instance, various social factors (6). The latter hypothesis is unlikely in our study population, as shown above.

Acknowledgments:

The authors thank the colleagues and fields workers of the Health Administration Office (Gesundheitsamt) of the city of Leipzig for their help and support.

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Keywords:

Helicobacter pylori; Gastritis; Growth retardation; Children; Breath tests

© 2001 Lippincott Williams & Wilkins, Inc.