Papers

Short stature and Helicobacter pylori infection in Italian children: prospective multicentre hospital based case-control study

Giuseppina Oderda, researcher, ^a D Palli, medical epidemiologist, ^b C Saieva, fellow in public health, ^b Elena Chiorboli, fellow in paediatrics, ^a G Bona, associate professor, ^a on behalf of the Italian Study Group on Short Stature and H pylori.

^a Clinica Pediatrica, Università di Torino, 28100 Novara, Italy, ^b Unità Operativo Epidemiologia, Centro per lo Studio e la Prevenzione Oncologica, Azienda Ospedaliera Careggi, 50131 Florence, Italy

Correspondence to: Dr Oderda oderda{at}med.no.unipmn.it

Members of the study group are listed at the end of the article

Helicobacter pylori is mainly acquired in childhood,¹ but the diseases associated with such infection remain unknown. Scottish and Italian schoolchildren infected with H pylori showed reduced growth in height, ^{2 3} and H pylori gastritis was found in 55% of French children examined for short stature.⁴ To evaluate the role of H pylori and socioeconomic factors on growth we compared children with idiopathic short stature with those of normal height.

	Subjects, methods, and results

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This study was approved by and conducted within the guidelines of the gastric disease section of the Italian Society for Paediatric Gastroenterology and Hepatology (SIGEP). Between April 1996 and March 1997 we recruited 134 consecutive children aged 5-13 years (median 9.8 years) whose height was below the third centilethat is, two standard deviations below the mean height of their peersfrom 26 paediatric gastroenterology and endocrinology units in Italy. We individually matched them with children of the same age and sex from the same region whose height was above the 25th centile and who had been referred for minor diseases. Obvious medical reasons for short stature (chronic or neoplastic disease with or without genetic abnormalities) were excluded by history and appropriate tests. Information on risk factors was collected by structured questionnaires with questions on socioeconomic status (education, number of cohabiting relatives, and number of rooms at home) and anthropometric data. Weight and height were measured and serum samples collected.

Serum was tested for H pylori IgG in a central laboratory by enzyme linked immunosorbent assay (ELISA) (Helori, Eurospital, Italy). The assay was concurrently validated in 127 children of similar age whose H pylori status was known from the results of gastric biopsy. Children were considered to be infected when their titre was >12 AU/ml, the cut off point determined from receiver operating characteristic curves (sensitivity 87%, specificity 94%). The Wilcoxon rank sum test was used to evaluate differences in continuous variables. Categorical data analysis was used on matched sets. Conditional logistic regression models were used for multivariate matched analyses.

Cases had a lower birth weight (P<0.01) and their parents were shorter (P<0.01) and had attended school for fewer years (P<0.01) (table). Families of controls had fewer children but the same number of rooms at home. A high crowding index and presence of more than one type of pet was significantly associated with short stature (table). Serology showed H pylori infection in 27 cases (20%) and 18 controls (13%) (P=0.191). Prevalence tended to be higher in boys, but the difference was significant only in cases (27% (23/85) in short boys v 10% (5/49) in short girls, P=0.03) and tended to be higher in cases with lower growth hormone concentrations (22% (10/46) in those with peak hormone concentrations <10 pg/l v 12% (6/50) in those with concentrations 10 pg/l; P=0.314). Parental height, lower birth weight, and a crowded home persisted in a multivariate analysis as independent predictors of short stature.

	Comment

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Our results show that H pylori is not a risk factor for short stature and that reduced growth is related to genetic determinants such as parental height and to mixed genetic and environmental factors such as birth weight. Low socioeconomic status was relevant. The decreased growth found in Scottish and Italian schoolchildren infected with H pylori might be related to the association between lower socioeconomic group and H pylori acquisition. ^{2 3} The higher prevalence of H pylori in disadvantaged children suggests that infection should be considered a marker of low socioeconomic group in studies on growth, with other factors causing the reduced growth. Although genetic factors cannot be modified, more attention should be paid to pregnancy, living conditions, nutrition, infections, and emotional deprivation. The association between short stature and low socioeconomic group seems particularly relevant in view of the reported unsatisfactory long term efficacy of expensive treatment with growth hormone.⁵

	Acknowledgments

Members of the study group were M Baldassarre (Bari), V Benigno (Palermo), E Braggion (Palermo), A Carlucci (Lanciano), G L de'Angelis (Parma), F De Luca (Messina), T Gentile (l'Aquila), G Guariso (Padua), L Iughetti (Florence), G Lauriola (Manfredonia), P Lionetti (Florence), A Liotta (Palermo), F Lizzoli (Pavia), R Longhi (Como), V Lucidi (Rome), A Masciale (Bitonto), M Pastore (San Giovanni Rotondo), A Pavanello (Pordenone), F Rea (Naples), C Romano (Messina), P Roggero (Milan), V Rutigliano (Bari), S Salardi (Bologna), M S Scotta (Varese), M Spina (Catania), A Tozzi (Naples).

Contributors: GO designed and coordinated the study and wrote the manuscript. DP contributed to the epidemiological aspect of the study design, was responsible for the statistical analysis, and contributed to writing the manuscript. CS was jointly responsible for statistical analysis and interpreting data and revised the final version of the manuscript. EC supervised the collection of clinical data and critically revised the manuscript. GB was jointly responsible for the original study proposal and for coordination. The members of the study group approved the study proposal after extensive discussion, recruited all cases and controls at the 26 participating centres, completed the questionnaires, and collected blood for antibody determination. They also agreed to the adding of their names to the manuscript as members of the study group to show where the recruitment centres were. All approved the final version of the manuscript that was submitted for publication. GO and DP are guarantors for the study.

Funding: None.

Conflict of interest: None.

	References

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2. Patel P, Mendall MA, Khulusi S, Northfiel TC, Strachan DP. Helicobacter pylori infection in childhood: risk factors and effect on growth. BMJ 1994; 309: 1119-1123[Abstract/Free Full Text].
3. Raymond J, Bergeret M, Benhamou PH, Mensah K, Dupont C. A 2 year study of Helicobacter pylori in children. J Clin Microbiol 1994; 32: 461-463[Abstract/Free Full Text].
4. Perri F, Pastore M, Leandro G, Clemente R, Ghoos Y, Peeters M, et al. Helicobacter pylori infection and growth delay in older children. Arch Dis Child 1997; 77: 46-49[Abstract/Free Full Text].
5. Coste J, Letrait M, Carel JC, Tresca JP, Chatelain P, Rochiccioli P, et al. Long term results of growth hormone treatment in France in children of short stature: population, register based study. BMJ 1997; 315: 708-713[Abstract/Free Full Text].

(Accepted 19 February 1998)