a Department of Epidemiology, German Centre for Research on Ageing, Heidelberg, Germany.
b Department of Epidemiology, University of Ulm, Ulm, Germany.
Dietrich Rothenbacher, Department of Epidemiology, German Centre for Research on Ageing, Bergheimerstr. 20, D-69115 Heidelberg, Germany. E-mail: rothenbacher{at}dzfa.uni-heidelberg.de
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Abstract |
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Methods Study subjects were all pre-school children in the city of Ulm, located in southern Germany and two nearby communities who were screened for school fitness between January and July 1997. The infection status of the children and of the accompanying mother was determined by the 13C-urea breath test. The parents provided additional information through a standardized questionnaire.
Results In all, 946 children (mean age 5.9 years) and their mothers were included in the final analysis (response in study population 80.2%). Overall, H. pylori prevalence was 9.8% in children and 34.7% in their mothers; there was a strong association between children's and mother's infection. Of the children, 82.5% had ever been breastfed. Prevalence of H. pylori infection was higher in children breastfed compared to never breastfed children (10.1% versus 8.4%) and showed a positive relationship with duration of breastfeeding. After controlling for covariates, including mother's H. pylori status, by means of multivariable analysis, the odds ratio (OR) for children's H. pylori infection was 1.56 (95% CI: 0.793.11) for any versus never breastfeeding and 2.57 (95% CI: 1.195.55) given the child was breastfed 6 months.
Conclusions These data suggest that breastfeeding in infancy does not protect against H. pylori infection among pre-school children in industrialized countries.
Keywords Helicobacter pylori, breastfeeding, observational study
Accepted 27 June 2001
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Introduction |
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As breastfeeding has a protective effect on a variety of infant illnesses6 and breast milk contains a large number of bioactive compounds which give specific and non-specific protection against infectious agents,7 childhood nutrition may influence acquisition of H. pylori infection. Thomas et al. and others found a positive relation between the amount of anti-H. pylori IgA in human breast milk and age at acquisition of the infection among 12 Gambian children,8,9 and, in a later analysis, among 64 Gambian children.10 They concluded that specific human milk IgA may have a crucial role in delaying the onset of H. pylori infection. To our knowledge, however, there is no current epidemiological data describing the association of breastfeeding and H. pylori infection in industrialized countries, where children are rarely breastfed beyond the first year of life.
The aim of this analysis was to investigate the relation between history and duration of breastfeeding and H. pylori infection in a large population-based sample of pre-school children, taking into account the H. pylori status of the mother.
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Methods |
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Data collection
Infection status was determined using the 13C-urea breath test which indicates current infection with H. pylori. The children received 200 ml of apple juice (pH 2.22.4) which contained 60 mg of non-radioactive labelled 13C-urea (Mass Trace, Woburn, USA). In addition, the accompanying parent was also asked to participate actively in the study; she or he received 75 mg of non-radioactive labelled 13C-urea. The breath samples were analysed with an isotope selective non-dispersive infrared spectrometer (NDIRS; Wagner-Analytical-Systems, Bremen, Germany). A change in the 13C value over baseline of more than 4 was considered positive. The accuracy of the 13C-urea breath test in children is similar to that seen in adults.13 Sensitivities and specificities of the 13C-urea breath test close to 100% have been reported.14
In addition, the children's parents were asked to fill out a standardized questionnaire which was sent to the parents 1 or 2 weeks prior to the examination. The questionnaire requested information regarding family demographics, socioeconomic status, housing, and living conditions, and breastfeeding practice during infancy. The questionnaire was also offered in Turkish, as a large proportion of the families were Turkish.
Statistical analysis
The association of various covariates with history of breastfeeding was assessed comparing the proportions of breastfed children among the various levels of the covariate by calculating a 2 statistic. We have previously identified the infection status of the mother as by far the strongest determinant of children's H. pylori infection11 and so only children whose mother also participated in H. pylori testing were included. We analysed the association of children's H. pylori infection status with breastfeeding history calculating a Mantel-Haenzel
2 statistic after stratification for maternal infection status; results of Fisher's Exact Test were considered if expected cell frequency was <5. We then used unconditional logistic regression to estimate prevalence odds ratios (OR) and their 95% CI to describe the independent association of breastfeeding history and duration of breastfeeding with children's infection status. This enabled simultaneous adjustment for known or suggested potential confounding variables. The following covariates were considered: H. pylori infection status of mother (yes, no), nationality of child (German, other), age (in years), sex, place of birth (in Germany, elsewhere), birthweight (
2500 g, >25003500 g,
3500 g), education of father (
9 years, 10 or 11 years,
12 years), education of mother (
9 years, 10 or 11 years,
12 years), any previous antibiotic use by child (yes/no), housing density (m2 per person living in household:
21, >2128.75, >28.75 [in tertiles]), smoking of mother in the household (yes, no), and smoking of the father in the household (yes, no). In addition, tests for trend were performed by including duration of breastfeeding as an ordinal variable (levels 0, 1, 2, 3 for never, <3, 36,
6 months, respectively) into the model. All statistical procedures were carried out with the SAS statistical software package.15
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Results |
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Table 2 shows the association of various covariates with history of breastfeeding. An association was observed between maternal infection status, nationality, sex, number of siblings, birthweight, school education of mother and father, and household smoking of mother and father. In contrast, history of child's antibiotic use and housing density were not associated with history of breastfeeding.
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Discussion |
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These data are in concordance with the observations of Gold et al.16 who showed, in 80 newborns from Taiwan, that breastfeeding of infants was associated with an increased risk for H. pylori IgG-seroconversion during 14 months of follow-up. In contrast to our study and the study of Gold et al., only breastfed children were included in the Gambian study8 in which a delayed onset of infection was related to specific H. pylori IgA in breast milk. A meaningful characteristic of this study by Thomas et al.8 which could in part explain these differences is the nutritional situation of the study population. In the Gambia the nutritional situation of children is very poor and one important implication of breastfeeding is to protect children against malnourishment which could then delay acquisition of H. pylori infection in better nourished infants. This hypothesis is concordant with the observation that chronic diarrhoea and malnutrition were associated with increased H. pylori prevalence in an earlier seroprevalence study from this region including 217 children up to 60 months.17 However, another study from Bangladesh could not confirm this positive relationship and suggested lack of adjustment for other covariates as one possible explanation for these findings;18 notably, this study from Bangladesh also described a positive relationship between breastfeeding and H. pylori prevalence in children 60 months. Another study, from England, investigated childhood living conditions, among them childhood nutrition, with H. pylori seroprevalence at age 70.19 This study suggested a tendency towards a negative association, however, results were not controlled for relevant covariates. Furthermore, given the possibility of loss of H. pylori infection, particularly among older adults, these data are hardly comparable to the results of our study.
It has been demonstrated that breastfeeding is protective against a variety of infant illnesses including lower respiratory and gastrointestinal diseases and also has a beneficial effect on general morbidity.6,7,2022 One reason may be that breast milk has specific antibody protection through milk IgA, IgG, and IgM. In addition, non-specific protection is provided by several distinct mechanisms: lactoferrin, lysozyme, kappa-kasein and several other constituents cause a variety of effects that are bactericidal, bacteriostatic or inhibit the adhesion of infectious agents to the gastric mucosa.23,24 Therefore, the higher H. pylori prevalence in children who have been breastfed seems to be in conflict. Several factors, however, might explain this apparent inconsistency. Firstly, breastfed children may receive fewer antibiotic courses as a result of the above-mentioned protective effect of breastfeeding, therefore leading to lower rates of accidental eradication of H. pylori infection.25 Secondly, breastfeeding may serve as a marker for close contact with the mother who appears to play a major role in transmission of H. pylori to the child.11 This may explain why breastfeeding was positively related to H. pylori infection, and particularly so among children of infected mothers, although duration of breastfeeding was relatively short in our study population and many H. pylori infections may have occurred after weaning. The observation that the odds of infection were especially increased in children who were breastfed 6 months may also point to the importance of intensity of mother-infant contacts. However, other family contacts may play an additional role as H. pylori prevalence in children of other than German nationality of H. pylori negative mothers suggests.
When looking at the results of this study the following limitations have to be considered: we measured H. pylori prevalence in children years after they had been breastfed. As it seems likely that a spontaneous elimination of H. pylori infection may occur in children,26,27 a cross-sectional study in pre-school age may not reflect prevalence of infection in early infancy when acquisition of infection most likely may have taken place.3,4 However, as there is currently no evidence that elimination of infection may be related to breastfeeding practice, any resultant bias would most likely act towards null and the true OR would even be higher than the ones described. In addition, we adjusted for factors that may incidentally eliminate H. pylori infection during childhood by means of multivariate analysis (e.g. history of antibiotic medication25).
Furthermore, we had to rely on maternal self-reported breastfeeding history. As the questionnaire was collected before the 13C-urea breath test was conducted, differential recall seems very unlikely and would also be an unlikely explanation for the observed results. As this population-based study included all children within a certain age range within a defined geographical region and as the response rate was very good, results should be valid and representative for populations with similar socioeconomic characteristics.
In conclusion, although our study reveals no information on the time of acquisition of H. pylori infection and its relation to breastfeeding habits, it suggests that breastfeeding does not protect against H. pylori infection in industrialized countries. Moreover, duration of breastfeeding showed a positive association with H. pylori prevalence in pre-school age. This was especially evident in children who have been breastfed 6 months which may reflect the close contact between the child and their mother thereby facilitating mother-child transmission. The observed patterns might also be an indication that acquisition of H. pylori infection does not occur to a major extent within the first 6 months of life, a hypothesis supported by the observation of passive transplacental transfer of maternal anti-H. pylori IgG among infants of infected mothers which lasts about 6 months.16,28 Further, in particular longitudinal, studies are needed to clarify the role of breastfeeding in acquisition of H. pylori infection.
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