THE CIRCUMCISION REFERENCE LIBRARY
S Mårild, S Hansson, U Jodal, A Odén1 and K Svedberg
Department of Paediatrics, The Queen Silvia Children's Hospital, Sahlgrenska University Hospital, Göteborg, Sweden; Romelanda1, Sweden
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Aim: To assess the possible protective effect of exclusive breastfeeding against first-time febrile urinary tract infection (UTI) in children. Methods: Two children's hospitals and local child health centres in the Goteborg area, Sweden, participated in a prospective case-control study. In total, 200 consecutive cases (89M, 111F), aged 0-6y, presenting with first-time febrile UTI were enrolled. The mean +/- SD age was 0.98 +/- 1.15 y. As control subjects, 336 children (147M, 189F) were recruited from the child health centre of the case, matched for age and gender and included consecutively for each case during the first days after diagnosis. The duration of exclusive breastfeeding was obtained from the case and controls by a standardized procedure. Results: Ongoing exclusive breastfeeding gave a significantly lower risk of infection. A longer duration of breastfeeding gave a lower risk of infection after weaning, indicating a long-term mechanism. The protective role of breastfeeding was strongest directly after birth, then decreased until 7 mo of age, after which age no effect was demonstrated. Conclusion: A protective role of breastfeeding against UTI was demonstrated. The study provides statistical support to the view that breast milk is a part of the natural defence against UTI. Key words: Breastfeeding, infant, urinary tract infection S Mårild, Department of Paediatrics, The Queen Silvia Children’s Hospital/Sahlgrenska University Hospital, SE-416 85 Göteborg, Sweden (Fax. +46 31 843653, e-mail. staffan.marild@pediat.gu.se) |
[CIRP Note: This file does not include table one, figures one and two, and the statistical appendix.]
A previous case–control study indicated that cases with urinary tract infection (UTI) had a shorter duration of breastfeeding than controls (1). In a similar study, breastfeeding was shown to occur significantly less often at the time when a urinary infection was diagnosed compared with age-matched control subjects (2). It was suggested that the antiadhesive properties of breast milk could explain the protection offered by human milk (3).
The aim of the present study was to investigate the relationship between breastfeeding and the risk of firsttime febrile UTI and to assess the relation in girls and boys between the duration of breastfeeding and the momentary risk of acquiring an infection. The intention was also to illustrate the findings by determining the probability of acquiring a urinary infection in a population with a known incidence rate.
Patients and
methods
Cases
Eligible were children 0–6 y of age with a first-time
symptomatic UTI attending the Paediatric Departments at the
Hospital of Mölndal and the Queen Silvia
Children’s Hospital, Göteborg, Sweden. The
inclusion criteria were: fever of >38.5°C
within 24 h of diagnosis together with bacteriuria, defined
by one of the following: for suprapubic aspirates, growth of
any number of colony-forming units (cfu) per millilitre, one
strain; for midstream samples, growth >100000 cfu
ml-1, one strain; for bag urine, two separate
specimens with growth of >100000 cfu
ml-1, one and the same strain in both specimens.
The children also had to be living in the uptake area of the
two hospitals.
Control subjects
Controls were recruited among infants or children registered
at the Child Health Centre of the case. They had no history
of previous UTI or of urinary tract anomalies. The selection
aimed at two control subjects per case, matched for gender
and age.
Exclusion criteria
The following were excluded: families with language
difficulties or other obstacles for participation; those who
had not answered interview questions within the required time
limit (see below); children with concomitant serious diseases
or other major health impairment; those who declined to
participate; and other reasons, e.g. maternal disease or
missing records.
Background population data
During a 2 y period (1993–1995) the diagnostic rate of
first-time symptomatic UTI in children below 2 y of age in
the area was calculated to be 2.5% for girls and 2.5% for
boys (4). The present study included a
total of 300 girls, 111 cases and 189 control subjects, and
236 boys, 89 cases and 147 control subjects. None of the boys
was circumcised.
Exclusive breastfeeding Exclusive breastfeeding was defined as proposed by the World Health Organization (WHO) and according to the Swedish National Board of Health and Welfare Official statistics at the time of the start of the study, as complete nutrition with full meals of breast milk. Ingestion of small amounts of other food, one spoonful a day at most, to familiarize the child with the taste was accepted, but not a larger quantity (5, 6).
Interview procedure
An experienced and specially trained paediatric nurse
performed all the interviews (KS). Only mothers were
questioned. Immediately after the identification of a new
case, the nurse initiated recruitment of the corresponding
controls. A questionnaire was sent to the case and its
controls simultaneously before an interview by telephone. The
answers had to be obtained within 1 mo for infants below 1 y
of age and within 2 mo for older children. The mean number of
days until the interview was completed was 20.6 for cases and
23.6 for controls.
Statistics
Fisher’s non-parametric permutation test (7) was used to compare differences in
variables characterizing cases and controls. A p-value
>0.05 was considered significant. The effect of gender,
age and duration of exclusive breastfeeding on the risk of
having UTI was studied as a hazard function of UTI by the use
of Poisson regression models (8). The
hazard functions were assumed to be of the form exp(β0 +
β1x1 + β2x2 +. . .).
The probability of UTI was calculated from the hazard function determined by the Poisson regression analysis. The general relationship between survival and hazard function was applied. Adjustment for the enrichment in the study population of children with UTI was performed.
A full description of the statistical analysis is given in the appendix. Three Poisson models were applied to elucidate different aspects of the relation between breastfeeding and the risk of UTI. First, the general relationship was studied to show whether there was any preventive effect of breastfeeding on the risk of UTI (see Appendix, Table A1). Then, a second model was used to study gender differences with respect to the preventive effect (see Appendix, Table A2). Finally, to illustrate the importance of the duration of breastfeeding, a third model was used (see Appendix, Table A3). This last model was also applied repeatedly for various ages to obtain coordinates for the figures illustrating the risk patterns.
Ethics
The Research Ethics Committee of Göteborg University
approved the study (official record no. 158-91).
Results
Cases and control subjects
In total, 265 cases and 400 controls met the inclusion
criteria, whereas 65 cases and 64 controls were excluded. In
25 cases and 28 controls there were language difficulties, in
26 and 27 there were missing answers, or answers were
received too late, in 7 and 3 a serious concomitant disease
was present, and in 7 and 6 maternal disease made questioning
impossible. A final number of 200 cases (89M, 111F) and 336
controls (147M, 189F) was available for evaluation. One of
the cases had no matching control and 47 of the controls had
no matching case. Gender was successfully matched between
cases and controls. The mean ± SD age of cases was
0.98 ± 1.15 y and that of controls was 0.97 ±
1.15 y (ns).
Duration of exclusive
breastfeeding
The mean duration of exclusive breastfeeding in girls at the
time of the interview was 16 wk in cases and 18 wk in
controls (Table 1). Corresponding figures for boys were 11
and 12 wk. Girls had ongoing breastfeeding at the time of the
infection in 8 (7.5%) cases and 23 (12.5%) control subjects,
and boys in 36 (40%) and 52 (35%), respectively. The
gender-dependent difference reflects the higher age of girls
at the diagnosis of firsttime UTI (Table 1).
Urinary tract infection in relation to
ongoing breastfeeding
By the first Poisson regression model the impact of
breastfeeding on the risk of UTI was estimated by a hazard
ratio, non-breastfeeding versus breastfeeding, equal to 2.30,
95% confidence interval 1.56–3.39 (see Appendix, Table
A1). The ratio was significantly larger than 1 (p >
0.001). This finding means that there was a significantly
higher risk of UTI for babies who were not breastfed compared
with babies of similar age with ongoing breastfeeding.
In the second model (see Table A2), the interaction between gender and breastfeeding for the risk of UTI was studied. There was a general significant effect of gender (p = 0.0491). For girls the hazard ratio was 3.78, indicating an almost fourfold higher momentary risk, while it was 1.63 for boys, or a 63% increase for UTI for not breastfeeding.
The hazard function of the third model was used to calculate the risk of acquiring a UTI in girls during the first 2 y of life in relation to age at weaning. In Fig. 1. this is illustrated for two theoretical examples where exclusive breastfeeding is discontinued at 2 and 7 mo of age, respectively. If breastfeeding is ended at 2 mo of age, the risk of UTI is found to increase rapidly. After this, the risk is reduced, but remains at a higher level than in those discontinuing at 7 mo of age. In the latter case there is a momentary increase in the risk directly after weaning, followed by a lower risk of an infection until 2 y of age.
Urinary tract infection in relation to
duration of breastfeeding
Using the hazard function determined by the Poisson
regression analysis (see Table A3) and data from the
incidence study (4), the probability of
acquiring UTI during the first 2 y of life could be
calculated. The third model was used here to elucidate
temporal aspects of breastfeeding in relation to the risk of
UTI. The duration of breastfeeding has an impact on the risk
of UTI at any moment, both while ongoing and after weaning
until 2 y of age. The functions for girls and boys in the
model were permutated repeatedly to obtain coordinates for
Fig. 2. Thus, a longer duration of exclusive breastfeeding in
girls significantly reduced the probability of UTI. This
effect was seen for breastfeeding up to 7 mo of age and
thereafter no additional protection could be shown. For boys,
there was a trend in the same direction, but less marked, and
a constant decrease with age throughout infancy.
Discussion
In 1971 Winberg and Wessner presented a study suggesting a
protective effect of breastfeeding against septic infection
in newborns. The evidence was based on a case–control
study showing a significantly higher consumption of breast
milk in healthy controls than in the group of septic patients
(9). In studies from developing countries
infection-related morbidity and mortality were shown to be
lower in infants with longer duration of breastfeeding than
in those with early weaning (10, 11).
Lactating infants have been shown to be protected against
diarrhoea (12, 13), infantile respiratory
infections (14), otitis media (15) and other bacterial infections (16).
To optimize the information about breastfeeding, emphasis was placed on the details in the interview technique. Thus, only mothers were contacted, a single nurse conducted all interviews, the timing was matched between cases and controls, and a standard protocol was used. In addition, there was social matching between cases and controls. Therefore, the authors believe that the breastfeeding data are valid.
A protective effect of ongoing breastfeeding against UTI in infants was demonstrated in this study, in accordance with the previous pilot study (1). In this study, it appeared that breastfeeding was more beneficial in girls, although there was a similar effect in boys. Furthermore, breastfeeding also had a protective effect after weaning, with long-term protection until 2 y of age.
Population-based studies show the highest incidence of UTI in infancy, most often affecting males the first 6 mo of life, followed in older children by a female predominance (4, 17, 18). The difference in mean age at diagnosis of UTI between boys and girls in this study is in accordance with this knowledge. Since the majority of infants with first-time UTI have a normal anatomy of the urinary tract, functional immaturity with residual urine, combined with insufficient function of the immune system, are likely to be important pathogenic factors in both genders. For girls, the short distance from the bladder to the periurethral flora is an important factor in ascending infections. Closeness to the bacterial reservoir may explain the more pronounced and longer lasting benefit from breastfeeding in girls, through effects on the intestinal flora. In infant boys, the preputial flora has been shown to play a pathogenic role (19). Exclusive breastfeeding may provide protection by favouring colonization in the prepuce of bacteria with low virulence (20).
Several mechanisms have been suggested to explain the preventive effect of breastfeeding against infections (21–23). In the case of UTIs, there are several possibilities. A reduction in the risk of an ascending infection in breastfed babies has been associated with the presence of antiadhesive oligosaccharides in breast milk (3), contributing to the selection of and intestinal colonization by low-virulence bacteria (24). If left undisturbed by antibiotic treatment, the intestinal flora is quite constant and can provide long-term protection, which may explain the long-term effects found in this study. In addition, lactoferrin, with powerful unspecific antibacterial effects, is present in the urine of breastfed infants (25). Secretory immunoglobulin A antibodies are also present in the urine of breastfed babies, offering specific protection against the bacterial antigens characterizing the intestinal flora shared by the child and the mother (26).
Acknowledgements.–This study was supported by the Swedish Research Council and research grants from Frimurare-Barnhusfonden, Göteborg University and Bohuslandstinget, Sweden.
References
Received Sept. 9, 2002; revisions received Mar. 27, 2003 and Sept. 15, 2003; accepted Oct. 6, 2003
http://www.cirp.org/library/disease/UTI/marild4/