The Prepuce, Urinary Tract Infections, and the Consequences

Schoen and colleagues[1] have addressed several major issues concerning urinary tract infections (UTIs) in uncircumcised male infants. They studied a large, relatively captive patient population and were able to assess inpatient and outpatient diagnoses of UTI during the first year of life. These authors have corroborated the association between foreskin presence and an increased incidence of UTIs. Additionally, they have reported a relatively higher frequency of such infections than that which is generally recognized[2]. Finally, Schoen et al[1] have noted the greater economic burden of UTIs in this population, primarily because of their greater incidence during early infancy.

In 1993, we performed a meta-analysis[3] of all 9 published studies that compared incidence rates of UTIs in uncircumcised versus circumcised infant males. There was a 12.0-fold increased risk for such infections (95% confidence interval: 10.6,13.6) in boys with foreskins. Subsequent to that report, numerous other supportive publications have appeared. In the latter studies, the increased incidence ranged from 3.7-fold[6] to the 11.3- and 9.1-fold increases that Schoen et al[1] found in 1996 and 1997, respectively. Although most investigations documenting the prepuce-UTI association have been in children <1 year of age, it has also been reported in premature infants[8], as well as during later childhood[4], and in adults[7]. The Pediatric Research in Office Settings (PROS) network of the American Academy of Pediatrics has recently completed a large, prospective trial of >3000 febrile infants. The PROS practitioners found uncircumcised boys to have a rate of UTI >13 times greater than circumcised boys (Thomas B. Newman, personal communication, November 1999). Additionally, in the ongoing prospective trials being conducted at the Children's Hospital of Pittsburgh, the risk of UTI attributable to prepuce presence is on the order of 16-fold higher (calculated from data provided by A. Hoberman, personal communication, March 1998). To date, there have been absolutely no studies that contradict this association.

Why should uncircumcised boys be prone to UTI? The major factors are likely related to microbial colonization and to bacterial adherence. A decade ago, we[9] demonstrated that uncircumcised infants were significantly more likely to harbor known uropathogenic organisms (eg, Escherichia coli) in the urethral meatus and periurethral area. Moreover, boys with foreskins had significantly higher concentrations of these microbes, as well as multiple other bacterium. Glennon and colleagues[10] described similar findings. In addition, presence of the prepuce allows bacterial adherence. The work of Fussell et al[11] demonstrated that uropathogenic bacteria, particularly P-fimbriated E coli (those associated with pyelonephritis), adhered especially well to the inner mucosal surface of the foreskin as opposed to the keratinized external surface. These very adherent, more abundant uropathogenic organisms ascend to the bladder and subsequently to the kidneys, causing UTI and pyelonephritis.

What is the frequency of UTI in uncircumcised boys during infancy? From a large database, we reported the incidence to be 1.1%[12]. However, because only hospitalized children were included, this was likely an underrepresentation. When we originally assessed the incidence rate in a relatively captive population in Hawaii[13], we found a higher rate (4.1%). The UTI rate of 2.2% of Schoen et al[1] is identical to the minimum cumulative incidence by 2 years of age in Sweden recently reported by Jakobsson and colleagues[14]. Hoberman and Wald[15] reported a UTI rate of 2.5% in all boys. However, because they have noted 70% of the UTIs to occur in the 14% of boys that are uncircumcised, the rate in the latter group is likely considerably higher. Thus, it would seem that the rate of UTI occurrence in uncircumcised boys during infancy is at least 2.2% or greater.

Urinary tract infections early in life are not benign. A high proportion of infants with UTIs (~10%) will have concurrent bacteremia[16-18]. The risk is considerably higher (21%-36%) when the infections occur during the first month of life. Additionally, concomitant meningitis occurs in 3% to 5% of children in the latter age group[16,18]. Severe dehydration, electrolyte imbalances, transient pseudohypoaldosteronism, and cachexia are other acute complications of UTI during infancy. Finally, renal failure[16,18] or death[16,19] may occur among the youngest affected infants.

Long-term sequelae of UTIs are primarily related to the effects of renal scarring. More than 90% of UTIs during the first year of life have kidney involvement (pyelonephritis)[20]. Renal scintigraphy, particularly with ^99mTechnitium-labeled dimercaptosuccinic acid, has led to the recent recognition that 36% to 52% or more of infants with acute pyelonephritis will subsequently develop renal scarring[20-24]. These figures are substantially higher than previous estimates that were based on lower resolution contrast studies (eg, intravenous pyelography). Moreover, multiple investigators have confirmed that renal parenchymal infection and inflammation, rather than vesicourethral reflux (VUR), are the prerequisite for acquired renal scarring[22-24]. The majority of children with renal scarring do not have VUR[24]. The late sequelae of renal scarring include hypertension, hyposthenuria, proteinuria, and chronic renal insufficiency, which may proceed to end-stage renal disease (ESRD). The most severe complications of UTI and renal scarring (hypertension and ESRD) are generally not seen by pediatricians because they are often not manifest until adulthood. Thus, many pediatricians are not aware of the very real risk for these sequelae and consider UTIs during infancy to be relatively benign disorders. Although more large follow-up series are needed to accurately assess the frequency of these complications, there are some limited long-term data. Smellie[25] followed a group of 241 children with VUR and UTI until they were 18 years of age or greater: 3 (1.5%) died (1 from renal failure); 3 (1.5%) had renal transplants; 8 (3%) had borderline hypertension; 10 (4%) had abnormally elevated serum creatinine levels; and 20 (8%) were being treated for hypertension. Jacobson and colleagues[26] assessed the prognosis after a period of at least 27 years among subjects with renal scarring that was noted during childhood. They found 23% of the patients to have hypertension and 10% to have ESRD. The 90% of patients without ESRD all had significantly lower glomerular filtration rates and lower renal plasma flow compared with healthy controls.

Many UTIs are not diagnosed because urine cultures are not obtained. Even the highly motivated group of PROS investigators frequently (48% of the time) did not assess for UTI in febrile young infants. Such infections in young children may cause few recognizable signs or symptoms other than fever. The presence of another potential source of fever, such as an upper respiratory infection or otitis media, is not reliable in excluding UTI[5]. A urinalysis can only suggest the diagnosis of UTI. The only way to verify the diagnosis is by culturing a properly collected specimen of urine (ideally via suprapubic aspiration or bladder catheterization). All too often when a UTI is diagnosed, the past medical history reveals that in the past when identical symptoms existed, antibiotics were prescribed but no urine cultures were obtained[27]. Additionally, "one would be amazed at the number of children with renal scarring who have had treatment in the past for multiple episodes of `otitis media' without urine cultures having been obtained."[28] The American Academy of Pediatrics Committee on Quality Improvement, Subcommittee on Urinary Tract Infection[29] has recently issued a practice parameter concerning UTIs in febrile infants and young children. This group recommended that if any child under 2 years of age with unexplained fever is assessed as being sick enough to warrant antibiotic therapy, a urine culture should be obtained.

Finally, Schoen et al[1] have found the costs of UTIs during early childhood to be considerably greater among uncircumcised male infants. These authors did not examine longer-term expenses, such as follow-up ^99mTechnitium-labeled dimercaptosuccinic acid scanning to assess for scarring, screening for subsequent infection, or the costs that would be incurred should the sequelae of renal scarring manifest. Thus, the true cost of UTI among uncircumcised male infants is considerably higher than what is described in the current report.

Conclusion

In summary, UTIs are relatively common infections among uncircumcised male infants, a group who are at least 10- to 12-fold more likely to develop these infections compared with their circumcised counterparts. UTIs can cause substantial acute and long-term morbidity. The prevention, recognition, proper treatment, and adequate follow-up of UTIs are important measures in preventing renal scarring and sequelae.

Footnotes

Received for publication Jan 3, 2000; accepted Jan 3, 2000.

Address correspondence to Thomas E. Wiswell, MD, Department of Pediatrics, Thomas Jefferson University, 1025 Walnut St, Suite 700, Philadelphia, PA 19107. E-mail: thomas.wiswell@mail.tju.edu

Abbreviations

UTI, urinary tract infection; PROS, Pediatric Research in Office Settings; VUR, vesicourethral reflux; ESRD, end-stage renal disease.

References

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