FAMILY HISTORY AND BEHAVIORAL ABNORMALITIES IN GIRLS WITH RECURRENT URINARY TRACT INFECTIONS: A CONTROLLED STUDY

0022-5347/04/1714-1663/0 THE JOURNAL OF UROLOGY® Copyright © 2004 by AMERICAN UROLOGICAL ASSOCIATION

Vol. 171, 1663–1665, April 2004 Printed in U.S.A.

DOI: 10.1097/01.ju.0000117701.81118.f0

FAMILY HISTORY AND BEHAVIORAL ABNORMALITIES IN GIRLS WITH RECURRENT URINARY TRACT INFECTIONS: A CONTROLLED STUDY CHRISTINE M. STAUFFER, BOUDEWIJN VAN DER WEG, REBECCA DONADINI, GIAN PAOLO RAMELLI, SABINE MARCHAND AND MARIO G. BIANCHETTI* From the Departments of Pediatrics (CMS, BvdW, RD) and Pediatric Surgery (SM), University Hospital, Bern and Department of Pediatrics, San Giovanni Hospital (RD, GPR, MGB), Bellinzona, Switzerland, and Pediatric Renal Unit, University of Milan Medical School, Clinica De Marchi (MGB), Milan, Italy

ABSTRACT

Purpose: We evaluated the role of family history, infrequent voiding, poor fluid intake, functional stool retention and inadequate anogenital hygiene or toilet habits in girls with recurrent urinary tract infections. Materials and Methods: The possible occurrence of these risk factors was assessed in 90 Swiss girls with recurrent urinary tract infections and in a control group of 45 girls. Results: Family history was positive in 42% of patients and in 11% of controls (p ⬍0.001). Behavioral abnormalities were also more frequently noted in girls with recurrent urinary tract infections than in the control group (81% vs 56%, p ⬍0.01). There were 137 abnormalities in 73 girls with recurrent urinary tract infections and 30 abnormalities in 25 controls. Two or more abnormalities each, that is 2 in 32 girls and 3 in 16, were noted in 48 girls with recurrent urinary tract infections and in 5 control girls. No controls presented with more than 2 abnormalities. Infrequent voiding (54% vs 24%, p ⬍0.001), poor fluid intake (53% vs 16%, p ⬍0.001) and functional stool retention (30% vs 13%, p ⬍0.05) were more frequently disclosed in girls with recurrent urinary tract infections than in control girls. In contrast, the frequency of inadequate stool hygiene or toilet habits was similar in patients and controls (14% and 13%, respectively). Conclusions: The evaluation of girls with recurrent urinary tract infections should focus on identifying behavioral aspects, including infrequent voiding, poor fluid intake and functional stool retention. KEY WORDS: urinary tract infections, urination, risk factors, hygiene, constipation

Recurrent urinary tract infections are common in girls, resulting in considerable morbidity, and they are often vexing management problems for pediatricians. This diagnosis leads to diagnostic imaging to uncover anatomical abnormalities.1, 2 Nonetheless, the majority of children 3 years or older with recurrent urinary tract infections do not have congenital abnormalities of the urinary tract. Recent uncontrolled data suggest that girls with recurrent urinary tract infections have behavioral abnormalities, including infrequent voiding, poor fluid intake, functional stool retention, voiding dysfunction, or inadequate anogenital hygiene or toilet habits.3 We evaluated these abnormalities and family history in a group of Swiss girls with recurrent urinary tract infections and in a matched control group. MATERIALS AND METHODS

Eligible for the study were girls with normal renal tract ultrasonography referred to the division of pediatric nephrology, University of Bern, Switzerland for evaluation of 3 or more symptomatic urinary tract infections. The diagnosis of urinary tract infection was made by the referring physicians in the presence of suggestive symptoms using a clean catch urine specimen sent for urinalysis and culture. Patients with the first infection at age 36 months or younger, patients with asymptomatic urinary tract infections, adolescents with a history of sexual activity, patients with history and findings

suggestive of sexual abuse, patients with known urinary tract malformations or neuropathic bladder dysfunction, patients with moderate to severe mental retardation or disorders of posture and movement and patients with overt encopresis were excluded. Between 2001 and 2003, 90 girls 3.9 to 16 years old (median age 8.4) were prospectively evaluated. None of the patients had history of a recent (8 weeks or less) urinary tract infection. They underwent evaluation, including a complete history, physical and neurological examinations, urinalysis, an extensive written questionnaire, a voiding-drinking diary and a noninvasive urodynamic assessment. The extensive written questionnaire evaluated family history, urinary, bowel and toilet habits, and anogenital hygiene by closed questions. The volume of any intake or urination was recorded for 3 days by a voiding-drinking diary. For this purpose each subject received several graduated measuring cups. Daytime functional bladder capacity was taken as the maximum voided volume recorded excluding first morning voiding. The quantity of fluid intake from beverage and plain water was also determined. Noninvasive urodynamic assessment was done according to our standard procedure.3 Briefly, the children were asked to void when they sensed the call to micturition. Subsequently the urine flow rate (by a uroflowmeter) and electromyographic activity of the external urinary sphincter (by perineal surface electrodes) were assessed. The diagnosis of dysfunctional voiding was made in patients with an interrupted urinary stream and unsustained relaxation of the pelvic floor muscles during micturition. Finally, voiding cystourethrography was performed in girls with history of upper urinary tract infections. Vesicoureteral

Accepted for publication November 14, 2003. Study received local ethics committee approval. Supported by the Associazione Bambino Nefropatico. * Correspondence: Department of Pediatrics, San Giovanni Hospital, 6500 Bellinzona, Switzerland (e-mail: mario.bianchetti@ pediatrician.ch). 1663

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reflux was graded according to the International Reflux Study Committee.4 Lower and upper urinary tract infections were differentiated based on clinical history. The diagnosis of lower urinary tract infection was retained in girls with a history of pain on micturition, incontinence, urgency, frequency or suprapubic pain, while that of upper urinary tract infection was retained in those with an additional history of chills, fever (rectal body temperature 38.5C or more) and abdominal or back pain.3 The Appendix shows the working definitions of infrequent voiding, functional stool retention, poor fluid intake from beverage and plain water, and inadequate anogenital hygiene or toilet habits that were used.3 The written questionnaire and the voiding-drinking diary were also applied to a control group of 45 girls 4.0 to 14 years old (median age 7.3). None of them had a history of urinary tract infections. They had a history of idiopathic childhood nephrotic syndrome cured for 2 or more years (9 controls), allergic rhinitis (19), treated celiac disease (12) or tensiontype headache (5). The chi-square test for k independent samples with the Yates correction for continuity was used for analysis with p ⬍0.05 considered statistically significant. RESULTS

Of the 90 girls in the survey 60 who were 3.9 to 16 years old (median age 8.3) had a history of lower urinary tract infections. The remaining 30 girls, who were 4.5 to 14 years old (median age 9.2) had history of mixed urinary tract infections, namely upper in 16, and upper and lower in 14. Family history was positive for recurrent urinary tract infections in 42% of patients and in 11% of controls (p ⬍0.001, see table). Behavioral abnormalities were also more frequently noted in girls with recurrent urinary tract infections than in controls (81% vs 56%, p ⬍0.01). There were 137 abnormalities in 73 girls with recurrent urinary tract infections and 30 abnormalities in 25 controls. Two or more abnormalities were noted in 48 girls with recurrent urinary tract infections (2 in 32 and 3 in 16) and in 5 controls, of whom none presented with more than 2 abnormalities. Infrequent voiding (54% vs 24%, p ⬍0.001), poor fluid intake (53% vs 16%, p ⬍0.001) and functional stool retention (30% vs 13%, p ⬍0.05) were more frequently observed in girls with recurrent urinary tract infections than in controls. In contrast, the frequency of inadequate anogenital hygiene or toilet habits was similar in patients and controls (14% and 13%, respectively). Noninvasive urodynamic assessment in girls with recurrent urinary tract infections revealed signs consistent with dysfunctional voiding in 19 (20%). Vesicoureteral reflux was detected by voiding cystography in 7 of the 30 girls (23%) with a history of mixed urinary tract infections. It was unilateral in 4 cases and bilateral in 3. Reflux grade was I to III in 6, 3 and 1 renal units, respectively. Four girls with recurrent urinary tract infections were consistently found to have vesicoureteral reflux and dysfunctional voiding. DISCUSSION

The current controlled trial indicates that Swiss girls with normal renal tract ultrasonography referred for the evaluaFamily history and behavioral abnormalities in 90 girls with recurrent urinary tract infections and in 45 controls No. Pts (%)

No. Controls (%)

p Value

Pos family history 38 (42) 5 (11) ⬍0.001 Abnormalities: 73 (81) 25 (56) ⬍0.01 Infrequent voiding 49 (54) 11 (24) ⬍0.001 Poor fluid intake 48 (53) 7 (16) ⬍0.001 Functional stool retention 27 (30) 6 (13) ⬍0.05 Inadequate toilet habit hygiene 13 (14) 6 (13) Not significant Two or more abnormalities were found in 48 patients (53%) and 5 controls (11%).

tion of 3 or more symptomatic urinary tract infections often present with a corresponding family history and behavioral abnormalities such as infrequent voiding, poor fluid intake and functional stool retention. The major limitations of this study were the limited financial resources that prevented us from performing renal tract ultrasound and urodynamic assessment in the control group. Furthermore, it is tempting to assume some recall bias. Parents with children who have recurrent urinary tract infections might be more likely to recall that they had urinary infections than parents of children without urinary infections. Although some bacteria are more virulent in the urinary tract, the pedigrees of our patients suggest a familial predisposition. Girls with recurrent urinary tract infections tend to mimic some behavioral habits of their parents or they have a genetic susceptibility to urinary tract infections resulting from a greater propensity for uropathogens to adhere to the uroepithelium.5–7 Vesicoureteral reflux is more prevalent in children with than without urinary tract infections.1, 4 In this study vesicoureteral reflux was detected in approximately a quarter of the girls with mixed urinary tract infections and it was often associated with dysfunctional voiding, as previously noted.8 However, no voiding cystourethrography was performed in our patients with lower urinary tract infections. Infrequent voiding, poor fluid intake, functional stool retention, and inadequate anogenital hygiene and toilet practices were frequently noted in girls with recurrent urinary tract infections as well as in the control group. Nonetheless, infrequent voiding, poor fluid intake and functional stool retention were more frequent in the girls with urinary tract infections, as previously noted in adults.9 –11 The association of infrequent voiding, poor fluid intake or functional stool retention and urinary tract infections is worthy of speculation. Bacteria are washed out of the bladder by voiding. Most children after age 3 years pass urine 4 to 6 times daily. In some girls the habit develops of passing urine only once or twice daily and cold or dirty toilets are often said to be the reason. However, in some cases infrequent voiding might be acquired following the first urinary infection because of fear of pain on micturition. Whatever the underlying cause, the longer the interval between bladder emptying, the greater might be the opportunity for bacterial multiplication. In addition, infrequent voiding sometimes massively distends the bladder with subsequent poor emptying. Poor fluid intake is a further cause of recurrent urinary tract infections, likely by impairing the elimination of bacteria from the bladder. Finally, the current data confirm the close association of functional stool retention with recurrent urinary tract infections.12 It has been suggested that stool retention causes fecal soiling in the region of the external urethral opening and some urinary retention. Inadequate anogenital hygiene and toilet practices are traditionally considered important causes of recurrent urinary tract infections in adults.13 In this study the frequency of this abnormality was similar in patients and controls. This observation concurs with recent data indicating that in childhood urinary tract infections are not necessarily related to inadequate anogenital hygiene or toilet habits.14

CONCLUSIONS

A combination of inherited and behavioral influences are present in a population of girls with recurrent urinary tract infections, which were not seen in a control population without infections. The evaluation of girls with recurrent urinary tract infections should focus on identifying behavioral aspects, including infrequent voiding, poor fluid intake and functional stool retention, with therapy directed toward correcting abnormal findings.

RECURRENT URINARY TRACT INFECTIONS IN GIRLS APPENDIX

Criteria for the definition of infrequent voiding, poor fluid intake, functional stool retention and inadequate genital hygiene or toilet habits used in the present investigation. Infrequent voiding. At least 2 of the following: – habit of passing urine 3 or less times daily – voiding postponement – increased daytime bladder capacity – daytime urinary incontinence Functional stool retention. At least 3 of the following: – 72-hour or more interval between bowel movements – habit of passing small, hard stools – history of painful defecation – stool retention on abdominal examination after defecation Poor fluid intake (from beverage and plain water): daily fluid intake 600 ml/m2 body surface area or less Inadequate anogenital hygiene or toilet habits. At least 3 of the following: – underpants frequently contaminated with fecal material at the end of the day – passing toilet paper back to front or using 2 or more times the same piece of paper – use of tight fitting clothes – toilet trained child aged 5 years or less – small children using regular toilets (rather than a potty chair)* * These patients do not have sufficient leverage to eliminate stool or urine because they cannot push against the floor. REFERENCES

1. Johnson, C. E.: New advances in childhood urinary tract infections. Pediatr Rev, 20: 335, 1999 2. Larcombe, J.: Urinary tract infection in children. BMJ, 319: 1173, 1999

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3. Mazzola, B. L., Von Vigier, R. O., Marchand, S., Tonz, M. and Bianchetti, M. G.: Behavioral and functional abnormalities linked with recurrent urinary tract infections in girls. J Nephrol, 16: 133, 2003 4. Olbing, H.: Vesico-uretero-renal reflux and the kidney. Pediatr Nephrol, 1: 638, 1987 5. Roberts, J. A.: Factors predisposing to urinary tract infections in children. Pediatr Nephrol, 10: 517, 1996 6. Mannhardt, W., Putzer, M., Zepp, F. and Schulte-Wissermann, H.: Host defense within the urinary tract. II. Signal transducing events activate the uroepithelial defense. Pediatr Nephrol, 10: 573, 1996 7. Mannhardt, W., Becker, A., Putzer, M., Bork, M., Zepp, F., Hacker, J. et al: Host defense within the urinary tract. I. Bacterial adhesion initiates an uroepithelial defense mechanism. Pediatr Nephrol, 10: 568, 1996 8. Greenfield, S. P. and Wan, J.: The relationship between dysfunctional voiding and congenital vesicoureteral reflux. Curr Opin Urol, 10: 607, 2000 9. Adatto, K., Doebele, K. G., Galland, L. and Granowetter, L.: Behavioral factors and urinary tract infection. JAMA, 241: 2525, 1979 10. Eckford, S. D., Keane, D. P., Lamond, E., Jackson, S. R. and Abrams, P.: Hydration monitoring in the prevention of recurrent idiopathic urinary tract infections in pre-menopausal women. Br J Urol, 76: 90, 1995 11. Nygaard, I. and Linder, M.: Thirst at work—an occupational hazard? Int Urogynecol J Pelvic Floor Dysfunct, 8: 340, 1997 12. Blethyn, A. J., Jenkins, H. R., Roberts, R. and Verrier Jones, K.: Radiological evidence of constipation in urinary tract infection. Arch Dis Child, 73: 534, 1995 13. Tchoudomirova, K., Mardh, P. A., Kallings, I., Nilsson, S. and Hellberg, D.: History, clinical findings, sexual behavior and hygiene habits in women with and without recurrent episodes of urinary symptoms. Acta Obstet Gynecol Scand, 77: 654, 1998 14. Jaquiery, A., Stylianopoulos, A., Hogg, G. and Grover, S.: Vulvovaginitis: clinical features, aetiology, and microbiology of the genital tract. Arch Dis Child, 81: 64, 1999