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Is Age at Toilet Training Associated With the Presence of Vesicoureteral Reflux or the Occurrence of Urinary Tract Infection?
Pediatric Urology
Is Age at Toilet Training Associated With the Presence of Vesicoureteral Reflux or the Occurrence of Urinary Tract Infection? John J. Chen,* Hyeong Jun Ahn and George F. Steinhardt From the Department of Preventive Medicine, Stony Brook University, Stony Brook, New York (JJC, HJA), and Departments of Urology, Wayne State University, Detroit and Helen DeVos Children’s Hospital, Grand Rapids, Michigan (GFS)
Abbreviations and Acronyms DES ⫽ dysfunctional elimination syndrome UTI ⫽ urinary tract infection VUR ⫽ vesicoureteral reflux Submitted for publication November 17, 2009. Study received institutional review board approval. * Correspondence: Department of Preventive Medicine, HSC L-3, Room 086, Stony Brook University Medical Center, Stony Brook, New York 11794-8036 (telephone: 631-444-2191; FAX: 631444-7525; e-mail: [email protected]).
Purpose: We sought to determine whether age at toilet training is influenced by a history of vesicoureteral reflux or urinary tract infection. Materials and Methods: We reviewed records on 1,184 patients treated at a pediatric urology practice. All patients had information available regarding age at toilet training, renal sonography and voiding cystourethrography, and presence or absence of urinary tract infection. We evaluated possible associations between vesicoureteral reflux and urinary tract infection, and age at toilet training. Results: Of 1,184 patients 280 had unilateral reflux, 339 had bilateral reflux and 565 had normal anatomy. Also, 926 patients had urinary tract infections. Girls tended to be toilet trained 3 months earlier than boys (p ⬍0.001) in all subgroups (normal anatomy, unilateral reflux, bilateral reflux). Children with and without urinary tract infections were toilet trained at similar ages. However, timing of the first urinary tract infection seemed to be associated with age at toilet training. For girls a urinary tract infection occurring earlier tended to delay toilet training, while earlier toilet training seemed to be associated with a later urinary tract infection (p ⬍0.001). The patterns were similar for boys but were not statistically significant. Conclusions: Age at toilet training seems to be independent of the presence of vesicoureteral reflux. Urinary tract infection itself is not necessarily associated with age at toilet training. However, timing of the first urinary tract infection seems to be related to age at toilet training. Key Words: toilet training; urinary bladder, neurogenic; urinary tract infections; vesico-ureteral reflux
268
www.jurology.com
AGE at toilet training is an important developmental milestone determined by complex interactions between the developing nervous system, the bladder and the social milieu.1 The dependence of this milestone on cognitive perception of the maturing bladder implies a high susceptibility to disruption. Disturbances in toilet training can have medical consequences, since children who persistently wet are more likely to have urinary tract infections.2 The recent literature suggests that some infants with VUR may have urody-
namic abnormalities with obvious implications on voiding habits.3–5 Regarding voiding patterns our work and that of others has demonstrated no association between VUR and subsequent DES.6,7 However, it is possible that purported urodynamic abnormalities associated with reflux influence age at toilet training. To our knowledge this relationship has not specifically been examined. Also, our work and that of others has shown that UTI might promote subsequent dysfunctional voiding.6,8,9 This observation suggests that early UTI
0022-5347/09/1821-0268/0 THE JOURNAL OF UROLOGY® Copyright © 2009 by AMERICAN UROLOGICAL ASSOCIATION
Vol. 182, 268-271, July 2009 Printed in U.S.A. DOI:10.1016/j.juro.2009.02.137
AGE AT TOILET TRAINING, VESICOURETERAL REFLUX AND URINARY TRACT INFECTION
might also impact age at toilet training. We reviewed our data to examine whether infants with VUR and UTI might be expected to toilet train at a different age than normal children.
MATERIALS AND METHODS Patient Data A computerized database was initiated in 1988 to track patients referred to the pediatric urology service at St. Louis University School of Medicine for evaluation and treatment. This institutional review board approved database was closed to further enrollment in 2002. We previously used this database to evaluate associations between DES and VUR status, and UTI.6 Patient enrollment criteria and definitions used in the current analysis were similar. Briefly all patients enrolled underwent renal sonography and voiding cystourethrogram. Patients with normal anatomy (no VUR, no hydronephrosis) usually presented with UTI or DES, or were screened for genitourinary problems (sibling VUR, urethrorrhagia, hematuria). Age at toilet training was defined as age at which the child was fully toilet trained in terms of urine and stool (ie fully transitioned from diapers to normal underwear), based on information provided by the care providers when questioned during clinic visits. This approach to determining age at toilet training has been found useful by others.10 Age at first UTI, if any, was also extracted from the database to evaluate whether there was any effect of early UTI on age at toilet training.
Statistical Analysis For VUR we first grouped subjects according to the presence and laterality of VUR (normal anatomy, unilateral, bilateral). To evaluate the possible relationship between VUR severity and age at toilet training, we further grouped subjects according to the worst grade of VUR into normal, mild (grades I and II) and moderate to severe (grades III to V). For UTI we grouped patients by the presence or absence of UTI. We further divided individuals with UTI into 3 subgroups according to date of first recorded infection relative to toilet training date, ie similar timing (UTI occurred within 6 months of toilet training), earlier (UTI occurred more than 6 months before toilet training) and later (UTI occurred more than 6 months after toilet training).
269
Continuous variables such as age at first UTI and age at toilet training were summarized as mean ⫾ standard deviation. Categorical variables such as gender, VUR subgroup (normal anatomy, unilateral, bilateral) were summarized as frequencies and percentages. Ages at toilet training were compared between boys and girls using 2-sample t tests. Within each gender ages at toilet training were further compared using ANOVA among multiple subgroups (eg VUR status) and using 2-sample t tests for 2 subgroups (eg UTI status). Data for timing of first UTI relative to age at toilet training were analyzed using ANOVA within each gender. Duncan’s post hoc multiple range test was used for further comparison of subgroups when overall ANOVA was statistically significant. All statistical analyses were done using SAS®, version 9.0 software, with p ⬍0.05 considered statistically significant.
RESULTS Table 1 summarizes age at toilet training for boys and girls stratified by VUR group (normal anatomy, unilateral, bilateral) and UTI status. Girls were toilet trained 3 months earlier than boys (p ⬍0.001). This pattern was consistent among all VUR and UTI subgroups. However, for each gender the 3 VUR subgroups and 2 UTI subgroups had similar ages at toilet training. Also, for each gender age at toilet training did not seem to differ according to VUR severity. We also analyzed cases according to age at first infection in relation to age at toilet training (table 2). Although UTI did not affect age at toilet training, the timing of the first UTI seemed to be related to the timing of toilet training. For girls with UTI at an earlier age the age at toilet training tended to be several months later compared to other girls, whereas those with a UTI later tended to be toilet trained earlier compared to other girls (p ⬍0.0001). The patterns were similar for boys, although not statistically significant.
DISCUSSION Age at toilet training is an important developmental milestone, and disturbances in toilet training can
Table 1. Patient age at toilet training stratified by UTI, VUR subgroup and gender Females Variable VUR: Unilat Bilat Absent UTI: Present Absent Totals
No. Pts Overall
No.
Males
Mean ⫾ SD Age (mos)
p Value
No.
Mean ⫾ SD Age (mos)
p Value
Overall p Value
280 339 565
236 286 480
26.6 ⫾ 7.6 26.3 ⫾ 7.1 26.5 ⫾ 8.3
0.91
44 53 85
30.0 ⫾ 7.5 29.9 ⫾ 6.9 29.3 ⫾ 9.6
0.86
0.0054 0.0008 0.006
926 258 1,184
843 159 1,002
26.4 ⫾ 7.9 27.0 ⫾ 7.4 26.5 ⫾ 7.8
0.32
83 99 182
30.0 ⫾ 8.3 29.4 ⫾ 8.4 29.6 ⫾ 8.4
0.64
⬍0.0001 0.021 ⬍0.0001
270
AGE AT TOILET TRAINING, VESICOURETERAL REFLUX AND URINARY TRACT INFECTION
Table 2. Average age at toilet training stratified by age at first UTI and gender Timing of UTI and Toilet Training* No UTI Overall No. pts Females: No. Mean ⫾ SD age (mos) Males: No. Mean ⫾ SD age (mos) Overall p value
Similar
UTI Earlier
UTI Later
p Value (ANOVA)
258
224
190
511
159 27.0 ⫾ 7.4
211 26.8 ⫾ 7.1
169 29.0 ⫾ 10.1†
462 25.2 ⫾ 7.1†
⬍0.0001
99 29.4 ⫾ 8.4 0.021
13 31.5 ⫾ 8.3 0.022
21 32.0 ⫾ 9.8 0.21
49 28.7 ⫾ 7.6 0.0011
0.39
* Similar timing indicates UTI occurred within 6 months of toilet training, earlier indicates more than 6 months before and later indicates more than 6 months after. † Statistically significantly higher than other subgroups based on Duncan’s post hoc multiple range test.
have medical consequences. There has been much investigation regarding the interrelationships between VUR, UTI and DES. Our recent analyses suggest no association between VUR and DES, even for patients diagnosed with VUR before age 6 months.6,11 Shaikh et al reported similar observations.7 However, it is possible that VUR is complicated by underlying urodynamic abnormalities in infants and older children.12,13 Also, voiding dysfunction in an already toilet trained child may be different from that in a toilet training child regarding its association with the etiology of reflux and/or recurrent urinary infection. No previous analysis has focused on whether VUR affects age at toilet training, as one might expect if the urodynamic abnormalities had clinical significance. In this large cohort we found no effect of VUR (unilateral or bilateral) on age at toilet training. While delay in toilet training confers risk of UTI, it is equally apparent that UTI can reasonably be a cause for delay in achieving urinary control. Dysuria attendant to infection can conceivably lead to postponement of voiding similar to the way rectal discomfort deriving from large bowel movements leads to fecal hoarding, thereby perpetuating the clinical problem. We found that while the occurrence of UTI is not associated with age at toilet training, the timing of the first UTI seems to be associated with age at toilet training. Children with a UTI at least 6 months before toilet training tend to have delayed toilet training compared to children without UTI. There could be several reasons for this finding. For example an early UTI might contribute to bladder irritability that is more difficult for the infant to learn to control, hence delaying age at toilet training. Also, early vs late UTI might result in more dyssynergic voiding with a similar delay. In examining the associations between UTI and toilet training we found more subsequent UTIs in children undergoing toilet training early. It may be that pre-
mature toilet training results in inadequate bladder control, allowing for the development of UTI. Since UTIs are positively associated with subsequent DES, the current epidemic of DES may derive from attempts to toilet train prematurely, although some suggest that toilet training ages are increasing.14 Our investigation has several limitations. The study is retrospective in nature and, thus, the observed association does not infer causality. Also, possible selection bias exists since all enrolled patients were referred to our pediatric urology practice. However, this is the largest database relating to these patients, and as such our findings have applicability to patients typically seen at a pediatric practice, particularly those with UTI and VUR. Additionally our reliance on parental information regarding date of toilet training may result in recall bias. However, others have noted this type of assessment to be useful.10 To simplify the presentation we have combined all grades of VUR in the current analysis and grouped only according to laterality (unilateral or bilateral). Our previous analyses have revealed that VUR grade is not an important factor associated with DES.6,11 UTI was defined by the usually accepted criteria,15 and for this analysis we did not distinguish febrile UTI from that with lower urinary tract symptoms. Since our database does not include urodynamic information, we cannot comment on the urodynamic status of the patients with VUR. We can only state that toilet training occurs at a normal age independent of VUR status. Many other factors, such as race, single parenting and socioeconomic standing, may have an impact on age at toilet training.16 Perhaps an equally important contributing factor is the temperament of the child.17 These factors were not considered in the current evaluation. Our findings should inspire further investi-
AGE AT TOILET TRAINING, VESICOURETERAL REFLUX AND URINARY TRACT INFECTION
gations on the interrelationships among these important parameters.
271
first UTI occurs seems to have a significant association with age at toilet training.
CONCLUSIONS Children with VUR begin toilet training at ages comparable to normal children. Age at which the
ACKNOWLEDGMENTS Wenyang Mao provided data management support.
REFERENCES 1. Brazelton TB, Christophersen ER, Frauman AC, Gorski PA, Poole JM, Stadtler AC et al: Instruction, timeliness, and medical influences affecting toilet training. Pediatrics 1999; 103: 1353. 2. Bakker E, van Sprundel M, van der Auwera JC, van Gool JD and Wyndaele JJ: Voiding habits and wetting in a population of 4332 Belgian schoolchildren aged between 10 and 14 years. Scand J Urol Nephrol 2002; 36: 354. 3. Greenfield SP and Wan J: The relationship between dysfunctional voiding and congenital vesicoureteral reflux. Curr Opin Urol 2000; 10: 607. 4. Godley ML, Desai D, Yeung CK, Dhillon HK, Duffy PG and Ransley PG: The relationship between early renal status, and the resolution of vesicoureteric reflux and bladder function at 16 months. BJU Int 2001; 87: 457. 5. Sjostrom S, Sillen U, Bachelard M, Hansson S and Stokland E: Spontaneous resolution of high grade infantile vesicoureteral reflux. J Urol 2004; 172: 694. 6. Chen JJ, Mao W, Homayoon K and Steinhardt GF: A multivariate analysis of dysfunctional elimination syndrome, and its relationships with gen-
der, urinary tract infection and vesicoureteral reflux in children. J Urol 2004; 171: 1907. 7. Shaikh N, Hoberman A, Wise B, Kurs-Lasky M, Kearney D, Naylor S et al: Dysfunctional elimination syndrome: is it related to urinary tract infection or vesicoureteral reflux diagnosed early in life? Pediatrics 2003; 112: 1134.
12. Yeung CK, Godley ML, Dhillon HK, Duffy PG and Ransley PG: Urodynamic patterns in infants with normal lower urinary tracts or primary vesicoureteric reflux. Br J Urol 1998; 81: 461. 13. Soygur T, Arikan N, Yesilli C and Gogus O: Relationship among pediatric voiding dysfunction and vesicoureteral reflux and renal scars. Urology 1999; 54: 905.
8. Hellstrom A, Hanson E, Hansson S, Hjalmas K and Jodal U: Association between urinary symptoms at 7 years old and previous urinary-tract infection. Arch Dis Child 1991; 66: 232.
14. Bakker E and Wyndaele JJ: Changes in the toilet training of children during the last 60 years: the cause of an increase in lower urinary tract dysfunction? BJU Int 2000; 86: 248.
9. Hansen A, Hansen B and Dahm TL: Urinary tract infection, day wetting and other voiding symptoms in seven- to eight-year-old Danish children. Acta Paediatr 1997; 86: 1345.
15. Bergman DA, Baltz RD and Cooley JR; American Academy of Pediatrics Committee on Quality Improvement: Practice parameters: the diagnosis, treatment, and evaluation of the initial urinary tract infection in febrile infants and young children. Pediatrics 1999; 103: 843.
10. Bloom DA, Seeley WW, Ritchey ML and McGuire EJ: Toilet habits and continence in children: an opportunity sampling in search of normal parameters. J Urol 1993; 149: 1087. 11. Homayoon K, Chen JJ, Cummings JM and Steinhardt GF: Voiding dysfunction: outcome in infants with congenital vesicoureteral reflux. Urology 2005; 66: 1091.
16. Schum TR, McAuliffe TL, Simms MD, Walter JA, Lewis M and Pupp R: Factors associated with toilet training in the 1990s. Ambul Pediatr 2001; 1: 79. 17. Schonwald A, Sherritt L, Stadtler A and Bridgemohan C: Factors associated with difficult toilet training. Pediatrics 2004; 113: 1753.
Is Age at Toilet Training Associated With the Presence of Vesicoureteral Reflux or the Occurrence of Urinary Tract Infection? John J. Chen,* Hyeong Jun Ahn and George F. Steinhardt From the Department of Preventive Medicine, Stony Brook University, Stony Brook, New York (JJC, HJA), and Departments of Urology, Wayne State University, Detroit and Helen DeVos Children’s Hospital, Grand Rapids, Michigan (GFS)
Abbreviations and Acronyms DES ⫽ dysfunctional elimination syndrome UTI ⫽ urinary tract infection VUR ⫽ vesicoureteral reflux Submitted for publication November 17, 2009. Study received institutional review board approval. * Correspondence: Department of Preventive Medicine, HSC L-3, Room 086, Stony Brook University Medical Center, Stony Brook, New York 11794-8036 (telephone: 631-444-2191; FAX: 631444-7525; e-mail: [email protected]).
Purpose: We sought to determine whether age at toilet training is influenced by a history of vesicoureteral reflux or urinary tract infection. Materials and Methods: We reviewed records on 1,184 patients treated at a pediatric urology practice. All patients had information available regarding age at toilet training, renal sonography and voiding cystourethrography, and presence or absence of urinary tract infection. We evaluated possible associations between vesicoureteral reflux and urinary tract infection, and age at toilet training. Results: Of 1,184 patients 280 had unilateral reflux, 339 had bilateral reflux and 565 had normal anatomy. Also, 926 patients had urinary tract infections. Girls tended to be toilet trained 3 months earlier than boys (p ⬍0.001) in all subgroups (normal anatomy, unilateral reflux, bilateral reflux). Children with and without urinary tract infections were toilet trained at similar ages. However, timing of the first urinary tract infection seemed to be associated with age at toilet training. For girls a urinary tract infection occurring earlier tended to delay toilet training, while earlier toilet training seemed to be associated with a later urinary tract infection (p ⬍0.001). The patterns were similar for boys but were not statistically significant. Conclusions: Age at toilet training seems to be independent of the presence of vesicoureteral reflux. Urinary tract infection itself is not necessarily associated with age at toilet training. However, timing of the first urinary tract infection seems to be related to age at toilet training. Key Words: toilet training; urinary bladder, neurogenic; urinary tract infections; vesico-ureteral reflux
268
www.jurology.com
AGE at toilet training is an important developmental milestone determined by complex interactions between the developing nervous system, the bladder and the social milieu.1 The dependence of this milestone on cognitive perception of the maturing bladder implies a high susceptibility to disruption. Disturbances in toilet training can have medical consequences, since children who persistently wet are more likely to have urinary tract infections.2 The recent literature suggests that some infants with VUR may have urody-
namic abnormalities with obvious implications on voiding habits.3–5 Regarding voiding patterns our work and that of others has demonstrated no association between VUR and subsequent DES.6,7 However, it is possible that purported urodynamic abnormalities associated with reflux influence age at toilet training. To our knowledge this relationship has not specifically been examined. Also, our work and that of others has shown that UTI might promote subsequent dysfunctional voiding.6,8,9 This observation suggests that early UTI
0022-5347/09/1821-0268/0 THE JOURNAL OF UROLOGY® Copyright © 2009 by AMERICAN UROLOGICAL ASSOCIATION
Vol. 182, 268-271, July 2009 Printed in U.S.A. DOI:10.1016/j.juro.2009.02.137
AGE AT TOILET TRAINING, VESICOURETERAL REFLUX AND URINARY TRACT INFECTION
might also impact age at toilet training. We reviewed our data to examine whether infants with VUR and UTI might be expected to toilet train at a different age than normal children.
MATERIALS AND METHODS Patient Data A computerized database was initiated in 1988 to track patients referred to the pediatric urology service at St. Louis University School of Medicine for evaluation and treatment. This institutional review board approved database was closed to further enrollment in 2002. We previously used this database to evaluate associations between DES and VUR status, and UTI.6 Patient enrollment criteria and definitions used in the current analysis were similar. Briefly all patients enrolled underwent renal sonography and voiding cystourethrogram. Patients with normal anatomy (no VUR, no hydronephrosis) usually presented with UTI or DES, or were screened for genitourinary problems (sibling VUR, urethrorrhagia, hematuria). Age at toilet training was defined as age at which the child was fully toilet trained in terms of urine and stool (ie fully transitioned from diapers to normal underwear), based on information provided by the care providers when questioned during clinic visits. This approach to determining age at toilet training has been found useful by others.10 Age at first UTI, if any, was also extracted from the database to evaluate whether there was any effect of early UTI on age at toilet training.
Statistical Analysis For VUR we first grouped subjects according to the presence and laterality of VUR (normal anatomy, unilateral, bilateral). To evaluate the possible relationship between VUR severity and age at toilet training, we further grouped subjects according to the worst grade of VUR into normal, mild (grades I and II) and moderate to severe (grades III to V). For UTI we grouped patients by the presence or absence of UTI. We further divided individuals with UTI into 3 subgroups according to date of first recorded infection relative to toilet training date, ie similar timing (UTI occurred within 6 months of toilet training), earlier (UTI occurred more than 6 months before toilet training) and later (UTI occurred more than 6 months after toilet training).
269
Continuous variables such as age at first UTI and age at toilet training were summarized as mean ⫾ standard deviation. Categorical variables such as gender, VUR subgroup (normal anatomy, unilateral, bilateral) were summarized as frequencies and percentages. Ages at toilet training were compared between boys and girls using 2-sample t tests. Within each gender ages at toilet training were further compared using ANOVA among multiple subgroups (eg VUR status) and using 2-sample t tests for 2 subgroups (eg UTI status). Data for timing of first UTI relative to age at toilet training were analyzed using ANOVA within each gender. Duncan’s post hoc multiple range test was used for further comparison of subgroups when overall ANOVA was statistically significant. All statistical analyses were done using SAS®, version 9.0 software, with p ⬍0.05 considered statistically significant.
RESULTS Table 1 summarizes age at toilet training for boys and girls stratified by VUR group (normal anatomy, unilateral, bilateral) and UTI status. Girls were toilet trained 3 months earlier than boys (p ⬍0.001). This pattern was consistent among all VUR and UTI subgroups. However, for each gender the 3 VUR subgroups and 2 UTI subgroups had similar ages at toilet training. Also, for each gender age at toilet training did not seem to differ according to VUR severity. We also analyzed cases according to age at first infection in relation to age at toilet training (table 2). Although UTI did not affect age at toilet training, the timing of the first UTI seemed to be related to the timing of toilet training. For girls with UTI at an earlier age the age at toilet training tended to be several months later compared to other girls, whereas those with a UTI later tended to be toilet trained earlier compared to other girls (p ⬍0.0001). The patterns were similar for boys, although not statistically significant.
DISCUSSION Age at toilet training is an important developmental milestone, and disturbances in toilet training can
Table 1. Patient age at toilet training stratified by UTI, VUR subgroup and gender Females Variable VUR: Unilat Bilat Absent UTI: Present Absent Totals
No. Pts Overall
No.
Males
Mean ⫾ SD Age (mos)
p Value
No.
Mean ⫾ SD Age (mos)
p Value
Overall p Value
280 339 565
236 286 480
26.6 ⫾ 7.6 26.3 ⫾ 7.1 26.5 ⫾ 8.3
0.91
44 53 85
30.0 ⫾ 7.5 29.9 ⫾ 6.9 29.3 ⫾ 9.6
0.86
0.0054 0.0008 0.006
926 258 1,184
843 159 1,002
26.4 ⫾ 7.9 27.0 ⫾ 7.4 26.5 ⫾ 7.8
0.32
83 99 182
30.0 ⫾ 8.3 29.4 ⫾ 8.4 29.6 ⫾ 8.4
0.64
⬍0.0001 0.021 ⬍0.0001
270
AGE AT TOILET TRAINING, VESICOURETERAL REFLUX AND URINARY TRACT INFECTION
Table 2. Average age at toilet training stratified by age at first UTI and gender Timing of UTI and Toilet Training* No UTI Overall No. pts Females: No. Mean ⫾ SD age (mos) Males: No. Mean ⫾ SD age (mos) Overall p value
Similar
UTI Earlier
UTI Later
p Value (ANOVA)
258
224
190
511
159 27.0 ⫾ 7.4
211 26.8 ⫾ 7.1
169 29.0 ⫾ 10.1†
462 25.2 ⫾ 7.1†
⬍0.0001
99 29.4 ⫾ 8.4 0.021
13 31.5 ⫾ 8.3 0.022
21 32.0 ⫾ 9.8 0.21
49 28.7 ⫾ 7.6 0.0011
0.39
* Similar timing indicates UTI occurred within 6 months of toilet training, earlier indicates more than 6 months before and later indicates more than 6 months after. † Statistically significantly higher than other subgroups based on Duncan’s post hoc multiple range test.
have medical consequences. There has been much investigation regarding the interrelationships between VUR, UTI and DES. Our recent analyses suggest no association between VUR and DES, even for patients diagnosed with VUR before age 6 months.6,11 Shaikh et al reported similar observations.7 However, it is possible that VUR is complicated by underlying urodynamic abnormalities in infants and older children.12,13 Also, voiding dysfunction in an already toilet trained child may be different from that in a toilet training child regarding its association with the etiology of reflux and/or recurrent urinary infection. No previous analysis has focused on whether VUR affects age at toilet training, as one might expect if the urodynamic abnormalities had clinical significance. In this large cohort we found no effect of VUR (unilateral or bilateral) on age at toilet training. While delay in toilet training confers risk of UTI, it is equally apparent that UTI can reasonably be a cause for delay in achieving urinary control. Dysuria attendant to infection can conceivably lead to postponement of voiding similar to the way rectal discomfort deriving from large bowel movements leads to fecal hoarding, thereby perpetuating the clinical problem. We found that while the occurrence of UTI is not associated with age at toilet training, the timing of the first UTI seems to be associated with age at toilet training. Children with a UTI at least 6 months before toilet training tend to have delayed toilet training compared to children without UTI. There could be several reasons for this finding. For example an early UTI might contribute to bladder irritability that is more difficult for the infant to learn to control, hence delaying age at toilet training. Also, early vs late UTI might result in more dyssynergic voiding with a similar delay. In examining the associations between UTI and toilet training we found more subsequent UTIs in children undergoing toilet training early. It may be that pre-
mature toilet training results in inadequate bladder control, allowing for the development of UTI. Since UTIs are positively associated with subsequent DES, the current epidemic of DES may derive from attempts to toilet train prematurely, although some suggest that toilet training ages are increasing.14 Our investigation has several limitations. The study is retrospective in nature and, thus, the observed association does not infer causality. Also, possible selection bias exists since all enrolled patients were referred to our pediatric urology practice. However, this is the largest database relating to these patients, and as such our findings have applicability to patients typically seen at a pediatric practice, particularly those with UTI and VUR. Additionally our reliance on parental information regarding date of toilet training may result in recall bias. However, others have noted this type of assessment to be useful.10 To simplify the presentation we have combined all grades of VUR in the current analysis and grouped only according to laterality (unilateral or bilateral). Our previous analyses have revealed that VUR grade is not an important factor associated with DES.6,11 UTI was defined by the usually accepted criteria,15 and for this analysis we did not distinguish febrile UTI from that with lower urinary tract symptoms. Since our database does not include urodynamic information, we cannot comment on the urodynamic status of the patients with VUR. We can only state that toilet training occurs at a normal age independent of VUR status. Many other factors, such as race, single parenting and socioeconomic standing, may have an impact on age at toilet training.16 Perhaps an equally important contributing factor is the temperament of the child.17 These factors were not considered in the current evaluation. Our findings should inspire further investi-
AGE AT TOILET TRAINING, VESICOURETERAL REFLUX AND URINARY TRACT INFECTION
gations on the interrelationships among these important parameters.
271
first UTI occurs seems to have a significant association with age at toilet training.
CONCLUSIONS Children with VUR begin toilet training at ages comparable to normal children. Age at which the
ACKNOWLEDGMENTS Wenyang Mao provided data management support.
REFERENCES 1. Brazelton TB, Christophersen ER, Frauman AC, Gorski PA, Poole JM, Stadtler AC et al: Instruction, timeliness, and medical influences affecting toilet training. Pediatrics 1999; 103: 1353. 2. Bakker E, van Sprundel M, van der Auwera JC, van Gool JD and Wyndaele JJ: Voiding habits and wetting in a population of 4332 Belgian schoolchildren aged between 10 and 14 years. Scand J Urol Nephrol 2002; 36: 354. 3. Greenfield SP and Wan J: The relationship between dysfunctional voiding and congenital vesicoureteral reflux. Curr Opin Urol 2000; 10: 607. 4. Godley ML, Desai D, Yeung CK, Dhillon HK, Duffy PG and Ransley PG: The relationship between early renal status, and the resolution of vesicoureteric reflux and bladder function at 16 months. BJU Int 2001; 87: 457. 5. Sjostrom S, Sillen U, Bachelard M, Hansson S and Stokland E: Spontaneous resolution of high grade infantile vesicoureteral reflux. J Urol 2004; 172: 694. 6. Chen JJ, Mao W, Homayoon K and Steinhardt GF: A multivariate analysis of dysfunctional elimination syndrome, and its relationships with gen-
der, urinary tract infection and vesicoureteral reflux in children. J Urol 2004; 171: 1907. 7. Shaikh N, Hoberman A, Wise B, Kurs-Lasky M, Kearney D, Naylor S et al: Dysfunctional elimination syndrome: is it related to urinary tract infection or vesicoureteral reflux diagnosed early in life? Pediatrics 2003; 112: 1134.
12. Yeung CK, Godley ML, Dhillon HK, Duffy PG and Ransley PG: Urodynamic patterns in infants with normal lower urinary tracts or primary vesicoureteric reflux. Br J Urol 1998; 81: 461. 13. Soygur T, Arikan N, Yesilli C and Gogus O: Relationship among pediatric voiding dysfunction and vesicoureteral reflux and renal scars. Urology 1999; 54: 905.
8. Hellstrom A, Hanson E, Hansson S, Hjalmas K and Jodal U: Association between urinary symptoms at 7 years old and previous urinary-tract infection. Arch Dis Child 1991; 66: 232.
14. Bakker E and Wyndaele JJ: Changes in the toilet training of children during the last 60 years: the cause of an increase in lower urinary tract dysfunction? BJU Int 2000; 86: 248.
9. Hansen A, Hansen B and Dahm TL: Urinary tract infection, day wetting and other voiding symptoms in seven- to eight-year-old Danish children. Acta Paediatr 1997; 86: 1345.
15. Bergman DA, Baltz RD and Cooley JR; American Academy of Pediatrics Committee on Quality Improvement: Practice parameters: the diagnosis, treatment, and evaluation of the initial urinary tract infection in febrile infants and young children. Pediatrics 1999; 103: 843.
10. Bloom DA, Seeley WW, Ritchey ML and McGuire EJ: Toilet habits and continence in children: an opportunity sampling in search of normal parameters. J Urol 1993; 149: 1087. 11. Homayoon K, Chen JJ, Cummings JM and Steinhardt GF: Voiding dysfunction: outcome in infants with congenital vesicoureteral reflux. Urology 2005; 66: 1091.
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