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Meta-Analysis
. 2019 Feb 20;2(2):CD001532.
doi: 10.1002/14651858.CD001532.pub5.

Interventions for primary vesicoureteric reflux

Gabrielle Williams  1 , Elisabeth M Hodson, Jonathan C Craig
Affiliations
Meta-Analysis

Interventions for primary vesicoureteric reflux

Gabrielle Williams et al. Cochrane Database Syst Rev. .

Abstract

Background: Vesicoureteric reflux (VUR) results in urine passing retrograde up the ureter. Urinary tract infections (UTI) associated with VUR have been considered a cause of permanent renal parenchymal damage in children with VUR. Management has been directed at preventing UTI by antibiotic prophylaxis and/or surgical correction of VUR. This is an update of a review first published in 2004 and updated in 2007 and 2011.

Objectives: The aim of this review was to evaluate the available evidence for both benefits and harms of the currently available treatment options for primary VUR: operative, non-operative or no intervention.

Search methods: We searched the Cochrane Kidney and Transplant Specialised Register to 3 May 2018 through contact with the Information Specialist using search terms relevant to this review. Studies contained in the Specialised Register are identified through search strategies specifically designed for CENTRAL, MEDLINE, and EMBASE; handsearching conference proceedings, and searching the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.

Selection criteria: RCTs in any language comparing any treatment of VUR and any combination of therapies.

Data collection and analysis: Two authors independently determined study eligibility, assessed quality and extracted data. Dichotomous outcomes were expressed as risk ratios (RR) with 95% confidence intervals (CI) and continuous data as mean differences (MD) with 95% CI. Data were pooled using the random effects model.

Main results: Thirty four studies involving 4001 children were included. Interventions included; long-term low-dose antibiotics, surgical reimplantation of ureters, endoscopic injection treatment, probiotics, cranberry products, circumcision, and oxybutynin. Interventions were used alone and in combinations. The quality of conduct and reporting of these studies was variable, with many studies omitting crucial methodological information used to assess the risk of bias. Only four of the 34 studies were considered at low risk of bias across all fields of study quality. The majority of studies had many areas of uncertainty in the risk of bias fields, reflecting missing detail rather than stated poor design.Low-dose antibiotic prophylaxis compared to no treatment/placebo may make little or no difference to the risk of repeat symptomatic UTI (9 studies, 1667 children: RR 0.77, 95% CI 0.54 to 1.09; low certainty evidence) and febrile UTI (RR 0.83, 95% CI 0.56 to 1.21; low certainty evidence) at one to two years. At one to three years, antibiotic prophylaxis made little or no difference to the risk of new or progressive renal damage on DMSA scan (8 studies, 1503 children: RR 0.73, 95% CI 0.33 to 1.61; low certainty evidence). Adverse events were reported in four studies with little or no difference between treatment groups (1056 children: RR 0.94, 95% CI 0.81 to 1.08; ), but antibiotics increased the likelihood of bacterial drug resistance threefold (187 UTIs: RR 2.97, 95% CI 1.54 to 5.74; moderate certainty evidence).Seven studies compared long-term antibiotic prophylaxis alone with surgical reimplantation of ureters plus antibiotics, but only two reported the outcome febrile UTI (429 children). Surgery plus antibiotic treatment may reduce the risk of repeat febrile UTI by 57% (RR 0.43, 95% CI 0.27 to 0.70; moderate certainty evidence). There was little or no difference in the risk of new kidney defects detected using intravenous pyelogram at 4 to 5 years (4 studies, 572 children, RR 1.09, 95% CI 0.79 to 1.49; moderate certainty evidence)Four studies compared endoscopic injection with antibiotics alone and three reported the outcome febrile UTI. This analysis showed little or no difference in the risk of febrile UTI with endoscopic injection compared to antibiotics (RR 0.74, 95% CI 0.31 to 1.78; low certainty evidence). Four studies involving 425 children compared two different materials for endoscopic injection under the ureters (polydimethylsiloxane (Macroplastique) versus dextranomer/hyaluronic acid polymer (Deflux), glutaraldehyde cross-linked (GAX) collagen (GAX) 35 versus GAX 65 and Deflux versus polyacrylate polyalcohol copolymer (VANTRIS)) but only one study (255 children, low certainty evidence) had the outcome of febrile UTI and it reported no difference between the materials. All four studies reported rates of resolution of VUR, and the two studies comparing Macroplastique with Deflux showed that Macroplastique was probably superior to dextranomer/hyaluronic acid polymer (3 months: RR 0.50, 95% CI 0.33 to 0.78; 12 months: RR 0.54 95% CI 0.35 to 0.83; low certainty evidence)Two studies compared probiotic treatment with antibiotics and showed little or no difference in risk of repeat symptomatic UTI (RR 0.82 95% CI 0.56 to 1.21; low certainty evidence)Single studies compared circumcision with antibiotics, cranberry products with no treatment, oxybutynin with placebo, two different surgical techniques and endoscopic injection with no treatment.

Authors' conclusions: Compared with no treatment, the use of long-term, low-dose antibiotics may make little or no difference to the number of repeat symptomatic and febrile UTIs in children with VUR (low certainty evidence). Considerable variation in the study designs and subsequent findings prevented drawing firm conclusions on efficacy of antibiotic treatment.The added benefit of surgical or endoscopic correction of VUR over antibiotic treatment alone remains unclear since few studies comparing the same treatment and with relevant clinical outcomes were available for analysis.

PubMed Disclaimer

Conflict of interest statement

  1. JC Craig, GJ Williams and E Hodson are authors of the PRIVENT 2009

  2. JC Craig is an author of Craig 2002.

Figures

1
1
Study flow diagram.
2
2
Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.
3
3
Methodological quality summary: review authors' judgements about each methodological quality item for each included study.
1.1
1.1. Analysis
Comparison 1 Antibiotic prophylaxis versus placebo or no treatment, Outcome 1 Urinary tract infection.
1.2
1.2. Analysis
Comparison 1 Antibiotic prophylaxis versus placebo or no treatment, Outcome 2 All symptomatic UTI by 1‐2 years: allocation concealment.
1.3
1.3. Analysis
Comparison 1 Antibiotic prophylaxis versus placebo or no treatment, Outcome 3 All symptomatic UTI by 1‐2 years: blinding.
1.4
1.4. Analysis
Comparison 1 Antibiotic prophylaxis versus placebo or no treatment, Outcome 4 Renal parenchymal abnormality on DMSA scan: unit of analysis (children).
1.5
1.5. Analysis
Comparison 1 Antibiotic prophylaxis versus placebo or no treatment, Outcome 5 Resolution of VUR.
1.6
1.6. Analysis
Comparison 1 Antibiotic prophylaxis versus placebo or no treatment, Outcome 6 Adverse events.
1.7
1.7. Analysis
Comparison 1 Antibiotic prophylaxis versus placebo or no treatment, Outcome 7 Microbial resistance to prophylactic drug.
1.8
1.8. Analysis
Comparison 1 Antibiotic prophylaxis versus placebo or no treatment, Outcome 8 GFR at 3 years.
1.9
1.9. Analysis
Comparison 1 Antibiotic prophylaxis versus placebo or no treatment, Outcome 9 Renal growth at 3 years.
1.10
1.10. Analysis
Comparison 1 Antibiotic prophylaxis versus placebo or no treatment, Outcome 10 All symptomatic UTI by 1‐2 years: addressing of incomplete outcome data.
1.11
1.11. Analysis
Comparison 1 Antibiotic prophylaxis versus placebo or no treatment, Outcome 11 Febrile UTI by 1‐2 years: allocation concealment.
1.12
1.12. Analysis
Comparison 1 Antibiotic prophylaxis versus placebo or no treatment, Outcome 12 Febrile UTI by 1‐2 years: blinding.
1.13
1.13. Analysis
Comparison 1 Antibiotic prophylaxis versus placebo or no treatment, Outcome 13 Febrile UTI by 1‐2 years: addressing of incomplete outcome data.
1.14
1.14. Analysis
Comparison 1 Antibiotic prophylaxis versus placebo or no treatment, Outcome 14 Febrile UTI by 1‐2 years according to gender.
2.1
2.1. Analysis
Comparison 2 Surgical reimplantation of ureters plus antibiotics versus antibiotics alone, Outcome 1 Urinary tract infection.
2.2
2.2. Analysis
Comparison 2 Surgical reimplantation of ureters plus antibiotics versus antibiotics alone, Outcome 2 Renal parenchymal defects (scars and thinning) on IVP: unit of analysis (children).
2.3
2.3. Analysis
Comparison 2 Surgical reimplantation of ureters plus antibiotics versus antibiotics alone, Outcome 3 Renal scars on IVP: unit of analysis (children).
2.4
2.4. Analysis
Comparison 2 Surgical reimplantation of ureters plus antibiotics versus antibiotics alone, Outcome 4 Repeat positive urine culture.
2.5
2.5. Analysis
Comparison 2 Surgical reimplantation of ureters plus antibiotics versus antibiotics alone, Outcome 5 Renal parenchymal abnormalities on DMSA scan: unit of analysis (children).
2.6
2.6. Analysis
Comparison 2 Surgical reimplantation of ureters plus antibiotics versus antibiotics alone, Outcome 6 Renal parenchymal defects on IVP: unit of analysis (kidneys).
2.7
2.7. Analysis
Comparison 2 Surgical reimplantation of ureters plus antibiotics versus antibiotics alone, Outcome 7 Hypertension and ESKD.
2.8
2.8. Analysis
Comparison 2 Surgical reimplantation of ureters plus antibiotics versus antibiotics alone, Outcome 8 GFR measured by Schwartz formula.
2.9
2.9. Analysis
Comparison 2 Surgical reimplantation of ureters plus antibiotics versus antibiotics alone, Outcome 9 Height Standard Deviation Score (SDS).
2.10
2.10. Analysis
Comparison 2 Surgical reimplantation of ureters plus antibiotics versus antibiotics alone, Outcome 10 Correction of VUR: unit of analysis (children).
2.11
2.11. Analysis
Comparison 2 Surgical reimplantation of ureters plus antibiotics versus antibiotics alone, Outcome 11 Correction of VUR: unit of analysis (ureters).
3.1
3.1. Analysis
Comparison 3 Surgical reimplantation type 1 versus surgical reimplantation type 2, Outcome 1 Repeat positive urine culture.
3.2
3.2. Analysis
Comparison 3 Surgical reimplantation type 1 versus surgical reimplantation type 2, Outcome 2 Persistent VUR (ureters).
3.3
3.3. Analysis
Comparison 3 Surgical reimplantation type 1 versus surgical reimplantation type 2, Outcome 3 Peri‐operative complications.
4.1
4.1. Analysis
Comparison 4 Endoscopic injection treatment versus antibiotics alone, Outcome 1 Urinary tract infection.
4.2
4.2. Analysis
Comparison 4 Endoscopic injection treatment versus antibiotics alone, Outcome 2 Renal parenchymal abnormalities on DMSA scan: unit of analysis (children).
4.3
4.3. Analysis
Comparison 4 Endoscopic injection treatment versus antibiotics alone, Outcome 3 Renal damage on ultrasound.
4.4
4.4. Analysis
Comparison 4 Endoscopic injection treatment versus antibiotics alone, Outcome 4 VUR status after treatment: unit of analysis (children).
4.5
4.5. Analysis
Comparison 4 Endoscopic injection treatment versus antibiotics alone, Outcome 5 Microbial resistance to the prophylactic drug.
5.1
5.1. Analysis
Comparison 5 Endoscopic injection treatment versus no treatment, Outcome 1 Symptomatic urinary tract infection.
5.2
5.2. Analysis
Comparison 5 Endoscopic injection treatment versus no treatment, Outcome 2 Febrile urinary tract infection.
5.3
5.3. Analysis
Comparison 5 Endoscopic injection treatment versus no treatment, Outcome 3 Renal parenchymal abnormality.
6.1
6.1. Analysis
Comparison 6 Different materials for endoscopic injection to correct VUR, Outcome 1 Macroplastique versus dextranomer/hyaluronic acid polymer (Deflux).
6.2
6.2. Analysis
Comparison 6 Different materials for endoscopic injection to correct VUR, Outcome 2 GAX 65 versus GAX 35.
6.3
6.3. Analysis
Comparison 6 Different materials for endoscopic injection to correct VUR, Outcome 3 Dexcel versus Vantris.
7.1
7.1. Analysis
Comparison 7 Probiotics versus antibiotic prophylaxis, Outcome 1 Urinary tract infection.
7.2
7.2. Analysis
Comparison 7 Probiotics versus antibiotic prophylaxis, Outcome 2 E coli resistance to prophylactic drug.
7.3
7.3. Analysis
Comparison 7 Probiotics versus antibiotic prophylaxis, Outcome 3 Renal parenchymal defects on DMSA scan.
7.4
7.4. Analysis
Comparison 7 Probiotics versus antibiotic prophylaxis, Outcome 4 Probiotics plus antibiotics versus antibiotics alone.
8.1
8.1. Analysis
Comparison 8 Other interventions, Outcome 1 Reimplantation surgery versus endoscopic treatment.
8.2
8.2. Analysis
Comparison 8 Other interventions, Outcome 2 Cranberry product versus no treatment.
8.3
8.3. Analysis
Comparison 8 Other interventions, Outcome 3 Circumcision plus antibiotics versus antibiotics alone.
8.4
8.4. Analysis
Comparison 8 Other interventions, Outcome 4 Oxybutynin versus placebo.
See this image and copyright information in PMC

Update of

References

References to studies included in this review

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Gucuk 2013 {published data only}
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Habeeb Abid 2015 {published data only}
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Hari 2015 {published data only}
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Kojima 2012 {published data only}
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Lee 2007a {published and unpublished data}
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Mohseni 2013 {published data only}
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Moore 2014 {published data only}
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Nordenstrom 2016 {published data only}
    1. Nordenstrom J, Holmdahl G, Brandstrom P, Sixt R, Stokland E, Sillen U, et al. The Swedish infant high‐grade reflux trial: Study presentation and vesicoureteral reflux outcome. Journal of Pediatric Urology 2016;13(2):130‐8. [MEDLINE: ] - PubMed
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Pennesi 2008 {published data only (unpublished sought but not used)}
    1. Pennesi M, Peratoner L, Bordugo A, Saccari A, Minisini S, Travan L. Uneffectiveness of antibiotic prophylaxis in children with vesicoureteral reflux. Preliminary data from a controlled study [abstract no: MP239]. Nephrology Dialysis Transplantation 2006;21(Suppl 4):iv378. [CENTRAL: CN‐00602044]
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PRIVENT 2009 {published and unpublished data}
    1. Craig J, Hodson E, Reynolds G, Carapetis J, McTaggart S, Irwig L, et al. A placebo‐controlled randomised trial of antibiotics for the prevention of urinary tract infection in children [abstract no: SA‐PO3072]. Journal of the American Society of Nephrology 2008;19(Abstracts Issue):808A.
    1. Craig J, Simpson J, Lowe A, Reynolds G, McTaggart S, Hodson E, et al. A placebo‐controlled randomized trial of antibiotics for the prevention of urinary tract infection in children [abstract no: O87]. Nephrology 2008;13(Suppl 3):A122. [CENTRAL: CN‐00689116]
    1. Craig JC, Simpson JM, Williams GJ, Lowe A, Reynolds GJ, McTaggart SJ, et al. Antibiotic prophylaxis and recurrent urinary tract infection in children.[Erratum appears in N Engl J Med. 2010 Apr 1;362(13):1250]. New England Journal of Medicine 2009;361(18):1748‐59. [MEDLINE: ] - PubMed
Reddy 1997 {published data only}
    1. Reddy PP, Evans MT, Hughes PA, Dangman B, Cooper J, Lepow ML, et al. Antimicrobial prophylaxis in children with vesico‐ureteral reflux: a randomized prospective study of continuous therapy vs intermittent therapy vs surveillance [abstract]. Pediatrics 1997;100(3):555‐6. [CENTRAL: CN‐00427967]
RIVUR 2008 {published data only}
    1. Carpenter MA, Hoberman A, Mattoo TK, Mathews R, Keren R, Chesney RW, et al. The RIVUR trial: profile and baseline clinical associations of children with vesicoureteral reflux. Pediatrics 2013;132(1):e34‐45. [MEDLINE: ] - PMC - PubMed
    1. Chesney RW, Carpenter MA, Moxey‐Mims M, Nyberg L, Greenfield SP, Hoberman A, et al. Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR): background commentary of RIVUR investigators. Pediatrics 2008;122 Suppl 5:S233‐9. [MEDLINE: ] - PMC - PubMed
    1. Edmonson MB, Eickhoff JC. Weight gain and obesity in infants and young children exposed to prolonged antibiotic prophylaxis. JAMA Pediatrics 2017;171(2):150‐6. [MEDLINE: ] - PubMed
    1. Greenfield S, Carpenter M, Hoberman A, Mattoo T, Mathews R, Keren R, et al. The RIVUR trial: baseline demographic and clinical characteristics [abstract no: 641]. Journal of Urology 2013;189(4 Suppl):e262. [EMBASE: 71031583]
    1. Greenfield SP, Carpenter MA, Chesney RW, Zerin JM, Chow J. The RIVUR voiding cystourethrogram pilot study: experience with radiologic reading concordance. Journal of Urology 2012;188(4 Suppl):1608‐12. [MEDLINE: ] - PMC - PubMed
Roussey‐Kesler 2008 {published and unpublished data}
    1. Cunto A, Pennesi M, Salierno P. Re: Antibiotic prophylaxis for the prevention of recurrent urinary tract infection in children with low grade vesicoureteral reflux: results from a prospective randomized study. Journal of Urology 2008;180(5):2258‐9. [MEDLINE: ] - PubMed
    1. Roussey‐Kesler G, Gadjos V, Idres N, Horen B, Guyot C. Antibiotic prophylaxis for the prevention of urinary tract infection in children with low grade vesicoureteral reflux: results from a prospective randomized study [abstract no: 204 (FC)]. Pediatric Nephrology 2007;22(9):1450. - PubMed
    1. Roussey‐Kesler G, Gadjos V, Idres N, Horen B, Ichay L, Leclair MD, et al. Antibiotic prophylaxis for the prevention of recurrent urinary tract infection in children with low grade vesicoureteral reflux: results from a prospective randomized study. Journal of Urology 2008;179(2):674‐9. [MEDLINE: ] - PubMed
Scott 1968 {published data only}
    1. Scott JE, Stansfeld JM. Treatment of vesico‐ureteric reflux in children. Archives of Disease in Childhood 1968;43(229):323‐8. [MEDLINE: ] - PMC - PubMed
Smellie 2001 {published and unpublished data}
    1. Barratt TM, Chantler C, Prescod NP, Woolf AS, Smellie JM. Randomised trial comparing medical and surgical treatment in children with bilateral vesicoureteric reflux and nephropathy [abstract]. Renal Association 50th Anniversary Meeting; 2000 Sep 27‐29; St John College, Cambridge, UK. 2000.
    1. Roseau E. Vesico‐ureteral reflux and nephropathy in the child: medical or surgical treatment? [Reflux vesico‐ureteral et nephropathie de l'enfant: traitement medical ou chirurgical?]. Presse Medicale 2001;30(23):1157‐8. [MEDLINE: ] - PubMed
    1. Smellie JM, Barratt TM, Chantler C, Gordon I, Prescod NP, Ransley PG, et al. Medical versus surgical treatment in children with severe bilateral vesicoureteric reflux and bilateral nephropathy: a randomised trial. Lancet 2001;357(9265):1329‐33. [MEDLINE: ] - PubMed
Swedish Reflux Trial 2010 {published and unpublished data}
    1. Brandstrom P, Esbjorner E, Herthelius M, Holmdahl G, Lackgren G, Neveus T, et al. The Swedish reflux trial in children: I. Study design and study population characteristics.[Erratum appears in J Urol. 2011 Jan;185(1):365]. Journal of Urology 2010;184(1):274‐9. [MEDLINE: ] - PubMed
    1. Brandstrom P, Esbjorner E, Herthelius M, Swerkersson S, Jodal U, Hansson S. The Swedish reflux trial in children: III. Urinary tract infection pattern. Journal of Urology 2010;184(1):286‐91. [MEDLINE: ] - PubMed
    1. Brandstrom P, Hansson S. Growth in children with dilating VUR ‐ a follow up of the Swedish Reflux Trial [abstract no: P‐SAT044]. Pediatric Nephrology 2013;28(8):1391. [EMBASE: 71127064]
    1. Brandstrom P, Jodal U, Sillen U, Hansson S. The Swedish Reflux Trial: review of a randomized, controlled trial in children with dilating vesicoureteral reflux. Journal of Pediatric Urology 2011;7(6):594‐600. [MEDLINE: ] - PubMed
    1. Brandstrom P, Neveus T, Sixt R, Stokland E, Jodal U, Hansson S. The Swedish Reflux Trial in children: IV. Renal damage. Journal of Urology 2010;184(1):292‐7. [MEDLINE: ] - PubMed
Takvani 2015 {published data only}
    1. Takvani A, Gokani C, Malaviya P. Vesicoureteral reflux ‐ a prospective study of 11 years [abstract]. European Urology Supplements 2015;14(2):e505‐e505a. [EMBASE: 71831431]

References to studies excluded from this review

Akin 2014 {published data only}
    1. Akin M, Erginel B, Karadag CA, Yildiz A, Ozcelik GS, Sever N, et al. A comparison of the double hydrodistention implantation technique (HIT) and the HIT with a polyacrylate/polyalcohol copolymer (PPC) for the endoscopic treatment of primary vesicoureteral reflux. International Urology & Nephrology 2014;46(11):2057‐61. [MEDLINE: ] - PubMed
Bailey 1991 {published data only}
    1. Bailey RR, Lynn KL, McRae CU, Smith AH. Prospective randomised study of the effect of nephrectomy on blood pressure of patients with unilateral reflux nephropathy. 2nd CJ Hodson Symposium on Reflux Nephropathy; 1991 Feb 26; Christchurch, NZ. 1991:37‐40.
COBSG 1973 {published data only}
    1. Sequelae of covert bacteriuria in schoolgirls. A four‐year follow‐up study. Lancet 1978;311(8070):889‐93. [MEDLINE: ] - PubMed
    1. Aggarwal VK, Verrier Jones K, Asscher AW, Evans C, Williams LA. Covert bacteriuria: long term follow up. Archives of Disease in Childhood 1991;66(11):1284‐6. [MEDLINE: ] - PMC - PubMed
    1. Asscher AW, McLachlan MS, Jones RV, Meller S, Sussman M, Harrison S, et al. Screening for asymptomatic urinary‐tract infection in schoolgirls. A two‐centre feasibility study. Lancet 1973;2(7819):1‐4. [MEDLINE: ] - PubMed
Coupris 1988 {published data only}
    1. Coupris L. Antibiotic prophylaxis for surgery after vesico‐ureteral reflux in children. Drugs 1988;35 Suppl 2:154‐7. [MEDLINE: ] - PubMed
Kajbafzadeh 2010 {published data only}
    1. Kajbafzadeh AM, Baradaran N, Sadeghi Z, Tourchi A, Saeedi P, Madani A, et al. Vesicoureteral reflux and primary bladder neck dysfunction in children: urodynamic evaluation and randomized, double‐blind, clinical trial on effect of alpha‐blocker therapy. Journal of Urology 2010;184(5):2128‐33. [MEDLINE: ] - PubMed
Montini 2007 {published data only}
    1. Hewitt IK, Tomasi L, Pavanello L, Maschio F, Molinari PP, Toffolo A, et al. Early treatment of acute pyelonephritis in children fails to reduce renal scarring [abstract no: SA‐PO1100]. Journal of the American Society of Nephrology 2006;17(Abstracts):804A. [CENTRAL: CN‐00653791]
    1. Hewitt IK, Zucchetta P, Rigon L, Maschio F, Molinari PP, Tomasi L, et al. Early treatment of acute pyelonephritis in children fails to reduce renal scarring: data from the Italian Renal Infection Study Trials. Pediatrics 2008;122(3):486‐90. [MEDLINE: ] - PubMed
    1. Scola C, Mutiis C, Hewitt IK, Puccio G, Toffolo A, Zucchetta P, et al. Different guidelines for imaging after first UTI in febrile infants: yield, cost, and radiation. Pediatrics 2013;131(3):e665‐71. [MEDLINE: ] - PubMed
    1. Montini G, Murer L, Gobber D, Comacchio S, Toffolo A, Dall'Amico R, et al. Oral vs initial intravenous antibiotic treatment of urinary tract infections in children: a multicentre study [abstract no: W833]. Nephrology Dialysis Transplantation 2003;18(Suppl 4):816‐7.
    1. Montini G, Toffolo A, Zucchetta P, Dall'Amico R, Gobber D, Calderan A, et al. Antibiotic treatment for pyelonephritis in children: multicentre randomised controlled non‐inferiority trial. BMJ 2007;335(7616):386‐8. [MEDLINE: ] - PMC - PubMed
N0012116994 {published data only}
    1. Ransley PG. Clinical trial of deflux for endoscopic correction of severe vesicoureteric reflux and the effects on improving bladder function outcome. National Research Register UK (www.nrr.nhs.uk/) (accessed prior to 10 September 2018).
NCBRG 1981 {published data only}
    1. Covert bacteriuria in schoolgirls in Newcastle upon Tyne: a 5‐year follow‐up. Newcastle Covert Bacteriuria Research Group. Archives of Disease in Childhood 1981;56(8):585‐92. [MEDLINE: ] - PMC - PubMed
    1. Davison JM, Sprott MS, Selkon JB. The effect of covert bacteriuria in schoolgirls on renal function at 18 years and during pregnancy. Lancet 1984;2(8404):651‐5. [MEDLINE: ] - PubMed
Scholtmeijer 1988 {published data only}
    1. Scholtmeijer RJ. Treatment of vesicoureteric reflux. Results of a prospective study. British Journal of Urology 1993;71(3):346‐9. [MEDLINE: ] - PubMed
    1. Scholtmeijer RJ. Treatment of vesicoureteric reflux: results after 3 years in a prospective study. Child Nephrology & Urology 1991;11(1):29‐32. [MEDLINE: ] - PubMed
    1. Scholtmeijer RJ, Griffiths DJ. Treatment of vesicoureteric reflux. Preliminary report of a prospective study. British Journal of Urology 1988;61(3):205‐9. [MEDLINE: ] - PubMed
Uberos 2012 {published data only}
    1. Fernandez‐Puentes V, Uberos J, Rodriguez‐Belmonte R, Nogueras‐Ocana M, Blanca‐Jover E, Narbona‐Lopez E. Efficacy and safety profile of cranberry in infants and children with recurrent urinary tract infection [Eficacia y perfil de seguridad del arandano americano en lactantes y ninos con infeccion urinaria recurrente]. Anales de Pediatria 2015;82(6):397‐403. [MEDLINE: ] - PubMed
    1. Uberos J, Nogueras‐Ocana M, Fernandez‐Puentes V, Rodriguez‐Belmonte R, Narbona‐Lopez E, Molina‐Carballo A, et al. Cranberry syrup vs trimethoprim in the prophylaxis of recurrent urinary tract infections among children: a controlled trial. Open Access Journal of Clinical Trials 2012;4:31‐8. [EMBASE: 2012351759]
    1. Uberos J, Rodriguez‐Belmonte R, Fernandez‐Puentes V, Narbona‐Lopez E, Molina‐Carballo A, Munoz‐Hoyos A. Cranberry syrup vs. trimethoprim in the prophylaxis of recurrent urinary infection: A double‐blind randomized clinical trial [abstract no: PP003]. Acta Paediatrica 2010;99(Suppl 462):48. [EMBASE: 70313001]

Additional references

Belman 1995
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References to other published versions of this review

Hodson 2007
    1. Hodson EM, Wheeler DM, Smith GH, Craig JC, Vimalachandra D. Interventions for primary vesicoureteric reflux. Cochrane Database of Systematic Reviews 2007, Issue 3. [DOI: 10.1002/14651858.CD001532.pub3] - DOI - PubMed
Nagler 2011
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Wheeler 1999
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Wheeler 2003
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Wheeler 2004
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