Predictors of grade 3–5 vesicoureteral reflux in infants ≤ 2 months of age with pyelonephritis

  • Hilla Bahat
  • Mai Ben-Ari
  • Tomer Ziv-Baran
  • Amos Neheman
  • Ilan Youngster
  • Michael Goldman
Original Article



This study aimed to assess predictors for grade 3–5 vesicoureteral reflux (VUR) in infants ≤ 2 months of age admitted for first urinary tract infection (UTI).


Retrospective cohort study of 195 infants ≤ 2 months admitted to a pediatric ward for first UTI between 2006 and 2017. Clinical, laboratory, and imaging data were collected from electronic medical charts. We examined associations between grade 3–5 VUR and different patient characteristics.


Twenty infants (10%) were diagnosed with grade 3–5 VUR; all had fever. Infants with grade 3–5 VUR had higher blood neutrophil percentage (BNP) (65% vs. 46%, P < 0.001), higher neutrophil-to-lymphocyte ratio (NLR) (2.6 vs. 1.3, P < 0.001), more renal ultrasound abnormalities (prenatal 26% vs. 5%, P = 0.007; postnatal 84% vs. 55%, P = 0.015), and Pseudomonas UTI (15% vs. 1%, respectively, P < 0.001). NLR > 1.65 showed sensitivity 100% and specificity 61% for detecting grade 3–5 VUR. BNP > 53% showed sensitivity 100% and specificity 60% for detecting grade 3–5 VUR. BNP was the best single marker for grade 3–5 VUR with area under the curve (AUC) of 0.82 (95% CI 0.75–0.89). In a multivariate model, AUC for combination of BNP and hydronephrosis was 0.86 (95% CI 0.79–0.93, P = 0.007).


Infants ≤ 2 months of age admitted for a first UTI are at risk for grade 3–5 VUR and thus should undergo a voiding cystourethrography (VCUG) if their renal ultrasound is abnormal or if they have Pseudomonas UTI. Avoiding VCUG can be considered in afebrile infants and in infants with BNP < 53% or NLR < 1.65.


Urinary tract infection Young infants Vesicoureteral reflux Voiding cystourethrography 


Compliance with ethical standards

The study was approved by the institutional Research Ethics Board, waiving the need for informed consent.

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Morley EJ, Lapoint JM, Roy LW, Cantor R, Grant WD, Paolo WF, Wojcik S (2012) Rates of positive blood, urine, and cerebrospinal fluid cultures in children younger than 60 days during the vaccination era. Pediatr Emerg Care 28:125–130. CrossRefPubMedGoogle Scholar
  2. 2.
    Swerkersson S, Jodal U, Sixt R, Stokland E, Hansson S (2017) Urinary tract infection in small children: the evolution of renal damage over time. Pediatr Nephrol 32:1907–1913. CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Ylinen E, Ala-Houhala M, Wikström S (2003) Risk of renal scarring in vesicoureteral reflux detected either antenatally or during the neonatal period. Urology 61:1238–1242. CrossRefPubMedGoogle Scholar
  4. 4.
    Tekgül S, Riedmiller H, Hoebeke P, Kočvara R, Nijman RJ, Radmayr C, Stein R, Dogan HS, European Association of Urology (2012) EAU guidelines on vesicoureteral reflux in children. Eur Urol 62:534–542. CrossRefPubMedGoogle Scholar
  5. 5.
    RIVUR Trial Investigators, Hoberman A, Greenfield SP, Mattoo TK, Keren R, Mathews R, Pohl HG, Kropp BP, Skoog SJ, Nelson CP, Moxey-Mims M, Chesney RW, Carpenter MA (2014) Antimicrobial prophylaxis for children with vesicoureteral reflux. N Engl J Med 370:2367–2376. CrossRefGoogle Scholar
  6. 6.
    Subcommittee on Urinary Tract Infection, Steering Committee on Quality Improvement and Management, Roberts KB (2011) Urinary tract infection: clinical practice guideline for the diagnosis and management of the initial UTI in febrile infants and children 2 to 24 months. Pediatrics 43:595–610. CrossRefGoogle Scholar
  7. 7.
    Mori R, Lakhanpaul M, Verrier-Jones K (2007) Diagnosis and management of urinary tract infection in children: summary of NICE guidance. BMJ 335:395–397. CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Lebowitz RL, Olbing H, Parkkulainen KV, Smellie JM, Tamminen-Möbius TE (1985) International system of radiographic grading of vesicoureteric reflux. International Reflux Study in Children. Pediatr Radiol 15:105–109CrossRefGoogle Scholar
  9. 9.
    Weiss R, Duckett J, Spitzer A (1992) Results of a randomized clinical trial of medical versus surgical management of infants and children with grades III and IV primary vesicoureteral reflux (United States). The International Reflux Study in Children. J Urol 148:1667–1673CrossRefGoogle Scholar
  10. 10.
    Cleper R, Krause I, Eisenstein B, Davidovits M (2004) Prevalence of vesicoureteral reflux in neonatal urinary tract infection. Clin Pediatr (Phila) 43:619–625. CrossRefGoogle Scholar
  11. 11.
    Ismaili K, Lolin K, Damry N, Alexander M, Lepage P, Hall M (2011) Febrile urinary tract infections in 0- to 3-month-old infants: a prospective follow-up study. J Pediatr 158:69–72. CrossRefGoogle Scholar
  12. 12.
    Kanellopoulos TA, Salakos C, Spiliopoulou I, Ellina A, Nikolakopoulou NM, Papanastasiou DA (2006) First urinary tract infection in neonates, infants and young children: a comparative study. Pediatr Nephrol 21:1131–1137. CrossRefPubMedGoogle Scholar
  13. 13.
    Wallace SS, Zhang W, Mahmood NF, Williams JL, Cruz AT, Macias CG, Quinonez RA, Orth RC (2015) Renal ultrasound for infants younger than 2 months with a febrile urinary tract infection. AJR Am J Roentgenol 205:894–898. CrossRefPubMedGoogle Scholar
  14. 14.
    Fernbach SK, Maizels M, Conway JJ (1993) Ultrasound grading of hydronephrosis: introduction to the system used by the Society for Fetal Urology. Pediatr Radiol 23:478–480CrossRefGoogle Scholar
  15. 15.
    Lee MD, Lin CC, Huang FY, Tsai TC, Huang CT, Tsai JD (2009) Screening young children with a first febrile urinary tract infection for high-grade vesicoureteral reflux with renal ultrasound scanning and technetium-99m-labeled dimercaptosuccinic acid scanning. J Pediatr 154:797–802. CrossRefPubMedGoogle Scholar
  16. 16.
    Dayan PS, Hanson E, Bennett JE, Langsam D, Miller SZ (2004) Clinical course of urinary tract infections in infants younger than 60 days of age. Pediatr Emerg Care 20:85–88. CrossRefPubMedGoogle Scholar
  17. 17.
    Littlewood JM (1972) 66 infants with urinary tract infection in first month of life. Arch Dis Child 47:218–226. CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Chang PW, Abidari JM, Shen MW, Greenhow TL, Bendel-Stenzel M, Roman HK, Biondi EA, Schroeder AR, PRIS Bacteremic UTI Investigators (2016) Urinary imaging findings in young infants with bacteremic urinary tract infection. Hosp Pediatr 6:647–652. CrossRefPubMedGoogle Scholar
  19. 19.
    Leroy S, Romanello C, Smolkin V, Galetto-Lacour A, Korczowski B, Tuerlinckx D, Rodrigo C, Gajdos V, Moulin F, Pecile P, Halevy R, Gervaix A, Duhl B, Vander Borght T, Prat C, Foix-L'Hélias L, Altman DG, Gendrel D, Bréart G, Chalumeau M (2012) Prediction of moderate and high grade vesicoureteral reflux after a first febrile urinary tract infection in children: construction and internal validation of a clinical decision rule. J Urol 187:265–271. CrossRefPubMedGoogle Scholar
  20. 20.
    Halimi-Asl A, Hosseini AH, Nabavizadeh P (2014) Can procalcitonin reduce unnecessary voiding cystoureterography in children with first febrile urinary tract infection? Iran J Pediatr 24:418–422PubMedPubMedCentralGoogle Scholar
  21. 21.
    Han SY, Lee IR, Park SJ, Kim JH, Shin JI (2016) Usefulness of neutrophil-lymphocyte ratio in young children with febrile urinary tract infection. Korean J Pediatr 59:139–144. CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Oostenbrink R, van der Heijden AJ, Moons KGM, Moll HA (2000) Prediction of vesico-ureteric reflux in childhood urinary tract infection: a multivariate approach. Acta Paediatr Int J Paediatr 89:806–810. CrossRefGoogle Scholar

Copyright information

© IPNA 2019

Authors and Affiliations

  • Hilla Bahat
    • 1
    • 2
  • Mai Ben-Ari
    • 1
  • Tomer Ziv-Baran
    • 2
    • 3
  • Amos Neheman
    • 2
    • 4
  • Ilan Youngster
    • 1
    • 2
  • Michael Goldman
    • 1
    • 2
  1. 1.Department of PediatricsAssaf Harofeh Medical CenterZerifinIsrael
  2. 2.Sackler School of MedicineTel Aviv UniversityTel AvivIsrael
  3. 3.Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of MedicineTel Aviv UniversityTel AvivIsrael
  4. 4.Department of UrologyAssaf Harofeh Medical CenterZerifinIsrael

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