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Urinary Tract Infection in Asymptomatic Newborns with Prolonged Unconjugated Hyperbilirubunemia: A Hospital based Observational study from Western Region of Nepal

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Background Urine culture is usually not a part of work-up for neonatal unconjugated hyperbilirubinemia; hence its prevalence remains unknown. Objective This study was done to determine the incidence of urinary tract infection (UTI) in asymptomatic newborns with prolonged unconjugated hyperbilirubinemia and to evaluate which other laboratory parameters are associated with UTIs. Method A prospective observational study where jaundiced newborns otherwise clinically well, were evaluated for UTI. The study was carried out in neonatal intensive care unit of Manipal Teaching Hospital, Pokhara from June 2012 -April 2013. The babies were divided in two groups group I- late prolonged jaundice and Group II - early physiological jaundice. Serum bilirubin, Septic screening and suprapubic urine sample analysis was performed for all subjects. Data was analyzed using SPSS version 16 and p 7lt; 0.05 was considered statistically significant. Result Of the 85 neonates, 33(38.8%) were females and 52(61.2%) males; 68(80%) were of term gestation and 17(20%) were preterms. The age at onset of jaundice for group I (n=53) was 13.6±4.88 days and for Group II (n= 32) was 5.0± 1.04 days. 11 /85 (12.9%) were diagnosed to have UTI [10 (90.9%) in group I and 1 in group II (9.01%] (p=0.04). UTI was more prevalent in group I [OR 7.20, 95% CI (0.87, 59.27)], more prevalent in male [OR 8.40, 95% CI (0.59, 74.13) and term babies of group I [OR 4.39, 95% CI (0.48, 39.82) when compared to Group II. Among other lab parameters only total WBC count was statistically significant (p=0.03). Escherichia coli was the predominant pathogen (45.45%) isolated. The sensitive antibiotics were aminoglycosides, fluroquinolones, nitrofurantoin and vancomycin and resistant antibiotics were most cephalosporins and penicillins for the isolated organisms. Conclusion The present study highlights significant association between late prolonged unconjugated hyperbilirubinemia and UTI. It is suggested that evaluation for UTI may be considered as a screening test for such cases.
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VOL. 14 | NO. 1 | ISSUE 53 | JAN-MAR 2016
1Department of Pediatrics
2Department of Community Medicine
Manipal College of medical science,
Pokhara, Nepal.
Corresponding Author
Tejesh Malla
Department of Pediatrics
Manipal College of Medical Science,
Pokhara, Nepal.
E-mail: tejeshmalla@hotmail.com
Citaon
Malla T, Sathian B, Malla KK, Adhikari S. Urinary tract
infecon in asymptomac newborns with prolonged
unconjugated hyperbilirubunemia: a hospital based
observaonal study from Western Region of Nepal.
Kathmandu Univ Med J 2016;53(1):41-6.
ABSTRACT
Background
Urine culture is usually not a part of work-up for neonatal unconjugated
hyperbilirubinemia; hence its prevalence remains unknown.
Objecve
This study was done to determine the incidence of urinary tract infecon (UTI) in
asymptomac newborns with prolonged unconjugated hyperbilirubinemia and to
evaluate which other laboratory parameters are associated with UTIs.
Method
A prospecve observaonal study where jaundiced newborns otherwise clinically
well, were evaluated for UTI. The study was carried out in neonatal intensive care
unit of Manipal Teaching Hospital, Pokhara from June 2012 -April 2013. The babies
were divided in two groups group I- late prolonged jaundice and Group II - early
physiological jaundice. Serum bilirubin, Sepc screening and suprapubic urine
sample analysis was performed for all subjects. Data was analyzed using SPSS version
16 and p < 0.05 was considered stascally signicant.
Result
Of the 85 neonates, 33(38.8%) were females and 52(61.2%) males; 68(80%) were of
term gestaon and 17(20%) were preterms. The age at onset of jaundice for group I
(n=53) was 13.6±4.88 days and for Group II (n= 32) was 5.0± 1.04 days. 11 /85 (12.9%)
were diagnosed to have UTI [10 (90.9%) in group I and 1 in group II (9.01%] (p=0.04).
UTI was more prevalent in group I [OR 7.20, 95% CI (0.87, 59.27)], more prevalent in
male [OR 8.40, 95% CI (0.59, 74.13) and term babies of group I [OR 4.39, 95% CI (0.48,
39.82) when compared to Group II. Among other lab parameters only total WBC count
was stascally signicant (p=0.03). Escherichia coli was the predominant pathogen
(45.45%) isolated. The sensive anbiocs were aminoglycosides, uroquinolones,
nitrofurantoin and vancomycin and resistant anbiocs were most cephalosporins
and penicillins for the isolated organisms.
Conclusion
The present study highlights signicant associaon between late prolonged
unconjugated hyperbilirubinemia and UTI. It is suggested that evaluaon for UTI
may be considered as a screening test for such cases.
KEY WORDS
Neonatal hyperbilirubinemia, newborn, sepc screening, urinary tract infecon
Urinary Tract Infecon in Asymptomac Newborns with
Prolonged Unconjugated Hyperbilirubunemia: A Hospital
based Observaonal study from Western Region of Nepal
Malla T,1 Sathian B,2 Malla KK,1 Adhikari S1
Original Arcle
KATHMANDU UNIVERSITY MEDICAL JOURNAL
Page 42
INTRODUCTION
Urinary tract infecon (UTI) is the most common disease
of the urogenital system.1 Its incidence varies from 0.1 to
1% among neonates.2,3 Hyperbilirubinemia in newborns
may be associated with bacterial infecon especially
UTI.4 Hence evaluaon of UTI should be a part workup
for neonatal hyperbilirubinemia but the current scienc
guidelines, that of the American Academy of Pediatrics
(AAP) do not recommend any evaluaon for UTI among
babies with hyperbilirubinemia.5 Above that the clinical
presentaon of UTI in neonates are nonspecic hence
the diagnosis may be missed. Considering these points
this study aimed to determine whether late prolonged
unconjugated hyperbilirubinemia in asymptomac
newborns is associated with UTI.
METHODS
A hospital based observaonal study was undertaken in
NICU of Manipal Teaching Hospital, Pokhara for a period of
10 months from June 2012 to April 2013. Ethical approval
was taken from the Instuonal Review Commiee,
Manipal Teaching hospital (IRC/MTH). The purpose of the
study was explained to the parents and a wrien consent
from parents of the neonates was also obtained before
the commencement of the study. Sample size was based
in a pilot study done before original study which showed
standard deviaon of age at onset of late prolonged
jaundice to be 4.9 and 1.2 for early physiological jaundice.
Sample size required for 95% condence interval and
allowable Error 1.5 and 0.5 were 41 and 23 respecvely.
But we have taken 53 for late jaundice and 32 for early
jaundice. Of the 85/200 (42.5%) who fullled the criteria
for inclusion were selected for the study. Inclusion criteria
was the newborns who presented with jaundice aer 24
hours of life and had no clinical symptoms and signs of any
disease. The Exclusion criteria were : a) Jaundice on rst 24
hours of life, b) those having clinical features of sepsis, c)
congenital and chromosomal anomalies ,d) Gestaon age ≤
28 weeks, e) preterm with complicaons, f) any features of
hemolysis, g) Rh and ABO incompability and h) suspected
metabolic diseases.
The populaon was divided in two groups: Group I [late
prolonged jaundice] – jaundice appearing or prolonged
more than 10 days for term and 14 days or later for preterm.
Group II [early physiological jaundice] – jaundice on 2-9
days for term and 2-13 days for preterm which is the me
for physiological jaundice to appear and then disappear.6
Detailed informaon including gestaon age, sex and
blood group for baby and mother were recorded. Then
all babies were examined and serum bilirubin (direct,
indirect), sepc screening (complete blood count with
peripheral smear, C-reacve protein,blood culture and
where required Cerebrospinal uid culture) and suprapubic
urine sample (taken under strict asepc precauon) was
analysed. Centrifuged samples of urine were stained and
then studied with High power eld; leukocyte count (more
than ve) and bacterial count (many, moderate, few, none)
were reported. All samples were sent for quantave
urine culture - single pathogen, obtained by suprapubic
puncture was considered as posive. In cases where the
urine culture was posive, ultrasound and renal funcon
tests were performed.
Data was collected, tabulated and analyzed using stascal
package SPSS 16.0 version. Microso Excel (2003) and SPSS
were used for plong gures. Chi- square test was used
to compare the parameters and p <0.05 was considered
stascally signicant.
RESULTS
Out of total 85 cases of neonatal hyperbilirubunemia there
were 52(61.20%) males and 33(38.80%) females, 68(80%)
were of term gestaon and 17(20%) were preterms.
Fiy three had late prolonged (Group I) and 32 had early
physiological jaundice (Group II) with mean age at onset of
jaundice 13.60±4.88 days and 5.00±1.04 days respecvely
(Table1).
Of the 11/85 (12.90%) cases had UTI based on posive urine
culture. Ten (90.90%) were in group I and only 1(9.09%)
was in group II (p<0.046) [g1 and table 2]. Escherichia
coli was the predominant pathogen (45.45%) isolated
followed by Klebsiella (27.27%), Enterococcus (18.18%) and
Staphylococcus aureus (9.09% %) shown in Table 1.
Table 1. Sample characteriscs.
Variables N % Total
Sex :
Male 52 61.20
85
Female 33 38.80
Gestaon age
Term 68 80
Preterm 17 20
Age at onset -jaundice
Group I (Late jaundice) 53 62.40
Group II (Early jaundice) 32 37.60
UTI
Yes 11 12.90
No 74 87.10
Growth in urine C/S
11
Escherichia coli 5 45.45
Enetrococcus 2 18.18
Klebsiella 327.27
Staphylococcus aureus 19.09
**Mean age at onset of jaundice
Group I (late) = 13.60±4.88 days
Group II (Early) = 5.00±1.04 days
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VOL. 14 | NO. 1 | ISSUE 53 | JAN-MAR 2016
Table 2. Relaon of variables in group I and group II with UTI
Variables UTI p value Odds rao
(95% CI)
Yes No
Total (N=85)
Group I(n=53) 10
18.9%
43
81.1%
0.04 7.21(0.87, 59.27)
Group II (n=32) 1
3.1%
31
96.9%
1
Male (n=52)
Group I(n=27) 7
25.9%
20
74.1%
0.055 8.40(0.59, 74.13)
Group II(n=25) 1
4%
24
96%
1
Female (n=33)
Group I (n=26) 3
11.5%
23
88.5%
1 -
Group II(n=7) 0
0%
7
100%
Term (n=68)
Group I(n=38) 5
13.2%
33
86.8%
0.218 4.39(0.48, 39.82)
Group II(n=30) 1
3.3%
29
96.7%
1
Preterm (n=17)
Group I(n=15) 5
33.3%
10
66.7%
1 -
Group II(n=2) 0
0%
2
100%
Table 3. Lab parameters of two groups.
Lab parameters Group Chi-
square
test
p value
I (n=53): II (n=32)
Total count
High 16(30.2%) 2(6.2%)
13.53 0.001
Normal 30 (56.6%) 30 93.8%)
Low 7(13.2%) 0 (0%)
Neutrophil count
High 18(34%) 4(12.5%) 4.72 0.029
Normal 35(66%) 28(87.5%)
CRP
Posive 38(71.7%) 15(46.9%)
5.24 0.022
Negave 15(28.3%) 17(53.1%)
Urine C/S
No growth 43(81.1%) 31(96.9%) 4.39 0.036
Growth 10 18.9%) 1 (3.1%)
GroupI GroupII
90.90%
9.09%
Fig1PercentageofUTIintwogroups(n=11)
GroupIGroupII
Figure 1. Percentage of UTI in two groups (n=11)
Table 4. The mean values ± SD of lab parameters in two groups:
Lab parameters Group N Mean ±SD p value
Total count Group I 53 10996 ±6844 0.01
Group II 32 8187±2757
Neutrophil Group I 53 64.566±18.49 0.005
Group II 32 3.750±15.25
CRP Group I 53 21.056±18.62 0.001
Group II 32 8.625 ±12.92
Total bilirubin Group I 53 18.611 ±3.05 0.497
Group II 32 18.196±2.48
Direct bilirubin Group I 53 1.196 ±0.52 0.073
Group II 32 1.450 ±0.67
Indirect bilirubin Group I 53 17.226 ±3.11 0.429
Group II 32 16.747 ±2.39
0.00%
10.00%
20.00%
30.00%
40.00%
50.00%
60.00%
70.00%
80.00%
90.00%
100.00%
E.Coli Klebsiella Enterococcus S.aureus Nogrowth
GroupI7.50% 5.70% 3.80% 1.90% 81.10%
GroupII 3.10% 0% 0% 0% 96.90%
Percentage
Fig2.Growthpatterninurinecultureintwogroups
Figure 2. Growth paern of urine culture in two groups.
Determinants of sociodemographic factors and UTI with
two groups by logisc regression.
Logisc regression analysis revealed that UTI was more
prevalent in group I [OR 7.209, 95% CI (0.877, 59.278)]
when compared to group II. Again UTI was more prevalent
in male of group I [OR 8.400 (0.592, 74.138) and Term
gestaon newborn of group I [OR 4.394 (0.485, 39.823)
when compared to Group II.
Other lab parameters
Lab parameters with mean values ± standard deviaon
(SD) in two groups are shown in table 3 and 4 where
total white blood cell (WBC) count, neutrophil count and
C-reacve protein (CRP) levels are stascally signicant.
The growth paern of urine culture in two groups is
highlighted in gure 2. Table 5 shows the anbiogram of
isolated organisms.
Original Arcle
KATHMANDU UNIVERSITY MEDICAL JOURNAL
Page 44
Table 5. Anmicrobial suscepbility paern of isolated
organisms from urine samples:
Organism Type of anbioc Suscepbility level
Sensive Resistant Not done
Esch-
erichia
coli =5
Gentamycin 41 0
Amikacin/nelmycin 4 0 1
Nitrofurantoin/ Norox 3 1 1
Imipenem 2 0 3
Ciprooxacin/cefotaxim 2 1 2
Ceriaxone 2 2 1
Amoxicillin / Piperacillin 1 3 1
Penicillin/ Cotrimoxa-
zole
10 4
Cefexim 1 1 3
Ampicillin 0 4 1
Cefazolin 03 2
Cefalexin 0 2 3
Klebsiella
(n=3)
Imipenem 3 0 0
Amikacin/nelmycin 2 0 1
Gentamicin/Ciprooxa-
cin/ vancomycin
2 1 0
Ceriaxone/cefotaxim/
Piperacillin
1 1 1
Cefazolin 1 2 0
Nitrofurantoin 1 0 2
Cotrimoxazole/Norox/
Cloxacillin
0 3 0
Ampi/ Amoxycillin/Ce-
falexin/ penicillin
0 1 2
Entero-
coccus
(n=2)
Gentamicin/Nitrofuran-
toin/ Vancomycin
2 0 0
Imipenem/ Ciprooxa-
cin
1 1 0
Norox/ Penicillin 1 0 1
Cefazolin /cefalexin/
Piperacillin/ cloxacillin /
ampicillin
0 1 1
Ceriaxone/cefotaxim /
Amoxicillin
0 2 0
Staphy-
lococcus
aureus
(n=1)
Gentamicin/Nitrofuran-
toin/Cefazoli/Vancomy-
cin/ Erythromycin
1 0 0
Amikacin/Nelmycin/
Cefotaxim /cefalexin/
Amoxicillin/penicillin/
Ciprooxacin/piperacil-
lin/ampicillin/Cefexim
0 1 0
may possibly be missed in such cases. American Academy
of Pediatrics (AAP) has published guidelines where they
recommend invesgaon for urinary tract infecon only in
direct hyperbilirubinemia.5 Mulple studies have described
paents with proven bacterial infecon, who developed
jaundice during the course of their illness.10-12 Other
studies, have noted that jaundice may be one of the rst
signs of bacterial sepsis in neonates in the rst few days
of life.13 But none of these studies have menoned about
UTI. According to this study 12.9% cases of asymptomac
babies with indirect hyperbilirubinemia had UTI. This was
reported to be 15 and 18% in other studies.14,15 Ghaemi et
al. studies evaluated late and prolonged icterus and found
UTI in 5.8%.4 The reason for lower incidence of UTI in laer
study maybe due to the fact that they had evaluated only
late and prolonged jaundice and had excluded physiological
jaundice whereas other studies including our study had
included physiological jaundice. Most of the studies have
evaluated late jaundice with UTI where mean age was at
range of 5-12.1 days.3,16 In our study we compared early
physiological jaundice with mean age at onset of jaundice
5.0±1.04 days with late prolonged jaundice with mean
age 13.60±4.88. To our knowledge, very few studies have
compared the incidence of UTI in asymptomac jaundiced
newborns between early physiological and late prolonged
jaundice. The incidence of UTI was found to be double in
late than early icterus (27.2% Vs 14.2%) in one study.15 We
also had high incidence of UTI in late prolonged jaundice
10/11 (90.9%) Vs 1/11 (10.1%) with p<0.046 and [OR
7.210, 95% CI (0.870, 59.270)]. Another study where
mean age at onset of jaundice was 8.9 days the incidence
of jaundice was found to be 8.2%.17 In this study, one
case with early physiological jaundice had UTI, however
in this case sepsis could have been the cause of jaundice
as some asymptomac babies had high total WBC count
and posive CRP. In a study from Turkey Hulya Bilgen et al.
emphasized on the importance of urine culture as roune
workup in all neonatal jaundice.9
Neonatal hyperbilirubunemia was more frequent in males
in our study. Similar nding was noted in another study.4
Again, unlike our study UTI was more prevalent in females,
suggesng that there are no sex predominance for UTI in
newborns.18 UTI was noted more in term gestaon babies
with prolonged jaundice in this study. Supporng our
study all culture posive newborns were of term gestaon
in Chamdine Omar et al. study and other two studies
reported that hyperbilirubinemia was the main clinical
nding among term newborns with UTI.19-21
Although Garcia et al. reported that an elevated
conjugated bilirubin fracon was more likely to have
UTI; none of our paents had a high direct bilirubin
level.22 The hyperbilirubinemia associated with UTIs can
be unconjugated and related to hemolysis caused by
Escherichia coli and other Gram-negave organisms, or
conjugated secondary to cholestasis.10,23-26 The mechanism
by which a UTI causes cholestasis is not clear, but possible
DISCUSSION
Hyperbilirubinemia is one of the presenng signs of
bacterial infecon in newborns, and its associaon with
urinary tract infecon (UTI) has been reported by several
Authors.8,9 Urinary evaluaon is rounely done in seriously
ill jaundiced newborns who present with features of
sepsis But in cases where newborns are asymptomac
and present with indirect hyperbilirubinemia urine
evaluaon is not a roune test hence the diagnosis of UTI
Page 45
VOL. 14 | NO. 1 | ISSUE 53 | JAN-MAR 2016
mechanisms include microcirculatory changes in the
liver, direct eects from bacterial products, and/or from
endotoxin-induced mediators.27,28 It is postulated that even
mild hemolysis can overload the immature liver conjugang
mechanism, leading to an increase in serum bilirubin levels.
Supporng the statement, E. coli is responsible for the
vast majority of UTI in young infants, E. coli (45.45%) was
the predominant pathogen isolated in this study followed
by Klebsiella (27.27%), enterococcus (18.18%) and Staph.
aureus (9.09% %). Similar organisms were isolated in other
studies but the anbioc sensivity paern diered.15 Other
lab parameters like total WBC count, neutrophil count and
CRP was signicantly elevated in prolonged jaundice cases
so maybe these could also be included as roune screening
tool even in asymptomac hyperbilirubinemic newborns.
CONCLUSION
UTI can occur in asymptomac, unconjugated neonatal
jaundice and was 12.9% in this study. In addion, UTI
was signicantly high in late prolonged unconjugated
hyperbilirubinema. Therefore, based on the result of this
study we suggest that urine culture to be considered as part
of the diagnosc evaluaon for asymptomac newborns
with late prolonged unconjugated hyperbilirubinemia.
Since this was just a hospital based study a sucient
large cohort study is essenal for beer conclusion. This
may help idenfy UTI before signs and symptoms become
evident and help in mely treatment.
ACKNOWLEDGEMENT
We thank the newborns and mothers of newborns who
parcipated in this study. We also express our gratude
to Professor and Head of department Dr. K Seshagiri
Rao, Manipal Teaching Hospital, Pokhara for granng us
permission to do the study. We are also thankful to Dr. Isha
Bhandari for her contribuon in collecng data.
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Original Arcle
KATHMANDU UNIVERSITY MEDICAL JOURNAL
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... UTI increases bilirubin load by causing hemolysis in erythrocytes, and causes hyperbilirubinemia by decreasing conjugation in the liver, and decreasing excretion of bilirubin [11]. In some studies, the prevalence of UTI in prolonged jaundice was as low as 5-10%, while it was found to be higher as 15-36% in other studies [1,8,[12][13][14][15][16][17]. ...
Article
Full-text available
Objectives: Prolonged jaundice is a common condition among neonates. İt is defined as persisting hyperbilirubinemia after the 14th day following birth for term babies and after the 21st day for premature babies with serum bilirubin level higher than 5mg/dL. Prolonged unconjugated hyperbilirubinemia may be associated with some pathological conditions. We aimed to evaluate the etiological, clinical and laboratory findings of babies with prolonged jaundice. Methods: This descriptive cross-sectional study included 90 infants with prolonged jaundice in the pediatric outpatient clinic of Ordu University Training and Research Hospital between 1 January 2015 and 1 October 2020. Demographic characteristics, physical examination and laboratory findings of the babies were collected and analyzed to determine the etiology of neonatal hyperbilirubinemia. Results: In total 90 infants with prolonged jaundice were presented in this study, including 50 male and 40 female neonates. The most common causes of prolonged neonatal jaundice were breastfeeding, Rh or ABO incompatibility, and urinary tract infection 73%, 13% and 8% of neonates, respectively. Conclusion: Breast milk jaundice is the most common cause of prolonged jaundice in infants. Although there are some explanations for breast milk jaundice, the exact mechanism leading to breast milk jaundice is not clear. Other reasons that may affect the infants later in life should be investigated in a short time.
... However, according to the literature, several studies showed a significant prevalence of UTI in unconjugated neonatal hyperbilirubinemia. Besides, studies showed that unconjugated hyperbilirubinemia might reportedly be a significant or even the first presentation of UTI in neonates (4,7,(34)(35)(36)(37)(38)(39). In our systematic review, the prevalence of UTI in neonates with unexplained unconjugated hyperbilirubinemia was 4.01%, which seems to be lower than the pooled prevalence of UTI in all studies (i.e., 6.81%). ...
Article
Full-text available
Background: The prevalence and risk factors of urinary tract infection (UTI) in neonates with unexplained hyperbilirubinemia are not studied thoroughly. Since the prevalence of UTI is highly variable in different areas and countries, this study aimed to review the existing data of Iranian neonates with UTI presented with unexplained hyperbilirubinemia. Methods: This study is a meta-analysis of Iranian newborns with unexplained hyperbilirubinemia. We identified all studies indexed in international (Web of Science, PubMed, Scopus, Google Scholar) and national (Science Information Database, Magiran) databases from 2000-2018. Search terms included: Urinary Tract Infections OR UTI AND urine OR culture OR microbio, jaundice OR icter OR hyperbili, AND Iran. Results: Overall, 4210 neonates from 17 studies were included. The pooled prevalence of UTI in neonates with unexplained hyperbilirubinemia was 6.81% (95% CI: 4.86-8.77). Considering the subgroups analyses; the prevalence of UTI was higher in the prolonged vs. not-prolonged state (8.34% vs. 4.00%), low birth weight vs. normal birth weight (7.81% vs. 4.51%), and exclusive vs. non-exclusive breastfeeding (8.84% vs. 4.72%). Male gender and low birth weight increased the risk of UTI about two times compared to the female gender and normal birth weight, respectively. The results of the analyses in neonates with unconjugated hyperbilirubinemia also showed the above-mentioned subgroup differences. Conclusion: Due to considerable prevalence of UTI in neonates with unexplained hyperbilirubinemia and risk factors in this age group, investigation for UTI is essential for the workup in this situation.
... Furthermore, relaxation of muscle precontracted with KCl occurs at physiological (3-35 M, 0.2-2 mg/dl) and pathophysiological concentrations, suggesting that bilirubin may reduce Ca 2ϩ sensitivity and that hyperbilirubinemic individuals may experience increased risk of urinary tract infections (UTI) (61). Interestingly, UTI prevalence is marginally but significantly increased in healthy infants with prolonged hyperbilirubinemia versus those with physiological hyperbilirubinemia (58). Bilirubin also potentiates NO-induced gastric smooth muscle relaxation [Colpaert et al. (26); Table 1]; however, pathophysiological (200 M) rather than physiologically relevant concentrations of conjugated BRT were tested. ...
Article
Bilirubin, a potentially toxic catabolite of heme and indicator of hepato-biliary insufficiency, exhibits potent cardiac and vascular protective properties. Individuals with Gilbert's syndrome (GS) may experience hyperbilirubinemia in response to stressors including reduced hepatic bilirubin excretion/increased red blood cell breakdown, with individuals usually informed by their clinician that their condition is of little consequence. However, GS appears to protect from all-cause mortality, with progressively elevated total bilirubin associated with protection from ischemic heart and chronic obstructive pulmonary diseases. Bilirubin may protect against these diseases and associated mortality by reducing circulating cholesterol, oxidative lipid/protein modifications and blood pressure. In addition, bilirubin inhibits platelet activation and protects the heart from ischemia-reperfusion (I-R) injury. These effects attenuate multiple stages of the atherosclerotic process, in addition to protecting the heart during resultant ischemic stress, likely underpinning the profound reduction in cardiovascular mortality in hyperbilirubinemic GS. This review outlines our current knowledge of and uses for bilirubin in clinical medicine, and summarises recent progress in revealing the physiological importance of this poorly understood molecule. We believe that this review will be of significant interest to clinicians, medical researchers and individuals who have GS.
Article
Background and objective: Previously reported prevalence of urinary tract infections (UTIs) in infants with jaundice range from <1% to 25%. However, UTI criteria are variable and, as demonstrated in a meta-analysis on UTI prevalence in bronchiolitis, disease prevalence is greatly impacted by disease definition. The objective of this study was to conduct a systemic review and meta-analysis examining the impact of including positive urinalysis (UA) results as a diagnostic criterion on the estimated UTI prevalence in young infants with jaundice. Methods: The data sources used were Medline (1946-2020) and Ovid Embase (1976-2020) through January 2020 and bibliographies of retrieved articles. We selected studies reporting UTI prevalence in young infants with jaundice. Data were extracted in accordance with meta-analysis of observational studies in epidemiology guidelines. Random-effects models produced a weighted pooled event rate with 95% confidence intervals (CI). Results: We screened 526 unique articles by abstract and reviewed 53 full-text articles. We included 32 studies and 16 contained UA data. The overall UTI prevalence in young infants with jaundice from all 32 studies was 6.2% (95% CI, 3.9-8.9). From the 16 studies with UA data, the overall UTI prevalence was 8.7% (95% CI, 5.1-13.2), which decreased to 3.6% (95% CI, 2.0-5.8) with positive UA results included as a diagnostic criterion. Conclusions: The estimated UTI prevalence in young infants with jaundice decreases substantially when UA results are incorporated into the UTI definition. Due to the heterogeneity of study subjects' ages and definitions of jaundice, positive UA results, and UTI, there is uncertainty about the exact prevalence and about which infants with hyperbilirubinemia warrant urine testing.
Article
Background: Neonatal hyperbilirubinemia (NH) may be the initial and solitary sign of infectious condition in neonates. This retrospective cohort study aims to evaluate the risk of sepsis or urinary tract infection in well-appearing infants with NH below 7 days old. Methods: All neonates (n = 8,779) born in Taipei Veterans General Hospital from 2013 to 2017 were evaluated retrospectively. A total of 2,523 initially well-appearing babies were admitted because of NH. After being hospitalized, patients were categorized into two groups according to the initial transcutaneous bilirubin (TCB) level. Infectious screening results, which include C-reactive protein (CRP), differential count, blood culture, urinalysis, and urine culture, were analyzed. Results: Regarding CRP, 2.7% (18/667) of neonates with NH had elevated CRP (≥1 mg/dL). Among 547 blood cultures, eight were positive, with 0.4% (2/547) non-coagulase-negative staphylococcus (CoNS) bacteremia and 1.1% (6/547) CoNS bacteremia. In urinalysis, 16.6% (182/1,094) of NH neonates had pyuria, and 6.7% (25/372) had positive urine cultures. NH with a higher initial TCB level was related to an increased chance of elevated CRP (4.7% vs. 1.5%, odds ratio: 3.29, p = 0.024) and pyuria (20.6% vs. 12.6%, odds ratio: 1.79, p < 0.001). The rate of positive urine culture between the higher- and lower-TCB groups had no significant difference (6.6% vs. 6.9%, p > 0.99). Significant bacteriuria was more common in NH neonates admitted at later age (>2 days) (4.9% vs. 11.5%, p = 0.035). Conclusion: In well-appearing neonates below 7 days old, NH with a higher initial TCB is associated with an increased rate in pyuria and abnormal CRP. No difference was found in the rate of positive urine culture between higher and lower TCB levels. Significant bacteriuria was more common in older NH neonates. Septicemia is rare among well-appearing neonates with NH.
Article
Full-text available
Jaundice is a common problem during the neonatal period. About 60% of the full term and 80% of premature infants develop jaundice. It can be associated with serious illnesses such as Urinary tract infections. The aim of this study is to evaluate the incidence and prevalence of urinary tract infection in newborns with indirect hyperbilirubinemia and to find a relationship with prolonged jaundice. We retrospectively evaluated asymptomatic, jaundiced neonates for evidence of a urinary tract infection. Data reviewed including demographic and historical data were included with data of blood studies, radiological evaluation and treatment. 32 neonates of 152 cases had urinary tract infection. Most commonly isolated organisms were Klebsiella and Escherishia coli. Maximum duration of phototherapy was 4 days in the urinary tract infection group versus 7 in the non-urinary tract infection group. Intensive phototherapy was used in 18.7% in the urinary tract infection group versus 29.16% in the non-urinary tract infection group. None of the newborns in the urinary tract infection group underwent exchange transfusion therapy. Urinary tract infection can occur in asymptomatic, jaundiced newborns. Thus, it may be the first in these babies before other signs become evident.
Article
Full-text available
This study was performed on 100 jaundiced neonates as cases and on 100 neonates without hyperbilirubinemia as controls to investigate the incidence of UTI in neonates with hyperbilirubinemia. Medical history, physical examinations and laboratory tests were done on all cases and data was analyzed by SPSS software. The urinary analysis and culture (U/A, U/C) were performed on the urinary samples which were collected by bladder catheterization under sterile condition. Of the total of 100 jaundiced neonates, 11 cases had UTI, while there was no case of UTI in neonates without jaundice. This difference in the incidence of UTI between two groups was significance (p-value = 0.001). Vesicourethral reflux was the most common finding anomaly in the neonates with UTI. Our results indicate that UTI is one of the important factors in neonatal jaundice. Therefore it is necessary to do U/A and U/C in all the neonates with hyperbilirubinemia. In addition, radiological studies such as sonography and voiding cystourethrography (VCUG) in all the neonates with UTI are necessary.
Article
Objective: Jaundice is one of the presenting signs of urinary tract infection (UTI). Prevalence of UTI in febrile infants is between 5% and 11%. Previous studies have shown that jaundice may be one of the presenting signs of sepsis or urinary tract infection in newborns. The goal of this study was to determine the prevalence of UTI in asymptomatic, jaundiced neonates. Methods: Eighty five asymptomatic unexplained jaundice evaluated for evidence of UTI by suprapubic bladder aspiration. UTI defined as one colony forming units per milliliter of single pathogen obtained on all study infants. Detailed questionnaires were completed include demographic information. Results Seven (8.2%) of 85 infants had UTI. Isolated pathogens included E. coli, Kelebsiella, Entrococcous, Coagulase negative Staphylococcus and Entrobacter Aerogenese. There were no correlation between total and direct serum bilirubin level and positive urine culture (P = 0.78 and P = 0.44 respectively). Conclusion: A UTI was found in 8.2% of asymptomatic unexplained afebrial jaundiced neonate. More studies is necessary to answer this question: should urine culture be considered in asymptomatic jaundiced neonate.
Article
Hyperbilirubinemia is one of the presenting signs of bacterial infection in newborns, and the association of neonatal jaundice with urinary tract infection (UTI) has been particularly emphasized. The aim of this study was to determine the prevalence of UTI in asymptomatic jaundiced neonates younger than 4 weeks old. We prospectively evaluated 120 asymptomatic jaundiced and 122 healthy neonates without jaundice younger than 4 weeks old for UTI. Patients with UTI, defined as >10,000 colony-forming units of a single pathogen per milliliter urine obtained by bladder catheterization, were evaluated for sepsis. Of 120 asymptomatic jaundiced neonates with a mean age of 7 ± 4 days, 15 (12.5%) had a UTI. Of 122 healthy neonates, positive urine cultures from a urine bag were found in eight cases; however on reevaluation, urine cultures from bladder catheterization were negative. The most common pathogen isolated from the UTI cases was Klebsiella pneumoniae. Also, unconjugated hyperbilirubinemia was detected in all jaundiced patients with UTI. UTI was found in 12.5% of the asymptomatic jaundiced neonates with the onset of unconjugated hyperbilirubinemia in the first week of life. Therefore, we suggest that urine culture should be considered as a part of the diagnostic evaluation of jaundiced neonates older than 3 days with an unexplained etiology.
Article
Twenty-four infants 8--62 days of age with urinary tract infection have presented with a chief complaint of jaundice. The bilirubin determinations have ranged from 6--48.2 mg/dl, with elevation of both the direct and indirect reacting bilirubin fractions except for the youngest infants (under 10 days old), where only indirect bilirubin elevation was present. The BUNs ranged from 18--153 mg/dl with general correlation to the bilirubin elevation. Hemolysis was documented in 21 infants. The infecting organisms were predominantly Escherichia coli (20 patients) of the low-number serotypes. We have been able to test 11 of the isolates and have found that all produced hemolysis on blood agar plates. Another interesting observation has been the reversal of the expected frequency of the A and B blood groups in our series. There is an excessive number of infants of blood group B with a paucity of blood group A; blood group O is as expected. The relationship of blood group type and E. coli infection and the presence or absence of jaundice needs to be explored in a larger group of infants.
Article
In this prospective study of 442 infants younger than 8 weeks of age who attended a pediatric emergency department with temperature greater than or equal to 100.6 degrees F (38.1 degrees C), urinary tract infections (UTIs) were found in 33 patients (7.5%), 2 of whom were bacteremic. Clinical and laboratory data were not helpful for identifying UTIs. Of the 33 patients with UTIs, 32 had urinalyses recorded; 16 were suggestive of a UTI (more than five white blood cells per high-power field or any bacteria present). Of the 16 infants with apparently normal urinalysis results, three had an emergency department diagnosis suggesting an alternative bacterial focus of infection. If the physician had decided on the basis of apparently normal urinalysis results to forgo obtaining a urine culture, more than half of the UTIs would have been missed. Bag-collected specimens were significantly more likely to yield indeterminate urine culture results than either catheter or suprapubic specimens. In addition, uncircumcised males were significantly more likely to have a UTI than circumcised boys. These results suggest that a suprapubic or catheter-obtained urine specimen for culture is a necessary part of the evaluation of all febrile infants younger than 8 weeks of age, regardless of the urinalysis findings or another focus of presumed bacterial infection.
Article
This prospective study was performed to determine the frequency of unexplained unconjugated hyperbilirubinemia associated with bacterial infection during the first week of life. Of 5805 infants delivered between September 1984 and December 1986, 93 jaundiced newborns without evidence of septicemia fulfilled the following criteria to be enrolled in the study: weight greater than 2500 g, gestational age greater than 38 weeks, age less than 7 days, and unexplained unconjugated bilirubin greater than 170 mumol/L (greater than 10 mg/dL) during the first 48 hours of life and/or greater than 255 mumol/L (greater than 15 mg/dL) thereafter. Evaluation for septicemia included blood and urine cultures, and white cell and thrombocyte counts. The study disclosed three (3.2%) infants who developed septicemia before any clinical suspicion had been aroused. It is concluded that bacterial infections should be considered a possible cause of neonatal unconjugated hyperbilirubinemia during the first week of life, regardless of the clinical condition of the infant.