Journal of Obstetrics and Gynaecology

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Urinary tract infection during pregnancy: current

concepts on a common multifaceted problem

Kallirhoe Kalinderi, Dimitrios Delkos, Michail Kalinderis, Apostolos

Athanasiadis & Ioannis Kalogiannidis

To cite this article: Kallirhoe Kalinderi, Dimitrios Delkos, Michail Kalinderis, Apostolos
Athanasiadis & Ioannis Kalogiannidis (2018): Urinary tract infection during pregnancy: current
concepts on a common multifaceted problem, Journal of Obstetrics and Gynaecology, DOI:
10.1080/01443615.2017.1370579

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Published online: 06 Feb 2018.

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JOURNAL OF OBSTETRICS AND GYNAECOLOGY, 2018
https://doi.org/10.1080/01443615.2017.1370579

REVIEW ARTICLE

Urinary tract infection during pregnancy: current concepts on a common

multifaceted problem
Kallirhoe Kalinderia, Dimitrios Delkosa, Michail Kalinderisb, Apostolos Athanasiadisa and Ioannis Kalogiannidisa
a
3rd Department of Obstetrics and Gynaecology, Aristotle University of Thessaloniki, Thessaloniki, Greece; bDepartment of Obstetrics and
Gynaecology, King’s College Hospital NHS Foundation Trust, Princess Royal University Hospital, Orpington, UK

ABSTRACT KEYWORDS
Urinary tract infections (UTIs) are the most common bacterial infection in pregnancy, increasing the risk Urinary tract infection;
of maternal and neonatal morbidity and mortality. Urinary tract infections may present as asymptomatic asymptomatic bacteriuria;
bacteriuria, acute cystitis or pyelonephritis. Escherichia coli is the most common pathogen associated pyelonephritis; preeclamp-
sia; urinary microbiome
with both symptomatic and asymptomatic bacteriuria. If asymptomatic bacteriuria is untreated, up to
30% of mothers develop acute pyelonephritis, with an increased risk of multiple maternal and neonatal
complications, such as preeclampsia, preterm birth, intrauterine growth restriction and low birth weight.
Urinary tract infection is a common, but preventable cause of pregnancy complications, thus urinary
tests, such as urine culture or new technologies such as high-throughput DNA sequence-based analy-
ses, should be used in order to improve antenatal screening of pregnant women.

Introduction uretero-vesical reflux. Additionally, differences in urine pH

Urinary tract infection (UTI) is a common health problem
characterised by the presence of microbial pathogens in any
part of the urinary tract including the kidneys, ureters, blad-
der or urethra. UTI is more common in women due to
shorter urethra, closer proximity of the anus with vagina, as
well as easier entry of pathogenic microorganisms by sexual
activity (Mittal and Wing 2005). In pregnancy, it is consid-
ered as the most common bacterial infection with increased
risks of maternal and neonatal (perinatal) morbidity and
mortality (Foxman 2002). This review highlights the current
knowledge on a UTI during pregnancy, focussing on the
possible adverse maternal and neonatal outcomes, as well
as the perspective of introduction of high-throughput DNA
sequence-based techniques for urinary testing, in order to
explore the role of resident urinary bacterial communities in
health and disease.
Pathophysiology
In pregnancy, many hormonal and anatomical changes favour
a UTI (Hannan et al. 2013). Early in a pregnancy at around
seven weeks, the ureters begin to dilate due to smooth
muscle relaxation induced by progesterone. Later on, with a
peak at 22–26 weeks, mechanical compression from the
enlarging gravid uterus further aggravates the phenomenon
of hydronephrosis of pregnancy (Jeyabalan and Lain 2007).
Moreover, an increased plasma volume during pregnancy
leads to decrease urine concentration and increased bladder
volume. All of these factors promote urinary stasis and
and osmolality, as well as pregnancy-induced glycosuria and
aminoaciduria further facilitate bacterial growth and UTI (Ipe
et al. 2016).
Classification
Urinary tract infections in pregnancy are classified as either
asymptomatic or symptomatic. Asymptomatic bacteriuria is
defined as the isolation of bacteria in at least 1
105 colony-
forming units per mL of cultured urine, in the absence of
signs or symptoms of a UTI. Symptomatic UTIs are divided
into lower tract (acute cystitis) or upper tract (acute pyelo-
nephritis) infections (Bahadi et al. 2010). Asymptomatic bac-
teriuria occurs in 2–15% of pregnant women and is a major
risk factor for developing symptomatic UTIs during pregnancy
(Ipe et al. 2013). The prevalence of symptomatic urine infec-
tion during pregnancy is less common, complicating about
1–2% of all pregnancies (Schnarr and Smaill 2008). Among
symptomatic UTI, cystitis is defined as significant bacteriuria
with associated bladder mucosal invasion, whereas pyelo-
nephritis is defined as significant bacteriuria with associated
inflammation of the renal parenchyma, calices and pelvis. The
major symptoms of cystitis are dysuria, urgency and frequent
urination and the affected patient may present with suprapu-
bic tenderness. Pyelonephritis is usually accompanied by
fever, lumbar pain, nausea and vomiting. If asymptomatic
bacteriuria is untreated, 20–40% of cases progress to acute
UTI, such as pyelonephritis and can likely cause multiple
pregnancy complications, including premature delivery in

CONTACT Kallirhoe Kalinderi roey111@hotmail.com 3rd Department of Obstetrics and Gynaecology, Aristotle University of Thessaloniki, 49
Konstantinoupoleos Str, GR-54642, Thessaloniki, Greece
ß 2018 Informa UK Limited, trading as Taylor & Francis Group
2 K. KALINDERI ET AL.
Table 1. Risk factors related to bacteriuria in pregnancy.
Risk factors
Previous UTI
Anatomic urinary tract abnormalities
Functional urinary tract abnormalities
Diabetes mellitus
Sickle cell disease
Low socioeconomic status
Multiparity
Increased frequency of sexual activity
UTI: urinary tract infection.
20–50% of cases (Whalley 1967; Patterson and Andriole 1997;
MacLean 2001).
Risk factors and pathogenic microorganisms
The prevalence of bacteriuria in pregnancy has been related
to some risk factors (Matuszkiewicz-Rowin
ska et al. 2015)
(Table 1). The more frequent risk factor which contributes to
the bacteriuria in pregnancy is previous UTI, and one of the
biggest risk factors for symptomatic infection is asymptomatic
bacteriuria. Hydroureter, hydronephrosis are the most com-
mon anatomical while vesico-ureteric reflux are the com-
moner functional abnormalities in pregnancy that predispose
to UTIs. Furthermore, pathogenic microorganisms associated
with both symptomatic and asymptomatic bacteriuria are
Escherichia coli, accounting for up to 86% of cases,
Staphylococcus saprophyticus, Klebsiella spp, Enterobacter spp,
Proteus spp, Enterococcus spp, group B Streptococcus, etc.
(Sheiner et al. 2009; Celen et al. 2011; Ipe et al. 2013).
Screening methods
Various methods are used to detect bacteriuria, with the gold
standard being urine culture. The presence of a urinary culture
composed of greater than 100,000 colony-forming units of a
single organism in a symptomatic pregnant woman confirms
the diagnosis of UTI. Urinalysis can be used to look for protein,
white blood cells (WBCs) and red blood cells, as well as urine
dipstick for nitrites and leukocyte esterase; however, these
tests have poor predictive values and increased false negatives
results (Loh and Sivalingam 2007). Positive nitrites suggest the
presence of gram-negative bacteria, such as Escherichia coli,
Klebsiella, Proteus and Enterobacter, as these organisms convert
urinary nitrates to nitrites, however, this test will be negative
in the presence of gram-positive species such as
Staphylococcus or Streptococcus. The detection of leukocyte
esterase reflects an increased number of WBCs in the urine,
such as in pyuria, however, in the initial phase of an infection
and until a certain threshold has been reached, the test can
be negative (Mignini et al. 2009). Urine microscopy can also
be helpful in detecting bacteria. If a significant amount of
squamous epithelia cells (>15–20 per high-power field) are
present, then the sample is likely to be contaminated and a
new sample should be collected (Bachman et al. 1993).
UTI and antibiotic treatment in pregnancy
By the time bacteriuria is diagnosed in pregnancy, even if
asymptomatic, antibiotic treatment should be commenced
Table 2. Antibiotics used in UTI during pregnancy.
Antibiotics Key points
Amoxicillin If susceptible
Ampicillin If susceptible
Fosfomycin Alternative of amoxicillin-ampicillin
Cephalexin Least preferred option
Trimethoprim Avoid in first trimester (folate antagonist)
Nitrofurantoin Avoid at 36 weeks (haemolysis in the newborn)
(U.S. Preventive Services Task Force 2008; National Institute
for Clinical Excellence 2010) (Table 2). Almost 20–40% of
cases of E. coli show resistance to Ampicillin and Amoxicillin,
so their use is not optimal when this organism is detected.
Fosfomycin is a useful alternative (Delzell and Lefevre 2000).
Women with asymptomatic bacteriuria in pregnancy should
be treated by the standard regimen of antibiotics for seven
days (Delzell and Lefevre 2000; Widmer et al. 2015), except
for recurrent infections where treatment should last for
10–14 days. Notably, group B streptococcus (GBS) is com-
monly associated with vertical transmission from mother to
infant, and maternal treatment with intrapartum intravenous
antibiotics is needed when GBS bacteriuria is detected during
pregnancy. Adequate prophylaxis is exposure to penicillin
(preferred agent), ampicillin or cefazolin, given for >4 h
before delivery. In cases of frequent UTI associated with sex-
ual intercourse, postcoital antibiotics can be used. In cases of
pyelonephritis, hospital admission and intravenous antibiotics
should be given for 48 hours together with antipyretics, until
the patient becomes afebrile. Thereafter, oral antibiotics
should be continued for 10–14 days. Several antibiotics can
be used. A clinical trial comparing three parenteral regiments
found no difference in the length of hospitalisation, recur-
rence of pyelonephritis or preterm delivery (Wing et al. 1998).
However, it is important to consider antimicrobial resistance
patterns when choosing an agent (Jolley and Wing 2010).
Further addressing this issue, it should be underlined that
unnecessary use of antibiotics in everyday clinical practice
should be avoided and asymtomatic bacteriuria should not
be treated in adults (Trautner 2011). Special treatment should
only be administered in pregnancy (Millar and Cox 1997;
Imade et al. 2010) and the eradication of bacteriuria should
be confirmed with a second urine culture 1–2 weeks after the
antibiotic course has been completed.
UTI and pre-eclampsia
Pre-eclampsia (PE) is a pregnancy-specific syndrome char-
acterised by new onset hypertension and proteinuria after
the 20th week of gestation in a previously normotensive
woman. The understanding of PE pathophysiology is
unclear and it seems that multiple factors act in concert
leading to its clinical manifestations. A generalised inflam-
matory response primarily governed by cytokines has
been considered to have a pivotal role in the pathogen-
esis of this syndrome (Conrad et al. 1998). Interestingly,
while a normal pregnancy is considered a mild inflamma-
tory state, PE is considered to be an exaggerated inflam-
matory state (Kalinderis et al. 2011; Kalinderis et al. 2015).
What triggers this excessive inflammatory response is cur-
rently unknown.
 JOURNAL OF OBSTETRICS AND GYNAECOLOGY 3

Table 3. Studies with positive/negative association of UTI with complications in pregnancy.

Studies Type of study Cases, n PE Preterm birth LBW IUGR
Izadi et al. (2016) (19) Cohort 239 þ 1 1 1
Rezavand et al. (2015) (20) Case-control 250 þ 1 1 1
Easter et al. (2016) (21) Prospective 2607 þ 1 1 1
Bilano et al. (2014) (22) Cross-sectional (multi-country) 276,388 þ 1 1 1
Conde-Agudelo et al. (2008) (23) Meta-analysis 49 studies þ 1 1 1
Shamsi et al. (2010) (24) Case-control 393 – 1 1 1
Qureshi et al. (1994) (25) Prospective 1579 – 1 1 1
Mittendorf et al. (1996) (26) Case-control (nested) 2741 þ 1 1 1
Lee et al. (2015) (27) RCT (cluster) 24 clusters (each 4000 population) 1 þ 1 1
Romero et al. (1989) (30) Meta-analysis 21 cohorts 1 þ þ 1
Smaill and Vazquez (2015) (31) Meta-analysis 2000 1 þ þ 1
Mazor-Dray et al. (2009) (32) Retrospective 4742 þ þ þ þ
Agger et al. (2014) (33) Prospective 676 1 þ 1 1
Alijahan et al. (2014) (34) Case-control 935 1 þ 1 1
Vogel et al. (2014) (35) Cross-sectional (multi-country) 172,461 1 þ 1 1
Chiabi et al. (2013) (36) Cross-sectional 1066 1 þ 1 1
Jain et al. (2013) (37) Prospective 582 þ þ þ þ
Kiss et al. (2004) (38) RCT 4429 1 þ 1 1
Mirzaie and Mohammah-Alizadeh (2007) (39) Retrospective 988 1 – 1 1
Chen et al. (2010) (40) Retrospective (cross-sectional) 85,484 1 – – 1
Kazemier et al. (2015) (41) Prospective 4283 1 – 1 1
Sheiner et al. (2009) (42) Retrospective 199,093 1 þ þ þ
Hantush Zadeh et al. (2013) (43) Retrospective 163 1 1 þ þ
Kessous et al. (2012) (44) Retrospective Positive vs negative GBS 1 þ þ þ
(þ): positive association of UTI with complicated pregnancy; (–): negative association of UTI with complicated pregnancy; 1: not abdicable; PE: preeclampsia;
LBW: low birth weight; IUGR: intra-uterine growth restriction; RCT: randomised controlled trial; ASB: asymptomatic bacteriuria; GBS: group-B streptococcus.

Considering the high prevalence of bacteriuria in pregnancy,
the role of UTI as a risk factor of PE has been widely examined.
A number of studies have found that UTI in pregnancy is
associated with increased risk of PE and suggest that screen-
ing for UTI in the first antenatal visit and during the second
and third trimester of gestation could prevent the occurrence
of this pregnancy complication. A recent study by Izadi et al.
found that a UTI is significantly more frequent in cases of
severe PE compared to healthy pregnant women (Izadi et al.
2016), whereas Rezavand et al. reported that the rate of
asymptomatic bacteriuria was 6.8 times higher in women
with PE compared to controls (Rezavand et al. 2015). Easter
et al. also supported that UTI represent a source of inflamma-
tion that can have additive effects and trigger the clinical
presentation of PE, especially in the third trimester or before
34 weeks (Easter et al. 2016). In a study conducted in 23
developing countries in Africa, Latin America and Asia, UTI
was associated with PE, as well (Bilano et al. 2014). Moreover,
in a previous meta-analysis study, a UTI was found to
increase the risk of PE with an odds ratio of 1.57 (Conde-
Agudelo et al. 2008). However, some studies have failed to
confirm this association and question the causal effect of UTI
on PE (Brumfitt 1975; Shamsi et al. 2010). Factors such as the
timing of infection in relation to PE, underlying kidney prob-
lems that can act as confounding factors or bias by increased
ascertainment of UTI in pregnancy should be further assessed
in order to establish a true association of UTI and PE.
Notably, a previous study had shown that nulliparous women
with a history of UTI in pregnancy were five times more likely
to develop PE compared to nulliparous pregnant women
without UTI and the use of antibiotics may decrease the inci-
dence of PE (Mittendorf et al. 1996). Thus, a careful monitor-
ing of pregnant women for UTI may be proved useful in early
detection and prevention of PE. However, larger studies are
needed to elucidate the exact association of UTI with PE. The
relationship between UTIs and PE of the former studies is
presented in Table 3.
UTI and preterm birth and low birth weight
Preterm birth, defined as delivery before 37 weeks of gesta-
tion, is the most important cause of neonatal mortality and
morbidity worldwide. Maternal infection accounts for an esti-
mated 50% of preterm births (Lee et al. 2015), the exact
mechanism has not been definitely clarified, however it is
believed that an inflammatory cascade is triggered resulting
in an increased production of cytokines, prostaglandins and
matrix-degrading enzymes that promotes uterine contrac-
tions, cervical dilatation, preterm rupture of the membranes
(PROM), as well as an easier entry of pathogens into the uter-
ine cavity (Keelan et al. 2003). A UTI is the most common
infection in pregnancy, and there is strong evidence of its
association with preterm birth (Table 3).
Approximately, 30% of women with untreated bacteriuria
develop pyelonephritis (Whalley 1967). Untreated pyeloneph-
ritis is a recognised risk factor for preterm birth (Klein and
Gibbs 2005). A meta-analysis by Romero et al., showed that
asymptomatic bacteriuria increased by two-fold the risk of
preterm delivery (Romero et al. 1989). In line with this, in
another meta-analysis conducted by Smaill and Vazquez, anti-
biotic treatment for asymptomatic bacteriuria and UTI
avoided complications such as pyelonephritis and reduced
the risks of preterm birth and low birth weight (Smaill and
Vazquez 2015) (Table 3). Other studies have also found a sig-
nificant association of UTI and preterm birth, especially in low
income countries (Mazor-Dray et al. 2009; Chiabi et al. 2013;
Agger et al. 2014; Alijahan et al. 2014; Vogel et al. 2014; Lee
et al. 2015) and routine screening has been recommended in
order to avoid such complications. In a recent prospective
4 K. KALINDERI ET AL.
study among North Indian pregnant women, no association
between asymptomatic bacteriuria diagnosed early during
pregnancy and adverse pregnancy outcomes were reported
(Jain et al. 2013). This result was attributed to early diagnosis
and effective antibiotic treatment, thus early screening of
pregnancy women for asymptomatic bacteriuria was pro-
posed as a cost effective methodology. Moreover, a multi-
centre randomised control trial by Kiss et al., reported a 56%
reduction in preterm birth rates when implementing this
antenatal screening programme (Kiss et al. 2004). However,
other studies did not confirm a significant association of UTI
and preterm birth (Mirzaie and Mohammah-Alizadeh 2007;
Chen et al. 2010), including a recent study by Kazemier et al.
which did not find an association between asymptomatic
bacteriuria and preterm birth in uncomplicated singleton
pregnancies (Kazemier et al. 2015) (Table 3). The role of GBS
has specifically been underlined as it has been associated
with adverse pregnancy outcomes including preterm delivery
and premature rupture of membranes. A small randomised
control trial have shown a reduction of preterm rupture of
membranes and preterm delivery when antibiotics where
administered in the group of pregnant women with GBS bac-
teriuria compared to placebo (Thomsen et al. 1987).
Moreover, the presence of GBS in urine is an independent
risk factor for GBS neonatal disease, thus its detection at lev-
els of 103 cfu/ml (lower than usual values reported for
asymptomatic bacteriuria) requires antibiotic therapy in preg-
nancy (Smaill 2007; Kessous et al. 2012).
UTI and intra-uterine growth restriction
Intra-uterine Growth Restriction (IUGR) refers to a condition
in which a foetus is unable to achieve its genetically deter-
mined potential size. Infection may be an aetiological factor
due to endothelial damage and/or aggravating maternal
inflammatory responses. Sheiner et al., in a retrospective
study found an association of asymptomatic bacteriuria with
IUGR (Sheiner et al. 2009). In the study of Jain et al., late
detected women showed 3.79 times increased chances of
developing PE and IUGR as compared to asymptomatic bac-
teriuria negative women, whereas women detected and
treated early in pregnancy did not show increased chances
of these complications (Jain et al. 2013). Other studies have
also confirmed the association of asymptomatic bacteriuria
with IUGR (Kessous et al. 2012; Hantush Zadeh et al. 2013);
asymptomatic infections could possibly promote endothelial
damage and impair foetal growth. The positive/negative
association between UTIs and IUGR of the relative studies is
presented in Table 3. Results may differ according to the
ethnicity studied, as well as the inclusion and exclusion crite-
ria used.
Other complications
UTIs have been associated with additional adverse maternal
and neonatal outcomes such as anaemia (Fede 1983; Cox
et al. 1991), chorioamnionitis (Anderson et al. 2007) and
developmental delay/mental retardation (McDermott et al.
2000; McDermott et al. 2001), perinatal mortality (McDermott
et al. 2001), respectively. A significant association has also
been reported between maternal genitourinary infection and
childhood epilepsy, with a stronger association in children of
women with epilepsy; maternal UTI was also associated with
the increased risk of epilepsy in children of women without
epilepsy, however, more weakly (McDermott et al. 2010).
Interestingly in a recent study, maternal genitourinary infec-
tion was associated with increased risk of attention deficit
hyperactivity disorder (ADHD), too (Mann and McDermott
2011). The exact mechanism explaining these findings is cur-
rently unknown, however, in utero inflammation seems to
trigger an inflammatory cascade that can have detrimental
effects in the foetal brain. Additional studies are needed in
order for more definite conclusions to be drawn.
Urinary microbiome: a new challenging concept
The general belief that the urinary tract is sterile, has recently
been questioned since the discovery of the female urinary
microbiota. The term urinary microbiota is defined as the
microorganisms that exist within the bladder, and the urinary
microbiome is the collection of all their genomes. In the
human body, there are 10 bacterial cells for every one human
cell. The Human Microbiome Project was the first large-scale
mapping of the human microbiome. Five body sites were
examined (gastrointestinal tract, mouth, vagina, skin and
nasal cavity) using culture-independent methods (Human
Microbiome Project Consortium 2012). However, the bladder
was not tested as it was considered to be sterile. Standard
testing limits detection to certain organisms, e.g. urine cul-
ture cannot detect slow-growing bacteria that die in the pres-
ence of oxygen. Importantly, two new techniques, expanded
quantitative urine culture (EQUC) and 16S ribosomal RNA
gene sequencing can detect previously unrecognised organ-
isms with greater sensitivity than traditional methods
(Brubaker and Wolfe 2015). EQUC can isolate and identify
many organisms that standard culture misses because it uses
100 times more urine and a variety of media and atmospheric
conditions (Wolfe and Brubaker 2015). Moreover, the develop-
ment of EQUC showed that the DNA detected by sequencing
represents live bacteria, as many organisms detected by
sequencing can only be grown by the advanced EQUC cultur-
ing method. A direct comparison between EQUC and the
standard protocol revealed an impressive 90% false-negative
rate for the standard clinical approach (Hilt et al. 2014). With
this new approach, it has also been found that resident urin-
ary bacteria are distinct from bacteria that cause overt clinical
UTI and urinary bacterial community (microbiota) may be
associated with a certain health status. Thus, the assumption
that urine is sterile seems to be incorrect and the role of resi-
dent urinary bacterial communities in health and disease
should be further assessed, with much of the currently estab-
lished knowledge probably needed to be reconsidered. The
exact role of bladder microbiome is currently unknown and
whether it is a friend or foe is to be investigated. Disruptions
in maternal urinary microbiome may be associated with preg-
nancy complications, as well as maternal, foetal and neonatal
health. Undoubtedly, a new era in our understanding of the

urinary bacterial community in women has emerged and the
development and maintenance of a healthy urinary micro-
biome appears to be of crucial importance.
Conclusions
Urinary tract infections are the most common bacterial infec-
tion in pregnancy, increasing the risk of maternal and neo-
natal morbidity and mortality. Both asymptomatic and
symptomatic UTIs should be treated with appropriate anti-
microbial agents. Urine culture is currently the gold standard
for the diagnosis of bacteriuria, however, the implementation
of high-throughout DNA sequence technologies is awaited in
the near future to pave the way for the identification of the
exact role of resident urinary bacterial communities in health
and disease.
Disclosure statement
The authors have no conflicts of interest to declare.
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