Pregnancy causes numerous
changes in the woman’s body. Hormonal and mechanical changes increase the risk
of urinary stasis and vesicoureteral reflux. These changes, along with an
already short urethra (approximately 3-4 cm in females) and difficulty with
hygiene due to a distended pregnant belly, increase the frequency of urinary
tract infections (UTIs) in pregnant women. Indeed, UTIs are among the most
common bacterial infections during pregnancy.
In general, pregnant
patients are considered immunocompromised UTI hosts because of the physiologic
changes associated with pregnancy (see Pathophysiology). These changes increase
the risk of serious infectious complications from symptomatic and asymptomatic
urinary infections even in healthy pregnant women. (See Urinary Tract
Infection in Females.)
Oral antibiotics are the
treatment of choice for asymptomatic bacteriuria and cystitis. The standard
course of treatment for pyelonephritis is hospital admission and intravenous
antibiotics. Antibiotic prophylaxis is indicated in some cases. (See Treatment
of UTI in Pregnancy and Urethral Catheterization in Women.) Patients
treated for symptomatic UTI during pregnancy should be continued on daily
prophylactic antibiotics for the duration of their pregnancy.
Annual health costs for UTI
exceed $1 billion. Although the condition-specific cost of asymptomatic
bacteriuria or UTI in pregnancy is unknown, screening for these conditions in
pregnant women is cost-effective as compared with treating UTI and pyelonephritis
without screening. Goals for future research include targeting low-income
groups and women in developing countries for screening and early treatment, as
well as determining whether a causal relation exists between maternal UTI and
childhood neurologic consequences.
UTI is defined as the
presence of at least 100,000 organisms per milliliter of urine in an
asymptomatic patient, or as more than 100 organisms/mL of urine with
accompanying pyuria (> 7 white blood cells [WBCs]/mL) in a symptomatic
patient. A diagnosis of UTI should be supported by a positive culture for a
uropathogen, particularly in patients with vague symptoms. UTIs are associated
with risks to both the fetus and the mother, including pyelonephritis,
preterm birth, low birth weight, and increased perinatal mortality.
Asymptomatic bacteriuria
Asymptomatic bacteriuria is
commonly defined as the presence of more than 100,000 organisms/mL in 2
consecutive urine samples in the absence of declared symptoms. Untreated
asymptomatic bacteriuria is a risk factor for acute cystitis (40%) and
pyelonephritis (25-30%) in pregnancy. These cases account for 70% of all cases
of symptomatic UTI among unscreened pregnant women.
Acute cystitis
Acute cystitis involves
only the lower urinary tract; it is characterized by inflammation of the
bladder as a result of bacterial or nonbacterial causes (eg, radiation or viral
infection). Acute cystitis develops in approximately 1% of pregnant patients,
of whom 60% have a negative result on initial screening. Signs and symptoms
include hematuria, dysuria, suprapubic discomfort, frequency, urgency, and
nocturia. These symptoms are often difficult to distinguish from those due to
pregnancy itself.
Acute cystitis is complicated
by upper urinary tract disease (ie, pyelonephritis) in 15-50% of cases.
Acute pyelonephritis
Pyelonephritis is the most
common urinary tract complication in pregnant women, occurring in approximately
2% of all pregnancies. Acute pyelonephritis is characterized by fever, flank
pain, and tenderness in addition to significant bacteriuria. Other symptoms may
include nausea, vomiting, frequency, urgency, and dysuria. Furthermore, women
with additional risk factors (eg, immunosuppression, diabetes, sickle cell
anemia, neurogenic bladder, recurrent or persistent UTIs before pregnancy)
are at an increased risk for a complicated UTI.
Pathophysiology
Infections result from
ascending colonization of the urinary tract, primarily by existing vaginal,
perineal, and fecal flora. Various maternal physiologic and anatomic factors
predispose to ascending infection. Such factors include urinary retention caused
by the weight of the enlarging uterus and urinary stasis due to
progesterone-induced ureteral smooth muscle relaxation. Blood-volume expansion
is accompanied by increases in the glomerular filtration rate and urinary
output.
Loss of ureteral tone
combined with increased urinary tract volume results in urinary stasis, which
can lead to dilatation of the ureters, renal pelvis, and calyces. Urinary
stasis and the presence of vesicoureteral reflux predispose some women to upper
urinary tract infections (UTIs) and acute pyelonephritis.
Calyceal and ureteral
dilatation are more common on the right side; in 86% of cases, the dilatation
is localized to the right. The degree of calyceal dilatation is also more
pronounced on the right than the left (average 15 mm vs 5 mm). This dilatation
appears to begin by about 10 weeks’ gestation and worsens throughout pregnancy.
This is underscored by the distribution of cases of pyelonephritis during
pregnancy: 2% during the first trimester, 52% during the second trimester, and
46% in the third trimester.
Although the influence of
progesterone causes relative dilatation of the ureters, ureteral tone
progressively increases above the pelvic brim during pregnancy. However,
whether bladder pressure increases or decreases during pregnancy is
controversial.
Glycosuria and an increase
in levels of urinary amino acids (aminoaciduria) during pregnancy are
additional factors that lead to UTI. In many cases, glucose excretion increases
during pregnancy over nonpregnant values of 100 mg/day. Glycosuria is due to
impaired resorption by the collecting tubule and loop of Henle of the 5% of the
filtered glucose, which escapes proximal convoluted tubular resorption.
The fractional excretion of
alanine, glycine, histidine, serine, and threonine is increased throughout
pregnancy. levels of cystine, leucine, lysine, phenylalanine, taurine, and
tyrosine are elevated in the first half of pregnancy but return to reference range
levels by the second half. The mechanism of selective aminoaciduria is unknown,
although its presence has been postulated to affect the adherence of Escherichia
coli to the urothelium.
Etiology
E coli is the most
common cause of urinary tract infection (UTI), accounting for approximately
80-90% of cases. It originates from fecal flora colonizing the periurethral
area, causing an ascending infection. Other pathogens include the following:
- Klebsiella pneumoniae (5%)
- Proteus mirabilis (5%)
- Enterobacter species (3%)
- Staphylococcus saprophyticus (2%)
- Group B beta-hemolytic Streptococcus (GBS; 1%)
- Proteus species (2%)
Gram-positive organisms,
particularly Enterococcus faecalis and GBS, are clinically important
pathogens. Infection with S saprophyticus, an aggressive
community-acquired organism, can cause upper urinary tract disease, and this
infection is more likely to be persistent or recurrent.
Urea-splitting bacteria,
including Proteus, Klebsiella, Pseudomonas, and coagulase-negative Staphylococcus, alkalinize
the urine and may be associated with struvite stones. Chlamydial infections are
associated with sterile pyuria and account for more than 30% of atypical
pathogens.
GBS colonization has
important implications during pregnancy. Intrapartum transmission that leads to
neonatal GBS infection can cause pneumonia, meningitis, sepsis, and death.
Current guidelines recommend universal vaginal and rectal screening in all
pregnant women at 35-37 weeks’ gestation rather than treatment based on risk
factors.
Preeclampsia
Women who develop
preeclampsia during pregnancy seem to be predisposed to UTI. A retrospective
review of the perinatal database at a major tertiary center revealed a UTI rate
of 16.2% in normotensive patients, but this increased to 27.3% in women with
mild preeclampsia and 35.9% in women with severe preeclampsia. The authors
hypothesize that underlying renal damage weakens patients’ systemic defense
mechanisms against ascending infection.
Cesarean delivery
Cesarean delivery is
associated with UTI (increasing the likelihood 2.7-fold), but this association
may be confounded by bladder catheterization or prolonged rupture of membranes
(PROM). The incidence of symptomatic UTI is 9.3%, and that of asymptomatic bacteriuria
is 7.6%.
Orthotopic continent urinary diversion
Many women who, in the
past, would have been counseled against pregnancy are now attempting pregnancy.
In orthotopic continent diversion (OCD), an ileal-ascending colon conduit is
made (OCD, Kock pouch) and reattached to the in situ urethra (OCD) or a
continent abdominal stoma (Kock pouch).
Typical candidates are
patients born with congenital exstrophy of the bladder in whom primary
reconstruction has failed. Recurrent UTI and hydronephrosis are common because
of outflow obstruction of the orthotopic stoma secondary to uterine compression
or uterine prolapse. Indwelling catheterization of the urethra or continent
stoma may be necessary, particularly during the later stages of pregnancy. In
rare cases, a percutaneous nephrostomy tube or antegrade passage of a ureteral
stent may be indicated.
Beta streptococci
Beta streptococci are
important pathogens in pregnancy because early and late complications of
neonatal beta-streptococcal infection are well documented. Incidental
documentation of beta-streptococcal bacteriuria suggests a higher colonization
count than is revealed by a screening vaginal or rectal culture.
Beta-streptococcal colonization in the urine warrants immediate treatment and
antibiotic prophylaxis when the patient presents in labor.
Whether beta streptococci
are associated with preterm labor is controversial. In a prospective study,
McKenzie et al found no relation between beta-streptococcal bacteriuria and
preterm labor, but they described the use of urinary antibodies to identify
at-risk women. In 2043 consecutive women, those with E coli antibodies
at the initial visit and at 28 weeks’ gestation and women with
beta-streptococcal antibodies at 28 weeks’ gestation had a significantly higher
chance of preterm delivery.
Epidemiology
The frequency of urinary
tract infection (UTI) in pregnant women (0.3-1.3%) is similar to that in
nonpregnant women. Changes in coital patterns (eg, position, frequency,
postcoital antibiotics) can offset recurrence in at-risk individuals.
Overall, UTIs are 14 times
more frequent in women than in men. This difference is attributed to the
following factors:
- The urethra is shorter in women
- In women, the lower third of the urethra is continually contaminated with pathogens from the vagina and the rectum
- Women tend not to empty their bladders as completely as men do
- The female urogenital system is exposed to bacteria during intercourse
A difference between
pregnant and nonpregnant women is that the prevalence of asymptomatic bacteriuria
in pregnant women is 2.5-11%, as opposed to 3-8% in nonpregnant women. In as
many as 40% of these cases, bacteriuria may progress to symptomatic upper UTI
or pyelonephritis; this rate is significantly higher than that seen in
nonpregnant women.
Several patient-level
factors are associated with an increased frequency of bacteriuria during
pregnancy. Compared with nonindigent patients, indigent patients have a 5-fold
increased incidence of bacteriuria. The risk is doubled in women with sickle
cell trait. Other risk factors for bacteriuria include diabetes mellitus, neurogenic
bladder retention, history of vesicoureteral reflux (treated or untreated), previous renal transplantation, and a history
of previous UTIs.
International statistics
Versi et al described a
higher prevalence of bacteriuria in pregnant white women (6.3%) than in
pregnant Bangladeshi women (2%). Pregnancies that resulted in preterm
deliveries were strongly associated with bacteriuria in white women; this
association was not observed in Bangladeshi women. The authors hypothesized
that the difference could be due to variation in hygiene practices and
clothing.
A large population-based
study of nearly 200,000 pregnant Israeli women demonstrated a 2.5% rate of
asymptomatic bacteriuria and a 2.3% rate
of symptomatic UTI. In this population,
asymptomatic bacteriuria was found to have an association with multiple
pregnancy complications, including hypertension, diabetes, intrauterine growth
retardation, prolonged hospitalization, and preterm labor.
The authors suggested that
these findings may be a marker for intensity of prenatal care rather than a
specific causal effect of the urinary infection. Additionally, their follow-up study examining
women with symptomatic UTI showed a clear association between UTI and low birth
weight and preterm delivery, a finding consistent with those of multiple
previous investigations.
Age- and race-related demographics
The prevalence of UTI
during pregnancy increases with maternal age.
A retrospective analysis of
24,000 births found the prevalence of UTI during pregnancy to be 28.7% in
whites and Asians, 30.1% in blacks, and 41.1% in Hispanics. When socioeconomic
status is controlled for, no significant interracial differences seem to exist.
A survey-based analysis of self-reported UTI found similar trends. This study
also considered Native American women and found the highest prevalence of UTI
in this population (24.2%) as compared with Asian (10.3%), white (16.6%),
Hispanic (18.3%), and black (20.3%) women.
UTI is associated with
preterm delivery in persons of all races. The adjusted odds ratio in infants
with very low birth weight is 2.8 in blacks and 5.6 in whites, adjusted for
parity, body mass index, maternal age, marital status, cigarette smoking,
education, and prenatal care. The overall relative risk of bacteriuria in
blacks or whites is estimated at 1.5-5, and the relative risk of preterm birth
in women with bacteriuria is 1.8-2.3.
Prognosis
In most cases of
bacteriuria and urinary tract infection (UTI) in pregnancy, the prognosis is
excellent. The majority of long-term sequelae are due to complications
associated with septic shock, respiratory failure, and hypotensive hypoxia (ie,
extremity gangrene).
Maternal UTI has few direct
fetal sequelae because fetal bloodstream infection is rare; however, uterine
hypoperfusion due to maternal dehydration, maternal anemia, and direct
bacterial endotoxin damage to the placental vasculature may cause fetal
cerebral hypoperfusion.
Untreated upper UTIs are
associated with low birth weight, prematurity, premature labor,
hypertension, preeclampsia, maternal anemia, and amnionitis. A retrospective population-based study by
Mazor-Dray et al showed that UTI during pregnancy is independently associated
with intrauterine growth restriction, preeclampsia, preterm delivery, and
cesarean delivery.
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