Pathophysiology, Etiology and Complications of UTI during Pregnancy

Tanvi S Madane^*, Prerana P Kulkarni and Gaurav S Memane ^*Correspondence: Tanvi S Madane, Department of Pharmacy, PES Modern College of Pharmacy, Pimpri-Chinchwad, Maharashtra, India, Email:

Author info »

Introduction

In all age groups, UTIs continue to be a major cause of morbidity and medical expenses. UTI is defined as the urothelium’s inflammatory reaction to bacterial invasion, which is typically accompanied by bacteriuria and pyuria. Anywhere along the urinary tract can develop UTI, which comprises abscess, pyelonephritis, cystitis and urethritis. Due to anatomical problems including the proximity of the urethra to the anus, it is one of the most prevalent infectious diseases which seen in sexually active women, during pregnancy and after menopause (Macejko M, et al., 2007). According to reports, 20% of the pregnant women are diagnosed with UTI due to physiological changes such an increase in the plasma volume that may induce reduction in urine concentration and enable bacterial growth that may or may not create symptoms. Additionally, 90% of the pregnant women have structural changes such as urethral dilatation and decreased bladder tone that cause urine stasis (due to pregnancy-related increases in progesterone and oestrogen levels) (Habak PJ and Griggs Jr RP, 2023). The risk of UTI may start in the 6^th week and peak between 22 and 24 weeks later. Untreated UTIs or asymptomatic bacteriuria during pregnancy can have devastating effects on the mother and the fetus, increasing the risk of kidney failure, pyelonephritis, sepsis and other complications such intrauterine growth restriction, preeclampsia and premature delivery. In order to minimise UTI-related complaints, it is crucial to screen for this illness, raise suspicion and recognise it, which will allow to swiftly start the right therapy (Michelim L, et al., 2016). All the pregnant women should undergo urine culture screening, the standard for detecting asymptomatic bacteriuria, at least once during early pregnancy (12-16 weeks), according to the Infectious Diseases Society of America (IDSA) and the United States of America (USA) preventive services task force (Nicolle LE, et al., 2019). Romero RO, et al., 1989, conducted a meta-analysis of 8 clinical studies and found that antibiotic treatment for asymptomatic bacteriuria reduced the incidence of low birthweight with relative risk of 0.56% (95% Confidence Interval (CI): 0.43-0.73). Obstetricians are concerned about it because of its link to high rates of maternal, neonatal illness and mortality (Widmer M, et al., 2015).

Literature Review

UTI classification in pregnancy

Pregnancy urinary tract infections are divided as symptomatic and asymptomatic true bacteriuria (>1,00,000/ml). Cystitis and pyelonephritis are the two types, upper and lower tract infections that cause symptomatic bacteriuria.

Asymptomatic Bacteriuria (ASB): ASB is a type of UTI caused by bacteria which is identified by the presence of >10⁵ Colony Forming Units (CFU)/ml of urine in a clinically asymptomatic individual. Approximately 10% of pregnancies have ASB (Glaser AP and Schaeffer AJ, 2015). Untreated ASB during pregnancy can result in symptomatic UTI in 20%-40% of women, putting both the mother and unborn child at risk (Matuszkiewicz-Rowińska J, et al., 2015). It frequently happens in the 1^st trimester of pregnancy and may be related to prior UTIs, diabetes mellitus, multiparity, low socioeconomic level and illiteracy (Fatima N and Ishrat S, 2006). Low birth weight babies and intrauterine growth retardation are both more likely as a result. Preeclampsia, anemia, chorioamnionitis and postpartum endometritis are also at higher risk. Fetal hazards include perinatal mortality, mental impairment, stillbirth, fetal growth restriction and developmental delay. So, it is advised to perform urinalysis and keep an eye on the quantity, colour, etc., of the urine during the course of the pregnancy (Getaneh T, et al., 2021; Kalinderi K, et al., 2018).

The most typical organism found in urine samples from women with ASB is E. coli. There are frequent correlations between enterobacterial species such Streptococcus, Klebsiella sp. (Behzadi P, et al., 2010).

Acute cystitis: It is an infection of the bladder that frequently spreads to the urethra. About 1% of all pregnant mothers are affected. The presence of symptoms like dysuria, urgency, frequency, nocturia, haematuria and suprapubic discomfort in afebrile women with no signs of systemic illness distinguishes it from asymptomatic bacteriuria, which is defined as significant bacteriuria without associated bladder mucosal invasion (Mc- Cormick T, et al., 2008; Gilstrap III LC and Ramin SM, 2001). When a pregnant woman with symptoms has bacterial growth of a urine culture, the diagnosis is established by the presence of pyuria (>7 white blood cells/ ml) and quantitative count of 10⁵ CFU/ml or 10³ CFU/ml (Macejko AM and Schaeffer AJ, 2007). In 15%-50% of patients, pyelonephritis, an upper urinary tract infection complicates acute cystitis (Guptha K, 2010).

Pyelonephritis: It is an infection of the kidneys and upper urinary system, which is a serious pregnancy complication that can cause serious morbidity for both the mother and fetus (Delzell Jr JE and Lefevre ML, 2000). It is a disease that is suspected when a Midstream Specimen of Urine (MSSU) culture identifies at least 1,00,000 bacteria/ml of single uropathogen with concomitant inflammation of the renal parenchyma, calices, and pelvis in the presence of systemic illness (Mittal P and Wing DA, 2005). Pyelonephritis is most common in the 2^nd and 3^rd trimesters (Patterson TF and Andriole VT, 1987). Pyuria is typically prevalent in pyelonephritis-affected women whose absence may indicate different diagnosis or total obstruction. Immunosuppression, already existing diabetes, history of sickle cell anaemia, neurogenic bladder, frequent or chronic UTIs before pregnancy, tobacco use, age<20 years and being late for prenatal care are additional risk factors for complex UTI in pregnancy (Lucas MJ and Cunningham FG, 1993).

Epidemiology: In comparison to most data gathered in the 1980s and the end of the 1990s in diverse populations throughout the world, the incidences of asymptomatic bacteriuria and the related problems documented by Kass in 1962 are higher (Pastore LM, et al., 1999). Up to 15% of women will experience one episode of UTI at some point in their lives, and UTI accounts for roughly 10% of the primary care consultations made by pregnant women. Pregnant women report getting UTIs about 8% of the time (Andriole VT and Patterson TF, 1991). Women are 14 times as likely than men to have a UTI. Pyelonephritis is the most common cause of shock in pregnant women and affects 2%-4% of pregnancies. It is more frequently right-sided but can be bilateral in up to 25% of cases, and it has 23% recurrence rate right after birth. Pyelonephritis is most common in the second trimester of pregnancy. Asymptomatic Bacteriuria (ASB), with a rate of up to 2%-7%, is the main risk factor for UTI in pregnant women. Contrarily, 1.3% of pregnancies are complicated with cystitis. ASB is more common in women with low socioeconomic status and sickle cell trait carriers. A postpartum UTI is likely to occur in about 25% of cases of ASB that are not treated during pregnancy. Between 2%-13% of studies from the USA, Europe, and Australia found asymptomatic bacteriuria. It has been asserted in the past that bacteriuria increases the risk of anemia and high blood pressure during pregnancy. It is advised that all pregnant women get an ASB screening at their first prenatal appointment due to the high prevalence and probable severity of pyelonephritis. Treatment for ASB reduces clinical infection rates to 3%-4% (Schnarr J and Smaill F, 2008).

Etiology: Numerous bacterial species, the majority of which are part of the normal perineal flora, are responsible for causing urinary infections in females. About 70%-80% of pregnancies are caused by E.coli, making it the most frequent cause of UTI. Other pathogens that cause UTI include Proteus sp. (2%) and Klebsiella pneumonia (5%) as well as Enterobacter sp. (3%) and Staphylococcus saprophyticus (3%) and GBS (2%-5%) (Balachandran L, et al., 2022; Corrales M, et al., 2022).

Infection with GBS

Penicillin vs. placebo treatment for GBS bacteriuria was compared in a randomized, controlled trial. Results showed that women who took antibiotics experienced significantly lower rates of premature membrane rupture and preterm delivery. Although it is unknown whether GBS bacteriuria is the same as GBS vaginal colonization, pregnant women who have the condition ought to be treated as GBS carriers and given a preventative antibiotic during childbirth (Schnarr J and Smaill F, 2008).

During childbirth, urinary catheterization is a common procedure that might introduce bacteria and cause UTI. Changes in bladder reactivity and bladder excessive expansion during the postpartum period may predispose to UTI (Easter SR, et al., 2016).

The risk of UTI is significantly increased in women who engage in sexual activity. The distal urethra’s urothelium can become traumatized during sexual contact, which increases bacterial invasion. Inoculation can be facilitated by the vagina acting as a repository for stomach germs. Gram negative bacteria from the bowel flourish in urine, in contrast to the majority of vulval and perineal commensal microorganisms. As a result, aerobic Gram-negative bacilli from the gastrointestinal system are the main source of urine infections. The issue might be made worse by a swollen, gravid abdomen that makes it difficult to maintain personal hygiene. The same bacteria that cause UTIs in non-pregnant patients also cause UTIs in pregnant women (Amiri M, et al., 2015).

Pathophysiology

Same uropathogens that frequently cause UTI in non-pregnant patients also cause UTI in pregnant women. Ureteral dilatation occurs in 90% of pregnant women and lasts till birth (hydronephrosis of pregnancy). Increased urine stasis and ureterovesical reflux are caused by increased bladder volume, decreased bladder tone, and decreased ureteral tone. This decreased the kidneys’ defences against bacterial reflux. Bacterial reservoirs may exist in urinary stasis. The glomerular filtration rate and urine output both rise in response to blood volume expansion. Urine stasis, which can arise from an increase in urine output volume and the lack of ureteral tone, can cause the ureters, renal pelvis, and calyces to enlarge. This dilatation seems to start at 10 week’s gestation, increase throughout pregnancy and resolve between 6 and 12 weeks after delivery. Progesterone also causes urinary stasis by relaxing the ureteral smooth muscle (Loh KY and Sivalingam N, 2007).

Because of urine pH, vesicoureteral valve, and other immunological and mucosal barriers, urine is devoid of germs, viruses, and fungus. The major defense against UTI is complete bladder emptying during urination. The pathophysiology of urinary tract infection may be influenced by a variety of bacteria that have the ability to infiltrate the urinary tract. When bacteria from the vaginal, perineal, and fecal flora spread to the entrance of the urethra and begin to grow, infection develops (Kaptilyy VA, 2015).

Significant physiologic changes to the entire urinary system occur during pregnancy and significantly alter the occurrence of UTIs and pyelonephritis. The presence of glucose in the urine and an increase in urinary amino acid levels during pregnancy are other causes of UTI. Glycosuria results from proximal collecting tubule and loop of Henle dysfunction in glucose reabsorption. Although it has been hypothesized that its presence will interfere with E.coli’s ability to adhere to the urothelium (Le J, et al., 2004).

Due to the physiologic changes brought on by pregnancy, pregnant individuals are typically regarded as an immunocompromised potential UTI host. Additionally, there is a significant increase in wetness during pregnancy, which tends to boost the growth of bacteria (Millar LK and Cox SM, 1997).

Clinical signs and symptoms

Asymptomatic bacteriuria is characterized by a lack of symptoms. These patients can have a record of recurrent UTI or ASB from a previous pregnancy. Cystitis usually begins suddenly, often with urgency, burning, or painful emptying of little amounts of urine. Nocturia with suprapubic discomfort. Hematuria can happen and urine is murky. A low-grade fever could appear. When an infection occurs from a vesicoenteric or vesicovaginal perforation or from emphysematous cystitis, pneumaturia may happen.

Pyelonephritis: Dysuria, fever, shivering, flank pain, constant abdomen unease, nausea, vomiting, and lethargy are symptoms of acute pyelonephritis (Santos JF, et al., 2002).

Complications among mother and fetus

• Acute Respiratory Distress Syndrome (ARDS) or pulmonary edema may be present as a result of endotoxin-mediated alveolar injury. Monitoring of urine production and oxygen levels is recommended (MacLean AB, 2001)

• Anemia is caused by the release of endotoxins

• Endotoxin secretion may also trigger uterine contractions in preterm labor

• Preeclampsia

• Septic shock

• An ongoing infection

• Acute pyelonephritis

• Chorioamnionitis

• Acute cystitis with symptoms

• Hypertension

• Low birth weight

• Premature birth

• Embryonic death (Widmer M, et al., 2015)

• Growth retardation within the womb

Differential diagnosis

Important differential diagnosis includes nephrolithiasis, placental abruption, intraamniotic infection, and bacterial infection in pregnant women who report with fever and flank or lower back pain. Significant flank or back discomfort and abnormal urine results are symptoms of nephrolithiasis.

The differential diagnosis includes pregnancy-related issues including preterm labor, chorioamnionitis, or placental abruption as well as acute intraabdominal disorders such appendicitis, pancreatitis, or cholecystitis (Ovalle A and Levancini M, 2001).

Diagnosis

Acute pyelonephritis, cystitis, and asymptomatic bacteriuria are diagnosed by examining the presence of bacteria in the urine. For the diagnosis of acute pyelonephritis and asymptomatic bacteriuria, a concentration of at least 10⁵ cfu/ml of a single uropathogen is required, but only 10³ CFU/ ml are required for the diagnosis of cystitis. Urine culture is the standard for detecting bacteriuria in pregnancy. However, urine cultures are pricy, call extensive laboratory competence, and take 24-48 hours to provide findings (Wing DA, et al., 2000). In 90% of cases of pyelonephritis, it is positive. Prior to beginning antibiotic therapy, cultures should be acquired as soon as feasible. For the diagnosis of UTI, urine microscopy has a poor sensitivity (between 40% and 70%) but a good specificity (between 85% and 95%). Pyuria is found in around 90% of instances of pyelonephritis. The diagnosis of acute pyelonephritis is more sensitive (95%) and specific (71%) when pyuria is present. White blood casts are a dead giveaway for an upper tract infection (Teppa RJ and Roberts JM, 2005).

Due to its dependable rates and quick results, the dipstick method (for nitrites and leukocyte esterase) has emerged as the most used test. With dipstick analysis and clinical judgement, accuracy in patients with vague symptoms is significantly increased. Protein, white blood cells, and red blood cells are examined during a urine test. False negative test findings are frequent, and these tests have relatively low predictive values.

A complete blood count, electrolytes, and serum creatinine test are among the laboratory tests that are typically used to diagnose pyelonephritis. Pyelonephritis can be diagnosed routinely in patients who are critically ill, have symptoms of renal colic or a history of renal stones, have diabetes mellitus, a history of prior urologic surgery, immunosuppression, repeated episodes of pyelonephritis, or have urosepsis using Computed Tomography (CT), renal ultrasound (to avoid contrast or radiation exposure) or Magnetic Resonance Imaging (MRI).

When comparing inpatient treatment for pyelonephritis to screening for bacteriuria in pregnant women, studies found that screening resulted in a significant reduction in overall costs. One patient’s test for bacteriuria to detect the onset of pyelonephritis cost $1,605, but one patient’s pyelonephritis treatment cost $2,485. In a family practice obstetric population, Wadland and Plante carried out a comparable analysis and discovered that screening for asymptomatic bacteriuria was cost-effective (Szweda H and Jóźwik M, 2016).

Pharmacological treatment

Antibiotic therapy was observed to be successful in eradicating asymptomatic bacteriuria and lowering the frequency of pyelonephritis, premature delivery, and low birthweight when compared to placebo or no therapy (Smaill FM and Vazquez JC, 2019). The effect of administering antibiotics for asymptomatic urinary tract infections on recurring bacteria in the urine during pregnancy, the possibility of premature delivery, and the occurrence of pyelonephritis after pregnancy were all assessed in a Cochrane review of 13 studies. The antibiotic sensitivity of Gram-negative urinary pathogens acquired from pregnant women with asymptomatic bacterial infections or cystitis was examined in a study (Table 1).

Table 1: Pharmacological treatment of UTIs in pregnancy

The infectious agent(s) can typically be eliminated with a 7-10 day antibiotic course. Shorter treatment durations, including one-day therapy, have been recommended by some experts. There is still debate over when pregnant patients should receive shorter antibiotic regimens of treatment. In ampicillin-sensitive isolates, Masterton achieved an 88 percent cure rate with a single 3 g dosage of ampicillin. According to several other trials, cure rates for bacteriuria ranged from 50%-78% when a single administration of amoxicillin, cephalexin (Keflex), or nitrofurantoin was administered.

When taken as directed, a single 3 g sachet of fosfomycin is effective. Analgesia is required because significant renal angle discomfort affects many women. Simple analgesics are usually sufficient, but opiates may be required in extreme circumstances or if there is concurrent renal colic. Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) should be avoided since they raise the risk of stomach mucosal ulcers and impaired renal perfusion in mothers and the fetal condition oligohydramnios and early ductus arteriosus closure.

If the lady has restricted mobility or needs to be bedridden for a while, thromboprophylaxis should be utilized. Low molecular weight heparin and progressive compression stockings are advised.

Acute pyelonephritis episodes dramatically enhance the risks of premature labor. Often, tocolysis is required. If there is evidence of suspected preterm labor, antenatal steroids for fetal lung development should be taken into consideration. Regarding tocolysis and the administration of prenatal steroids, we point readers to the Royal College of Obstetricians and Gynaecologist (RCOG) recommendations (Johnson EK, 2016).

Because of how some antibiotics affect the developing fetus, some should not be used during pregnancy (Schneeberger C, et al., 2012), they consist of the following-

• Tetracyclines can harm fetus teeth and bones.

• Avoid fluroquinolones during pregnancy and nursing as they are harmful to growing cartilage.

• During the first and third trimesters, avoid taking trimethoprim-sulphamethoxazole.

• If at all possible, avoid using aminoglycosides because they have been linked to ototoxicity after extended exposure during fetal development.

Preventive actions

You can prevent UTI from developing and saving yourself. The trouble of subsequently treating it by taking the following precautions (Rahiman F, et al., 2015)

• Practicing good hygiene, such as cleaning the genital region and urinating after sexual activity, had a protective impact. After using the bathroom, wipe your genital area from front to back to keep it clean.

• The chemical in cranberry juice may help prevent bacteria from adhering to the lining of the urinary tract. This action aids in infection control and prevention.

• Vaccination.

• Eat foods and supplements high in vitamin C or ascorbic acid, which can raise urine acidity. The acidity prevents infection and aids in the death of germs.

• Urinating whenever the desire strikes, which promotes faster removal of microorganisms from the urinary system.

• Taking specific supplements, such as a vitamin C, cranberry and probiotic combination, may help treat recurring UTIs in females.

• Drinking enough fluids, especially water, can assist the urinary tract’s bacteria be flushed out.

• Consuming yogurt, which includes live lactobacilli.

• Remember not to wear tighter or wet clothing, and wear cotton underwear.

• Avoid clear of soap or cleansing products that might harm your genitalia.

Conclusion

Urinary tract infections, whether symptomatic or asymptomatic, present a major risk to expectant mothers. This article has reviewed the pathophysiology, etiology, complications, diagnosis, preventative strategies, and therapy of UTI in pregnancy. urine cultures should be used to check for asymptomatic bacteriuria in pregnant women, and the right antimicrobials should be used to treat it. On the basis of cost, safety during pregnancy, and availability, broad-spectrum antibiotics with activity against E.coli should be selected as the initial course of treatment for symptomatic UTI. While pyelonephritis necessitates hospitalization and intravenous antibiotics, asymptomatic bacteriuria and cystitis are best treated with oral antibiotics, 7 day course of treatment is preferable to a one-dose course.

References

1. Macejko AM, Schaeffer AJ. Asymptomatic bacteriuria and symptomatic urinary tract infections during pregnancy. Urol Clin. 2007; 34(1): 35-42.

   [Crossref] [Google Scholar] [Pubmed]

2. Habak PJ, Griggs Jr RP. Urinary tract infection in pregnancy. StatPearls. 2023.

   [Google Scholar] [Pubmed]

3. Michelim L, Bosi GR, Comparsi E. Urinary tract infection in pregnancy: Review of clinical management. J Clin Nephrol. 2016; 3(1): 1030.

   [ Google Scholar]

4. Nicolle LE, Gupta K, Bradley SF, Colgan R, DeMuri GP, Drekonja D, et al. Clinical practice guideline for the management of asymptomatic bacteriuria: 2019 update by the Infectious Diseases Society of America. Clin Infect Dis. 2019; 68(10): 83-110.

   [Google Scholar]

5. Romero RO, Oyarzun EN, Mazor MO, Sirtori MA, Hobbins JC, Bracken MI. Meta-analysis of the relationship between asymptomatic bacteriuria and preterm delivery/low birth weight.  Obstet Gynecol. 1989; 73(4): 576-82.

   [Google Scholar] [Pubmed]

6. Widmer M, Lopez I, Gülmezoglu AM, Mignini L, Roganti A. Duration of treatment for asymptomatic bacteriuria during pregnancy. Cochrane Database Syst Rev. 2015; 11: CD000491.

   [Crossref] [Google Scholar] [Pubmed]

7. Glaser AP, Schaeffer AJ. Urinary tract infection and bacteriuria in pregnancy. Urol Clin. 2015; 42(4): 547-60.

   [Crossref] [Google Scholar] [Pubmed]

8. Matuszkiewicz-Rowińska J, Małyszko J, Wieliczko M. State of the art paper urinary tract infections in pregnancy: Old and new unresolved diagnostic and therapeutic problems. Arch Med Sci. 2015; 11(1): 67-77.

   [Google Scholar]

9. Fatima N, Ishrat S. Frequency and risk factors of asymptomatic bacteriuria during pregnancy.  J Coll Physicians Surg Pak. 2006; 16(4): 273-275.

   [Crossref] [Google Scholar] [Pubmed]

10. Getaneh T, Negesse A, Dessie G, Desta M, Tigabu A. Prevalence of urinary tract infection and its associated factors among pregnant women in Ethiopia: A systematic review and meta‐analysis. Biomed Res Int. 2021; 1: 6551526.

    [Crossref] [Google Scholar] [Pubmed]

11. Kalinderi K, Delkos D, Kalinderis M, Athanasiadis A, Kalogiannidis I. Urinary tract infection during pregnancy: Current concepts on a common multifaceted problem. J Obstet Gynaecol. 2018; 38(4): 448-453.

    [Crossef] [Google Scholar] [Pubmed]

12. Behzadi P, Behzadi E, Yazdanbod H, Aghapour R, Cheshmeh MA, Omran DS. A survey on urinary tract infections associated with the three most common uropathogenic bacteria.  Maedica. 2010; 5(2): 111.

    [Google Scholar] [Pubmed]

13. McCormick T, Ashe RG, Kearney PM. Urinary tract infection in pregnancy. Obstet Gynaecol. 2008; 10(3): 156-162.

    [Google Scholar]

14. Gilstrap III LC, Ramin SM. Urinary tract infections during pregnancy. Obstet Gynecol Clin North Am. 2001; 28(3): 581-591.

    [Crossref] [Google Scholar] [Pubmed]

15. Macejko AM, Schaeffer AJ. Asymptomatic bacteriuria and symptomatic urinary tract infections during pregnancy. Urol Clin North Am. 2007; 34(1): 35-42.

    [Crossref] [ Google Scholar] [Pubmed]

16. Guptha K. Urinary tract infections and asymptomatic bacteriuria in pregnancy. UpToDate. 2010.
17. Delzell Jr JE, Lefevre ML. Urinary tract infections during pregnancy. Am Fam Physician 2000; 61(3): 713-720.

    [Google Scholar] [Pubmed]

18. Mittal P, Wing DA. Urinary tract infections in pregnancy. Clin Perinatol. 2005; 32(3): 749-764.

    [Crossref] [Google Scholar] [Pubmed]

19. Patterson TF, Andriole VT. Bacteriuria in pregnancy. Infect Dis ClinNorth Am. 1987; 1(4): 807-822.

    [Crossref] [Google Scholar] [Pubmed]

20. Lucas MJ, Cunningham FG. Urinary infection in pregnancy. Clin Obstet Gynecol. 1993; 36(4): 855-868.

    [Crossref] [Google Scholar] [Pubmed]

21. Pastore LM, Savitz DA, Thorp Jr JM. Predictors of urinary tract infection at the first prenatal visit. Epidemiology. 1999; 10(3): 282-287.

    [Google Scholar] [Pubmed]

22. Andriole VT, Patterson TF. Epidemiology, natural history, and management of urinary tract infections in pregnancy. Med Clin North Am. 1991; 75(2): 359-373.

    [Crossref] [Google Scholar] [Pubmed]

23. Schnarr J, Smaill F. Asymptomatic bacteriuria and symptomatic urinary tract infections in pregnancy. Eur J Clin Investig. 2008; 38: 50-57.

    [Crossref] [Google Scholar] [Pubmed]

24. Balachandran L, Jacob L, Al Awadhi R, Yahya LO, Catroon KM, Soundararajan LP, et al. Urinary tract infection in pregnancy and its effects on maternal and perinatal outcome: A retrospective study. Cureus. 2022; 14(1).

    [Crossref] [Google Scholar] [Pubmed]

25. Corrales M, Corrales-Acosta E, Corrales-Riveros JG. Which antibiotic for urinary tract infections in pregnancy? A literature review of international guidelines. J Clin Med. 2022; 11(23): 7226.

    [Crossref] [Google Scholar] [Pubmed]

26. Schnarr J, Smaill F. Asymptomatic bacteriuria and symptomatic urinary tract infections in pregnancy. Eur J Clin Invest. 2008; 38: 50-57.

    [Crossref] [Google Scholar] [Pubmed]

27. Easter SR, Cantonwine DE, Zera CA, Lim KH, Parry SI, McElrath TF. Urinary tract infection during pregnancy, angiogenic factor profiles, and risk of preeclampsia. Am J Obstet Gynecol. 2016; 214(3): 387-e1.

    [Crossref] [Google Scholar] [Pubmed]

28. Amiri M, Lavasani Z, Norouzirad R, Najibpour R, Mohamadpour M, Nikpoor AR, et al. Prevalence of urinary tract infection among pregnant women and its complications in their newborns during the birth in the hospitals of Dezful city, Iran, 2012-2013. Iran Red Crescent Med J. 2015; 17(8): e26946.

    [Crossref] [Google Scholar] [Pubmed]

29. Loh KY, Sivalingam N. Urinary tract infections in pregnancy. Malays Fam Phy. 2007; 2(2): 54.

    [Google Scholar] [Pubmed]

30. Kaptilyy VA. Urinary tract infection in pregnancy. VF Snegirev Arch Obstet Gynecol. 2015; 2(4): 10-19.

    [Google Scholar]

31. Le J, Briggs GG, McKeown A, Bustillo G. Urinary tract infections during pregnancy. Ann Pharmaco Ther. 2004; 38(10): 1692-1701.

    [Crossref] [Google Scholar] [Pubmed]

32. Millar LK, Cox SM. Urinary tract infections complicating pregnancy. Infect Dis Clin. 1997; 11(1): 13-26.

    [Crossref] [Google Scholar] [Pubmed]

33. Santos JF, Ribeiro RM, Rossi PD, Haddad JM, Guidi HG, Pacetta AM, et al. Urinary tract infections in pregnant women. Int Urogynecol J. 2002; 13: 204-209.

    [Crossref] [Google Scholar] [Pubmed]

34. MacLean AB. Urinary tract infection in pregnancy. Int J Antimicrob Agents. 2001; 17(4): 273-277.

    [Crossref] [Google Scholar] [Pubmed]

35. Widmer M, Lopez I, Gülmezoglu AM, Mignini L, Roganti A. Duration of treatment for asymptomatic bacteriuria during pregnancy. Cochrane Database Syst Rev. 2015; 11: CD000491.

    [Crossref] [Google Scholar] [Pubmed]

36. Ovalle A, Levancini M. Urinary tract infections in pregnancy. Curr Opin Urol. 2001; 11(1): 55-59.

    [Crossref] [Google Scholar] [Pubmed]

37. Wing DA, Park AS, DeBuque L, Millar LK. Limited clinical utility of blood and urine cultures in the treatment of acute pyelonephritis during pregnancy. Am J Obstet Gynecol. 2000; 182(6): 1437-1441.

    [Crossref] [Google Scholar] [Pubmed]

38. Teppa RJ, Roberts JM. The uriscreen test to detect significant asymptomatic bacteriuria during pregnancy.  J Soc Gynecol Investig. 2005,12:50-53.

    [Crossref] [Google Scholar] [Pubmed]

39. Szweda H, Jóźwik M. Urinary tract infections during pregnancy-An updated overview.  Dev Period Med. 2016; 20(4): 263-272.

    [Google Scholar] [Pubmed]

40. Smaill FM, Vazquez JC. Antibiotics for asymptomatic bacteriuria in pregnancy. Cochrane Database Syst Rev. 2019; 11: CD000490.

    [Crossref] [Google Scholar] [Pubmed]

41. Johnson EK. Urinary tract infections in pregnancy treatment and management. Drugs Diseases. 2016.

    [Google Scholar]

42. Schneeberger C, Geerlings SE, Middleton P, Crowther CA. Interventions for preventing recurrent urinary tract infection during pregnancy. Cochrane Database Syst Rev. 2012; 11: CD009279.

    [Crossref] [Google Scholar] [Pubmed]

43. Rahiman F, Balasubramnian T, Shejina M, Musambil M. A review on urinary tract infection in pregnancy. Int J Pharm Res Rev. 2015; 4(2): 1-7.

    [Google Scholar]