PREVALENCE OF ASYMPTOMATIC BACTERIURIA IN PRETERM LABOUR A CASE- CONTROL STUDY

Submitted by,
Dr. R. K.VIDHYALAKSHMI P.G. STUDENT, DNB (OBG) DEPT OF OBSTETRICS & GYNAECOLOGY JUBILEE MISSION HOSPITAL, THRISSUR.

Under the guidance of,

Dr. ANNIE. V. THADICAREN ASSOCIATE PROFESSOR DEPT OF OBSTETRICS & GYNAECOLOGY JUBILEE MISSION HOSPITAL, THRISSUR.

NATIONAL BOARD OF EXAMINATIONS, NEW DELHI Thesis Protocol Submission: 1) Title: Prevalence of asymptomatic bacteriuria in preterm labour: A Case-Control study 2) Candidate: Dr. R. K. Vidhyalakshmi, DNB Resident- first year, Department of Obstetrics & Gynaecology Jubilee Mission Hospital, Thrissur. 3) Guide: Dr. Annie. V. Thadicaren, Associate professor, Department of Obstetrics & Gynaecology Jubilee Mission Hospital, Thrissur. . 4) Co-Guide: Dr. Neetha George, Associate Professor, Department of Obstetrics & Gynaecology Jubilee Mission Hospital, Thrissur. 5) Hospital: Jubilee mission hospital, Thrissur, Kerala. 6) Department: Obstetrics & Gynaecology 7) Name Of Funding Agency: Jubilee Mission Hospital, Thrissur, Kerala 8) Duration Of Scheme: 1 year & 6 months.

INTRODUCTION Urinary tract infection (UTI) is one of the most frequent bacterial infections 1. It is also one of the most common bacterial infections seen during pregnancy2. It could be either symptomatic or asymptomatic. The symptomatic urinary tract infection may be complicated or uncomplicated. Complicated urinary tract infection is symptomatic urinary infection in women with structural or functional abnormalities of genitourinary tract involving either bladder or kidney or both4. Uncomplicated urinary tract infection is also symptomatic urinary infection characterized by dysuria, urgency, frequency or suprapubic pain with a normal genitourinary tract3. Asymptomatic bacteriuria is defined as persistently and actively multiplying bacteria in significant numbers (more than 10 5 per ml) within the urinary tract without any obvious symptom5. The pregnant women are two times more commonly affected than age matched non-pregnant females6,7. Asymptomatic bacteriuria is found in 2-10% of pregnant women8. If asymptomatic bacteriuria is not treated approximately 25% of women will subsequently develop acute symptoms of an infection during pregnancy9. Asymptomatic bacteriuria is an entity with serious consequences in the form of maternal and fetal morbidity10. It can cause maternal anemia, pyelonephritis, recurrent infection, preterm labour11, septicemia and even death of the mother12. It can cause Intra Uterine Growth restriction (IUGR)13, prematurity, low birth weight of the fetus14 and the fetal mortality12. Out of which preterm labour pain and pyelonephritis are the most common adverse effect11. The association between ASB and preterm delivery (<37 weeks of gestation) and that between asymptomatic bacteruria and low birth weight (<2500 gram) were unknown until 1962 when Kass observed an increased risk among untreated bacteruric women for the delivery of low birth weight. The mean duration of pregnancy among untreated bacteriuric women was found to be reduced by one week on average15. Also ASB in pregnant women as a risk factor for preterm birth and antibiotic therapy has been found to significantly reduce the risk. (16,17).

AIMS & OBJECTIVES: 1) To find out the prevalence of Asymptomatic Bacteriuria (ASB) in pregnant women presenting with preterm labour pain. 2) To determine the common pathogenic micro organisms associated with Asymptomatic Bacteriuria (ASB). 3) To determine their antibiotic sensitivity. REVIEW OF LITERATURE 1) Definition: Delzell JE et al defined Asymptomatic Bacteriuria (ASB) as persistent and actively multiplying bacteria of more than or equal to 10,000 colony forming unit per ml of urine without any urinary tract symptoms18. 2) Prevalence: Masindei A et al studied 247 pregnant womaen out of which 78 were symptomatic and 169 are asymptomatic19. Gayathri et al studied 900 pregnant women and found the prevelance as 6.2% out of which it is more in third trimester than in first and second trimester20. 3) Risk factors: Pregnancy- It itself is a risk factor for Asymptomatic Bacteriuria (ASB), studied by Stenquist et al and found that the frequency of bacteriuria increases by 1 % during pregnancy21. Socio economic status- Wesley et al 2002 and Kunningam et al 1993 found that the prevelance of Asymptomatic Bacteriuria (ASB) higher in low socio economic status22. 4) Maternal age: Marachine et al proved in 1997 that the prevelance of ASB increase with maternal age23. 5) Anemia: Lavanya & Jogalakshmi found that Asymptomatic Bacteriuria (ASB) associated with anemia24. Fathima et al didnt find association with Asymptomatic Bacteriuria (ASB) and anemia25. 6) Diabetes: Greelings et al concluded that the Asymptomatic Bacteriuria (ASB) is increased in women with diabetes26. 7) Sexual activity: Scholes et al 2001 found that women who are sexually active in the past month are 6 times more likely to get infected than those not sexually active27. 8) Other factors: Contraception and Catheterization also increases the risk of developing Asymptomatic Bacteriuria (ASB)(28,29).

OUTCOME IN RELATION TO PRETERM LABOUR: Patterson et al 1987 found that subclinical chorioamnionitis and phospholipid A2 production by bacteria may be the proposed cause of initiation of preterm labour. It may also be due to release of proinflammatory cytokines by maternal and fetal monocytes in response to bacterial products30. Fathima N et al 2006 studied 590 women, 6 out of 28 bacteriuric and 27 out of 552 women with out bacteriuria went into preterm labour which is statistically significant31. But Cardiff birth study 1995 prospectively studied 25844 births and reported that asymptomatic bacteriuria adjusted for demographic and social factors are not associated with preterm labour. However if preterm deliveries are categorised into medically indicated or spontaneous preterm births, medically indicated are more associated with asymptomatic bacteriuria than spontaneous and authors concluded that Asymptomatic Bacteriuria (ASB) not progressing to Pyelonephritis is not associated with preterm labour32. In the meta analysis of four cohort studies where the out come included preterm delivery, Romero et al concluded that there was a strong association between asymptomatic bacteriuria and preterm labour pain and antibiotics are useful in prevention of preterm labour33. In the Cochrane review of antibiotic treatment of asymptomatic bacteriuria in pregnancy in ten randomized control trials and quasi-randomized controlled clinical trials where the outcome of preterm labour and low birth weight reported, and antibiotic treatment shown to be associated with reduction in this outcome34. IMPORTANCE OF SCREENING The American College of Obstetrics and Gynaecology strongly recommends that the urine culture to be obtained in the first prenatal visit itself. The American Academy of Family Physicians recommends screening for ASB at 12-16 wks of gestation by culture method. The United State Preventive Service Task Force (USPSTF) recommends screening for ASB with urine culture for pregnant women at 12-16 wks or at the 1st prenatal visit if later. This is Grade A recommendation. The USPSTF

recommends against screening for ASB in men and non pregnant. This is Grade D recommendation. The National Institute for Clinical Excellence, The Europeon Association of Urology, The Canadian Task Force on Preventive Care and The Scottish Inter Collegiate Guidelines Network also recommend screening for ASB in pregnancy. MATERIALS AND METHODS: Study Area- Obstetrics & Gynaecology and Microbiology Study Method: A prospective case-control clinical study. This study will be carried out in 50 pregnant women with preterm(2437wks) labour pain admitted in the labour room and 50 preterm(2437wks) pregnant women who are not in labour, in the out-patient department of Jubilee Mission Hospital. Case- Primigravida or multigravida, singleton pregnancy who present with preterm labour pain after 24 weeks and before 37 completed weeks of gestation who are admitted in the labour room. Control- Primigravida or multigravida, singleton pregnancy who do not present with preterm labour pain after 24 weeks and before 37 completed weeks of gestation in the out-patient department. Type of study- A prospective case-control clinical study. Sample size- around 100 pregnant women (50+50) Period Of Study- From Oct 2013 to March 2015. A predesigned proforma will be used to record relevant information (patient data, finding, inv report) from individual patients selected with inclusion and exclusion criteria. Informed written consent.

INCLUSION CRITERIA: 1) For preterm group in labour: Primigravida or multigravida, singleton pregnancy who present with preterm labour pain after 24 weeks and before 37 completed weeks of gestation. 2) For preterm group not in labour: Primigravida or multigravida, singleton pregnancy who do not present with preterm labour pain after 24 weeks and before 37 completed weeks of gestation. EXCLUSION CRITERIA: 1) Women with present history of UTI or any clinical presentation of UTI (frequency of micturition, burning micturition, loin pain, etc) in present pregnancy or in past 1 yr. 2) Women known to be diabetic, hypertensive, women who are immune compromised as in long-term corticosteroid therapy. 3) Women already on any antibiotic therapy in past 1 month. 4) Multiple pregnancy. CLEAN CATCH METHOD Patients and labour room staff will be instructed to take clean catch mid stream urine sample for urine culture and also for quantitative and microscopic examination. The sample must reach the lab in 2hrs. If the culture is positive, antibiotic sensitity also to be done. STATISTICAL METHODOLOGY Data will be statistically described in terms of range, mean and standard deviation, frequency(no. of cases), relative frequency(percentages) when appropriate. Comparison of quantitative variables between study groups will be done by Chi-Squares(X2) test. Probability value (p value) less than 0.05 will be considered to be significant.