Background
Methods
Protocol and methodological approach
Search strategy and study selection
Eligibility criteria
Study characteristics
Questions 1 and 2 (ASB screening) | Question 3 (ASB treatment) | |
---|---|---|
Population | • Pregnant women taking part in routine maternal care • Without symptoms of UTI • With unknown ASB status | • Pregnant women with ASB detected in screening |
Study intervention | • Any ASB screening strategy followed by treatment, if necessary | • Any treatment for ASB |
Control intervention | • No ASB screening, but treatment if symptoms of UTI occur (question 1) • Any other ASB screening strategy followed by treatment, if necessary (question 2) | • No treatment or placebo |
Patient-relevant outcomes | • Pyelonephritis • UTI • Symptoms linked directly or indirectly to UTI (e. g. headache or visual impairment as symptoms of pre-eclampsia, fever) • Infant morbidity (e. g. respiratory distress syndrome, sepsis, cerebral haemorrhage, necrotising enterocolitis) • Perinatal mortality • Early preterm birth (< 32 weeks of gestation) • Very low birth weight (< 1500 g) • Health-related quality of life and psychosocial functioning • Any adverse event |
Document characteristics
Data extraction
Assessment of risk of bias
Data analysis
Results
Literature search
Study characteristics
Comparison study | Study design | Participants randomised (intervention / control) | Treatment regimen | Location / Setting / recruitment period | Length of follow-up | Urine collection / methods used for diagnosis | Inclusion and exclusion criteria |
---|---|---|---|---|---|---|---|
Sulphasymazine vs. placebo | |||||||
Elder [19] | RCT, double-blind, parallel | 106 (54 / 52) | Sulphasymazine 0.5 g/d until birth or onset of pyelonephritis; if bacteriuria persisted medication was changed to nitrofurantoin or tetracycline, dosage not stated | USA / outpatient maternal care / 06 / 1965 – 03 / 1966 | Until immediately after birtha
| Clean voided / UC | I: pregnant; same species of bacteria in first 3 uncontaminatedb specimens, ≥ 104 /ml in one and ≥ 105/ml in 2 E: > 32th week of gestation at first examination |
Sulphadimethoxine vs. no treatment | |||||||
Mulla [20] | RCT, blinding not stated | 100 (50 / 50) | Sulphadimethoxine 2 x 250 mg/d 7 days; if bacteriuria persisted treatment was repeated | USA / not stated / not stated | Until immediately after birtha
| Catheter (not specified) / UC and “stained smear”c not further specified | I: 30th – 32th week of gestation; bacteriuria (not specified) E: not stated |
Sulphadimidine vs. no treatment | |||||||
Williams [22] | RCT, blinding not stated | Not stated (85 / 78)d
| Sulphadimidine 3 x 1 g 7 days; if bacteriuria persisted until 2 to 3 weeks after finishing primary treatment, then nitrofurantoin 2 x 100 mg/d for 7 days if still persisting ampicillin 3 x 250 mg for 7 days | GB / maternal care / 1967 | 10 days post partem | Voided midstream / UC | I: < 30th week of gestation at recruitment; > 105 g-negative bacteria /ml in ≥ 2 consecutive specimens E: not stated |
Nitrofurantoin vs. placebo | |||||||
Kazemier [21] | Double-blind, placebo-controlled RCT, embedded in a multicentre cohort study | 85 (40 / 45) | Nitrofurantoin 100 mg 2x/d 5 days, self-administered if follow-up culture positive one week after end of treatment, 1x repeated (masked) medication at the same dose and schedule | NL / hospitals and ultrasound centres / 10 / 2011 – 6 / 2013e
| Until 08 / 2014 | Not stated / dip slide with two culture media | I: women ≥ 18 years with a singleton pregnancy between 16 and 22 weeks; without symptoms of UTI; ≥ 1x105 CFU /ml of a single microorganism or when 2 different colony types were present but 1 with ≥ 1x105 CFU / ml E: history of preterm delivery < 34 weeks; warning signs of an imminent preterm delivery; fetal congenital malformations; antibiotic use within 2 weeks of screening; known glucose-6-phosphate dehydrogenase deficiency; hypersensitivity to nitrofurantoin; risk factors for complicated UTI |
Risk of bias
Study | Randomisation appropriate | Allocation concealment appropriate | Blinding patient / investigator / outcome assessor | Selective reporting improbable | Absence of other factors potentially causing bias | ITT analysis appropriate | Risk of bias (study level) |
---|---|---|---|---|---|---|---|
Elder [19] | unclear | unclear | yes / unclear / unclear | uncleara, b
| noc
| nod
| high |
Mulla [20] | unclear | unclear | no / no / unclear | noa, e
| noc, f
| unclear | high |
Williams [22] | unclear | unclear | no / no / unclear | noa, g
| noc
| noh
| high |
Kazemier [21] | yes | yes | yes / yes / yes | yes | yes | yes | low |
Effects of interventions
Pyelonephritis and lower UTI
Outcome measure | Study | Treatment group | Control group | Difference between groups | ||
---|---|---|---|---|---|---|
Specification |
N
| Events (%) |
N
| Events (%) | OR [95 % CI]; p-value | |
Pyelonephritis | ||||||
Kazemier [21] | 40 | 0 (0) | 45 | 1 (2.2) | 0.37a [0.01; 9.25]a; 0.515b
| |
Williams [22] | 85c
| 5 (6) | 78c
| 18 (23) | 0.21a [0.07–0.59]a; 0.002b
| |
Lower UTI | ||||||
Treated with AB during pregnancy | Kazemier [21] | 40 | 4 (10) | 45 | 8 (18) | POR 0.53a [0.16; 1.79]a; 0.357b
|
Recurrent UTI treated with AB during pregnancy | Kazemier [21] | 40 | 0 (0) | 45 | 1 (2.2) | 0.37a [0.01; 9.25]a; 0.515b
|
Treated with AB postpartum (within 6 weeks) | Kazemier [21] | 40 | 3 (7.5) | 45 | 1 (2.2) | POR 3.20a [0.43; 23.63]a; 0.296b
|
Pre- and post-partald
| Mulla [20] | 50 | 3 (6) | 50 | 20 (40) | 0.10a [0.03–0.35]a; < 0.001b
|
Preterm birth | ||||||
< 37 weekse
| Kazemier [21] | 40 | 2f (5) | 45 | 2 (4.4) | POR 1.13a [0.15; 8.35]a; 0.975b
|
< 32 weeks | Kazemier [21] | 40 | 1 (2.5) | 45 | 0 (0) | 3.46a [0.14; 87.26]a; 0.357b
|
Infant morbidity | ||||||
Kernicterus | Elder [19] | 54 | 0g
| 52 | 0g
| n. a. |
Composite severe morbidityh
| Kazemier [21] | 40 | 0 (0) | 45 | 2 (4.4) | 0.21a [0.01; 4.61]a; 0.220b
|
Admission to NICU | Kazemier [21] | 40 | 2 (5) | 45 | 0 (0) | 5.91a [0.28; 126.85]a; 0.169b
|
Neonatal sepsis confirmed with culture | Kazemier [21] | 40 | 0 (0) | 45 | 2 (4.4) | 0.21a [0.01; 4.61]a; 0.220b
|
Congenital abnormalities | Kazemier [21] | 40 | 0 (0) | 45 | 1 (2.2) | 0.37a [0.01; 9.25]a; 0.515b
|
Infant mortality | ||||||
Perinatal death | Kazemier [21] | 40 | 1 (2.5) | 45 | 0 (0) | 3.46a [0.14; 87.26]a; 0.357b
|
Adverse events | ||||||
Vomiting | Elder [19] | 54 | 1 | 52 | 0 | n. a. |
Rashes, pruritus | Elder [19] | 54 | 0f
| 52 | 0f
| n. a. |
Photosensitivity | Elder [19] | 54 | 0f
| 52 | 0f
| n. a. |
Discontinuations due to adverse events | Mulla [20] | 50 | 0 | 50 | 0 | n. a. |
Pre-eclampsiae
| Kazemier [21] | 40 | 2 (5) | 45 | 1 (2.2) | POR 2.24a [0.23; 22.22]a; 0.596b
|
HELLP syndrome | Kazemier [21] | 40 | 2 (5) | 45 | 0 (0) | 5.91a [0.28; 126.85]a; 0.169b
|
Kidney stones, cholestasis | Kazemier [21] | 40 | 0 (0) | 45 | 0 (0) | RD 0 [-9,4; 10,5] |
Thrombo-embolic events | Kazemier [21] | 40 | 0 (0) | 45 | 0 (0) | RD 0 [-9,4; 10,5] |
Endometritis (within 6 weeks of delivery) | Kazemier [21] | 40 | 0 (0) | 45 | 0 (0) | RD 0 [-9,4; 10,5] |
Mastitis (within 6 weeks of delivery) | Kazemier [21] | 40 | 1 (2.5) | 45 | 1 (2.2) | POR 1.13a [0.07; 18.41]a; 0.997b
|
Outcome measure | Treatment group | Control group | Difference between groups | ||
---|---|---|---|---|---|
Study |
N
| Events (%) |
N
| Events (%) | OR [95 % CI]; p-value |
Pyelonephritis | |||||
Williams [22] Sensitivity analysis I | 106a
| 5 (5) | 105a
| 18 (17) | 0.24b [0.19–1.05]b; 0.004c
|
Williams [22] Sensitivity analysis II | 106a
| 9 (8)d
| 105a
| 18 (17) | 0.45b [0.19–1.05]b; 0.066c
|