Kazemier 2015.

Methods	Randomised, placebo‐controlled trial, 2 parallel groups, embedded within multicentre prospective cohort study
Participants	Inclusion: women 18 years or older, singleton pregnancy, between 16 and 22 weeks of pregnancy, without symptoms of urinary tract infection Positive urine dipslide (≥ 1 x 10⁵ CFU/mL of a single organism or when 2 organisms were present, 1 had concentration of ≥ 1 x 10⁵ CFU/mL) Exclusion: women with history of preterm delivery before 34 weeks, warning signs of an imminent preterm delivery, fetal congenital malformations, antibiotic use within 2 weeks of screening, known G6PD deficiency, hypersensitivity to nitrofurantoin, risk factors for complicated urinary tract infection (e.g. diabetes, immunosuppression, abnormalities of the urinary tract) Setting: 8 hospitals and 5 ultrasound centres, The Netherlands Number of participants: 85
Interventions	Nitrofurantoin 100 mg twice daily for 5 consecutive days (N = 40) or identical placebo capsules (N = 45) Women whose follow‐up dipslide 1 week after the end of treatment was persistently positive were given a further course of nitrofurantoin or matching placebo at the same dose and schedule according to their original allocation group, repeated for a maximum of 2 rounds of treatment.
Outcomes	Primary outcomes: pyelonephritis, defined as hospital admission with at least 2 of the following: fever (≥ 38.0 °C), symptoms of pyelonephritis (nausea, vomiting, chills, and costovertebral tenderness) and a positive urine culture. Delivery before 34 weeks' gestation (treatment 1, placebo 0) Secondary outcomes: adverse neonatal outcome, neonatal death before discharge, or severe neonatal morbidity (presence of 1 or more of the following: severe respiratory distress syndrome, bronchopulmonary dysplasia, periventricular leukomalacia > grade 1, intracerebral haemorrhage > grade 2, necrotising enterocolitis > grade 1, or proven sepsis) Other outcomes: neonatal birthweight (treatment mean (SE) 3453 g (84), placebo 3585 g (82)), time to delivery, spontaneous preterm birth between 32 and 37 weeks, admission to the neonatal intensive care unit, and maternal morbidity including urinary tract infection (clinical report of a urinary tract infection treated with antibiotics); treatment 4, placebo 8
Notes	This study was a multicentre prospective cohort study with an embedded randomised trial. In the final cohort of 4283 women screened for asymptomatic bacteriuria, 248 were asymptomatic bacteriuria‐positive: 40 were randomly assigned to nitrofurantoin, 45 to placebo, and 163 women refused to be enrolled into the randomised component of the study and were followed without treatment. Only the women randomised to treatment or placebo have contributed data to this review, and only outcomes that were reported separately for the treatment and placebo groups have been included. Details of the uropathogen were provided for the ASB‐positive women who received nitrofurantoin: 29/36 were E. coli, 5 Staphylococcus spp, 1 Acinetobacter, and 1 'other' Dates of study: October 2011 to June 2013 Funding sources: ZonMw (the Netherlands Organisation for Health Research and Development) Declarations of interest: Ben WJ Mol received fees from ObsEva, Ferring and Merck; other authors declared no competing interests
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Group assignment was based on a web‐based application with a computer generated list with random block sizes of 2, 4, or 6 participants rendered by an independent data manager"
Allocation concealment (selection bias)	Low risk	Allocation performed by an independent data manager
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Women received 100 mg capsules of nitrofurantoin or identical appearing capsules of placebo.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Women, treating physicians, and researchers remained unaware of the treatment allocation
Incomplete outcome data (attrition bias) All outcomes	Low risk	5 randomised patients communicated by laboratory as ASB‐positive were strictly ASB‐negative (1 yeast, 3 uropathogens at low colony count, 1 contaminated dipslide) included in intention‐to‐treat analysis (4 nitrofurantoin, 1 placebo)
Selective reporting (reporting bias)	Low risk	The study protocol was published and the study's prespecified comes were reported as specified.
Other bias	Low risk	This has been judged as low risk. Of 248 women with asymptomatic bacteriuria, 163 refused to be randomised to treatment or no treatment and may have introduced an unknown bias.
Overall Risk of Bias	Low risk	Overall low