Kass 1960.

Methods	Placebo‐controlled trial, 2 parallel groups. Quasi‐RCT
Participants	Inclusion: bacteriuric (> 100,000 bacteria/mL at first prenatal visit, confirmed x 2). Women were randomised after the second positive sample, but only included if the third sample was positive. Exclusion: > 32 weeks' gestation; chronic renal insufficiency Setting: Boston City Hospital, US (approximately 50% black) Number of participants: N = 214 (includes 11 women identified through Renal Clinic)
Interventions	Sulfamethoxypyridazine 500 mg daily with nitrofurantoin for failures (N = 103) or placebo tablet (N = 100) supplied by same manufacturer Treatment continued until term.
Outcomes	Pyelonephritis (dysuria, frequency, and flank pain, fever or chills); however, it was not clear that women were indeed febrile Low birthweight (< 2500 g); prematurity was defined as birthweight < 2500 g Long‐term persistence of bacteriuria (10 to 14 years): 18/63 treatment vs 18/71 placebo Mean gestational age: 39.6 ±3.6 SD for treated bacteriurics; 38.6 ± 3.6 SD for placebo bacteriurics There were 2 stillbirths, both in the placebo group; there were 5 neonatal deaths in the placebo group, and no neonatal deaths in the treatment group.
Notes	For outcome of low birthweight, results are given for total number of deliveries (3 twin deliveries in placebo group vs none in treated group). There are several publications related to this study; where there is a discrepancy in methodology, the most detailed description was used. Dates of study: October 1956 to April 1960 Funding sources: National Institute of Child Health and Human Development, National Institutes of Health, United States Public Health Service (HD‐01288); National Institute of Allergy and Infectious Diseases (TOI AI‐00068); Massachusetts Heart Association Declarations of interest: none reported
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	High risk	"Alternate women received a placebo".
Allocation concealment (selection bias)	High risk	Allocation was based on alternation: "Alternate women received a placebo".
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Placebo was used, and "the nature of the treatment was not know to the patient or to the attending obstetrical staff".
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Although a placebo was used, there are no further details provided to know whether the outcome assessment was blinded.
Incomplete outcome data (attrition bias) All outcomes	High risk	40 women, initially identified, were not enrolled, either because they were > 32 weeks before treatment could be started (N = 30), or they had already received treatment for symptomatic infection (N = 10). Loss to follow‐up: 23 (11%) for outcomes of pyelonephritis and low birthweight; no details provided. 69 (34%) for long‐term persistence of bacteriuria
Selective reporting (reporting bias)	High risk	3 women had a subsequent pregnancy in the study period and were reassigned to their original treatment group and included in the analysis. In 5 patients in the placebo group, it was assumed they had symptomatic disease but no symptoms were documented. Not all women in the symptomatic group were confirmed to have fever and women treated for infections other that in the urinary tract were also included in the symptomatic group if they were found to have cleared their bacteriuria.
Other bias	Low risk	The study appears to be free of other sources of bias.
Overall Risk of Bias	Unclear risk	Overall unclear