Elder 1971.

Methods	Placebo‐controlled; 2 parallel groups. Quasi‐RCT
Participants	Inclusion criteria: bacteriuria (in clean‐voided specimen with 2 samples > 100,000 bacteria/mL and 1 sample > 10,000 bacteria/mL) at first prenatal visit Exclusion: > 32 weeks' gestation; previously treated for a urinary tract infection during the current pregnancy prior to their first obstetrical visit, delivered or aborted after registering but before first obstetric visit, went elsewhere for prenatal care after registering; did not deliver a singleton pregnancy Setting: Boston City Hospital, USA Number of participants: N = 281
Interventions	Tetracycline 250 mg 4 times a day x 6 weeks (N = 133) vs identically appearing placebo taken similarly (N = 145). If infection did not clear, an alternative drug (usually nitrofurantoin) was given.
Outcomes	Persistent bacteriuria (bacteriuria was said to have cleared if the colony count was less than 1000/mL on 2 successive cultures) up to the time of delivery; includes recurrences Pyelonephritis (fever with signs and symptoms localised to the urinary tract, without other explanation) Low birthweight (< 2500 g) Neonatal outcomes (neonatal deaths (respiratory distress syndrome, other respiratory causes, perforated ulcer), congenital malformations, birth trauma, infection, anaemia) Mean gestational age (38.46 weeks in treated group N = 107 vs 38.25 weeks in placebo group N = 122 (calculated from numbers in paper))
Notes	Tetracycline associated with staining of teeth in one‐third of children. No women lost to follow‐up for outcome of pyelonephritis: 3 women (1%) lost to follow‐up for outcome of persistent bacteriuria and low birthweight. Outcome of persistent bacteriuria in placebo group does not include women who developed pyelonephritis. 7 women moved out of Boston and the outcome of their pregnancies is not known. 4 bacteriuric women delivered twins and are not included. Only live births included in outcome of low birthweight. Prematurity was defined as birthweight of < 2500 g regardless of gestational length. Dates of study: January 1963 to July 1965 Funding sources: National Institute of Child Health and Human Development (HD‐01288), National Institute of Allergy and Infectious Diseases (TO1 AI‐00068) and Division of Research Facilities and Resources (FR‐76‐02), National Institutes of Health. Declarations of interest: none reported
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	High risk	"...alternate bacteriuric ... were assigned".
Allocation concealment (selection bias)	High risk	Participants were allocated by alternation.
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	"identical‐appearing placebo"; insufficient information provided to permit judgement
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	"identical‐appearing placebo"; insufficient information provided to permit judgement
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Insufficient information provided to judge
Selective reporting (reporting bias)	Unclear risk	Unable to judge; twin deliveries were excluded
Other bias	Low risk	The study appears to be free of other sources of bias.
Overall Risk of Bias	High risk	Judged at overall high risk of bias.