Study sample
Our protocol and details on the search strategy can be found in PROSPERO (CRD42019153728). We used the search strategy of a previously published Cochrane umbrella review, systematically assessing all Cochrane reviews evaluating interventions to prevent PTB in pregnancy (Supporting information Box S1), performed on November 2nd2017.(8) We updated this search on November 14th, 2019. Reviews were included if they prespecified or reported PTB as an outcome, with PTB defined as birth before 37 weeks’ gestation. The population studied in this project are pregnant women with a singleton or multiple pregnancy without signs of preterm labour or ruptured amniotic membranes and irrespective of risk status for PTB or co-morbidities. Interventions that assessed PTB as an indirect effect of their intervention (e.g. insulin treatment vs metformin in diabetic pregnant women) were included. Interventions to prevent miscarriage were not included.
Progesterone is the most studied drug intervention on prevention of PTB. However, we found no update of the 2013 Cochrane review on this subject in singleton pregnant women,(9) therefore we decided to include the trials included in the most recent Individual Participant Data (IPD) meta-analysis project on progesterone (EPPPIC) as we assumed that this project might be the reason for the lack of update from Cochrane.(10)
We included RCTs regardless of language, provided that full-text articles were available. RCTs that did not explicitly report PTB or gestational age at delivery as an outcome were not included. We focused on RCTs included in Cochrane reviews, since these trials have already been systematically searched and screened by Cochrane reviewers.
One reviewer screened the titles and abstracts of all retrieved reports to exclude any obvious reports of non-eligible trials. A copy of the full article was then obtained for all non-excluded reports.