Should empiric antibiotic therapy be withheld when aetiology of preterm birth is non-infectious? A protocol for a systematic review.

Introduction Preterm birth (PTB) at <37 weeks of gestation is the leading cause of perinatal morbidity and mortality in developed countries. The traditional approach has been based on the assumption that PTB is primarily a result of intrauterine infection, which triggers preterm labour and puts the newborn at risk of early onset sepsis (EOS). We are currently experiencing a rise in prematurity that results from maternal and fetal diseases unrelated to infection. We have designed a systematic review to assess whether chemoprophylaxis should be withheld when the aetiology of preterm birth is non-infectious. Methods and analysis Our study will focus on studies evaluating EOS in preterm infants. We will conduct a comprehensive search of literature available up to 28 February 2018. An information specialist will search for eligible studies in Medline (Ovid interface, 1948 and onwards), Embase (Ovid interface, 1980 onwards) and the Cochrane Central Register of Controlled Trials (Wiley interface, current issue). We will search databases and registries including records of ongoing research, conference proceedings and thesis (clinical trials, WHO International Clinical Trials Registry Platform). Two authors will independently extract data from eligible studies and assess risk of bias. For continuous outcomes, which follow discrete distribution, mean difference will be calculated. Dichotomous data will be presented using risk ratios, while count data will be expressed using rate ratios. Time-to-event outcomes will be reported as HRs. All estimates will be presented together with 95% CI. Studies comparable with respect to methodology and reporting the same outcomes will be combined in a meta-analysis. Ethics and dissemination Our systematic review does not require approval from the research and ethics board. We will use the findings to prepare a future multicentre randomised control trial in order to establish safe and adequate antibiotics policies for preterm infants, based on the aetiology of PTB.