Abstract: Out of 173 articles screened, three studies were included. There were two comparisons: chlorhexidine dressing following alcohol cleansing versus polyurethane dressing following povidone-iodine cleansing (one study); and silver-alginate patch versus control (two studies). A total of 855 infants from level III neonatal intensive care units (NICUs) were evaluated, 705 of whom were from a single study. All studies were at high risk of bias for blinding of care personnel or unclear risk of bias for blinding of outcome assessors. There was moderate-quality evidence for all major outcomes. The single study comparing chlorhexidine dressing/alcohol cleansing against polyurethane dressing/povidone-iodine cleansing showed no significant difference in the risk of CRBSI (RR 1.18, 95% CI 0.53 to 2.65; RD 0.01, 95% CI −0.02 to 0.03; 655 infants, moderate-quality evidence) and sepsis without a source (RR 1.06, 95% CI 0.75 to 1.52; RD 0.01, 95% CI −0.04 to 0.06; 705 infants, moderate-quality evidence). There was a significant reduction in the risk of catheter colonisation favouring chlorhexidine dressing/alcohol cleansing group (RR 0.62, 95% CI 0.45 to 0.86; RD −0.09, 95% CI −0.15 to −0.03; number needed to treat for an additional beneficial outcome (NNTB) 11, 95% CI 7 to 33; 655 infants, moderate-quality evidence). However, infants in the chlorhexidine dressing/alcohol cleansing group were significantly more likely to develop contact dermatitis, with 19 infants in the chlorhexidine dressing/alcohol cleansing group having developed contact dermatitis compared to none in the polyurethane dressing/povidone-iodine cleansing group (RR 43.06, 95% CI 2.61 to 710.44; RD 0.06, 95% CI 0.03 to 0.08; number needed to treat for an additional harmful outcome (NNTH) 17, 95% CI 13 to 33; 705 infants, moderate-quality evidence). The roles of chlorhexidine dressing in the outcomes reported were unclear, as the two assigned groups received different co-interventions in the form of different skin cleansing agents prior to catheter insertion and during each dressing change. In the other comparison, silver-alginate patch versus control, the data for CRBSI were analysed separately in two subgroups as the two included studies reported the outcome using different denominators: one using infants and another using catheters. There were no significant differences between infants who received silver-alginate patch against infants who received standard line dressing in CRBSI, whether expressed as the number of infants (RR 0.50, 95% CI 0.14 to 1.78; RD −0.12, 95% CI −0.33 to 0.09; 1 study, 50 participants, moderate-quality evidence) or as the number of catheters (RR 0.72, 95% CI 0.27 to 1.89; RD −0.05, 95% CI −0.20 to 0.10; 1 study, 118 participants, moderate-quality evidence). There was also no significant difference between the two groups in mortality (RR 0.55, 95% CI 0.15 to 2.05; RD −0.04, 95% CI −0.13 to 0.05; two studies, 150 infants, I² = 0%, moderate-quality evidence). No adverse skin reaction was recorded in either group. Based on moderate-quality evidence, chlorhexidine dressing/alcohol skin cleansing reduced catheter colonisation, but made no significant difference in major outcomes like sepsis and CRBSI compared to polyurethane dressing/povidone-iodine cleansing. Chlorhexidine dressing/alcohol cleansing posed a substantial risk of contact dermatitis in preterm infants, although it was unclear whether this was contributed mainly by the dressing material or the cleansing agent. While silver-alginate patch appeared safe, evidence is still insufficient for a recommendation in practice. Future research that evaluates antimicrobial dressing should ensure blinding of caregivers and outcome assessors and ensure that all participants receive the same co-interventions, such as the skin cleansing agent. Major outcomes like sepsis, CRBSI and mortality should be assessed in infants of different gestation and birth weight.

Plain-language summary: Three studies (total participants: 855) fit our inclusion criteria. There were two main comparisons: i) chlorhexidine dressing and alcohol skin cleansing against standard polyurethane dressing and povidone-iodine skin cleansing (from one large study), and ii) silver-alginate patch against a control group without patch (from two smaller studies). The quality of the included studies are high, except that the people closely involved in the trials such as the care personnel were not masked from knowing whether or not the infants in the study were given antiseptic or antibiotic dressing, which might have affected their recording or interpretation of the results. One of the studies was funded in part by Johnson and Johnson Medical; Children's Foundation; Children's Hospital, Milwaukee and National Institutes of Health. Another study was funded by the Vanderbilt NICU Research Fund. Funding source was not stated in the third study. In our main findings, chlorhexidine dressing/alcohol skin cleansing made no difference to catheter-related blood stream infection (CRBSI) and blood stream infection ("sepsis") without an identifiable source, although it significantly reduced the chance of micro-organisms lodging in the CVCs ("catheter colonisation"), with an average of 9% reduction in risk among newborn infants with a baseline risk of 24% (1 study, 655 infants). However, infants who received chlorhexidine dressing/alcohol skin cleansing were more likely to develop skin irritation ("contact dermatitis"), as 19 out of 335 infants (5.7%) in the chlorhexidine group developed this complication compared to none in the group that received standard dressing/povidone-iodine cleansing. However, it was unclear whether the dressing or the alcohol solution was mainly responsible for the skin irritation, as the other group did not use alcohol solution for skin cleansing. In the other comparison, silver-alginate patch made no overall differences in CRBSI and mortality compared to no dressing, neither did it cause any adverse reaction. There was moderate-quality evidence for all the major outcomes. The major factor that affected the quality of evidence was the lack of precision in the result estimates, as the calculated plausible range of the effects (the 95% confidence intervals) were wide. Chlorhexidine CVC dressing with alcohol skin cleansing posed a high risk of skin irritation against a modest reduction in catheter colonisation. For silver-alginate patch, evidence is still insufficient for a clear picture of benefit an harm. We have made recommendations for future research that evaluate these interventions.