Pentoxifylline for treatment of sepsis and necrotising enterocolitis in neonates

Background Mortality and morbidity due to neonatal sepsis and necrotising enterocolitis (NEC) remain high despite the use of potent antimicrobial agents. Agents that modulate inflammation may improve outcomes. Pentoxifylline (PTX), a phosphodiesterase inhibitor, is one such agent. This is an update of a review first published in 2003 and updated in 2011 and 2015. Objectives To assess the effectiveness and safety of intravenous PTX as an adjunct to antibiotic therapy on mortality and morbidity in neonates with suspected or confirmed sepsis and neonates with NEC. Search methods We searched CENTRAL, MEDLINE, Embase, CINAHL, and trial registries in July 2022. We also searched the reference lists of identified clinical trials and handsearched conference s. Selection criteria We included randomised controlled trials (RCTs) or quasi‐RCTs assessing the efficacy of PTX with antibiotics (any dose or duration) for treatment of suspected or confirmed sepsis or NEC in neonates. We included three comparisons: (1) PTX with antibiotics compared to placebo or no intervention with antibiotics; (2) PTX with antibiotics compared to PTX with antibiotics and adjunct treatments such as immunoglobulin M‐enriched intravenous immunoglobulin (IgM‐enriched IVIG); (3) PTX with antibiotics compared to adjunct treatments such as IgM‐enriched IVIG with antibiotics. Data collection and analysis We reported typical risk ratio (RR) and risk difference (RD) with 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) for continuous outcomes derived from a fixed‐effect model of meta‐analysis. We calculated the number needed to treat for an additional beneficial outcome (NNTB) if there was a statistically significant reduction in RD. Main results We identified no new studies for this update. We included six RCTs (416 neonates). All of the included studies examined neonates with sepsis; we identified no studies on neonates with NEC. Four of the six trials had high risk of bias for at least one risk of bias domain. Comparison 1: PTX with antibiotics compared to placebo with antibiotics, or antibiotics alone, in neonates with sepsis may reduce all‐cause mortality during hospital stay (typical RR 0.57, 95% CI 0.35 to 0.93; typical RD −0.08, 95% CI −0.14 to −0.01; NNTB 13, 95% CI 7 to 100; 6 studies, 416 participants, low‐certainty evidence) and may decrease length of hospital stay (LOS) (MD −7.74, 95% CI −11.72 to −3.76; 2 studies, 157 participants, low‐certainty evidenc