Gut microbiota and intestinal rehabilitation: a prospective childhood cohort longitudinal study of short bowel syndrome (the MIRACLS study): study protocol.

INTRODUCTION: Short bowel syndrome (SBS) is the predominant cause of paediatric intestinal failure. Although life-saving, parenteral nutrition (PN) is linked to complications and may impact quality of life (QoL). Most children will experience intestinal rehabilitation (IR), but the mechanisms underpinning this remain to be understood. SBS is characterised by abnormal microbiome patterns, which might serve as predictive indicators for IR. We aim to characterise the microbiome profiles of children with SBS during IR, concurrently exploring how parental perspectives of QoL relate to IR. METHODS AND ANALYSIS: This study will enrol a minimum of 20 paediatric patients with SBS (0-18 years). Clinical data and biological samples will be collected over a 2-year study period. We will apply 16S rRNA gene sequencing to analyse the microbiome from faecal and gut tissue samples, with additional shotgun metagenomic sequencing specifically on samples obtained around the time of IR. Gas chromatography with flame ionisation detection will profile faecal short-chain fatty acids. Plasma citrulline and urinary intestinal fatty acid binding proteins will be measured annually. We will explore microbiome-clinical covariate interactions. Furthermore, we plan to assess parental perspectives on QoL during PN and post-IR by inviting parents to complete the Paediatric Quality of Life questionnaire at recruitment and after the completion of IR. ETHICS AND DISSEMINATION: Ethical approval was obtained from the East Midlands-Nottingham 2 Research Ethics Committee (22/EM/0233; 28 November 2022). Recruitment began in February 2023. Outcomes of the study will be published in peer-reviewed scientific journals and presented at scientific meetings. A lay summary of the results will be made available to participants and the public. TRIAL REGISTRATION NUMBER: ISRCTN90620576.

Topical emollient for preventing infection in preterm infants.

BACKGROUND: Breakdown of the developmentally immature epidermal barrier may permit entry for micro-organisms leading to invasive infection in preterm infants. Topical emollients may improve skin integrity and barrier function and thereby prevent invasive infection, a major cause of mortality and morbidity in preterm infants. OBJECTIVES: To assess the effect of topical application of emollients (ointments, creams, or oils) on the risk of invasive infection and mortality in preterm infants. SEARCH METHODS: We searched CENTRAL via Cochrane Register of Studies (CRS) Web and MEDLINE via Ovid (updated 08 January 2021) and the reference lists of retrieved articles. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials that assessed the effect of prophylactic application of topical emollient on the risk of invasive infection, mortality, other morbidity, and growth and development in preterm infants. DATA COLLECTION AND ANALYSIS: We used the standard methods of Cochrane Neonatal. Two review authors separately evaluated trial quality, extracted data, and synthesised effect estimates using risk ratio (RR), risk difference (RD), and mean difference. We used the GRADE approach to assess the certainty of evidence for effects on mortality and invasive infection. MAIN RESULTS: We included 22 trials with a total of 5578 infant participants. The main potential sources of bias were lack of clarity on the methods used to generate random sequences and conceal allocation in half of the trials, and lack of masking of parents, caregivers, clinicians, and investigators in all of the trials. Eight trials (2086 infants) examined the effect of topical ointments or creams. Most participants were very preterm infants cared for in healthcare facilities in high-income countries. Meta-analyses suggested that topical ointments or creams may have little or no effect on invasive infection (RR 1.13, 95% confidence interval (CI) 0.97 to 1.31; low certainty evidence) or mortality (RR 0.94, 95% CI 0.82 to 1.08; low certainty evidence). Fifteen trials (3492 infants) assessed the effect of topical plant or vegetable oils. Most of these trials were undertaken in low- or middle-income countries and were based in healthcare facilities. One large (2249 infants) community-based trial occurred in a rural field practice in India. Meta-analyses suggested that topical oils may reduce invasive infection (RR 0.71, 95% CI 0.52 to 0.96; I² = 52%; low certainty evidence) but have little or no effect on mortality (RR 0.94, 95% CI 0.82 to 1.08, I² = 3%; low certainty evidence). One trial (316 infants) that compared petroleum-based ointment versus sunflower seed oil in very preterm infants in Bangladesh showed little or no effect on invasive infection (RR 0.91, 95% CI 0.57 to 1.46; low certainty evidence), but suggested that ointment may lower mortality slightly (RR 0.82, 95% CI 0.68 to 0.98; RD -0.12, 95% CI -0.23 to -0.01; number needed to treat for an additional beneficial outcome 8, 95% CI 4 to 100; low certainty evidence). One trial (64 infants) that assessed the effect of coconut oil versus mineral oil in preterm infants with birth weight 1500 g to 2000 g in India reported no episodes of invasive infection or death in either group (very low certainty evidence). AUTHORS' CONCLUSIONS: The level of certainty about the effects of emollient therapy on invasive infection or death in preterm infants is low. Since these interventions are mostly inexpensive, readily accessible, and generally acceptable, further good-quality randomised controlled trials in healthcare facilities, and in community settings in low- or middle-income countries, may be justified.

Assessment of C-Reactive Protein Diagnostic Test Accuracy for Late-Onset Infection in Newborn Infants: A Systematic Review and Meta-analysis.

Importance: Rapid and accurate diagnosis of late-onset infection in newborn infants could inform treatment decisions and avoid unnecessary administration of antibiotics. Objective: To compare the accuracy of serum C-reactive protein (CRP) with that of microbiological blood culture for diagnosing late-onset infection in newborns. Data Sources: MEDLINE (1946-2019), Embase (1946-2019), and Science Citation Index (1900-2019) databases were searched for references (any language). The MeSH search terms included were "exp infant, newborn/" or "premature birth/" plus free text synonyms; and "C-reactive protein/" plus free text synonyms; and "exp sepsis/" or "exp bacterial infections/" plus free text synonyms. The proceedings from relevant conferences and references of identified papers were scrutinized. Authors were contacted to request missing data. Study Selection: Cohort and cross-sectional studies were included that compared the accuracy of serum CRP levels with microbiological culture results to diagnose late-onset (>72 hours after birth) infection in newborns (any gestational age) hospitalized after birth. Two reviewers assessed study eligibility. Among 10 394 records, 148 studies were assessed as full texts. Data Extraction and Synthesis: The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline extension for Diagnostic Test Accuracy (DTA) reviews was followed. Two reviewers assessed the method quality of each study using guidance from the Cochrane Screening and Diagnostic Test Methods Group (adapted from the Quality Assessment of Diagnostic Accuracy Studies 2). Main Outcomes and Measures: The primary meta-analysis outcome was diagnostic test accuracy of serum CRP level taken at initial investigation of an infant with suspected late-onset infection. The median specificity (proportion of true-negative results) and calculated pooled sensitivity (proportion of true-positive results) were determined by generating hierarchical summary receiver characteristic operating curves. Results: In total, 22 studies with 2255 infants were included (sample size range, 11-590 infants). Participants in most studies were preterm (<37 weeks) or very low-birth weight (<1500 g) infants. Two studies additionally enrolled infants born at term. Most studies (16) used a prespecified CRP level cutoff for a "positive" index test (5-10 mg/L), and most studies (17) used the culture of a pathogenic microorganism from blood as the reference standard. Risk of bias was low with independent assessment of index and reference tests. At median specificity (0.74), pooled sensitivity was 0.62 (95% CI, 0.50-0.72). Adding serum CRP level to the assessment of an infant with a 40% pretest probability of late-onset infection (the median for the included studies) generated posttest probabilities of 26% for a negative test result and 61% for a positive test result. Conclusions and Relevance: The findings suggest that determination of serum CRP level at initial evaluation of an infant with suspected late-onset infection is unlikely to aid early diagnosis or to select infants to undergo further investigation or treatment with antimicrobial therapy or other interventions.

C-reactive protein for diagnosing late-onset infection in newborn infants.

BACKGROUND: Late-onset infection is the most common serious complication associated with hospital care for newborn infants. Because confirming the diagnosis by microbiological culture typically takes 24 to 48 hours, the serum level of the inflammatory marker C-reactive protein (CRP) measured as part of the initial investigation is used as an adjunctive rapid test to guide management in infants with suspected late-onset infection. OBJECTIVES: To determine the diagnostic accuracy of serum CRP measurement in detecting late-onset infection in newborn infants. SEARCH METHODS: We searched electronic databases (MEDLINE, Embase, and Science Citation Index to September 2017), conference proceedings, previous reviews, and the reference lists of retrieved articles. SELECTION CRITERIA: We included cohort and cross-sectional studies evaluating the diagnostic accuracy of serum CRP levels for the detection of late-onset infection (occurring more than 72 hours after birth) in newborn infants. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed eligibility for inclusion, evaluated the methodological quality of included studies, and extracted data to estimate diagnostic accuracy using hierarchical summary receiver operating characteristic (SROC) models. We assessed heterogeneity by examining variability of study estimates and overlap of the 95% confidence interval (CI) in forest plots of sensitivity and specificity. MAIN RESULTS: The search identified 20 studies (1615 infants). Most were small, single-centre, prospective cohort studies conducted in neonatal units in high- or middle-income countries since the late 1990s. Risk of bias in the included studies was generally low with independent assessment of index and reference tests. Most studies used a prespecified serum CRP threshold level as the definition of a 'positive' index test (typical cut-off level between 5 mg/L and 10 mg/L) and the culture of a pathogenic micro-organism from blood as the reference standard.At median specificity (0.74), sensitivity was 0.62 (95% CI 0.50 to 0.73). Heterogeneity was evident in the forest plots but it was not possible to conduct subgroup or meta-regression analyses by gestational ages, types of infection, or types of infecting micro-organism. Covariates for whether studies used a predefined threshold or not, and whether studies used a standard threshold of between 5 mg/L and 10 mg/L, were not statistically significant. AUTHORS' CONCLUSIONS: The serum CRP level at initial evaluation of an infant with suspected late-onset infection is unlikely to be considered sufficiently accurate to aid early diagnosis or select infants to undergo further investigation or treatment with antimicrobial therapy or other interventions.

Meta-ethnography of experiences of early discharge, with a focus on paediatric febrile neutropenia.

PURPOSE (STATING THE MAIN PURPOSES AND RESEARCH QUESTION): Many children have no significant sequelae of febrile neutropenia. A systematic review of clinical studies demonstrated patients at low risk of septic complications can be safely treated as outpatients using oral antibiotics with low rates of treatment failure. Introducing earlier discharge may improve quality of life, reduce hospital acquired infection and reduce healthcare service pressures. However, the review raised concerns that this might not be acceptable to patients, families and healthcare professionals. METHODS: This qualitative synthesis explored experiences of early discharge in paediatric febrile neutropenia, including reports from studies of adult febrile neutropenia and from other paediatric conditions. Systematic literature searching preceded meta-ethnographic analysis, including reading the studies and determining relationships between studies, translation of studies and synthesis of these translations. RESULTS: Nine papers were included. The overarching experience of early discharge is that decision-making is complex and difficult and influenced by fear, timing and resources. From this background, we identified two distinct themes. First, participants struggled with practical consequences of treatment regimens, namely childcare, finances and follow-up. A second theme identified social and emotional issues, including isolation, relational and environmental challenges. Linking these, participants considered continuity of care and the need for information important. CONCLUSIONS: Trust and confidence appeared interdependent with resources available to families-both are required to manage early discharge. Socially informed resilience is relevant to facilitating successful discharge strategies. Interventions which foster resilience may mediate the ability and inclination of families to accept early discharge. Services have an important role in recognising and enhancing resilience.

Nutrition in the preterm infant: what's new?

PURPOSE OF REVIEW: The increasing recognition of the role of nutritional care for preterm infants continues to result in a proliferation of review articles, systematic reviews, observational studies and trials. In this article, we review a selection of important studies published in the last 12­18 months. RECENT FINDINGS: The selected studies demonstrate the potential importance of light protecting parenteral nutrition solutions, the benefits of standardized concentrated parenteral nutrition solutions and the importance of insulin-like growth factor I in early life. Trials of immunonutrients (such as bile salt-stimulated lipase) and other bioactive peptides such as lactoferrin are in progress, and emerging data highlight the importance of vitamin D for immune regulation, and therefore its role in sepsis and gut function. Early oro-pharyngeal administration of colostrum appears to safely improve early immune development, and supports the increasingly common practice of immediate commencement of mothers' own breast milk. Despite this, studies continue to show that breastfeeding continuation rates could be improved. Data also highlight the potential role of macronutrient supply on other functional outcomes, such as retinopathy of prematurity. Finally, the importance of the unique nutritional needs of late and moderately preterm infants is starting to be recognized ­ a much larger group than the extremely preterm infants in whom many studies are focused. SUMMARY: Earlier, more aggressive nutrient supply and feeding regimes, including optimal support of breastfeeding mothers to ensure adequate provision of own mother's milk, appear to improve growth and neurodevelopmental outcomes. The addition of bioactive proteins shows promise. Special focus needs to be reestablished for late and moderately preterm infants, who have particular nutritional and feeding support requirements. This review has highlighted the need for further research particularly in the areas of early parenteral nutrition, the optimal regime to improve early growth and neuronal effects, the optimal rate of growth and/or catch-up, and the role of immune nutrients.

Systematic review of reduced therapy regimens for children with low risk febrile neutropenia.

PURPOSE: Reduced intensity therapy for children with low-risk febrile neutropenia may provide benefits to both patients and the health service. We have explored the safety of these regimens and the effect of timing of discharge. METHODS: Multiple electronic databases, conference abstracts and reference lists were searched. Randomised controlled trials (RCT) and prospective observational cohorts examining the location of therapy and/or the route of administration of antibiotics in people younger than 18 years who developed low-risk febrile neutropenia following treatment for cancer were included. Meta-analysis using a random effects model was conducted. I (2) assessed statistical heterogeneity not due to chance. REGISTRATION: PROSPERO (CRD42014005817). RESULTS: Thirty-seven studies involving 3205 episodes of febrile neutropenia were included; 13 RCTs and 24 prospective observational cohorts. Four safety events (two deaths, two intensive care admissions) occurred. In the RCTs, the odds ratio for treatment failure (persistence, worsening or recurrence of fever/infecting organisms, antibiotic modification, new infections, re-admission, admission to critical care or death) with outpatient treatment was 0.98 (95% confidence interval (95%CI) 0.44-2.19, I (2) = 0 %) and with oral treatment was 1.05 (95%CI 0.74-1.48, I (2) = 0 %). The estimated risk of failure using outpatient therapy from all prospective data pooled was 11.2 % (95%CI 9.7-12.8 %, I (2) = 77.2 %) and using oral antibiotics was 10.5 % (95%CI 8.9-12.3 %, I (2) = 78.3 %). The risk of failure was higher when reduced intensity therapies were used immediately after assessment, with lower rates when these were introduced after 48 hours. CONCLUSIONS: Reduced intensity therapy for specified groups is safe with low rates of treatment failure. Services should consider how these can be acceptably implemented.

Topical emollient for preventing infection in preterm infants.

BACKGROUND: Breakdown of the developmentally immature epidermal barrier may permit entry for micro-organisms leading to invasive infection in preterm infants. Topical emollients may improve skin integrity and barrier function and thereby prevent invasive infection, a major cause of mortality and morbidity in preterm infants. OBJECTIVES: To assess the effect of topical application of emollients (ointments, creams, or oils) on the incidence of invasive infection, other morbidity, and mortality in preterm infants. SEARCH METHODS: We used the standard search strategy of the Cochrane Neonatal Review group to search the Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 7), MEDLINE via PubMed (1966 to August 2015), EMBASE (1980 to August 2015), and CINAHL (1982 to August 2015). We also searched clinical trials databases, conference proceedings, previous reviews and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials that assessed the effect of prophylactic application of topical emollient (ointments, creams, or oils) on the incidence of invasive infection, mortality, other morbidity, and growth and development in preterm infants. DATA COLLECTION AND ANALYSIS: Two review authors assessed trial eligibility and risk of bias and undertook data extraction independently. We analysed the treatment effects in the individual trials and reported the risk ratio and risk difference for dichotomous data and mean difference for continuous data, with respective 95% confidence intervals. We used a fixed-effect model in meta-analyses and explored the potential causes of heterogeneity in subgroup analyses. MAIN RESULTS: We identified 18 eligible primary publications (21 trial reports). A total of 3089 infants participated in the trials. The risk of bias varied with lack of clarity on methods to conceal allocation in half of the trials and lack of blinding of caregivers or investigators in all of the trials being the main potential sources of bias.Eight trials (2086 infants) examined the effect of topical ointments or creams. Most participants were very preterm infants cared for in health-care facilities in high-income countries. Meta-analyses did not show evidence of a difference in the incidence of invasive infection (typical risk ratio (RR) 1.13, 95% confidence interval (CI) 0.97 to 1.31; low quality evidence) or mortality (typical RR 0.87, 95% CI 0.75 to 1.03; low quality evidence).Eleven trials (1184 infants) assessed the effect of plant or vegetable oils. Nine of these trials were undertaken in low- or middle-income countries and all were based in health-care facilities rather than home or community settings. Meta-analyses did not show evidence of a difference in the incidence of invasive infection (typical RR 0.71, 95% CI 0.51 to 1.01; low quality evidence) or mortality (typical RR 0.94, 95% CI 0.81 to 1.08; moderate quality evidence). Infants massaged with vegetable oil had a higher rate of weight gain (about 2.55 g/kg/day; 95% CI 1.76 to 3.34), linear growth (about 1.22 mm/week; 95% CI 1.01 to 1.44), and head growth (about 0.45 mm/week; 95% CI 0.19 to 0.70). These meta-analyses contained substantial heterogeneity. AUTHORS' CONCLUSIONS: The available data do not provide evidence that the use of emollient therapy prevents invasive infection or death in preterm infants in high-, middle- or low-income settings. Some evidence of an effect of topical vegetable oils on neonatal growth exists but this should be interpreted with caution because lack of blinding may have introduced caregiver or assessment biases. Since these interventions are low cost, readily accessible, and generally acceptable, further randomised controlled trials, particularly in both community- and health care facility-based settings in low-income countries, may be justified.

Prophylactic systemic antifungal agents to prevent mortality and morbidity in very low birth weight infants.

BACKGROUND: Invasive fungal infection is an important cause of mortality and morbidity in very preterm and very low birth weight infants. Early diagnosis is difficult and treatment is often delayed. Systemically absorbed antifungal agents (usually azoles) are increasingly used as prophylaxis against invasive fungal infection in this population. OBJECTIVES: To assess the effect of prophylactic systemic antifungal therapy on mortality and morbidity in very preterm or very low birth weight infants. SEARCH METHODS: We used the standard search strategy of the Cochrane Neonatal Review Group. This included searches of the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2015, Issue 8), MEDLINE, EMBASE, and CINAHL (to May 2015), conference proceedings, and previous reviews. SELECTION CRITERIA: Randomised controlled trials or quasi-randomised controlled trials that compared the effect of prophylactic systemic antifungal therapy versus placebo or no drug or another antifungal agent or dose regimen in very low birth weight infants. DATA COLLECTION AND ANALYSIS: We extracted data using the standard methods of the Cochrane Neonatal Review Group, with separate evaluation of trial quality and data extraction by two review authors. MAIN RESULTS: We identified 15 eligible trials enrolling a total of 1690 infants. Ten trials (1371 infants) compared systemic antifungal prophylaxis versus placebo or no drug. These trials were generally of good methodological quality. Meta-analysis found a statistically significant reduction in the incidence of invasive fungal infection (typical risk ratio (RR) 0.43, 95% confidence interval (CI) 0.31 to 0.59; risk difference (RD) -0.09, 95% CI -0.12 to -0.06). The average incidence of invasive fungal infection in the control groups of the trials (16%) was much higher than that generally reported from large cohort studies. Meta-analysis did not find a statistically significant difference in the risk of death prior to hospital discharge (typical RR 0.79, 95% CI 0.61 to 1.02; typical RD -0.04, 95% CI -0.07 to 0.00). Very limited data on long-term neurodevelopmental outcomes were available. Three trials that compared systemic versus oral or topical non-absorbed antifungal prophylaxis did not detect any statistically significant effects on invasive fungal infection or mortality. Two trials that compared different dose regimens of prophylactic intravenous fluconazole did not detect any significant differences in infection rates or mortality. AUTHORS' CONCLUSIONS: Prophylactic systemic antifungal therapy reduces the incidence of invasive fungal infection in very preterm or very low birth weight infants. This finding should be interpreted and applied cautiously since the incidence of invasive fungal infection was very high in the control groups of many of the included trials. Meta-analysis does not demonstrate a statistically significant effect on mortality. There are currently only limited data on the long-term neurodevelopmental consequences for infants exposed to this intervention. In addition, there is a need for further data on the effect of the intervention on the emergence of organisms with antifungal resistance.

Prophylactic oral/topical non-absorbed antifungal agents to prevent invasive fungal infection in very low birth weight infants.

BACKGROUND: Invasive fungal infection is an important cause of mortality and morbidity in very preterm or very low birth weight infants. Uncertainty exists about the effect of prophylactic oral/topical non-absorbed antifungals to reduce mucocutaneous colonisation and so limit the risk of invasive fungal infection in this population. OBJECTIVES: To assess the effect of prophylactic oral/topical non-absorbed antifungal therapy on the incidence of invasive fungal infection, mortality and morbidity in very preterm or very low birth weight infants. SEARCH METHODS: We used the standard search strategy of the Cochrane Neonatal Review Group. This included searches of the Cochrane Central Register of Controlled Trials (CENTRAL: The Cochrane Library, 2015, Issue 7), MEDLINE, EMBASE, and CINAHL (to May 2015), conference proceedings, and previous reviews. SELECTION CRITERIA: Randomised controlled trials or quasi-randomised controlled trials that compared the effect of prophylactic oral/topical non-absorbed antifungal therapy versus placebo or no drug or another antifungal agent or dose regimen in very preterm or very low birth weight infants. DATA COLLECTION AND ANALYSIS: We extracted data using the standard methods of the Cochrane Neonatal Review Group with separate evaluation of trial quality and data extraction by two review authors. MAIN RESULTS: Four trials, in which a total of 1800 infants participated, compared oral/topical non-absorbed antifungal prophylaxis (nystatin or miconazole) with placebo or no drug. These trials had various methodological weaknesses including quasi-randomisation, lack of allocation concealment, and lack of blinding of intervention and outcomes assessment. The incidence of invasive fungal infection was very high in the control groups of three of these trials. Meta-analysis found a statistically significant reduction in the incidence of invasive fungal infection (typical risk ratio 0.20, 95% confidence interval 0.14 to 0.27; risk difference -0.18, -0.21 to -0.15) but substantial statistical heterogeneity was present. We did not find a statistically significant effect on mortality (typical risk ratio 0.87, 0.72 to 1.05; risk difference -0.03, -0.06 to 0.01). None of the trials assessed posthospital discharge outcomes. Three trials (N = 326) assessed the effect of oral/topical non-absorbed versus systemic antifungal prophylaxis. Meta-analyses did not find any statistically significant differences in the incidences of invasive fungal infection or all-cause mortality. AUTHORS' CONCLUSIONS: The finding of a reduction in risk of invasive fungal infection in very low birth weight infants treated with oral/topical non-absorbed antifungal prophylaxis should be interpreted cautiously because of methodological weaknesses in the included trials. Further large randomised controlled trials in current neonatal practice settings are needed to resolve this uncertainty. These trials might compare oral/topical non-absorbed antifungal agents with placebo, with each other, or with systemic antifungal agents and should include an assessment of effect on long-term neurodevelopmental outcomes.

Topical emollient for prevention of infection in preterm infants: a systematic review.

BACKGROUND: Breakdown of the developmentally immature epidermal barrier in the preterm infant can permit entry of microorganisms leading to invasive infection. Topical emollients might improve skin integrity and barrier function and thereby prevent invasive infection, a major cause of mortality and morbidity in these infants. The aim of this study was to appraise and synthesise the evidence for topical application of emollients in the prevention of invasive infection and mortality in preterm infants. METHODS: We conducted a systematic review of randomised controlled trials that assessed the effect of prophylactic application of topical emollient (ointments, creams, or oils) on the incidence of invasive infection, and other morbidity and mortality in preterm infants. We used the standard methods of the Cochrane Neonatal Group to identify and appraise trials and extract and synthesise data. We prespecified subgroup analyses of trials in low-income and middle-income versus high-income countries. FINDINGS: We included 16 trials (2809 infants). Methodological quality varied, with uncertainty about adequate allocation concealment methods in eight trials and lack of masking in all of the trials. Most trials in high-income countries compared expensive proprietary ointments or creams with standard care. Meta-analysis showed a significantly higher incidence of infection in infants treated with emollient (relative risk 1·20, 95% CI 1·01-1·42), but no significant effect on mortality or other morbidity. In low-income or middle-income countries, most trials compared low-cost natural plant oils with standard care, and meta-analyses did not show a significant effect on infection or mortality. Topical oil application increased rates of weight gain (∼2 g/kg per day) and gain in length (∼1 mm/kg per week). INTERPRETATION: The available trial data do not provide strong evidence that emollients prevent invasive infection or death in preterm infants. Given the burden of infectious morbidity and mortality in preterm infants in low-income or middle-income countries, further large, pragmatic trials of topical oils (which are low-cost, readily available, and widely accepted traditional neonatal skin care practices) are justified to improve the precision of the estimates of effect size. FUNDING: National Institute for Health Research.