Early removal versus expectant management of central venous catheters in neonates with bloodstream infection

BACKGROUND: Uncertainty exists regarding the management of newborn infants with a bloodstream infection and a central venous catheter in place. The central venous catheter may act as a nidus for infecting organisms and observational studies have suggested that early removal of the catheter is associated with a lower incidence of persistent or complicated infection. However, since central venous catheters provide secure vascular access to deliver nutrition and medications, the possible harms of early removal versus expectant management also need to be considered. OBJECTIVES: To determine the effect of early removal versus expectant management of central venous catheters on morbidity and mortality in newborn infants with bloodstream infections. 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 2015, Issue 11), MEDLINE (1966 to October 2015), EMBASE (1980 to October 2015), CINAHL (1982 to October 2015), conference proceedings and previous reviews. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials that compared early removal versus expectant management of central venous catheters in neonates with bloodstream infections. DATA COLLECTION AND ANALYSIS: We used the standard methods of the Cochrane Neonatal Review Group. MAIN RESULTS: We did not identify any eligible randomised controlled trials. AUTHORS' CONCLUSIONS: There are no trial data to guide practice regarding early removal versus expectant management of central venous catheters in newborn infants with bloodstream infections. A simple and pragmatic randomised controlled trial is needed to resolve the uncertainty about optimal management in this common and important clinical scenario

Newborn Length of Stay and Risk of Readmission.

BACKGROUND: Evidence on the association between newborn length of hospital stay (LOS) and risk of readmission is conflicting. We compared methods for modelling this relationship, by gestational age, using population-level hospital data on births in England between 2005-14. METHODS: The association between LOS and unplanned readmission within 30 days of postnatal discharge was explored using four approaches: (i) modelling hospital-level LOS and readmission rates; (ii) comparing trends over time in LOS and readmission; (iii) modelling individual LOS and adjusted risk of readmission; and (iv) instrumental variable analyses (hospital-level mean LOS and number of births on the same day). RESULTS: Of 4 667 827 babies, 5.2% were readmitted within 30 days. Aggregated data showed hospitals with longer mean LOS were not associated with lower readmission rates for vaginal (adjusted risk ratio (aRR) 0.87, 95% confidence interval (CI) 0.66, 1.13), or caesarean (aRR 0.89, 95% CI 0.72, 1.12) births. LOS fell by an average 2.0% per year for vaginal births and 3.4% for caesarean births, while readmission rates increased by 4.4 and 5.1% per year respectively. Approaches (iii) and (iv) indicated that longer LOS was associated with a reduced risk of readmission, but only for late preterm, vaginal births (34-36 completed weeks' gestation). CONCLUSIONS: Longer newborn LOS may benefit late preterm babies, possibly due to increased medical or psychosocial support for those at greater risk of potentially preventable readmissions after birth. Research based on observational data to evaluate relationships between LOS and readmission should use methods to reduce the impact of unmeasured confounding

Slow advancement of enteral feed volumes to prevent necrotising enterocolitis in very low birth weight infants

BACKGROUND: Early enteral feeding practices are potentially modifiable risk factors for necrotising enterocolitis (NEC) in very preterm or very low birth weight (VLBW) infants. Observational studies suggest that conservative feeding regimens, including slowly advancing enteral feed volumes, reduce the risk of NEC. However, slow feed advancement may delay establishment of full enteral feeding and may be associated with metabolic and infectious morbidities secondary to prolonged exposure to parenteral nutrition. OBJECTIVES: To determine effects of slow rates of enteral feed advancement on the incidence of NEC, mortality, and other morbidities in very preterm or VLBW infants. SEARCH METHODS: We used the standard Cochrane Neonatal search strategy to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 5), MEDLINE via PubMed (1966 to June 2017), Embase (1980 to June 2017), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to June 2017). We searched clinical trials databases, conference proceedings, previous reviews, and reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-randomised trials. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials that assessed effects of slow (up to 24 mL/kg/d) versus faster rates of advancement of enteral feed volumes upon the incidence of NEC in very preterm or VLBW infants. DATA COLLECTION AND ANALYSIS: Two review authors assessed trial eligibility and risk of bias and independently extracted data. We analysed treatment effects in individual trials and reported risk ratio (RR) and risk difference (RD) for dichotomous data, and mean difference (MD) for continuous data, with respective 95% confidence intervals (CIs). We used a fixed-effect model for meta-analyses and explored potential causes of heterogeneity via sensitivity analyses. We assessed the quality of evidence at the outcome level using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: We identified 10 RCTs in which a total of 3753 infants participated (2804 infants participated in one large trial). Most participants were stable very preterm infants of birth weight appropriate for gestation. About one-third of all participants were extremely preterm or extremely low birth weight (ELBW), and about one-fifth were small for gestational age (SGA), growth-restricted, or compromised in utero, as indicated by absent or reversed end-diastolic flow velocity (AREDFV) in the fetal umbilical artery. Trials typically defined slow advancement as daily increments of 15 to 20 mL/kg, and faster advancement as daily increments of 30 to 40 mL/kg. Trials generally were of good methodological quality, although none was blinded.Meta-analyses did not show effects on risk of NEC (typical RR 1.07, 95% CI 0.83 to 1.39; RD 0.0, 95% CI -0.01 to 0.02) or all-cause mortality (typical RR 1.15, 95% CI 0.93 to 1.42; typical RD 0.01, 95% CI -0.01 to 0.03). Subgroup analyses of extremely preterm or ELBW infants, or of SGA or growth-restricted or growth-compromised infants, showed no evidence of an effect on risk of NEC or death. Slow feed advancement delayed establishment of full enteral nutrition by between about one and five days. Meta-analysis showed borderline increased risk of invasive infection (typical RR 1.15, 95% CI 1.00 to 1.32; typical RD 0.03, 95% CI 0.00 to 0.05). The GRADE quality of evidence for primary outcomes was "moderate", downgraded from "high" because of lack of blinding in the included trials. AUTHORS' CONCLUSIONS: Available trial data do not provide evidence that advancing enteral feed volumes at daily increments of 15 to 20 mL/kg (compared with 30 to 40 mL/kg) reduces the risk of NEC or death in very preterm or VLBW infants, extremely preterm or ELBW infants, SGA or growth-restricted infants, or infants with antenatal AREDFV. Advancing the volume of enteral feeds at a slow rate results in several days of delay in establishing full enteral feeds and may increase the risk of invasive infection

International comparison of emergency hospital use for infants: data linkage cohort study in Canada and England.

OBJECTIVES: To compare emergency hospital use for infants in Ontario (Canada) and England. METHODS: We conducted a population-based data linkage study in infants born ≥34 weeks' gestation between 2010 and 2013 in Ontario (n=253 930) and England (n=1 361 128). Outcomes within 12 months of postnatal discharge were captured in hospital records. The primary outcome was all-cause unplanned admissions. Secondary outcomes included emergency department (ED) visits, any unplanned hospital contact (either ED or admission) and mortality. Multivariable regression was used to evaluate risk factors for infant admission. RESULTS: The percentage of infants with ≥1 unplanned admission was substantially lower in Ontario (7.9% vs 19.6% in England) while the percentage attending ED but not admitted was higher (39.8% vs 29.9% in England). The percentage of infants with any unplanned hospital contact was similar between countries (42.9% in Ontario, 41.6% in England) as was mortality (0.05% in Ontario, 0.06% in England). Infants attending ED were less likely to be admitted in Ontario (7.3% vs 26.2%), but those who were admitted were more likely to stay for ≥1 night (94.0% vs 55.2%). The strongest risk factors for admission were completed weeks of gestation (adjusted OR for 34-36 weeks vs 39+ weeks: 2.44; 95% CI 2.29 to 2.61 in Ontario and 1.66; 95% CI 1.62 to 1.70 in England) and young maternal age. CONCLUSIONS: Children attending ED in England were much more likely to be admitted than those in Ontario. The tendency towards more frequent, shorter admissions in England could be due to more pressure to admit within waiting time targets, or less availability of paediatric expertise in ED. Further evaluations should consider where best to focus resources, including in-hospital, primary care and paediatric care in the community

A review of the current policies and guidance regarding Apgar scoring and the detection of jaundice and cyanosis concerning Black, Asian and ethnic minority neonates

Background Ethnic inequalities in maternal and neonatal health in the UK are well documented. Concerns exist regarding the use of skin colour in neonatal assessments. Healthcare professionals should be trained to recognise symptoms of diverse skin tones, and comprehensive, and inclusive guidance is necessary for the safe assessment of all infants. Disparities in healthcare provision have been emphasised during the COVID-19 pandemic, and additional research is needed to determine whether such policies adequately address ethnic minority neonates. Methods A desktop search included searches of guidance produced for the United Kingdom (UK). Further searches of the Cochrane and World Health Organization (WHO) were used to identify any international guidance applicable in the UK context. Results Several policies and one training resource used descriptors ‘pink,’ ‘pale,’ ‘pallor,’ and ‘blue’ about neonatal skin and mucous membrane colour. No policies provided specific guidance on how these colour descriptors may appear in neonates with different skin pigmentation. Only the NICE guidance and HEE e-learning resource acknowledged the challenges of assessing jaundice in infants with diverse skin tones, while another guideline noted differences in the accuracy of bilirubin measurements for the assessment of jaundice. Three policies and one training resource advised against relying on visual observation of skin colour when diagnosing neonatal conditions. The training resource included images of ethnic minority neonates, although most images included white infants. Conclusions Inadequate consideration of ethnicity in UK policy and training perpetuates disparities, leading to inaccurate assessments. A review is needed for inclusivity in neonatal care, regardless of skin pigmentation

The cost-effectiveness of strategies preventing late-onset infection in preterm infants

Objective: Developing a model to analyse the cost-effectiveness of interventions preventing late-onset infection (LOI) in preterm infants and applying it to the evaluation of Anti-Microbial Impregnated Peripherally Inserted Central Catheters (AM-PICCs) compared with standard PICCs (S-PICCs). Design: Model-based cost-effectiveness analysis, using data from the PREVAIL randomised controlled trial linked to routine healthcare data, supplemented with published literature. The model assumes that LOI increases the risk of neurodevelopmental impairment (NDI). Setting: Neonatal Intensive Care Units in the UK National Health Service (NHS). Patients: Infants born ≤32 weeks gestational age, requiring a 1 French gauge PICC. Interventions: AM-PICC and S-PICC. Main outcome measures: Life expectancy, quality-adjusted life years and healthcare costs over the infants’ expected lifetime. Results: Severe NDI reduces life expectancy by 14.79 (95% confidence interval (CI) 4.43; 26.68; undiscounted) years, 10.63 (95%CI 7.74; 14.02; discounted) QALYs, and costs £19,060 (95%CI £14,197; £24,70; discounted) to the NHS. If LOI causes NDI, the maximum acquisition price of an intervention reducing LOI risk by 5% is £120. AM-PICCs increase costs (£54.85 (95%CI £25.95; £89.12)) but have negligible impact on health outcomes (-0.01 (95%CI -0.09; 0.04) QALYs), compared with S-PICCs. The NHS can invest up to £2.4 million in research to confirm that AM-PICCs are not cost-effective. Conclusions: The model quantifies health losses and additional healthcare costs caused by NDI and LOI during neonatal care. Given these consequences, interventions preventing LOI, even by a small extent, can be cost-effective. AM-PICCs, being less effective and more costly than S-PICC, are not likely to be cost-effective

Prebiotics to prevent necrotising enterocolitis in very preterm or very low birth weight infants

BACKGROUND: Dietary supplementation with prebiotic oligosaccharides to modulate the intestinal microbiome has been proposed as a strategy to reduce the risk of necrotising enterocolitis (NEC) and associated mortality and morbidity in very preterm or very low birth weight (VLBW) infants. OBJECTIVES: To assess the benefits and harms of enteral supplementation with prebiotics (versus placebo or no treatment) for preventing NEC and associated morbidity and mortality in very preterm or VLBW infants. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Maternity and Infant Care database and the Cumulative Index to Nursing and Allied Health Literature (CINAHL), from the earliest records to July 2022. We searched clinical trials databases and conference proceedings, and examined the reference lists of retrieved articles. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs comparing prebiotics with placebo or no prebiotics in very preterm ( 48 hours after birth) invasive infection, duration of hospitalisation, and neurodevelopmental impairment. We used the GRADE approach to assess the level of certainty of the evidence. MAIN RESULTS: We included seven trials in which a total of 705 infants participated. All the trials were small (mean sample size 100). Lack of clarity on methods to conceal allocation and mask caregivers or investigators were potential sources of bias in three of the trials. The studied prebiotics were fructo- and galacto-oligosaccharides, inulin, and lactulose, typically administered daily with enteral feeds during birth hospitalisation. Meta-analyses of data from seven trials (686 infants) suggest that prebiotics may result in little or no difference in NEC (RR 0.97, 95% CI 0.60 to 1.56; RD none fewer per 1000, 95% CI 50 fewer to 40 more; low-certainty evidence), all-cause mortality (RR 0.43, 95% CI 0.20 to 0.92; 40 per 1000 fewer, 95% CI 70 fewer to none fewer; low-certainty evidence), or late-onset invasive infection (RR 0.79, 95% CI 0.60 to 1.06; 50 per 1000 fewer, 95% CI 100 fewer to 10 more; low-certainty evidence) prior to hospital discharge. The certainty of this evidence is low because of concerns about the risk of bias in some trials and the imprecision of the effect size estimates. The data available from one trial provided only very low-certainty evidence about the effect of prebiotics on measures of neurodevelopmental impairment (Bayley Scales of Infant Development (BSID) Mental Development Index score < 85: RR 0.84, 95% CI 0.25 to 2.90; very low-certainty evidence; BSID Psychomotor Development Index score < 85: RR 0.24, 95% 0.03 to 2.00; very low-certainty evidence; cerebral palsy: RR 0.35, 95% CI 0.01 to 8.35; very low-certainty evidence). AUTHORS' CONCLUSIONS: The available trial data provide low-certainty evidence about the effects of prebiotics on the risk of NEC, all-cause mortality before discharge, and invasive infection, and very low-certainty evidence about the effect on neurodevelopmental impairment for very preterm or VLBW infants. Our confidence in the effect estimates is limited; the true effects may be substantially different. Large, high-quality trials are needed to provide evidence of sufficient validity to inform policy and practice decisions

Treating extravasation injuries in infants and young children : a scoping review and survey of UK NHS practice

BACKGROUND: Extravasation injuries are caused by unintended leakages of fluids or medicines from intravenous lines but there is no consensus on the best treatment approaches, particularly in infants and young children. METHODS: This paper presents a more succinct account of a study of treatments for extravasation injuries in infants and children which has also been reported in full as an NIHR HTA report. A systematic scoping review and survey of UK NHS practice were undertaken. Twelve databases - including MEDLINE and EMBASE - were searched for relevant studies in February 2017. Studies of children with extravasation injuries receiving any treatment for extravasation injury were eligible, providing they reported one of the following outcomes: wound healing time, infection, pain, scarring, functional impairment, and requirement for surgery. Studies were screened in duplicate. Data were extracted by one researcher and checked by another. Studies were summarised narratively. An online questionnaire was distributed to NHS staff at neonatal units, paediatric intensive care units and principal oncology/haematology units. RESULTS: The evidence identified in the scoping review was mostly comprised of small, retrospective, uncontrolled group studies or case reports. The studies covered a wide range of interventions including conservative management approaches, saline flush-out techniques (with or without prior hyaluronidase), hyaluronidase without flush-out, artificial skin treatments, debridement and plastic surgery. Few studies graded injury severity and the results sections and outcomes reported in most studies were limited. There was heterogeneity across study populations in many factors. The survey yielded 63 responses from hospital units across the UK. Results indicated that although most units had written documentation for treating extravasation injuries, only one-third of documents included a system for grading injury severity. The most frequently used interventions were elevation of the affected area and analgesics. Saline wash-out treatments, either with or without hyaluronidase, were regularly used in about half of all neonatal units. Most responders thought a randomised controlled trial might be a viable future research design. CONCLUSIONS: There is some uncertainty about which are most the promising treatments for extravasation injuries in infants and young children. Saline flush-out techniques and conservative management approaches are commonly used and may be suitable for evaluation in trials. Although conventional randomised trials may be difficult to perform a randomised registry trial may be an appropriate alternative design

Treatment of extravasation injuries in infants and young children : a scoping review and survey

BACKGROUND: Extravasation injuries are caused by unintended leakages of fluids or medicines from intravenous lines, but there is no consensus on the best treatment approaches. OBJECTIVES: To identify which treatments may be best for treating extravasation injuries in infants and young children. DESIGN: Scoping review and survey of practice. POPULATION: Children aged < 18 years with extravasation injuries and NHS staff who treat children with extravasation injuries. INTERVENTIONS: Any treatment for extravasation injury. MAIN OUTCOME MEASURES: Wound healing time, infection, pain, scarring, functional impairment, requirement for surgery. DATA SOURCES: Twelve database searches were carried out in February 2017 without date restrictions, including MEDLINE, CINAHL (Cumulative Index to Nursing and Allied Health Literature) Plus and EMBASE (Excerpta Medica dataBASE). METHODS: Scoping review - studies were screened in duplicate. Data were extracted by one researcher and checked by another. Studies were grouped by design, and then by intervention, with details summarised narratively and in tables. The survey questionnaire was distributed to NHS staff at neonatal units, paediatric intensive care units and principal oncology/haematology units. Summary results were presented narratively and in tables and figures. RESULTS: The evidence identified in the scoping review mostly comprised small, retrospective, uncontrolled group studies or case reports. The studies covered a wide range of interventions including conservative management approaches, saline flush-out techniques (with or without prior hyaluronidase), hyaluronidase (without flush-out), artificial skin treatments, debridement and plastic surgery. Few studies graded injury severity and the results sections and outcomes reported in most studies were limited. There was heterogeneity across study populations in age, types of infusate, injury severity, location of injury and the time gaps between injury identification and subsequent treatment. Some of the better evidence related to studies of flush-out techniques. The NHS survey yielded 63 responses from hospital units across the UK. Results indicated that, although most units had a written protocol or guideline for treating extravasation injuries, only one-third of documents included a staging system for grading injury severity. In neonatal units, parenteral nutrition caused most extravasation injuries. In principal oncology/haematology units, most injuries were due to vesicant chemotherapies. The most frequently used interventions were elevation of the affected area and analgesics. Warm or cold compresses were rarely used. Saline flush-out treatments, either with or without hyaluronidase, were regularly used in about half of all neonatal units. Most responders thought a randomised controlled trial might be a viable future research design, though opinions varied greatly by setting. LIMITATIONS: Paucity of good-quality studies. CONCLUSIONS: There is uncertainty about which treatments are most promising, particularly with respect to treating earlier-stage injuries. Saline flush-out techniques and conservative management approaches are commonly used and may be suitable for evaluation in trials. FUTURE WORK: Conventional randomised trials may be difficult to perform, although a randomised registry trial may be an appropriate alternative. FUNDING: The National Institute for Health Research Health Technology Assessment programme