Efficacy of Direct or Indirect Use of Probiotics for the Improvement of Maternal Depression during Pregnancy and in the Postnatal Period: A Systematic Review and Meta-Analysis.

The mother and infant form a unique bond, with maternal mental health affecting the interactions with the infant and infant behaviours impacting maternal mental health. One of the possible mechanisms influencing maternal mental health is the manipulation of the gut-brain axis by consuming probiotic supplements. Probiotics can also have an indirect influence on maternal mental health via the modulation of the infant microbiome and consequently improving the infant's health and thus, indirectly leading to an improvement in maternal mood. This systematic review evaluated the efficacy of probiotics on maternal mental health by searching for randomised controlled trials via international databases: Cochrane Library, PubMed, Scopus, ScienceDirect, and Web of Science until January 2022. A meta-analysis was performed using the Cochrane Collaboration methodology where possible. We found seven clinical trials that included the word probiotics and addressed maternal depression and/or anxiety. Of these, five trials investigated the influence of maternal probiotic supplementation on the gut-brain axis. Two trials investigated the indirect influence of probiotics on maternal depression via supplementation of probiotics by infants and subsequent influence on the crying of colicky infants. Meta-analysis of two studies of pregnant and postnatal women and two studies of infants consuming probiotics on the outcome of the Edinburgh Postnatal Depression Scale for mothers showed no statistical difference. The findings indicate that maternal depression is very complex and is influenced by various bidirectional factors. One of the factors that can improve maternal mental health is probiotics, however, careful consideration must be given to correct strain selection as strain-specific effectiveness was observed. Further well-designed, robust clinical studies are warranted.

Probiotics for preventing and treating infant regurgitation: A systematic review and meta-analysis.

Infant regurgitation is common during infancy and can cause substantial parental distress. Regurgitation can lead to parental perception that their infant is in pain. Parents often present in general practitioner surgeries, community baby clinics and accident and emergency departments which can lead to financial burden on parents and the health care system. Probiotics are increasingly reported to have therapeutic effects for preventing and treating infant regurgitation. The objective of this systematic review and meta-analysis was to evaluate the efficacy of probiotic supplementation for the prevention and treatment of infant regurgitation. Literature searches were conducted using MEDLINE, CINAHL, and the Cochrane Central Register of Controlled trials. Only randomised controlled trials (RCTs) were included. A meta-analysis was performed using the Cochrane Collaboration methodology where possible. Six RCTs examined the prevention or treatment with probiotics on infant regurgitation. A meta-analysis of three studies showed a statistically significant reduction in regurgitation episodes for the probiotic group compared to the placebo group (mean difference [MD]: -1.79 episodes/day: 95% confidence interval [CI]: -3.30 to -0.27, N = 560), but there was high heterogeneity (96%). Meta-analysis of two studies found a statistically significant increased number of stools per day in the probiotic group compared to the placebo group at 1 month of age (MD: 1.36, 95% CI: 0.99 to 1.73, N = 488), with moderate heterogeneity (69%). Meta-analysis of two studies showed no statistical difference in body weight between the two groups (MD: -91.88 g, 95% CI: 258.40-74.63: I2 = 23%, N = 112) with minimal heterogeneity 23%. Probiotic therapy appears promising for infant regurgitation with some evidence of benefit, but most studies are small and there was relatively high heterogeneity. The use of probiotics could potentially be a noninvasive, safe, cost effective, and preventative positive health strategy for both women and their babies. Further robust, well controlled RCTs examining the effect of probiotics for infant regurgitation are warranted.

Push versus gravity for intermittent bolus gavage tube feeding of preterm and low birth weight infants.

BACKGROUND: Many small, sick, and preterm infants are unable to co-ordinate sucking, swallowing, and breathing, and therefore require gavage feeding. In gavage feeding, milk feeds are delivered through a tube passed via the nose or the mouth into the stomach. Intermittent bolus milk feeds may be administered by a syringe to gently push milk into the infant's stomach (push feed). Alternatively, milk can be poured into a syringe attached to the tube and allowed to drip in by gravity (gravity feed). OBJECTIVES: To determine whether use of push feeding compared with gravity feeding results in more rapid establishment of full gavage feeds without increasing adverse events among preterm or low birth weight infants, or both, who require intermittent bolus tube feeding. SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 7), in the Cochrane Library; Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Daily and Versions(R); and the Cumulative Index to Nursing and Allied Health Literature (CINAHL), on 30 July 2020. We also searched clinical trials databases and the reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-RCTs. SELECTION CRITERIA: We included RCTs and quasi-RCTs comparing push versus gravity intermittent gavage tube feeding in preterm (less than 37 weeks' gestation) or low birth weight (less than 2500 grams) infants, or both. DATA COLLECTION AND ANALYSIS: We assessed the methods of trials regarding blinding of randomisation and outcome measurement. We evaluated treatment effects with a fixed-effect model using risk ratio (RR), relative risk reduction, risk difference (RD), and number needed to treat for an additional beneficial outcome (NNTB) for categorical data; and using mean, standard deviation, and mean difference (MD) for continuous data. We analysed outcomes measured as count data, for example, frequency of apnoea, bradycardia, and episodes of pulse oximeter oxygen (SpO2) desaturation, by comparing rates of events and the rate ratio. We evaluated heterogeneity to help determine the suitability of pooling results. We used the GRADE approach to assess the certainty of evidence. MAIN RESULTS: One small cross-over trial (31 infants) met the criteria for inclusion in this review. The certainty of evidence for all outcomes was very low due to imprecision of estimates, wide confidence intervals, and unclear risk of bias. The primary outcome - time taken to establish full gavage feeding (days) and feeding intolerance (number of episodes per day) - was not reported in the included study. The evidence is very uncertain about the effects of push versus gravity intermittent gavage tube feeding on all other outcomes. Investigators reported respiratory rate (breaths per minute) at completion of feeding (MD 0.58, 95% confidence interval (CI) -5.97 to 7.13; 1 study, 31 participants; very low-certainty evidence); respiratory rate (breaths per minute) 10 to 30 minutes after completion of feeding (MD 3.1, 95% CI -3.43 to 9.63; 1 study, 31 participants; very low-certainty evidence); heart rate (beats per minute) at completion of feeding (MD 2.6, 95% CI -9.71 to 4.51; 1 study, 31 participants; very low-certainty evidence); and heart rate (beats per minute) 10 to 30 minutes after completion of feeding (MD 2.4, 95% CI -9.16 to 4.36; 1 study, 31 participants; very low-certainty evidence). We are very uncertain of the effects of push versus gravity intermittent gavage feeding on respiratory rate during and after feeding. AUTHORS' CONCLUSIONS: We do not have sufficient evidence to determine the effects of intermittent bolus gavage feeding for preterm and low birth weight infants. The single small study of 31 infants comparing effects of push versus gravity bolus gavage feeding did not report the primary outcome identified in this review. Thus, evidence is insufficient to show whether use of push compared with gravity gavage feeding results in more rapid establishment of full gavage feeds without increasing adverse events in preterm or low birth weight infants who receive intermittent bolus gavage feeding. In addition, the included study was too small to measure potential adverse events that can occur during gavage tube feeding, for example, episodes of oxygen desaturation, apnoea, or bradycardia.

Continuous versus bolus intermittent intragastric tube feeding for preterm and low birth weight infants with gastro-oesophageal reflux disease.

BACKGROUND: Gastro-oesophageal reflux disease is a particularly common condition among preterm and low birth weight infants. These infants are more likely to have excessive regurgitation, as they do not have a fully developed antireflux mechanism. Preterm and low birth weight infants who are unable to suck oral feeds are required to be fed via an intragastric tube for varying lengths of time. Intragastric tube feeding can be delivered by the intermittent bolus method or by the continuous feeding method. Use of continuous or intermittent bolus intragastric feeding may have a positive or negative effect on the incidence or severity of gastro-oesophageal reflux disease. OBJECTIVES: • To determine whether continuous or intermittent bolus intragastric tube feeding reduces the number of episodes and the duration of gastro-oesophageal reflux disease (GORD) in preterm and low birth weight infants • To perform subgroup analyses for gestational age; birth weight; age in days from birth at full enteral feeding via intragastric tube (breast versus bottle); frequency of intermittent bolus feed; and type of medication for treatment of GORD (only if medication was prescribed and was given similarly to both intervention groups) SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 7), in the Cochrane Library; Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Daily and Versions(R); and the Cumulative Index to Nursing and Allied Health Literature (CINAHL), on 8 July 2020. We also searched clinical trials databases and the reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-RCTs. SELECTION CRITERIA: Published and unpublished RCTs and quasi-RCTs were eligible for inclusion in this review, as were cluster-randomised and cross-over randomised trials that compared the effects of continuous versus intermittent bolus intragastric tube feeding on gastro-oesophageal reflux disease in preterm and low birth weight infants. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed study eligibility and quality. We planned to use the GRADE approach to assess the certainty of evidence. MAIN RESULTS: We found no trials that met the inclusion criteria for this review. AUTHORS' CONCLUSIONS: We did not identify any randomised trials that evaluated the effects of continuous versus intermittent bolus intragastric tube feeding on gastro-oesophageal reflux disease in preterm and low birth weight infants. Well-designed and adequately powered trials are needed.

Cost-Effectiveness of Nasal High Flow Versus CPAP for Newborn Infants in Special-Care Nurseries.

BACKGROUND: Treating respiratory distress in newborns is expensive. We compared the cost-effectiveness of 2 common noninvasive therapies, nasal continuous positive airway pressure (CPAP) and nasal high-flow (nHF), for newborn infants cared for in nontertiary special care nurseries. METHODS: The economic evaluation was planned alongside a randomized control trial conducted in 9 Australian special care nurseries. Costs were considered from a hospital perspective until infants were 12 months of age. A total of 754 infants with respiratory distress, born ≥31 weeks' gestation and with birth weight ≥1200 g, <24 hours old, requiring noninvasive respiratory support and/or supplemental oxygen for >1 hour were recruited during 2015-2017. Inpatient costing records were obtained for 753 infants, of whom 676 were included in the per-protocol analysis. Two scenarios were considered: (1) CPAP versus nHF, with infants in the nHF group having "rescue" CPAP backup available (trial scenario); and (2) CPAP versus nHF, as sole primary support (hypothetical scenario). Effectiveness outcomes were rate of endotracheal intubation and transfer to a tertiary-level NICU. RESULTS: As sole primary support, CPAP is more effective and on average cheaper, and thus is superior. However, nHF with back-up CPAP produced equivalent cost and effectiveness results, and there is no reason to make a decision between the 2 treatments on the basis of the cost or effectiveness outcomes. CONCLUSIONS: Nontertiary special care nurseries choosing to use only 1 of the modes should choose CPAP. In units with both modes available, using nHF as first-line therapy may be acceptable if there is back-up CPAP.

Nasal High-Flow Therapy for Newborn Infants in Special Care Nurseries.

BACKGROUND: Nasal high-flow therapy is an alternative to nasal continuous positive airway pressure (CPAP) as a means of respiratory support for newborn infants. The efficacy of high-flow therapy in nontertiary special care nurseries is unknown. METHODS: We performed a multicenter, randomized, noninferiority trial involving newborn infants (<24 hours of age; gestational age, ≥31 weeks) in special care nurseries in Australia. Newborn infants with respiratory distress and a birth weight of at least 1200 g were assigned to treatment with either high-flow therapy or CPAP. The primary outcome was treatment failure within 72 hours after randomization. Infants in whom high-flow therapy failed could receive CPAP. Noninferiority was determined by calculating the absolute difference in the risk of the primary outcome, with a noninferiority margin of 10 percentage points. RESULTS: A total of 754 infants (mean gestational age, 36.9 weeks, and mean birth weight, 2909 g) were included in the primary intention-to-treat analysis. Treatment failure occurred in 78 of 381 infants (20.5%) in the high-flow group and in 38 of 373 infants (10.2%) in the CPAP group (risk difference, 10.3 percentage points; 95% confidence interval [CI], 5.2 to 15.4). In a secondary per-protocol analysis, treatment failure occurred in 49 of 339 infants (14.5%) in the high-flow group and in 27 of 338 infants (8.0%) in the CPAP group (risk difference, 6.5 percentage points; 95% CI, 1.7 to 11.2). The incidences of mechanical ventilation, transfer to a tertiary neonatal intensive care unit, and adverse events did not differ significantly between the groups. CONCLUSIONS: Nasal high-flow therapy was not shown to be noninferior to CPAP and resulted in a significantly higher incidence of treatment failure than CPAP when used in nontertiary special care nurseries as early respiratory support for newborn infants with respiratory distress. (Funded by the Australian National Health and Medical Research Council and Monash University; HUNTER Australian and New Zealand Clinical Trials Registry number, ACTRN12614001203640.).

Lower versus higher oxygen concentrations titrated to target oxygen saturations during resuscitation of preterm infants at birth.

BACKGROUND: Initial resuscitation with air is well tolerated by most infants born at term. However, the optimal fractional inspired oxygen concentration (FiO2 - proportion of the breathed air that is oxygen) targeted to oxygen saturation (SpO2 - an estimate of the amount of oxygen in the blood) for infants born preterm is unclear. OBJECTIVES: To determine whether lower or higher initial oxygen concentrations, when titrated according to oxygen saturation targets during the resuscitation of preterm infants at birth, lead to improved short- and long-term mortality and morbidity. SEARCH METHODS: We conducted electronic searches of the Cochrane Central Register of Controlled Trials (13 October 2017), Ovid MEDLINE (1946 to 13 October 2017), Embase (1974 to 13 October 2017) and CINAHL (1982 to 13 October 2017); we also searched previous reviews (including cross-references), contacted expert informants, and handsearched journals. SELECTION CRITERIA: We included randomised controlled trials (including cluster- and quasi-randomised trials) which enrolled preterm infants requiring resuscitation following birth and allocated them to receive either lower (FiO2 < 0.4) or higher (FiO2 ≥ 0.4) initial oxygen concentrations titrated to target oxygen saturation. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the eligibility of studies for inclusion, extracted data and assessed methodological quality. Primary outcomes included mortality near term or at discharge (latest reported) and neurodevelopmental disability. We conducted meta-analysis using a fixed-effect model. We assessed the quality of the evidence using GRADE. MAIN RESULTS: The search identified 10 eligible trials. Meta-analysis of the 10 included studies (914 infants) showed no difference in mortality to discharge between lower (FiO2 < 0.4) and higher (FiO2 ≥ 0.4) initial oxygen concentrations targeted to oxygen saturation (risk ratio (RR) 1.05, 95% confidence interval (CI) 0.68 to 1.63). We identified no heterogeneity in this analysis. We graded the quality of the evidence as low due to risk of bias and imprecision. There were no significant subgroup effects according to inspired oxygen concentration strata (FiO2 0.21 versus ≥ 0.4 to < 0.6; FiO2 0.21 versus ≥ 0.6 to 1.0; and FiO2 ≥ 0.3 to < 0.4 versus ≥ 0.6 to 1.0). Subgroup analysis identified a single trial that reported increased mortality from use of lower (FiO2 0.21) versus higher (FiO2 1.0) initial oxygen concentration targeted to a lowest SpO2 of less than 85%, whereas meta-analysis of nine trials targeting a lowest SpO2 of 85% to 90% found no difference in mortality.Meta-analysis of two trials (208 infants) showed no difference in neurodevelopmental disability at 24 months between infants receiving lower (FiO2 < 0.4) versus higher (FiO2 > 0.4) initial oxygen concentrations targeted to oxygen saturation. Other outcomes were incompletely reported by studies. Overall, we found no difference in use of intermittent positive pressure ventilation or intubation in the delivery room; retinopathy (damage to the retina of the eyes, measured as any retinopathy and severe retinopathy); intraventricular haemorrhage (any and severe); periventricular leukomalacia (a type of white-matter brain injury); necrotising enterocolitis (a condition where a portion of the bowel dies); chronic lung disease at 36 weeks' gestation; mortality to follow up; postnatal growth failure; and patent ductus arteriosus. We graded the quality of the evidence for these outcomes as low or very low. AUTHORS' CONCLUSIONS: There is uncertainty as to whether initiating post birth resuscitation in preterm infants using lower (FiO2 < 0.4) or higher (FiO2 ≥ 0.4) oxygen concentrations, targeted to oxygen saturations in the first 10 minutes, has an important effect on mortality or major morbidity, intubation during post birth resuscitation, other resuscitation outcomes, and long-term outcomes including neurodevelopmental disability. We assessed the quality of the evidence for all outcomes as low to very low. Further large, well designed trials are needed to assess the effect of using different initial oxygen concentrations and the effect of targeting different oxygen saturations.

Gastro-oesophageal reflux: a mixed methods study of infants admitted to hospital in the first 12 months following birth in NSW (2000-2011).

BACKGROUND: Gastro-oesophageal reflux (GOR) is common in infants. When the condition causes pathological symptoms and/or complications it is considered gastro-oesophageal reflux disease (GORD). It appears to be increasingly diagnosed and causes great distress in the first year of infancy. In New South Wales (NSW), residential parenting services support families with early parenting difficulties. These services report a large number of babies admitted with a label of GOR/GORD. The aim of this study was to explore the maternal and infant characteristics, obstetric interventions, and reasons for clinical reporting of GOR/GORD in NSW in the first 12 months following birth (2000-2011). METHODS: A three phase, mixed method sequential design was used. Phase 1 included a linked data population based study (n = 869,188 admitted babies). Phase 2 included a random audit of 326 medical records from admissions to residential parenting centres in NSW (2013). Phase 3 included eight focus groups undertaken with 45 nurses and doctors working in residential parenting centres in NSW. RESULTS: There were a total of 1,156,020 admissions recorded of babies in the first year following birth, with 11,513 containing a diagnostic code for GOR/GORD (1% of infants admitted to hospitals in the first 12 months following birth). Babies with GOR/GORD were also more likely to be admitted with other disorders such as feeding difficulties, sleep problems, and excessive crying. The mothers of babies admitted with a diagnostic code of GOR/GORD were more likely to be primiparous, Australian born, give birth in a private hospital and have: a psychiatric condition; a preterm or early term infant (37-or-38 weeks); a caesarean section; an admission of the baby to SCN/NICU; and a male infant. Thirty six percent of infants admitted to residential parenting centres in NSW had been given a diagnosis of GOR/GORD. Focus group data revealed two themes: "It is over diagnosed" and "A medical label is a quick fix, but what else could be going on?" CONCLUSIONS: Mothers with a mental health disorder are nearly five times as likely to have a baby admitted with GOR/GORD in the first year after birth. We propose a new way of approaching the GOR/GORD issue that considers the impact of early birth (immaturity), disturbance of the microbiome (caesarean section) and mental health (maternal anxiety in particular).

Heat and moisture exchangers versus heated humidifiers for mechanically ventilated adults and children.

BACKGROUND: Invasive ventilation is used to assist or replace breathing when a person is unable to breathe adequately on their own. Because the upper airway is bypassed during mechanical ventilation, the respiratory system is no longer able to warm and moisten inhaled gases, potentially causing additional breathing problems in people who already require assisted breathing. To prevent these problems, gases are artificially warmed and humidified. There are two main forms of humidification, heat and moisture exchangers (HME) or heated humidifiers (HH). Both are associated with potential benefits and advantages but it is unclear whether HME or HH are more effective in preventing some of the negative outcomes associated with mechanical ventilation. This review was originally published in 2010 and updated in 2017. OBJECTIVES: To assess whether heat and moisture exchangers or heated humidifiers are more effective in preventing complications in people receiving invasive mechanical ventilation and to identify whether the age group of participants, length of humidification, type of HME, and ventilation delivered through a tracheostomy had an effect on these findings. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase and CINAHL up to May 2017 to identify randomized controlled trials (RCTs) and reference lists of included studies and relevant reviews. There were no language limitations. SELECTION CRITERIA: We included RCTs comparing HMEs to HHs in adults and children receiving invasive ventilation. We included randomized cross-over studies. DATA COLLECTION AND ANALYSIS: We assessed the quality of each study and extracted the relevant data. Where possible, we analysed data through meta-analysis. For dichotomous outcomes, we calculated the risk ratio (RR) and 95% confidence interval (95% CI). For continuous outcomes, we calculated the mean difference (MD) and 95% CI or standardized mean difference (SMD) and 95% CI for parallel studies. For cross-over trials, we calculated the MD and 95% CI using correlation estimates to correct for paired analyses. We aimed to conduct subgroup analyses based on the age group of participants, how long they received humidification, type of HME and whether ventilation was delivered through a tracheostomy. We also conducted sensitivity analysis to identify whether the quality of trials had an effect on meta-analytic findings. MAIN RESULTS: We included 34 trials with 2848 participants; 26 studies were parallel-group design (2725 participants) and eight used a cross-over design (123 participants). Only three included studies reported data for infants or children. Two further studies (76 participants) are awaiting classification.There was no overall statistical difference in artificial airway occlusion (RR 1.59, 95% CI 0.60 to 4.19; participants = 2171; studies = 15; I2 = 54%), mortality (RR 1.03, 95% CI 0.89 to 1.20; participants = 1951; studies = 12; I2 = 0%) or pneumonia (RR 0.93, 95% CI 0.73 to 1.19; participants = 2251; studies = 13; I2 = 27%). There was some evidence that hydrophobic HMEs may reduce the risk of pneumonia compared to HHs (RR 0.48, 95% CI 0.28 to 0.82; participants = 469; studies = 3; I2 = 0%)..The overall GRADE quality of evidence was low. Although the overall methodological risk of bias was generally unclear for selection and detection bias and low risk for follow-up, the selection of study participants who were considered suitable for HME and in some studies removing participants from the HME group made the findings of this review difficult to generalize. AUTHORS' CONCLUSIONS: The available evidence suggests no difference between HMEs and HHs on the primary outcomes of airway blockages, pneumonia and mortality. However, the overall low quality of this evidence makes it difficult to be confident about these findings. Further research is needed to compare HMEs to HHs, particularly in paediatric and neonatal populations, but research is also needed to more effectively compare different types of HME to each other as well as different types of HH.

Orotracheal intubation in infants performed with a stylet versus without a stylet.

BACKGROUND: Neonatal endotracheal intubation is a common and potentially life-saving intervention. It is a mandatory skill for neonatal trainees, but one that is difficult to master and maintain. Intubation opportunities for trainees are decreasing and success rates are subsequently falling. Use of a stylet may aid intubation and improve success. However, the potential for associated harm must be considered. OBJECTIVES: To compare the benefits and harms of neonatal orotracheal intubation with a stylet versus neonatal orotracheal intubation without a stylet. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library; MEDLINE; Embase; the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and previous reviews. We also searched cross-references, contacted expert informants, handsearched journals, and looked at conference proceedings. We searched clinical trials registries for current and recently completed trials. We conducted our most recent search in April 2017. SELECTION CRITERIA: All randomised, quasi-randomised, and cluster-randomised controlled trials comparing use versus non-use of a stylet in neonatal orotracheal intubation. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed results of searches against predetermined criteria for inclusion, assessed risk of bias, and extracted data. We used the standard methods of the Cochrane Collaboration, as documented in the Cochrane Handbook for Systemic Reviews of Interventions, and of the Cochrane Neonatal Review Group. MAIN RESULTS: We included a single-centre non-blinded randomised controlled trial that reported a total of 302 intubation attempts in 232 infants. The median gestational age of enrolled infants was 29 weeks. Paediatric residents and fellows performed the intubations. We judged the study to be at low risk of bias overall. Investigators compared success rates of first-attempt intubation with and without use of a stylet and reported success rates as similar between stylet and no-stylet groups (57% and 53%) (P = 0.47). Success rates did not differ between groups in subgroup analyses by provider level of training and infant weight. Results showed no differences in secondary review outcomes, including duration of intubation, number of attempts, participant instability during the procedure, and local airway trauma. Only 25% of all intubations took less than 30 seconds to perform. Study authors did not report neonatal morbidity nor mortality. We considered the quality of evidence as low on GRADE analysis, given that we identified only one unblinded study. AUTHORS' CONCLUSIONS: Current available evidence suggests that use of a stylet during neonatal orotracheal intubation does not significantly improve the success rate among paediatric trainees. However, only one brand of stylet and one brand of endotracheal tube have been tested, and researchers performed all intubations on infants in a hospital setting. Therefore, our results cannot be generalised beyond these limitations.

A multicentre, randomised controlled, non-inferiority trial, comparing nasal high flow with nasal continuous positive airway pressure as primary support for newborn infants with early respiratory distress born in Australian non-tertiary special care nurseries (the HUNTER trial): study protocol.

INTRODUCTION: Nasal high-flow (nHF) therapy is a popular mode of respiratory support for newborn infants. Evidence for nHF use is predominantly from neonatal intensive care units (NICUs). There are no randomised trials of nHF use in non-tertiary special care nurseries (SCNs). We hypothesise that nHF is non-inferior to nasal continuous positive airway pressure (CPAP) as primary support for newborn infants with respiratory distress, in the population cared for in non-tertiary SCNs. METHODS AND ANALYSIS: The HUNTER trial is an unblinded Australian multicentre, randomised, non-inferiority trial. Infants are eligible if born at a gestational age ≥31 weeks with birth weight ≥1200 g and admitted to a participating non-tertiary SCN, are <24 hours old at randomisation and require non-invasive respiratory support or supplemental oxygen for >1 hour. Infants are randomised to treatment with either nHF or CPAP. The primary outcome is treatment failure within 72 hours of randomisation, as determined by objective oxygenation, apnoea or blood gas criteria or by a clinical decision that urgent intubation and mechanical ventilation, or transfer to a tertiary NICU, is required. Secondary outcomes include incidence of pneumothorax requiring drainage, duration of respiratory support, supplemental oxygen and hospitalisation, costs associated with hospital care, cost-effectiveness, parental stress and satisfaction and nursing workload. ETHICS AND DISSEMINATION: Multisite ethical approval for the study has been granted by The Royal Children's Hospital, Melbourne, Australia (Trial Reference No. 34222), and by each participating site. The trial is currently recruiting in eight centres in Victoria and New South Wales, Australia, with one previous site no longer recruiting. The trial results will be published in a peer-reviewed journal and will be presented at national and international conferences. TRIAL REGISTRATION NUMBER: Australian and New Zealand Clinical Trials Registry (ANZCTR): ACTRN12614001203640; pre-results.

Infant pacifiers for reduction in risk of sudden infant death syndrome.

BACKGROUND: Sudden infant death syndrome (SIDS) has been most recently defined as the sudden unexpected death of an infant less than one year of age, with onset of the fatal episode apparently occurring during sleep, that remains unexplained after a thorough investigation, including the performance of a complete autopsy and a review of the circumstances of death and clinical history. Despite the success of several prevention campaigns, SIDS remains a leading cause of infant mortality. In 1994, a 'triple risk model' for SIDS was proposed that described SIDS as an event that results from the intersection of three factors: a vulnerable infant; a critical development period in homeostatic control (age related); and an exogenous stressor. The association between pacifier (dummy) use and reduced incidence of SIDS has been shown in epidemiological studies since the early 1990s. Pacifier use, given its low cost, might be a cost-effective intervention for SIDS prevention if it is confirmed effective in randomised controlled trials. OBJECTIVES: To determine whether the use of pacifiers during sleep versus no pacifier during sleep reduces the risk of SIDS. SEARCH METHODS: We used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 2), MEDLINE via PubMed, Embase, and CINAHL to 16 March 2016. We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. SELECTION CRITERIA: Published and unpublished controlled trials using random and quasi-random allocations of infants born at term and at preterm (less than 37 weeks' gestation) or with low birth weight (< 2500 g). Infants must have been randomised by one month' postmenstrual age. We planned to include studies reported only by abstracts, and cluster and cross-over randomised trials. DATA COLLECTION AND ANALYSIS: Two review authors independently reviewed studies from searches. We found no eligible studies. MAIN RESULTS: We identified no randomised controlled trials examining infant pacifiers for reduction in risk of SIDS. AUTHORS' CONCLUSIONS: We found no randomised control trial evidence on which to support or refute the use of pacifiers for the prevention of SIDS.

Routine oro/nasopharyngeal suction versus no suction at birth.

BACKGROUND: Oro/nasopharyngeal suction is a method used to clear secretions from the oropharynx and nasopharynx through the application of negative pressure via a suction catheter or bulb syringe. Traditionally, airway oro/nasopharyngeal suction at birth has been used routinely to remove fluid rapidly from the oropharynx and nasopharynx in vigorous and non-vigorous infants at birth. Concerns relating to the reported adverse effects of oro/nasopharyngeal suctioning led to a practice review and routine oro/nasopharyngeal suctioning is no longer recommended for vigorous infants. However, it is important to know whether there is any clear benefit or harm for infants whose oro/nasopharyngeal airway is suctioned compared to infants who are not suctioned. OBJECTIVES: To evaluate the effect of routine oropharyngeal/nasopharyngeal suction compared to no suction on mortality and morbidity in newly born 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 2016, Issue 3), MEDLINE via PubMed (1966 to April 18, 2016), Embase (1980 to April 18, 2016), and CINAHL (1982 to April 18, 2016). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. SELECTION CRITERIA: Randomised, quasi-randomised controlled trials and cluster randomised trials that evaluated the effect of routine oropharyngeal/nasopharyngeal suction compared to no suction on mortality and morbidity in newly born infants with and without meconium-stained amniotic fluid. DATA COLLECTION AND ANALYSIS: The review authors extracted from the reports of the clinical trials, data regarding clinical outcomes including mortality, need for resuscitation, admission to neonatal intensive care, five minute Apgar score, episodes of apnoea and length of hospital stay. MAIN RESULTS: Eight randomised controlled trials met the inclusion criteria and only included term infants (n = 4011). Five studies included infants with no fetal distress and clear amniotic fluid, one large study included vigorous infants with clear or meconium-stained amniotic fluid, and two large studies included infants with thin or thick meconium-stained amniotic fluid. Overall, there was no statistical difference between oro/nasopharyngeal suction and no oro/nasopharyngeal suction for all reported outcomes: mortality (typical RR 2.29, 95% CI 0.94 to 5.53; typical RD 0.01, 95% CI -0.00 to 0.01; I2 = 0%, studies = 2, participants = 3023), need for resuscitation (typical RR 0.85, 95% CI 0.69 to 1.06; typical RD -0.01, 95% CI -0.03 to 0.00; I2 = 0%, studies = 5, participants = 3791), admission to NICU (typical RR 0.82, 95% CI 0.62 to 1.08; typical RD -0.03, 95% CI -0.08 to 0.01; I2 = 27%, studies = 2, participants = 997) and Apgar scores at five minutes (MD -0.03, 95% CI -0.08 to 0.02; I2 not estimated, studies = 3, participants = 330). AUTHORS' CONCLUSIONS: The currently available evidence does not support or refute the benefits or harms of routine oro/nasopharyngeal suction over no suction. Further high-quality studies are required in preterm infants or term newborn infants with thick meconium amniotic fluid. Studies should investigate long-term effects such as neurodevelopmental outcomes.

Frenotomy for tongue-tie in newborn infants.

BACKGROUND: Tongue-tie, or ankyloglossia, is a condition whereby the lingual frenulum attaches near the tip of the tongue and may be short, tight and thick. Tongue-tie is present in 4% to 11% of newborns. Tongue-tie has been cited as a cause of poor breastfeeding and maternal nipple pain. Frenotomy, which is commonly performed, may correct the restriction to tongue movement and allow more effective breastfeeding with less maternal nipple pain. OBJECTIVES: To determine whether frenotomy is safe and effective in improving ability to feed orally among infants younger than three months of age with tongue-tie (and problems feeding).Also, to perform subgroup analysis to determine the following.• Severity of tongue-tie before frenotomy as measured by a validated tool (e.g. Hazelbaker Assessment Tool for Lingual Frenulum Function (ATLFF) scores < 11; scores ≥ 11) (Hazelbaker 1993).• Gestational age at birth (< 37 weeks' gestation; 37 weeks' gestation and above).• Method of feeding (breast or bottle).• Age at frenotomy (≤ 10 days of age; > 10 days to three months of age).• Severity of feeding difficulty (infants with feeding difficulty affecting weight gain (as assessed by infant's not regaining birth weight by day 14 or falling off centiles); infants with symptomatic feeding difficulty but thriving (greater than birth weight by day 14 and tracking centiles). SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and CINAHL up to January 2017, as well as previous reviews including cross-references, expert informants and journal handsearching. We searched clinical trials databases for ongoing and recently completed trials. We applied no language restrictions. SELECTION CRITERIA: Randomised, quasi-randomised controlled trials or cluster-randomised trials that compared frenotomy versus no frenotomy or frenotomy versus sham procedure in newborn infants. DATA COLLECTION AND ANALYSIS: Review authors extracted from the reports of clinical trials data regarding clinical outcomes including infant feeding, maternal nipple pain, duration of breastfeeding, cessation of breastfeeding, infant pain, excessive bleeding, infection at the site of frenotomy, ulceration at the site of frenotomy, damage to the tongue and/or submandibular ducts and recurrence of tongue-tie. We used the GRADE approach to assess the quality of evidence. MAIN RESULTS: Five randomised trials met our inclusion criteria (n = 302). Three studies objectively measured infant breastfeeding using standardised assessment tools. Pooled analysis of two studies (n = 155) showed no change on a 10-point feeding scale following frenotomy (mean difference (MD) -0.1, 95% confidence interval (CI) -0.6 to 0.5 units on a 10-point feeding scale). A third study (n = 58) showed objective improvement on a 12-point feeding scale (MD 3.5, 95% CI 3.1 to 4.0 units of a 12-point feeding scale). Four studies objectively assessed maternal pain. Pooled analysis of three studies (n = 212) based on a 10-point pain scale showed a reduction in maternal pain scores following frenotomy (MD -0.7, 95% CI -1.4 to -0.1 units on a 10-point pain scale). A fourth study (n = 58) also showed a reduction in pain scores on a 50-point pain scale (MD -8.6, 95% CI -9.4 to -7.8 units on a 50-point pain scale). All studies reported no adverse effects following frenotomy. These studies had serious methodological shortcomings. They included small sample sizes, and only two studies blinded both mothers and assessors; one did not attempt blinding for mothers nor for assessors. All studies offered frenotomy to controls, and most controls underwent the procedure, suggesting lack of equipoise. No study was able to report whether frenotomy led to long-term successful breastfeeding. AUTHORS' CONCLUSIONS: Frenotomy reduced breastfeeding mothers' nipple pain in the short term. Investigators did not find a consistent positive effect on infant breastfeeding. Researchers reported no serious complications, but the total number of infants studied was small. The small number of trials along with methodological shortcomings limits the certainty of these findings. Further randomised controlled trials of high methodological quality are necessary to determine the effects of frenotomy.

Topical anaesthesia for needle-related pain in newborn infants.

BACKGROUND: Hospitalised newborn neonates frequently undergo painful invasive procedures that involve penetration of the skin and other tissues by a needle. One intervention that can be used prior to a needle insertion procedure is application of a topical local anaesthetic. OBJECTIVES: To evaluate the efficacy and safety of topical anaesthetics such as amethocaine and EMLA in newborn term or preterm infants requiring an invasive procedure involving puncture of skin and other tissues with a needle. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase and CINAHL up to 15 May 2016; previous reviews including cross-references, abstracts, and conference proceedings. We contacted expert informants. We contacted authors directly to obtain additional data. We imposed no language restrictions. SELECTION CRITERIA: Randomised, quasi-randomised controlled trials, and cluster and cross-over randomised trials that compared the topical anaesthetics amethocaine and eutectic mixture of local anaesthetics (EMLA) in terms of anaesthetic efficacy and safety in newborn term or preterm infants requiring an invasive procedure involving puncture of skin and other tissues with a needle DATA COLLECTION AND ANALYSIS: From the reports of the clinical trials we extracted data regarding clinical outcomes including pain, number of infants with methaemoglobin level 5% and above, number of needle prick attempts prior to successful needle-related procedure, crying, time taken to complete the procedure, episodes of apnoea, episodes of bradycardia, episodes of oxygen desaturation, neurodevelopmental disability and other adverse events. MAIN RESULTS: Eight small randomised controlled trials met the inclusion criteria (n = 506). These studies compared either EMLA and placebo or amethocaine and placebo. No studies compared EMLA and amethocaine. We were unable to meta-analyse the outcome of pain due to differing outcome measures and methods of reporting. For EMLA, two individual studies reported a statistically significant reduction in pain compared to placebo during lumbar puncture and venepuncture. Three studies found no statistical difference between the groups during heel lancing. For amethocaine, three studies reported a statistically significant reduction in pain compared to placebo during venepuncture and one study reported a statistically significant reduction in pain compared to placebo during cannulation. One study reported no statistical difference between the two groups during intramuscular injection.One study reported no statistical difference between EMLA and the placebo group for successful venepuncture at first attempt. One study similarly reported no statistically significant difference between Amethocaine and the placebo group for successful cannulation at first attempt.Risk for local redness, swelling or blanching was significantly higher with EMLA (typical risk ratio (RR) 1.65, 95% confidence interval (CI) 1.24 to 2.19; typical risk difference (RD) 0.17, 95% CI 0.09 to 0.26; n = 272; number needed to treat for an additional harmful outcome (NNTH) 6, 95% CI 4 to 11; I2 = 92% indicating considerable heterogeneity) although not for amethocaine (typical RR 2.11, 95% CI 0.72 to 6.16; typical RD 0.05, 95% CI -0.02 to 0.11, n = 221). These local skin reactions for EMLA and amethocaine were reported as short-lasting. Two studies reported no methaemoglobinaemia with single application of EMLA. The quality of the evidence on outcomes assessed according to GRADE was low to moderate. AUTHORS' CONCLUSIONS: Overall, all the trials were small, and the effects of uncertain clinical significance. The evidence regarding the effectiveness or safety of the interventions studied is inadequate to support clinical recommendations. There has been no evaluation regarding any long-term effects of topical anaesthetics in newborn infants.High quality studies evaluating the efficacy and safety of topical anaesthetics such as amethocaine and EMLA for needle-related pain in newborn term or preterm infants are required. These studies should aim to determine efficacy of these topical anaesthetics and on homogenous groups of infants for gestational age. While there was no methaemoglobinaemia in the studies that reported methaemoglobin, the efficacy and safety of EMLA, especially in very preterm infants, and for repeated application, need to be further evaluated in future studies.

Body positioning for spontaneously breathing preterm infants with apnoea.

BACKGROUND: It has been proposed that body positioning in preterm infants, as compared with other, more invasive measures, may be an effective method of reducing clinically significant apnoea. OBJECTIVES: To determine effects of body positioning on cardiorespiratory parameters in spontaneously breathing preterm infants with clinically significant apnoea.Subgroup analyses examined effects of body positioning of spontaneously breathing preterm infants with apnoea from the following subgroups.• Gestational age < 28 weeks or birth weight less than 1000 grams.• Apnoea managed with methylxanthines.• Frequent apnoea (> 10 events/d).• Type of apnoea measured (central vs mixed vs obstructive) SEARCH METHODS: We used the standard search strategy of the Cochrane Neonatal Review Group (CNRG) to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 10), MEDLINE via PubMed (1966 to 14 November 2016), Embase (1980 to 14 November 2016) and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to 2016 November 14). We also searched clinical trials databases and conference proceedings for randomised controlled trials and quasi-randomised trials. SELECTION CRITERIA: Randomised and quasi-randomised controlled clinical trials with parallel, factorial or cross-over design comparing the impact of different body positions on apnoea in spontaneously breathing preterm infants were eligible for our review. DATA COLLECTION AND ANALYSIS: We assessed trial quality, data extraction and synthesis of data using standard methods of the CNRG. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess the quality of evidence. MAIN RESULTS: The search conducted in November 2016 identified no new studies. Five studies (N = 114) were eligible for inclusion. None of the individual studies nor meta-analyses showed a reduction in apnoea, bradycardia, oxygen desaturation or oxygen saturation with body positioning (supine vs prone; prone vs right lateral; prone vs left lateral; right lateral vs left lateral; prone horizontal vs prone head elevated; right lateral horizontal vs right lateral head elevated, left lateral horizontal vs left lateral head elevated). AUTHORS' CONCLUSIONS: We found insufficient evidence to determine effects of body positioning on apnoea, bradycardia and oxygen saturation in preterm infants. No new studies have been conducted since the original review was published. Large, multi-centre studies are warranted to provide conclusive evidence, but it may be plausible to conclude that positioning of spontaneously breathing preterm infants has no effect on their cardiorespiratory parameters.

Non-nutritive sucking for increasing physiologic stability and nutrition in preterm infants.

BACKGROUND: Non-nutritive sucking (NNS) is used during gavage feeding and in the transition from gavage to breast/bottle feeding in preterm infants to improve the development of sucking behavior and the digestion of enteral feedings. OBJECTIVES: To assess the effects of non-nutritive sucking on physiologic stability and nutrition 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; 2016, Issue 1), MEDLINE via PubMed (1966 to 25 February 2016), Embase (1980 to 25 February 2016), and CINAHL (1982 to 25 February 2016). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials. SELECTION CRITERIA: Randomised controlled trials and quasi-randomised trials that compared non-nutritive sucking versus no provision of non-nutritive sucking in preterm infants. We excluded cross-over trials. 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 mean differences (MD) for continuous data, with 95% confidence intervals (CIs). We used a fixed-effect model in meta-analyses. We did not perform subgroup analyses because of the small number of studies related to the relevant outcomes. We used the GRADE approach to assess the quality of evidence. MAIN RESULTS: We identified 12 eligible trials enrolling a total of 746 preterm infants. Meta-analysis, though limited by data quality, demonstrated a significant effect of NNS on transition from gavage to full oral feeding (MD -5.51 days, 95% CI -8.20 to -2.82; N = 87), transition from start of oral feeding to full oral feeding (MD -2.15 days, 95% CI -3.12 to -1.17; N = 100), and the length of hospital stay (MD -4.59 days, 95% CI -8.07 to -1.11; N = 501). Meta-analysis revealed no significant effect of NNS on weight gain. One study found that the NNS group had a significantly shorter intestinal transit time during gavage feeding compared to the control group (MD -10.50 h, 95% CI -13.74 to -7.26; N = 30). Other individual studies demonstrated no clear positive effect of NNS on age of infant at full oral feeds, days from birth to full breastfeeding, rates and proportion of infants fully breastfeeding at discharge, episodes of bradycardia, or episodes of oxygen desaturation. None of the studies reported any negative outcomes. These trials were generally small and contained various methodological weaknesses including lack of blinding of intervention and outcome assessors and variability on outcome measures. The quality of the evidence on outcomes assessed according to GRADE was low to very low. AUTHORS' CONCLUSIONS: Meta-analysis demonstrated a significant effect of NNS on the transition from gavage to full oral feeding, transition from start of oral feeding to full oral feeding, and length of hospital stay. None of the trials reported any adverse effects. Well-designed, adequately powered studies using reliable methods of randomisation, concealment of treatment allocation and blinding of the intervention and outcome assessors are needed. In order to facilitate meta-analysis of these data, future research should involve outcome measures consistent with those used in previous studies.

Oral immunoglobulin for preventing necrotizing enterocolitis in preterm and low birth weight neonates.

BACKGROUND: Necrotizing enterocolitis (NEC) is the most common emergency involving the gastrointestinal tract occurring in the neonatal period. There have been published reports that suggest that oral immunoglobulins (Ig)A and IgG produce an immunoprotective effect in the gastrointestinal mucosa. OBJECTIVES: To determine the effect of oral immunoglobulin on the incidence of necrotizing enterocolitis and other complications in preterm or low birth weight (or both) neonates. SEARCH METHODS: We used the standard search strategy of the Cochrane Neonatal Group. We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2016, Issue 1), PubMed (1966 to January 2016), CINAHL (1982 to January 2016) and EMBASE (1980 to January 2016) and conference proceedings. SELECTION CRITERIA: All randomized or quasi-randomised controlled trials where oral immunoglobulins were used as prophylaxis against NEC in preterm (less than 37 weeks' gestation) or low birth weight (less than 2500 gram), or both, neonates. DATA COLLECTION AND ANALYSIS: We performed data collection and analysis in accordance with the standard methods of the Cochrane Neonatal Review Group. MAIN RESULTS: The search identified five studies on oral immunoglobulin for the prevention of NEC of which three met the inclusion criteria. In this review of the three eligible trials (including 2095 neonates), the oral administration of IgG or an IgG/IgA combination did not result in a significant reduction in the incidence of definite NEC (typical risk ratio (RR) 0.84, 95% confidence interval (CI) 0.57 to 1.25; typical risk difference (RD) -0.01, 95% CI -0.03 to 0.01; 3 studies, 1840 infants), suspected NEC (RR 0.84, 95% CI 0.49 to 1.46; RD -0.01, 95% CI -0.02 to 0.01; 1 study, 1529 infants), need for surgery (typical RR 0.21, 95% CI 0.02 to 1.75; typical RD -0.03, 95% CI -0.06 to 0.00; 2 studies, 311 infants) or death from NEC (typical RR 1.10, 95% CI 0.47 to 2.59; typical RD 0.00, 95% CI -0.01 to 0.01; 3 studies, 1840 infants). AUTHORS' CONCLUSIONS: Based on the available trials, the evidence does not support the administration of oral immunoglobulin for the prevention of NEC. There are no randomized controlled trials of oral IgA alone for the prevention of NEC.

Chest shielding for prevention of a haemodynamically significant patent ductus arteriosus in preterm infants receiving phototherapy.

BACKGROUND: Patent ductus arteriosus (PDA) is associated with mortality and morbidity in preterm infants. Phototherapy is a common treatment for jaundice in preterm infants. However, phototherapy has been associated with failure of closure of the ductus arteriosus in preterm infants. OBJECTIVES: To determine if chest shielding of preterm infants receiving phototherapy reduces the incidence of clinically and/or haemodynamically significant PDA and reduces morbidity secondary to PDA. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library; 2015, Issue 3), MEDLINE, EMBASE, CINAHL, previous reviews, cross-references, abstracts, proceedings of scientific meetings, and trial registries through March 2015. SELECTION CRITERIA: Randomised controlled trials (RCTs), cluster-RCTs, or quasi-RCTs of chest shielding during phototherapy compared to sham shielding or no shielding for the prevention of a haemodynamically or clinically significant PDA in preterm infants. DATA COLLECTION AND ANALYSIS: Three review authors independently assessed studies for eligibility and quality and extracted data. We defined a clinically significant PDA as the presence of a PDA with clinical signs of an effect on organ function attributable to the ductus arteriosus. We defined a haemodynamically significant PDA as clinical and/or echocardiographic signs of a significant ductus arteriosus effect on blood flow. MAIN RESULTS: We included two small trials enrolling very preterm infants (Rosenfeld 1986; Travadi 2006). We assessed both as at high risk of bias. No study reported clinically significant PDA, defined as the presence of a PDA with clinical symptoms or signs attributable to the effect of a ductus arteriosus on organ function. Rosenfeld 1986 reported a non-significant reduction in haemodynamically significant PDA with left atrial to aortic root ratio greater than 1.2 (risk ratio (RR) 0.23, 95% confidence interval (CI) 0.05 to 1.01; 74 infants) but a statistically significant risk difference (RD -0.18, 95% CI -0.34 to -0.03; number needed to treat for an additional beneficial outcome (NNTB) 5, 95% CI 3 to 33). Rosenfeld 1986 reported a significant reduction in PDA detected by murmur (RR 0.50, 95% CI 0.29 to 0.88; RD -0.30, 95% CI -0.52 to -0.08; NNTB 3, 95% CI 2 to 12; 74 infants). Rosenfeld 1986 reported a significant reduction in treatment with indomethacin (RR 0.12, 95% CI 0.02 to 0.88; RD -0.21, 95% CI -0.35 to -0.06; NNTB 5, 95% CI 3 to 17; 74 infants), and only one infant had a ductal ligation in the no-shield group. There were no other significant outcomes, including mortality to discharge or 28 days, days in oxygen, days on mechanical ventilation, days in hospital, intraventricular haemorrhage, retinopathy of prematurity, or exchange transfusion. AUTHORS' CONCLUSIONS: The available evidence is very low quality and insufficient to assess the safety or efficacy of chest shield during phototherapy for prevention of PDA in preterm infants. Further trials of chest shielding are warranted, particularly in settings where infants are not receiving prophylactic or early echocardiographic targeted cyclo-oxygenase inhibitors for PDA.

Intravenous in-line filters for preventing morbidity and mortality in neonates.

BACKGROUND: Venous access is an essential part of caring for the sick neonate. However, problems such as contamination of fluids with bacteria, endotoxins and particulates have been associated with intravenous infusion therapy. Intravenous in-line filters claim to be an effective strategy for the removal of bacteria, endotoxins and particulates associated with intravenous therapy in adults and are increasingly being recommended for use in neonates. OBJECTIVES: To determine the effect of intravenous in-line filters on morbidity and mortality in neonates. SEARCH METHODS: We used the standard search strategy of the Cochrane Neonatal Review Group. We searched the electronic databases MEDLINE (from 1966 to May, 2015), EMBASE (from 1980 to May, 2015), CINAHL (from 1982 to May 2015) and the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 5). We did not impose any language restrictions. Further searching included cross references, abstracts, conferences, symposia proceedings, expert informants and journal handsearching. SELECTION CRITERIA: We included randomised controlled trials (RCTs) or quasi-RCTs that compared the use of intravenous in-line filters with placebo or nothing in neonates. DATA COLLECTION AND ANALYSIS: We followed the procedures of the Cochrane Neonatal Review Group throughout. We checked titles and abstracts identified from the search. We obtained the full text of all studies of possible relevance. We independently assessed the trials for their methodological quality and subsequent inclusion in the review. We contacted authors for further information as needed. Statistical analysis followed the procedures of the Cochrane Neonatal Review Group. MAIN RESULTS: There were four eligible studies that recruited a total of 704 neonates. This review of low to very low quality evidence found that the use of in-line filters compared with unfiltered fluids for intravenous infusion had no statistically significant difference in effectiveness on overall mortality (typical RR 0.87, 95% CI 0.52 to 1.47; typical RD -0.01, 95% CI -0.06 to 0.04; two studies, 530 infants), proven and suspect septicaemia (typical RR 0.86, 95% CI 0.59 to 1.27; typical RD -0.02, 95% CI -0.09 to 0.04; two studies, 530 infants), or other secondary outcomes (including local phlebitis and thrombus, necrotising enterocolitis, duration of cannula patency, length of stay in hospital, number of catheters inserted and financial costs). AUTHORS' CONCLUSIONS: There is insufficient evidence to recommend the use of intravenous in-line filters to prevent morbidity and mortality in neonates.