Heterogeneity and Gaps in Reporting Primary Outcomes From Neonatal Trials.

OBJECTIVES: Clear outcome reporting in clinical trials facilitates accurate interpretation and application of findings and improves evidence-informed decision-making. Standardized core outcomes for reporting neonatal trials have been developed, but little is known about how primary outcomes are reported in neonatal trials. Our aim was to identify strengths and weaknesses of primary outcome reporting in recent neonatal trials. METHODS: Neonatal trials including ≥100 participants/arm published between 2015 and 2020 with at least 1 primary outcome from a neonatal core outcome set were eligible. Raters recruited from Cochrane Neonatal were trained to evaluate the trials' primary outcome reporting completeness using relevant items from Consolidated Standards of Reporting Trials 2010 and Consolidated Standards of Reporting Trials-Outcomes 2022 pertaining to the reporting of the definition, selection, measurement, analysis, and interpretation of primary trial outcomes. All trial reports were assessed by 3 raters. Assessments and discrepancies between raters were analyzed. RESULTS: Outcome-reporting evaluations were completed for 36 included neonatal trials by 39 raters. Levels of outcome reporting completeness were highly variable. All trials fully reported the primary outcome measurement domain, statistical methods used to compare treatment groups, and participant flow. Yet, only 28% of trials fully reported on minimal important difference, 24% on outcome data missingness, 66% on blinding of the outcome assessor, and 42% on handling of outcome multiplicity. CONCLUSIONS: Primary outcome reporting in neonatal trials often lacks key information needed for interpretability of results, knowledge synthesis, and evidence-informed decision-making in neonatology. Use of existing outcome-reporting guidelines by trialists, journals, and peer reviewers will enhance transparent reporting of neonatal trials.

Strengthening Reporting of Neonatal Trials.

BACKGROUND AND OBJECTIVES: There is variability in the selection and reporting of outcomes in neonatal trials with key information frequently omitted. This can impact applicability of trial findings to clinicians, families, and caregivers, and impair evidence synthesis. The Neonatal Core Outcomes Set describes outcomes agreed as clinically important that should be assessed in all neonatal trials, and Consolidated Standards of Reporting Trials (CONSORT)-Outcomes 2022 is a new, harmonized, evidence-based reporting guideline for trial outcomes. We reviewed published trials using CONSORT-Outcomes 2022 guidance to identify exemplars of neonatal core outcome reporting to strengthen description of outcomes in future trial publications. METHODS: Neonatal trials including >100 participants per arm published between 2015 to 2020 with a primary outcome included in the Neonatal Core Outcome Set were identified. Primary outcome reporting was reviewed using CONSORT 2010 and CONSORT-Outcomes 2022 guidelines by assessors recruited from Cochrane Neonatal. Examples of clear and complete outcome reporting were identified with verbatim text extracted from trial reports. RESULTS: Thirty-six trials were reviewed by 39 assessors. Examples of good reporting for CONSORT 2010 and CONSORT-Outcomes 2022 criteria were identified and subdivided into 3 outcome categories: "survival," "short-term neonatal complications," and "long-term developmental outcomes" depending on the core outcomes to which they relate. These examples are presented to strengthen future research reporting. CONCLUSIONS: We have identified examples of good trial outcome reporting. These illustrate how important neonatal outcomes should be reported to meet the CONSORT 2010 and CONSORT-Outcomes 2022 guidelines. Emulating these examples will improve the transmission of information relating to outcomes and reduce associated research waste.

Perinatal antecedents of moderate and severe neonatal hypoxic ischaemic encephalopathy: An Australian birth cohort study.

BACKGROUND: Neonatal hypoxic ischaemic encephalopathy (HIE) is the most common cause of encephalopathy in the neonatal period and carries a high risk of mortality and long-term morbidity. AIM: The aim of this study was to investigate key antecedents of moderate and severe HIE in a large contemporary birth cohort. METHODS: A retrospective cohort study of births meeting criteria was conducted between 2016 and 2020 at the Mater Mothers' Hospital, Brisbane, Australia. This is a quaternary perinatal centre and Australia's largest maternity hospital. Univariate and multivariate Firth logistic regression were used to account for imbalanced frequency classes between non-HIE and HIE groups. Maternal variables and intrapartum factors were investigated for associations with neonatal moderate and severe HIE. RESULTS: Overall, 133 of 46 041 (0.29%) infants were diagnosed with HIE: 77 (0.17%) with mild HIE and 56 (0.12%) with moderate/severe HIE. Nulliparity, type 1 diabetes mellitus and maternal intensive care unit admission were associated with increased odds of moderate/severe HIE. Intrapartum risk factors included emergency caesarean birth, emergency caesarean for non-reassuring fetal status or failure to process, intrapartum haemorrhage and an intrapartum sentinel event (shoulder dystocia, cord prolapse, uterine rupture and placental abruption). Neonatal risk factors included male sex, late preterm gestation (35+0 -36+6  weeks), Apgar score less than four at 5 min, severe respiratory distress requiring ventilatory support and severe acidosis at birth. CONCLUSIONS: This cohort study identified a series of potentially modifiable maternal and obstetric risk factors for HIE. Risk factors for HIE do not appear to have changed significantly with evolution in modern obstetric care.

Decreasing delivery room intubations: A quality improvement project.

AIM: The delivery room intubation rate for babies born less than 32 weeks postmenstrual age (PMA) at the Mater Mothers' Hospital in 2017 was 51%. Delivery room intubation of preterm infants may be associated with an increased risk of developing bronchopulmonary dysplasia. This quality improvement project aimed to decrease the rate of delivery room intubation for infants born less than 32 weeks PMA. METHODS: A quality improvement process using the evidence-based practice for improving quality framework and Plan-Do-Study-Act cycles was undertaken from October 2018 to December 2019. Commencing bubble continuous positive airway pressure for initial resuscitation in the delivery room was the principal change idea. RESULTS: The delivery room intubation rate for infants born less than 32 weeks PMA before the commencement of this project was 48% (cohort 1, n = 221). There was a significant decrease in the rate to 37.2% while the project was being conducted (cohort 2, n = 277) and a further significant reduction to 28.2% after introducing bubble continuous positive airway pressure in the delivery room (cohort 3, n = 202). There was a significant improvement in admission temperatures and a significant decrease in mortality rate between cohort 1 and cohort 2 but not between cohort 2 and cohort 3. There was no change in the rate of discharge home on oxygen between cohorts. CONCLUSIONS: This quality improvement project led to a significantly decreased delivery room intubation rate in infants born less than 32 weeks PMA. There was no evidence of any adverse outcomes with this approach.

Trial of aerosolised surfactant for preterm infants with respiratory distress syndrome.

OBJECTIVE: To evaluate the safety of an aerosolised surfactant, SF-RI 1, administered via nasal continuous positive airway pressure (nCPAP) and a prototype breath synchronisation device (AeroFact), to preterm infants with respiratory distress syndrome (RDS). DESIGN: Multicentre, open-label, dose-escalation study with historical controls. SETTING: Newborn intensive care units at Mater Mothers' Hospital, Brisbane, and Royal Hospital for Women, Sydney, Australia. PATIENTS: Infants 26 weeks through 30 weeks gestation who required nCPAP 6-8 cmH2O and fraction of inspired oxygen (FiO2) <0.30 at <2 hours of age. INTERVENTIONS: In part 1, infants received a single dose of 216 mg/kg of aerosolised surfactant. In part 2, infants could receive up to four doses of aerosolised surfactant. Three historical control infants were matched for each enrolled infant. MAIN OUTCOME MEASURES: Treatment failure was defined as Respiratory Severity Score (FiO2×cmH2O nCPAP) >2.4, nCPAP >8 cmH2O, arterial carbon dioxide >65 mm Hg, pH <7.20 or three severe apnoeas within 6 hours during the first 72 hours of life. Other outcomes included tolerance of the AeroFact treatment and complications of prematurity. RESULTS: 10 infants were enrolled in part 1 and 21 in part 2 and were compared with 93 historical controls. No safety issues were identified. In part 2, 6 of 21 (29%) AeroFact-treated infants compared with 30 of 63 (48%) control infants met failure criteria. Kaplan-Meier analysis of patients in part 2 showed a trend towards decreased rate of study failure in the AeroFact-treated infants compared with historical controls (p=0.10). CONCLUSION: The AeroFact system can safely deliver aerosolised surfactant to preterm infants with RDS who are on nCPAP. TRIAL REGISTRATION NUMBER: ACTRN12617001458325.

A quality appraisal using the AGREE II instrument of endotracheal tube suction guidelines in neonatal intensive care units.

BACKGROUND: Endotracheal tube (ETT) suction is among the most common procedures performed in neonatal intensive care units (NICUs). Although necessary, it is associated with significant risks. To mitigate these risks, clinical practice guidelines are developed to provide evidence-based recommendations. OBJECTIVE: The aim of the study was to appraise the quality of neonatal ETT suction guidelines from all NICUs in Australia and New Zealand. METHODS: All level III NICUs in Australia and New Zealand were invited to participate. Three researchers graded the methodological quality of the received guidelines using the AGREE II instrument. Item and domain scores were calculated by scaling as a percentage of the total possible score out of 100%. A threshold score of <50% is considered to be of limited potential use. RESULTS: Twenty-three (79.31%) clinical practice guidelines were received from 29 invited facilities. The scaled results of the AGREE II domains were as follows: Scope and Purpose, mean = 73%, 95% confidence interval (CI) = 63-83%; Stakeholder Involvement, mean = 23%, 95% CI = 15-31%; Rigour of Development, mean = 17%, 95% CI = 12-21%; Clarity of Presentation, mean = 63%, 95% CI = 56-70%; Applicability, mean = 5%, 95% CI = 20-30%; and Editorial Independence, mean = 50%, 95% CI = 50-50%. Overall assessment indicated low methodological quality (31%; 22-39%), with only five clinical practice guidelines scoring >50%, suggesting that they could be recommended for use with modifications. The remaining 18 could not be recommended for use. CONCLUSIONS: Neonatal ETT suction guidelines are of a low methodological quality. All guidelines poorly incorporated latest evidence in guideline development. This appraisal highlights the need to improve the quality of neonatal ETT suction guidelines to promote optimal patient care.

Nasal high flow in preterm infants: A dose-finding study.

OBJECTIVE: To investigate the relationship between applied flows of nasal high flow (NHF) and physiological outcomes and work of breathing (WOB), to identify an optimal delivery flow which results in reduced WOB in preterm infants. DESIGN: A prospective observational clinical study with randomly applied NHF rates. PATIENTS AND SETTING: Preterm infants within 72 hours of commencement of NHF respiratory support. INTERVENTIONS: Infants were initially placed on 8 L/min of NHF and flows of 2, 4, and 6 L/min were then applied in random order. MEASUREMENTS AND RESULTS: WOB was measured using transcutaneous electromyography and respiratory inductance plethysmography. Physiological variables were also recorded. Measurements taken 10 minutes after each flow change were compared with 8 L/min. Sixteen infants with a median gestational age of 28 (range 24-31) weeks and postnatal age of 14 (2-55) days were included in the study. The median flow rate before the study was 6 (4-8) L/min and a fraction of inspired oxygen (FiO2 ) was 0.21 (0.21-0.26). Changes in flow resulted in changes in activity in the front diaphragm (P = .027) and intercostals (P = .034). The electrical activity of the front diaphragm at 8 L/min was significantly lower than that at 2 L/min (P = .016). Respiratory rate was lowest at 6 L/min (P = .002) and SpO2 /FiO2 was highest at 8 L/min (P < .04). CONCLUSION: In preterm infants, changes in WOB resulting from randomly applied levels of NHF can be demonstrated by measuring the electrical activity of the diaphragm and intercostal muscles with transcutaneous electromyography. In combination with physiological measurements, the similarities in electrical activity between 4, 6, and 8 L/min suggest that these three flows may be equally as effective.

Chest wall mesenchymal hamartoma in an infant: Evaluation with electrical impedance tomography.

Mesenchymal hamartoma of the chest wall is a rare benign nonneoplastic lesion of infancy arising from chondro-osseous tissue. Although its natural history suggests spontaneous regression, we describe a fatal case in a neonate with significant respiratory compromise. We explored the use of electrical impedance tomography to evaluate the dynamic impact of such space occupying lesions on a ventilated infant.

Effect of randomization of nasal high flow rate in preterm infants.

OBJECTIVE: To assess the effect of nasal high flow (NHF) cannula on end-expiratory level (EEL), continuous distending pressure (CDP) and regional ventilation distribution in preterm infants. DESIGN: A prospective observational clinical study with randomly applied NHF rates. PATIENTS AND SETTING: Preterm infants requiring continuous positive airway pressure (CPAP) respiratory support in a Neonatal Intensive Care Unit. INTERVENTIONS: Infants were measured on randomly applied flow rates at 2, 4, and 6 L/min of NHF and compared with bubble CPAP. MEASUREMENTS AND RESULTS: Regional ventilation distribution and EEL were measured using electrical impedance tomography (EIT) and respiratory inductance plethysmography (RIP) in 24 preterm infants (31.19 ± 1.17 weeks corrected age). Changes in CDP were measured from the esophagus via the nasogastric tube. Physiological variables were also recorded. There were no differences in ventilation distribution, EEL or CDP between CPAP and NHF (P > .05). However, the physiological variables of FiO2 (P = .01) and SpO2 /FiO2 (P < .01) were improved on CPAP compared with NHF. CONCLUSION: NHF applied in random order with flow rates between 2 to 6 L/min was equally as good as CPAP in maintaining EEL and ventilation distribution in stable preterm infants. Overall oxygenation was better on CPAP compared to NHF.

A Randomized Trial of Baby Triple P for Preterm Infants: Child Outcomes at 2 Years of Corrected Age.

OBJECTIVE: To determine the efficacy of a hospital-based intervention that transitions into existing community support, in enhancing developmental outcomes at 2 years of corrected age in infants born at less than 32 weeks. STUDY DESIGN: In total, 323 families of 384 infants born <32 weeks were randomized to receive intervention or care-as-usual. The intervention teaches parents coping skills, partner support, and effective parenting strategies over 4 hospital-based and 4 home-phone sessions. At 2 years of corrected age maternally reported child behavior was assessed by the Infant and Toddler Social Emotional Adjustment Scale. Observed child behavior was coded with the Revised Family Observation Schedule. Cognitive, language, and motor skills were assessed with the Bayley Scales of Infant and Toddler Development III. RESULTS: Mean gestational age of infants was 28.5 weeks (SD = 2.1), and mothers' mean age was 30.6 years (SD = 5.8). A total of 162 families (n = 196 infants) were allocated to intervention and 161 families (n = 188 infants) received care-as-usual. There was no significant adjusted difference between treatment groups on dysregulation (0.2; 95% CI -2.5 to 3.0, P = .9) externalizing (0.3; 95% CI -1.6 to 2.2, P = .8), internalizing (-1.5; 95% CI -4.3 to 1.3, P = .3), observed aversive (0.00; -0.04 to 0.04, P = .9), or nonaversive behavior (-0.01; 95% CI -0.05 to 0.03, P = .7). Intervention children scored significantly higher on cognition (3.5; 95% CI 0.2-6.8, P = .04) and motor skill (5.5; 95% CI 2.5-8.4, P < .001), and approached significance on language (3.8; 95% CI -0.3 to 7.9, P = .07). CONCLUSIONS: Baby Triple P for Preterm Infants increases cognitive and motor skills but does not impact behavior. The results are evidence that hospital-based interventions can improve some developmental outcomes for infants <32 weeks. TRIAL REGISTRATION: ACTRN 12612000194864.

Integration of congenital cytomegalovirus screening within a newborn hearing screening programme.

AIM: Targeted screening by a salivary cytomegalovirus (CMV) polymerase chain reaction (PCR) of infants who 'refer' on their newborn hearing screen has been suggested as an easy, reliable and cost-effective approach to identify and treat babies with congenital CMV (cCMV) to improve hearing outcomes. This study aimed to investigate the feasibility and cost-effectiveness of introducing targeted salivary cCMV testing into a newborn hearing screening programme. METHODS: The study included three tertiary maternity hospitals in Queensland, Australia between August 2014 and April 2016. Infants who 'referred' on the newborn hearing screen were offered a salivary swab for CMV PCR at the point of referral to audiology. Swabs were routinely processed and tested for CMV DNA by real-time quantitative PCR. Parents of babies with a positive CMV PCR were notified, and the babies were medically assessed and, where appropriate, were offered treatment (oral valganciclovir). RESULTS: Of eligible infants, the parents of 83.0% (234/283) consented to the cCMV screen. Of these, 96.6% returned a negative result (226/234), and 3.4% (8/234) returned a positive result (three true positive; five false positive). The prevalence of cCMV for infants with confirmed hearing loss was 3.64% (P = 2/55; confidence interval = 0.44-12.53%). The cost comparison suggests the cost implementation of cCMV screening (and subsequent potential treatment benefits and management over time), compared to non-screening (and subsequent management), to be negligible. CONCLUSION: Incorporating cCMV testing into Universal Newborn Hearing Screening within Queensland is realistic and achievable, both practically and financially.

Work environment risks for health care workers with cystic fibrosis.

In Australia and New Zealand, >50% of people with cystic fibrosis (CF) are adults and many of these people are pursuing vocational training and undertaking paid employment. More than 6% of adults with CF are working in health care. There is limited guidance in literature to support health care workers with CF (HCWcf) in training and in employment to support safe practice and to provide protection for themselves and their patients from the acquisition of health care associated infection. A multidisciplinary team of CF and Infectious Disease Clinicians, Infection Prevention and Control Practitioners, HCWcf, academic experts in medical ethics and representatives from universities, appraised the available evidence on the risk posed to and by HCWcf. Specific recommendations were made for HCWcf, CF health care teams, hospitals and universities to support the safe practice and appropriate support for HCWcf.

Strategies for the discontinuation of humidified high flow nasal cannula (HHFNC) in preterm infants.

BACKGROUND: Humidified high flow nasal cannula (HHFNC) delivers humidified gas at increased flow rates via binasal prongs and is becoming widely accepted as a method of non-invasive respiratory support for preterm infants. While indications for the use of (HHFNC) and its associated risks and benefits are being investigated, the best strategy for the discontinuation of HHFNC remains unknown. At what point an infant is considered stable enough to attempt to start withdrawing their HHFNC is not known. The criteria for a failed attempt at HHFNC discontinuation is also unclear. OBJECTIVES: To determine the risks and benefits of different strategies used for the discontinuation of HHFNC in preterm infants. SEARCH METHODS: We searched the Cochrane Neonatal Review Group Specialized Register, PubMed (1966 to March 2015), CINAHL (1982 to March 2015), EMBASE (1980 to March 2015), and the Cochrane Central Register of Controlled Trials (CENTRAL). Also, we checked previous reviews, including cross references. We searched for following web sites for ongoing trials: ClinicalTrials.gov and controlled-trials.com. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs in which either individual newborn infants or clusters of infants (such as separate neonatal units) were randomised to different HHFNC withdrawal strategies (from the first time they come off HHFNC and any subsequent weaning, or withdrawal attempt, or both). DATA COLLECTION AND ANALYSIS: We used standard methods of Cochrane and the Cochrane Neonatal Review Group. MAIN RESULTS: We identified no eligible studies examining the best strategy to wean or withdraw HHFNC once started as respiratory support in preterm infants AUTHORS' CONCLUSIONS: There is currently no evidence available to suggest the best strategy for weaning and withdrawing HHFNC as a respiratory support in preterm infants. Research is required into the best strategy for withdrawal of HHFNC and to which subgroups this applies. Clear criteria for the definition of stability prior to attempting to withdraw HHFNC needs to be established. Furthermore, clear definitions are needed as to what constitutes failure of HHFNC.

Neonatal jaundice: phototherapy.

INTRODUCTION: About 50% of term and 80% of preterm babies develop jaundice, which usually appears 2 to 4 days after birth, and resolves spontaneously after 1 to 2 weeks. Jaundice is caused by bilirubin deposition in the skin. Most jaundice in newborn infants is a result of increased red cell breakdown and decreased bilirubin excretion. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of different wavelengths of light in hospital phototherapy as treatment for unconjugated hyperbilirubinaemia in term and preterm infants? What are the effects of different intensities of light in hospital phototherapy as treatment for unconjugated hyperbilirubinaemia in term and preterm infants? What are the effects of different total doses of light in hospital phototherapy as treatment for unconjugated hyperbilirubinaemia in term and preterm infants? What are the effects of starting hospital phototherapy at different thresholds in term and preterm infants? We searched Medline, Embase, The Cochrane Library, and other important databases up to January 2014 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: Fourteen studies were included. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of different wavelengths, intensities, total doses, and threshold for commencement of the following intervention: hospital phototherapy.

Prem Baby Triple P: a randomised controlled trial of enhanced parenting capacity to improve developmental outcomes in preterm infants.

BACKGROUND: Very preterm birth (<32 weeks gestation) is associated with motor, cognitive, behavioural and educational problems in children and maternal depression and withdrawal. Early interventions that target parenting have the greatest potential to create sustained effects on child development and parental psychopathology. Triple P (Positive Parenting Program) has shown positive effects on child behaviour and adjustment, parenting practices and family functioning. Baby Triple P for Preterm infants, has been developed to target parents of very preterm infants. This study tests the effectiveness of Baby Triple P for Preterm infants in improving child and parent/couple outcomes at 24 months corrected age (CA). METHODS/DESIGN: Families will be randomised to receive either Baby Triple P for Preterm infants or Care as Usual (CAU). Baby Triple P for Preterm infants involves 4 × 2 hr group sessions at the hospital plus 4 × 30 min telephone consultations soon after transfer (42 weeks C.A.). After discharge participants will be linked to community based Triple P and intervention maintenance up to 24 months C.A. Assessments will be: baseline, post-intervention (6 weeks C.A.), at 12 and 24 months C.A. The primary outcome measure is the Infant Toddler Social & Emotional Assessment (ITSEA) at 24 months C.A. Child behavioural and emotional problems will be coded using the mother-toddler version of the Family Observation Schedule at 24 months C.A. Secondary outcome will be the Bayley Scales of Infant and Toddler Development (BSID III) cognitive development, language and motor abilities. Proximal targets of parenting style, parental self-efficacy, parental mental health, parental adjustment, parent-infant attachment, couple relationship satisfaction and couple communication will also be assessed. Our sample size based on the ITSEA, has 80% power, predicted effect size of 0.33 and an 85% retention rate, requires 165 families are required in each group (total sample of 330 families). DISCUSSION: This protocol presents the study design, methods and intervention to be analysed in a randomised trial of Baby Triple P for Preterm infants compared to Care as Usual (CAU) for families of very preterm infants. Publications of all outcomes will be published in peer reviewed journals according to CONSORT guidelines. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12612000194864.

Methods for securing endotracheal tubes in newborn infants.

BACKGROUND: Securing the endotracheal tube is a common procedure in the neonatal intensive care unit. Adequate fixation of the tube is essential to ensure effective ventilation of the infant whilst minimising potential complications secondary to the intervention. Methods used to secure the endotracheal tube often vary between units and sometimes even between healthcare providers in the same nursery. OBJECTIVES: To compare the different methods of securing the endotracheal tube in the ventilated neonate and their effects on the risk of accidental extubation and other potential complications that can result from an unstable endotracheal tube. SEARCH METHODS: A literature search of MEDLINE (from 1966 to June 2013), CINAHL (from 1982 to June 2013) and CENTRAL in The Cochrane Library was conducted to identify relevant trials to be analysed. SELECTION CRITERIA: All randomised and quasi-randomised controlled trials of infants who were intubated for mechanical ventilation in a neonatal intensive care nursery where methods of stabilising the endotracheal tube were being compared. DATA COLLECTION AND ANALYSIS: Data were collected from individual studies to determine the methods being compared, the methodology of the trial, and whether there were areas of bias that could significantly affect the results of the studies. In particular, studies were assessed for blinding of randomisation and allocation, blinding of the intervention, completeness of follow up, blinding of outcome assessments and selective reporting. MAIN RESULTS: Five randomised controlled trials were identified and included for review. Accidental extubation was the most common outcome measured (five studies). None of the studies reported on the need for re-intubation or the rate of tube malposition, however one study did report on endotracheal tube slippage. A variety of other adverse effects were reported including mortality, incidence of perioral skin trauma and tube re-taping. All five studies were of poor methodological quality, small size, contained significant risks of bias and compared methods of securing the endotracheal tube that were too dissimilar for the data to be collated or included in a meta-analysis. We have not reported these further. AUTHORS' CONCLUSIONS: This review highlighted the need for further well designed and completed studies to be conducted for this common neonatal procedure. Evidence is lacking to determine the most effective and safe method to stabilise the endotracheal tube in the ventilated neonate.

Home- versus hospital-based phototherapy for the treatment of non-haemolytic jaundice in infants at more than 37 weeks' gestation.

BACKGROUND: Phototherapy is commonly used for the treatment of neonatal jaundice, and home-based phototherapy is now being used in certain centres. Home-based phototherapy offers possible advantages by avoiding prolonged hospital admissions, promoting mother-infant bonding and reducing hospitalisation costs. Potential problems include increased duration of phototherapy, increased readmission to hospital and increased risk of bilirubin encephalopathy. OBJECTIVES: To compare exclusively home-based versus exclusively hospital-based phototherapy or a combination of home- and hospital-based phototherapy for the management of non-haemolytic jaundice in term infants up to 28 days of age. We planned to include specific subgroups for duration in hospital, method of phototherapy and criteria for readiness for discharge. SEARCH METHODS: We searched the Cochrane Neonatal Review Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) January 2013, Issue 1, part of The Cochrane Library, MEDLINE (from 1966 to 15 February 2013), CINAHL (from 1982 to 15 February 2013) and EMBASE (from 1988 to 15 February 2013). We searched for abstracts from the Pediatric Academic Societies' Annual Meetings 2000 to 2013. We searched for ongoing trials on the following websites: ClinicalTrials.gov (http://clinicaltrials.gov/) and Current Controlled Trials (http://controlled-trials.com/). SELECTION CRITERIA: Randomised and quasi-randomised studies comparing term infants who received phototherapy exclusively at home versus phototherapy exclusively in the hospital or a combination of the two for non-haemolytic jaundice. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. MAIN RESULTS: No studies that met the predefined eligibility criteria were identified. AUTHORS' CONCLUSIONS: No high-quality evidence is currently available to support or refute the practice of home-based phototherapy for non-haemolytic jaundice in infants at more than 37 weeks' gestation.

Calcium channel blockers for inhibiting preterm labour and birth.

BACKGROUND: Preterm birth is a major contributor to perinatal mortality and morbidity, affecting around 9% of births in high-income countries and an estimated 13% of births in low- and middle-income countries. Tocolytics are drugs used to suppress uterine contractions for women in preterm labour. The most widely used tocolytic are the betamimetics, however, these are associated with a high frequency of unpleasant and sometimes severe maternal side effects. Calcium channel blockers (CCBs) (such as nifedipine) may have similar tocolytic efficacy with less side effects than betamimetics. Oxytocin receptor antagonists (ORAs) (e.g. atosiban) also have a low side-effect profile. OBJECTIVES: To assess the effects on maternal, fetal and neonatal outcomes of CCBs, administered as a tocolytic agent, to women in preterm labour. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (12 November 2013). SELECTION CRITERIA: All published and unpublished randomised trials in which CCBs were used for tocolysis for women in labour between 20 and 36 completed weeks' gestation. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial eligibility, undertook quality assessment and data extraction. Results are presented using risk ratio (RR) for categorical data and mean difference (MD) for data measured on a continuous scale with the 95% confidence interval (CI). The number needed to treat to benefit (NNTB) and the number needed to treat to harm (NNTH) were calculated for categorical outcomes that were statistically significantly different. MAIN RESULTS: This update includes 26 additional trials involving 2511 women, giving a total of 38 included trials (3550 women). Thirty-five trials used nifedipine as the CCB and three trials used nicardipine. Blinding of intervention and outcome assessment was undertaken in only one of the trials (a placebo controlled trial). However, objective outcomes defined according to timing of birth and perinatal mortality were considered to have low risk of detection bias.Two small trials comparing CCBs with placebo or no treatment showed a significant reduction in birth less than 48 hours after trial entry (RR 0.30, 95% CI 0.21 to 0.43) and an increase in maternal adverse effects (RR 49.89, 95% CI 3.13 to 795.02, one trial of 89 women). Due to substantial heterogeneity, outcome data for preterm birth (less than 37 weeks) were not combined; one placebo controlled trial showed no difference (RR 0.96, 95% CI 0.89 to 1.03) while the other (non-placebo controlled trial) reported a reduction (RR 0.44, 95% CI 0.31 to 0.62). No other outcomes were reported.Comparing CCBs (mainly nifedipine) with other tocolytics by type (including betamimetics, glyceryl trinitrate (GTN) patch, non-steriodal anti inflammatories (NSAID), magnesium sulphate and ORAs), no significant reductions were shown in primary outcome measures of birth within 48 hours of treatment or perinatal mortality.Comparing CCBs with betamimetics, there were fewer maternal adverse effects (average RR 0.36, 95% CI 0.24 to 0.53) and fewer maternal adverse effects requiring discontinuation of therapy (average RR 0.22, 95% CI 0.10 to 0.48). Calcium channel blockers resulted in an increase in the interval between trial entry and birth (average MD 4.38 days, 95% CI 0.25 to 8.52) and gestational age (MD 0.71 weeks, 95% CI 0.34 to 1.09), while decreasing preterm and very preterm birth (RR 0.89, 95% CI 0.80 to 0.98 and RR 0.78, 95% CI 0.66 to 0.93); respiratory distress syndrome (RR 0.64, 95% CI 0.48 to 0.86); necrotising enterocolitis (RR 0.21, 95% CI 0.05 to 0.96); intraventricular haemorrhage (RR 0.53, 95% CI 0.34 to 0.84); neonatal jaundice (RR 0.72, 95% CI 0.57 to 0.92); and admissions to neonatal intensive care unit (NICU) (average RR 0.74, 95% CI 0.63 to 0.87). No difference was shown in one trial of outcomes at nine to twelve years of age.Comparing CCBs with ORA, data from one study (which did blind the intervention) showed an increase in gestational age at birth (MD 1.20 completed weeks, 95% CI 0.25 to 2.15) and reductions in preterm birth (RR 0.64, 95% CI 0.47 to 0.89); admissions to the NICU (RR 0.59, 95% CI 0.41 to 0.85); and duration of stay in the NICU (MD -5.40 days,95% CI -10.84 to 0.04). Maternal adverse effects were increased in the CCB group (average RR 2.61, 95% CI 1.43 to 4.74).Comparing CCBs with magnesium sulphate, maternal adverse effects were reduced (average RR 0.52, 95% CI 0.40 to 0.68), as was duration of stay in the NICU (days) (MD -4.55, 95% CI -8.17 to -0.92). No differences were shown in the comparisons with GTN patch or NSAID, although numbers were small.No differences in outcomes were shown in trials comparing nicardipine with other tocolytics, although with limited data no strong conclusions can be drawn. No differences were evident in a small trial that compared higher- versus lower-dose nifedipine, though findings tended to favour a high dose on some measures of neonatal morbidity. AUTHORS' CONCLUSIONS: Calcium channel blockers (mainly nifedipine) for women in preterm labour have benefits over placebo or no treatment in terms of postponement of birth thus, theoretically, allowing time for administration of antenatal corticosteroids and transfer to higher level care. Calcium channel blockers were shown to have benefits over betamimetics with respect to prolongation of pregnancy, serious neonatal morbidity, and maternal adverse effects. Calcium channel blockers may also have some benefits over ORAs and magnesium sulphate, although ORAs results in fewer maternal adverse effects. However, it must be noted that no difference was shown in perinatal mortality, and data on longer-term outcomes were limited. Further, the lack of blinding of the intervention diminishes the strength of this body of evidence. Further well-designed tocolytic trials are required to determine short- and longer-term infant benefit of CCBs over placebo or no treatment and other tocolytics, particularly ORAs. Another important focus for future trials is identifying optimal dosage regimens of different types of CCBs (high versus low, particularly addressing speed of onset of uterine quiescence) and formulation (capsules versus tablets). All future trials on tocolytics for women in preterm labour should employ blinding of the intervention and outcome assessment, include measurement of longer-term effects into early childhood, and also costs.

Neonatal infections: group B streptococcus.

INTRODUCTION: One in four women carry group B streptococci vaginally, which can infect the amniotic fluid before delivery or can infect the baby during delivery, causing sepsis, pneumonia, or meningitis. Very low-birthweight infants are at much higher risk of infection or mortality, with up to 3% infected and mortality rates of up to 30%, even with immediate antibiotic treatment. Late-onset group B streptococcal infection begins from 7 days of age, and usually causes fever or meningitis, but is less often fatal compared with early infection. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical question: what are the effects of prophylactic treatment of asymptomatic neonates less than 7 days old with known risk factors for early-onset group B streptococcal infection? We searched: Medline, Embase, The Cochrane Library, and other important databases up to November 2013 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 5 studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: different antibiotics, monitoring and selective treatment, and routine antibiotic prophylaxis.