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.

Interventions to prevent hypothermia at birth in preterm and/or low birth weight infants.

BACKGROUND: Newborn admission temperature is a strong predictor of outcomes across all gestations. Hypothermia immediately after birth remains a worldwide issue and, if prolonged, is associated with harm. Keeping preterm infants warm is difficult even when recommended routine thermal care guidelines are followed in the delivery room. OBJECTIVES: To assess the efficacy and safety of interventions designed for prevention of hypothermia in preterm and/or low birth weight infants applied within 10 minutes after birth in the delivery room, compared with routine thermal care or any other single/combination of intervention(s) also designed for prevention of hypothermia in preterm and/or low birth weight infants applied within 10 minutes after birth in the delivery room. SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 5), MEDLINE via PubMed (1966 to 30 June 2016), Embase (1980 to 30 June 2016), and CINAHL (1982 to 30 June 2016). We also searched clinical trials databases, conference proceedings, and reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. SELECTION CRITERIA: Trials using randomised or quasi-randomised allocations to test interventions designed to prevent hypothermia (apart from 'routine' thermal care) applied within 10 minutes after birth in the delivery room for infants at < 37 weeks' gestation and/or birth weight ≤ 2500 grams. DATA COLLECTION AND ANALYSIS: We used Cochrane Neonatal methods when performing data collection and analysis. MAIN RESULTS: Twenty-five studies across 15 comparison groups met the inclusion criteria, categorised as: barriers to heat loss (18 studies); external heat sources (three studies); and combinations of interventions (four studies).Barriers to heat loss Plastic wrap or bag versus routine carePlastic wraps improved core body temperature on admission to the neonatal intensive care unit (NICU) or up to two hours after birth (mean difference (MD) 0.58°C, 95% confidence interval (CI) 0.50 to 0.66; 13 studies; 1633 infants), and fewer infants had hypothermia on admission to the NICU or up to two hours after birth (typical risk ratio (RR) 0.67, 95% CI 0.62 to 0.72; typical risk reduction (RD) -0.25, 95% CI -0.29 to -0.20; number needed to treat for an additional beneficial outcome (NNTB) 4, 95% CI 4 to 5; 10 studies; 1417 infants). Risk of hyperthermia on admission to the NICU or up to two hours after birth was increased in infants in the wrapped group (typical RR 3.91, 95% CI 2.05 to 7.44; typical RD 0.04, 95% CI 0.02 to 0.06; number needed to treat for an additional harmful outcome (NNTH) 25, 95% CI 17 to 50; 12 studies; 1523 infants), but overall, fewer infants receiving plastic wrap were outside the normothermic range (typical RR 0.75, 95% CI 0.69 to 0.81; typical RD -0.20, 95% CI -0.26 to -0.15; NNTH 5, 95% CI 4 to 7; five studies; 1048 infants).Evidence was insufficient to suggest that plastic wraps or bags significantly reduce risk of death during hospital stay or other major morbidities, with the exception of reducing risk of pulmonary haemorrhage.Evidence of practices regarding permutations on this general approach is still emerging and has been based on the findings of only one or two small studies.External heat sourcesEvidence is emerging on the efficacy of external heat sources, including skin-to-skin care (SSC) versus routine care (one study; 31 infants) and thermal mattress versus routine care (two studies; 126 infants).SSC was shown to be effective in reducing risk of hypothermia when compared with conventional incubator care for infants with birth weight ≥ 1200 and ≤ 2199 grams (RR 0.09, 95% CI 0.01 to 0.64; RD -0.56, 95% CI -0.84 to -0.27; NNTB 2, 95% CI 1 to 4). Thermal (transwarmer) mattress significantly kept infants ≤ 1500 grams warmer (MD 0.65°C, 95% CI 0.36 to 0.94) and reduced the incidence of hypothermia on admission to the NICU, with no significant difference in hyperthermia risk.Combinations of interventionsTwo studies (77 infants) compared thermal mattresses versus plastic wraps or bags for infants at ≤ 28 weeks' gestation. Investigators reported no significant differences in core body temperature nor in the incidence of hypothermia, hyperthermia, or core body temperature outside the normothermic range on admission to the NICU.Two additional studies (119 infants) compared plastic bags and thermal mattresses versus plastic bags alone for infants at < 31 weeks' gestation. Meta-analysis of these two studies showed improvement in core body temperature on admission to the NICU or up to two hours after birth, but an increase in hyperthermia. Data show no significant difference in the risk of having a core body temperature outside the normothermic range on admission to the NICU nor in the risk of other reported morbidities. AUTHORS' CONCLUSIONS: Evidence of moderate quality shows that use of plastic wraps or bags compared with routine care led to higher temperatures on admission to NICUs with less hypothermia, particularly for extremely preterm infants. Thermal mattresses and SSC also reduced hypothermia risk when compared with routine care, but findings are based on two or fewer small studies. Caution must be taken to avoid iatrogenic hyperthermia, particularly when multiple interventions are used simultaneously. Limited evidence suggests benefit and no evidence of harm for most short-term morbidity outcomes known to be associated with hypothermia, including major brain injury, bronchopulmonary dysplasia, retinopathy of prematurity, necrotising enterocolitis, and nosocomial infection. Many observational studies have shown increased mortality among preterm hypothermic infants compared with those who maintain normothermia, yet evidence is insufficient to suggest that these interventions reduce risk of in-hospital mortality across all comparison groups. Hypothermia may be a marker for illness and poorer outcomes by association rather than by causality. Limitations of this review include small numbers of identified studies; small sample sizes; and variations in methods and definitions used for hypothermia, hyperthermia, normothermia, routine care, and morbidity, along with lack of power to detect effects on morbidity and mortality across most comparison groups. Future studies should: be adequately powered to detect rarer outcomes; apply standardised morbidity definitions; focus on longer-term outcomes, particularly neurodevelopmental outcomes.

Online information for parents caring for their premature baby at home: A focus group study and systematic web search.

BACKGROUND: Online resources are a source of information for parents of premature babies when their baby is discharged from hospital. OBJECTIVES: To explore what topics parents deemed important after returning home from hospital with their premature baby and to evaluate the quality of existing websites that provide information for parents post-discharge. METHODS: In stage 1, 23 parents living in Northern Ireland participated in three focus groups and shared their information and support needs following the discharge of their infant(s). In stage 2, a World Wide Web (WWW) search was conducted using Google, Yahoo and Bing search engines. Websites meeting pre-specified inclusion criteria were reviewed using two website assessment tools and by calculating a readability score. Website content was compared to the topics identified by parents in the focus groups. RESULTS: Five overarching topics were identified across the three focus groups: life at home after neonatal care, taking care of our family, taking care of our premature baby, baby's growth and development and help with getting support and advice. Twenty-nine sites were identified that met the systematic web search inclusion criteria. Fifteen (52%) covered all five topics identified by parents to some extent and 9 (31%) provided current, accurate and relevant information based on the assessment criteria. CONCLUSION: Parents reported the need for information and support post-discharge from hospital. This was not always available to them, and relevant online resources were of varying quality. Listening to parents needs and preferences can facilitate the development of high-quality, evidence-based, parent-centred resources.

Treatment of retinopathy of prematurity in Northern Ireland, 2000-2011: a population-based study.

PURPOSE: To evaluate the incidence of treatment-requiring retinopathy of prematurity (ROP) over a 12-year-period in Northern Ireland. METHODS: The medical records of all infants treated for ROP from January 2000 to December 2011 were retrospectively reviewed and cross-referenced with the Neonatal Intensive Care Outcomes Research and Evaluation (NICORE) database. RESULTS: The Northern Ireland population data showed an increase in the number of live births from 2000 to 2011. The proportion of babies born with a birth weight <1501 g and/or <32 weeks' gestational age remained constant (χ(2) trend = 3.220, P = 0.0727), although the proportion of these babies who died prior to 42 weeks' gestation decreased from 2000 to 2011 (P = 0.0196 using χ(2) for trend = 5.445; P = 0.0354 using χ(2) = 20.809). The prevalence of treatment-requiring ROP in these infants increased from 1.05% in 2000 to 5.78% in 2011 (P < 0.001 using χ(2) trend = 16.309; P < 0.001 using χ(2) = 31.378). CONCLUSIONS: The present population-based study highlights that the incidence of treatment- requiring ROP is increasing in Northern Ireland. The increasing number of infants requiring treatment will need to be taken into consideration in the commissioning process for ROP services in Northern Ireland.

Regional follow up of late preterm neonatal intensive care graduates.

AIM: To guide researchers who are contemplating embarking on research by discussing the methodological challenges encountered in a retrospective follow-up study of three-year-old, late preterm infants (LPIs) who received neonatal intensive care (NIC) in Northern Ireland in 2006. BACKGROUND: The importance of effective research examining the longer term outcomes of infants admitted to NIC has received increasing recognition. Follow-up cohort and longitudinal studies have grown in number globally, yet the research methodology relating to follow up of NIC graduates is unclear. DATA SOURCES: Neonatal Intensive Care Outcomes and Research Evaluation (NICORE) database; maternity unit delivery records. REVIEW METHODS: This is a reflective-practice methodology paper. DISCUSSION: This paper highlights the methodological challenges of conducting retrospective follow-up research, from the initial planning stages through to the collection of data from the children, including identification of infants from a retrospective database, ethical issues, child-safety concerns and recruitment challenges. CONCLUSION: The important lessons learned from this study were that: Input from a multidisciplinary team is central to the success of the study. Protocols and guidelines should be in place before the study to ensure that problems are dealt with quickly. A realistic timeframe for each phase and ongoing monitoring of recruitment rates are essential. IMPLICATIONS FOR RESEARCH/PRACTICE: This paper creates an awareness of potential issues that may arise in follow-up research with NIC graduates. The paper also offers practical and effective examples of dealing with these issues, helping to ensure the smooth running of an ethical, professionally conducted, methodologically sound and clinically relevant follow-up study.

Reducing nosocomial infections in neonatal intensive care.

BACKGROUND: Nosocomial infection is a common problem in neonatal intensive care. A pilot quality improvement initiative focussing on hand hygiene and aimed at reducing nosocomial infection in very low birth weight (VLBW) infants was introduced in five Neonatal Intensive Care Units. METHODS: Line associated laboratory confirmed bloodstream infection (LCBSI) and ventilator associated pneumonia (VAP) were chosen as main outcome measures. RESULTS: In VLBW infants, the rate of line associated LCBSI per 1000 central venous catheter days fell by 24%. The rate of VAP per 1000 ventilator days in VLBW infants fell by 38%. Pre- and post-intervention questionnaires showed a statistically significant increase in use of alcohol-based gels and increased knowledge of hand hygiene.

Interventions to prevent hypothermia at birth in preterm and/or low birthweight infants.

BACKGROUND: Keeping vulnerable preterm infants warm is problematic even when recommended routine thermal care guidelines are followed in the delivery suite. OBJECTIVES: To assess efficacy and safety of interventions designed for prevention of hypothermia in preterm and/or low birthweight infants applied within 10 minutes after birth in the delivery suite compared with routine thermal care. SEARCH STRATEGY: We used the standard search strategy of the Cochrane Neonatal Review Group (CNRG). The review was updated in October 2009. SELECTION CRITERIA: Trials using randomised or quasi-randomised allocations to test a specific intervention designed to prevent hypothermia, (apart from 'routine' thermal care) applied within 10 minutes after birth in the delivery suite to infants of < 37 weeks' gestational age or birthweight