Antenatal magnesium sulphate and adverse neonatal outcomes: A systematic review and meta-analysis.

BACKGROUND: There is widespread, increasing use of magnesium sulphate in obstetric practice for pre-eclampsia, eclampsia, and preterm fetal neuroprotection; benefit for preventing preterm labour and birth (tocolysis) is unproven. We conducted a systematic review and meta-analysis to assess whether antenatal magnesium sulphate is associated with unintended adverse neonatal outcomes. METHODS AND FINDINGS: CINAHL, Cochrane Library, LILACS, MEDLINE, Embase, TOXLINE, and Web of Science, were searched (inceptions to 3 September 2019). Randomised, quasi-randomised, and non-randomised trials, cohort and case-control studies, and case reports assessing antenatal magnesium sulphate for pre-eclampsia, eclampsia, fetal neuroprotection, or tocolysis, compared with placebo/no treatment or a different magnesium sulphate regimen, were included. The primary outcome was perinatal death. Secondary outcomes included pre-specified and non-pre-specified adverse neonatal outcomes. Two reviewers screened 5,890 articles, extracted data, and assessed risk of bias following Cochrane Handbook and RTI Item Bank guidance. For randomised trials, pooled risk ratios (RRs) or mean differences, with 95% confidence intervals (CIs), were calculated using fixed- or random-effects meta-analysis. Non-randomised data were tabulated and narratively summarised. We included 197 studies (40 randomised trials, 138 non-randomised studies, and 19 case reports), of mixed quality. The 40 trials (randomising 19,265 women and their babies) were conducted from 1987 to 2018 across high- (16 trials) and low/middle-income countries (23 trials) (1 mixed). Indications included pre-eclampsia/eclampsia (24 trials), fetal neuroprotection (7 trials), and tocolysis (9 trials); 18 trials compared magnesium sulphate with placebo/no treatment, and 22 compared different regimens. For perinatal death, no clear difference in randomised trials was observed between magnesium sulphate and placebo/no treatment (RR 1.01; 95% CI 0.92 to 1.10; 8 trials, 13,654 babies), nor between regimens. Eleven of 138 non-randomised studies reported on perinatal death. Only 1 cohort (127 babies; moderate to high risk of bias) observed an increased risk of perinatal death with >48 versus ≤48 grams magnesium sulphate exposure for tocolysis. No clear secondary adverse neonatal outcomes were observed in randomised trials, and a very limited number of possible adverse outcomes warranting further consideration were identified in non-randomised studies. Where non-randomised studies observed possible harms, often no or few confounders were controlled for (moderate to high risk of bias), samples were small (200 babies or fewer), and/or results were from subgroup analyses. Limitations include missing data for important outcomes across most studies, heterogeneity of included studies, and inclusion of published data only. CONCLUSIONS: Our findings do not support clear associations between antenatal magnesium sulphate for beneficial indications and adverse neonatal outcomes. Further large, high-quality studies (prospective cohorts or individual participant data meta-analyses) assessing specific outcomes, or the impact of regimen, pregnancy, or birth characteristics on these outcomes, would further inform safety recommendations. PROSPERO: CRD42013004451.

Canadian Guidelines for Controlled Pediatric Donation After Circulatory Determination of Death-Summary Report.

OBJECTIVES: Create trustworthy, rigorous, national clinical practice guidelines for the practice of pediatric donation after circulatory determination of death in Canada. METHODS: We followed a process of clinical practice guideline development based on World Health Organization and Canadian Medical Association methods. This included application of Grading of Recommendations Assessment, Development, and Evaluation methodology. Questions requiring recommendations were generated based on 1) 2006 Canadian donation after circulatory determination of death guidelines (not pediatric specific), 2) a multidisciplinary symposium of national and international pediatric donation after circulatory determination of death leaders, and 3) a scoping review of the pediatric donation after circulatory determination of death literature. Input from these sources drove drafting of actionable questions and Good Practice Statements, as defined by the Grading of Recommendations Assessment, Development, and Evaluation group. We performed additional literature reviews for all actionable questions. Evidence was assessed for quality using Grading of Recommendations Assessment, Development, and Evaluation and then formulated into evidence profiles that informed recommendations through the evidence-to-decision framework. Recommendations were revised through consensus among members of seven topic-specific working groups and finalized during meetings of working group leads and the planning committee. External review was provided by pediatric, critical care, and critical care nursing professional societies and patient partners. RESULTS: We generated 63 Good Practice Statements and seven Grading of Recommendations Assessment, Development, and Evaluation recommendations covering 1) ethics, consent, and withdrawal of life-sustaining therapy, 2) eligibility, 3) withdrawal of life-sustaining therapy practices, 4) ante and postmortem interventions, 5) death determination, 6) neonatal pediatric donation after circulatory determination of death, 7) cardiac and innovative pediatric donation after circulatory determination of death, and 8) implementation. For brevity, 48 Good Practice Statement and truncated justification are included in this summary report. The remaining recommendations, detailed methodology, full Grading of Recommendations Assessment, Development, and Evaluation tables, and expanded justifications are available in the full text report. CONCLUSIONS: This process showed that rigorous, transparent clinical practice guideline development is possible in the domain of pediatric deceased donation. Application of these recommendations will increase access to pediatric donation after circulatory determination of death across Canada and may serve as a model for future clinical practice guideline development in deceased donation.

Pathogenesis and Management of Indirect Hyperbilirubinemia in Preterm Neonates Less Than 35 Weeks: Moving Toward a Standardized Approach.

Premature infants have a higher incidence of indirect hyperbilirubinemia than term infants. Management of neonatal indirect hyperbilirubinemia in late preterm and term neonates has been well addressed by recognized, consensus-based guidelines. However, the extension of these guidelines to the preterm population has been an area of uncertainty because of limited evidence. This leads to variation in clinical practice and lack of recognition of the spectrum of bilirubin-induced neurologic dysfunction (BIND) in this population. Preterm infants are metabolically immature and at higher risk for BIND at lower bilirubin levels than their term counterparts. Early use of phototherapy to eliminate BIND and minimize the need for exchange transfusion is the goal of treatment in premature neonates. Although considered relatively safe, phototherapy does have side effects, and some NICUs tend to overuse phototherapy. In this review, we describe the epidemiology and pathophysiology of BIND in preterm neonates, and discuss our approach to standardized management of indirect hyperbilirubinemia in the vulnerable preterm population. The proposed treatment charts suggest early use of phototherapy in preterm neonates with the aim of reducing exposure to high irradiance levels, minimizing the need for exchange transfusions, and preventing BIND. The charts are pragmatic and have additional curves for stopping phototherapy and escalating its intensity. Having a standardized approach would support future research and quality improvement initiatives that examine dose and duration of phototherapy exposure with relation to outcomes.

Neonatal outreach simulation.

Numerous factors contribute to neonatal morbidity and mortality, and inexperienced providers managing crisis situations is one major cause. Simulation-based medical education is an excellent modality to employ in community hospitals to help refine and refresh resuscitation skills of providers who infrequently encounter neonatal emergencies. Mounting evidence suggests that simulation-based education improves patient outcomes. Academic health centers have the potential to improve neonatal outcomes through collaborations with community hospital providers, sharing expertise in neonatal resuscitation and simulation. Community outreach programs using simulation have been successfully initiated in North America. Two examples of programs are described here, including the models for curricular development, required resources, limitations, and benefits. Considerations for initiating outreach simulation programs are discussed. In the future, research demonstrating improved neonatal outcomes using outreach simulation will be important for personnel conducting outreach programs. Neonatal outreach simulation is a promising educational endeavor that may ultimately prove important in decreasing neonatal morbidity and mortality.

Elevated triglycerides levels in two infants with hypoxic-ischemic encephalopathy undergoing therapeutic hypothermia and receiving parenteral nutrition.

Therapeutic hypothermia has been widely applied to improve the survival/neurodevelopmental outcomes among infants with moderate-to-severe hypoxic ischemic encephalopathy (HIE). Due to their critical condition and concerns over feeding tolerance, it is not uncommon to withhold enteral feeds and provide parenteral nutrition (PN) during hypothermia and early rewarming. Here we report 2 infants with HIE undergoing therapeutic hypothermia, and receiving PN, who exhibited early elevated triglyceride levels. Hypertriglyceridemia can be associated with neurologic complications, ranging from altered mental status, or irritability to seizures. Given the possible altered lipid metabolism under hypothermic conditions, we advocate close monitoring of lipid tolerance and conducting further prospective trials to elucidate lipid metabolism in these infants.