Outcomes of Neonates with Hypoxic-Ischemic Encephalopathy Treated with Magnesium Sulfate: A Systematic Review with Meta-analysis.

OBJECTIVE: To assess magnesium sulfate (MgSO4) as a neuroprotective agent in hypoxic-ischemic encephalopathy. STUDY DESIGN: For this systematic review, PubMed, EMBASE, the Cochrane Library, EMCARE, and MedNar were searched in November 2022 for randomized controlled trials (RCTs). Meta-analysis was conducted using Stata 16.0 and RevMan 5.3. RESULTS: Twenty RCTs with a total sample size of 1485 were included, of which 16 were from settings where therapeutic hypothermia (TH) was not offered. Regarding MgSO4 in settings where TH was not offered, only 1 study evaluated composite outcome of death or disability at ≥18 months and reported such poor outcome in 8 of 14 control infants and 4 of 8 in the MgSO4 group. MgSO4 was not associated with mortality (RR, 0.86; 95% CI, 0.72-1.03; 13 RCTs) or hypotension (RR, 1.02; 95% CI, 0.88-1.18; 5 RCTs). Thirteen studies reported that MgSO4 improved in-hospital outcomes, such as reduced seizure burden and improved neurological status at discharge. MgSO4 reduced the risk of poor suck feeds (RR, 0.52; 95% CI, 0.40-0.68; 6RCTs) and abnormal electroencephalogram (RR, 0.64; 95% CI, 0.45-0.93; 5 RCTs). Certainty of evidence was moderate for mortality and low or very low for other outcomes. For studies with MgSO4 as an adjunct to TH, none reported on death or neurodevelopmental disability at ≥18 months. MgSO4 was not associated with mortality (RR, 0.65; 95% CI, 0.34-1.27; 3 RCTs) or hypotension (RR, 1.0; 95% CI, 0.71-1.40; 3 RCTs). CONCLUSIONS: Evidence around long-term outcomes of MgSO4 when used with or without TH was scant. MgSO4 therapy may improve in-hospital neurological outcomes without affecting mortality in settings where TH is not offered. Well-designed RCTs for neuroprotection are needed, especially in low-resource settings. TRIAL REGISTRATION: "Open Science Forum" (https://doi.org/10.17605/OSF.IO/FRM4D).

Utility of the Ages and Stages Questionnaire to Identify Developmental Delay in Children Aged 12 to 60 Months: A Systematic Review and Meta-analysis.

Importance: The Ages and Stages Questionnaire (ASQ) is a commonly used developmental screening tool, but its utility is debated. Objectives: To conduct a a systematic review and meta-analysis to evaluate ASQ's utility as a screening or diagnostic tool to identify developmental delay in children aged 12-60 months. Data Sources: Medline, EMBASE, CINAHL, PsycINFO, and Mednar were searched from inception until December 2021. Study Selection: Studies meeting both criteria were included. ASQ was performed at age 12 to 60 months or where the median age at ASQ was at least 12 months and formal developmental assessments were done within 2 months of ASQ. Data Extraction and Synthesis: True positive, false positive, false negative, and true negatives from individual studies were extracted. Meta-analysis was conducted with Stata version 16.1. Risk of bias was assessed using the QUADAS-2 tool. Certainty of evidence (COE) was assessed using GRADE guidelines. Main Outcomes and Measures: Ability of ASQ scores more than 2 SDs below the mean in more than 1 domain (ASQ-2SD) to identify any developmental delay or severe delay. Based on generally accepted interpretation of likelihood ratio (LR) values, a positive LR (PLR) more than 5 and a negative LR (NLR) of 0.2 or less were considered necessary to rule in or rule out developmental delay, respectively, with at least moderate probability. Results: Initial search yielded 5777 citations of which 43 were included in the review. Of them, 36 were included in the meta-analysis. The pooled sensitivity, specificity, PLR, and NLR are as follows: ASQ-2SD to predict any delay in 1 or more domain (n = 16), 0.77 (95% CI, 0.64-0.86), 0.81 (95% CI, 0.75-0.86), 4.10 (95% CI, 3.17-5.30), and 0.28 (95% CI, 0.18-0.44); ASQ-2SD to predict severe delay in 1 or more domain (n = 15), 0.84 (95% CI, 0.75-0.90), 0.77 (95% CI, 0.71-0.82), 3.72 (95% CI, 2.98-4.64), and 0.20 (95% CI, 0.13-0.32); ASQ-2SD motor domain to predict motor delay (n = 7), 0.41 (95% CI, 0.26-0.57), 0.94 (95% CI, 0.87-0.97), 6.5 (95% CI, 3.8-11.1), and 0.63 (95% CI, 0.50-0.81); and ASQ-2SD cognitive domain to predict cognitive delay (n = 2), 0.44 (95% CI, 0.24-0.65), 0.93 (95% CI, 0.81-0.95), 6.4 (95% CI, 2.4-16.8), and 0.61 (95% CI, 0.43-0.86). The COE was low/very low. Conclusions and Relevance: If a child aged 12 to 60 months passes all ASQ domains, there is a moderate probability that they do not have severe developmental delay (low COE). If a child aged 12-60 months fails the motor or cognitive domain of ASQ, there is a moderate probability that they have some motor or cognitive delay, respectively (very low COE). Trial Registration: PROSPERO (CRD42021268543).

Outcomes of very preterm infants with neonatal hyperglycaemia: a systematic review and meta-analysis.

OBJECTIVE: To explore the association between hyperglycaemia and adverse outcomes in very preterm infants. DESIGN: Systematic review and meta-analysis. Data were pooled separately for adjusted and unadjusted odds ratios (ORs) using random-effects model. Subgroup analysis was conducted based on study design (cohort and case control). MAIN OUTCOME MEASURES: Association between hyperglycaemia in preterm neonates (<32 weeks or <1500 g) and mortality and morbidities. FINDINGS: Forty-six studies (30 cohort and 16 case control) with data from 34 527 infants were included. Meta-analysis of unadjusted ORs from cohort studies found hyperglycaemia to be significantly associated with mortality, any-grade intraventricular haemorrhage (IVH), severe IVH, any-stage retinopathy of prematurity (ROP), severe ROP, sepsis, chronic lung disease and disability. However, pooling of adjusted ORs found significant associations only for mortality (adjusted OR (CI): 2.37 (1.40 to 4.01); I2: 36%; 6 studies), 'Any grade IVH' (adjusted OR (CI): 2.60 (1.09 to 6.20); I2: 0%; 2 studies) and 'Any stage ROP' (adjusted OR (CI): 3.70 (1.55 to 8.84); I2: 0%; 2 studies). Meta-regression analysis found glucose levels >10 mmol/L to be associated with increased odds of mortality compared with <10 mmol/L. Pooled analysis from case-control studies were similar to cohort studies for most outcomes but limited by small sample size. Longer duration of hyperglycaemia was associated with adverse outcomes. GRADE of evidence was 'Low' or 'Very low'. CONCLUSION: Hyperglycaemia in very preterm infants is associated with higher odds of mortality, any-grade IVH and any-stage ROP. A limitation was lack of availability of adjusted ORs from many of the included studies. PROSPERO REGISTRATION NUMBER: CRD42020193016.

The role of skin testing and extended antibiotic courses in assessment of children with penicillin allergy: An Australian experience.

AIM: To determine if skin testing (ST) in addition to extended oral provocation challenge (OPC) is necessary for beta-lactam allergy verification in an Australian paediatric population. METHODS: This was a retrospective study (176 children) that undertook assessments for beta-lactam allergy from 2006 to 2015 at a tertiary paediatric hospital. Patients either underwent direct OPC without ST or ST plus challenge if ST was negative. RESULTS: The analysis included children with a history of varying rash types/severity as well as angioedema and reported anaphylaxis. A direct OPC was undertaken in 73 children. Three children reacted with one anaphylaxis. A total of 103 children underwent ST, with 13 children (12.6%) reacting. Of the 90 who subsequently proceeded to OPC, 4 reacted. A total of 132 children were given an extended oral course of the culprit antibiotic, to which 6 children reacted. CONCLUSIONS: A direct OPC with the culprit drug in Australian children can be safely performed, avoiding resource-intensive and painful ST. Our data demonstrate that a prior history of anaphylaxis does not necessarily predict IgE-mediated allergy, as detected by positive immediate ST or reactions to oral challenge. Such history should not detract from efforts to assess these children for antibiotic allergy. We suggest that extended courses of at least 5 days are important in paediatric antibiotic de-labelling as six children (4.5% of those who were prescribed the extended course) reacted in our study and even developed symptoms late in the extended course, from days 2 to 6.