OBJECTIVES: This study aimed to determine EnCPAP rates in 36 neonatal intensive care units of the Malaysian National Neonatal Registry (MNNR) in 2013, to compare the outcomes of VLBW neonates with and without EnCPAP, and to determine whether the availability of CPAP facilities and unit policies played a significant role in EnCPAP rates.
METHODS: First, a retrospective cohort study was conducted of VLBW neonates born in the hospitals participating in the study without major congenital abnormalities in the MNNR. This was followed by a questionnaire survey of these hospitals focussed on CPAP facilities and unit policies.
RESULTS: Of the 2,823 neonates, 963 (34.1%) received EnCPAP. Amongst EnCPAP neonates significantly fewer deaths were recorded (10.9 vs. 21.7%; p < 0.001), less bronchopulmonary dysplasia was observed (BPD; 8.0 vs. 11.7%; p = 0.002) and fewer mechanical ventilation days were necessary (p < 0.001) than in non-EnCPAP neonates. Logistic regression analysis showed that EnCPAP was significantly associated with a lower mortality (adjusted OR 0.623; 95% CI 0.472, 0.824; p = 0.001) and BPD among survivors (adjusted OR 0.585; 95% CI 0.427, 0.802; p = 0.001). The median EnCPAP rate of the 36 hospitals was 28.4% (IQR 14.3-38.7). Hospitals with CPAP facilities in the delivery suites (p = 0.001) and during transport (p = 0.001) and a policy for EnCPAP (p = 0.036) had significantly higher EnCPAP rates.
CONCLUSION: EnCPAP reduced mortality and BPD in Malaysian VLBW neonates. Resource-strapped developing countries should prioritise the use of this low-cost therapy.
METHODS: We assessed the use of composite outcomes in neonatal RCTs included in Cochrane Neonatal reviews published till November 2017. Two authors reviewed the components of the composite outcomes to compare their patient importance and computed the ratios of effect sizes and event rates between the components, with an a priori threshold of 1.5, indicating a substantial difference. Descriptive statistics were presented.
RESULTS: We extracted 7,766 outcomes in 2,134 RCTs in 312 systematic reviews. Among them, 55 composite outcomes (0.7%) were identified in 46 RCTs. The vast majority (92.7%) of composite outcomes had 2 components, with death being the most common component (included 51 times [92.7%]). The components in nearly three-quarters of the composite outcomes (n = 40 [72.7%]) had different patient importance, while the effect sizes and event rates differed substantially between the components in 27 (49.1%) and 35 (63.6%) outcomes, respectively, with up to 43-fold difference in the event rates observed.
CONCLUSIONS: The majority of composite outcomes in neonatal RCTs had different patient importance with contrasting effect sizes and event rates between the components. In patient communication, clinicians should highlight individual components, rather than the composites, with explanation on the relationship between the components, to avoid misleading impression on the effect of the intervention. Future trials should report the estimates of all individual components alongside the composite outcomes presented.
OBJECTIVES: We examined data from Cochrane Neonatal reviews to assess whether conditions that constituted KSD were included as key outcomes and how commonly they occurred in the population studied.
METHODS: We identified Cochrane reviews, published till November 2017 that evaluated interventions for neonatal jaundice (NNJ). We extracted the following information at the review and study levels: included population, outcomes assessed (in particular, whether PIOs such as KSD were listed as the primary outcomes), as well as their cumulative incidence in the reviews.
RESULTS: Out of 311 reviews, 11 evaluated interventions for NNJ with 78 randomized controlled trials (RCTs) included. Among the reviews, a total number of 148 outcomes were predefined and 30 (20.3%) were PIOs related to KSD, with 11 (36.7%) listed as primary outcomes. Among the 78 included RCTs (total participants = 8,232), 38 (48.7%) enrolled predominantly high-risk and 40 (51.3%) enrolled predominantly low-risk population. A total number of 431 outcomes were reported, and 40 (9.2%) were PIOs related to KSD (of which 37 were from studies with high-risk infants), with 13 (32.5%) listed as primary outcome. Cumulatively, no infant developed KSD across all studies.
CONCLUSIONS: There is suboptimal representation of PIOs such as KSD in neonatal trials and Cochrane reviews on NNJ. Over half of the trials included populations with very low risk of KSD, which does not represent judicious use of resources. Amidst our continued search for a more reliable surrogate marker for NNJ, studies should evaluate the whole spectrum KSD alongside serum bilirubin in high-risk populations with sufficiently significant event rates, as this will make the trial methodologically feasible, with findings that will impact the population concerned.
OBJECTIVES: We determined the proportion of PIOs in neonatal RCTs included in Cochrane Neonatal reviews.
METHODS: We extracted up to 5 outcomes from each RCT included in Cochrane Neonatal reviews published until January 2018, with independent determination of PIOs among authors followed by a discussion leading to a consensus. We defined PIOs as outcomes that matter to patient care, such as clinical events or physiological or laboratory parameters that are widely used to guide management.
RESULTS: Among 6,832 outcomes extracted from 1,874 RCTs included in 276 reviews, 5,349 (78.3%) were considered PIOs; 461 studies (24.5%) included 5 or more PIOs, 1,278 (68.2%) included 1-4 PIOs, while 135 (7.2%) had no PIO included. PIOs were observed more often among dichotomous than among continuous outcomes (94.9 vs. 61.5%; RR: 1.54; 95% CI: 1.50-1.58), and more among subjective than among objective outcomes (95.9 vs. 76.8%; RR: 1.25; 95% CI: 1.22-1.28). Newer studies were more likely to have a greater number of PIOs (adjusted OR: 1.033 [95% CI: 1.025-1.041] with each publication year).
CONCLUSIONS: The large and increasing representation of PIOs over the years suggests an improving awareness by neonatal trialists of the need to incorporate important outcomes in order to justify the utilization of resources. Further research should explore the reasons for non-inclusion or non-reporting of PIOs in a small proportion of RCTs.
OBJECTIVES: We described the ROB profile of neonatal RCTs published since the 1950s.
METHODS: We analyzed individual studies within the Cochrane Neonatal reviews published up to December 2016. We extracted the reviewers' judgments on the ROB domains including random sequence generation, allocation concealment, blinding, incomplete outcome data, and selective reporting. We evaluated blinding of personnel in trials in which blinding was considered feasible.
RESULTS: We assessed 1980 RCTs published between 1952 and 2016 from 294 Cochrane Neonatal systematic reviews, with full ROB assessments performed in 848 trials (42.8%). Among the ROB domains, the highest proportion of trials (73%) were judged as satisfactory ("low risk") in handling incomplete outcome data, while fewest trials achieved blinding of outcome assessor (38.4%). In the last 6 decades, a progressive increase has been observed in the proportion of trials that were rated as low risk in random sequence generation, allocation concealment, and selective reporting. However, blinding was achieved in less than half of the trials with no clear improvement across decades (23-44% since the 1980s).
CONCLUSIONS: Despite steady improvement in the overall quality of neonatal RCTs over the last 6 decades, blinding remained unsatisfactory in the majority of the trials.
OBJECTIVES: We evaluated the association between TSB and kernicterus spectrum disorder (KSD).
METHODS: We searched PubMed, EMBASE, and CENTRAL till July 2021. Two authors independently selected relevant cohort studies, extracted data (CHARMS checklist), assessed risk of bias (RoB) (QUIPS tool), and rated certainty-of-evidence (Grades of Recommendation, Assessment, Development, and Evaluation). We pooled adjusted odds ratio (aOR) (random-effect) via generic inverse variance methods.
RESULTS: From 2,826 records retrieved, we included 37 studies (n = 648,979). Fifteen studies had low, 16 moderate, and 6 high RoB, with majority having concerns on confounder adjustment and statistical analysis. Twenty-two studies contributed meta-analysis data, and 15 were summarized narratively. TSB appears associated with KSD in infants with certain risk factors (aOR 1.10, 95% CI: 1.07-1.13; 5 studies [n = 4,484]). However, TSB (aOR 1.10, 95% CI: 0.98-1.23; 1 study [n = 34,533]) or hyperbilirubinemia (aOR 1.00, 95% CI: 0.51-1.95; 2 studies [n = 56,578]) have no clear association with kernicterus or neurological diagnosis in overall neonatal population (moderate-certainty-evidence). One study shows that infants with hyperbilirubinemia appear likelier to develop attention-deficit disorder (aOR 1.90, 95% CI: 1.10-3.28) and autistic spectrum disorder (aOR 1.60, 95% CI: 1.03-2.49, n = 56,019) (low-certainty-evidence). Certain clinical factors appear associated with KSD, although very few studies contributed to the analyses.
CONCLUSIONS: Despite the importance of this question, there is insufficient high-quality evidence on the independent prognostic value of TSB for adverse neurodevelopmental outcomes in most neonatal populations. Future studies should incorporate all known risk factors alongside TSB in a multivariable analysis to improve certainty-of-evidence.
METHODS: A web-based survey (REDCap) was distributed via emails, social networking sites, and professional groups from October 2020 to February 2021 to neonatal clinicians in 35 countries.
RESULTS: A total of 484 responses were obtained from 35 countries and categorized into low/middle-income (43%, LMIC) or high-income (57%, HIC) countries. Of the 484 respondents, 53% would provide TH in mild HIE on case-to-case basis and only 25% would never cool. Clinicians from LMIC were more likely to routinely offer TH in mild HIE (25% v HIC 16%, p < 0.05), have a unit protocol for providing TH (50% v HIC 26%, p < 0.05), use adjunctive tools, e.g., aEEG (49% v HIC 32%, p < 0.001), conduct an MRI post TH (48% v HIC 40%, p < 0.05) and less likely to use neurological examinations as a HIE severity grading tool (80% v HIC 95%, p < 0.001). The majority of respondents (91%) would support a randomized controlled trial that was sufficiently large to examine neurodevelopmental outcomes in mild HIE after TH.
CONCLUSIONS: This is the first survey of global opinion for TH in mild HIE. The overwhelming majority of professionals would consider "cooling" an infant with mild HIE, but LMIC respondents were more likely to routinely cool infants with mild HIE and use adjunctive tools for diagnosis and follow-up. There is wide practice heterogeneity and a sufficiently large RCT designed to examine neurodevelopmental outcomes, is urgently needed and widely supported.