Blinding Assessments in Neonatal Ventilation Meta-Analyses: A Systematic Meta-Epidemiological Review

Randomization and blinding are generally important in randomized trials. In neonatology, blinding of ventilation strategies is unfeasible if not impossible and we hypothesized that its importance has been overestimated, while the peculiarities of the neonatal patient and the specific outcomes have not been considered.

For this meta-epidemiological review, we searched PubMed and Scopus databases in November 2023. We included all meta-analyses focusing on ventilation, published in past 5 years, and reporting either mortality or bronchopulmonary dysplasia (BPD) as an outcome. We extracted the information about how the authors had analyzed risk of bias and evidence certainty.

We screened 494 abstracts and included 40 meta-analyses. Overall, 13 of the 40 reviews assessed blinding properly. Australian and European authors were most likely to perform correct assessment of the blinding (p = 0.03) and the use of RoB 2.0 tool was also associated with proper assessment (p < 0.001). In multivariate regression, the use of RoB 2.0 was the only factor associated with a proper assessment (Beta 0.57 [95% confidence interval: 0.29-0.99]). GRADE ratings were performed in 25 reviews, and the authors downgraded the evidence certainty due to risk of bias in 19 of these and none of these reviews performed the blinding assessment correctly.

In past neonatal evidence syntheses, the role of blinding has been mostly overestimated, which has led to downgrading of evidence certainty. Objective outcomes (such as mortality and BPD) do not need to be downgraded due to lack of blinding, as the knowledge of the received intervention does not influence the outcome assessment.