Continuous glucose monitoring for the prevention of morbidity and mortality in preterm infants.

Abstract

Preterm infantsare susceptible tohyperglycemia andhypoglycemia, conditions which may lead to adverse neurodevelopment. The use of continuous glucose monitoring devices(CGM) might help keeping glucose levels in the normal range, and reduce the need for blood sampling. However, the useof CGM might be associated with harms in the preterm infant. Objective one: to assess the benefits and harms of CGM alone versus standard method of glycemic measure in preterm infants. Objective two: to assess the benefits and harms of CGM with automated algorithm versus standard method of glycemic measure in preterm infants. Objective three: to assess the benefits and harms of CGM with automated algorithm versus CGM without automated algorithm in preterm infants. We adopted the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 9), in the Cochrane Library; MEDLINE via PubMed (1966 to 25September 2020); Embase (1980 to 25September 2020); and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to 25September 2020). We also searched clinical trials databases, conference proceedings, and reference lists of retrieved articles for randomized controlled trials and quasi-randomized trials. Randomized controlled trials (RCTs) and quasi-RCTs in preterm infants comparing: 1)the use ofCGMversus intermittent modalities to measure glycemia (comparison 1); orCGM associated with prespecified interventions to correct hypoglycemiaor hyperglycemia versus CGM without such prespecified interventions(comparison 2). We assessed the methodological quality of included trials using Cochrane Effective Practice and Organisation of Care Group (EPOC) criteria (assessing randomization, blinding, loss to follow-up, and handling of outcome data). We evaluated treatment effects using a fixed-effect model with risk ratio (RR) for categorical data and mean, standard deviation (SD), and mean difference (MD) for continuous data. We used the GRADE approach to assess the certainty of the evidence. Four trials enrolling 138 infants met our inclusion criteria. Investigators in three trials (118 infants) comparedthe use ofCGM to intermittent modalities (comparison one); however one of these trialswas analyzedseparately because CGMwas used as a standalone device, without being coupled to a control algorithm like in the other trials. A fourth trial (20infants) assessed CGM with an automated algorithm versus CGM with a manual algorithm. None of the four included trials reported the neurodevelopmental outcome, i.e. the primary outcome of this review. Within comparison one, the certainty of the evidence on the use of CGM on mortality during hospitalization is very uncertain (typical RR 3.00,95% CI 0.13 to70.30; typical RD 0.04, 95% CI -0.06to 0.14; 50 participants; 1 study; very low certainty). The number of hypoglycemic episodes was reported in two studies with conflicting data. The number of hyperglycemic episodes was reported in one study(typical MD -1.40,95% CI -2.84to 0.04; 50 participants; 1 study). The certaintyof the evidence was very low for all outcomesbecause of limitations in study design, and imprecision of estimates. Threestudiesareongoing. There is insufficient evidence to determine if CGM improves preterm infant mortality or morbidities. Long-term outcomeswerenot reported. Clinical trials are required to determine the most effective CGM and glycemic management regimens in preterm infants before larger studies can be performed to assess the efficacy of CGMfor reducing mortality, morbidity and long-term neurodevelopmental impairments.The absence of CGM labelled for neonatal use is still a major limit in its use as well as the absence of dedicated neonatal devices.