Devices to continuously monitor sugar (glucose) levels in the blood in newborns born preterm

Review questions:

1) What are the benefits and harms of the use of subcutaneous (under the skin) sensors for continuous glucose monitoring (CGM) with or without an algorithm to correct too high or too low ​​​​​​ levels of blood glucose versus intermittent modalities to measure blood glucose with or without an algorithm to correct too high or too low ​​​​​​ levels in preterm infants?

2) What are the benefits and harms of the use of of CGM associated with an algorithm to correct too high or too low ​​​​​​ levels of blood glucose versus CGM without an algorithm to correct too high or too low ​​​​​​ levels of blood glucose in preterm infants?

Background

Newborns born too early ("preterm") are susceptible to levels of blood glucose that are too high or too low . Most preterm babies with these abnormal concentrations may make a full recovery, or may have only mild problems. For some preterm babies with extremely high or low (or more prolonged) levels of glucose, this may lead to death or to problems later in life.

The aim of this review was to assess whether the use of CGM could improve the long-term development, or reduce mortality in preterm newborns. CGM devices are inserted subcutaneously, and provide data on glucose levels in real time. The standard method of measuring glucose levels consists of withdrawing small amounts of the baby's blood or performing frequent heel pricks. 

Study characteristics
We collected and analyzed all relevant studies to answer the review question, and found four studies enrolling 138 babies. Three of those studies compared the use of CGM to intermittent modalities, and one study evaluated CGM combined with an algorithm versus CGM as a standalone tool to correct low and high glucose levels.

Key results

None of the four included studies reported on the long-term neurodevelopmental outcome of preterm infants. The studies were too small to determine if use of CGM has an effect on survival. The number of low blood glucose episodes was reported in two studies with conflicting data.  Three studies are ongoing. Further research is needed.

Certainty of evidence:

The certainty of evidence was very low due to the overall limited number of studies, with few babies enrolled.

How up-to-date is this review?

We searched for studies that were available up to 25 September 2020. 

Authors' conclusions: 

There is insufficient evidence to determine if CGM improves preterm infant mortality or morbidities. Long-term outcomes were not 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 CGM  for 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. 

Read the full abstract...
Background: 

Preterm infants are susceptible to hyperglycemia and hypoglycemia, 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 use of CGM might be associated with harms in the preterm infant.

Objectives: 

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.

Search strategy: 

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 25 September 2020); Embase (1980 to 25 September 2020); and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to 25 September 2020). We also searched clinical trials databases, conference proceedings, and reference lists of retrieved articles for randomized controlled trials and quasi-randomized trials.

Selection criteria: 

Randomized controlled trials (RCTs) and quasi-RCTs in preterm infants comparing: 1) the use of CGM versus intermittent modalities to measure glycemia (comparison 1); or CGM associated with prespecified interventions to correct hypoglycemia or hyperglycemia versus CGM without such prespecified interventions (comparison 2).

Data collection and analysis: 

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.

Main results: 

Four trials enrolling 138 infants met our inclusion criteria. Investigators in three trials (118 infants) compared the use of CGM to intermittent modalities (comparison one); however one of these trials was analyzed separately because CGM was used as a standalone device, without being coupled to a control algorithm like in the other trials. A fourth trial (20 infants) 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 to 70.30; typical RD 0.04, 95% CI -0.06 to 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 -2.84 to 0.04; 50 participants; 1 study). The certainty of the evidence was very low for all outcomes because of limitations in study design, and imprecision of estimates. 

Three studies are ongoing.