Review questions
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 (a set of mathematical rules) to correct too high or too low levels of blood glucose versus intermittent modalities to measure blood glucose with or without an algorithm to guide the correction of too high or too low blood glucose in preterm infants 1. at risk of too high or too low levels of blood glucose; 2. with proven too low levels of blood glucose; and 3. with proven too high levels of blood glucose?
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 have a full recovery, or only mild problems. For some preterm babies with extremely high or low (or more prolonged) blood glucose, this may lead to death or to problems later in life.
The aim of this updated review was to assess whether the use of CGM could improve the long-term development or reduce deaths in preterm newborns. CGM devices are inserted subcutaneously, and provide data on blood glucose in real time. The standard method of measuring blood glucose consists of measuring blood glucose concentrations intermittently by withdrawing small amounts of blood, often by heel pricks.
Study characteristics
We collected and analyzed all relevant studies to answer the review question, and found four studies enrolling 300 babies. These studies compared the use of CGM to intermittent measurements in infants at risk of too high or too low levels of blood glucose.
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 CGM has an effect on survival. One study is ongoing. Although one study published in 2021 reported the incidence of serious intestinal injury (necrotizing enterocolitis, a serious inflammation of the intestines that can be life threatening) was lower in the CGM group, this finding is very uncertain because the results were very imprecise. Further research is needed.
Quality of the evidence
The quality of the 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 1 April 2021.
There is insufficient evidence to determine if CGM affects preterm infant mortality or morbidities. We are very uncertain of the safety of CGM and the available management algorithms, and many morbidities remain unreported. Preterm infants at risk of hypoglycaemia or hyperglycaemia were enrolled in all four included studies. No studies have been conducted in preterm infants with proven hypoglycaemia or hyperglycaemia. Long-term outcomes were not reported. Events of necrotizing enterocolitis, reported in the study published in 2021, were lower in the CGM group. However, the effect of CGM on this outcome remains very uncertain. Clinical trials are required to determine the most effective CGM and glycaemic 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.
Preterm infants are susceptible to hyperglycaemia and hypoglycaemia, which may lead to adverse neurodevelopment. The use of continuous glucose monitoring (CGM) devices might help in 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.
To assess the benefits and harms of CGM versus intermittent modalities to measure glycaemia in preterm infants 1. at risk of hypoglycaemia or hyperglycaemia; 2. with proven hypoglycaemia; or 3. with proven hyperglycaemia.
We searched CENTRAL (2021, Issue 4); PubMed; Embase; and CINAHL in April 2021. We also searched clinical trials databases, conference proceedings, and reference lists of retrieved articles for randomized controlled trials (RCTs) and quasi-RCTs.
We included RCTs and quasi-RCTs comparing the use of CGM versus intermittent modalities to measure glycaemia in preterm infants at risk of hypoglycaemia or hyperglycaemia; with proven hypoglycaemia; or with proven hyperglycaemia.
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) with 95% confidence intervals (CI) 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.
We included four trials enrolling 300 infants in our updated review. We included one new study and excluded another previously included study (because the inclusion criteria of the review have been narrowed). We compared the use of CGM to intermittent modalities in preterm infants at risk of hypoglycaemia or hyperglycaemia; however, one of these trials was analyzed separately because CGM was used as a standalone device, without being coupled to a control algorithm as in the other trials. We identified no studies in preterm infants with proven hypoglycaemia or hyperglycaemia.
None of the four included trials reported the neurodevelopmental outcome (i.e. the primary outcome of this review), or seizures. The effect of the use of CGM on mortality during hospitalization is uncertain (RR 0.59, 95% CI 0.16 to 2.13; RD −0.02, 95% CI −0.07 to 0.03; 230 participants; 2 studies; very low-certainty evidence). The certainty of the evidence was very low for all outcomes because of limitations in study design, and imprecision of estimates. One study is ongoing (estimated sample size 60 infants) and planned to be completed in 2022.