Beardsall, Kathryn, Thomson, Lynn, Guy, Catherine, Bond, Simon, Allison, Annabel, Pantaleo, Beatrice, Petrou, Stavros, Kim, Sungwook, Dunger, David and Hovorka, Roman (2021) Continuous glucose monitoring in extremely preterm infants in intensive care : the REACT RCT and pilot study of ‘closed-loop’ technology. Efficacy and Mechanism Evaluation, 8 (16). pp. 1-142. doi:10.3310/eme08160

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Abstract

Background: Hyperglycaemia and hypoglycaemia are common in preterm infants and are associated with increased mortality and morbidity. Continuous glucose monitoring is widely used to target glucose control in adults and children, but not in neonates.
Objective: To evaluate the role of continuous glucose monitoring in the preterm infant.
Design: The REAl-time Continuous glucose moniToring in neonatal intensive care project combined (1) a feasibility study, (2) a multicentre randomised controlled trial and (3) a pilot of ‘closed-loop’ continuous glucose monitoring. The feasibility study comprised a single-centre study (n = 20). Eligibility criteria included a birthweight ≤ 1200 g and aged ≤ 48 hours. Continuous glucose monitoring was initiated to support glucose control. The efficacy and safety outcomes guided the design of the randomised controlled trial. The randomised controlled trial comprised a European multicentre trial (n = 182). Eligibility criteria included birthweight ≤ 1200 g and aged ≤ 24 hours. Exclusion criteria included any lethal congenital abnormality. Continuous glucose monitoring was initiated to support glucose control within 24 hours of birth. In the intervention group, the continuous glucose monitoring sensor provided real-time data on glucose levels, which guided clinical management. In control infants, the continuous glucose monitoring data were masked, and glucose level was managed in accordance with standard clinical practice and based on the blood glucose levels. The primary outcome measure was the percentage of time during which the sensor glucose level was within the target range of 2.6–10 mmol/l. Secondary outcome measures included mean sensor glucose level, the percentage of time during which the sensor glucose level was within the target range of 4–8 mmol/l, the percentage of time during which the sensor glucose level was in the hyperglycaemic range (i.e. > 15 mmol/l) and sensor glucose level variability. Safety outcomes included hypoglycaemia exposure. Acceptability assessment and health economic analyses were carried out and further exploratory health outcomes were explored. The mean percentage of time in glucose target range of 2.6–10 mmol/l was 9% higher in infants in the continuous glucose monitoring group (95% confidence interval 3% to 14%; p = 0.002), and the mean time in the target range of 4–8 mmol/l was 12% higher in this group (95% confidence interval 4% to 19%; p = 0.004). There was no difference in the number of episodes of hypoglycaemia. Exploratory outcomes showed a reduced risk of necrotising enterocolitis in the intervention arm (odds ratio 0.33, 95% confidence interval 0.13 to 0.78; p = 0.01). Health economic analyses demonstrated that continuous glucose monitoring was cost-effective on the basis of the cost per additional case of adequate glucose control between 2.6 and 10 mmol/l. The ‘closed-loop’ study was a single-center pilot study, with eligibility criteria including a birthweight of ≤ 1200 g and aged ≤ 48 hours. Infants underwent continuous glucose monitoring for the first week of life (n = 21), with those in the intervention group receiving closed-loop insulin delivery between 48 and 72 hours of age. The primary outcome of percentage of time in the target range (i.e. sensor glucose 4–8 mmol/l) increased from a median of 26% (interquartile range 6–64%) to 91% (interquartile range 78–99%) during closed-loop insulin delivery (p < 0.001).
Limitations: These studies have not defined the optimal targets for glucose control or the best strategies to achieve them in these infants.
Future work: Studies are needed to evaluate the longer-term impact of targeting glucose control on clinical outcomes.
Conclusions: Continuous glucose monitoring in extremely preterm infants can improve glucose control, with closed-loop insulin delivery having further potential to target glucose levels. Staff and parents felt that the use of continuous glucose monitoring improved care and the results of the health economic evaluation favours the use of continuous glucose monitoring.
Trial registration: Current Controlled Trials ISRCTN12793535.
Funding: This project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a MRC and National Institute for Health Research (NIHR) partnership. This will be published in full in Efficacy and Mechanism Evaluation; Vol. 8, No. 16. See the NIHR Journals Library website for further project information. Medtronic plc provided some MiniMed™ 640G systems and Nova Biomedical (Waltham, MA, USA) provided point-of-care devices.

Item Type:	Journal Article
Subjects:	R Medicine > RJ Pediatrics
Divisions:	Faculty of Medicine > Warwick Medical School
SWORD Depositor:	Library Publications Router
Library of Congress Subject Headings (LCSH):	Hypoglycemia in newborn infants, Blood sugar monitoring, Blood sugar -- Analysis
Journal or Publication Title:	Efficacy and Mechanism Evaluation
Publisher:	NIHR Journals Library
ISSN:	2050-4365
Official Date:	October 2021
Dates:	Date Event October 2021 Published
Volume:	8
Number:	16
Page Range:	pp. 1-142
DOI:	10.3310/eme08160
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open Access
RIOXX Funder/Project Grant:	Project/Grant ID RIOXX Funder Name Funder ID UNSPECIFIED Efficacy and Mechanism Evaluation programme http://dx.doi.org/10.13039/501100001922 UNSPECIFIED [MRC] Medical Research Council http://dx.doi.org/10.13039/501100000265 UNSPECIFIED [NIHR] National Institute for Health Research http://dx.doi.org/10.13039/501100000272

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