Lower versus Traditional Treatment Threshold for Neonatal Hypoglycemia.
Blood Glucose
/ analysis
Child Development
/ drug effects
Enteral Nutrition
Glucose
/ administration & dosage
Humans
Hypoglycemia
/ blood
Infant Nutritional Physiological Phenomena
Infant, Newborn
Infant, Newborn, Diseases
/ blood
Infusions, Intravenous
Psychomotor Disorders
/ prevention & control
Reference Values
Journal
The New England journal of medicine
ISSN: 1533-4406
Titre abrégé: N Engl J Med
Pays: United States
ID NLM: 0255562
Informations de publication
Date de publication:
06 02 2020
06 02 2020
Historique:
entrez:
6
2
2020
pubmed:
6
2
2020
medline:
19
2
2020
Statut:
ppublish
Résumé
Worldwide, many newborns who are preterm, small or large for gestational age, or born to mothers with diabetes are screened for hypoglycemia, with a goal of preventing brain injury. However, there is no consensus on a treatment threshold that is safe but also avoids overtreatment. In a multicenter, randomized, noninferiority trial involving 689 otherwise healthy newborns born at 35 weeks of gestation or later and identified as being at risk for hypoglycemia, we compared two threshold values for treatment of asymptomatic moderate hypoglycemia. We sought to determine whether a management strategy that used a lower threshold (treatment administered at a glucose concentration of <36 mg per deciliter [2.0 mmol per liter]) would be noninferior to a traditional threshold (treatment at a glucose concentration of <47 mg per deciliter [2.6 mmol per liter]) with respect to psychomotor development at 18 months, assessed with the Bayley Scales of Infant and Toddler Development, third edition, Dutch version (Bayley-III-NL; scores range from 50 to 150 [mean {±SD}, 100±15]), with higher scores indicating more advanced development and 7.5 points (one half the SD) representing a clinically important difference). The lower threshold would be considered noninferior if scores were less than 7.5 points lower than scores in the traditional-threshold group. Bayley-III-NL scores were assessed in 287 of the 348 children (82.5%) in the lower-threshold group and in 295 of the 341 children (86.5%) in the traditional-threshold group. Cognitive and motor outcome scores were similar in the two groups (mean scores [±SE], 102.9±0.7 [cognitive] and 104.6±0.7 [motor] in the lower-threshold group and 102.2±0.7 [cognitive] and 104.9±0.7 [motor] in the traditional-threshold group). The prespecified inferiority limit was not crossed. The mean glucose concentration was 57±0.4 mg per deciliter (3.2±0.02 mmol per liter) in the lower-threshold group and 61±0.5 mg per deciliter (3.4±0.03 mmol per liter) in the traditional-threshold group. Fewer and less severe hypoglycemic episodes occurred in the traditional-threshold group, but that group had more invasive diagnostic and treatment interventions. Serious adverse events in the lower-threshold group included convulsions (during normoglycemia) in one newborn and one death. In otherwise healthy newborns with asymptomatic moderate hypoglycemia, a lower glucose treatment threshold (36 mg per deciliter) was noninferior to a traditional threshold (47 mg per deciliter) with regard to psychomotor development at 18 months. (Funded by the Netherlands Organization for Health Research and Development; HypoEXIT Current Controlled Trials number, ISRCTN79705768.).
Sections du résumé
BACKGROUND
Worldwide, many newborns who are preterm, small or large for gestational age, or born to mothers with diabetes are screened for hypoglycemia, with a goal of preventing brain injury. However, there is no consensus on a treatment threshold that is safe but also avoids overtreatment.
METHODS
In a multicenter, randomized, noninferiority trial involving 689 otherwise healthy newborns born at 35 weeks of gestation or later and identified as being at risk for hypoglycemia, we compared two threshold values for treatment of asymptomatic moderate hypoglycemia. We sought to determine whether a management strategy that used a lower threshold (treatment administered at a glucose concentration of <36 mg per deciliter [2.0 mmol per liter]) would be noninferior to a traditional threshold (treatment at a glucose concentration of <47 mg per deciliter [2.6 mmol per liter]) with respect to psychomotor development at 18 months, assessed with the Bayley Scales of Infant and Toddler Development, third edition, Dutch version (Bayley-III-NL; scores range from 50 to 150 [mean {±SD}, 100±15]), with higher scores indicating more advanced development and 7.5 points (one half the SD) representing a clinically important difference). The lower threshold would be considered noninferior if scores were less than 7.5 points lower than scores in the traditional-threshold group.
RESULTS
Bayley-III-NL scores were assessed in 287 of the 348 children (82.5%) in the lower-threshold group and in 295 of the 341 children (86.5%) in the traditional-threshold group. Cognitive and motor outcome scores were similar in the two groups (mean scores [±SE], 102.9±0.7 [cognitive] and 104.6±0.7 [motor] in the lower-threshold group and 102.2±0.7 [cognitive] and 104.9±0.7 [motor] in the traditional-threshold group). The prespecified inferiority limit was not crossed. The mean glucose concentration was 57±0.4 mg per deciliter (3.2±0.02 mmol per liter) in the lower-threshold group and 61±0.5 mg per deciliter (3.4±0.03 mmol per liter) in the traditional-threshold group. Fewer and less severe hypoglycemic episodes occurred in the traditional-threshold group, but that group had more invasive diagnostic and treatment interventions. Serious adverse events in the lower-threshold group included convulsions (during normoglycemia) in one newborn and one death.
CONCLUSIONS
In otherwise healthy newborns with asymptomatic moderate hypoglycemia, a lower glucose treatment threshold (36 mg per deciliter) was noninferior to a traditional threshold (47 mg per deciliter) with regard to psychomotor development at 18 months. (Funded by the Netherlands Organization for Health Research and Development; HypoEXIT Current Controlled Trials number, ISRCTN79705768.).
Identifiants
pubmed: 32023373
doi: 10.1056/NEJMoa1905593
doi:
Substances chimiques
Blood Glucose
0
Glucose
IY9XDZ35W2
Banques de données
ISRCTN
['ISRCTN79705768']
Types de publication
Comparative Study
Equivalence Trial
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
534-544Subventions
Organisme : ZonMw
ID : Project number 94507406
Pays : International
Investigateurs
Anne A M W van Kempen
(AAMW)
Nicole Boluyt
(N)
Joke H Kok
(JH)
Martin Offringa
(M)
Johanna H van der Lee
(JH)
Lea M Dijksman
(LM)
Nicole R van Veenendaal
(NR)
Ben A Semmekrot
(BA)
Anneloes L van Baar
(AL)
Marcel G W Dijkgraaf
(MGW)
Harrie N Lafeber
(HN)
Joris A M van der Post
(JAM)
P Frank Eskes
(PF)
Debbie H G M Nuytemans
(DHGM)
Flip J P C M van der Hulst
(FJPCM)
Rob M J Moonen
(RMJ)
Han J M J Sijstermans
(HJMJ)
Luc J I Zimmermann
(LJI)
Pieter L J M Degraeuwe
(PLJM)
Ellen Van't Verlaat
(E)
Johannes B van Goudoever
(JB)
Minouche van Dongen-van Baal
(M)
Hélène G Stas
(HG)
Ron H T van Beek
(RHT)
José J Vlietman
(JJ)
Petra A van Setten
(PA)
Peter H Dijk
(PH)
Jacqueline U M Termote
(JUM)
Sophie R D van der Schoor
(SRD)
H Carlijn Kraakman
(HC)
Rogier C J de Jonge
(RCJ)
Amerik C de Mol
(AC)
Marianne W A Huysman
(MWA)
Commentaires et corrections
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Informations de copyright
Copyright © 2020 Massachusetts Medical Society.