Early insulin therapy in very-low-birth-weight infants.
BACKGROUND
Studies involving adults and children being treated in intensive care units indicate that insulin therapy and glucose control may influence survival. Hyperglycemia in very-low-birth-weight infants is also associated with morbidity and mortality. This international randomized, controlled trial aimed to determine whether early insulin replacement reduced hyperglycemia and affected outcomes in such neonates.


METHODS
In this multicenter trial, we assigned 195 infants to continuous infusion of insulin at a dose of 0.05 U per kilogram of body weight per hour with 20% dextrose support and 194 to standard neonatal care on days 1 to 7. The efficacy of glucose control was assessed by continuous glucose monitoring. The primary outcome was mortality at the expected date of delivery. The study was discontinued early because of concerns about futility with regard to the primary outcome and potential harm.


RESULTS
As compared with infants in the control group, infants in the early-insulin group had lower mean (+/-SD) glucose levels (6.2+/-1.4 vs. 6.7+/-2.2 mmol per liter [112+/-25 vs. 121+/-40 mg per deciliter], P=0.007). Fewer infants in the early-insulin group had hyperglycemia for more than 10% of the first week of life (21% vs. 33%, P=0.008). The early-insulin group had significantly more carbohydrate infused (51+/-13 vs. 43+/-10 kcal per kilogram per day, P<0.001) and less weight loss in the first week (standard-deviation score for change in weight, -0.55+/-0.52 vs. -0.70+/-0.47; P=0.006). More infants in the early-insulin group had episodes of hypoglycemia (defined as a blood glucose level of <2.6 mmol per liter [47 mg per deciliter] for >1 hour) (29% in the early-insulin group vs. 17% in the control group, P=0.005), and the increase in hypoglycemia was significant in infants with birth weights of more than 1 kg. There were no differences in the intention-to-treat analyses for the primary outcome (mortality at the expected date of delivery) and the secondary outcome (morbidity). In the intention-to-treat analysis, mortality at 28 days was higher in the early-insulin group than in the control group (P=0.04).


CONCLUSIONS
Early insulin therapy offers little clinical benefit in very-low-birth-weight infants. It reduces hyperglycemia but may increase hypoglycemia (Current Controlled Trials number, ISRCTN78428828.)
Beardsall
Kathryn
K
University of Cambridge, Cambridge, United Kingdom.
Vanhaesebrouck
Sophie
S
Ogilvy-Stuart
Amanda L
AL
Vanhole
Christine
C
Palmer
Christopher R
CR
van Weissenbruch
Mirjam
M
Midgley
Paula
P
Thompson
Michael
M
Thio
Marta
M
Cornette
Luc
L
Ossuetta
Iviano
I
Iglesias
Isabel
I
Theyskens
Claire
C
de Jong
Miranda
M
Ahluwalia
Jag S
JS
de Zegher
Francis
F
Dunger
David B
DB
D001786:Blood Glucose / Q000032:analysis; D016903:Drug Monitoring / Q000295:instrumentation / Q000379:methods; D005260:Female; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy*; D007003:Hypoglycemia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007226:Infant Mortality; D007231:Infant, Newborn; D019102:Infant, Very Low Birth Weight / Q000097:blood*; D007262:Infusions, Intravenous; D007328:Insulin / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D016896:Treatment Outcome
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin