Interventions for treatment of neonatal hyperglycemia in very low birth weight infants.
BACKGROUND
Early neonatal hyperglycemia is common among very low birth weight (VLBW) neonates. Increased risks for death and major morbidities have been observed among VLBW neonates who develop hyperglycemia. It is uncertain whether the hyperglycemia per se is a cause of adverse clinical outcomes or whether the incidence of adverse outcomes can be reduced by treatment.


OBJECTIVE
To assess the effects on clinical outcomes of interventions for treating neonatal hyperglycemia in the VLBW neonate receiving total or partial parenteral nutrition.


METHODS
We searched The Cochrane Central Register of Controlled Trials (CENTRAL), The Cochrane Library, Issue 3, 2008; MEDLINE (1966 - July 2008); EMBASE (1980 - July 2008); and CINAHL (1982 - July 2008). We searched for abstracts submitted for the annual meetings of The Society for Pediatric Research 2000 - 2008 and The European Society for Paediatric Research 2005-2007.


METHODS
Randomized or quasi-randomized trials of interventions for the treatment of hyperglycemia in hyperglycemic VLBW neonates were eligible for inclusion in this review.


METHODS
Two review authors independently selected studies for eligibility and extracted data on study design, methodology, clinical features, and treatment outcomes. Additional information on study design and outcomes was obtained from the lead investigator of each of the two included trials. The included trials were assessed for blinding of randomization, blinding of caretakers to the intervention, completeness of follow-up, and blinding of outcome measurement. The treatment effect measures for categorical outcomes were relative risk (RR) and risk difference (RD) with their 95% confidence intervals (CI); for continuous outcomes the measure was mean difference and 95% CI.


RESULTS
Only two eligible trials were found (Collins 1991; Meetze 1998). Both were randomized but of very small size (24 and 23 neonates randomized in each trial, respectively).No trial compared reduction vs. no reduction of glucose infusion.Collins 1991 compared insulin infusion with standard care. Insulin infusion had no significant effect on death or bacterial sepsis; effects on other major morbidities were not assessed. Insulin infusion resulted in significant increases in non-protein energy intake, glucose intake, and short-term weight gain.Meetze 1998 compared insulin infusion with reduction of glucose infusion. Insulin infusion had no significant effects on death, severe intraventricular hemorrhage, retinopathy of prematurity, bacterial sepsis, fungal sepsis, or necrotizing enterocolitis; effects on other major morbidities were not assessed. Insulin infusion resulted in significant increases in glucose intake and total energy intake.


CONCLUSIONS
Evidence from randomized trials in hyperglycemic VLBW neonates is insufficient to determine the effects of treatment on death or major morbidities. It remains uncertain whether the hyperglycemia per se is a cause of adverse clinical outcomes or how the hyperglycemia should be treated. Much larger randomized trials in hyperglycemic VLBW neonates that are powered on clinical outcomes are needed in order to determine whether, and how, the hyperglycemia should be treated.
Bottino
Marcela
M
Division of Neonatology, Instituto Fernandes Figueira, Avenida Rui Barbosa 716, Flamengo, Rio de Janeiro, Brazil, 22250-020. mabottino@hotmail.com
Cowett
Richard M
RM
Sinclair
John C
JC
D005947:Glucose / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D006943:Hyperglycemia / Q000150:complications / Q000188:drug therapy*; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007231:Infant, Newborn; D007235:Infant, Premature, Diseases / Q000188:drug therapy; D019102:Infant, Very Low Birth Weight; D007328:Insulin / Q000627:therapeutic use*; D010288:Parenteral Nutrition; D016032:Randomized Controlled Trials as Topic
D007004:Hypoglycemic Agents; D007328:Insulin; D005947:Glucose