Tight glycemic control not beneficial for premature infants

Share this article:

The benefits of tight glycemic control may not outweigh the risks among premature infants with hyperglycemia, clinical trial results indicate.

Infants who were randomly assigned to intensive glycemic control (target blood glucose 4 to 6 mmol/L) experienced slower linear growth and had a higher risk for hypoglycemia compared with preterm neonates treated to a more standard 8 to 10 mmol/L target, without improved survival or morbidity, Jane M. Alsweiler, MBChB, PhD, of the University of Auckland, New Zealand, and colleagues found.

"Insulin may not be a safe and effective treatment in hyperglycemic preterm neonates," the researchers wrote in Pediatrics.

Hyperglycemia is a common outcome among preterm infants weighing less than 1,500 g (3 lbs. 5 oz.), and is associated with poorer survival rates and other risks, including retinopathy of prematurity.

Although treating hyperglycemic premature infants with insulin is common, there is little evidence available to support this practice in the neonatal intensive care unit (NICU). Currently, the American College of Physicians recommends against tight glycemic control in adult ICU patients due to concerns about hypoglycemia risks without mortality benefit.

To weigh the risks and benefits in the neonatal population, Alsweiler and colleagues randomly assigned 88 infants born before 30 weeks' gestation or who weighed less than 1,500 g, who had hyperglycemia, to either tight glycemic control (target blood glucose 4-5 mmol/L using insulin) or standard glycemic control (8-10 mmol/L with restrictive guidelines for starting insulin). Study researchers were not blinded to group assignment.

Although two-thirds of the control group were eventually treated with insulin, total mean and daily insulin doses were higher in the tight glycemic control group. Mean differences in blood glucose levels between groups was 2.4 mmol/L while on insulin, and 0.7 mmol/L overall.

For the primary endpoint of lower leg length, a measure of linear growth, children in the tight glycemic control group grew less than those in the standard care group (adjusted P<0.05), but the groups did not significantly differ at what would have been 36 weeks' gestation (109 vs. 111 mm, adjusted P=0.43).

Overall weight gain and increased head circumference were greater among the tight glycemic control group compared with the standard care group (adjusted P<0.001 and P<0.0005), but the groups did not differ at 36 weeks' postmenstrual age.

Although greater head circumference could mean better neurodevelopment, the researchers noted this benefit would have to outweigh neurodevelopmental disabilities that occur with increased hypoglycemia. But hypoglycemia was more common among the tight gylcemic control group -- 58% fell below 2.6 mmol/L blood glucose during the trial compared with 27% in the usual care group (adjusted P<0.01). Recurrent hypoglycemia rates were also higher among the tight glycemic control group -- 16% vs. 4% (adjusted P=0.11).

"Tight glycemic control with insulin in hyperglycemic preterm infants increases weight gain and head growth, but at the expense of reduced linear growth and increased risk of hypoglycemia," the researchers wrote. "The balance of risks and benefits of insulin treatment in hyperglycemic preterm neonates remains uncertain."

Outcomes were similar among both groups for secondary endpoints, including sepsis (P=0.28), necrotizing entercolitis (P=0.67), intraventricular hemorrhage (P=0.35), retinopathy of prematurity requiring treatment (P=0.20), days on mechanical ventilation (P=0.77), days to full enteral feeds (P=0.75) and days to discharge (P=0.89).

Study limitations included the unblinded nature of the intervention. Furthermore, the study did not use subcutaneous glucose monitors, which could make tighter glycemic control safer and result in less hypoglycemia in the future, the researchers noted.

Alsweiler JM et al. Pediatrics. 2012; 129: 639-647; doi:10.1542/peds.2011-2470.

Share this article:
You must be a registered member of Clinical Advisor to post a comment.

More in Web Exclusives

Antimicrobials commonly prescribed for acute respiratory tract infections

Antimicrobials commonly prescribed for acute respiratory tract infections

Antimicrobial agents were prescribed in 56.9% of acute respiratory tract infections encounters, representing an estimated 11.4 million potentially preventable antimicrobial prescriptions.

HPV knowledge doesn't predict vaccine compliance

HPV knowledge doesn't predict vaccine compliance

After surveying low-income communities, researchers found that human papillomavirus knowledge did not sway vaccination compliance.

Poverty linked to increased respiratory-related hospitalizations

Poverty linked to increased respiratory-related hospitalizations

Low income patients had nearly three times the odds of hospitalization compared with high income patients.