In a randomized study of hyperglycemic preterm infants, they found that tight glycemic control with insulin increased weight gain and head growth but at the expense of reduced linear growth and increased risk of hypoglycemia.
Insulin therapy has become widespread in neonatal nurseries, with some units targeting tight glycemic control despite a lack of data to support the practice or indicate an optimal glycemic range, the study team notes.
In an email to Reuters Health, Dr. Jane M. Alsweiler, from Newborn Services, Auckland City Hospital noted that, “While tight control of blood glucose concentrations in the normal range has been shown to be beneficial in diabetics, our study has shown that this approach in hyperglycaemic preterm babies decreases the rate of growth for length despite increased weight and head circumference growth and increases the risk of low blood glucose concentrations, which is potentially detrimental. This suggests that tight glycaemic control might not be beneficial in preterm babies and also raises questions about whether insulin should be used at all in preterm babies,” she wrote.
The investigators enrolled in their study 88 infants born at <30 weeks’ gestation or <1500 g who developed hyperglycemia (blood glucose concentration >8.5 mmol/L on two separate occasions four hours apart).
They randomly assigned 43 infants to tight glycemic control targeting a BGC of 4-6 mmol/L and 45 to a control group (target BGC 8-10 mmol/L). All but one infant in the “tight” group and two-thirds of infants in the control group (n=29) were treated with insulin. Age at randomization was 4 days and 5 days in these two groups, respectively. Nutritional intakes were similar in the two groups.
The researchers report that from randomization to 36 weeks’ postmenstrual age, infants in the tight group had a lesser lower leg growth rate (p<.05) but greater head circumference growth (p<.0005) and greater weight gain (p<.001) compared to infants in the control group.
The researchers note that by 6 weeks of age, adjusted leg length was 8% less and adjusted weight was 4% greater in infants in the tight group compared to infants in the control group. At 36 weeks’ PMA there were no between-group differences in weight, length or head circumference. However, the decrease in z score for head circumference from birth to 36 weeks’ PMA was 0.5 SD less in the tight group.
The researchers say it’s unclear why infants in the tight group had slower linear growth. It could be that the greater weight gain in these infants was primarily due to an increase in fat mass rather than muscle mass or bone growth.
“This is of concern,” they say, “because preterm infants have a higher proportion of intra-abdominal adipose tissue at term-corrected age and insulin resistance in childhood and young adulthood. Our data suggest that insulin treatment to maintain tight glycemic control in preterm infants may further aggravate their cardiovascular risk in later life.”
Of added concern is the fact that twice as many infants in the tight group as in the control group experienced at least one episode of hypoglycemia (25 vs 12). Recurrent episodes were also more common in the tight group. There were no significant differences in mortality or neonatal morbidity in the two groups.
The researchers conclude, “The balance of risks and benefits of insulin treatment in hyperglycemic preterm neonates remains uncertain.” Dr. Alsweiler told Reuters Health a larger trial is planned to “to investigate whether insulin treatment in hyperglycaemic preterm babies improves outcomes at 2 years of age.”