Neurodevelopmental outcome after neonatal hypoglycemia: a multi-center randomized controlled trial comparing intensive treatment versus expectant glucose monitoring in 'high risk' newborns.

Rationale: Hypoglycemia is the most common metabolic problem in neonatology: around 25% of all newborns are at risk for neonatal hypoglycemia. In the Netherlands this means that around 40.000 newborns are at risk annually. Because hypoglycemia can lead to permanent brain damage, 'high risk' infants for hypoglycemia are admitted, screened and, if necessary, treated. However, there is still much controversy about the definition of a 'safe' plasma glucose concentration. Currently used limits for hypoglycemia vary between 2.0 and 2.6 mmol/l. As a result, current clinical practice varies widely, especially for infants with 'moderate' hypoglycemia (glucose 2.0-2.5 mmol/l). This leads to both over- and under-treatment of hypoglycemic infants.

Objective: This study-protocol is directed at the comparison of two accepted management strategies at both ends of the current treatment-spectrum of moderate hypoglycemia in 'high risk' newborns: an intensive treatment versus an expectant monitoring strategy.

Study design: Multi-center randomized controlled trial.

Study population: 800 'high risk' newborn infants with moderate hypoglycemia >35 weeks gestational age and birth weight >2000 gram.

Intervention: In the intensive treatment arm the aim is to increase the glucose concentration above 2.5 mmol/l within 3 hours by increasing the carbohydrate intake by oral nutrition and/or intravenous glucose administration. In the expectant arm the aim is to maintain the glucose concentration above 1.9 mmol/l by the usual oral nutrition protocol.

Main study parameters/endpoints: Primary outcome is neurodevelopment at 18 months.

Current clinical practice varies widely, especially for infants with 'moderate' hypoglycemia, due to lack of methodological sound studies. This leads to both over- and under-treatment of hypoglycemic infants.
This study-protocol is directed at the comparison of two accepted management strategies at both ends of the current treatment-spectrum of moderate hypoglycemia in 'high risk' newborns: an intensive treatment versus an expectant monitoring strategy.

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In the intensive treatment arm the aim is to increase the glucose concentration above 2.5 mmol/l within 3 hours by increasing the carbohydrate intake by oral nutrition and/or intravenous glucose administration.
In the expectant arm the aim is to maintain the glucose concentration above 2.0 mmol/l by the usual oral nutrition protocol.