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Operational Thresholds in Neonatal Hypoglycemia

Am Fam Physician. 2000 Nov 15;62(10):2322-2324.

The level and duration of neonatal hypoglycemia that is associated with acute or long-term effects is uncertain, making it difficult to define a particular level of hypoglycemia at which intervention is required. Cornblath and associates provide a consensus statement based on neonatal hypoglycemia research data.

Glucose is the main fuel used by the brain, but research has shown that neonates are able to use ketone bodies, lactate and maybe amino acids for oxidation. This makes the significance of a particular blood glucose level somewhat uncertain. The definition of neonatal hypoglycemia has been based on the following approaches (or combination of approaches): clinical symptoms (see Table 1), epidemiologic approach based on a range of glucose values, acute changes in metabolic and endocrine response and their neurologic sequelae, or an approach that only takes into account long-term neurologic sequelae. Plasma glucose concentration in the neonate is approximately 60 to 80 percent of the maternal venous glucose level. A steady-state level occurs by approximately three hours after birth. Many factors can contribute to derangements in this physiology, ranging from congenital problems to intrapartum clinical management of the mother.

TABLE 1

Clinical Signs Associated with Hypoglycemia*

Changes in levels of consciousness

Irritability

Lethargy

Stupor

Apnea, cyanotic spells

Coma

Feeding poorly after feeding well

Hypothermia

Hypotonia, limpness

Tremor

Seizures


*—Clinical signs should be alleviated with concomitant correction of plasma glucose levels.

Reprinted with permission from Cornblath M, Hawdon JM, Williams AF, Aynsley-Green A, Ward-Platt MP, Schwartz R, et al. Controversies regarding definition of neonatal hypoglycemia: suggested operational thresholds. Pediatrics 2000;105:1142.

TABLE 1   Clinical Signs Associated with Hypoglycemia*

View Table

TABLE 1

Clinical Signs Associated with Hypoglycemia*

Changes in levels of consciousness

Irritability

Lethargy

Stupor

Apnea, cyanotic spells

Coma

Feeding poorly after feeding well

Hypothermia

Hypotonia, limpness

Tremor

Seizures


*—Clinical signs should be alleviated with concomitant correction of plasma glucose levels.

Reprinted with permission from Cornblath M, Hawdon JM, Williams AF, Aynsley-Green A, Ward-Platt MP, Schwartz R, et al. Controversies regarding definition of neonatal hypoglycemia: suggested operational thresholds. Pediatrics 2000;105:1142.

From the available literature, the authors attempted to determine intervention guidelines based on the neonatal blood glucose level. The authors determined that no one level should always prompt intervention, and no consensus was reached on what duration of hypoglycemia is associated with adverse sequelae. However, they developed some guidelines for physicians who are treating neonates.

In the full-term, asymptomatic healthy infant, there is no need to routinely measure blood glucose levels. Only if the infant is known to be at risk (see Table 2) does the level need to be monitored. In an infant with clinical findings, a blood glucose less than 45 mg per dL (2.5 mmol per L) is considered abnormal, and steps should be taken to increase the blood glucose level. In addition, underlying causes for the hypoglycemia should be sought. In infants with risk factors, a blood glucose level should be measured right after birth, again within the next two to three hours, before feeding and whenever abnormal signs exist. An infant with a level less than 36 mg per dL (2.0 mmol per L) requires close monitoring. If the infant has a blood glucose level less than 20 to 25 mg per dL (1.1 to 1.4 mmol per L), treatment with intravenous glucose should be initiated with a target level of 45 mg per dL (2.5 mmol per L). In cases of rare persistent hyperinsulinemic hypoglycemia, a target level of 60 mg per dL (3.3 mmol per L) may be more appropriate.

TABLE 2

At-Risk Infants and Blood Glucose Monitoring

A. Associated with changes in maternal metabolism

1. Intrapartum administration of glucose

2. Drug treatment

a. Terbutaline, ritodrine, propranolol

b. Oral hypoglycemic agents

3. Diabetes in pregnancy/infant of diabetic mother

B. Associated with neonatal problems

1. Idiopathic condition or failure to adapt

2. Perinatal hypoxia-ischemia

3. Infection

4. Hypothermia

5. Hyperviscosity

6. Erythroblastosis fetalis, fetal hydrops

7. Other

a. Iatrogenic causes

b. Congenital cardiac malformations

C. Intrauterine growth restriction

D. Hyperinsulinism

E. Endocrine disorders

F. Inborn errors of metabolism


Reprinted with permission from Cornblath M, Hawdon JM, Williams AF, Aynsley-Green A, Ward-Platt MP, Schwartz R, et al. Controversies regarding definition of neonatal hypoglycemia: suggested operational thresholds. Pediatrics 2000;105:1143.

TABLE 2   At-Risk Infants and Blood Glucose Monitoring

View Table

TABLE 2

At-Risk Infants and Blood Glucose Monitoring

A. Associated with changes in maternal metabolism

1. Intrapartum administration of glucose

2. Drug treatment

a. Terbutaline, ritodrine, propranolol

b. Oral hypoglycemic agents

3. Diabetes in pregnancy/infant of diabetic mother

B. Associated with neonatal problems

1. Idiopathic condition or failure to adapt

2. Perinatal hypoxia-ischemia

3. Infection

4. Hypothermia

5. Hyperviscosity

6. Erythroblastosis fetalis, fetal hydrops

7. Other

a. Iatrogenic causes

b. Congenital cardiac malformations

C. Intrauterine growth restriction

D. Hyperinsulinism

E. Endocrine disorders

F. Inborn errors of metabolism


Reprinted with permission from Cornblath M, Hawdon JM, Williams AF, Aynsley-Green A, Ward-Platt MP, Schwartz R, et al. Controversies regarding definition of neonatal hypoglycemia: suggested operational thresholds. Pediatrics 2000;105:1143.

It has been suggested that preterm infants should have a lowered operational threshold for hypoglycemia; the authors find no evidence that hypoglycemia in the preterm infant is associated with more long-term abnormalities. However, one study reported a decrease in math and motor scores up to eight years after birth in premature infants with hypoglycemia. Results from another study revealed a correlation between hypoglycemia and abnormal intellectual performance at 18 months of age. A cutoff value of 47 mg per dL (2.6 mmol per L) is probably reasonable. Finally, infants receiving parenteral nutrition may have higher levels of insulin, so blood sugar levels should probably be maintained at higher levels (i.e., at least 45 mg per dL).

The authors conclude that many questions remain about the effects of hypoglycemia on neonates, although some guidelines can be reasonably derived from currently available literature.

Cornblath M, et al. Controversies regarding definition of neonatal hypoglycemia: suggested operational thresholds. Pediatrics. May 2000;105:1141–5.


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