Hyperglycemia neonatal

hipoglucemia neonatal

1. NEONATAL HYPERGLYCEMIA
·INTRODUCTION
·PARENTERAL GLUCOSE
·DEFINITION
·Glucosuria
·PATHOGENESIS
·CAUSES
·High rates of glucose infusion
·Prematurity
·Stress
·Sepsis
·Drugs
·Neonatal diabetes mellitus
·- Transient
·- Permanent
·MANAGEMENT
·Insulin therapy
·- Routine early insulin therapy
·- Amino acid infusion
·- Risk of hypoglycemia
·- Dose
·- Adherence of insulin to plastic tubing
·- Monitoring
·Our approach
·SUMMARY AND RECOMMENDATIONS
·REFERENCES
Authors
See Wai Chan, MD, MPH
Ann R Stark, MD
Section Editors
Steven A Abrams, MD
Joseph I Wolfsdorf, MB, BCh
Deputy Editor
Melanie S Kim, MD
Disclosures
Last literature review version 19.3: Fri Sep 30 00:00:00 GMT 2011 | This topic last
updated: Mon Sep 12 00:00:00 GMT 2011 (More)
INTRODUCTION — Glucose supply and metabolism are of central importance for
growth and normal brain development in the fetus and newborn. Disorders in glucose
supply or metabolism can result in hypoglycemia or hyperglycemia. Hyperglycemia in
the neonatal period is reviewed here. Neonatal hypoglycemia is discussed separately.
(See "Neonatal hypoglycemia".)
PARENTERAL GLUCOSE — Most infants who are preterm or ill require parenteral
administration of glucose because adequate enteral feeding is delayed. Neonatal
hyperglycemia often occurs in this setting.

2. Immediately after birth, sufficient glucose is provided to avoid hypoglycemia, typically
at a rate of 5 to 8 mg/kg per minute. As an example, administration of 10 percent
dextrose solution at 100 mL/kg per day provides glucose at a rate of 7 mg/kg per
minute. Although dextrose is a hydrated form of glucose and is 91 percent glucose, the
correction usually is not applied in clinical practice.
The glucose infusion rate is increased to approximately 11 to 12 mg/kg per minute in
the first two to three days after birth to provide calories for growth. In general, glucose
infusion rates >15 mg/kg per minute are avoided, as this exceeds the ability of most
infants to oxidize glucose and may promote excessive lipogenesis. (See "Parenteral
nutrition in premature infants", section on 'Glucose'.)
DEFINITION — The definition of hyperglycemia is uncertain. It is often defined as
blood glucose >125 mg/dL (6.9 mmol/L) or plasma glucose >150 mg/dL (8.3 mmol/L).
These glucose levels are frequently observed during glucose infusions in newborns,
especially in extremely preterm infants, and may not require intervention [1].
Plasma osmolality increases by 1 mosmol/L for each 18 mg/dL increase in plasma
glucose concentration. Thus, a rise in glucose concentration from 110 to 200 mg/dL (6.1
to 11.1 mmol/L) only increases osmolality by 5 mosmol/L, which is a relatively small
change. More marked hyperglycemia is required to produce the osmotic diuresis and
hyperosmolality that may be clinically important. Most neonatologists become
concerned about hyperglycemia when the blood glucose concentration exceeds
approximately 180 to 200 mg/dL (10 to 11.1 mmol/L).
Glucosuria — Glucose excretion in the urine in hyperglycemic neonates is determined
by the degree of hyperglycemia and renal tubular reabsorptive capacity for glucose.
Newborns have variable reabsorptive capacity for glucose, which may be particularly
reduced in those who are ill or premature.
The net effect is that glucosuria alone is not a good marker for hyperglycemia since it
can occur at normal blood glucose concentrations. In one study of sick preterm infants
25 to 33 weeks gestation, for example, fractional glucose excretion varied widely and
glucosuria was often seen at normal blood glucose concentrations [2]. These variations
presumably are related to immaturity of the proximal tubule.
On the other hand, mild hyperglycemia may be associated with little or no glucosuria in
infants with mature proximal tubules. This was illustrated in a study of newborns who
were given glucose infusions; at a mean blood glucose concentration of 197 mg/dL (11
mmol/L), there was little glucosuria and no significant osmotic diuresis [3].
PATHOGENESIS — Hyperglycemia typically occurs when a newborn cannot adapt to
parenteral glucose infusion by decreasing endogenous glucose production or increasing
peripheral glucose uptake [ 4 ]. This is usually related to an associated clinical condition .
Hyperglycemia is more common in preterm than in term infants, although the
mechanism is uncertain. Glucose production rate and regulation are comparable in
moderately preterm and term infants. In both [4]:

3. ·Hepatic glucose production is suppressed by infusion of glucose (with or
without amino acids), hyperglycemia, and insulin.
·Glucose production is not changed by intravenous lipid infusion.
·Circulating insulin concentrations increase appropriately with hyperglycemia
and increase hepatic and peripheral glucose uptake.
However, insulin responses may be inappropriate in extremely low birth weight
(ELBW) infants. In one study, 23 of 56 ELBW infants became hyperglycemic during
intravenous glucose infusions that were incrementally increased to a maximum rate of
12 mg/kg per minute between days two and six of age [5]. Baseline insulin levels were
similar in hyperglycemic and euglycemic infants, but only 15 of 23 hyperglycemic
infants had a normal insulin response.
The inappropriate insulin response in hyperglycemic ELBW infants may be related to
defective islet beta cell processing of proinsulin. In a study comparing 15
hyperglycemic to 12 normoglycemic ELBW infants during the first week of life,
proinsulin levels were significantly higher in the hyperglycemic ELBW infants, who
also needed higher insulin levels to reach euglycemia compared to normoglycemic
infants [6].
Suppression of hepatic glucose production in response to glucose infusion also varies in
very immature infants and may be incomplete. In a series of 10 infants born at 25 to 30
weeks gestation, glucose production rates decreased from 4.3 to 1.4 mg/kg per minute
as glucose infusion was increased from 1.7 to 6.5 mg/kg per minute [7]. Plasma
concentrations of glucose and insulin also increased.
What remains unclear is why the same degree of glucose infusion produces variable
elevations in blood glucose in newborns. A possible contributing factor is increased
secretion of counterregulatory hormones associated with stress (particularly epinephrine
and cortisol). (See "Physiologic response to hypoglycemia in normal subjects and
patients with diabetes mellitus", section on 'Response to hypoglycemia in normal
subjects'.)
The role of stress was demonstrated in a report of metabolic responses to glucose
infusion in preterm infants (weight 700 to 1550 g) [8]. Measurements were made before
and after infusion in controls and in infants who required assisted ventilation and were
considered stressed. Stressed infants had higher levels of glucose and cortisol compared
to controls and were more likely to have hyperglycemia (13 of 18 versus 1 of 12
infants). This difference was not due to decreased insulin or increased cortisol levels,
because, among the stressed infants, insulin levels were higher and cortisol levels lower
in the hyperglycemic compared to euglycemic newborns.
CAUSES — In general, neonatal hyperglycemia is associated with a clinical condition,
rather than a specific disorder of glucose metabolism, and occurs in infants receiving
intravenous glucose infusions. A rare cause of hyperglycemia is neonatal diabetes
mellitus.
High rates of glucose infusion — Administration of 10 percent dextrose solution to
meet maintenance fluid requirements in the first few days after birth typically results in
glucose infusion rates of approximately 5 to 8 mg/kg per minute. Rates that exceed 10

4. to 12 mg/kg per minute (in infants who do not have hyperinsulinemic hypoglycemia)
may result in hyperglycemia, particularly in ELBW infants [5].
Prematurity — Hyperglycemia during glucose infusion is common in premature infants,
especially very low birth weight (VLBW) infants (birth weights below 1500 g). In a
prospective study of continuous glucose monitoring of 188 VLBW infants during the
first week of life, 80 percent of patients had glucose levels greater than 8 mmol/L (144
mg/dL), and a third had glucose levels greater than 10 mmol/L (180 mg/dL) for more
than 10 percent of the time [9]. Risk factors associated with hyperglycemia included
increasing prematurity, small for gestational age, use of inotropic agents, lipid infusions,
and sepsis. Other studies also demonstrate an increased risk of hyperglycemia with
decreasing gestational age [10-12].
ELBW infants frequently develop hyperglycemia in the absence of high rates of glucose
infusion [13]. Proposed underlying mechanisms include reduced insulin secretion,
incomplete suppression of hepatic glucose production, and stress response resulting in
counter hormone regulation.
Several studies have found that hyperglycemia in extremely premature infants
(gestational age less than 27 weeks) is associated with an increased risk of mortality
[10,11,14]. However, one study from a single NICU reported that hyperglycemia
(defined as a glucose level >150 mg/dL [8.3 mmol/L] on two separate occasions) was
not associated with death. Differences in study results may be due to lack of consensus
in defining hyperglycemia and the number of episodes and duration of hyperglycemia
[15].
Further research is needed to provide a better understanding of the consequences of
hyperglycemia and determine which infants require therapy. (See 'Definition' above and
'Insulin therapy' below.)
In one report of 93 ELBW infants cared for at a single tertiary unit, persistent
hyperglycemia during the first week of life, defined as plasma glucose >150 mg/dL (8.3
mmol/L), was associated with an increased risk of early death and severe (grade III and
IV) intraventricular hemorrhage by 10 days of life [14].
Stress — The stress response to critical illness (epinephrine and cortisol) may result in
hyperglycemia, especially in preterm infants who require mechanical ventilation. The
stress response also may be responsible for hyperglycemia occurring after surgery. In
this setting, increased rates of fluid administration may also contribute.
Sepsis — Hyperglycemia may be a presenting sign of sepsis in an infant with
previously normal blood glucose concentrations and no change in glucose infusion rate.
Potential mechanisms include the stress response, decreased insulin release, and reduced
peripheral utilization of glucose [16].
Drugs — Administration of certain drugs can result in hyperglycemia. Hyperglycemia
is a common complication of glucocorticoid therapy, especially in ELBW infants [17].
It also has been noted following phenytoin administration; the mechanism may be
suppression of insulin release or insulin insensitivity [18]. Plasma glucose levels

5. increase slightly following theophylline administration in preterm infants, but the effect
is not clinically significant [19].
Neonatal diabetes mellitus — Neonatal diabetes is a rare cause of hyperglycemia, with
an estimated incidence of one in 500,000 births [20]. It is defined as persistent
hyperglycemia occurring in the first months of life that lasts more than two weeks and
requires insulin for management. The majority of infants are small for gestational age,
which may be related to decreased insulin secretion in the fetus [4]. They present with
weight loss, volume depletion, hyperglycemia, and glucosuria with or without ketonuria
and ketoacidosis.
Neonatal diabetes is caused by mutations in a number of genes that encode proteins that
play a critical role in the normal function of the pancreatic beta-cell such as proteins that
are subunits in the ATP-sensitive potassium channel [21]. The course of neonatal
diabetes is variable depending on the affected gene. Genetic mutations of the KIR6.2
subunit of the ATP-sensitive potassium channel can result in permanent neonatal
diabetes mellitus, whereas mutations of the SUR1 subunit can result in either permanent
or transient neonatal disease. In a series of 57 infants presenting before one month of
age with hyperglycemia requiring insulin therapy for more than two weeks, the disorder
was transient in 18, transient with recurrence between seven and 20 years of age in 13,
and permanent in 26 [20].
Transient — Either paternal uniparental disomy of chromosome 6 or an unbalanced
duplication of paternal chromosome 6 is present in the majority of cases of transient
neonatal diabetes [22-26]. Mutations of the imprinting gene ZAC/PLAG1, a
transcriptional regulator of the type 1 receptor for pituitary adenylate cyclase-activating
polypeptide, (an important regulator of insulin secretion), at chromosome 6q24 has been
shown to be the major cause of neonatal transient DM [23-26].
Activating mutations of the ABCC8 gene that encodes SUR1, the type 1 subunit of the
sulfonylurea receptor, can cause either transient or permanent neonatal diabetes as
discussed in the next section.
Permanent — About one-half of patients with neonatal diabetes mellitus have a
permanent form that is primarily due to gene mutations related to the ATP-sensitive
potassium channel. In rare cases, permanent neonatal diabetes mellitus is due to
pancreatic agenesis or hypoplasia. In one case series of four patients with
developmental failure of the pancreas, who were products of a consanguineous kinship,
a specific gene defect was not identified [27].
Most patients with permanent neonatal diabetes mellitus have mutations that affect the
ATP-sensitive potassium channel (KATP channel), which regulates the release of
insulin from pancreatic beta cells. Activating mutations increase the number of open
KATP channels at the plasma membrane, hyperpolarizing the beta cells, and preventing
the release of insulin.
In contrast, inactivating mutations, described in children with persistent
hyperinsulinemic hypoglycemia of infancy, reduce the number of open KATP channels,
resulting in depolarization of the beta cells and persistent hypersecretion of insulin [28].

6. (See "Pathogenesis, clinical features, and diagnosis of persistent hyperinsulinemic
hypoglycemia of infancy".)
The KATP channel is composed of a small subunit Kir6.2 that surrounds a central pore
and four regulatory SUR1 subunits. Activating gene mutations that affect these subunits
can prevent insulin release, resulting in hyperglycemia.
·KCNJ11 gene encoding Kir6.2 — The most common cause of permanent
neonatal diabetes is due to activating mutations in the KCNJ11 gene, which
encodes Kir6.2 [29-31]. The diagnosis is made within the first two months of
life [29]. Infants are small for gestational age but exhibit postnatal catch-up
growth with insulin therapy [32]. Affected patients can also have neurologic
abnormalities including severe developmental delay, epilepsy, muscle weakness,
and dysmorphic features [29]. These findings are also known as the DEND
syndrome (developmental delay, epilepsy, neonatal diabetes) [33].
Subcutaneous insulin was routinely used in the past to treat patients with this
disorder. However, oral sulfonylurea therapy appears to be more effective in
controlling hyperglycemia [34,35]. In a study of 49 patients with neonatal
diabetes due to activating mutations of KCNJ11 gene, 44 were able to
discontinue insulin therapy after starting oral sulfonylurea therapy [34]. In
patients switched to sulfonylurea therapy, insulin secretion and glycated
hemoglobin (8.1 to 6.4 percent) improved.
·SUR1 — Activating mutations of the ABCC8 gene, which encodes SUR1 (the
type 1 subunit of the sulfonylurea receptor), can cause both transient and
permanent forms of neonatal diabetes. In a series of 73 patients with neonatal
diabetes, nine had activating mutations of the ABCC8 gene [36]. Two had
permanent diabetes and the others had transient diabetes. The patients were
diagnosed at a median of 32 days (range 3 to 125 days). Oral sulfonylurea
therapy normalized glycemic control in patients with genetic mutations of
SUR1.
Neonatal diabetes mellitus has also been associated with mutations in other genes
including RfX6, IPF-1, EIF2AK3, GCK, FOXP3, PTF1A, GLIS3, and the Ins2 genes
[37-54]. In some cases, these mutations result in pancreatic agenesis or hypoplasia, or
absent beta cells. As an example, patients with permanent neonatal diabetes mellitus due
to Wolcott-Rallison syndrome (diabetes mellitus, exocrine pancreatic insufficiency, and
multiple epiphyseal dysplasia) have been shown to have hypoplastic pancreatic islets
and a mutation in the EIF2AK3 gene that encodes translation initiation factor 2-alpha
kinase 3 [43,44]. FOXP3 mutations cause a rare, x-linked disorder that presents in
infancy with autoimmune endocrinopathy, enteropathy, and eczema. (See "IPEX:
Immune dysregulation, polyendocrinopathy, enteropathy, X-linked".)
MANAGEMENT — Interventions to reduce the blood glucose concentration are
initiated at values above 180 to 200 mg/dL (10 to 11.1 mmol/L). The first step in
management is to decrease the glucose infusion rate. Reducing the rate to 4 to 6 mg/kg
per minute usually lowers the blood glucose concentration. In most cases, this is
accomplished by reducing the concentration of the dextrose solution from 10 to 5
percent. If provided with parenteral nutrition solution and lipid emulsion, infants can

7. maintain normoglycemia with the reduced glucose supply by gluconeogenesis from
glycerol and amino acids [55].
However, reducing the glucose infusion rate is a short-term solution because it results in
decreased caloric intake and compromises growth. Glucose tolerance typically improves
when enteral feedings are established. (See "Nutritional composition of human milk and
preterm formula for the premature infant".)
Insulin therapy — Insulin improves glucose tolerance, allows provision of more
calories, and promotes growth in infants who remain hyperglycemic at reduced glucose
infusion rates. The exact indications for insulin therapy are not well defined. Most
neonatologists would begin an insulin infusion in infants with persistent hyperglycemia
(>200 to 250 mg/dL [11.1 to 13.9 mmol/L]) despite reductions in glucose infusion rate,
and in infants who fail to thrive because of reduced caloric intake.
The efficacy of insulin therapy was illustrated by a study of 24 ELBW infants with
glucose intolerance who were randomly assigned to receive standard intravenous
therapy with glucose and total parenteral nutrition with or without a continuous insulin
infusion [56]. Over a mean duration of 15 days, insulin therapy resulted in significantly
higher glucose infusion rates (20.1 versus 13.2 mg/kg per min), greater nonprotein
energy intake (124 versus 86 kcal/kg per day), and greater weight gain (20.1 versus 7.8
g/kg per day) compared to control. There were no differences between groups in
hypoglycemia, electrolyte abnormalities, chronic lung disease, or mortality.
Benefit from insulin therapy was also demonstrated in a trial of 23 ELBW infants who
became hyperglycemic while receiving glucose at a rate up to 12 mg/kg per min [5].
The infants were randomly assigned to reduced glucose intake or to insulin infusion.
The duration of caloric intake less than 60 kcal/kg per day was significantly shorter with
the insulin infusion (4.1 versus 8.6 days). There were no differences in morbidity or
mortality between the two groups.
In infants receiving parenteral nutrition, improvement in glucose tolerance by
continuous insulin infusion appears to be comparable with and without the addition of
lipid emulsion [57].
Routine early insulin therapy — The routine use of early insulin therapy in premature
infants has been proposed to prevent catabolism, improve glucose control, and increase
energy intake, which might improve growth. However, early insulin therapy does not
appear to improve growth and may be associated with an increased risk of mortality at
28 days of age and hypoglycemia.
This was illustrated in a multicenter, open-label trial of 389 very low birth weight
(VLBW) infants (birth weights <1500 g) who were randomly selected to receive either
standard care for glycemic control or a parenteral infusion of 20 percent dextrose with
early insulin therapy (0.05 U/Kg per hour) starting within 24 hours of birth until seven
days of age [58]. The following findings were noted:
·The early insulin group had lower mean glucose levels compared to the standard
care group (112 vs 121 mg/dL [6.2 vs 6.7 mmol/L]), were less likely to be
hyperglycemic (defined as serum glucose greater than 180 mg/dL [10 mmol/L])

8. for more than 10 percent of the first week of life (21 versus 33 percent), were
able to receive greater amounts of glucose infusion (51 versus 43 kcal/kg per
day), and had less weight loss during the first week of life.
·More patients who received early insulin had episodes of hypoglycemia (29
versus 17 percent), which was defined as serum glucose levels less than 47
mg/dL (2.6 mmol/L) for more than one hour.
·There were no differences between the groups in the primary end point of
mortality at the expected date of delivery or in the secondary end points of
sepsis, necrotizing enterocolitis, retinopathy of prematurity, and growth
parameters (ie, weight, length, and head circumference) at 28 days of age.
However, the early insulin group had a higher mortality rate at 28 days of life.
This trial was ended early because of concerns of futility with regard to outcomes and
concern for potential harm from insulin therapy. Follow-up is ongoing to determine
whether the increased incidence of hypoglycemia in the early insulin group had a
detrimental effect on neurodevelopmental outcomes. (See "Neonatal hypoglycemia",
section on 'Neurodevelopmental outcome'.)
Based upon these data, routine insulin therapy should NOT be used in VLBW infants.
Insulin should, however, be used to treat hyperglycemia when reducing the glucose
infusion rate to approximately 6 mg/kg per minute is ineffective or not possible.
Amino acid infusion — Insulin infusion during euglycemia reduces proteolysis and
protein synthesis in preterm infants who are not also given amino acids. In a report of
four ELBW infants at two to five days of age, whole body proteolysis and protein
synthesis decreased by 20 percent during a continuous infusion of insulin (0.05 units/kg
per hour) and glucose (without amino acids) [59]. Glucose utilization doubled (8 to 16.7
mg/kg per min) but there was no net anabolic effect. In addition, plasma lactate
concentration tripled (2.1 to 5.7 mmol/L), possibly because the high rate of glucose
infusion exceeded the maximal capacity for glucose oxidation. Whether administration
of amino acids during insulin infusion would further reduce proteolysis or increase
protein synthesis and improve protein balance is uncertain.
Based upon the limited current data, we suggest amino acid solution and lipid emulsion
also should be administered to infants receiving glucose infusion to provide substrate
for gluconeogenesis, spare glucose utilization, and stimulate insulin release.
Risk of hypoglycemia — The blood glucose concentration should be monitored
frequently during insulin infusion, although the risk of hypoglycemia appears to be
small. This was documented in a retrospective review of 34 ELBW infants who
developed hyperglycemia and glucosuria while receiving parenteral nutrition and were
treated with insulin [60]. Before therapy, mean blood glucose concentration was 195
mg/dL (11.1 mmol/L) while receiving glucose at a mean rate of 7.9 mg/kg per min.
During insulin infusion, given for 1 to 58 days, blood glucose values of 25 to 40 mg/dL
(1.4 to 2.2 mmol/L) were detected in fewer than 0.5 percent of samples (26 episodes of
hypoglycemia in 7368 samples) and no values <25 mg/dL were seen.
Similar findings were noted in another study of 10 ELBW infants treated with insulin
[61]. Glucose measurements were normal (46 to 130 mg/dL [2.6 to 7.2 mmol/L]) in 78

9. percent of samples and less than 24 mg/dL (1.3 mmol/L) in less than 1 percent [61].
(See "Neonatal hypoglycemia".)
Dose — Regular insulin (100 U/mL) is usually diluted in normal saline to a
concentration of 0.1 U/mL. In some centers, concentration of 0.5 untits/mL is used.
The initial step in management of a persistently elevated glucose level is administering
a bolus insulin infusion via a syringe pump over 15 minutes at a dose between 0.05 and
0.1 units/kg. The blood glucose level is monitored every 30 to 60 minutes, and if it
remains elevated, the insulin dose is repeated as a bolus every four to six hours. If the
glucose level remains elevated after three bolus doses, a continuous infusion is
considered at an initial rate of between 0.01 and 0.05 units/kg per hour and is adjusted
in small increments up to a maximum rate 0.1 units/kg per hour to maintain glucose
levels of 150 to 200 mg/dL (8.3 to 11 mmol/L).
As glucose tolerance improves, the insulin infusion should be tapered and discontinued
to avoid hypoglycemia. In general, reductions in the insulin infusion rate can be made
more rapidly than can increases.
Adherence of insulin to plastic tubing — Plastic tubing used for infusion should be
primed with insulin for at least 20 minutes before treatment because insulin
nonspecifically binds to the tubing, resulting in decreased availability to the patient. In
one report, recovery of insulin from effluent of primed polyvinyl chloride tubing at a
flow rate of 0.2 mL/h was greater at one, two, four, and eight hours (42, 85, 91, and 95
versus 22, 38, 67, and 75 percent, respectively) compared to unprimed tubing [62].
Monitoring — The blood glucose concentration should be monitored within 30 minutes
to one hour of the start of the infusion and after any change in the rate of glucose or
insulin infusion. Glucose concentration should be monitored hourly until stable, and
then less frequently.
Our approach — Blood glucose concentration should be monitored in all infants
receiving intravenous glucose infusions. For most infants, daily monitoring is
recommended until blood glucose concentration is stable. For ELBW, stressed, or septic
infants, or those receiving insulin infusion, more frequent monitoring is needed.
·In infants with blood glucose concentration greater than 180 to 200 mg/dL (10 to
11.1 mmol/L), the glucose infusion rate should be decreased; this should be
done by decreasing the concentration of infused glucose, as long as it does not
go below 5 percent.
·Insulin therapy should be considered in neonates with persistent hyperglycemia
(blood glucose >200 to 250 mg/dL [11.1 to 13.9 mmol/L]) despite reductions in
glucose infusion rate, and in infants who fail to thrive because of reduced caloric
intake. Therapy is initially administered as a bolus of insulin administered via a
syringe pump over 15 minutes as a dose between 0.05 and 0.1 units/kg.
Continuous insulin infusion should be considered in infants with persistent
hyperglycemia (blood glucose >200 to 250 mg/dL [11.1 to 13.9 mmol/L])
despite reductions in glucose infusion rate and after administering three insulin
boluses. Infusion begins at a rate between 0.01 to 0.05 units/kg per hour and is

10. adjusted in small increments up to a maximum rate of 0.1 units/kg per hour to
maintain blood glucose levels between 150 to 200 mg/dL. (See 'Insulin
therapy' above.)
·Enteral feedings should be initiated as soon as possible in order to wean and
discontinue parenteral nutrition.
SUMMARY AND RECOMMENDATIONS — Increased blood glucose levels (>125
mg/dL [6.9 mmol/L) are often seen in neonates, especially in preterm infants who
receive glucose infusions as parenteral nutrition. With marked hyperglycemia defined as
glucose concentration exceeding 180 mg/dL (10 mmol/L), there is a marked increase in
plasma osmolality resulting in osmotic diuresis and potential cellular injury due to
significant fluid shifts. (See "Parenteral nutrition in premature infants", section on
'Glucose'.)
·Although the mechanisms are uncertain, it is speculated that the increased risk of
hyperglycemia in preterm infants compared with term infants is due to poorer
insulin response, incomplete suppression of hepatic glucose production, and
increased secretions of counterregulatory hormones associated with stress. (See
'Pathogenesis' above.)
·In general, neonatal hyperglycemia is caused by the administration of parenteral
glucose, especially in very low birth weight infants (birth weight below 1500 g).
Other contributing conditions include stress response to critical illness, sepsis,
and drugs associated with hyperglycemia, such as phenytoin and theophylline.
Rarely is neonatal hyperglycemia due to neonatal diabetes mellitus, which is
caused by mutations in genes that encode for proteins that are involved with
insulin release from the pancreatic beta-cell. (See 'Causes' above.)
·Blood glucose concentration should be monitored in all infants receiving
intravenous glucose infusions. For most infants, daily monitoring is
recommended until blood glucose concentration is stable. More frequent
monitoring is recommended for extremely low birth weight infants (birth weight
<1000 g), stressed, or septic infants, or those receiving insulin infusion. (See
'Management' above.)
·In our practice, we use the following stepwise management approach for
neonates whose blood glucose exceeds 180 to 200 mg/dL (10 to 11.1 mmol/L).
(See 'Our approach' above.)
·In neonates receiving parenteral glucose infusion, the glucose infusion rate
should be reduced by decreasing the concentration of infused glucose, as long as
it does not go below 5 percent.
·Insulin therapy should be considered in neonates with persistent hyperglycemia
(blood glucose >200 to 250 mg/dL [11.1 to 13.9 mmol/L]) despite reductions in
glucose infusion rate and in infants who fail to thrive because of reduced caloric
intake. Therapy is initially administered as a bolus of insulin administered via a
syringe pump over 15 minutes as a dose between 0.05 and 0.1 unit/kg.
·Continuous insulin infusion should be considered in infants with persistent
hyperglycemia (blood glucose >200 to 250 mg/dL [11.1 to 13.9 mmol/L])
despite reductions in glucose infusion rate and administration of three insulin
boluses. Infusion begins at a rate between 0.01 and 0.05 unit/kg per hour and is
adjusted in small increments up to a maximum rate of 0.1 units/kg per hour to
maintain blood glucose level between 150 and 200 mg/dL (8.3 to 11.1 mmol/L).

11. ·Initiate enteral feeds as soon as possible.
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