DOI: 10.1542/peds.2010-3851
2011;127;575-579; originally published online Feb 28, 2011; Pediatrics
Committee on Fetus and Newborn
Postnatal Glucose Homeostasis in Late-Preterm and Term Infants
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Clinical Report—Postnatal Glucose Homeostasis in
Late-Preterm and Term Infants
abstract
This report provides a practical guide and algorithm for the screening
and subsequent management of neonatal hypoglycemia. Current evi-
dence does not support a specific concentration of glucose that can
discriminate normal from abnormal or can potentially result in acute
or chronic irreversible neurologic damage. Early identification of the
at-risk infant and institution of prophylactic measures to prevent neo-
natal hypoglycemia are recommended as a pragmatic approach de-
spite the absence of a consistent definition of hypoglycemia in the
literature. Pediatrics 2011;127:575–579
INTRODUCTION
This clinical report provides a practical guide for the screening and
subsequentmanagement of neonatal hypoglycemia (NH) in at-risk late-
preterm (34–366⁄7 weeks’ gestational age) and term infants. An expert
panel convened by the National Institutes of Health in 2008 concluded
that there has been no substantial evidence-based progress in defining
what constitutes clinically important NH, particularly regarding how it
relates to brain injury, and that monitoring for, preventing, and treat-
ing NH remain largely empirical.1 In addition, the simultaneous occur-
rence of othermedical conditions that are associatedwith brain injury,
such as hypoxia-ischemia or infection, could alone, or in concert with
NH, adversely affect the brain.2–5 For these reasons, this report does
not identify any specific value or range of plasma glucose concentra-
tions that potentially could result in brain injury. Instead, it is a prag-
matic approach to a controversial issue for which evidence is lacking
but guidance is needed.
BACKGROUND
Blood glucose concentrations as low as 30 mg/dL are common in
healthy neonates by 1 to 2 hours after birth; these low concentrations,
seen in all mammalian newborns, usually are transient, asymptomatic,
and considered to be part of normal adaptation to postnatal life.6–8
Most neonates compensate for “physiologic” hypoglycemia by produc-
ing alternative fuels including ketone bodies, which are released from
fat.
Clinically significant NH reflects an imbalance between supply and use
of glucose and alternative fuels and may result from a multitude of
disturbed regulatory mechanisms. A rational definition of NH must
account for the fact that acute symptoms and long-term neurologic
sequelae occur within a continuum of low plasma glucose values of
varied duration and severity.
David H. Adamkin, MD and COMMITTEE ON FETUS AND
NEWBORN
KEY WORDS
newborn, glucose, neonatal hypoglycemia, late-preterm infant
ABBREVIATIONS
NH—neonatal hypoglycemia
D10W—dextrose 10% in water
This document is copyrighted and is property of the American
Academy of Pediatrics and its Board of Directors. All authors
have filed conflict of interest statements with the American
Academy of Pediatrics. Any conflicts have been resolved through
a process approved by the Board of Directors. The American
Academy of Pediatrics has neither solicited nor accepted any
commercial involvement in the development of the content of
this publication.
The guidance in this report does not indicate an exclusive
course of treatment or serve as a standard of medical care.
Variations, taking into account individual circumstances, may be
appropriate.
www.pediatrics.org/cgi/doi/10.1542/peds.2010-3851
doi:10.1542/peds.2010-3851
All clinical reports from the American Academy of Pediatrics
automatically expire 5 years after publication unless reaffirmed,
revised, or retired at or before that time.
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).
Copyright © 2011 by the American Academy of Pediatrics
FROM THE AMERICAN ACADEMY OF PEDIATRICS
Guidance for the Clinician in
Rendering Pediatric Care
PEDIATRICS Volume 127, Number 3, March 2011 575
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The authors of several literature re-
views have concluded that there is not
a specific plasma glucose concentra-
tion or duration of hypoglycemia that
can predict permanent neurologic in-
jury in high-risk infants.3,9,10 Data that
have linked plasma glucose concentra-
tionwith adverse long-termneurologic
outcomes are confounded by variable
definitions of hypoglycemia and its du-
ration (seldom reported), the omis-
sion of control groups, the possible in-
clusion of infants with confounding
conditions, and the small number of
asymptomatic infants who were fol-
lowed.3,11,12 In addition, there is no sin-
gle concentration or range of plasma
glucose concentrations that is associ-
ated with clinical signs. Therefore,
there is no consensus regarding when
screening should be performed and
which concentration of glucose re-
quires therapeutic intervention in the
asymptomatic infant. The generally
adopted plasma glucose concentra-
tion that defines NH for all infants
(�47 mg/dL) is without rigorous sci-
entific justification.1,3,4,9,12
WHICH INFANTS TO SCREEN
Because plasma glucose homeostasis
requires glucogenesis and ketogene-
sis to maintain normal rates of fuel
use,13 NH most commonly occurs in in-
fants with impaired glucogenesis
and/or ketogenesis,14,15 which may oc-
cur with excessive insulin production,
altered counterregulatory hormone
production, an inadequate substrate
supply,14–16 or a disorder of fatty acid
oxidation.15 NH occurs most commonly
in infants who are small for gesta-
tional age, infants born to mothers
who have diabetes, and late-preterm
infants. It remains controversial
whether otherwise normal infants
who are large for gestational age are
at risk of NH, largely because it is diffi-
cult to exclude maternal diabetes or
maternal hyperglycemia (prediabe-
tes) with standard glucose-tolerance
tests.
A large number of additional maternal
and fetal conditions may also place in-
fants at risk of NH. Clinical signs are
common with these conditions, and it
is likely that patients with such a con-
dition are already being monitored
and that plasma glucose analyses are
being performed.13,17 Therefore, for
practicality, “at risk” in the manage-
ment approach outlined in Fig 1 in-
cludes only infants who are small for
gestational age, infants who are large
for gestational age, infants who were
born to mothers who have diabetes,
and late-preterm infants. Routine
screening andmonitoring of blood glu-
cose concentration is not needed in
healthy term newborn infants after an
entirely normal pregnancy and deliv-
ery. Blood glucose concentration
should only be measured in term in-
fants who have clinical manifestations
or who are known to be at risk. Plasma
or blood glucose concentration should
bemeasured as soon as possible (min-
utes, not hours) in any infant whoman-
ifests clinical signs (see “Clinical
Signs”) compatible with a low blood
glucose concentration (ie, the symp-
tomatic infant).
Breastfed term infants have lower con-
centrations of plasma glucose but
higher concentrations of ketone bodies
than do formula-fed infants.13,17 It is pos-
tulated that breastfed infants tolerate
lower plasma glucose concentrations
withoutanyclinicalmanifestationsorse-
quelae of NH because of the increased
ketone concentrations.8,12–14
WHEN TO SCREEN
Neonatal glucose concentrations de-
crease after birth, to as low as 30
mg/dL during the first 1 to 2 hours af-
ter birth, and then increase to higher
and relatively more stable concentra-
tions, generally above 45 mg/dL by 12
hours after birth.6,7 Data on the optimal
timing and intervals for glucose
screening are limited. It is controver-
sial whether to screen the asymptom-
atic at-risk infant for NH during this
FIGURE 1
Screening for and management of postnatal glucose homeostasis in late-preterm (LPT 34–366⁄7
weeks) and term small-for-gestational age (SGA) infants and infants who were born to mothers with
diabetes (IDM)/large-for-gestational age (LGA) infants. LPT and SGA (screen 0–24 hours), IDM and LGA
�34 weeks (screen 0–12 hours). IV indicates intravenous.
576 FROM THE AMERICAN ACADEMY OF PEDIATRICS
by on March 1, 2011 www.pediatrics.orgDownloaded from
normal physiologic nadir. No studies
have demonstrated harm from a few
hours of asymptomatic hypoglycemia
during this normal postnatal period
of establishing “physiologic glucose
homeostasis.”9
Infants born to mothers with diabetes
may develop asymptomatic NH as early
as 1 hour after birth18 and usually by 12
hours of age.18 In contrast, infants who
are large for gestational age or small
for gestational age may develop low
plasma glucose concentrations at as
early as 3 hours of age,19 and these
infantsmay be at risk of NH for up to 10
days after birth.20 Therefore, at-risk in-
fants should be screened for NH with a
frequency and duration related to risk
factors specific to the individual in-
fant.5 Screening the asymptomatic at-
risk infant can be performed within
the first hours of birth and continued
throughmultiple feed-fast cycles. Late-
preterm infants and infants who are
small for gestational age should be fed
every 2 to 3 hours and screened before
each feeding for at least the first 24
hours. After 24 hours, repeated
screening before feedings should be
continued if plasma glucose concen-
trations remain lower than 45 mg/dL.
LABORATORY DATA
When NH is suspected, the plasma or
blood glucose concentration must be
determined immediately by using one
of the laboratory enzymatic methods
(eg, glucose oxidase, hexokinase, or
dehydrogenase method). Plasma
blood glucose values tend to be ap-
proximately 10% to 18% higher than
whole-blood values because of the
higher water content of plasma.21,22
Although a laboratory determination is
the most accurate method of measur-
ing the glucose concentration, the re-
sults may not be available quickly
enough for rapid diagnosis of NH,
which thereby delays the initiation of
treatment.23 Bedside reagent test-strip
glucose analyzers can be used if the
test is performed carefully and the cli-
nician is aware of the limited accuracy
of these devices. Rapid measurement
methods available at the bedside in-
clude the handheld reflectance color-
imeter and electrode methods. The
blood sample is usually obtained from
a warmed heel.
Test-strip results demonstrate a rea-
sonable correlation with actual
plasma glucose concentrations, but
the variation from the actual level may
be as much as 10 to 20 mg/dL.24–27 Un-
fortunately, this variation is greatest
at low glucose concentrations. There is
no point-of-care method that is suffi-
ciently reliable and accurate in the low
range of blood glucose to allow it to be
used as the sole method for screening
for NH.
Because of limitations with “rapid”
bedside methods, the blood or plasma
glucose concentration must be con-
firmed by laboratory testing ordered
stat. A long delay in processing the
specimen can result in a falsely low
concentration as erythrocytes in the
sample metabolize the glucose in the
plasma. This problem can be avoided
by transporting the blood in tubes that
contain a glycolytic inhibitor such as
fluoride.
Screening of the at-risk infant for NH and
institution of prophylactic measures to
prevent prolonged or symptomatic NH is
a reasonable goal. Treatment of sus-
pected NH should not be postponed
while waiting for laboratory confirma-
tion. However, there is no evidence to
show that such rapid treatment will mit-
igate neurologic sequelae.
CLINICAL SIGNS
The clinical signs of NH are not specific
and include a wide range of local or
generalized manifestations that are
common in sick neonates.12,13,17 These
signs include jitteriness, cyanosis, sei-
zures, apneic episodes, tachypnea,
weak or high-pitched cry, floppiness or
lethargy, poor feeding, and eye-rolling.
It is important to screen for other pos-
sible underlying disorders (eg, infec-
tion) as well as hypoglycemia. Such
signs usually subside quickly with nor-
malization of glucose supply and
plasma concentration.9,13 Coma and
seizures may occur with prolonged NH
(plasma or blood glucose concentra-
tions lower than 10 mg/dL range) and
repetitive hypoglycemia. The more se-
rious signs (eg, seizure activity) usu-
ally occur late in severe and pro-
tracted cases of hypoglycemia and are
not easily or rapidly reversed with glu-
cose replacement and normalization
of plasma glucose concentrations.28–30
Development of clinical signs may be
ameliorated by the presence of alter-
native substrates.31
Because avoidance and treatment of
cerebral energy deficiency is the prin-
cipal concern, greatest attention
should be paid to neurologic signs. To
attribute signs and symptoms to NH,
Cornblath et al12 have suggested that
the Whipple triad be fulfilled: (1) a low
blood glucose concentration; (2) signs
consistent with NH; and (3) resolution
of signs and symptoms after restoring
blood glucose concentrations to nor-
mal values.12
MANAGEMENT
Any approach tomanagement needs to
account for the overall metabolic and
physiologic status of the infant and
should not unnecessarily disrupt the
mother-infant relationship and breast-
feeding. The definition of a plasma glu-
cose concentration at which interven-
tion is indicated needs to be tailored to
the clinical situation and the particular
characteristics of a given infant. For
example, further investigation and im-
mediate intravenous glucose treat-
ment might be instituted for an infant
with clinical signs and a plasma glu-
cose concentration of less than 40 mg/
FROM THE AMERICAN ACADEMY OF PEDIATRICS
PEDIATRICS Volume 127, Number 3, March 2011 577
by on March 1, 2011 www.pediatrics.orgDownloaded from
dL, whereas an at-risk but asymptom-
atic term formula-fed infant may only
require an increased frequency of
feeding and would receive intravenous
glucose only if the glucose values de-
creased to less than 25 mg/dL (birth to
4 hours of age) or 35 mg/dL (4–24
hours of age).32 Follow-up glucose con-
centrations and clinical evaluation
must always be obtained to ensure
that postnatal glucose homeostasis is
achieved and maintained.
Because severe, prolonged, symptom-
atic hypoglycemia may result in neuro-
nal injury,27,28,32 prompt intervention is
necessary for infants who manifest
clinical signs and symptoms. A reason-
able (although arbitrary) cutoff for
treating symptomatic infants is 40mg/
dL. This value is higher than the physi-
ologic nadir and higher than concen-
trations usually associated with
clinical signs. A plasma sample for a
laboratory glucose determination
needs to be obtained just before giving
an intravenous “minibolus” of glucose
(200mg of glucose per kg, 2mL/kg dex-
trose 10% in water [D10W], intrave-
nously) and/or starting a continuous
infusion of glucose (D10W at 80–100
mL/kg per day). A reasonable goal is to
maintain plasma glucose concentra-
tions in symptomatic infants between
40 and 50 mg/dL.
Figure 1 is a guideline for the screen-
ing and management of NH in late-
preterm infants and term infants who
were born to mothers with diabetes,
small for gestational age, or large for
gestational age. In developing a prag-
matic approach to the asymptomatic
at-risk infant during the first 24 hours
after birth, mode of feeding, risk fac-
tors, and hours of age were consid-
ered. This strategy is based on the fol-
lowing observations from Cornblath
and Ichord13: (1) almost all infants with
proven symptomatic NH during the
first hours of life have plasma glucose
concentrations lower than 20 to 25
mg/dL; (2) persistent or recurrent NH
syndromes present with equally low
plasma glucose concentrations; and
(3) little or no evidence exists to indi-
cate that asymptomatic NH at any con-
centration of plasma glucose in the
first days of life results in any adverse
sequelae in growth or neurologic
development.13
Figure 1 is divided into 2 time periods
(birth to 4 hours and 4–12 hours) and
accounts for the changing values of
glucose that occur over the first 12
hours after birth. The recommended
values for intervention are intended to
provide a margin of safety over con-
centrations of glucose associated with
clinical signs. The intervention recom-
mendations also provide a range of
values over which the clinician can de-
cide to refeed or provide intravenous
glucose. The target glucose concentra-
tion is greater than 45 mg/dL before
each feeding. At-risk infants should be
fed by 1 hour of age and screened 30
minutes after the feeding. This recom-
mendation is consistent with that of
the World Health Organization. Gavage
feeding may be considered in infants
who are not nippling well. Glucose
screening should continue until 12
hours of age for infants born to moth-
ers with diabetes and those who are
large for gestational age and maintain
plasma glucose concentrations of
greater than 40 mg/dL. Late-preterm
infants and infants who are small for
gestational age require glucose moni-
toring for at least 24 hours after birth,
because they may be more vulnerable
to low glucose concentrations, espe-
cially if regular feedings or intrave-
nous fluids are not yet established.20 If
inadequate postnatal glucose ho-
meostasis is documented, the clinician
must be certain that the infant can
maintain normal plasma glucose con-
centrations on a routine diet for a rea-
sonably extended period (through at
least 3 feed-fast periods) before dis-
charge. It is recommended that the at-
risk asymptomatic infant who has glu-
cose concentrations of less than 25
mg/dL (birth to 4 hours of age) or less
than 35 mg/dL (4–24 hours of age) be
refed and that the glucose value be re-
checked 1 hour after refeeding. Subse-
quent concentrations lower than 25
mg/dL, or lower than 35mg/dL, respec-
tively, after attempts to refeed, neces-
sitate treatment with intravenous glu-
cose. Persistent hypoglycemia can be
treated with aminibolus (200mg/kg [2
mL/kg] D10W) and/or intravenous infu-
sion of D10W at 5 to 8mg/kg perminute,
80 to 100 mL/kg per day; the goal is to
achieve a plasma glucose concentra-
tion of 40 to 50 mg/dL (higher concen-
trations will only stimulate further in-
sulin secretion). If it is not possible to
maintain blood glucose concentra-
tions of greater than 45 mg/dL after 24
hours of using this rate of glucose in-
fusion, consideration should be given
to the possibility of hyperinsulinemic
hypoglycemia, which is the most com-
mon cause of severe persistent hypo-
glycemia in the newborn period. A
blood sample should be sent for mea-
surement of insulin along with a glu-
cose concentration at the time when a
bedside blood glucose concentration
is less than 40 mg/dL, and an endocri-
nologist should be consulted.
SUMMARY
Current evidence does not support a
specific concentration of glucose that
can discriminate euglycemia from hy-
poglycemia or can predict that acute
or chronic irreversible neurologic
damage will result. Therefore, similar
to the Canadian Paediatric Society
guidelines, a significantly low concen-
tration of glucose in plasma should be
reliably established and treated to re-
store glucose values to a normal phys-
iologic range.5 Recognizing infants at
risk of disturbances in postnatal glu-
cose homeostasis and providing a
margin of safety by early measures to
5
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