Article

endocrinology

Neonatal Hypoglycemia: Are Evidence-based Clinical

Guidelines Achievable?
Jane M. Hawdon, MA,
MBBS, MRCP, FRCPCH,
PhD*

Author Disclosure
Dr Hawdon has

Educational Gaps:
1. There is a lack of evidence to inform definitive clinical guidelines for neonatal
hypoglycemia.
2. In infants who do not have risk factors for impaired or delayed neonatal metabolic
adaptation, blood glucose levels uniformly and steadily fall and then increase for the first
3 to 4 hours after birth, allowing for establishment of feedings to lead to glucose balance.

disclosed that she

speaks at and chairs

Abstract

sponsored meetings

Differing risk factors, biological variability, and lack of high-quality research studies lead
to the impossibility of genuine evidence-based clinical guidelines for neonatal hypoglycemia. However, texts to date have described a pragmatic approach that, in the absence of high-quality evidence, should be adopted. Understanding of normal physiology
should also inform practice. Blood glucose levels fall in the hours after birth in all infants.
For most, the normal process of neonatal metabolic adaptation initiates glucose release
and production, as well as the mobilization of alternative fuels (eg, ketone bodies) from
stores so that the physiologic fall in blood glucose is tolerated. However, some infants are
at risk of impaired neonatal metabolic adaptation in that blood glucose levels may not
rise and the protective metabolic responses do not occur. For these infants, it is important to prevent hypoglycemia, to recognize clinically signicant hypoglycemia, and to
manage this situation without causing unnecessary separation of mother and infant
or disruption of breastfeeding. Investigations for the underlying cause of hypoglycemia
should be performed if hypoglycemia is persistent, resistant, or unexpected.

and receives honoraria

from Chiesi
Pharmaceuticals Inc.
This commentary does
not contain a discussion
of an unapproved/
investigative use of a
commercial product/
device.

Objectives
1.
2.
3.
4.
5.

After completing this article, readers should be able to:

Understand the processes of metabolic adaptation at birth.

Appreciate that infants vary in their ability to tolerate low blood glucose levels.
Identify those infants at risk of impaired metabolic adaptation.
Understand that a single cutoff value for hypoglycemia cannot be defined.
Apply operational thresholds to the prevention and management of neonatal
hypoglycemia.

Introduction
Much debate surrounds neonatal hypoglycemia in terms of the denition of the condition,
its clinical signicance, and its optimal management. This debate exists in part because there
is a continuum between the normal postnatal metabolic changes, with a physiologic fall in
blood glucose after birth accompanied by protective metabolic responses, and the more
worrying situation in which there is delay or failure of the normal metabolic adaptation
after birth. Therefore, hypoglycemia cannot strictly be applied as a pathologic diagnostic
term, and it is preferable to consider a diagnosis of impaired metabolic adaptation. Invariably, neonatal hypoglycemia is used as a shorthand term for this condition.
For many decades, clinicians and scientists have been struggling to evaluate or even provide an evidence base for the diagnosis and management of neonatal hypoglycemia. I joined
these ranks in 1989 when I commenced a research project to investigate the processes of

*Consultant Neonatologist, Clinical Academic Group Director, Womens and Childrens Health, Barts Health NHS Trust, London,
United Kingdom.

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endocrinology

neonatal hypoglycemia

metabolic adaptation after birth. One aspect of the project was to investigate the endocrine and metabolic responses to neonatal hypoglycemia, which are described
in the following sections.
Looking back, the case selection for the project was below the standard that would be required for high-quality
research. The study sample size was larger than it should
have been as the diagnostic cutoff of 2.6 mmol/L (47
mg/dL) had found its way into use (discussed later in detail). Many infants on my arrival seemed surprisingly well
and were physically resisting all efforts to insert nasogastric
tubes and intravenous cannulae, and their condition was in
part explained by laboratory measurements that did not
conrm the diagnosis of hypoglycemia according to initial
reagent strip ndings. Other study infants were admitted
to the neonatal unit for another reason and had a blood
glucose measurement very shortly after birth or at the time
of the universal nadir. Based on this single measurement,
infants were labeled as hypoglycemic, while if left to their
own devices or with routine NICU care, their blood glucose levels would have subsequently risen.
As the study elapsed and after discussion with experts
(including Marvin Cornblath [now deceased]), it became
evident that many of these infants did not have a pathologic
condition. Rather, they were simply doing what infants do
in the process of adaptation after birth: mounting a metabolic response to a physiologic fall in blood glucose level.
Marvin and I discussed the ood of litigation that the
diagnosis of hypoglycemia had unleashed, and this occurrence has been well recognized in the United States and
United Kingdom. Marvin summed this up in a lecture at
Hot Topics in Neonatology (Washington, DC, 2000), stating that we had become human litogens (a litogen having
previously been described as a drug that does not cause
malformations but does cause lawsuits). We enjoyed many
continued years of discussion and when he knew he was dying, he said to Dr Tony Williams and me: you seem to
have common sense, I pass the baton to you.

cycle and to the change in major energy source, from glucose transfer across the placenta to fat released from adipose tissue stores and ingested with milk feedings. After
birth, plasma insulin levels fall, and there are rapid surges
of catecholamine and pancreatic glucagon release. These
endocrine changes switch on the essential enzymes for
glycogenolysis (the release of glucose stored as glycogen
in liver, cardiac muscle, and brain), gluconeogenesis (glucose production from three-carbon precursor molecules
by the liver), lipolysis (release of fatty acids from adipose
tissue stores), and ketogenesis (the b-oxidation of fatty
acids by the liver to produce ketone bodies). Some tissues
(eg, the kidney) are obligate glucose users, but others burn
fatty fuels to provide energy. Of the organs that use fuels
alternative to glucose, it is most signicant that the neonatal brain takes up and oxidizes ketone bodies at higher
rates than seen in adults and uses ketone bodies more efciently than glucose. Lactate has also been identied as an
alternative fuel. In each group of infants studied, after correcting for blood glucose level, ketone body levels were
lower for bottle-fed infants than for breastfed infants.
To translate these ndings into clinical practice:
Low blood glucose concentrations are commonly found
during the rst postnatal days in healthy, normally grown,
term neonates, particularly those who are breastfed.
These infants have high ketone body levels when blood
glucose concentrations are low, and it is likely that these
alternative fuels protect them from neurologic injury.
Formula feeding is associated with lower ketone body
levels compared with levels in breastfed infants.

Impaired or Delayed Metabolic Adaptation

Certain groups of infants are at risk of a more profound or
prolonged fall in blood glucose, or more importantly,
a failure to mount the normal metabolic responses to this
fall. At-risk groups include infants who have hyperinsulinism (eg, after poor control of maternal diabetes in pregnancy), those who have intrauterine growth restriction,

Neonatal Metabolic Adaptation

It is important to keep in mind what is known about normal physiology and neonatal metabolic adaptation (Table 1).
During pregnancy, the human fetus receives from its
mother, via the placental circulation, a supply of substrates necessary for growth, for the deposition of fuel
stores that are essential after birth, and for energy to meet
the basal metabolic rate and requirements for growth.
When the continuous ow of nutrients from the placenta
is abruptly discontinued at birth, immediate postnatal
metabolic changes preserve fuel supplies for vital organ
function. The newborn infant must adapt to the fast-feed

Endocrine and Metabolic

Changes of Neonatal Metabolic
Adaptation

Table 1.

Hormonal

Metabolic

YInsulin
[Glucagon
[Catecholamines
[Cortisol

Glycogenolysis
Gluconeogenesis
Lipolysis/free fatty acids
Ketogenesis

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endocrinology

preterm infants, and those who have other pathologic

conditions such as infection or inborn errors of metabolism. Untreated, the low blood glucose levels in the absence of fuels alternative to glucose will cause clinical
signs and, in the extreme case, brain injury.

Clinical Significance of Impaired or Delayed

Metabolic Adaptation
No study has yet satisfactorily addressed the duration of
absent or reduced availability of metabolic fuels that is
harmful to the human neonate. Animal studies indicate
that hours (rather than minutes) of hypoglycemia are required to cause injury and that injury is unlikely to occur
if abnormal clinical signs are absent. For infants in whom
prolonged neonatal hypoglycemia has been associated
with abnormal clinical signs (most usually hypotonia, reduced level of consciousness, or seizures), adverse longterm outcomes have been reported. There is evidence
from case reports that profound and prolonged hypoglycemia is associated with both transient and permanent
structural changes in the brain, especially if seizures occur. Grey matter damage is most commonly reported,
with the parieto-occipital regions being most affected.
Clinical experience and data from studies and case reports
indicate that when neonatal hypoglycemia results in clinical
signs or brain injury, the temporal evolution is as follows:
Low blood glucose levels are found, but the infant
does not have clinical signs because he or she is still
able to draw on alternative fuel stores (eg, glycogen
and fat). This condition could be termed biochemical
hypoglycemia with adequate metabolic adaptation.
If untreated, the infant exhausts alternative fuel stores
and develops subtle clinical signs that are not specic
to hypoglycemia (eg, irritability, lethargy, poor feeding), but hypoglycemia is not damaging at this stage.
This state is the onset of impaired metabolic adaptation.
If untreated, the infant develops obvious and severe
clinical signs (eg, seizures, coma) but may escape damage if treated promptly. Metabolic adaptation has failed.
If not treated sufciently soon after the onset of these
severe clinical signs, hypoglycemia becomes damaging
and in severe cases results in cardiorespiratory arrest.
The time period for this process will be highly variable.
For example, with severe hyperinsulinism, metabolic adaptation is completely suppressed, and the infant is extremely vulnerable to a sustained postnatal fall in blood
glucose. For the moderately preterm infant who does
not attain sufcient milk intake, the process (if left unmanaged) will be more gradual as the infants reduced fat

neonatal hypoglycemia

stores become exhausted. Therefore, the duration of

low blood glucose cannot be woven into the denition.

Evidence-based Clinical Diagnosis

The challenge is to arrive at a diagnostic denition of signicant hypoglycemia, taking into account that the levels
of fuels alternative to glucose cannot easily be measured
in clinical practice. The process of diagnosis must rst
identify those infants at risk of failure or delay in metabolic adaptation and then monitor blood glucose levels
and clinical signs. Alternatively, for an infant not previously thought to be at risk but who presents with any
concerning clinical signs, there must be prompt and accurate blood glucose measurements.
There have been swings in opinion and controversy over
the years regarding the numerical denition of neonatal hypoglycemia. This debate arises from the clinical scientic
world setting itself an unrealistic task in an area that contains
so many variables. Attempts to arrive at a single denition,
usually to 1 decimal place in the context of devices that cannot measure accurately to 0.5 mmol/L (9 mg/dL) and
failing to take into account biological variability, have no rational basis. Of concern was the widespread adoption of a single numerical value based on two published papers (whose
results are now generally considered not to justify their conclusions) that a level of less than 2.6 mmol/L (<47 mg/dL)
should be used to dene neonatal hypoglycemia.
As described earlier, this numerical denition generally leads to overdiagnosis and treatment but, more worrisome, measurement with inaccurate devices could give
false reassurance regarding infants for whom a recorded
level of 2.6 mmol/L is too low should metabolic adaptation fail. Despite widespread knowledge of the concern
regarding inaccuracy of near-patient testing devices in
both the United Kingdom and the United States, the
use of these devices remains prevalent.
Any attempt to arrive at an evidence-based denition
of hypoglycemia should include consideration of:
The blood glucose concentration considered to be the
minimum safe level.
The duration beyond which the low blood glucose
level is considered to be harmful.
The presence of clinical signs.
The group of infants studied.
The consideration of alternative fuel availability.
The conditions of sampling and the assay methods.
These factors have not been adequately addressed in
scientic studies, and it is unlikely that they will be in
the future. Therefore, a pragmatic approach based on
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thresholds for intervention was proposed in 2000 by

a group of interested clinicians from the United Kingdom
and the United States:
If there are neurologic signs in association with blood
glucose levels less than 2.5 mmol/L (<45.0 mg/dL),
there should be an urgent investigation to identify an
underlying cause and institution of treatment.
For infants who have no clinical signs but are at risk of
impaired metabolic adaptation (ie, hyperinsulinism, intrauterine growth restriction, prematurity, infection,
inborn error of metabolism), intervention to raise
the infants blood glucose level should be instituted
if two consecutive blood glucose levels are less than
2 mmol/L (<36 mg/dL), measured by using an accurate device, or a single blood glucose level is less than 1
mmol/L (<18 mg/dL).
The paper by the group from the United Kingdom
and the United States sets higher therapeutic goals than
the blood glucose levels for intervention, especially for infants thought to have signicant hyperinsulinism.
Groups of experts since 2000 have reviewed the evidence
base in light of more recent publications and have presented
no arguments to move from this pragmatic consensus.

Prevention and Management of Neonatal

Hypoglycemia
It is important to prevent potentially damaging hypoglycemia in vulnerable infants, but this goal must be balanced against the risks of overly invasive management:
separation of mother and infant, placing at risk the establishment of breastfeeding, and unnecessary administration of formula or intravenous glucose, which in turn
impairs metabolic adaptation to postnatal life.
There is a sufcient evidence base that healthy, normally
grown, term neonates often have low blood glucose concentrations in the rst postnatal days but are protected by the
presence of ketone bodies and lactate as alternative fuels.
These infants do not need routine blood glucose monitoring
or formula supplementation of breastfeedings. However,
staff should be alert to systemic conditions (eg, neonatal infection) that may affect feeding and the risk of neonatal hypoglycemia, as well as the very rare risk that an infant who is
apparently healthy at birth may have an underlying metabolic disorder. Appropriate investigations, including a blood
glucose measurement, should be performed for any infant
who presents with abnormal clinical signs.
Similarly, there is sufcient evidence base from clinical
experience and published studies to advise management
of infants at risk of impaired metabolic adaptation.

At-risk infants should have regular clinical monitoring

to include feeding behavior and prefeeding blood glucose monitoring (approximately every 4 hours).
Blood glucose monitoring should commence before
the second feeding (ie, not so soon after birth that
the physiologic fall in blood glucose level causes confusion and overtreatment), and prefeeding monitoring
should be continued until the infant has had at least
two satisfactory measurements.
Monitoring should be recommenced if the infants
clinical condition worsens or energy intake decreases.
If monitoring is performed by using reagent strips,
low levels must be conrmed promptly by accurate
measurement.
The importance of early milk feeding has been appreciated for many years and more recently the recognition
of provision of important gluconeogenic precursors and
fatty acids for b-oxidation. Therefore, all infants who
are expected to tolerate enteral feedings should be fed
with milk as soon as possible after birth and then at frequent intervals thereafter. Infants who are capable of
sucking should be offered the breast at each feeding (if
this is the mothers wish). If it is likely that infants will
need supplementary formula feedings, maternal human
milk expression should be encouraged. The requirement
for formula feedings must be titrated against the clinical
condition of the infant, blood glucose monitoring, and
the supply of maternal human milk. In the breastfed infant, formula intake should be kept to the minimum necessary, with the goal of enhancing breastfeeding and
avoiding suppression of normal metabolic adaptation.
A recent high-quality, randomized, double-blind,
placebo-controlled intervention study by Harris et al
demonstrated that at-risk infants who develop hypoglycemia benet from buccal dextrose gel in terms of avoiding
additional treatments and supporting breastfeeding.
In the at-risk infant who is establishing oral feedings, there
is a potential nadir at which body stores are steadily reducing
but milk feedings have not yet started to replenish these
stores. For this reason, vulnerable infants should not be transferred to the community at less than age 48 hours and only
when experienced staff are satised that feeding is effective.
If an infant requires intravenous glucose, usually 10%
dextrose at 3 mL/kg/h (5 mg glucose/kg/min) is sufcient to prevent or reverse hypoglycemia. If uid restriction is required, a central line should be inserted for infusion
of more concentrated dextrose solutions. Boluses of concentrated glucose solution should be avoided because of
the risk of rebound hypoglycemia and cerebral edema. If
boluses are required (eg, if there are neurologic signs of

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hypoglycemia), they should be of 10% dextrose (35 mL/

kg), given slowly, and always followed by an infusion. All
reductions in infusion rate should be gradual, and any interruption of infusion should be promptly remedied.
There are a number of additional specic treatments
for specic causes of neonatal hypoglycemia (eg, neonatal
hyperinsulinism). These are covered in standard texts.

Conclusions
If neonatal hypoglycemia is to continue in use as
a shorthand diagnostic term, it should be accurately dened as a persistently low blood glucose level, measured
with an accurate device, in an infant at risk of impaired
metabolic adaptation but with no abnormal clinical signs;
or a single low blood glucose level in an infant presenting
with abnormal clinical signs. There has been no recent
evidence to argue against the pragmatic operational
threshold values described in 2000.
The impact of hypoglycemia and its treatment on the
mother and infant must be considered. The early neonatal period is an emotionally sensitive time, and the diagnosis of hypoglycemia may create or increase anxiety for
the parents. Treatment of the infant with intravenous
glucose involves separation of the infant and mother,
with a negative impact on breastfeeding, and may be perceived as invasive or painful. Because formula supplementation also disrupts breastfeeding and has a negative effect
on normal neonatal metabolic adaptation, it should be
avoided unless there is a clear clinical indication. Emphasis should be on the early prevention of hypoglycemia and
strategies of management that do not involve the separation of mother and infant.
We are trained as clinicians to make assessments and
decisions to avoid harm arising from the underlying condition but also to avoid iatrogenic harm, such as the effects of separation of mother and infant. Attempting to
apply evidence-based numerical denitions of hypoglycemia and algorithms for management cannot replace
these clinical skills (Table 2).

Factors to Identify and

Document

Table 2.

Risk factors
Coexisting conditions
Clinical signs/normality
Accurate blood glucose measurements
Response to treatment

neonatal hypoglycemia

American Board of Pediatrics NeonatalPerinatal

Content Specifications
Know the fuels used for brain metabolism.
Know the causes (including
hyperinsulinemic hypoglycemia) of
neonatal hypoglycemia syndromes.
Recognize the clinical and laboratory
features of neonatal hypoglycemia.
Recognize the approach to therapy and prevention of
neonatal hypoglycemia.
Know the potential sequelae of neonatal hypoglycemia.

Suggested Reading
Auer RN, Siesj BK. Hypoglycaemia: brain neurochemistry and
neuropathology. Baillieres Clin Endocrinol Metab. 1993;7(3):
611625
Boluyt N, van Kempen A, Offringa M. Neurodevelopment after
neonatal hypoglycaemia: a systematic review and design of
optimal future study. Pediatrics. 2006;117(6):22312243
Cornblath M, Hawdon JM, Williams AF, et al. Controversies
regarding denition of neonatal hypoglycemia: suggested operational thresholds. Pediatrics. 2000;105(5):11411145
de Rooy LJ, Hawdon JM. Nutritional factors that affect the
postnatal metabolic adaptation of full-term small- and largefor-gestational-age infants. Pediatrics. 2002;109(3):E42
Eidelman AI. Hypoglycemia and the breastfed neonate. Pediatr
Clin North Am. 2001;48(2):377387
Harris DL, Weston PJ, Signal M, Chase JG, Harding JE. Dextrose gel
for neonatal hypoglycaemia (the Sugar Babies Study): a randomised, double-blind, placebo-controlled trial [published online
ahead of print September 24, 2013]. Lancet. doi:10.1016/S01406736(13)61645-1
Hawdon JM. Disorders of metabolic homeostasis in the neonate. In:
Rennie JM, ed. Textbook of Neonatology. 5th edition. Edinburgh
UK: Churchill Livingstone;2012:850867
Hawdon JM. Neonatal complications after diabetes in pregnancy.
In: Rennie JM, ed. Textbook of Neonatology. 5th edition.
Edinburgh UK: Churchill Livingstone;2012:387394
Hawdon JM, Aynsley-Green A, Bartlett K, Ward Platt MP. The
role of pancreatic insulin secretion in neonatal glucoregulation.
II. Infants with disordered blood glucose homoeostasis. Arch
Dis Child. 1993;68(3 spec no):280285
Hawdon JM, Ward Platt MP, Aynsley-Green A. Patterns of
metabolic adaptation for preterm and term infants in the
rst neonatal week. Arch Dis Child. 1992;67(4 spec no):
357365
Hay WW Jr, Raju TN, Higgins RD, Kalhan SC, Devaskar SU.
Knowledge gaps and research needs for understanding and
treating neonatal hypoglycemia: workshop report from Eunice
Kennedy Shriver National Institute of Child Helath and Human
Development. J Pediatr. 2009;155(5):612617
Medical Devices Agency. Extra-laboratory use of blood glucose meters
and test strips: contraindications, training and advice to the users.
Safety Notice MDA SN 9616, 1996. Available at: www.mhra.gov.
uk/home/groups/dts-bi/documents/publication/con007332.pdf.
Accessed December 30, 2013
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Rozance PJ, Hay WW. Hypoglycemia in newborn infants: features

associated with adverse outcomes. Biol Neonate. 2006;90(2):7486
Srinivasan G, Pildes RS, Cattamanchi G, Voora S, Lilien LD. Plasma glucose
values in normal neonates: a new look. J Pediatr. 1986;109(1):114117

Vannucci RC, Vannucci SJ. Hypoglycemic brain injury. Semin

Neonatol. 2001;6(2):147155
Williams AF. Neonatal hypoglycaemia: clinical and legal aspects.
Semin Fetal Neonatal Med. 2005;10(4):363368

Parent Resources from the AAP at HealthyChildren.org

English only: http://www.healthychildren.org/English/health-issues/conditions/chronic/Pages/Causes-of-High-

Blood-Glucose-and-Low-Blood-Glucose.aspx

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1. You are called to evaluate a newborn female infant who was born at 39-weeks gestational age and is now 30
minutes old. Although the reason for the test is unclear, a bedside reagent strip test has been completed and
results indicate a blood glucose level of 50 mg/dL. The infant is crying vigorously and otherwise appears well.
Which of the following statements regarding glucose testing and metabolic changes occurring in this infant is
correct?
A. In infants who do not have diabetes or hyperinsulinemic states, blood glucose levels increase uniformly and
steadily for the first 2 to 4 hours after birth, allowing for establishment of feedings and eventual glucose
balance.
B. Although the infant appears well, the glucose level noted is low for this age, and this finding alone
indicates a high likelihood of potential brain injury.
C. This low level is due largely to the normal rapid and large neonatal insulin release that occurs shortly after
birth until w6 hours of age, along with a simultaneous decrease in catecholamine release.
D. During the time after birth, enzymes for glycogenolysis and ketogenesis will be switching on to facilitate
glucose release and production of ketone bodies, respectively.
E. This patients liver function should be watched closely, as the liver is an obligate glucose user, whereas
organs such as the kidneys and brain burn fatty fuels for energy.
2. You are told that a newborn infant has been followed up with several glucose tests for hypoglycemia due to
symptoms of jitteriness. You are reviewing the medical record for possible risk factors. Which of the following
statements regarding metabolic risk factors is correct?
A. The most common cause of persistent hypoglycemia in the newborn period is remnants of maternally
injected insulin for diabetes that have crossed the placenta.
B. Although preterm birth is associated with poor growth, hypoglycemia is very rare in the first several hours
after birth because there are sufficient mechanisms for maternal transfer and neonatal adaptation.
C. Infants with intrauterine growth restriction are at risk for a longer and deeper fall in glucose, as well as
decreased ability to achieve an adequate metabolic response to hypoglycemia.
D. One of the main challenges a newborn infant faces is that the neonatal brain is unable to use alternative
fuels such as ketones and lactate and, therefore, even a short period of low glucose levels can lead to longterm brain injury.
E. Serum glucose levels can be misleading after birth because there is a rapid increase in gluconeogenesis in
the first 6 hours, leading to decreased glucose levels in the serum but sufficient energy substrates in vital
organs.
3. You are reviewing a case of an infant who is now 5 years old who has developmental delays that were
appreciated starting at age 6 months. He has a history of brain injury that may have been caused by neonatal
hypoglycemia. Which of the following statements most accurately describes a step in the pathway that may
have led to this injury?
A. During the neonatal period, it is unlikely that there were any clinical symptoms; severe hypoglycemic injury
that leads to long-term adverse outcomes generally does not manifest until school-age.
B. The initial noticeable symptoms of hypoglycemia that may indicate exhaustion of alternative fuel stores
are often nonspecific, such as irritability, lethargy, or poor feeding.
C. The time course of hypoglycemia leading to permanent brain injury is fairly consistent across gestational
age and predisposing factors such as maternal diabetes, hyperinsulinism, growth restriction, or infection.
D. The infant who is formula feeding is more likely to have increased ketone bodies compared with
breastfeeding infants and is therefore more likely to have brain injury compounded by ketotic coma.
E. When a low blood glucose level is found in the first 1 to 2 hours, but the infant does not have any clinical
signs or symptoms, the bulk of the brain injury is likely to have already occurred.
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4. A healthy term infant in was noted to have poor feeding and lethargy at age 24 hours, and a glucose level was
checked and found to be 35 mg/dL. Results of a repeat test after 30 minutes show a level of 34 mg/dL. Which
of the following is true regarding this clinical scenario?
A. Because the patient has been well until this fairly late time after delivery, these levels are highly unlikely,
and a repeat level should be obtained after 3 hours with a new instrument, while testing for other
etiologies of symptoms is considered.
B. Although the evidence is still accumulating regarding an absolute number to define hypoglycemia, it is
fairly clear that 2.5 mmol/L (45 mg/dL) is a safe level in all circumstances to provide reassurance even in
the context of any clinical symptom.
C. At this stage of the clinical course, the patient probably still has sufficient and adequate stores of glycogen
and fat to use for energy.
D. Because there are no evidence-based studies to show any benefit of interventions for hypoglycemia, the
main utility of these tests is not to guide any intervention but to provide reassurance that there is no other
cause of the symptoms, which in this case would be the difficulty feeding.
E. In this scenario, it would be reasonable to investigate the etiology of the hypoglycemia and to institute
treatment to increase glucose levels.
5. You are on a committee that is developing procedural policies for your maternalinfant care unit. Which of the
following steps to prevent and treat neonatal hypoglycemia is most appropriate to consider including in your
policy?
A. Any infant who presents with abnormal clinical signs, such as lethargy, should undergo blood glucose
measurement, with other relevant testing based on symptoms.
B. Due to the inherent risk of transitioning from placental to intermittent, sporadic feedings, all newborns
should have at least 1 glucose check within the first 24 hours after delivery.
C. For infants who require intravenous glucose, the minimum dose of initiating therapy should be 6 mL/kg/h
(10 mg glucose/kg/min), with increases as needed based on response.
D. The standard feeding regimen for term infants of diabetic mothers should include formula
supplementation starting with the second feeding and continuing until 48 hours, after which formula can
be weaned off if breastfeeding has been well established.
E. For infants who are small for gestational age, blood glucose levels should be checked at 30 minutes, 1 hour,
and 90 minutes, and if greater than 50 mg/dL at those time points, the infant can be transferred to regular
newborn care.

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Neonatal Hypoglycemia: Are Evidence-based Clinical Guidelines Achievable?

Jane M. Hawdon
NeoReviews 2014;15;e91
DOI: 10.1542/neo.15-3-e91

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Neonatal Hypoglycemia: Are Evidence-based Clinical Guidelines Achievable?

Jane M. Hawdon
NeoReviews 2014;15;e91
DOI: 10.1542/neo.15-3-e91

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