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Official reprint from UpToDatewww.uptodate.com ©2015 UpToDate

Author 

Paul J Rozance, MD

Section Editors

Joseph A Garcia-Prats, MD

Joseph I Wolfsdorf, MB,

BCh

Deputy Editor 

Melanie S Kim, MD

Pathogenesis, screening, and diagnosis of neonatal hypoglycemia

 All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Aug 2015. | This topic last updated: Aug 04, 2015.

INTRODUCTION — During the normal transition to extrauterine life, blood glucose concentration in the healthy

term newborn falls during the first two hours after delivery, reaching a nadir that usually is no lower than 40 mg/dL. It

is important to differentiate this normal physiologic transitional response from disorders that result in persistent or 

recurrent hypoglycemia, which may lead to neurologic sequelae.

This topic will discuss the normal transient neonatal low glucose levels, causes of persistent or pathologic neonatal

hypoglycemia, and the clinical manifestations and diagnosis of neonatal hypoglycemia. The management of 

neonatal hypoglycemia, including evaluation of persistent hypoglycemia and outcome of neonatal hypoglycemia, is

discussed separately. (See "Management and outcome of neonatal hypoglycemia".)

CHALLENGE OF DEFINING NEONATAL HYPOGLYCEMIA — Clinically significant neonatal hypoglycemia

requiring intervention cannot be defined by a precise numerical blood glucose concentration because of the

following:

Nevertheless, most guidelines used in clinical practice provide arbitrary treatment thresholds of blood glucose

concentrations to initiate intervention and bypass the controversies surrounding the definition of hypoglycemia [1,3].

This approach tries to reduce the harm due to hypoglycemia, identify newborns with a serious underlying

hypoglycemia disorder, and at the same time, minimize overtreatment of newborns with normal transitional low

glucose concentrations that resolve without intervention. This has resulted in guidelines that favor simplicity and

ease of use over an emphasis on the physiology of normal neonatal glucose homeostasis, the normal age-related

increase in glucose concentrations over the first few days of life, and the varying pathophysiological conditions that

may lead to clinical hypoglycemia. (See "Management and outcome of neonatal hypoglycemia".)

When using guidelines based on low glucose concentrations, it is important to recognize that glucose

concentrations measured in whole blood are approximately 15 percent lower than those in plasma and may be

further reduced if the hematocrit is high. In addition, when reviewing the literature and guidelines one must be

careful to note whether the normal values are mean glucose values (used in this topic review), as opposed to using

a threshold range of glucose values (below the 5 percentile used in the American Academy of Pediatrics [AAP]

guidelines). (See 'How glucose testing is performed' below.)

®

®

Normal low neonatal blood glucose levels − Low blood glucose concentrations normally occur in the first

hours after birth and may persist for up to several days. Although most newborns remain asymptomatic

despite very low blood glucose concentrations, some newborns become symptomatic at the same or even

higher blood glucose concentrations than are observed in asymptomatic infants. This variability in the clinical

response in neonates to low blood glucose concentrations is due to a number of factors that include the

infant's gestational age and postnatal age, the presence of other sources of energy (eg, lactate and ketonebodies), and circumstances that affect glucose metabolism and cerebral glucose uptake and utilization.

●

Lack of outcome data − Ideally, clinically significant neonatal hypoglycemia would be defined as the blood

glucose concentration at which intervention should be initiated to avoid significant morbidity, especially

neurologic sequelae. However, this definition remains elusive because the blood glucose concentration and

duration of hypoglycemia associated with poor neurodevelopmental outcome has not been established [1,2].

●

th

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NORMAL TRANSITIONAL LOW GLUCOSE LEVELS — Transient low blood glucose concentrations in neonates

are normal, as the source of glucose at delivery changes from a continuous supply from the mother to an

intermittent supply from milk feeds [4]. With loss of the continuous transplacental supply of glucose, plasma

glucose concentration in the healthy term newborn falls during the first two hours after delivery, reaching a nadir that

usually is no lower than 40 mg/dL (2.2 mmol/L), and then stabilizes by four to six hours of age in the range of 45 to

80 mg/dL (2.5 to 4.4 mmol/L) [1,2,5,6]. Mean concentrations then rise more slowly in the next few days to

concentrations similar to those seen in older children and adults.

Immediately after birth, the plasma glucose concentration is maintained by the breakdown of hepatic glycogen

(glycogenolysis) in response to increased plasma epinephrine and glucagon concentrations, and falling insulin

levels. Glycogen stores are depleted during the first 8 to 12 hours of life. Thereafter, plasma glucose levels are

maintained by the synthesis of glucose from lactate, glycerol, and amino acids (gluconeogenesis). As feeds with

adequate carbohydrate are established, maintenance of plasma glucose concentrations is no longer solely

dependent on gluconeogenesis. However, if the first feeding is delayed for three to six hours after birth,

approximately 10 percent of normal term newborns cannot maintain a plasma glucose concentration above 30

mg/dL (1.7 mmol/L) [7,8].

PATHOLOGIC AND/OR PERSISTENT HYPOGLYCEMIA — Hypoglycemia is caused by a lower rate of glucose

production than glucose utilization. The underlying mechanisms of neonatal hypoglycemia in at-risk neonates that

usually require intervention (pathologic or persistent) include the following (see "Etiology of hypoglycemia in infants

and children"):

Diminished glucose supply

Inadequate glycogen stores — Inadequate glycogen stores can lead to a diminished supply of glucose and

present in the following sett ings:

Impaired glucose production — Impaired glucose production is due to the disruption of either glycogenolysis

or gluconeogenesis. (See "Etiology of hypoglycemia in infants and children", section on 'Disorders of 

glycogenolysis' and "Etiology of hypoglycemia in infants and children", section on 'Disorders of glycosylation' and

"Etiology of hypoglycemia in infants and children", section on 'Disorders of gluconeogenesis'.)

Inborn errors of metabolism — Inborn errors of metabolism that may cause neonatal hypoglycemia

include (table 1):

Inadequate glucose supply●

Inadequate glycogen stores•

Impaired glucose production (ie, glycogenolysis or gluconeogenesis)•

Increased glucose utilization●

Excessive insulin secretion•

Other causes•

Prematurity – Because glycogen is deposited during the third trimester of pregnancy, infants born prematurely

have diminished glycogen reserves.

●

Fetal growth restriction (FGR) – Infants with FGR, also referred to as intrauterine growth restriction (IUGR),

may have reduced glycogen stores or may rapidly deplete their glycogen stores if the transition to extrauterine

life is difficult, which increases their metabolic needs (ie, increased glucose utilization). After delivery, there

may also be impaired glucose production due to a poorly coordinated response to hypoglycemia by counter 

regulatory hormones (epinephrine and glucagon) and increased insulin sensitivity [5,9]. (See "Infants with fetal

(intrauterine) growth restriction", section on 'Hypoglycemia'.)

●

Disorders of glycogen metabolism (glycogenolysis) resulting from mutations in genes that encode proteins

involved in glycogen synthesis, degradation, or regulation of these processes. (See "Overview of inherited

●

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Endocrine disorders — Deficiency of the hormones (eg, cortisol and growth hormone) that regulate glucose

homeostasis result in hypoglycemia. The hormonal deficiency can be isolated or associated with other pituitary

hormone deficiencies, or primary adrenocortical insufficiency. (See "Etiology of hypoglycemia in infants and

children", section on 'Hormone deficiencies'.)

Other causes — Other causes of impaired glucose production resulting in neonatal hypoglycemia include:

Increased glucose utilization

Hyperinsulinism — Increased glucose utilization primarily results from hyperinsulinism. Excess insulin also

suppresses hepatic glucose production. The infant of a diabetic mother is the most common neonatal clinical

situation in which hyperinsulinism causes hyperinsulinemic hypoglycemia. In this setting, it is postulated that

intermittent maternal hyperglycemia causes fetal hyperglycemia, which leads to hypertrophied and hyperfunctioning

beta cells resulting in fetal and neonatal hyperinsulinemia. After termination of the maternal glucose supply at

delivery, hypoglycemia from persistent hyperinsulinism in the newborn usually is transient and typically resolves

two to four days after birth. (See "Infant of a diabetic mother", section on 'Hypoglycemia'.)

Other conditions associated with hyperinsulinism and transient hypoglycemia include:

disorders of glucose and glycogen metabolism" and "Etiology of hypoglycemia in infants and children",

section on 'Disorders of glycogenolysis'.)

Disorders of gluconeogenesis (eg, fructose-1,6-bisphosphatase deficiency, pyruvate carboxylase deficiency),

defects in amino acid metabolism (eg, maple syrup urine disease, propionic acidemia, and methylmalonic

academia), disorders of carbohydrate metabolism (eg, hereditary fructose intolerance, galactosemia), and

fatty acid metabolism (eg, medium or long-chain acyl-CoA dehydrogenase deficiency) [10]. (See "Etiology of 

hypoglycemia in infants and children", section on 'Disorders of gluconeogenesis' and "Etiology of 

hypoglycemia in infants and children", section on 'Disorders of amino acid metabolism' and "Etiology of 

hypoglycemia in infants and children", section on 'Disorders of fatty acid metabolism' and "Inborn errors of 

metabolism: Metabolic emergencies", section on 'Hypoglycemia' and "Organic acidemias" and "Inborn errors

of metabolism: Metabolic emergencies", section on 'Hypoglycemia'.)

●

Maternal treatment with beta-sympathomimetic agents (eg, terbutaline), which interrupts glycogenolysis by

blocking epinephrine's effect

●

Hypothermic infants who have diminished availability of glucose and increased rates of glucose utilization●

Severe hepatic dysfunction due to impairment of both glycogenolysis and gluconeogenesis●

Fetal growth restriction (FGR) − In addition to a decrease in glucose/glycogen stores (as noted above),

hyperinsulinism may contribute to hypoglycemia in newborns with FGR [5,11]. (See "Infants with fetal

(intrauterine) growth restriction".)

●

Beckwith-Wiedemann syndrome (BWS) − About half of all neonates with BWS have transient or prolonged

hypoglycemia caused by hyperinsulinism. (See "Beckwith-Wiedemann syndrome", section on 'Metabolic

abnormalities'.)

●

Perinatal asphyxia or stress [5,12,13]. (See "Systemic effects of perinatal asphyxia".)●

Maternal intrapartum treatment with glucose or with antihyperglycemic agents such as sulfonylureas.●

 Abrupt interruption of an infusion of a solution with a high glucose concentration. Rarely, glucose infusion

through an umbilical artery catheter with its tip near the celiac or superior mesenteric arteries will stimulate

excessive insulin release.

●

Persistent hyperinsulinemic hypoglycemia of infancy − Infants with persistent hyperinsulinemia typically

develop severe hypoglycemia that requires high rates of glucose infusion to maintain normal blood glucose

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Without hyperinsulinism — Conditions associated with glucose utilization that exceeds production without

hyperinsulinism include the following:

Neuroglycopenia — The transport protein GLUT1 facilitates glucose diffusion across blood vessels into the brain

and cerebrospinal fluid (CSF). Although blood glucose concentrations are normal, deficiency of GLUT1, a rare

condition, results in low CSF glucose concentrations and neurologic symptoms associated with hypoglycemia [ 16].

CLINICAL MANIFESTATIONS — Infants with low blood glucose concentrations frequently are asymptomatic;hypoglycemia in these cases is usually detected by screening of blood glucose in at-risk infants or as an incidental

laboratory finding.

In the symptomatic infant, signs are nonspecific and reflect responses of the nervous system to glucose

deprivation. These can be categorized as neurogenic or neuroglycopenic findings [6]:

levels in the first postnatal days. Mutations in genes encoding enzymes that control intracellular metabolic

pathways of the pancreatic beta cell or transport of cations across the beta cell membrane have been

identified in as many as 50 percent of patients. The genes most often affected control the sulfonylurea

receptor (SUR1) and the inward rectifier potassium channel (Kir6.2); these proteins form the functional ATP-

dependent potassium channel in the beta cell membrane. Persistent hyperinsulinemic hypoglycemia of 

infancy is discussed separately. (See "Pathogenesis, clinical features, and diagnosis of persistent

hyperinsulinemic hypoglycemia of infancy".)

Excess exogenous insulin given to newborns with hyperglycemia may result in hypoglycemia [14]. (See

"Neonatal hyperglycemia", section on 'Risk of hypoglycemia'.)

●

Neonatal conditions associated with excess insulin secretion include alloimmune hemolytic disease of the

newborn (see "Postnatal diagnosis and management of hemolytic disease of the fetus and newborn" ),

meconium aspiration syndrome (see "Clinical features and diagnosis of meconium aspiration syndrome"),

hypothermia, and polycythemia [5]. (See "Neonatal polycythemia", section on 'Hypoglycemia'.)

●

 Asymmetric neonates with FGR have relatively large (spared) head and brain size compared with their birth

weight. Because the neonatal brain accounts for a large proportion of total glucose utilization, many of these

infants become hypoglycemic if provided a glucose supply that seems appropriate relative to body weight (4 to

6 mg/kg/min) rather than the higher appropriate glucose supply required to prevent hypoglycemia relative to

the larger head size.

●

Conditions associated with anaerobic glycolysis due to decreased tissue perfusion, poor oxygenation, or 

biochemical defects that interfere with aerobic glucose metabolism [15]. The energy (ATP) per molecule of 

glucose produced by anaerobic glycolysis is only about 5 percent of that produced by aerobic glucose

metabolism.

●

Hypoglycemia associated with polycythemia may result from greater glucose utilization by the increased

mass of red blood cells. (See "Neonatal polycythemia", section on 'Hypoglycemia'.)

●

Increased glucose consumption can occur with heart failure or perinatal asphyxia; hyperinsulinism has also

been documented in infants who experience perinatal asphyxia [12].

●

 Although the mechanism is not known, sepsis is sometimes associated with hypoglycemia. Proposed

contributing factors include increased glucose utilization, depleted glycogen stores, or impaired

gluconeogenesis.

●

Neurogenic (autonomic) symptoms result from changes due to neural sympathetic discharge triggered by

hypoglycemia.

●

Jitteriness/tremors•

Sweating•

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In newborns, additional signs of hypoglycemia include apnea, bradycardia, cyanosis, and hypothermia.

Because these findings are nonspecific, further evaluation for other possible causes (eg, sepsis) should be

conducted if symptoms do not resolve after normalization of the blood glucose concentration. (See 'Differential

diagnosis' below.)

EVALUATION

Who should be evaluated? — Blood glucose concentrations should not be measured in healthy

asymptomatic term infants born after an uncomplicated pregnancy and delivery [5,6]. Blood glucose concentration

should be measured in infants at risk for hypoglycemia and in infants who exhibit signs or symptoms consistent

with hypoglycemia [6]. (See 'Clinical manifestations' above.)

Infants at risk for hypoglycemia include:

Irritability•

Tachypnea•

Pallor •

Neuroglycopenic symptoms are caused by brain dysfunction from impaired brain energy metabolism due to a

deficient glucose supply.

●

Poor suck or poor feeding•

Weak or high-pitched cry•

Change in level of consciousness (lethargy, coma)•

Seizures•

Hypotonia•

Preterm infants including late preterm infants with gestational age less than 37 weeks (see "Late preterm

infants", section on 'Hypoglycemia')

●

Infants who are large for gestational age (see "Large for gestational age newborn", section on 'Hypoglycemia')●

Infants with fetal growth restriction (FGR) (see "Infants with fetal (intrauterine) growth restriction", section on'Hypoglycemia')

●

Infants of diabetic mothers (see "Infant of a diabetic mother", section on 'Hypoglycemia')●

Infants who have experienced perinatal stress due to:●

Birth asphyxia/ischemia; this includes infants delivered by Cesarean birth for fetal distress (see

"Systemic effects of perinatal asphyxia", section on 'Organ involvement')

•

Maternal preeclampsia/eclampsia or hypertension•

Meconium aspiration syndrome (see "Clinical features and diagnosis of meconium aspiration

syndrome", section on 'Clinical features')

•

Erythroblastosis fetalis (see "Postnatal care of hydrops fetalis")•

Polycythemia (see "Neonatal polycythemia")•

Postmature infants, as these infants are at risk for placental insufficiency due to either the infant "outgrowing

the placenta" or due to decreasing placental function as a result of aging (see "Postterm infant")

●

Infants who require intensive care●

Infants whose mothers were treated with beta adrenergic or oral hypoglycemic agents●

Family history of a genetic form of hypoglycemia●

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 A prospective study of at-risk neonates (ie, large or small for gestational age, infant of diabetic mother, late preterm

infants) with a gestational age of 35 weeks or greater reported that one-half of this cohort had at least one

documented blood glucose concentration ≤47 mg/dL (2.6 mmol/L) and 20 percent had a blood glucose

concentration ≤36 mg/dL (2 mmol/L) [17]. Twenty percent of patients had more than one episode of a documented

low blood glucose level. Most of the low glucose concentrations occurred within the first 24 hours of life and were in

asymptomatic infants. However, in some newborns, their first low glucose concentration occurred after 48 hours of 

age and/or after three glucose concentrations greater than 47 mg/dL (2.6 mmol/L).

Blood glucose concentration should also be monitored at least weekly in infants receiving total parenteral nutrition

(TPN), and in infants transitioning from parenteral to enteral nutrition. No single concentration has been shown to be

"safe" for preterm infants who are enterally fed prior to 40 weeks postconceptual age as there is a significant

amount of variability in patients' glucose concentrations (both hyper- and hypoglycemic episodes) throughout the

day [18,19]. For preterm infants, many experts in the field, including the author, would suggest a target blood

glucose concentration of 50 to 60 mg/dL (2.8 to 3.3 mmol/L) [1,20]. In all neonatal cases, glucose concentrations

should be considered in the context of the patient's overall clinical and nutritional status.

Timing and frequency of glucose screening — The schedule for glucose screening is dependent on the clinical

setting as follows:

How glucose testing is performed — Most nurseries perform capillary blood glucose measurements using a

point of care glucose meter as a rapid screening method. However, glucose meters show large variations in values

compared with laboratory methods, especially at low glucose concentrations, and are of unproven reliability to

document hypoglycemia in newborns [21,22]. Thus, the plasma glucose concentration in an infant with a low

glucose value determined by a glucose meter should be confirmed by laboratory measurement [6]. Likewise,

laboratory confirmation of the plasma glucose concentration should be performed in any infant who shows signs

consistent with hypoglycemia. However, treatment should be started immediately after the blood sample isobtained and before confirmatory results are available.

Laboratory measurement of glucose concentration is affected by the type of sample. Glucose concentration

measured in whole blood is approximately 15 percent lower than that in plasma and may be further reduced if the

hematocrit is high. Prompt analysis should be performed because delays in processing and assaying glucose can

reduce the glucose concentration by up to 6 mg/dL/hour (0.3 mmol/L/hour) due to red cell glycolysis [5].

Continuous glucose monitoring using a sensor that measures interstitial glucose concentration was reported to be

reliable (when compared with blood glucose measurement), safe, and tolerable [23,24]. However, it is unclear how

to interpret the clinical significance of low interstitial blood glucose levels and whether treatment should be initiated.

Further studies are needed to determine whether continuous interstitial glucose monitoring has a useful role in the

Congenital syndromes (eg, Beckwith-Wiedemann) and abnormal physical features (eg, midline facial

malformations, and microphallus) associated with hypoglycemia

●

Glucose concentrations should be determined whenever symptoms consistent with hypoglycemia occur.●

In infants who are at risk for hypoglycemia, glucose screening is performed after the first feed, which should

occur within one hour after birth. Surveillance should be continued by measuring a prefeeding glucose

concentration every three to six hours for the first 24 to 48 hours of life because many at-risk newborns

present with their first documented low glucose concentrations during this period [17].

●

In neonates identified with low blood glucose concentrations, monitoring should continue until concentrations

can be maintained with regular feedings in a normal range: >50 mg/dL (2.8 mmol/L) in newborns <48 hours

old, and >60 mg/dL (3.3 mmol/L) in newborns >48 hours old [5].

●

If an infant is unable to maintain glucose concentrations >60 mg/dL after 48 hours of age, a hypoglycemia

disorder should be considered and further evaluation is warranted [5]. (See "Management and outcome of 

neonatal hypoglycemia", section on 'Persistent hypoglycemia'.)

●

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screening and management of neonatal hypoglycemia [25].

DIAGNOSIS — As discussed previously, pathologic neonatal hypoglycemia cannot be defined by a precise

numerical blood glucose concentration because of the lack of outcome data that accurately identify a threshold

level of blood glucose at which intervention should be initiated to prevent morbidity (see 'Challenge of defining

neonatal hypoglycemia' above). Nevertheless, defining a clinical diagnosis of neonatal hypoglycemia is important to

provide guidance for when and if therapy should be initiated to increase blood glucose levels.

We use the following parameters outlined by the 2011 American Academy of Pediatrics (AAP) clinical report and

guidelines from the Pediatric Endocrine Society to make the diagnosis of neonatal hypoglycemia requiring medicalintervention [5,6] (see "Management and outcome of neonatal hypoglycemia"):

DIFFERENTIAL DIAGNOSIS — Because the clinical manifestations are nonspecific, the following disorders can

present with similar findings. In general, neonatal hypoglycemia is differentiated from these conditions by the

resolution of symptoms as blood glucose levels normalize. However, in some cases, it is still challenging to confirm

the underlying diagnosis, as interventions that address these other disorders may be administered during the same

time period.

Symptomatic patients (eg, jitteriness/tremors, hypotonia, changes in level of consciousness,

apnea/bradycardia, cyanosis, tachypnea, poor suck or feeding, hypothermia, and/or seizures) (see 'Clinical

manifestations' above):

●

Who are less than 48 hours of life with plasma glucose levels <50 mg/dL (2.8 mmol/L)•

Who are greater than 48 hours of life with plasma glucose levels <60 mg/dL (3.3 mmol/L)•

 Asymptomatic patients at risk for hypoglycemia (eg, preterm infant or an infant with fetal growth restriction) or

patients in whom low glucose was identified as an incidental laboratory finding (see 'Who should be

evaluated?' above):

●

Who are less than 4 hours of life with plasma glucose levels <25 mg/dL (1.4 mmol/L)•

Who are between 4 and 24 hours of life with plasma glucose <35 mg/dL (1.9 mmol/L)•

Who are between 24 and 48 hours of life with plasma glucose levels <50 mg/dL (2.8 mmol/L)•

Who are greater than 48 hours of life with plasma glucose levels <60 mg/dL (3.3 mmol/L)•

Sepsis – In neonates, nonspecific signs of sepsis are often similar to those of hypoglycemia, such as

irritability, lethargy, and tachypnea. Because of the serious consequences, empiric antibiotic therapy should

be provided (after cultures are obtained) to infants with suspected sepsis pending definitive culture-based

diagnosis, in addition to administrating interventions directed towards hypoglycemia. (See "Clinical features,

evaluation, and diagnosis of sepsis in term and late preterm infants" and "Clinical features and diagnosis of 

bacterial sepsis in the preterm infant".)

●

Inborn errors of metabolism – Metabolic diseases that often present between 12 and 72 hours of age after the

initiation of oral feeding include hyperglycinemia, urea cycle disorders, and branched-chain organic acidemias.

Hypoglycemia may also be an associated finding in patients with some metabolic diseases (table 1) and willpersist despite measures to increase blood glucose levels. The diagnosis of inborn errors of metabolism and

specific disorders is discussed separately. (See "Inborn errors of metabolism: Metabolic emergencies",

section on 'Initial evaluation' and "Inborn errors of metabolism: Identifying the specific disorder", section on

'Laboratory evaluation'.)

●

Hyponatremia – Patients typically are not symptomatic until serum or plasma sodium falls below 125 mEq/L,

and present with neurologic manifestations including lethargy, obtundation, and, eventually, seizures. The

diagnosis of hyponatremia is made by obtaining serum electrolyte levels. (See "Hyponatremia in children",

section on 'Clinical manifestations'.)

●

Neonatal encephalopathy due to perinatal asphyxia – Neonatal encephalopathy can present with lethargy and●

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INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and

"Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5 to 6 grade

reading level, and they answer the four or five key questions a patient might have about a given condition. These

articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the

Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the

10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with

some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these

topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on

"patient info" and the keyword(s) of interest.)

SUMMARY AND RECOMMENDATIONS

irritability, but symptoms fail to improve with an increase in blood glucose levels. Evidence by magnetic

resonance imaging of acute brain injury confirms the diagnosis of encephalopathy. (See "Clinical features,

diagnosis, and treatment of neonatal encephalopathy".)

th th

th th

Basics topic (see "Patient information: Newborn hypoglycemia (The Basics)")●

Transient low blood glucose concentrations are common in healthy term infants after birth as the glucose

supply changes from a continuous transplacental supply from the mother to an intermittent supply from feeds.

(See 'Normal transitional low glucose levels' above.)

●

Hypoglycemia is caused by a rate of glucose production that is lower than that of glucose utilization. (See

'Pathologic and/or persistent hypoglycemia' above and "Etiology of hypoglycemia in infants and children".)

●

In neonates, diminished glucose supply is due to inadequate energy stores or impaired glucose

production (ie, glycogenolysis or gluconeogenesis). (See 'Inadequate glycogen stores' above.)

•

Increased glucose utilization is primarily due to various causes of hyperinsulinism (eg, infant of a

diabetic mother) or conditions associated with increased metabolic needs or anaerobic glycolysis. (See

'Increased glucose utilization' above and 'Without hyperinsulinism' above.)

•

Infants with low blood glucose concentrations frequently are asymptomatic, and are usually detected by

screening of at-risk infants. In symptomatic neonates, the findings are nonspecific and include

 jitteriness/tremors, hypotonia, changes in level of consciousness, apnea/bradycardia, cyanosis, tachypnea,

poor suck or feeding, hypothermia, and/or seizures. (See 'Clinical manifestations' above.)

●

We do not recommend screening for neonatal hypoglycemia in healthy asymptomatic term infants born

after an uncomplicated pregnancy and delivery (Grade 1C).

●

We recommend blood glucose concentration should be measured in infants at risk for hypoglycemia (eg,

preterm infants, infants who are large or small for gestational age, infants of mothers with diabetes or who

required beta adrenergic or oral antihyperglycemic agents, and infants who have some evidence of perinatal

stress) and in infants who exhibit signs or symptoms consistent with hypoglycemia (Grade 1C). (See 'Who

should be evaluated?' above.)

●

Timing of glucose testing is dependent on the clinical setting (see 'Timing and frequency of glucose screening'

above):

●

Glucose should be measured whenever an infant presents with symptoms consistent with

hypoglycemia.

•

In infants who are at risk, glucose screening is performed after the first feed, which should occur within

one hour after birth.

•

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GRAPHICS

Distinguishing biochemical findings of inborn errors of metabolism

Findings

Maple

syrup

urine

disease

Organic

acidemias

Urea

cycle

defects

Disorders of 

carbohydrate

metabolism

Fatty

acid

oxidation

disorders

Mitoch

diso

Metabolic acidosis ± ++ - ± ± ±

Respiratory

alkalosis

- - + - - -

Hyperammonemia ± + ++ - ± -

Hypoglycemia ± ± - + + ±

Ketones A/H H A A/H A/L A/H

Lactic acidosis ± ± - + ± ++

-: usually absent; ±: sometimes present; +: usually present; ++: always present; A: appropriate;

H: inappropriately high; L: inappropriately low.

* Within disease categories, not all diseases have all findings; for disorders with episodic

decompensation clinical and laboratory findings may be present only during acute crisis; for

progress ive disorders, findings may not be present early in the course of disease.

 Adapted from: Weiner DL. Metabolic Emergencies. In: Textbook of Pediatric Emergency Medicine, 5th ed,

Fleisher GR, Ludwig S, Henretig FM (Eds), Lippincott, Williams & Wilkins, Philadelphia 2006. p.1193.

Graphic 76373 Version 5.0

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Disclosures: Paul J Rozance, MD Nothing to disclose. Joseph A Garcia-Prats, MD Nothing to

disclose. Joseph I Wolfsdorf, MB, BCh Nothing to disc lose. Melanie S Kim, MD Nothing to disclose.

Contributor disclosures are review ed for conflicts of interest by the editorial group. When found, these

are addressed by vetting through a multi-level review process, and through requirements for references

to be provided to support the content. Appropriately referenced content is required of all authors and

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