Neonatal Glucose Management

Glucose management in neonates is rather important in the immediate phase after delivery, as hypoglycemia is considered a medical emergency. In utero and after birth, babies require a higher glucose utilization due to the metabolic demands on brain development (Rosenfeld & Thornton, 2023).

It is often the nurses caring for high-risk neonates who are tasked with maintaining glucose homeostasis. Both hyperglycemia and hypoglycemia are serious and are significant risks for many newborns. Because the neonatal brain is dependent on glucose to operate, a lack of circulating glucose can result in neurological damage. Deficient glucose in the brain can lead to seizures and brain damage, causing long-term consequences such as learning disabilities and developmental delays. The neonate with hypoglycemia may be asymptomatic or symptomatic. Those with symptomatic and recurrent hypoglycemia are more likely to have a poorer prognosis than those who are asymptomatic.

Nurses working with infants, whether in the Mother-Baby Unit or the Neonatal Intensive Care Unit (NICU), must be knowledgeable, competent, and skilled in the identification and management of hyperglycemia and hypoglycemia of the newborn to prevent morbidity and mortality. Nurses have a responsibility to understand the physiological processes that regulate glucose production and utilization; in addition to understanding nursing interventions necessary to prevent or manage glucose instability. This course will be reviewing definitions, pathophysiology, recognition, prevention, and nursing management of neonatal hypoglycemia and hyperglycemia in newborns. Hypoglycemia is addressed in two states:

1. Excessive glucose utilization
2. Insufficient supply of glucose

Optimal fetal glucose levels predominately depend on the constant maternal supply (Nakrani & Wineland, 2023). During the third trimester of pregnancy, the fetus prepares for extrauterine survival by increasing energy stores and developing metabolic processes for rapid glucose production and consumption (Nakrani & Wineland, 2023). The key metabolic processes that influence optimal glucose levels are (Nakrani & Wineland, 2023):

• Glycolysis – the conversion of glucose to lactate and pyruvate resulting in adenosine triphosphate (ATP) storage
• Glycogenesis – the release of glycogen from the liver to form glucose
• Gluconeogenesis – the production of glucose by the liver and kidneys from non-carbohydrate substrates like fatty acids and amino acids

The transition from intrauterine to extrauterine life involves many physiologic changes. The fetus receives a continuous supply of glucose from the mother across the placenta (Rosenfeld & Thornton, 2023). At delivery, termination of the maternal glucose supply results in a decrease in neonatal blood glucose levels, which reach a nadir at one to three hours post-delivery. During this initial "starvation period," glycolysis, glycogenolysis, and gluconeogenesis are initiated. These processes are the major energy sources for the neonate in the first hours of life. Baseline glucose levels are determined around 30 minutes to one hour after delivery (Rosenfeld & Thornton, 2023).

Effective activation of the metabolic processes that are responsible for maintaining optimal glucose levels depends on an adequate amount of fat and glycogen as well as mature or intact hormonal regulatory mechanisms (Fasoulakis et al., 2023). Insulin and glucagon are important hormones for regulating glucose levels. As early as twelve weeks of gestation, the fetus can create these hormones but has a limited ability to secrete them from the pancreas, even when presented with a high glucose level (Fasoulakis et al., 2023). Insulin suppresses glucose production in the liver (Fasoulakis et al., 2023). Insulin also plays an important role in the growth of the fetus because it stimulates the growth of cardiac muscle as well as hepatic, connective, adipose, and skeletal tissue (Fasoulakis et al., 2023). This provides a better understanding as to why infants of diabetic mothers are often large for gestational age (LGA), whereas infants with neonatal diabetes mellitus are at a higher risk for intrauterine growth restriction (IUGR) (Fasoulakis et al., 2023).

Let’s review some of the most common terminology of neonatal glucose management. It is important to note here that the clinical definition of specific levels of what is considered hypoglycemia and hyperglycemia might differ depending on the age of the neonate (hours of life can impact this) and how your unit defines it to guide treatment (Nakrani & Wineland, 2023):

• Hypoglycemia – plasma glucose concentration < 40 mg/dL
• Hyperglycemia – plasma glucose concentration > 150 mg/dL
• Gluconeogenesis – formation of glucose from non-carbohydrate substances
• Glycogen – stored form of glucose
• Glycogenesis – the process of making glycogen from glucose
• Glycogenolysis – the breakdown via phosphorylation pathway
• Glycolysis – the breakdown of glucose to make adenosine triphosphate (ATP)

We will be further reviewing these key terms in greater detail throughout the rest of this course.

Neonatal glucose metabolism is a very complex process, with a challenging pathophysiology. As we know, ATP is the energy source for cells to carry out their processes (Rosenfeld & Thornton, 2023). Glucose is the body's main substance to create ATP. Most ingested carbohydrates are used to make ATP. The breakdown of glucose to make ATP is known as glycolysis and occurs in two ways depending upon the presence or absence of oxygen (Rosenfeld & Thornton, 2023). In the presence of oxygen, aerobic metabolism breaks down glucose into ATP. When oxygen is absent, anaerobic metabolism is a less efficient glycolysis method. Both methods burn pyruvic acid, creating carbon dioxide and water as by-products (Rosenfeld & Thornton, 2023).

Most glucose comes from the diet as either carbohydrates or starches. Glucose can also be made from various body substrates. First, it can come from stored glucose, called glycogen, which is found in all cells. It is stored in the liver, skeletal and cardiac muscles, and the kidney, intestine, brain, and placenta, with the liver having the largest amount of glycogen (Carbó & Rodriguez, 2023). Glycogenesis is the process of making glycogen from glucose until the storage is full. The rest is stored as fat.

Glycogenolysis is the breakdown of glycogen via a phosphorylation pathway. Phosphorylation is a series of events where a phosphate group is added to a protein to either activate or deactivate it (Carbó & Rodriguez, 2023). Glucose can also be made from non-carbohydrate substances through gluconeogenesis. Proteins, fats, and acids are key substrates, or molecules, for gluconeogenesis strongly affected by glucocorticoids and thyroid hormones (Carbó & Rodriguez, 2023). Whether ingested or made in the body, glucose in the bloodstream cannot be used as an energy source. To be utilized by the body, glucose must enter the cells, which can be difficult, given its size. Insulin is required to move glucose into most cells, except for the liver and brain (Carbó & Rodriguez, 2023).

Fetal glucose homeostasis, or optimal fetal glucose levels, predominantly depends on a continuous maternal glucose supply. Maternal glucose is the primary source of energy during fetal development. Maternal glucose crosses the placenta by carrier-mediated diffusion. The glucose concentration in the fetus is approximately 80% of that in maternal blood. Changes in maternal metabolism, including increased caloric intake and decreased sensitivity of the maternal tissues to insulin, provide additional substrates needed to meet the demands of the growing fetus.

As early as the third month of gestation, the human fetal liver has the enzymatic capacity for gluconeogenesis and glycogenolysis (Deleus et al., 2020). If maternal nutrition and placental supply of glucose to the fetus are normal, there is no need for fetal gluconeogenesis to take place. The fetus produces little, if any, glucose, although the enzymes for gluconeogenesis are present. Additional evidence suggests that the fetus relies on fuels other than glucose, such as lactate and amino acids, even in the basal state, to meet some of its energy demands. However, when the exogenous supply of glucose is limited, such as during maternal starvation, the fetus can augment the glucose supply endogenously through gluconeogenesis and glycogenolysis (Deleus et al., 2020).

In the event of maternal starvation, the fetus also has the potential to use beta-hydroxybutyrate as an energy substrate. Fetal hepatic glycogen stores have been identified by the ninth week of gestation, and fetal hepatic glycogen content increases linearly at this early gestational age when maternal nutrition is normal.

Hepatic glycogen stores are three times greater than those of a well-fed adult once at term. Skeletal muscles and cardiac muscles also contain several times greater glycogen concentrations at term than found in adults. During the last trimester, the fetus also stores energy in the form of triglycerides in fetal adipose tissue. Since the transfer of free fatty acids from the mother to the fetus is limited, this occurs primarily as a result of synthesis from glucose.

Insulin is considered a major stimulus for fetal growth, but it does not cross the placenta (Kaur, et al., 2021). By the eighth week of gestation, insulin is present in the plasma and pancreatic tissue of the fetus, suggesting that pancreatic beta-cell function is present. Fetal pancreatic alpha cells are present at eight to eleven weeks of gestation. Pancreatic insulin content increases in late gestation, exceeding adult levels when the infant reaches term.

This elevated insulin concentration increases both fetal glucose utilization and glucose oxygen consumption. Glucagon cannot cross the placenta and is present in plasma by fifteen weeks of gestation, reaching peak concentrations by 24 to 26 weeks (Harding et al., 2024). In early gestation, the fetal insulin response to maternal hyperglycemia is insignificant. At term, the fetus is capable of significant response, but it is diminished, and there is a lag in the response. In maternal diabetes, the fetal beta-cell sensitivity is induced by repeated episodes of maternal hyperglycemia because of greater insulin response (Usman et al., 2023).

The fetus prepares for extrauterine life during the third trimester by increasing energy stores and developing metabolic processes for rapid glucose production and use. The glucose concentration in the umbilical vein is 70% to 80% of maternal glucose concentration. At delivery, the maternal supply of glucose to the infant ceases.

In the term infant, the blood glucose concentration falls to 50 to 60 mg/dL during the first four to six hours. By 72 hours, the blood glucose concentration stabilizes to 60 to 70 mg/dL in term infants and at lower levels in low birth weight infants.

Several hormonal and metabolic changes occur at birth, facilitating the adaptation necessary to maintain glucose homeostasis. Catecholamines increase dramatically at birth due to the decrease in environmental temperature and loss of the placenta. Increased glucagon and growth hormone levels and a relatively low plasma insulin level accompany the decrease in blood glucose following delivery. Elevated glucagon and norepinephrine levels activate hepatic glycogen phosphorylase, which induces glycogenolysis. At the same time, the falling glucose concentration and the perinatal surge in fetal cortisol secretion stimulate hepatic glucose-6-phosphatase activity, which results in increased hepatic gluconeogenesis.

Within minutes after birth, there is a rapid rise in plasma-free fatty acid and glycerol, which is evidence of intense lipid mobilization. Also, within a few hours after birth, there is an elevation of blood ketones that reaches its peak within two to three days due to increased oxidation of free fatty acids. These changes represent a change from predominantly glucose metabolism to predominantly fat metabolism. Increased use of fat for neonatal energy requirements allows the preferential sparing of glucose for the brain's metabolic needs (Rosenfeld & Thornton, 2023).

Glycogen stores in newborns are greater than in adults, but the newborn uses glucose twice that in adults (Rosenfeld & Thornton, 2023; Rodgers, 2022). Within two to three hours after birth, the neonate begins to deplete the liver glycogen stores that remain low for several days and gradually increase to adult levels. Cardiac and skeletal muscle glycogen levels fall more slowly. Rapid depletion of glycogen stores occurs during asphyxia. Premature infants and small for gestational age (SGA) infants have diminished glycogen reserves that may be rapidly depleted within even twelve hours after birth (Rosenfeld & Thornton, 2023; Rodgers, 2022).

The newborn infant has increased plasma levels of amino acids due to active placental transport, but gluconeogenesis is deficient. In both adults and newborns, many hormones regulate metabolism. There is a balance between those hormones and substances that lower and raise blood glucose (Rodgers, 2022).

The most important hormone is insulin. However, there are some differences. Insulin is not as affected by amino acids in newborns as in adults. Glucagon secretion is less affected by serum glucose levels in neonates than adults. Glucagon also induces phosphoenolpyruvate carboxykinase (PEPCK), the rate-limiting enzyme for gluconeogenesis (Rodgers, 2022). Glucocorticoids induce liver glycogen synthesis (which increases glycogen). The catecholamine effect is the same as in adults, but there may be a slower insulin response to hyperglycemia (Rodgers, 2022).

Pregnancy creates a diabetic-like state in all mothers due to the efforts of anti-insulin hormones including placental lactogen, progesterone, and estrogen (Aldahmash et al., 2023). Glucose can cross the placenta along a concentration gradient via carrier-mediated diffusion. Only 40% to 50% of glucose volume delivered to the placenta reaches the fetus. Insulin and glucagon do not cross the placenta (Aldahmash et al., 2023).

Altered maternal states, either hyperglycemia or hypoglycemia, can profoundly affect the fetus. Mild to moderate maternal hyperglycemia can cause fetal hypoxemia, hyperinsulinemia, increased oxygen consumption, CO2 production, and glucose-lactate uptake (Kua et al., 2019). If hyperglycemia is severe, the effects can include further hypoxemia, hypoinsulinemia, increased erythropoietin levels, decreased placental perfusion, metabolic acidosis, and even potential fetal demise (Kua et al., 2019). Infants born from pregnancy impacted by diabetes are at a higher risk of developing insulin resistance (Kua et al., 2019).

The effects of maternal hypoglycemia on the fetus can also be significant. With a decrease in fetal blood sugar, there may be an increase in catecholamines and cortisol levels. Certain maternal states may predispose the fetus or infant to abnormal glucose environments. Maternal diabetes is a classic example of excessive substrate presented to the fetus. The increased circulating glucose crosses the placenta and causes fetal hyperglycemia.

When exposed to high maternal glucose levels, the fetus of a diabetic mother produces large amounts of insulin to maintain normoglycemia. Insulin suppresses glycogenolysis and lipolysis of adipose tissue, limiting the neonate's ability to use alternative sources of glucose supply that are eliminated at delivery, neonatal hyperinsulinemia continues, and the newborn becomes hypoglycemic within one to two hours of life (Nakrani & Wineland, 2023). These infants can often achieve glucose homeostasis within 48 hours but may take up to five days to achieve normoglycemia (Nakrani & Wineland, 2023).

Maternal hypertensive states, especially pregnancy-induced hypertension, are the classic examples of reduced availability of substrates and fetal accretion of stores. Maternal drugs may result in hypoglycemia in the newborn (Rozance, 2024). Oral beta-sympathomimetic tocolytic drugs cause sustained hypoglycemia and elevated cord blood insulin levels in infants delivered within two days of terminating tocolytic therapy (Rozance, 2024). Tocolytic therapy, used to delay preterm labor, has been shown to cause maternal hyperglycemia, thus leading to fetal hyperinsulinemia (Rozance, 2024). Other maternal hyperglycemia causes include large infusions of intravenous (IV) glucose solutions before delivery (Rozance, 2024).

At birth, the maternal glucose source is cut off after the umbilical cord is cut. The infant is tasked with transitioning from a high-carbohydrate diet to a high-fat diet (Tas et al., 2020). Glycogen stores are usually gone by three to twelve hours. Even if feeding occurs, the usual intake is limited, so the infant must initiate gluconeogenesis (Tas et al., 2020).

There are major changes in glucoregulatory hormones that occur with birth. Epinephrine, norepinephrine, and glucagon levels increase, while insulin levels decrease. These changes result in the mobilization of glycogen stores and free fatty acids. The infant’s body must perform glycogenolysis and gluconeogenesis to prevent hypoglycemia and survive.

During the immediate post-natal period, there is a progressive refinement of the transition to self- "feeding." The ability to perform gluconeogenesis through increases in PEPCK improves. The balance between intake or stores and the utilization of these substrates also becomes more stable. Routine monitoring of blood glucose levels in healthy-term newborns is unnecessary unless high-risk conditions exist that indicate monitoring (Rosenfeld & Thornton, 2023).

Several hormones regulate glucose metabolism in neonates, with insulin being the most important. Produced by the beta cells of the pancreas, insulin facilitates the entry of glucose into cells by altering cell membrane permeability. This process reduces blood glucose levels and allows glucose to be used as an energy source. Insulin also enhances the activity of enzymes involved in phosphorylation, which further helps transport proteins and fats into cells.

Glucagon is secreted by the alpha cells of the pancreas; its effects are the opposite of insulin. Glucagon’s main role is to raise blood glucose levels by stimulating glycogen breakdown (glycogenolysis) and promoting the production of glucose from non-carbohydrate sources (gluconeogenesis) (Nakrani & Wineland, 2023). Additionally, glucagon triggers the release of free fatty acids into the bloodstream.

Glucocorticoids, particularly cortisol, also contribute to blood glucose regulation. These hormones, produced by the adrenal cortex, help maintain glucose levels by promoting the mobilization and utilization of amino acids (Chourpiliadis, 2023). Cortisol can increase blood sugar levels significantly. Other hormones, such as human growth hormone (HGH) and thyroxine, also play a role in glucose regulation, supporting growth and development (Chourpiliadis, 2023).

Epinephrine, synthesized in the adrenal medulla, is another important regulator of blood glucose (Khalil & Rosani, 2024). It promotes glycogenolysis, gluconeogenesis, and glucagon secretion, while simultaneously inhibiting insulin secretion. Together, these hormones contribute to the maintenance of stable blood glucose levels, particularly in times of stress or increased metabolic demand (Barrington, 2024).

The blood glucose level is the dissolved glucose in the bloodstream. The level is always in flux and reflects the balance between intake or production of glucose and utilization for energy or storage. A variety of other hormones may also impact blood glucose levels, with insulin being the main blood glucose-lowering hormone. Glucagon, cortisol, and epinephrine are the main glucose-raising hormones.

Hypoglycemia can be defined as any plasma glucose level of less than 55 mg/dL with symptoms that resolve with glucose treatment (some may consider a level of 70 or below to be hypoglycemic) (Rosenfeld & Thornton, 2023). The blood glucose level in the newborn is a balance between the amount of glucose taken in and the amount used by the cells. The level drops to its lowest point by about two hours of age. How rapidly or low an insulin level may drop after birth may depend on the pre-birth insulin level. Hypothermia may also contribute to hypoglycemia because the infant rapidly depletes body stores to increase heat production (Rosenfeld & Thornton, 2023).

In all neonates during the first 24 hours, plasma glucose less than 40 mg/dL is defined as hypoglycemia. Beyond 24 hours, 40 to 45 mg/dL constitutes hypoglycemia (Adamkin et al., 2011).

The blood sample from which the level is determined greatly impacts the level. The level can be determined in both plasma and whole blood. In general, plasma is the preferred source because whole blood values can be 10 to 15 mg/dL less, especially with increased time from a blood draw to analysis (Harding et al., 2024). If an infant is receiving IV dextrose, then it is not recommended to collect a sample from a vein in the side where the infusion is occurring. This poses a risk of contamination, and subsequent false laboratory specimen results. Infusions often occur in the umbilical artery, which is also not a recommended collection site for an accurate reading (Harding et al., 2024).

Recognition of infants at risk for disturbances in glucose homeostasis is the most basic step in preventing hypoglycemia. In infants with conditions predisposing them to hypoglycemia, glucose levels should always be assessed, screened, and appropriately treated.

Risk factors for neonatal hypoglycemia can include (Harding et al., 2024; Narvey & Marks, 2019):

1. Decreased glycogen availability due to:
   • Prematurity
   • Intrauterine growth restriction (IUGR)
   • Glycogen storage disease
   • Inborn errors of metabolism (IEM)
2. Endocrine issues causing hyperinsulinemia due to:
   • Infant of diabetic mother (IDM)
   • Beckwith-Weidman syndrome
   • Erythroblastosis fetalis due to Rh incompatibility
   • Islet cell dysplasia, nesidioblastosis
   • Medications given to mother (beta-sympathomimetics, beta-blockers, chlorpropamide, beta-agonist tocolytics)
3. Endocrine disorders, including:
   • Hypothyroidism
   • Hypopituitarism
   • Adrenal insufficiency
4. Increased use of glucose due to:
   • Perinatal asphyxia at birth
   • True knots in the umbilical cord
   • Nuchal umbilical cord
   • Meconium aspiration
   • Antepartum administration of IV dextrose
   • Hypothermia

Additional potential causes of hypoglycemia can include congenital heart disease, central nervous system (CNS) abnormalities, and sepsis (Harding et al., 2024).

The successful initiation of a newborn's metabolic processes is crucial for maintaining glucose homeostasis. This process relies on sufficient fetal glycogen and fat reserves, along with a fully developed and functional hormonal regulatory system (Möllers et al., 2022). Preterm infants and those small for gestational age (SGA) often have inadequate fat and glycogen stores. Similarly, post-term infants, who may experience depleted glycogen levels due to placental insufficiency, are also at an increased risk of hypoglycemia. These infants are most vulnerable to developing low blood sugar within the first 6 to 12 hours of life, especially if they do not receive adequate oral or parenteral nutrition (Möllers et al., 2022).

Blood glucose sampling techniques and analysis methods can have a significant impact on the measured glucose levels. Bedside glucose monitoring with glucose meters (glucometers) has become the standard practice for assessing blood glucose. While these devices offer rapid and relatively accurate results and are easy to use, operators must adhere to standardized procedures, understand how the device works, calibrate it properly, and perform regular quality control checks.

Glucose meters allow for quick screening and timely detection of hypoglycemia, but they must be used with caution. Since these devices measure whole blood glucose, they can sometimes underestimate the true blood glucose level. Various factors, such as the pressure applied when blotting or wiping the skin, how test strips are handled, and the expiration date of strips, can all influence the results. Bedside glucose testing should primarily be considered a screening tool, as these devices can significantly differ from actual blood glucose levels, particularly when readings are below 50 mg/dL.

Differences in blood sample sources, as well as contamination from substances like isopropyl alcohol, can lead to inaccurate readings, with alcohol contamination causing falsely lowered glucose levels (Jońca et al., 2021). To improve accuracy, it is important to allow any isopropyl alcohol to fully evaporate before puncturing the skin (waiting approximately 30 seconds), and to wipe away the first drop of blood before applying it to the test strip (Jońca et al., 2021).

Further laboratory confirmation of serum glucose values collected from a point-of-care glucose meter should be performed when the test strip results are abnormal or suspicious for error. Because of the potential significant risk to the patient if treatment is delayed, interventions should be initiated if test strips results or if clinical symptoms suspect hypoglycemia, even if the laboratory confirmation is not yet available.

The following information is important to keep in mind when drawing blood samples for glucose analysis (Mathew & Zubair, 2023):

1. Whole blood glucose concentrations are about 15% lower than plasma glucose concentrations because the erythrocytes will continue to metabolize the glucose in the sample. The higher the hematocrit (which we know is the percentage of red blood cells (RBCs) in the sample of whole blood), the greater the difference between the whole blood and the plasma values.
2. Venous blood glucose concentrations are approximately 10% to 15% lower than arterial blood glucose concentrations that are approximately 10% less than capillary specimens because the venous blood returns from the tissues where glucose has been extracted from the arterial supply and utilized.
3. Blood samples should be put immediately on ice to slow glucose metabolism in the sample. The glucose concentration can fall as much as 18 mg/dL/hour when waiting to be analyzed, sitting at room temperature.
4. The infant's heel needs to be warmed (most commonly with an instant heel warmer) prior to drawing capillary samples, as venous stasis may cause an underestimation of actual blood glucose value. Heel warming helps to increase capillary blood flow to the area that is about to be sampled and is said to reduce the discomfort for the infant. It is important to note that recent research has found that warming already warmed heels (above 37.0°C) can result in skin injury (Toennseen et al., 2023). It is recommended that gentle selective warming take place.
5. Ideally, a sample tube containing a glycolytic inhibitor should be used to prevent erythrocytes in the sample from continuing to metabolize glucose and falsely reducing the glucose level. If tubes containing glycolytic inhibitors are not available, the sample should be transported on ice and analyzed quickly.

Nurses who care for newborns should assess the infant for signs and symptoms of hypoglycemia on an ongoing basis. These symptoms are often subtle, nonspecific, and extremely variable.

Signs and symptoms of hypoglycemia can include(Rozance, 2024; Adamkin et al., 2011):

• Abnormal, weak, or high-pitched cry
• Poor feeding
• Vomiting
• Diaphoresis
• Hypothermia
• Neurologic instability:
  • Tremors
  • Hypotonia/ Floppiness
  • Irritability
  • Jitteriness
  • Seizures
  • Lethargy
  • Abnormal eye movements
  • Exaggerated Moro reflex
• Cardio-respiratory disturbances:
  • Cyanosis
  • Pallor
  • Apneic episodes
  • Tachypnea

Nurses providing ongoing care at the bedside are often the first to identify an infant at risk for developing hypoglycemia.

Prophylactic care for any infant at risk for hypoglycemia includes (Cranmer, 2024; Narvey & Marks, 2019):

1. Early enteral feeding, if appropriate, or IV infusion of dextrose
2. Maintenance of a normal body temperature
3. Treatment of problems that increase energy requirements

When a newborn arrives in the nursery, a protocol that includes a head-to-toe physical examination and gestational age assessment of predisposing risk factors should be followed. A nurse's recognition of hypoglycemia begins with the nursing process:

When hypoglycemia is suspected, the plasma glucose concentration must be determined, preferably by laboratory chemical analysis. However, even when ordered “STAT”, laboratory analysis takes a minimum of up to one hour to obtain, unless your facility carries a point-of-care system.

It is important to note here, as we are discussing nursing care, that nurses have a role in helping to prevent or reduce the risk for hypoglycemia for all infants. This role can include regard to ensuring access to breastfeeding, whenever safe and possible. Hypoglycemia in breastfed newborns can be prevented or greatly reduced by hospital policies that support breastfeeding. These pro-breastfeeding practices can include (Giouleka et al., 2023):

• Breastfeeding as quickly after delivery as possible (preferably in the first hour)
• Skin-to-skin contact between mother and newborn (to prevent cold stress and use of glucose stores)
• Breastfeeding 8 to 12 times per day (to maintain blood glucose level)
• Feeding in response to readiness cries, not on a schedule (on demand)
• Not letting the newborn get to the point of crying (crying depletes glycogen stores rapidly and can contribute to a steep decline in blood sugar levels)
• Pump or hand expressing colostrum into a spoon or cup for the newborn that is reluctant to suckle at the breast and feed the newborn colostrum several times per hour until the newborn can feed adequately at the breast (to maintain blood glucose level)

The treatment of neonatal hypoglycemia begins with anticipation and prevention. Early identification of the infant at risk for developing hypoglycemia and the use of prophylactic measures to prevent the occurrence constitutes the best treatment plan.

In those infants who become hypoglycemic, the treatment goals are twofold:

1. Return the glucose level to normal levels
2. Maintain glucose within the normal range

In the infant who is at risk for or has hypoglycemia secondary to increased utilization (such as in IDM), early feedings may be all that is needed for prevention or treatment. Other infants may require more complex care. Maintaining a neutral thermal environment is important to prevent increased metabolic demands due to hypothermia. Consider placing the infant in a closed isolette to help them maintain their temperature while minimizing metabolic needs. However, be careful to not overheat the infant by following protocol for placement in an isolette to include temperature monitoring and the removal of extra clothing and swaddle. Providing long periods of uninterrupted rest can also conserve energy, which also helps to maintain glucose levels.

Often hypoglycemia is treated in the NICU through IV dextrose infusions. For hypoglycemia requiring treatment, the general practice is to give a bolus of D10W, followed by a D10W infusion of 4-8 mg/kg/minute (80-100 mL/kg per day) (Giouleka et al., 2023).

Blood glucose needs to be monitored every 20-30 minutes if symptomatic or every 1-2 hours (if asymptomatic) to prevent hyperglycemia during the acute phase of treatment. It might also be helpful to attempt an upgrade from the D10W to D12.5W, as it has a higher dextrose concentration, depending on blood glucose level needs. It is important to note here that D12.5W is the highest dextrose concentration that can be safely administered through a peripheral IV (Kiyohara et al., 2022). Higher concentrations of dextrose require the placement of a central line. Steroids and glucagon may be used to increase blood glucose if IV dextrose fails to correct hypoglycemia.

The outcome for infants with neonatal hypoglycemia is directly related to the hypoglycemia's duration, severity, and underlying etiology. Infants with asymptomatic hypoglycemia usually have a normal developmental outcome, although minor abnormalities (such as learning disabilities and abnormal EEGs without seizure disorders) have been reported in long-term follow-up.

Symptomatic infants have a poorer prognosis, with issues ranging from learning disabilities to cerebral palsy and seizure disorders (Rozance, 2024). Prompt initiation of treatment is associated with positive outcomes.

The primary goals of managing neonatal hypoglycemia are to identify those at risk, pay attention to and correct blood glucose levels (as necessary), and prevent unnecessary interventions. The overall treatment will depend on symptomatology and risk factors.

Although a few different guidelines exist for the screening and management of hypoglycemia, the American Academy of Pediatrics (AAP) has one such guideline that came out originally in 2011 and was further reaffirmed in 2015 that guides specific care for late preterm infants (34 to 36 weeks gestation), term SGA infants, and IDM or LGA infants greater than or equal to 34 weeks gestation (Adamkin et al., 2011; Giouleka, et al., 2023).

If a newborn, matching the specific criteria above, is asymptomatic, the AAP recommends treatment in two divided time frames (Adamkin et al., 2011; Giouleka, et al., 2023).

1. Birth to 4 hours of age
2. 4 to 24 hours of age

The AAP recommends the following for the asymptomatic infant, birth to 4 hours of age(Adamkin et al., 2011; Giouleka, et al., 2023):

• Encourage the initiation of the first feed within one hour of delivery
• Check a blood glucose level 30 minutes after the first feeding
• If the glucose level is < 25 mg/dL, initiate another feeding and recheck the glucose level in one hour
• If the glucose level is still < 25 mg/dL, then IV dextrose will be necessary
• If the glucose level is 25-40 mg/dL, then attempt another feeding and consider IV dextrose as needed

The AAP recommends the following for the asymptomatic infant, 4 to 24 hours of age (Adamkin et al., 2011; Giouleka, et al., 2023):

• Feedings should occur every 2-3 hours
• Check blood glucose level prior to each feeding
• If the glucose level is < 35 mg/dL, initiate the feeding and recheck the glucose level in one hour
• If the glucose level is still < 35 mg/dL, then IV dextrose will be necessary
• If the glucose level is 35-45 mg/dL, then attempt another feeding and consider IV dextrose as needed

Management of a symptomatic neonate experiencing hypoglycemia may include (Adamkin et al., 2011; Giouleka, et al., 2023):

• Identifying the risks involved in not implementing rapid treatment.
• For glucose levels < 40 mg/dL, nurses must initiate immediate IV dextrose therapy as an IV bolus (typically of 200 mg/kg D10W, placed on a pump, normally over a short period of time, usually 1-2 minutes, or given IV push over 1-2 minutes).
• A maintenance rate will be administered following the initial bolus, with an expectation of a response within thirty minutes.
• As mentioned earlier in this course, the standard maintenance rate for D10W is 4-8 mg/kg/minute (80-100 mL/kg per day).
• The glucose level should be maintained between 40-50 mg/dL.
• For infants with lower glucose levels, the protocol is similar, but with a higher bolus amount.
• IV fluid rate should be driven by blood glucose levels. If the blood glucose level is not maintaining with the current maintenance rate of D10W, the rate can be increased, sometimes with each blood glucose check, depending on unit policy and provider orders.

Alternative therapy options may include the use of hydrocortisone, a potassium channel activator, octreotide, and even surgical interventions in severe cases (Giouleka, et al., 2023).

Another possible treatment option, 40% oral dextrose gel has gained more popularity in recent years, and is sometimes used as a first-line treatment for prevention of asymptomatic neonatal hypoglycemia, with one goal of trying to prevent a NICU stay, keeping infants with their mothers when possible (Giuseppe et al., 2024). According to the research, the early administration of oral glucose gel at a dosage of 200 mg/kg (0.5 mL/kg) can be effective in reducing incidence of hypoglycemia, admission to the NICU in infants at risk, and hospital costs as well as preserving exclusive breastfeeding (Giuseppe et al., 2024; Batra et al., 2024). The oral dextrose gel is applied to the inside of the infant’s mouth, massaged directly into the buccal mucosa, before allowing them to continue with a normal feeding at the breast or of formula (Edwards et al., 2022). General parameters of which infants would qualify for an oral dextrose gel attempt are those who are hypoglycemic, greater than or equal to 35 weeks of gestational age, AND less than 48 hours of life (Starship Hospital, 2024). The blood glucose should be rechecked 30 minutes after administration (Starship Hospital, 2024). Oral dextrose gel has shown to be a simple, inexpensive, and generally effective initial treatment for infants during their first 48 hours of life (Edward et al., 2022).

Once glucose levels have stabilized and are appropriate for the age of the infant, the weaning process for maintenance fluids (D10W) can begin slowly, while the blood glucose levels are carefully watched for rebounding hypoglycemia. After stabilization, many units have protocols that include Q3h (every 3 hours) prefeed glucose level checks, for at least three consecutive stable levels, before further weaning of the frequency of glucose level checks, and then their eventual discontinuation.

If glucose levels remain low despite the aforementioned interventions, it is important to consider potential sepsis. A sepsis evaluation should be done to include a complete blood count (CBC), C-reactive protein (CRP), blood cultures, and potentially urine or cerebrospinal fluid (CSF) studies if indicated (Alaska Native Medical Center, 2022). An endocrine consultation should be considered for persistent hypoglycemia (generally past 48 to 72 hours of life) (Abramowski & Ward, 2023).

Hyperglycemia is another glucose management issue that may be encountered in the NICU. Hyperglycemia is usually defined as plasma glucose >150 mg/dL (Balasundaram, 2023; Şimşek et al., 2018). Hyperglycemia is often asymptomatic and is frequently diagnosed during routine screening of an infant at risk.

When symptomatic, the signs and symptoms of hyperglycemia, which are generally non-specific, can include (Balasundaram, 2023):

• Polyuria
• Glycosuria
• Dry, hot, flushed skin
• Dehydration
• Fever
• Feeding difficulty
• Weight loss
• Lethargy

Intracranial hemorrhage may occur in the case of rapid hyperglycemia, often caused by an abrupt bolus of D25W or D50W glucose (Balasundaram, 2023; Widness, 2022).

The primary causes of hyperglycemia include stress, sepsis, and transient diabetes mellitus. Certain medications, such as methylxanthines and corticosteroids, can also contribute to elevated blood glucose levels. Preterm infants, particularly those born before 30 weeks gestation or weighing less than 1000 grams, are at higher risk for hyperglycemia due to their immature regulatory mechanisms (Butorac Ahel et al., 2022). These infants have a limited ability to secrete insulin from the pancreas, a decreased sensitivity to the insulin that is secreted, and an inability to suppress endogenous glucose production even when they receive an adequate exogenous supply. In general, the smaller the infant, the less likely they can tolerate maintenance rates of exogenous glucose. Critically ill infants, especially those with respiratory distress, hypoxia, or pain, are also at risk for hyperglycemia because these conditions cause increases in circulating catecholamine levels. Catecholamines cause increased lipolysis and glycogenolysis and antagonize the action of insulin.

Though it rarely occurs, neonatal diabetes is a genetic disease affecting 1 in 90,000 births (Chisnoiu et al., 2023). Often defined as severe hyperglycemia with little to no circulating insulin, this is often diagnosed within the first six months of life (Beltrand et al., 2020). It is recommended that infants with neonatal hyperglycemia have genetic testing done, specifically for neonatal diabetes, even in the event that the elevated blood glucoses resolve on their own (Fallabel, 2023).

The incidence of hyperglycemia in neonates varies based on birth weight, gestational age, illness severity, and glucose infusion levels. Approximately 5% of infants receiving IV D10W experience hyperglycemia, with premature infants at higher risk. Neonatal hyperglycemia can lead to complications such as increased intraventricular hemorrhage in preterm infants, possibly due to fluid shifts from changes in osmolality. It can also cause (Balasundaram, 2023; Beltrand et al., 2020):

• Glycosuria
• Osmotic diuresis
• Dehydration
• Electrolyte imbalances, with hypokalemia being a particular concern due to its potential to cause cardiac arrhythmias

Premature infants may develop hyperglycemia associated with group B strep or E. coli sepsis. Some infants with early sepsis have an increased glucose demand. As sepsis advances, depression of insulin secretion and impaired receptor response in target organs may contribute to hyperglycemia. Therefore, infants showing signs of hyperglycemia or an escalating need for glucose prior to the onset of hyperglycemia should be assessed for potential infection. (Centers for Disease Control and Prevention [CDC], 2024).

Nursing care for neonatal hyperglycemia will generally include (Balasundaram, 2023; Fallabel, 2023):

• Obtaining frequent blood glucose levels
• Monitoring fluid intake and output (watch for electrolyte imbalances)
• Administering insulin boluses or infusion as needed for persistent hyperglycemia
• Assessing for potential underlying cause

Certain factors involved in the care of sick newborns can cause hyperglycemia. Many infants are treated with theophylline or caffeine for apnea of prematurity or are on steroids for respiratory disease. These medications may cause an increase in blood glucose. Additional types of stress, such as surgery, pain, or sepsis, may also increase circulating catecholamines, which will result in hyperglycemia (Nimavat, 2022).

Glucose requirements depend on metabolic rate: the higher the metabolic rate, the higher the glucose requirement.

The large energy requirement of the brain affects the metabolic rate, increasing the glucose needed as the ratio of brain mass to body mass increases. Premature infants have a higher brain-to-body mass ratio than term infants, requiring more glucose (Cacciatore et al., 2022). Unfortunately, because of the immature regulatory mechanisms, few infants who weigh less than 1,000 grams tolerate maintenance amounts of glucose, especially in the first week of life.

Neonates with hyperglycemia are often started on a low-dose glucose infusion to normalize blood glucose, with labs checked every 4-6 hours (Parappil et al., 2022). If a blood glucose level returns higher than 8 mmol/L, then urine studies are ordered to assess for potential glycosuria (Parappil et al., 2022). When glycosuria is found to be significant (≥1+), the risk for increasing osmolality resulting in osmotic diuresis and weight loss is increased (Parappil et al., 2022). Infants are treated with IV hydration if urine studies demonstrate signs of osmotic diuresis (Parappil et al., 2022).

Insulin therapy is started when a blood glucose level is greater than 11.1 mmol/L (200 mg/dL) (Parappil et al., 2022). Insulin therapy is often comprised of small insulin boluses (0.05-0.1 units/kg given over 15 minutes via IV) with frequent blood glucose monitoring (30-60 minutes after bolus) (Parappil et al., 2022). Generally, a maximum of three boluses are recommended in a 4–6-hour time frame (Parappil et al., 2022). If blood glucoses still remain elevated after the boluses, an insulin infusion can be initiated (Parappil et al., 2022). The dosage for a continuous infusion should start at 0.01 and 0.05 units/kg/hour and increase, gradually, as needed, to a maximum of 0.1 units/kg/hour (Parappil et al., 2022). For a continuous insulin infusion, a blood glucose level must be taken within 30-60 minutes of its initiation and after any change to its rate (Parappil et al., 2022). Otherwise, blood glucose levels should be obtained hourly until the infant’s levels are stable (Parappil et al., 2022).

Insulin infusions are slowly titrated downward to avoid hypoglycemia as they are allowing glucose levels to stabilize (Parappil et al., 2022). A continuous infusion can be stopped when the infant’s blood glucose level is at or below 8.33 mmol/L (150 mg/dL). However, the blood glucose level must then be watched closely after infusion discontinuation for the next 12-24 hours, to catch any rebounding hyperglycemia (Parappil et al., 2022).

It is important to note here that insulin may bind to the polyvinyl IV tubing, causing fluctuations in the amount of insulin delivered, despite constant flow rates (Robert et al., 2021). Interventions to decrease the amount of insulin that binds to the IV tubing include flushing the tubing with the insulin solution and using special IV tubing. The most cost-effective method of administration is to use small-volume tubing, flush the tubing with the insulin solution, allow it to sit filled for 20 minutes to allow time for the insulin to “adsorb” into the tubing, and administer via a syringe pump (Robert et al., 2021).

Insulin is compatible with saline solution and dextrose solution, including total parenteral nutrition (TPN). Although insulin may be added to most maintenance fluids, a separate IV line should be used whenever possible to be able to titrate insulin’s dosage up or down as needed.

Sarah, a 38 and 6/7 week gestation infant, was born just one hour ago to a mother with gestational diabetes. Sarah's mother's pregnancy and Sarah's birth were without issues nor complications. However, Sarah now presents with jitteriness and irritability. Based on what you know about Sarah, what should your next steps be?

Because Sarah is symptomatic, you check her blood glucose level immediately instead of waiting until 2 hours of age. Sarah’s blood glucose level is 31 mg/dL. Because of this, you treat Sarah immediately with 1.5 mL of 40% dextrose gel per hospital protocol (Sarah weighs 3 kg), and encourage Sarah's mother to breastfeed her child on demand.

After treatment is administered, Sarah's symptoms resolve quickly. Upon the recheck of her blood glucose level after her feeding, it has risen to 55 mg/dL. You check Sarah's blood glucose levels every 3 hours until she is 12 hours old. At this point, with her glucose levels remaining stable, blood glucose checks are discontinued. Sarah continues to breastfeed well and is discharged home with her mother when her mother is cleared to leave.

Monitoring glucose balance can be challenging for neonatal nurses, as neonates are at risk for disruptions in glucose homeostasis due to a variety of factors. High-risk infants frequently show laboratory values and clinical signs indicating either hyperglycemia or hypoglycemia. Careful observation and assessment to identify infants at risk and implement timely interventions are crucial in preventing complications related to abnormal glucose levels, ultimately reducing neonatal morbidity and mortality. The accuracy of test results can be influenced by several clinical and technical factors, and abnormal results may require confirmation with a second sample. However, treatment should not be delayed during this confirmation process.

Insulin is a larger molecule than glucose and does not cross the placenta. As a result, maternal glucose levels are reflected in both the neonatal bloodstream and amniotic fluid. Maternal hyperglycemia can lead to fetal hyperglycemia. Since maternal insulin cannot cross the placenta, elevated glucose levels stimulate the fetal pancreas to release insulin, which also triggers beta cell hyperplasia and increased insulin production that continues after birth. Insulin acts as a primary growth hormone for the fetus, promoting fat accumulation and macrosomia. As a result of this hyperinsulinemia and the abrupt loss of maternal glucose after delivery, the infant may experience hypoglycemia within hours of birth and require close monitoring.

Neonatal nurses care for many infants at risk of abnormal blood glucose levels, so recognizing those at risk allows for timely and appropriate interventions. The quality of information gathered from both tests and clinical observations depends on the nurse's decision-making. Therefore, a solid understanding of glucose dynamics and monitoring techniques is essential for effective care.

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