What is Neonatal Hyperglycemia?

Neonatal hyperglycemia, or a high blood sugar level in newborns, is typically defined as having a serum glucose level (the sugar level in your blood) over 150 mg/dl (8.3 mmol/L), or a whole blood glucose level over 125 mg/dl (6.9 mmol/L). This is true regardless of the baby’s gestational or postmenstrual age, which means the baby’s age in weeks from the mother’s last period. Generally, a baby’s blood sugar level should be between 70 to 150 mg/dl for it to be considered safe. The safety threshold is determined based on the kidney’s ability to handle glucose in premature babies.

What Causes Neonatal Hyperglycemia?

Hyperglycemia, or high blood sugar, in newborn babies can occur due to various reasons such as prematurity, stress, feeding practices, infection, or wrong medications. These factors often work by affecting the body’s insulin level and function, and hence the sugar control.

Premature babies or those affected by intrauterine growth restriction, a condition where a baby doesn’t grow as expected in the womb, can suffer from low insulin levels or an inability to control sugar production in the liver. This condition can cause high sugar levels in newborns.

Increased levels of stress hormones like epinephrine and norepinephrine, which are released under different conditions such as after infusions, seizures, or physical stress (like surgery, pain, low oxygen, breathing difficulty, or severe infection), can also contribute to hyperglycemia. They do this by inhibiting the secretion and action of insulin, a hormone that controls blood glucose levels. Further, these stress hormones stimulate the production of glucagon, a hormone that increases sugar levels.

Feeding practices can also cause hyperglycemia in newborns. A delay in starting feeding can reduce the secretion of incretin, a hormone that helps lower blood sugar levels. Also, hyperosmolar formulas, which have a high concentration of certain particles, may lead to temporary high blood sugar. Further, total parenteral nutrition, a method of feeding that bypasses the gastrointestinal tract, can result in hyperglycemia if the provision of certain nutrients like amino acids is delayed or if the rate of lipid (fat) infusion is high. Lipids can increase free fatty acids in the body, which competitively inhibit glucose oxidation, leading to high sugar levels.

Healthcare professionals should suspect sepsis, a serious bodywide infection, or Necrotizing enterocolitis (NEC), a medical condition where a portion of the bowel dies, if hyperglycemia occurs without any change in the rate of sugar infusion.

Mistakes in calculating the sugar infusion rate can also cause hyperglycemia in newborns. Some medications given to the mother or the baby can also push up blood sugar levels. In instance, diazoxide given to the mother might result in high blood sugar, low blood pressure, and high heart rate in the newborn. Similarly, antenatal steroids, dopamine, dobutamine, epinephrine, caffeine, theophylline, phenytoin, and corticosteroids given to the newborn can trigger hyperglycemia.

In some cases, newborns who are unusually small for their gestational age can develop temporary diabetes, a condition marked by high blood sugar levels that resolve on their own after some time.

Risk Factors and Frequency for Neonatal Hyperglycemia

Hyperglycemia, which is high blood sugar, is more common in babies born prematurely than in those born at term, and it usually appears within the first week of their lives. Usually, it takes about two to three days for this condition to resolve in most newborns, but it can sometimes last up to ten days. Even though low blood sugar (hypoglycemia) is more common in newborns, high blood sugar levels can lead to higher risks of sickness and death among them. The risk of newborn hyperglycemia is related inversely to birth weight and the time the baby has spent in the womb. It happens in about one-third of babies who are born prematurely or are small for their gestational age.

Hyperglycemia is more common in premature babies than in full-term babies.
It usually appears in the first week of life.
It commonly resolves over two to three days, but can last up to ten days.
Although hypoglycemia (low blood sugar) is more common in newborns, hyperglycemia can lead to more serious health issues.
The risk of high blood sugar in newborns is inversely related to birth weight and the duration of pregnancy.
About one-third of pre-term and small-for-gestational-age babies experience hyperglycemia.

Signs and Symptoms of Neonatal Hyperglycemia

Hyperglycemia, or high blood sugar, doesn’t have specific physical signs that doctors can look for. When examining a patient, doctors might notice signs related to what’s causing the high blood sugar levels. For instance, someone with sepsis might have issues with temperature stability and blood flow. Here are some signs that could suggest high blood sugar, even though they aren’t exclusive to this condition:

Increased urine output
Dehydration
Weight loss
Fever
Difficulty feeding

Testing for Neonatal Hyperglycemia

If your newborn’s initial blood sugar test (taken using point-of-care blood glucose testing) shows a high sugar level, your doctor will want to confirm this by testing the sugar level in your baby’s blood serum. This confirmation is important before starting any treatment for high blood sugar in a newborn, also known as neonatal hyperglycemia.

For this follow-up test, blood taken from a vein (venous blood) is preferred over blood taken from a small prick on the heel (capillary blood). The reason being, heel-prick blood tests can show blood sugar levels that are about 15% lower than the actual amount. Plus, the proportions of different blood cells (the hematocrit value) can affect these tests as well.

If the urine has high sugar levels (2+ or higher), it may suggest that the baby’s body is trying to get rid of excess sugar by passing it out in the urine. This could potentially cause dehydration.

Other tests your doctor may order include a complete blood count and a C-reactive protein test. These will help to rule out sepsis, a severe infection that can spread in the bloodstream.

Monitoring the levels of your baby’s body salts (serum electrolytes) is also important because high blood sugar can cause increased urine production leading to a loss of these essential substances.

The doctor might also weigh the baby regularly to keep track of the hydration status, as weight loss can indicate dehydration.

If your baby’s high blood sugar condition persists, your doctor may want to check the baby’s serum insulin level, and serum and urine C-peptide levels. These tests help to rule out certain types of genetic diabetes and Type 1 diabetes, both of which can cause high blood sugar.

Treatment Options for Neonatal Hyperglycemia

In premature babies or infants with very low birth weight (less than 1500 grams), a sustained high blood sugar level of over 200 mg/dL is worrying. If a baby’s blood sugar hits this level or higher two times within 4 hours, along with high levels of glucose in urine, it’s a sign that treatment is needed. However, high blood sugar without an increase in bodily fluid concentration or excessive urination is not typically treated.

When diagnosing high blood sugar in newborns, health professionals use a formula known as the GIR (Glucose Infusion Rate). This involves calculating the rate that glucose is being supplied to the infant into their bloodstream by taking into account the volume and dextrose concentration of the IV fluids. This IV dextrose concentration can be reduced to lower the GIR, monitored carefully with frequent checks.

If high blood sugar levels persist, potential causes to investigate could include infection, stress, or medication use. In such situations, these underlying causes should be addressed.

Health professionals may resort to insulin treatment if the following occur:

The baby’s blood sugar consistently stays high even when their glucose intake is low,
The infant’s blood sugar level exceeds 250 mg/dL with high glucose level in the urine from two separate samples taken four hours apart.

However, using insulin to treat high blood sugar in newborns is a contentious approach because a large dose of insulin can potentially cause an unhealthy drop in blood sugar levels.

Insulin can be administered in two ways: it can be added to the IV fluids being supplied to the infant or administered separately. A separate approach is preferred because it allows adjusting the rate of insulin without changing the baby’s total IV fluid.

The primary goal of insulin therapy is to maintain the baby’s blood sugar levels between 100 mg/dL and 150 mg/dL. If the baby’s blood sugar level drops to 180 mg/dL, the insulin amount is reduced by half, and if it falls below 150 mg/dL, the insulin treatment is halted.

Also ensure to check the baby’s glucose levels every hour if they are on insulin treatment, especially after each change in insulin administration. If low blood sugar develops, the insulin treatment should be stopped immediately, and a small volume of concentrated (10%) dextrose solution should be given intravenously to quickly elevate the blood sugar levels.

Managing high blood sugar in newborns, especially premature babies, is crucial to prevent complications, such as an increased risk of infection, a weaker immune system, slower wound healing, and even death. We can prevent high blood sugar by initiating feeding early, supplementing TPN with amino acids to stimulate insulin production, monitoring and optimally adjusting the glucose rate in TPN, limiting lipid infusions during high blood sugar phase, and discontinuing stress hormone (like catecholamines) infusions or steroid treatments as soon as the infant’s health improves.

Generally, high blood sugar in newborns, or neonatal hyperglycemia, usually relates to a clinical condition rather than a specific problem with sugar metabolism. Neonatal hyperglycemia could signal another illness like infections, NEC (a disease that affects the intestines of premature infants), or seizures. A rare cause of this condition is neonatal diabetes mellitus, which typically happens in one in 400,000 births.

Neonatal diabetes has three types:

Transitory neonatal diabetes, which makes up more than 50% of cases. This often links to changes in receptors responsible for reacting to a certain type of diabetes medication. It usually starts shortly after birth and then resolves without treatment within 6 months.
Permanent neonatal diabetes which requires treatment throughout the person’s life. This commonly results from changes in the genes responsible for the part of the cell that regulates sugar, known as the ATP-sensitive potassium channel.
Syndromic neonatal diabetes which is usually associated with syndromes like Wolfram syndrome or IPEX syndrome (a disorder that involves a malfunction in the immune system, hormone glands, and it’s usually passed down through families).

What to expect with Neonatal Hyperglycemia

Neonatal hyperglycemia, which is high blood sugar in newborn babies, especially those born prematurely, is often linked to a higher risk of death and illness. The longer the baby has high blood sugar, the more severe the effects can be. Quick assessment and treatment of high blood sugar in newborns can help reduce these risks.

Possible Complications When Diagnosed with Neonatal Hyperglycemia

Babies born prematurely and those with very low birth weight face a higher risk of death. They also tend to have more health problems, especially if they have prolonged high blood sugar levels. These babies are more likely to experience:

Bleeding inside the brain: High blood sugar could lead to bleeding in the brain, a condition known as intracranial hemorrhage. This situation can happen because high sugar levels create an excess of molecules that can pull water out of cells, causing a disruption in the balance of fluids. Thus, every increase of 18 mg/dL in blood sugar concentration adds 1 mOsm/L in serum osmolarity. This condition could result in a quick water movement, leading to possible cerebral bleeding if serum osmolarity exceeds 300 mOsm/L.
Dehydration due to excessive urination: High blood sugar can lead to excessive peeing, causing dehydration.
Imbalance in the body’s salts and minerals: This imbalance can happen due to excessive peeing. Plus, high sugar levels can increase the excretion of sodium through the urine.
NEC: This is a medical condition primarily seen in premature babies where portions of the bowel undergo tissue death.
Eye disease common in premature babies, known as retinopathy of prematurity.
Severe lung disease.
Weakened immune system and increased risk of widespread bacterial infection throughout the body or sepsis.
Poor ability to heal wounds.

There may also be long-term problems, including:

Negative effects on brain development.
Resistance to insulin and difficulty processing sugar.

The potential side effects of the treatments include an increase in the risks of low potassium levels and low blood sugar levels due to insulin infusion.

Preventing Neonatal Hyperglycemia

Neonatal hyperglycemia, or high blood sugar levels in newborn babies, is a significant concern especially in premature infants. This is because their bodies have not yet fully developed the mechanisms needed to maintain balanced blood sugar levels. If your baby was born prematurely or is small for their gestational age (their developmental stage in the womb), you may have concerns about regular blood sugar testing.

As healthcare providers, it’s our role to help you understand why this monitoring is important, and what it means for your child’s health now and in the future. We will explain the immediate and long-term effects of neonatal hyperglycemia to make sure you’re fully informed about your baby’s condition.