What is Neonatal Hypoglycemia?
Hypoglycemia, or low blood sugar, is a common issue that can happen to newborn babies. It often requires doctors to perform screening tests and provide treatment during the first few days after birth. However, there is no universally agreed definition of what exactly constitutes low blood sugar levels in newborns, and currently, doctors tend to follow guidelines and treatment plans that are based mostly on opinions from medical experts rather than reliable scientific research.
Despite advances in our understanding, there are still gaps in our knowledge about low blood sugar in the first few days of a baby’s life. There is evidence that healthy babies may naturally experience transient hypoglycemia, or temporary low blood sugar, as part of the normal adjustment to life outside of the womb. Their blood sugar levels can drop to 20 to 25 mg/dL in the first two hours of life. But since we usually don’t measure blood sugar in babies without risk factors for hypoglycemia, it’s difficult to define what ‘normal’ blood sugar levels should be in the first 48 hours of life. It’s also unclear whether these values should apply to babies at risk of metabolic issues, or how low is too low.
In 1988, a study by Lucas and his team suggested that if blood glucose falls below 47 mg/dL, it can lead to negatively affected brain development. His findings were based on a study group of preterm infants who were born underweight and looked at how early feeding strategies affected cognitive outcomes. They found that a blood glucose level of less than 47 mg/dL for several days led to lower motor skills and mental development scores at 18 months. More so, babies who had five or more days of such low glucose levels had three to five times higher risk of neurodevelopmental issues. Therefore, the value of 47 mg/dL has been widely accepted as the defining threshold for hypoglycemia in newborns.
It’s well accepted that very low blood sugar levels can lead to problems like difficulty breathing, fussiness, tiredness, seizures, and even brain damage. Prolonged or symptomatic hypoglycemia might also correlate with long-term problems in brain development. Yet, we still don’t fully understand the long-term significance of brief periods of low glucose levels that don’t show any symptoms. There’s also no concrete evidence to suggest a specific numerical glucose value that predicts brain injury or negative brain development outcomes. Even Lucas acknowledged that the observed association between low glucose levels and poor brain development outcomes may not be strictly cause and effect, and may be influenced by other factors.
What Causes Neonatal Hypoglycemia?
Just after birth, it’s normal for a newborn baby’s blood sugar to drop a little. This is because when the umbilical cord is cut, the continuous supply of sugar (glucose) from the mother through the placenta stops abruptly. Thankfully, for most healthy babies, this minor drop in blood sugar is temporary and doesn’t cause any noticeable symptoms.
However, some babies are at a higher risk of experiencing more severe or longer-lasting low blood sugar, also known as neonatal hypoglycemia. This can be due to a few things: their bodies might not have enough stored glucose or fat; they produce too much insulin, a hormone that regulates blood sugar; their bodies consume glucose quickly; or, the systems in their bodies that respond to low blood sugar, such as the pituitary or adrenal glands, might not work properly. Certain groups of babies are more likely to experience neonatal hypoglycemia:
- Babies who are smaller than normal for their gestational age (the number of weeks they were in the womb)
- Babies born to mothers with diabetes or babies who are larger than normal for their gestational age
- Babies delivered slightly early (34 to 36.6 weeks into pregnancy)
Premature, small for their age, or growth-restricted babies have a higher risk of neonatal hypoglycemia because they have fewer glucose stores, less fat, and great energy needs due to their relatively large brain size. Very small premature babies (less than 2.2 lbs) have an additional risk factor: the enzymes in their bodies that produce glucose are not very active, so these babies can’t make enough glucose on their own.
Babies born to mothers with diabetes, or who are larger than normal, can experience high levels of insulin and increased sugar use, which puts them at risk for neonatal hypoglycemia. When a mother’s blood sugar levels are high during pregnancy, the baby’s pancreas can become overactive and produce too much insulin. After birth, this high insulin level can cause the newborn’s blood sugar to drop too much.
Babies facing stressful conditions around their birth, like difficulties during labor, infections, or congenital heart disease, use energy at a faster pace. This can put them at risk for hypoglycemia. Certain medications given to mothers during childbirth, delaying feeding, and giving babies extra insulin can also cause temporary low blood sugar.
If low blood sugar persists beyond the first two days of life, it may indicate an underlying condition, such as a congenital syndrome, a metabolic disorder that affects energy production, or an endocrine disorder that affects hormone production. Examples of such conditions include congenital hyperinsulinism (overproduction of insulin), Beckwith-Wiedemann syndrome (overgrowth of certain parts of the body), and thyroid or adrenal gland disorders. Inborn defects of metabolism can also lead to persistent neonatal hypoglycemia. These are rare genetic disorders that affect the body’s ability to breakdown certain nutrients.
Risk Factors and Frequency for Neonatal Hypoglycemia
Neonatal hypoglycemia, which is low blood sugar in new-born babies, is reported in varying numbers. The reported cases of this condition depend on several things, like:
- the group of babies studied,
- how often and when the glucose testing is done,
- the testing method used,
- and the definition of hypoglycemia used for the study.
In a 2006 study, researchers were trying to find out how often hypoglycemia happens in the first 48 hours of the life of babies over 35 weeks gestation who were likely to get hypoglycemia. They found that 25% of all births could be at risk for hypoglycemia. Out of these ‘at-risk’ babies, around 51% had at least one event of hypoglycemia.
Signs and Symptoms of Neonatal Hypoglycemia
Neonatal hypoglycemia, or low blood sugar in newborns, can manifest differently in different babies. Some infants, even when extremely low on blood sugar, might not show any outward signs. This condition is what’s known as transitional hypoglycemia. It’s important to note that clinical symptoms don’t mirror blood glucose levels.
The signs of neonatal hypoglycemia might include:
- Sweating
- Difficulty feeding or poor sucking reflex
- Weak or unusually high-pitched crying
- Tremors or shaking
- Cold body temperature
- Getting easily irritated
- Being unnaturally drowsy or lethargic
- Weak muscle tone
- Seizures
- Slipping into a coma
- Pausing in breathing (apnea) or fast breathing
- Blue or purple skin hue (cyanosis)
Testing for Neonatal Hypoglycemia
There are differing guidelines about when to test babies who are at increased risk of neonatal hypoglycemia, a condition where blood sugar levels are too low. These guidelines are set by the American Academy of Pediatrics (AAP) and the Pediatric Endocrine Society (PES).
The AAP suggests checking babies who show symptoms of hypoglycemia and those who have a high risk in the first 12 to 24 hours of life. Babies who are at high risk include those born slightly early (between about 34 and 37 weeks), those who are small or large for their time spent in the womb, and babies whose mothers have diabetes. However, they don’t see a need for regular checks in healthy babies born after a normal pregnancy and delivery.
The PES, on the other hand, suggests screening all infants who have factors that could lead to long-term or severe hypoglycemia. These include babies showing signs of hypoglycemia, those who are large for the time they spent in the womb, and those who experienced stress before or at birth, due to factors like a lack of oxygen or their mother having a condition called pre-eclampsia. The PES also includes babies born slightly too early or too late, those whose mothers have diabetes, babies with family histories of genetic hypoglycemia, and those with certain physical features or medical conditions.
The PES believes that babies who don’t maintain certain blood sugar levels at different points in their early life are at risk for persistent hypoglycemia. They suggest conducting further tests before the baby goes home. The PES also believes that babies should be examined for underlying causes of hypoglycemia after the first 48 hours of life.
Testing at the point of care can quickly and cost-effectively screen for hypoglycemia. However, these tests are less accurate at detecting lower glucose values than lab-based tests. Therefore, if glucose is detected to be abnormally low at the point of care, it should be confirmed by measuring plasma glucose concentration in a clinical lab.
The use of continuous glucose monitoring for detecting and managing neonatal hypoglycemia is being studied. One study found that using continuous monitoring found more cases of hypoglycemia.
In babies with persistent hypoglycemia and a suspected underlying condition, measuring different substances in the blood during hypoglycemic episodes can help identify the metabolic causes of persistent hypoglycemia, which can aid in diagnosing conditions like hyperinsulinism and disorders of fatty acid breakdown.
Treatment Options for Neonatal Hypoglycemia
The definition of neonatal hypoglycemia, which is low blood sugar in newborn babies, isn’t consistent, so doctors don’t always agree on how low a baby’s blood sugar levels have to be before treatment is needed. The ultimate goal of managing this condition is to prevent potential brain injury and long-term development-related issues that can occur because of low blood sugar.
Starting breastfeeding early is extremely important. For asymptomatic babies (those not showing symptoms) who are at risk of neonatal hypoglycemia, the American Academy of Pediatrics (AAP) suggests starting feeds immediately after birth and checking the baby’s glucose levels 30 minutes after their first feeding. The AAP recommends blood sugar levels equal to or greater than 45 mg/dL before regular feedings, and intervention if blood glucose drops to less than 40 mg/dL in the first 4 hours of life or less than 45 mg/dL within the first day of life. The best way to manage low blood sugar in symptomless babies is to increase the frequency of feeds. If difficulties with breastfeeding occur, infant formula can often be chosen as it’s inexpensive, contains a high level of carbohydrates, and is easy to give, which can lead to a fast rise in blood glucose levels. The glucose levels should be re-checked one hour after feeding.
Dextrose gel, an effective and cost-friendly alternative treatment, can be massaged into the inner lining of the baby’s cheek. It’s beneficial for promoting breastfeeding and bonding between the mother and the baby.
However, there are certain situations when babies need to be admitted to the neonatal intensive care unit for intensive treatment with intravenous dextrose, a type of sugar which is given through the vein. These situations include babies with symptoms of low blood sugar, persistent low blood sugar despite increased feeding, and babies at risk but not showing symptoms with extremely low blood glucose concentrations. Babies on intravenous dextrose must be monitored closely, with blood glucose levels checked frequently.
For the treatment of persistent hypoglycemia, corticosteroids, which decrease the body’s glucose utilization, or glucagon, a hormone that stimulates natural glucose production, can be used.
The Pediatric Endocrine Society recommends maintaining glucose concentrations above 50 mg/dL for babies at risk of hypoglycemia who don’t suffer from any inborn disorders within the initial two days of life and above 60 mg/dL thereafter. Infants unable to maintain these levels despite regular feedings should be evaluated to rule out other causes of persistent hypoglycemia before going home.
For babies with long-lasting hypoglycemia, the focus is to prevent recurring episodes of hypoglycemia. In specific conditions such as neonates with inborn defects of metabolism and conditions where the body cannot produce enough sugar, the aim is to prevent metabolic acidosis (a condition that occurs when the body produces too much acid) and potential growth failure. For these conditions, doctors recommend using medications that can help maintain suitable blood glucose levels. If the doctor suspects certain congenital conditions where the insulin secretion is more than normal, it’s recommended for the child to see an endocrinologist or a geneticist.
What else can Neonatal Hypoglycemia be?
Babies with low blood sugar, or neonatal hypoglycemia, may show symptoms that are quite general and can be seen in other health issues as well. These other conditions might include being born prematurely, having a severe infection (sepsis), experiencing a lack of oxygen to the brain at birth (hypoxic-ischemic encephalopathy), or having low levels of sodium in the blood (hyponatremia). Although it’s rare, doctors also need to ensure that there aren’t ongoing conditions causing the low blood sugar.
What to expect with Neonatal Hypoglycemia
It’s not yet fully understood how low blood sugar in the first two days of life, even if it shows no symptoms, can affect lifelong development of the brain and body. Previously, it was believed that even early, symptom-free low blood sugar could harm a child’s development in the long run. This theory was supported by a significant 1988 study and a few others. However, these studies aren’t quite perfect as they failed to include controls of normal blood sugar measures and were unclear in their definition of ‘hypoglycemia’, which means low blood sugar.
A review published in 2006 assessed the concrete evidence of newborn low blood sugar impacting developmental results. The authors concluded that the research till that point did not provide enough reliable proof regarding the effects of newborn low blood sugar on a child’s development. Thus, they called for a well-thought-out, forward-looking study on the topic.
Even though the scientific community has called for more research in this area, there have only been two studies that meet the strict methodological standards. One of these is a 15-year follow-up study from 2012 that looked at prematurely-born infants who experienced recurring low blood sugar in the first 10 days of life. The research found no difference in development or physical disability at 2 years old or later at 15 years, between those infants and those who had normal blood sugar levels. This study concluded that having repeated low blood sugar in the first ten days of life didn’t appear to harm prematurely-born infants as once thought.
Another landmark study, known as the CHYLD study, examined infants born after 32 weeks of gestation. It found that maintaining blood sugar above a certain level did not correlate with an increased risk of neurological or sensory development issues at 4.5 years of age. Even the infants who had more severe or prolonged low blood sugar episodes did not exhibit worse outcomes. Blood sugar stability in the first 48 hours of life was found to be the most predictive factor of a child’s development. Infants with the highest blood sugar instability faced two to three times the risk of neurological or sensorial problems. Interestingly, “hyperglycemia,” which means high blood sugar levels, correlated with an increased risk of poor visual motor and executive functioning. This leads to the question of whether infants with high or low early blood sugar values may be at risk of worse developmental outcomes in the future.
Possible Complications When Diagnosed with Neonatal Hypoglycemia
Extended and serious periods of low blood sugar in newborns can result in tragic outcomes such as long-lasting developmental disabilities, brain damage that affects physical coordination, and even death. In particular, babies born with medical conditions causing consistent low blood sugar face higher risks of serious illness or death, with as many as 25 to 50% developing disabilities.
Though it’s true that nerve tissues can continue to survive despite low blood sugar by using alternative nutrients like ketone bodies, certain proteins, and lactate, the concept is that these backup fuels may actually serve to protect the developing newborn brain. However, eventually, a source of glucose needs to be provided.
Back in 1967, a group of researchers shared their discovery on this topic after studying the medical cases of 6 infants suffering from severe and prolonged low blood sugar within their first week of life. What they found was severe and extended low blood sugar can lead to widespread damage in the central nervous system and can result in death if the condition is not addressed. However, brain damage was less severe in the babies who were given glucose as a treatment. So, it is crucial to quickly identify conditions that lead to persistent low blood sugar levels.
Possible Health Consequences for Infants:
- Long-lasting developmental disabilities
- Physical coordination issues (cerebral palsy)
- Potential death
- Persistent low blood sugar levels
- Severe damage to the central nervous system
Essential Treatments:
- Identifying and addressing conditions causing persistent low blood sugar
- Providing glucose as a treatment
Preventing Neonatal Hypoglycemia
Regular testing of a newborn baby’s blood sugar levels and diagnosing them with low blood sugar (or neonatal hypoglycemia) can be stressful for new mothers. The most effective way to control this situation is to encourage a strong initial connection between the mother and baby, and to start breastfeeding early on. This helps not only in controlling the baby’s blood sugar level but also in strengthening their overall health.
