Neonatal hypoglycaemia is defined as blood glucose levels < 2.6mmol/L.
It’s a common problem in the first days of life, affecting up to 15% of neonates. It can be due to a variety of reasons, stemming from factors such as maternal diabetes, preterm birth, congenital hyperinsulinism or transient hypoglycaemia of the newborn.
Recognising the condition early is vital as left unaddressed, hypoglycaemia can lead to serious consequences for the newborn including neurological impairment and seizures.
Contents
Neonatal physiology
Within the first few hours of life, blood glucose levels fall rapidly since the continuous glucose supply from the placenta in intrauterine life is removed. Glucose levels steadily begin to rise again over the first few days and return the normal range (3.9-5.6mmol/L). Some infants fail to make this adaptation to extrauterine life, and so are at a greater risk of symptomatic hypoglycaemia, therefore at-risk infants must have their blood glucose levels monitored regularly post-delivery.
The level of blood glucose at which hypoglycaemia leads to brain injury and impacts development is unknown. Less than 2.6mmol/L is the most widely used threshold in neonates for intervention to raise blood glucose. This is based on evidence currently available.
Persistently low blood sugar (<1mmol/L for >1 hour) is associated with neurological dysfunction and carries a high risk for cerebral injury which leads to adverse neurodevelopmental outcomes through widespread white matter injury. There is also evidence emerging in the literature that blood glucose levels < 2mmol/L can also impact development.
Risk factors
Risk factors for neonatal hypoglycaemia can be grouped into maternal and neonatal factors.
Maternal factors | Maternal diabetes (poorly controlled diabetes makes baby to be more likely affected) Certain medication use during pregnancy e.g. beta blockers |
Neonatal factors | Small for gestational age babies (SGA)/ birth weight ≤ 10th percentile for gestational age Large for gestational age babies (LGA)/ birth weight ≥ 90th percentile for gestational age Prematurity (<37 weeks gestation) Perinatal stress such as birth asphyxia, sepsis, hypothermia Congenital causes such as congenital hyperinsulinism, congenital adrenal hyperplasia and Beckwith- Wiedemann syndrome Inborn errors of metabolism Polycythaemia Rhesus haemolytic disease Poor feeding due to other issue, e.g. Prader Willi syndrome presents with small floppy baby not feeding, or babies with T21 can have a poor suck and low tone and don’t always feed well |
Signs and symptoms
The clinical presentation of neonatal hypoglycaemia is variable. While an otherwise healthy infant may remain completely asymptomatic with very low blood glucose levels, other infants may appear seriously unwell. Symptoms are unspecific but appearance of them should rouse suspicion of hypoglycaemia in the differential diagnosis. Manifestations include:
Sweating
Feeding difficulties or disinterest in feeding
Weak or high-pitched cry
Tremors
Hypothermia
Irritability
Lethargy/ stupor
Hypotonia (floppy baby)
Cyanosis
Episodes of apnoea, grunting or tachypnoea
Seizures

Other conditions that could lend themselves to hypoglycaemia would be jaundice [(makes babies sleepy and therefore, they have reduced feeds and are more prone to hypoglycaemia and hypernatraemic dehydration) with reduced urine output]
Hypothermia can also cause hypoglycaemia in babies, so in any hypothermic neonate you should check a blood glucose.
Differential Diagnosis
As there is such a wide list of differentials for neonatal hypoglycaemia, using your sings, symptoms, history, and investigation results will help narrow down this list and will guide your management.
Differentials include:
Cause of Neonatal Hypoglycaemia | Underlying physiology | Presentation | Investigations |
Transitional Hypoglycaemia | First few hours after birth newborns adjust from a continuous supply of glucose from the mother to regulating their glucose levels independently | Benign, self-limiting hypogylcaemia in the first 24 hours of life. Does not cause persistent or severe hypoglycaemia. | Normal hypo screen other than low blood glucose. |
Maternal Diabetes | Glucose moves freely across the placenta and causes elevated glucose in the foetus. Foetus produces excess insulin, causes hypoglycaemia. | Usually self-limiting hypoglycaemia but can be severe and refractory in first 24-48 hours. Macrosomia (insulin is anabolic) + difficult birth due to large size, e.g. shoulder dystocia. *infants born to mothers with diabetes are more likely to have congenital anomalies of the heart and spinal cord. | Hypoglycaemia with raised insulin and low ketone bodies (beta-hydroxybutyrate) |
Congenital Hyperinsulinism (CHI) | Insulin secretion is independent of plasma glucose. Occurs due to genetic defects in insulin secretion regulation from the pancreatic beta cells, e.g. mutations in ABCC8 and KCNJ11 Causes refractory severe hypoglycaemia. | Severe hypoketotic, hypoglycaemia, refractory to initial management. | Inappropriate concentration of serum insulin and C-peptide compare to plasma glucose. *in the context of hypoglycaemia, inappropriate insulin is more than 0. Low ketone bodies |
Sepsis | Infections trigger inflammatory response, affects glucose metabolism, causes hypoglycaemia. | Presents in first days-weeks, Gradual development of symptoms incl. temp instability, irritability May be history of risk factors for sepsis from delivery Late onset, refractory, severe hypoglycaemia. | Low glucose with normal ketones. Raised CRP / WCC Positive LP for meningitis Positive blood culture / urine culture |
Inborn errors of metabolism | Group of disorders, deficiencies in enzymes or substrates involved in metabolic pathways, Impairs ability to break down / utilise nutrients / proteins. | Presentation depends on type of IEM. Glycogen storage disorders present with hepatomegaly, lactic acidosis, failure to thrive May be history of consanguinuity or of relative with same disorder. | Will have abnormality in plasma amino acids / plasma organic acids / urine organic acids. May have raised lactate or metabolic acidosis. |
Adrenal insufficiency | Group of congenital / acquired conditions causing insufficient production of steroid hormones. Can be primary if due to pituitary dysfunction or secondary if adrenal gland dysfunction. Most common cause is congenital adrenal hyperplasia (CAH), caused by deficiency of 21-hydroxylase | Over virilised female / under virilised male, causing ambiguous genitalia. Hyperpigmentation. Can have primary adrenal insufficiency due to other condition such as septo-optic dysplasia, so may be signs of underlying syndrome.  | CAH tested for on Guthrie card. Low cortisol, inappropriate poor response to synacthen test. Low ACTH if primary. Can present in adrenal crisis with hyponatraemia, hyperkalaemia, hypoglycaemia and hypotension. |
Fructose intolerance | Deficiency of enzyme aldolase B, (required for metabolising fructose-1-phosphate into glyceraldehyde and dihydroxyacetone phosphate) Causing build up of fructose-1-phosphate which is hepatotoxic. Autosomal recessive | Nausea, vomiting, poor feeding, jaundice,. Present after consuming fructose containing products. | Hypoglycaemia, Hypophosphataemia, Hyperuricaemia, Lactic acidosis Test for reducing substances in urine |
Galactossaemia | Affects ability to metabolise galactose due to defect in galactose-1-phosphate uridyl transferase (GALT) | Presents after infant ingests galactose (present in milk) with vomiting, feeding difficulties, jaundice, hepatosplenomegaly | Tested for on guthrie. Can also be tested for with Beutler’s test. If they have had a red cell transfusion this can alter results. Raised levels of galactose-1-phosphate in red blood cells |
Management
The British Association of Perinatal Medicine (BAPM) provides comprehensive guidelines for the management of neonatal hypoglycaemia in full-term infants. The key aspects of these guidelines include:
Identification:
- Risk factors: Infants at risk should be identified, such as those who are small or large for gestational age, preterm, infants of diabetic mothers and those with perinatal stress (identified through poor cord gases with raised lactates, or prolonged foetal bradycardia prior to delivery)
- Screening: Blood glucose monitoring is recommended for all at risk infants, with the first measurement taking place 2-4 hours after birth and then regular pre-feed blood glucose monitoring until stable. Discharge can be considered after two consecutive blood glucose measurements >2.6mmol/L and a satisfactory feeding assessment. However, values <2.6 mmol/L warrant further monitoring and interventions depending on the level and presence of abnormal clinical signs.
Prevention of separation:
Efforts should be made to manage hypoglycaemia without avoidable separation of mother and baby to promote bonding and breastfeeding.
This means reviewing the baby regularly and putting in place a good feeding plan to prevent hypoglycaemia and reduce preventable admissions to NICU.
Treatment:
Feeding support:
- In the absence of abnormal clinical signs and if pre-feed glucose levels are between 2.0-2.5mmol, feeding support is offered (after treating hypoglycaemia with dextrose gel). Early and frequent feeding is crucial; you should observe a breastfeed for good attachment and effective feeding. Breast feeding should be encouraged and supplemental feeds should be considered if necessary
Glucose gels:
- If glucose levels are between 1.0-2.6mmol/l infants should be supplemented and subjected to a review by a neonatal doctor. The baby should be gievn a dose of 40% buccal glucose 200mg/kg (0.5ml/kg), and then a feed, and blood glucose levels should be checked again, after 30-60 minutes. If blood glucose (BG) levels remain between 1.0-2.6mmol, the baby should be assessed as soon as possible and given a second dose of buccal gel. The BG levels should be reviewed after a further 30-60 minutes.Â
- A normal feed amount for a baby on day 1 of life would be 50-60ml/kg/day, so the volume of one feed would be the total 24-hour volume divided by 8 to give a 3 hourly amount. (e.g. in a 2.5kg baby, one feed would be 12.5-19ml)
Feeding support:
- If blood glucose levels normalise following dex gel and a feed, then continued feeding support is crucial to help maintain stable blood glucose levels. Early and frequent feeding is crucial; breast feeding should be encouraged and the midwifery team can observe a breastfeed for good attachment and effective feeding. Supplemental feeds should be considered if necessary.
NICU Admission
Neonates who have a pre-feed BG < 1.0mmol/L, those who are displaying clinical signs consistent with hypoglycaemia, or those with three or more episodes of hypoglycaemia, should be admitted to a neonatal unit as soon as possible, and appropriate investigations for persistent hypoglycaemia should be commenced.
In the neonatal unit efforts should be made to obtain IV access and a 2.5ml/kg 10% glucose bolus should be given, followed by an infusion of 10% glucose 60ml/kg/day or regular NGT feeds of formula.
If there are any risk factors for sepsis present alongside severe or persistent hypoglycaemia then antibiotics should be considered
If you are unable to obtain immediate IV access, I.M glucagon 200mcg/kg can be administered. It is important to note that regular breast feeding should not stop unless there is a clinical contraindication or the infant is too sick to feed. BG should be checked regularly, ideally after 30 minutes, and managed as per the following:
Blood glucose level | BG < 1.0mmol/L or abnormal clinical signs | BG between 1.0-2.5mmol/L and no abnormal clinical signs | BG > 2.6mmol/L |
Management | Give IV 10% glucose 2.5ml/kg Increase glucose delivery rate by 2mg/kg/minute* Recheck BG after 30 minutes Repeat if BG < 1.0mmol/L or there are abnormal clinical signs | Increase glucose delivery rate by 2mg/kg/minute* Continue to feed if no contraindication Recheck BG after 30 minutes | Slowly wean off IV infusion Continue enteral feeds Monitor BG until infant is on full enteral feeds and blood glucose levels are > 2.5mmol/L or 3.0mmol/L in cases of hyperinsulinism |
Glucose Infusion rate (GIR) is calculated from the concentration and rate of dextrose running to the baby. There is a handy calculator here: https://starship.org.nz/health-professionals/calculators/glucose-calculator/. (or you can calculate it yourself using the formula below)
If glucose infusion rate > 8mg/kg/min, test for hyperinsulinism (with hypo screen)
You can increase the GIR by increasing the concentration of dextrose running, e.g. from 10 to 12.5, 15, 20 or even 50%. 10% and 12.5% dextrose can run peripherally, but for 15% and above, you need central access such as an umbilical venous catheter. You can also increase the GIR by increasing the rate of fluids, but in a newborn baby there is a risk of fluid overloading above 60-75ml/kg/day.

In babies who have transient hypoglycaemia, e.g. those born to diabetic mothers or who are SGA, and are admitted to NICU for IV fluids, as blood glucose levels normalise IV fluids are slowly weened as feeds are introduced, while monitoring blood glucose.
Hyposcreens
As per BAPM guidelines, a hypoglycaemia screen is indicated for any neonate with:
- More than 2 measurements of BG < 2.0mmol/L within the first 48 hours after birth,
- Severe hypoglycaemia (< 1.0mmol/L) at any time,
- Signs of neurological dysfunction and blood glucose < 2.6mmol/L
A hypoglycaemia screen is a set of diagnostic tests performed to identify the underlying causes of persistent or recurrent hypoglycaemic episodes. It is essential to perform during an episode of hypoglycaemia to capture relevant biochemical data
Components of a hypoglycaemic screen:
- Blood glucose: to measure the current glucose level
- Insulin: detectable insulin levels during hypoglycaemic episodes suggest hyperinsulinism as a cause
- Growth hormone: to evaluate for growth hormone deficiency associated with pituitary dysfunction
- Cortisol: to assess adrenal function; low levels may indicate adrenal insufficiency
- Lactate: elevated levels can indicate disorders of gluconeogenesis, glycogenolysis or sepsis
- Beta-hydroxybutyrate (ketones): low levels indicate impaired ketogenesis, which is common in hyperinsulinism
- Free Fatty Acids (FFA): low levels may also suggest hyperinsulinism
- Amino acids: abnormal profiles may be seen in certain metabolic conditions, e.g. low alanine levels are seen in Ketotic hypoglycaemia and starvation, and high levels of alanine is seen in lactic acidosis. Other anomalies in plasma amino acids can be due to inborn errors of metabolism.
- Acyl-carnitine profile to screen for fatty acid oxidation disorders
- Ammonia: raised in urea cycle disorders, Reyes syndrome and fatty acid oxidation disorders.
- Urine organic acids to detect organic acidaemias
- The flow chart below gives a basic interpretation of an abnormak hyposcreen


If there are abnormalities on the hypo screen and blood sugars are difficult to maintain in a normal range, then the endocrine team should be consulted.
Management of congenital hyperinsulinism
Management of CHI involves a multidisciplinary approach to stabilise blood glucose levels and address the underlying condition. The management typically includes medical therapy, dietary interventions, and in some cases, surgery.
In the setting of acute hypoglycaemia, the aim is to maintain blood glucose levels above 3.5mmol/L. Initially, children are managed with an IV bolus of 2.5ml/kg of 10% glucose, followed by a continuous infusion to prevent rebound hypoglycaemia. Alternatively, if IV therapy is not immediately available, intramuscular, or subcutaneous glucagon can be administered.
The first line treatment for CHI is diazoxide. Diazoxide is an oral medication taken three times daily. It works by activating the ATP sensitive potassium channel on the pancreatic beta-cells, thereby reducing insulin secretion. To avoid diazoxide associated fluid retention, chlorothiazide is usually prescribed alongside.
To assess the responsiveness of diazoxide, you can measure the blood glucose, insulin, and ketone levels; after initiating diazoxide, blood glucose levels should be stable and within the target range, insulin levels should decrease to appropriate levels for the blood glucose concentration and presence of normal ketone levels (beta-hydroxybutyrate) indicates the suppression of hyperinsulinaemia.
Babies starting diazoxide should be assessed with an echo beforehand as it can cause fluid overload and congestive heart failure.
A dose of diazoxide > 7mg/kg/day with no resolution of hypoglycaemia generally means that the patient is diazoxide unresponsive and warrants further discussion or referral to a specialist CHI centre.
Diazoxide unresponsive patients should be referred for a genetic analysis for the ABCC8 and KCNJ11 mutations as well as a 18F-DOPA PET-CT scan. Patients positive for the ABCC8 or KCNJ11 mutations should be commenced on high calorie diets and frequent feeds and trialled with octreotide before being referred for surgical management. Depending on the results of the scan, patients may require a curative lesionectomy for focal forms of CHI, or a subtotal pancreatectomy for diffuse forms.
Octreotide is a somatostatin analogue, used as second line therapy in children who are unresponsive to diazoxide. It acts on somatostatin receptor 5 (SSR5) to inhibit cAMP mediated insulin release. It can be given as subcutaneous injections with up to 8 doses per day, or a continuous IV infusion.


Overall
If you remember anything from this article let it be to follow local guidelines for monitoring for and managing hypoglycaemia in neonates.
Hypoglycaemia should be recognised and managed early through identifying risk factors and monitoring closely. This is to prevent hypoglycaemic brain damage and developmental impairment.
Severe refractory hypoglycaemia should be investigated early with a hypoglycaemia screen, while the baby is hypoglycaemic (if you struggle to get bloods from the baby the most important tests are insulin, c-peptide and ketones) and should be managed agressively with increasing dextrose concentrations until blood sugar is in normal range and stable.
References
Abramowski A, W. R. (2023, September 4). Neonatal hypoglycemia. Retrieved from National Library of Medicine: https://www.ncbi.nlm.nih.gov/books/NBK537105/
al, M. G. (2023, October ). Standardised practices in the networked management of congenital hyperinsulinism: a UK national collaborative consensus. Retrieved from Frontiers in Endocrinology: https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2023.1231043/full
Alegra, T. (2024, June). Metabolic presentations 3: Galactossaemia . Retrieved from Don’t Forget The Bubbles: https://dontforgetthebubbles.com/metabolic-presentations-3-galactossaemia/
BAPM, B. A. (October, 2017). Identification and Management of neonatal hypoglycaemia in the full term infant. Framework for practice. Retrieved from https://hubble-live-assets.s3.eu-west-1.amazonaws.com/bapm/file_asset/file/37/Identification_and_Management_of_Neonatal_Hypoglycaemia_in_the__full_term_infant_-_A_Framework_for_Practice_revised_Oct_2017.pdf
Diva D. De Leon, J. B. (2024, June). International Guidelines for the Diagnosis and Management of Hyperinsulinism. Retrieved from Karger: https://doi.org/10.1159/000531766
Dr Abiramy Saravanamuthu, D. P. (n.d.). Sweet Nothings: Neonatal Hypoglycaemia. Retrieved from Paedatric FOAMed: https://www.paediatricfoam.com/2017/04/neonatal-hypoglycaemia/
Hegde VS, S. T. (2024, January ). Hereditary fructose intolerance. Retrieved from National library of medicine : https://www.ncbi.nlm.nih.gov/books/NBK559102/
Robert C. Tasker, R. J. (2013). Oxford Handbook of Paediatrics, 2nd Edition. Oxford University Press.
Rose Wilson, R. (2023, February ). Neonatal Hypoglycaemia. Retrieved from rch.org.au: https://www.rch.org.au/rchcpg/hospital_clinical_guideline_index/Neonatal_hypoglycaemia/
Safer Care Victoria . (2019, May). Congenital adrenal hyperplasia (CAH) in neonates. Retrieved from https://www.safercare.vic.gov.au/best-practice-improvement/clinical-guidance/neonatal/congenital-adrenal-hyperplasia-cah-in-neonates#:~:text=Congenital%20adrenal%20hyperplasia%20(CAH)%20is,pressure%20and%20essential%20for%20life
Shien Chen Lee, E. S. (n.d.). Hypoglycaemia in adrenal insufficiency . Retrieved from Frontiers: https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2023.1198519/full
Written by Nikhita Rathod, 5th year medical student
Edited by Dr Bex Evans, Paediatric Registrar
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