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Three Part Question

In [otherwise healthy newborn babies] [what is the normal range of blood glucose] in [the first days of life]?

Clinical Scenario

You are the attending neonatal consultant. It is 6 pm on a Friday after a busy week on the unit. A rather flustered midwife appears from the postnatal ward with a baby and two anxious parents. The baby is full term and appropriately grown, following a normal vaginal delivery and just 8 hours old. Mum has been attempting to breast feed but the baby is reported to have been "not feeding well" and "jittery". There are no prenatal risk factors for sepsis. Your examination of the baby is normal—he is now not "jittery".
A capillary heel prick blood test (Medisense) done on the postnatal ward has given a blood glucose reading of 2.6 mmol. Because this result is perceived to be abnormal (low), one of the neonatal trainees has suggested to the parents that he may need admission to the neonatal unit. As she has had three previous babies, the mother was hoping for an early (six hour) discharge from hospital.
The midwife asks you to "sort out the situation".
Some hours later, the laboratory plasma glucose result (taken at the same time as the Medisense capillary sample) is available. This result is 3.4 mmol/l.
The mother agreed to stay overnight with the baby on the postnatal ward, received breast feeding support, and was discharged home next morning. No further blood samples were taken. A phone call to the mother on day 3 confirmed that the baby remained well and fully breast fed.

Search Strategy

Cochrane and Medline.
[newborn] AND [blood glucose OR hypoglycaemia] AND [Exp cohort studies]

Search Outcome

Cochrane Library: no relevant studies found. Primary sources (Medline): 3 observational studies.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Hawdon JM et al, 1992	156 term infants, breast or bottle fed	Observational, cross sectional (1b)	Assay of whole blood glucose, gluconeogenic precursors, and ketone bodies from day 1 to day 6	12% had blood glucose <2.6 mmol/l, days 1–3	Range of blood glucose was <1.5 to 6.2 mmol/l Lowest levels were on day 1 Widest range on day 2
Hoseth E et al, 2000	223 term infants, exclusively breast fed	Observational, cross sectional (1b)	Assay of whole blood glucose between 1 and 96 hours of age	14% had blood glucose <2.6 mmol/l	Range of blood glucose was 1.4 to 5.3 mmol/l. Lowest levels were on day 1
Diwakar KK & Sasidhar MV, 2002	220 healthy term infants, AGA, exclusively breast fed	Observational, longitudinal (1b)	Assay of plasma glucose at 3, 6, 24, and 72 hours of age	14% had blood glucose <2.6 mmol/l	Range of blood glucose was 1.3 to 8.3 mmol/l Levels similar at each timepoint

Comment(s)

There was remarkable agreement between the results of these three studies in spite of different populations (UK, Denmark, and India) and different methods of assay (whole blood glucose: microenzymatic and glucose dehydrogenase photometric methods; plasma glucose: glucose oxidase method). Breast fed babies have statistically significantly lower blood glucose concentrations (mean 3.6 mmol/l; range 1.5–5.3) in the first week of life, compared to formula fed babies (mean 4.0 mmol/l; range 2.5–6.2). Breast fed full term babies with low blood glucose concentrations produce ketones and other fuels as an adaptive mechanism. Jitteriness is an extremely common and usually benign finding in otherwise well term newborns (3) In a study of 102 full term babies with "jitteriness", (1) sucking on the examiner's hand stopped the tremor in over 80%. Of the 18 babies whose tremor continued, only five had hypoglycaemia and 13 had hypocalcaemia In our case, the difference between the Medisense heel prick (2.6 mmol/l) and the laboratory plasma glucose of 3.4 mmol/l, highlights the poor predictive value of reagent strips to detect true hypoglycaemia (PPV 0.18 for blood glucose of <2.0 mmol/l). Use of reagent strips will on average wrongly diagnose hypoglycaemia in one out of four babies who are in fact normoglycaemic (2). If a baby appears well but "jittery", he or she should be examined carefully and have a suckling stimulation test. If he or she fails this test, blood assay of calcium and glucose should be done. Blood glucose of less than 1.5 mmol/l should prompt further investigation in any baby (well or otherwise).

Clinical Bottom Line

The normal range of blood glucose is around 1.5–6 mmol/l in the first days of life, depending on the age of the baby, type of feed, assay method used, and possibly the mode of delivery. Up to 14% of healthy term babies may have blood glucose less than 2.6 mmol/l in the first three days of life. Lowest concentrations are more likely on day 1. There is no reason to routinely measure blood glucose in appropriately grown term babies who are otherwise well. "Jitteriness" is a mostly benign finding. Feeding difficulty should be overcome with education, promotion, and support for breast feeding.

References

1. Hawdon, JM, Ward-Platt MP, Aynsley-Green A. Patterns of metabolic adaptation for preterm and term infants in the first neonatal week. Arch Dis Child 1992;67:357–65.
2. Hoseth E, Joergensen A, Ebbesen F, et al. Blood glucose levels in a population of healthy, breast fed, term infants of appropriate size for gestational age. Arch Dis Child Fetal Neonatal Ed 2000;83:F117–F119.
3. Diwakar KK, Sasidhar MV. Plasma glucose levels in term infants who are appropriate size for gestation and exclusively breast fed. Arch Dis Child Fetal Neonatal Ed 2002;87:F46–F48.
4. D'Harlingue AE, Durand DJ. Recognition, stabilization and transport of the high-risk newborn. In: Klaus MH, Fanaroff AA, eds. Care of the high risk neonate. Philadelphia: Saunders. 1993:62–85.
5. Linder N, Moser AM, Asli I, et al. Suckling stimulation test for neonatal tremor. Arch Dis Child 1989;64:44–6.
6. WHO. Hypoglycaemia of the newborn: review of the literature. Geneva: WHO. 1997:30–1.