Neonatal Hypoglycaemia Overview & Sugar Babie's Trial

Neonatal Hypoglycaemia

• Overview of Neonatal Hypoglycaemia – Why do we care?

– Detection & Prevention

– Queensland Neonatal Clinical Guideline

• The Sugar Babies Trial (Lancet 2013) – Methods

– Findings

– Impacts on Clinical Practice

• Common metabolic problem in Newborns

• Glucose is the primary fuel for the brain

• Left untreated, Hypoglycaemia can cause Neurological Injury

– mental retardation, recurrent seizure activity, developmental delay, personality disorders and more….

Depending on where you work, the definition of Neonatal Hypoglycaemia varies.

• QLD Health – Less than 2.6 mmol/L (47 mg/dL)

• American Academy of Paediatrics – Less than 2.2 mmol/L (40 mg/dL) during the first 24

hours of life

– Less than 2.8 mmol/L (50 mg/dL) after 24 hours

Whipple's triad is a collection of three criteria that suggest a patient's symptoms result from a ‘true hypoglycaemia’.

1. Symptoms known or likely to be caused by hypoglycaemia

2. A low plasma glucose measured at the time of the symptoms

3. Relief of symptoms when the glucose is raised to normal

• Inadequate glucose supply

– Poor feeds

– Inadequate glycogen stores

– Impaired glucose production (ie, glycogenolysis or gluconeogenesis)

• Increased glucose utilization (primarily due to hyperinsulinism)

• A baby’s risk of developing neonatal hypoglycaemia can be due to maternal and neonatal risk factors.

• The next two slides highlight some common risk factors.

• Identification of risk factors is important, as it will determine whether you screen for hypoglycaemia.

• Maternal diabetes mellitus

• Intra-partum administration of Glucose

• Maternal drug therapy including:

– β-blockers

– Oral hypoglycaemic agents

– Valproate

• Family history of metabolic disorders deficiency (e.g. Medium chain acyl-A dehydrogenase deficiency)

• Prematurity (<37 weeks)

• Low Birth Weight (<less than 2500g)

• Neonates who are large (>90th percentile) or small for gestational age (<10th percentile)

• Neonates who require intensive care (e.g. sepsis and asphyxia)

• Inadequate feeding

• Neonates with polycythemia

• Regular BGLs.

• Feed immediately

– EBM

– Formula

• IV Dextrose

• Maintain close surveillance

• Pharmacological Intervention

• Keep Baby Warm (36.5-37.2 OC)

– Dry Baby

– Early Skin-to-Skin Contact

• Initiate early feeds within 30-60mins of birth.

– Support mother’s choice for newborn feeding

– NGT feeds if <35 weeks

– If enteral feeding is no possible, start IV Dextrose.

• Avoid Separation of Mother & Baby

A randomised , double-blind, placebo controlled trial.

P: Neonates at risk of developing Hypoglycaemia

I: 40% dextrose gel (200mg/kg)

C: Placebo Gel

O: Treatment Failure and other secondary outcomes

Hypoglycaemia: blood or interstitial glucose concentration less than 2.6 mmol/L

Rebound Hypoglycaemia: further episode of hypoglycaemia within 6hrs, after successful treatment.

Recurrent Hypoglycaemia: further episode of hypoglycaemia after successful treatment, within 48 h after birth.

Neonates born in a tertiary hospital in New Zealand between Dec 1, 2008, and Nov 31, 2010; • 35+ weeks gestation • in the first 48 hours of life • at risk of hypoglycaemia.

Risk Factors included

– infants of diabetic mothers; – preterm; – small or large birthweight (i.e. less than 10th centile or over

90th centile) – infants with poor feeding.

• Previous treatment for Neonatal Hypoglycaemia

• Serious Congenital Malformation

• Terminal Disorders

• Skin conditions that would prevent the use of continuous glucose monitoring.

• BSLs were measured in these babies from one hour after birth, then every 3-4 hours pre-feeds for the first couple of days until hypoglycaemia was or was not detected.

• Babies who developed hypoglycaemia (BSL <2.6) were randomised to receive either

(0.5ml/kg) or (carboxymethyl cellulose - 0.5ml/kg).

• Gel was administered by rubbing into the buccal mucosa and was then followed by a feed (or syringe feed if the baby refused a normal feed).

• After 30 mins, if the baby was still hypoglycaemic, the same process was repeated.

• Up to 6 doses of gel could be given over 48hrs.

Primary Outcome – Treatment Failure: BGL less than 2.6mmol/L,

30 minutes after the second of two doses of gel.

Secondary Outcomes – Admission to the NICU – Feeding frequency – Volume of expressed breast milk – Need for further dextrose (IV or oral) – Rebound hypoglycaemia; – Time to resolve hypoglycaemia (BGLs >2.6) – Duration of Hypoglycaemia (up to 48hrs after birth)

Primary outcome data were available for 116 (98%) babies in the dextrose group, and 118 (99%) in the placebo group. Fewer babies in the dextrose gel group failed treatment compared to the placebo group (p value 0.04).

Dextrose gel (n=118)

Placebo gel (n=119)

Volume of Study Gel 0·84 (0·43–2·44) 0·97 (0·47–2·49)

Treatment Failure 16 (14%) 29 (24%)

• Babies in the dextrose gel group were less likely to need extra doses of dextrose.

• But those who did receive intravenous dextrose had similar amounts.

Dextrose gel (n=118)

Placebo gel (n=119)

Number of Babies 12 (10%) 28 (24%)

Dose (g/kg) 4·5 (0·2–10·8) 6·6 (0·2–16·2)

• Admission rate to NICU were similar in both groups, but the reason for admission in the dextrose gel group was less like to be for hypoglycaemia.

NICU ADMISSION

Dextrose gel (n=118)

Placebo gel (n=119)

Number of Babies 45 (38%) 55 (46%)

For Hypoglycaemia 16 (14%) 30 (25%)

• Giving dextrose gel had no adverse effects on breastfeeding, and in fact babies in this group were more likely to still be breastfeeding at 2 weeks. (Dextrose 5 [4%] vs Placebo 15 [13%]; RR 0·34. 95% CI 0·13–0·90; p=0·03)

• There were no adverse effects noted from the dextrose gel.

• Computer generated block randomisation

• Clinician’s, family and investigators masked to group allocation

• Groups were similar.

• Groups were treated equally.

• Losses to inclusion in analysis were explained, justified and demonstrated to have no significant impact on study findings.

A higher rate of treatment failure in the placebo compared to the dextrose group was statistically significant. RR 0·57 (0·33 to 0·98) | p value: 0.04 The population group in this study is similar to population groups in Australia. Further clarification of mechanism of action would be useful (i.e. baby’s could have done better with the dextrose gel due to pain relief, much like sucrose).

Dextrose Gel provides a viable first-line/intermediate treatment for neonatal hypoglycaemia.

It’s easy to administer, keeps mother and baby together whilst treatment is administered and is relatively cheap.

References

• Queensland Maternity and Neonatal Clinical Guideline: Newborn Hypoglycaemia

• Postnatal glucose homeostasis in late-preterm and term infants. Pediatrics. 2011

• Harris DL, Weston PJ, Signal BE, Chase JG, Harding JE, Dextrose gel for neonatal hypoglycaemia (the Sugar Babies Study): a randomised, double-blind, placebo-controlled trial, The Lancet, 2013, 382(9910): 2077-2083.

• Photos – Anne: (17) Red is all mine! – Garhol: Jelly Babies 02 – EMPEM.org