CLINICAL PROTOCOL – MUHC (PROTOCOLE CLINIQUE - CUSM)

Medication included No Medication included

MCH MGH RVH MNH MCI LACHINE

THIS IS NOT A MEDICAL ORDER

Title: Management of newborn at risk or affected by hypoglycemia in the first 36 hours of life

This document is attached to:

Collective Order for Neonatal Hypoglycemia Risk Screening, Testing, and Management After Birth

MUHC Patient Double Identifier

MUHC Hand Hygiene Policy

Interprofessional Protocol - Blood Glucose (BG) testing with Nova STATSTRIP® Glucometer for Adults and Pediatrics.

MUHC Interprofessional Protocol - Obtaining a Blood Specimen by Heelstick, Using a Quickheel Lancet - Pediatric

1. PURPOSE

This protocol aims to standardize three components of management of newborns at risk for hypoglycemia:

1. The screening of risk factors for hypoglycemia in all newborns born at the Royal Victoria Hospital

2. The testing of glycemia in newborns deemed “at risk” by the screening tool

3. The treatment of hypoglycemia in those newborns at the Royal Victoria Hospital (RVH), who test low in glycemia testing

Screening of risk factors for hypoglycemia for all newborns is a standard of care. Management of hypoglycemia should be standardized to correct hypoglycemia and to prevent as much as possible the separation of the newborn from his mother associated with a Neonatal Intensive Care Unit (NICU) admission. This management should also promote breastfeeding as much as possible as long as the health of the newborn affected by hypoglycemia is not compromised.

Glycemia testing in the case of this protocol refers to glucose testing at the point of care, as per the Interprofessional Protocol - Blood Glucose (BG) testing with Nova STATSTRIP® Glucometer for Adults and Pediatrics.

2. PROFESSIONALS

Nurses who are caring for newborns in the birthing center and in the maternity unit at the RVH.

Residents, nurses’ practitioners, pediatricians and neonatologists who are caring for newborns in the birthing center and in the maternity unit at the Royal Victoria Hospital (RVH).

3. PATIENT POPULATION

This protocol applies to newborns older than 346/7 weeks gestational age, who are born or hospitalized at the MUHC’s Birthing Center and Maternity Care Unit in their first 36 hours of life.

Exclusion criteria:

Management of newborn at risk or affected by hypoglycemia in the first 36 hours of life, Final Dec 18th 2017 Revision date: Dec 2021 1

• Preterm infants less than 35 weeks gestational age (less than or equal to 34 6/7 weeks of gestational age)

• Patients requiring an intravenous (IV) infusion for hypoglycemia

• Unstable patients requiring NICU admission for any medical condition

• Newborns who are older than 36 hours of life

4. ELEMENTS OF CLINICAL ACTIVITY

Professionals are responsible to know the limits and extent of their practice as related to the particular protocol.

The following procedure aims to insure three major steps:

• Screening of risk factors for hypoglycemia in all newborns. • Testing of glycemia in all newborns who present at least one risk factor starting at 2 hours

of life and after the baby was fed as soon as possible within the first hour of life and then as prescribe in the Protocol for the management of newborns at risk or affected by hypoglycemia in the first 36 hours of life.

• Ensure treatment of hypoglycemia as describe in the Protocol for the management of newborns at risk or affected by hypoglycemia in the first 36 hours of life.

Procedure for Screening & Glucose Testing (see Appendix I for algorithm):

1. All mothers and newborns of imminent delivery must be screened for risk factors for neonatal hypoglycemia (Tables 1 & 2). Screening must be documented on the Risk factors for Neonatal Hypoglycemia – Screening Form DM-5777 (See Appendix II).

2. If a mother or newborn has one or more risk factors identified, the newborn must be fed as soon

as possible BEFORE the first set of vital signs at one hour of life, with the parental method of choice. If the newborn is breastfeeding, he or she should be offered manually expressed colostrum after time at the breast. If parents choose formula feeding, the baby should be offered the bottle (pre-

Table 1. Risk Factors for Neonatal Hypoglycemia

• Gestational age less than 37 weeks • Small for gestational age (birth weight below 10th percentile) – see Table 2 • Identified as intrauterine growth restriction (IUGR) during the pregnancy, even if normal

birth weight • Large for gestational age (Birth weight above 90th percentile) – see Table 2 • APGAR score of less than 6 at five minutes • Infant of diabetic mother (includes diabetes type 1 and 2, and gestational diabetes

treated with diet, oral hypoglycemic agent or insulin) • Beta-blockers administration to mother during pregnancy (ex: labetalol, propranolol,

metoprolol) • Betamethasone (Celestone MD) administration to mother during the last week of

pregnancy

Table 2: Weight for Gestational Age, 10th and 90th Percentiles by Sex

Gestational Age (completed weeks)

Birthweight (g) 10th Percentile 90th Percentile

Male Female Male Female 37 2552 2452 3665 3543 38 2766 2658 3877 3738 39 2942 2825 4049 3895 40 3079 2955 4200 4034 41 3179 3051 4328 4154 42 3233 3114 4433 4251

Management of newborn at risk or affected by hypoglycemia in the first 36 hours of life, Final Dec 18th 2017 Revision date: Dec 2021 2

prepared infant formula (67 kcal/100 mL/regular formula)). In both cases, the amount of expressed breast milk or pre-prepared infant formula (67 kcal/100 mL/regular formula) taken must be documented in the nursing notes.

A. Glucose testing must then be done with the second set of vital signs at 2 hours of life:

Part I: If first glycemia LESS THAN 1.4 mmol/L (or repeat glycemia LESS THAN 2 mmol/L):

a. Administer 0.5 mL/kg of 40% dextrose gel immediately (see administration procedure below). NOTE: Can be administered for first and second hypoglycemic episodes only. If the newborn has already received 2 doses of dextrose gel, he MUST be given pre-prepared infant formula (67 kcal/100mL/regular).

b. If breastfeeding: i. Place baby to the breast for a maximum of 20 minutes of effective

breastfeeding. ii. Manually express remaining breastmilk after breastfeeding iii. Give maximum of expressed breastmilk available. iv. If LESS THAN 5 mL of expressed breastmilk available after

breastfeeding, or if baby unable to breastfeed, baby must be given 5-10 mL/kg of pre-prepared infant formula (67 kcal/100 mL/regular formula).

c. If parents prefer not to breastfeed, give 5-10 mL/kg of pre-prepared infant formula (67 kcal/100mL/regular).

d. If newborn is in Birthing Centre, NICU should be advised as per indications to call medical team and if newborn is in post-partum unit, pediatrician on-call should be advised as per indication to call medical team 1. Indications to call medical team:

i. Symptomatic hypoglycemia ii. Any concerns for the patients iii. More than two episodes of hypoglycemia despite appropriate

intervention iv. Dropping glycemia despite appropriate intervention v. Indications to receive IV therapy are met (listed at the end of the

document) e. Glucose testing should then be repeated at 1 hour post-feed.

i. If glycemia at this point is less than 2 mmol/L, repeat steps in part I. Do not repeat dextrose gel if two doses already given and pre-prepared infant formula (67 kcal/100 mL/regular formula) must be given in those circumstances.

ii. If glycemia at this point is 2 – 2.5 mmol/L, follow steps below in part 2. Pre-prepared infant formula (67 kcal/100 mL/regular formula) should be considered if less than 5 mL of express breast milk are available. Do not repeat dextrose gel if two doses already given and pre-prepared infant formula (67 kcal/100 mL/regular formula) must be given in those circumstances.

iii. If glycemia at this point is greater or equal to 2.6 mmol/L, follow steps below in part III.

Part 2: If first glycemia between 1.4 – 1.9 mmol/L (or repeat glycemia is 2 - 2.5):

a. Administer 0.5 mL/kg of 40% dextrose gel immediately (see administration procedure below). NOTE: Can be administered for first and second hypoglycemic episodes only. If the newborn has already received 2 doses of dextrose gel, he MUST be given pre-prepared infant formula (67 kcal/100mL/regular).

b. If breastfeeding: i. Place baby to the breast for a maximum of 20 minutes of effective

breastfeeding ii. Manually express remaining breastmilk after breastfeeding iii. Give maximum of expressed breastmilk available iv. If expressed breastmilk not available, consider giving 5-10 mL/kg of

pre-prepared infant formula (67 kcal/100 mL) – discuss risks and benefits with parents.

Management of newborn at risk or affected by hypoglycemia in the first 36 hours of life, Final Dec 18th 2017 Revision date: Dec 2021 3

c. If parents prefer not to breastfeed, give 5-10 mL/kg of pre-prepared infant formula (67 kcal/100mL/regular).

d. If newborn is in Birthing Centre, NICU should be advised as per indications to call medical team and if newborn is in post-partum unit, pediatrician on-call should be advised as per indication to call medical team 1. Indications to call medical team:

i. Symptomatic hypoglycemia ii. Any concerns for the patients iii. More than two episodes of hypoglycemia despite appropriate

intervention iv. Dropping glycemia despite appropriate intervention v. Indications to receive IV therapy are met (listed at the end of the

document) e. Glucose testing should then be repeated at 1 hour post-feed.

i. If glycemia at this point is less than 2 mmol/L, follow steps above in part 1. If the newborn has already received 2 doses of dextrose gel, he MUST be given pre-prepared infant formula (67 kcal/100mL/regular).

iv. If glycemia at this point is 2 – 2.5 mmol/L, repeat steps in part 2. Pre-prepared infant formula (67 kcal/100 mL/regular formula) should be considered if less than 5 mL of express breast milk are available. If the newborn has already received 2 doses of dextrose gel, he MUST be given pre-prepared infant formula (67 kcal/100mL/regular).

ii. If glycemia at this point is greater or equal to 2.6 mmol/L, follow steps below in part 3.

Part 3: If first glycemia is 2 mmol/L or GREATER (or repeat glycemia is 2.6 mmol/L or GREATER):

a. Encourage breastfeeding. b. Complete each breastfeeding with manually expressed breastmilk. c. If parents prefer not to breastfeed, give a minimum of 5 to 10 mL/kg of pre-

prepared infant formula (67 kcal/100mL/regular). d. Newborn should be fed ad lib, but never go longer than 3 hours between

feeds. e. Glucose testing should then be repeated BEFORE each feed, no longer than 3

hours between each testing: i. If glycemia at this point is less than 2 mmol/L, follow steps above in part

1. If the newborn has already received 2 doses of dextrose gel, he MUST be given pre-prepared infant formula (67 kcal/100mL/regular).

ii. If glycemia at this point is 2 – 2.5 mmol/L, repeat steps in part 2. Pre-prepared infant formula (67 kcal/100 mL/regular formula) should be considered if less than 5 mL of express breast milk are available. If the newborn has already received 2 doses of dextrose gel, he MUST be given pre-prepared infant formula (67 kcal/100mL/regular).

i. If glycemia at this point is greater or equal to 2.6 mmol/L, continue with part 3.

f. Glycemia testing can be spaced to Q6 hours if 3 consecutive samples are greater or equal to 2.6 mmol/L

g. Discontinue testing after 36 hours of life if at least 5 glycemias are greater or equal to 2.6 mmol/L of which 3 are consecutive

3. Any newborn (with or without risk factors) presenting with symptoms of hypoglycemia (see Table 3) must be tested immediately for hypoglycemia:

• Perform testing for glycemia. • If glycemia less than 2.6 mmol/L, call NICU if baby is in Birthing Centre, or

pediatrician if baby is in post-partum. • If glycemia greater or equal to 2.6 mmol/L, investigate for other causes of

symptoms.

Table. 3. Symptoms of Neonatal Hypoglycemia

• Hypothermia (axillary temperature lower than 36.5 degrees Celsius) despite warming

Management of newborn at risk or affected by hypoglycemia in the first 36 hours of life, Final Dec 18th 2017 Revision date: Dec 2021 4

measures • Jitteriness and/or tremors • Seizures and/or eye-rolling • Weak and/or high-pitched cry • Limpness and/or lethargy • Cyanosis, intermittent apneic spells, and/or tachypnea • Feeding difficulty and/or poor suck • Diaphoresis • Sudden pallor

NOTE: Respiratory distress immediately after birth should receive proper assessment and care by NICU before patient is tested for hypoglycemia

4. If a mother or newborn has no risk factors identified, proceed with post-partum care as per

standard of care. 5. Risk screening, glycemia testing, and interventions must be documented in nursing notes, the Plan

therapeutic infirmier, and on the Computerized Medication Administration Record (CMAR) (Maternity unit) or centricity (Birthing Center). as per protocol.

Procedure for Administration of Dextrose Gel 40%:

Do not repeat dextrose gel if two doses already given.

i. Prepare dose of dextrose gel (0.5 mL/kg or 200 mg/kg):

1. Transfer dextrose gel into syringe by squeezing tube. Ensure dose in syringe is as prescribed.

ii. Perform hand hygiene as per MUHC Hand Hygiene Policy.

iii. Don clean gloves.

iv. Dry baby’s mouth with a clean gauze.

v. Massage dose of dextrose gel directly on the oral mucosa (buccal and lingual surfaces). Dextrose may be absorbed directly from the oral mucosa, thus bypassing the portal circulation and gaining more rapid access to the circulation. Dextrose is rapidly absorbed by the gastrointestinal mucosa because it does not require digestion. Some proportion of the dose may be swallowed and absorbed from the gastrointestinal tract.

vi. The baby should be encouraged to feed immediately after dextrose gel application.

vii. Once dextrose gel package is open, it must be used within 24 hours.

viii. Always use a new oral syringe to pick up dextrose gel.

Indications to transfer newborn to the NICU to receive intravenous (IV) fluid therapy:

1. Any glycemia LESS THAN 2.6 mmol/L in a symptomatic infant. 2. Two consecutive glycemias, including the first one, LESS THAN 1.5 mmol/L despite appropriate

interventions (dextrose gel + feeding with at least 5-10 mL/kg of pre-prepared infant formula (67 kcal/100mL/regular) or breastmilk) within the first 4 hours of life.

3. Two consecutive glycemias LESS THAN 2.2 mmol/L, in a baby fed at least every three hours with between 5-10 mL/kg of pre-prepared infant formula (67 kcal/100mL/regular) or breastmilk. These two glycemias exclude the first glycemia at two hours of life.

4. Three glycemias LESS THAN 2.6 mmol/L, with the two most recent being consecutive, in a baby fed at least every three hours with between 5-10 mL/kg of pre-prepared infant formula (67 kcal/100mL/regular) or breastmilk. These three glycemias exclude the first glycemia at two hours of life.

Management of newborn at risk or affected by hypoglycemia in the first 36 hours of life, Final Dec 18th 2017 Revision date: Dec 2021 5

Formula should always be considered for hypoglycemia (if parents agree) if expressed breast milk is not available in appropriate amount (minimum 5 mL) and before considering a transfer to the NICU for IV therapy.

Exclusive breastfeeding should not be the only intervention if a baby presents with hypoglycemia.

Consider critical sample & endocrinology consultation for patients with persistent hypoglycemia despite high glucose infusion rates (10.4 mg/kg/min) or repeated episodes of hypoglycemia.

MAIN AUTHOR:

François Olivier M.D., MSc., FRCPC, Neonatologist, MUHC Division of Neonatology

CONSULTANTS:

• Thérèse Perreault, M.D., FRCPC, FAAP, Director, MUHC Division of Neonatology

• Denis Leduc, M.D., FRCPC, Pediatrician, MUHC Division of Pediatrics

• Robert Sternszus, M.D., FRCPC, Pediatrician, MUHC Division of Pediatrics

• Elizabeth Hailu M.D., Neonatologist, MUHC Division of Neonatology

• Julia Elisabeth Von Oettingen, Pediatric Endocrinologist, MUHC Division of Pediatrics

• Alicia Lambrinakos-Raymond, M.D., Neonatology Fellow, MUHC Division of Neonatology

• Christine Héroux, Assistant Nurse Manager, Birthing center, RVH

• Sabrina Haas, MScN, PNC(C), IBCLC, Assistant Nurse Manager, Maternity Unit, RVH

• Francine Brissette, Nurse Manager, Birthing center, RVH

• Malisa Khongkham, NPDE Labour & Delivery, Antepartum & Post-Partum, RVH

• Eleanor Scharf, RN BA, MSc(A), Nurse Manager, Postpartum department, RVH

• Elissa Remmer, RN, MSc(A), NPDE - NICU, MCH

6. APPROVAL PROCESS

Institutional and professional approval

Committees Date approved

[yyyy-mm-dd]

Clinical Practice Review Committee (CPRC) (if applicable) 2017-10-05

Adult Pharmacy and Therapeutics (P&T) (if applicable)

Pediatric Medication Administration Policy (PMAP) (if applicable) 2017-11-09

Pediatric Pharmacy and Therapeutics (Peds P&T) (if applicable)

Multidisciplinary Council (MDC) (if applicable)

7. REVIEW DATE

To be updated in maximum of 4 years or sooner if presence of new evidence or need for practice change.

Management of newborn at risk or affected by hypoglycemia in the first 36 hours of life, Final Dec 18th 2017 Revision date: Dec 2021 6

REFERENCES 1. Harding JE, Harris DL, Hegarty JE, Alsweiler JM, McKinlay CJ. An emerging evidence base for the management of neonatal hypoglycaemia. Early Hum Dev. 2016;104:51-56. doi:10.1016/j.earlhumdev.2016.12.009.

2. Kang P, Liao M, Wester MR, Leeder JS, Pearce RE. NIH Public Access. Ratio. 2010;36(3):490-499. doi:10.1124/dmd.107.016501.CYP3A4-Mediated.

3. Güemes M, Rahman SA, Hussain K. What is a normal blood glucose? Arch Dis Child. 2015:archdischild-2015-308336. doi:10.1136/archdischild-2015-308336.

4. Harris DL, Weston PJ, Harding JE. Incidence of neonatal hypoglycemia in babies identified as at risk. J Pediatr. 2012;161(5):787-791. doi:10.1016/j.jpeds.2012.05.022.

5. Adamkin DH. Postnatal Glucose Homeostasis in Late-Preterm and Term Infants Clinical Report—Postnatal Glucose Homeostasis in Late-Preterm and Term Infants. Pediatrics. 2013;127(3):575-579. doi:10.1542/peds.2010-3851.

6. Hawdon JM, Platt MPW. Patterns of metabolic adaptation for preterm and term infants in the first neonatal week. 1992;(October 1991):357-365.

7. Aziz K, Dancey P, Society CP. Screening guidelines for newborns at risk for low blood glucose. Can Paediatr Soc Position Statement. 2014;(March 2004):1-7.

8. Healey M, Bradford M. ) and Implications for Management. Can J Fish Aquat Sci. 2011;68(4):718-737. doi:10.1139/f2011-010.

9. Tin W. Defining neonatal hypoglycaemia: A continuing debate. Semin Fetal Neonatal Med. 2014;19(1):27-32. doi:10.1016/j.siny.2013.09.003.

10. Lucas A, Morley R, Cole TJ. Adverse neurodevelopmental outcome of moderate neonatal hypoglycaemia. 1988;1304(November).

11. McKinlay CJ, Alsweiler JM, Ansell JM, et al. Neonatal Glycemia and Neurodevelopmental Outcomes at 2 Years. N Engl J Med. 2015;373(16):1507-1518. doi:10.1056/NEJMoa1504909.

12. Deshpande S, Platt MW. The investigation and management of neonatal hypoglycaemia. Semin Fetal Neonatal Med. 2005;10(4):351-361. doi:10.1016/j.siny.2005.04.002.

13. Rozance PJ. Update on neonatal hypoglycemia. Curr Opin Endocrinol Diabetes Obes. 2014;21(1):45-50. doi:10.1097/MED.0000000000000027.

14. Gyamfi-Bannerman C, Thom EA, Blackwell SC, et al. Antenatal Betamethasone for Women at Risk for Late Preterm Delivery. N Engl J Med. 2016;374(14):1311-1320. doi:10.1056/NEJMoa1516783.

15. Pettit KE, Tran SH, Lee E, et al. The association of antenatal corticosteroids with neonatal hypoglycemia and hyperbilirubinemia. 2014;7058(January 2017). doi:10.3109/14767058.2013.832750.

16. Chertok IRA, Raz I, Shoham I, Haddad H, Wiznitzer A. Effects of early breastfeeding on neonatal glucose levels of term infants born to women with gestational diabetes. J Hum Nutr Diet. 2009;22(2):166-169. doi:10.1111/j.1365-277X.2008.00921.x.

17. Harris DL, Weston PJ, Signal M, Chase JG, Harding JE. Dextrose gel for neonatal hypoglycaemia (the Sugar Babies Study): A randomised, double-blind, placebo-controlled trial. Lancet. 2013;382(9910):2077-2083. doi:10.1016/S0140-6736(13)61645-1.

18. Ter M, Halibullah I, Leung L, Jacobs S. Implementation of dextrose gel in the management of neonatal hypoglycaemia. J Paediatr Child Health. 2016:6-9. doi:10.1111/jpc.13409.

19. Stewart CE, Sage ELM, Reynolds P. Supporting “Baby Friendly”: a quality improvement initiative for the management of transitional neonatal hypoglycaemia. Arch Dis Child - Fetal Neonatal Ed. 2016;101(4):F344-F347. doi:10.1136/archdischild-2015-308950.

20. Weston PJ, Harris DL, Battin M, Brown J, Hegarty JE, Harding JE. Oral dextrose gel for the treatment of hypoglycaemia in newborn infants. Cochrane Database Syst Rev. 2016;2016(5). doi:10.1002/14651858.CD011027.pub2.

Version History

(for Administrative use only)

Version Description Author/responsable Date

Management of newborn at risk or affected by hypoglycemia in the first 36 hours of life, Final Dec 18th 2017 Revision date: Dec 2021 7

No 1 Development and Approbation Francois Olivier, M.D., MSc., FRCPC, Neonatologist, MUHC Division of Neonatology

2017-12-11

No Description (Création, Adoption, Révision avec modification, Révision sans modifications, etc.)

Acronyme direction, Nom fonction

Management of newborn at risk or affected by hypoglycemia in the first 36 hours of life, Final Dec 18th 2017 Revision date: Dec 2021 8

BOX A

Indications to call medical team: Symptomatic hypoglycemia, or any concern for the patient, or more than two episodes of hypoglycemia despite appropriate intervention, or dropping glycemia despite appropriate intervention, or indications to receive IV therapy are met (see box below)

Indications to transfer the NICU to receive IV fluid therapy 1. Any glycemia less than 2.6 mmol/L in a symptomatic infant 2. Two consecutive glycemias less than 1.5 mmol/L despite appropriate interventions (dextrose gel + feeding with at least 5-10 mL/kg of pre-prepared infant formula

(67 kcal/100mL/regular) or breastmilk) within the first 4 hours of life 3. Two consecutive glycemias less than 2.2 mmol/L with at least two consecutive, in a baby fed at least every three hours with between 5-10 mL/kg of pre-prepared

infant formula (67 kcal/100mL/regular) or breastmilk. These two glycemias exclude the first glycemia at 1 hour of life. 4. Three glycemias less than 2.6 mmol/L, with at least two consecutive, in a baby fed at least every three hours with between 5-10 mL/kg of or breastmilk. These

three glycemias exclude the first glycemia at 1 hour of life.

Formula should always be considered for hypoglycemia (if parents agree) if expressed breast milk is not available in appropriate amount (minimum 5 mL) and before considering a transfer to the NICU for IV therapy.

Exclusive breastfeeding should not be the only intervention if a baby presents with hypoglycemia. Consider critical sample & endocrinology consultation for patients with persistent hypoglycemia despite high glucose infusion rates (10.4 mg/kg/min) or repeated

episodes of hypoglycemia

Management of newborn at risk or affected by hypoglycemia in the first 36 hours of life, Final Dec 18th 2017 Revision date: Dec 2021 9

1- Verify hypoglycemia risk factors in the newborn (Check the box if present) Newborn younger than 37 0/7 weeks Small for gestational age (Birth weight below 10th percentile)* Identified as intrauterine growth restriction (IUGR) during the pregnancy even if normal birth weight Large for gestational age (Birth weight above 90th percentile)* APGAR below 6 at five minutes of life Infant of diabetic mother (include diabetes type 1 and 2 and gestational diabetes treated with diet, oral hypoglycemic agent or insulin) Beta-blockers administration to the mother during the last week of pregnancy (ex: labetalol, propranolol, metoprolol) Betamethasone (Celestone R) administration to the mother during the last week of pregnancy

2a. No risk factor for hypoglycemia identified NO ROUTINE TESTING is indicated for hypoglycemia. Proceed with post-partum care as per standard.

2b. At least ONE risk factor is identified Refer to the Protocol for the management of newborns at risk

or affected by hypoglycemia in the first 36 hours of life, and continue with steps 3 to 5 below.

3- The newborn must be fed (breastfeeding, manually expressed breast milk or pre-prepared infant formula (67 kcal/100mL/regular) as soon as possible within the FIRST hour of life and BEFORE first glycemia testing.

4- The first glycemia testing must be done at TWO hours of life

5- Glycemia testing is indicated immediately in any baby if hypoglycemia symptoms** are present, and the medical team must be notified

*Weight for gestational age

Gestational age (completed weeks)

Birthweight (g)

10th percentile 90th percentile Male Female Male Female

37 2552 2452 3665 3543

38 2766 2658 3877 3738

39 2942 2825 4049 3895

40 3079 2955 4200 4034

41 3179 3051 4328 4154

42 3233 3114 4433 4251

**Hypothermia (axillary temperature lower than 36.5 degrees Celsius) despite warming measures, jitteriness and/or tremors, seizures and/or eye-rolling, weak and/or high-pitched cry, limpness and/or lethargy, cyanosis, intermittent apneic spells, and/or tachypnea, feeding difficulty and/or poor suck, diaphoresis, sudden pallor

Name in print Signature License No.

Time 00:00

Date AAYY/MM/J

D

Nurse

Management of newborn at risk or affected by hypoglycemia in the first 36 hours of life, Final Dec 18th 2017 Revision date: Dec 2021 10

Appendix III

LITERATURE REVIEW: NEONATAL HYPOGLYCEMIA

Hypoglycemia is a frequent metabolic disorder presented by neonates and is a preventable cause of neonatal brain injury. 1 Indeed, glucose is the major energy source for the brain, particularly in neonates who have a higher brain to body ratio. 2 Neurologic sequelae, including psychomotor retardation, cognitive deficits (in short-term memory, visuomotor integration, and arithmetic skills), and epilepsy may result from repeated or prolonged episodes of hypoglycemia.

Newborns lose their exogenous glucose supply at birth once umbilical cord is cut. This normally result in a fall of blood glucose level, decrease insulin secretion and increase counter-regulator hormones (e.g. glucagon, catecholamines, glucocorticoids) which promote glycogenolysis. 1 3 Glucose endogenous production is therefore initiated in the newborn via gluconeogenesis and glycogenolysis. Blood glucose stabilization (3.5 mmol/L to 5.5 mmol/L) usually occurs in the first 72 hours of life. 1 3

Hypoglycemia affects between 5 and 15% of healthy newborns. 4 Nonetheless, the true incidence of hypoglycemia is difficult to establish since many references use different cut off for diagnosis (less than 1.7 mmol/L to less than 2.6 mmol/L). In one study including 514 newborn infants presenting risk factors for hypoglycemia, 51% of infants had 1 episode of blood glucose lower than 2.6 mmol/L and 19% had 1 episode of blood glucose lower than 2.0 mmol/L during the first 48 hours of life. 4 Most episodes were documented within the first 24 hours of life and 19% of patients had more than 1 episode of hypoglycemia. 4

Hypoglycemia mostly occurs in the first few hours of life. For most newborns, this hypoglycemia is only transient (transitional hypoglycemia). The harmful effect of asymptomatic hypoglycemia during the transitional phase following birth has never been demonstrated. 5

Normal glucose level

Appropriate for gestational newborns present a postnatal drop in blood glucose concentrations during the first 2 to 4 hours of life. During this initial transitional phase, normal blood glucose value can be as low as 1.3 mmol/L in healthy breastfed infants. 3 2 Breastfed infants tend to have lower blood glucose than those formula fed.2 One study report that glucose concentration in breastfed infants was below 2.0 mmol/L for almost half of them during the first 24 hours. 6 In infants fed with formula, blood glucose usually exceeds 2.2 mmol/L by 6 to 12 hours of life. Almost all infants with proven symptomatic hypoglycemia during first hours of life have glucose concentrations lower than 1.4 mmol/L. 5

The threshold of 2.6 mmol/L after the transitional period is often used to defined hypoglycemia. It seems that recurrent symptomatic episodes of glucose concentration lower than 2.6 mmol/L might be associated with adverse outcomes. 7 In fact, newborns exhibit and increased hormonal response (glucagon and epinephrine) when blood glucose is below 2.6 mmol/L. 8 Abnormal auditory evoque potential was also documented with blood glucose below 2.6 mmol/L, although this finding was not replicated in other studies. 9

A follow up study including 661 infants (mean gestational age 30 weeks) enrolled in a randomized control trial of feeding regimes report an association between the number of days (exceeding 5) on which blood glucose was below 2.6 mmol/L and lower Bayley developmental scores at 18 months of age. 10 The risk increased according to the number of days where blood glucose was found to be lower than 2.6 mmol/L. 10 A cohort study did not show any association between hypoglycemia and adverse neurologic outcomes when treatment was provided to maintain blood glucose at 2.6 mmol/L or higher. 11

Unfortunately, no study provided a valid estimate of effect of neonatal hypoglycemia on neuro-development and threshold for intervention remains uncertain. 9 Some suggest that for at risk infants but otherwise healthy and asymptomatic, intervention to increase blood glucose should be done if blood glucose is persistently below 2.0 mmol/L. 12 The Canadian Pediatric Society recommends intravenous blood glucose for neonates who present blood glucose below 1.8 mmol/L after an efficient feed in the first 2 hours of life or below 2.0 mmol/L after subsequent feeding. It also recommends IV therapy for newborns who repeatedly present with blood glucose below 2.6 mmol/L or immediately if the infant is symptomatic..7

The American Academy of Pediatrics recommends immediate intravenous glucose infusion in infants who present symptomatic hypoglycemia based on a limit of 2.2 mmol/L. 5 Infants at risk who are asymptomatic should receive intravenous glucose only if blood glucose concentration decreased below 1.4 mmol/L from birth to 4 hours of life or below 2.0 mmol/L between 4 and 24 hours of life despite an appropriate

Management of newborn at risk or affected by hypoglycemia in the first 36 hours of life, Final Dec 18th 2017 Revision date: Dec 2021 11

intervention. 5 Repeated glucose value below 2.2 mmol/L despite appropriate intervention also required and IV intervention between birth and 4 hours of life or repeated glucose value below 2.6 mmol/L after 4 hours of life. 5

Risk factors for neonatal hypoglycemia

Many characteristics increase the risk of hypoglycemia in newborns. The following account among the most frequent: 5 7 13 14 15 12

• Newborn younger than 37 0/7 weeks • Small for gestational age (Birth weight below the 10th percentile) • Intrauterine growth restriction (IUGR) • Large for gestational age (Birth weight above the 90th percentile) • APGAR below 6 at 5 minutes of life • Infant of diabetic mother (include diabetes type 1, type 2 and gestational diabetes) • Beta-blockers exposure during pregnancy (ex: labetalol, propranolol, metoprolol) • Prenatal betamethasone (Celestone MD) administration

Prevention of hypoglycemia

Establishing breastfeeding (within 30 minutes of life) has been associated with a reduction of hypoglycemia during transitional period after birth for infants of diabetic mother. 16 Feeding does not only raise the blood glucose, it also stimulates ketosis, an alternative source of energy for the brain. 7 Therefore, at risk infants should be fed at regular intervals.

Intervention for hypoglycemia

Breastfeeding or feeding the newborn with expressed breast milk and formula are the baseline interventions usually attempt for infants with asymptomatic hypoglycemia. Nonetheless, breastfeeding might not be possible in some circumstances and express breast milk is not always available. If the glucose level does not rise above the targeted threshold, a glucose infusion can be initiated. A new alternative, dextrose gel, has been studied to manage neonates with hypoglycemia.

Dextrose gel

Dextrose gel 40% is a concentrated of an aqueous solution of dextrose, a simple carbohydrate, which can be administered by a direct application to mucosal surfaces of the mouth, including buccal and lingual surfaces. The usual dose that has been used in most studies is 0,5 mL/kg (200 mg/kg). Absorption from these sites may allow for rapid access to the circulation. Some proportion may be swallowed and absorbed from the gastrointestinal tract.

In a randomized control trial (Sugar Baby Trial, 2013, N = 514) including late preterm a term infants at risk for hypoglycemia, administration of 0.5 mL of dextrose gel 40% to neonates who presented with neonatal hypoglycemia within the first 48 hours of life was associated with a reduction of persisting blood glucose below 2.6 mmol/L and a reduction of NICU admission for hypoglycemia compared to placebo. 17

In an Australian center, implementation of dextrose gel resulted in a reduction of NICU admission for hypoglycemia from 29% in the pre-implementation (N = 100) phase to 14% in the post implementation phase (N = 100) (p = 0.01). 18 Most patients required only one dose of dextrose gel.

In a quality improvement initiative for the management of transitional neonatal hypoglycemia, 40% dextrose gel was introduced as a first-line treatment for the first two hypoglycemia, to allow at least 6h to establish breastfeeding before using formula milk supplementation. This initiative included 362 newborns and resulted in a reduction of the number of admissions to the NICU for hypoglycemia. It also results in an 88% increase of breastfeeding rates at 3 months. 19

A Cochrane review summarizes that the benefits associated with dextrose gel include the reduction of maternal-infant separation and improved the rate of exclusive breastfeeding after discharge, without altering the rate of developmental impairment at two years. 20 This review also states that outcomes are sufficient to warrant consideration of dextrose gel as a first-line treatment for infants with neonatal

Management of newborn at risk or affected by hypoglycemia in the first 36 hours of life, Final Dec 18th 2017 Revision date: Dec 2021 12

hypoglycemia. The Available evidence is derived from a group of at-risk infants born at a minimum of 35 weeks gestational age and treated with dextrose gel during the first 48 hours after birth.

When control blood glucose after an intervention

The Canadian Pediatric Society recommends that blood glucose should be control 60 minutes after enteral supplementation in asymptomatic newborns. 7 In fact, blood glucose concentration shows a cyclic response to enteral feed, reaching a peak about 1 hour after the feed and a nadir just before subsequent feed. 12

Duration of screening

Most infants will present hypoglycemia episodes during the first 24 hours of life (up to 94%). The measurement of 3 normal blood glucose value does not guaranty that hypoglycemia will not occur again. Indeed, up to 37% of hypoglycemia have been documented in a cohort of patients after 3 normal glycemia. 13

Management of newborn at risk or affected by hypoglycemia in the first 36 hours of life, Final Dec 18th 2017 Revision date: Dec 2021 13