Case 1. Managing Neonatal Hypoglycemia: Can formula supplementation be avoided? Faculty Financial Disclosures 3/8/2018

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1 Managing Neonatal Hypoglycemia: Can formula supplementation be avoided? Shawnte R. James, MD, FAAP Assistant Professor Newborn Medicine Hospitalist Emory University School of Medicine Department of Pediatrics Division of Neonatal-Perinatal Medicine Faculty Financial Disclosures In accordance with the ACCME standards for commercial support, all faculty members are required to disclose to the program audience any real or apparent conflict(s) of interest to the content of their presentation. I have nothing to disclose. Case 1 Baby Carlton is an early term newborn (38.0 weeks) who was delivered by STAT C/S after loss of fetal heart tones. His APGARs were 6/9/9, he is AGA. He arrives in the holding nursery at 45 minutes of life, and his initial glucose is 44. Because of the STAT C/S, his mother was under general anesthesia for the delivery. What is the most appropriate next step in the management of Baby Carlton? A. No supplementation, await mother s availability for S2S and breastfeeding B. No supplementation and immediately have L+D nurse hand express mother s colostrum to feed to baby C. No supplementation and recheck sugar in 1 hour D. Supplement with 5-10mL of formula via cup or syringe E. Supplement with bottle/nipple to feed to satisfaction 1

2 Case 1 Answer How do we define hypoglycemia? How do we define hypoglycemia? 2

3 Case 1 (If you re curious, here s what I would choose) Baby Carlton is an early term newborn (38.0 weeks) who was delivered by STAT C/S after loss of fetal heart tones. His APGARs were 6/9/9, he is AGA. He arrives in the holding nursery at 30 minutes of life, and his initial glucose is 44. Because of the STAT C/S, his mother was under general anesthesia for the delivery. What is the most appropriate next step in the management of Baby Carlton? A. No supplementation, await mother s availability for S2S and breastfeeding B. No supplementation and immediately have L+D nurse hand express mother s colostrum to feed to baby C. No supplementation and recheck sugar in 1 hour D. Supplement with 5-10mL of formula via cup or syringe E. Supplement with bottle/nipple to feed to satisfaction Endocrinology Plasma glucose concentration low enough to cause signs of symptoms of impaired brain function. If unable to communicate symptoms, PG levels below the normal threshold for neurogenic responses <60 mg/dl (<3.3 mmol/l) Merck Manual of Diagnosis and Therapy Plasma glucose concentration < 40 mg/dl (< 2.2 mmol/l) in term neonates or < 30 mg/dl (< 1.7 mmol/l) in preterm neonates 3

8 mmol/l) Acceptable and stable value of >40 mg/dl (>2.2 mmol/l) How do we define hypoglycemia?

4 American Academy of Pediatrics American Academy of Breastfeeding Medicine A reasonable (although arbitrary) goal is to maintain plasma glucose concentrations between 40 and 50 mg/dl (between 2.2and 2.8 mmol/l) Acceptable and stable value of >40 mg/dl (>2.2 mmol/l) How do we define hypoglycemia? TAKE HOME POINT: The definition of neonatal hypoglycemia in the first 48hrs of life for term and late preterm newborns remains one of the most contested and controversial topics in Neonatal/Perinatal Medicine. 4

Alexis Hartmann, MD and Joseph Jaudon, MD (1937) the frequent occurrence in normal newborn infants of cyanosis,

is almost a normal occurrence during the first few days of life. Heather J. Shelley, D.Phil and G.A. Neligan D.M. M.

Needs to be kept relatively constant to ensure steady growth of fetus Levels controlled by three mechanisms:

5 Alexis Hartmann, MD and Joseph Jaudon, MD (1937) the frequent occurrence in normal newborn infants of cyanosis, irritability, listlessness and muscular disorders might very well be due sometimes to hypoglycemia. is almost a normal occurrence during the first few days of life. Heather J. Shelley, D.Phil and G.A. Neligan D.M. M.R.C.P (British Medical Bulletin, Jan 1966) Intrauterine Glucose Principal energy substrate for placenta and fetus Needs to be kept relatively constant to ensure steady growth of fetus Levels controlled by three mechanisms: Maintenance of maternal glucose concentration Transfer of maternal glucose to fetus through placenta Production of insulin by the fetal pancreas 5

6 Fetal oxidation of intrauterine glucose Regulated by glucose transporters (GLUT4) in the insulin sensitive tissues (tissues with IR s) Up or down-regulated in response to changes in fetal glucose concentration RATE is dependent on the relative interaction between two components: Fetal plasma glucose Fetal insulin concentration Regulation of glucose metabolism by insulin Glucose in the healthy newborn Decreases by 25-35mg/dL in the first 2-3 hours of life Reaches a nadir at ~3hrs of life Steadily increases to reach normal levels in 24-48hrs 6

7 Clinical Hypoglycemia Serum glucose concentration low enough to cause symptoms and or signs of impaired brain function. Symptoms Autonomic Adrenergic Palpitations, tremor, anxiety Cholinergic Sweating, hunger, paresthesia Neuro-glycopenic Brain fog Confusion Coma How does exclusive breastfeeding affect a newborn s glucose? Exclusively breastfed infants do not receive full caloric intake for several days after birth, resulting in hypoglycemia. Ketogenesis is partially activated, but measured ketones in neonatal serum in the first days of life are low ( mmol/L) Are ketones an acceptable alternative fuel source for neonates in the first 24-48hrs of life? Without specific measurement of ketone levels during the period of hypoglycemia in question, it CANNOT be assumed ketones are available and sufficient to support brain metabolism. It CANNOT be assumed that ketones will protect brain metabolism in a breast-fed infant if post-natal fasting state/hypoglycemia is prolonged. 7

8 So what should we do?! So what should we do?! (I m kidding, I actually know what we should do this time) So what should we do?! 8

How to effectively increase glucose concentration in

Intravenous dextrose fluids Volume PO feeds and for

9 How to effectively increase glucose concentration in hypoglycemic neonate? Intravenous dextrose fluids PO feeds with EBM or formula and for bonus points? How to effectively increase glucose concentration in hypoglycemic neonate? Intravenous dextrose fluids Volume PO feeds and for bonus points? ORAL DEXTROSE GEL!!! Like this? 9

10 Actually, more like this, but close! Implementing a Protocol Using Glucose Gel to Treat Neonatal Hypoglycemia. (Bennett, Fagan, et. al.) Abstract Neonatal hypoglycemia is a leading cause of admission of neonates to the NICU. Typical treatment for neonatal hypoglycemia includes supplementation with formula or, in some cases, intravenous glucose administration. These treatments, though effective at treating hypoglycemia, interrupt exclusive breastfeeding and interfere with mother-infant bonding. Our institution developed a treatment algorithm for newborns at risk for neonatal hypoglycemia. The new algorithm called for the oral administration of 40% glucose gel. This intervention resulted in a 73% decrease in admission rates to the NICU for hypoglycemia, and it supported exclusive breastfeeding, skin-to-skin contact, and mother-infant bonding. Basic steps in glucose gel algorithm Neonates are placed skin to skin and breastfed within the first hour of life. A BG level is obtained 30 minutes after this feeding is completed. If the BG level is <35 mg/dl, the nurse administers a weight-based dose of 40% glucose gel by syringe to the neonate s buccal cavity and then places the neonate with the mother to feed. A BG level is then repeated 1 hour after gel administration. If this BG level is >35 mg/dl, the neonate s BG levels are assessed before feedings until two consecutive readings are >45 mg/dl. If the neonate s BG level is <35 mg/dl, a second dose of the gel is administered, and the neonate is again placed with the mother to feed. In the event that a second dose is needed, a BG level is obtained 1 hour after gel administration. If hypoglycemia is not reversed after the second dose of 40% glucose, the physician is contacted for further orders. 10

3/8/2018 Results of Protocol Implementation Reduction of NICU admissions Since implementation, 73% reduction in NICU admits with primary diagnosis of hypoglycemia.

11 3/8/2018 Results of Protocol Implementation Reduction of NICU admissions Since implementation, 73% reduction in NICU admits with primary diagnosis of hypoglycemia. Effect on exclusive breastfeeding During 14mo post-implementation, 494 out of 1,089 women with neonates at risk for hypoglycemia chose exclusive breastfeeding as first feeding choice 49% were successful Me imagining the potential decrease in frequency of my Come to Jesus talks Baby-Friendly team hearing increase in exclusive breastfeeding rates Neos/NICU nurses hearing 73% decrease in NICU hypoglycemia admissions Clinical Nurse Specialist realizing how much work we re going to dump on her to make protocol go-live EUHM Neonatal Hypoglycemia Protocol - Implementation Protocol: Newborn - Hypoglycemia Entity: Respon Dept/Group: Database: Category: Emory Hospitals Perinatal Services Patient Care Protocols CPOE, Diagnostic/Therapeutic/Preventive Content: * All babies must be plotted on the weight chart in the delivery room based on gestation by dates (EGA). * Babies who plot LGA (90% or greater) or SGA (10% or less) should be placed on the glucose monitoring protocol. * All babies born to a mother with insulin dependent diabetes mellitus (IDDM) or gestational diabetes mellitus (GDM) should be placed on the glucose monitoring protocol. * All late preterm infants ( /7 weeks) or post-dates infants (greater or equal to 42 weeks) should be placed on the glucose monitoring protocol. * All babies who exhibit signs and symptoms of hypoglycemia (irritability, jittery, lethargy) should have an initial glucose screen reported to the MD/NNP. The MD/NNP may require the glucose monitoring protocol to be initiated. * Breast fed babies (who meet glucose monitoring criteria) should initiate skin to skin and breastfeeding in the delivery room. The initial glucose screen should be done by one (1) hour of age, even if skin to skin. * Bottle fed babies (who meet glucose monitoring criteria) can be skin to skin with mother in the first hour. The initial blood glucose screen should be done by one (1) hour of age, even if skin to skin. * If initial and/or repeat blood glucose screen result is > or equal to 45 mg/dl: Ad lib feed at least every 3 hours and continue blood glucose monitoring before feedings for 24 hours. * If initial blood glucose screen result is mg/dl: * Feed immediately * For exclusively bottle-fed infant, feed 10 15mL by mouth immediately, then obtain a 90 minute PC glucose reading. * If 90 minute PC result is < 45mg/dL, notify MD/NNP * For exclusively breastfed infants * Administer 0.5mL/kg of dextrose gel and then send to breastfeed immediately. * Recheck glucose in 30 minutes * If result is > or equal to 45mg/dL, continue protocol 11

12 Newborn Hypoglycemia Protocol Algorithm Newborns to Place on Glucose Monitoring: SGA(10%or <),LGA (90% or >),IDDM/GDM Moms,Late preterm ( /7 wks),post dates( 42 wks) Any Symptomatic infants (irritable, jittery, lethargic)-obtain BG immediately and notify MD/NNP Breast Fed Babies Formula Fed Babies Skin to skin/breastfeed Initial glucose at one Skin to skin hourof age Initial glucose at one hour of age even if skin to even if skin to skin skin Initial Blood Glucose 45mg/dl Ad lib feed at least every 3 hours and continue BG screen for 24 hours Any BG < 25 (or too low to register) Administer 0.5ml /kg Dextrose gel AND feed formula immediately Recheck BG one hour after initial glucose screen then notify MD/NNP results Any BG result mg/dl Breast fed babies Any BG result mg/dl Formula Fed babies Administer 0.5ml/kg dextose gel and breast feed immediately Feed formula ad lib immediately as able * Recheck BG one hour after initial glucose Recheck BG one hour after initial glucose screen screen Repeat BG <45mg/dl Administer 0.5ml/kg Dextrose gel AND ad lib feed formula immediatley Recheck BG 30 minutes after formula supplementation If result <45 mg/dl notify MD/NNP Repeat BG 45 mg/dl Ad lib feed at least every 3 hours and continue BG monitoring before feeds for 24 hours and at least 12 hours after any glucose <45 * Volume of supplemental feeding is not limited EBM is the first choice Minimum volume is 10-15ml if available Weight Dose (ml) Dose (g) ml 0.4 g kg kg 1.5 ml 0.6 g kg 2.0 ml 0.8 g > 4.5 kg 2.5 ml 1.0 g EUHM Neonatal Hypoglycemia Protocol - RESULTS to an Emory Breastfeeding Conference Near YOU! Take Home Points The definition of hypoglycemia is strongly contested in Neonatology, so your institution should develop its own policy for diagnosis. Relying on baby s fasting mechanisms to self-regulate serum glucose concentrations is NOT recommended. Managing neonatal hypoglycemia can be safely managed *without* large volume formula feeds, and often is wellmanaged using consistent supplementation with mother s EBM and oral glucose gel 12

13 Baby Carlton is an early term newborn (38.0 weeks) who was delivered by STAT C/S after loss of fetal heart tones. His APGARs were 6/9/9, he is AGA. He arrives in the holding nursery at 45 minutes of life, and his initial glucose is 35. Because of the STAT C/S, his mother was under general anesthesia for the delivery and is not available to breastfeed. You decide to supplement Baby Carlton with formula to manage his hypoglycemia. Which is the best option for formula supplementation for Baby Carlton? a. 5-10mL via cup or syringe b. 5-10mL via bottle c mL via syringe d mL via bottle e. Bottle-feed to baby s satisfaction Baby Carlton is an early term newborn (38.0 weeks) who was delivered by STAT C/S after loss of fetal heart tones. His APGARs were 6/9/9, he is AGA. He arrives in the holding nursery at 45 minutes of life, and his initial glucose is 35. Because of the STAT C/S, his mother was under general anesthesia for the delivery and is not available to breastfeed. You decide to supplement Baby Carlton with formula to manage his hypoglycemia. Which is the best option for formula supplementation for Baby Carlton? a. 5-10mL via cup or syringe b. 5-10mL via bottle c mL via syringe d mL via bottle e. Bottle-feed to baby s satisfaction Take Home Point Small amounts of formula supplementation (5-10mL) for neonates with hypoglycemia is AS EFFECTIVE as large volume feeds in normalization and stabilization of neonatal hypoglycemia.* Syringe/Cup/Spoon feeding is AS EFFECTIVE as bottle feeding to deliver this small volume supplement.* *as caveat, this is preliminary data from EUHM Women s Services Late Preterm Hypoglycemia study. 13

14 Many Thanks and Much Love! References 1. Thornton PS, Stanley CA, De Leon DD, et al. Recommendations from the Pediatric Endocrine Society for Evaluation and Management of Persistent Hypoglycemia in Neonates, Infants, and Children. J Pediatr 2015; 167: Trans Am Clin Climatol Assoc. 2006; 117: Placental-Fetal Glucose Exchange and Fetal Glucose Metabolism William W Hay, Jr, MD 3. Acta Paediatr Jpn Apr;39 Suppl 1:S7-11. Neonatal hypoglycemia 30 years later: does it injure the brain? Historical summary and present challenges. Cornblath M1. 4. Bennett C1, Fagan E2, Chaharbakhshi E3, Zamfirova I4, Flicker J Feb-Mar;20(1): doi: /j.nwh Epub 2016 Feb 12. Implementing a Protocol Using Glucose Gel to Treat Neonatal Hypoglycemia. 5. PediatricsMay 2000, VOLUME 105 / ISSUE 5 Controversies Regarding Definition of Neonatal Hypoglycemia: Suggested Operational Thresholds - Marvin Cornblath, Jane M. Hawdon, Anthony F. Williams, Albert Aynsley-Green, Martin P. Ward-Platt, Robert Schwartz, Satish C. Kalhan 6. Pediatrics in Review April 2017, VOLUME 38 / ISSUE 4 Neonatal Hypoglycemia Alecia Thompson-Branch, Thomas Havranek 7. New approaches to management of neonatal hypoglycemia Paul J. Rozance, William W. Hay, Jr. Matern Health Neonatol Perinatol. 2016; 2: 3. Published online 2016 May 10. doi: /s Hegarty JE, Harding JE, Crowther CA, et al. Oral dextrose gel to prevent hypoglycaemia in at-risk neonates. Cochrane Database Syst Rev Rozance PJ, Hay WW. Hypoglycemia in newborn infants: Features associated with adverse outcomes. Biol Neonate 2006; 90: Committee on Fetus and Newborn, Adamkin DH. Postnatal glucose homeostasis in late-preterm and term infants. Pediatrics 2011; 127: Imperfect Advice: Neonatal Hypoglycemia. Adamkin DH, Polin RA, J Pediatr Sep;176: Epub 2016 Jun

Learning Objectives. At the conclusion of this module, participants should be better able to:

Learning Objectives. At the conclusion of this module, participants should be better able to: Learning Objectives At the conclusion of this module, participants should be better able to: Treat asymptomatic neonatal hypoglycemia with buccal dextrose gel Develop patient-specific approaches to intravenous