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HYPOGLYCEMIA

:
Neonatal Hypoglycemia
Making Sense of Different Opinions

PQCNC Maternal and Newborn Kickoff Meeting
Raleigh North Carolina, January, 2019
David H Adamkin
Professor Of Pediatrics
Associate Director of Division of Neonatology
Director of Nutritional Research
Associate Director of Neonatal Fellowship
Disclosures

I have no financial disclosures

I will not discuss any off-label use and/or
investigational drug use in my presentation

Other:
I am not a Neurologist nor a Developmental Pediatrician.
My goal is to prevent my patients from needing one.
BACKGROUND
1) NEONATAL HYPOGLCYEMIA IS THE MOST
COMMON METABOLIC PROBLEM IN
NEONATES

2) THERE IS NO UNIVERSALLY ACCEPTED
THRESHOLD FOR SAFE BLOOD GLUCOSE
CONCENTRATION DUE TO UNCERTAINTY
REGARDING EFFECTS ON
NEURODEVELOPMENT
Normal Levels of Glucose
WHAT IS A NORMAL BLOOD
GLUCOSE?
36 Mg/dl
20 (2.0)
(mmol/l)

(1.1)
40 60

(2.2) (3.3)
30
47
(1.7) 50
(2.6)
45
(2.7)
55 – 110
“ pragmatic intervention thresholds”
(2.5) (that also provide a margin of safety)

(3.0) (6.0)
Level
Operational threshold
Hypoglycemia damage?
duration Nondisease term
Postnatal Glucose Homeostasis
Critical in AAP approach
Feed and Not Sample NADIR
Insulin

Glucagon (mobilize
glycogen)

1
Figure 1: Profile of blood glucose concentrations in the immediate
postnatal period

Pildes 1986
Transitional Neonatal Hypoglycemia
The Fetal Glucose “Set Point” Normally Persists For Up To 48
Hours And Then Transitions To An Adult Set Point

THE PES
USES MEAN
VALUES

AAP
CONSIDERS
LOWER
RANGES FOR Maternal
OPERATIONAL Glucose
THRESHOLDS Concentrations
and CLINICAL
Fetal Glucose
CONDITION
Concentrations

Marconi, 1996
Srinivasan, 1986
Transitional Neonatal Hypoglycemia
Suppression of insulin occurs at a LOWER plasma glucose
concentration in Term Newborns first 48 hours than Children or Adults
HYPERINSULINISM (First 48 hours) ( mmol x 18=mg/dl)

Normal Suppression of Insulin Secretion in Children (85 mg/dL); Term Baby (55-65mg/dl) First 48 hours only!
Hawdon, 1993
Transitional Neonatal Hypoglycemia
(TNH) Is Hyperinsulinemia
• Mean plasma glucose for suppression of insulin secretion is 55-65 first 48
hours of life.

• Mean plasma glucose level for suppression of insulin in older infants is 80
-85mg/dl
(Glucose sensor-insulin secretion changes after 48 hours of life)

Cant make the diagnosis of Persistent Hypoglycemic Syndromes until > 48
hours.
IMPLICATIONS of TNH for ENDOCRINOLOGIST
• This TNH GLUCOSE THRESHOLD for suppression of insulin is the same
level as neuroendocrine responses to prevent brain injury in the adult : ie
insulin suppression, glucagon and epinephrine surge .“Neurogenic
Response”

• Therefore this Defines “normal” level for the first 48 hours of life
(PES)………55 to 65 mg/dl. Their recommendation is for glucose >
50mg/dl first 48 hours.
Suckling
Breastfeeding
Ketogenesis
Controversy
CALORIC DEPRIVATION VS 12 – 14% of
PROTECTION as normal, AGA,
ALTERNATIVE SOURCE OF breastfed
ENERGY. KETONES newborns
INCREASE after 24 hours have a blood
glucose level
of <47mg/dl in
Breastfeeding the first 3
average intake of days of life
colostrum ± 7
mls/feed in the first
24 hours. About 15
to 20 ml/k
(Houston et al Early
Human Development
1983)
Normal Newborn Fasting Glucose
Concentrations Are Stable (Mean)
Data from 1950s-1960s. Fasted 8 to 27 hours.
PES CONCLUDES glucose levels unaffected by Initiation or Feeding Interval
AAP believes lower glucose levels are affected by feedings

Glucose (mg/dL)

8 18 27
Duration of Fast (Hours)
2015: PES Neonatal Hypoglycemia Guidelines
Neonatal Regulation of Plasma Glucose TNH
“Beneficial Effects of Biochemical Hypoglycemia”

• The fall in plasma glucose concentrations postnatally is believed to be essential for
survival. Includes increased glucose production by glycogenolysis and
gluconeogenesis

• Also stimulation of appetite, adaptation to fast-feed cycles and stimulation of fat
metabolism.

• Breast fed infants have lower plasma glucose concentrations than formula fed
infants, but ketone levels are increased in response to breast feeding.

• Normal physiologic response that all mammals have the first days of life
Approaches to Define “Hypoglycemia”

Epidemiological –Statistical
- Cross sectional data
- Longitudinal data

• Clinical: Based on clinical manifestations

• Physiologic: Based on acute changes in metabolic and
hormonal responses. (PES)

• Outcomes: Based on neurologic and neurodevelopmental
outcome. (Functional Definition) Sentinel in AAP Statement
CLINICAL APPROACH Classic Report
Where did 40 Come From? 1959
First two days of life, hypoglycemia was arbitrarily defined
as <30mg/dl in the full term infant and < 20 mg/dl in PT.
(1950’s)

• Glucose concentration is safe if clinical symptoms
associated with hypoglycemia are not observed, or if
these symptoms disappeared at that specific
concentration
• Symptoms at 1.4 mmol/L (25mg/dl) resolved at >2.2
mmol/L (40mg/dl) by increasing the blood glucose
concentration

40 “classic standard” Cornblath, J of Peds 1959
Clinical Approach Is Flawed
Many concerns with this approach:
1) Observation of extremely low blood glucose
concentrations in asymptomatic infants.
2) Nonspecificity of symptoms, especially when
also associated with other neonatal diseases.
Symptoms just as likely among
normoglycemic.
3) Studies did not evaluate availability of other
energy substrates to neonate that may
compensate for lower glucose concentration
that might protect the brain (ketogenesis with
human milk feeding spares glucose for brain
consumption).
ADOPTED AS GOSPEL IN MANY COUNTRIES

47mg/dl 2.6mmol/l

Applied to all babies after 1988 including
normal breast feeding infants with no risk
factors
EVOLUTION of the DEFINITION (1988)
of NH as 47
NEURODEVELOPMENTAL APPROACH

• BW <1850 g
• N= 661 infants, 6808 samples,
• Mean (SD) BW 1337 (315) g
• Mean (SD) gestation 30.5 (2.7) wks
• Large Nutrition Study (5 centers)

Sampling
- Daily for all requiring intensive care until clinically stable
(2nd to 3rd week)
- Weekly till discharge or weighed 2000g (9th week)
- Developmental Testing (18 mos)
Lucas A, Morley R, Cole TJ. BMJ 1988; 297: 1304-8.
EVOLUTION of the DEFINITION (1988)
of NH as 47
NEURODEVELOPMENTAL APPROACH

• BW <1850 g
• N= 661 infants, 6808 samples,
• Mean (SD) BW 1337 (315) g
• Mean (SD) gestation 30.5 (2.7) wks
• Large Nutrition Study (5 centers)

Sampling
- Daily for all requiring intensive care until clinically stable
(2nd to 3rd week)
- Weekly till discharge or weighed 2000g (9th week)
- Developmental Testing
Lucas A, Morley R, Cole TJ. BMJ 1988; 297: 1304-8.
NEURODEVELOPMENTAL APPROACH
Lucas A, Morley R, Cole TJ. BMJ 1988; 297: 1304-8.

• Maximum slope and significance were seen for PDI and MDI when a cut
off of 45mg/dl was used
• 2/3 had <47mg/dl ranging from 3 to 30 days. Median age onset was 2
days
• Reduced development scores were associated independently with number
of days on which level was < 47mg/dl.
(A number of infants had glucose < 20 for 5 days)

Not sustained at 7-8 years of age!!!!!!!!
Later author says method not optimal
Days of NH Adjusted RR
0 1
3-4 2.2 : 1
>5 3.5 : 1
The Northern Neonatal Nursing Initiative
“Hypoglycemia” Study (1990-91) 2005
Aim and Design:

• To compare the neurodevelopmental outcome of preterm (<32 weeks)
who had frequent low blood glucose levels (<47 mg/dl ) in the first ten
days of life vs that of matched controls.
• Prospective, Observational
• Daily glucose as well as other samples recorded the first 10 days
• Index cases 3 days <47, controls all > 47 (47/566)

TIN W Early Human Devt 2005
MEAN GRIFFITHS DEVELOPMENTAL
QUOTIENTS OF 47 MATCHED PAIRS
(2 Years) Index

Control

110

105

100

95

90
General Locomotor Personal & Hearing & Eye-Hand Performance
Quotient Social Speech Coordination

Tin W. Early Human Develop 2005
The NNNI “Hypoglycemia” Study (81% follow up)

Win Tin et al Pediatrics 2012
Incidence of Neonatal Hypoglycemia in Babies Identified
as at Risk In The First 48 Hours Of Life < (“47”)

• At risk groups - SGA, IDM, LGA, Late Preterm (<2500,>4500g)

• Plasma glucose measured before feeds q 3-8 first 48 hours (d/c

514 levels after 3 consecutive normals) Glucose Oxidase
(100%)

• Dextrose gel and placebo gel ( gel x 2 still <47, admit to NICU)

254 (49%) 260 (51%) Also expressed milk prior to delivery for IDM
• These at risk groups represent over 25% of all newborns
Normal Low
Glucose Glucose • At least 12.5% of all newborns have a low glucose concentration

– >550,000/year in the United States

– 10 % admitted to NICU and about 2 billion $/yr
2012
Continuous Interstitial Glucose Monitoring (glucose every 5 mins) CGM

Provided Courtesy of Jane Harding
Low Glucose Concentrations Are More Common
Than Clinically Recognized Using CGM
81% not detected by Plasma Sampling 2010

N=102 @ risk
>32 weeks
265 episodes
< 47 on CGM 81% 19%
107 episodes CGM
lasted > 30 mins, 75%
of those not detected on
blood sampling

Low glucose concentrations are also common in normal newborns
Physiologic importance of undetected low CGM is unknown
Targeting glucose control in preterm infants : Pilot studies
of Continuous Glucose Monitoring (CGM) 2018
CGM in VLBW has the potential to improve glucose control. Study assessed feasibility and safety of CGM.

BW < 1200g

- Accuracy test compared CGM with POC glucose levels in n=20

- Efficacy test compared CGM combined with a paper guideline (n=20) to target glucose control
47-180mg/dl compared with standard care

RESULTS

1)Sensor performed well vs POC, Percent time in target range 77% CGM vs 59% in standard
2) Percent time >180mg/dl was 24% with CGM vs 40% in Standard
3) CGM also detected clinically unsuspected episodes of hypoglycemia (Up to 5 hrs with intermittent, none >
30 minutes on CGM)

CONCLUSION
Study suggests that CGM has sufficient accuracy and utility in preterm to warrant formal testing in RCT
Thomson et al (UK) Arch Dis Child Fetal 2018
Continuous Glucose Monitoring (CGM) in NICU: Not Quite
ready for ‘plug and play’ (editorial)
PREMISE : CGM in VLBW has the potential to minimize the incidence of hypo and hyperglycemic episodes
and increase glycemic stability providing new opportunities to improve long term neurocognitive outcomes

EDITORIAL

Instrumentation was developed for DM patients with glucose target aimed at 70-180mg/dl. This contrasts with
narrower range for VLBW and devices are not sufficiently accurate for these patients. Need testing and device
aimed at 0-47mg/dl range for term and LPT newborns at risk.

No firm or widely accepted cut-off values for low or high glucose concentrations in neonates or the meaning of
any glucose concentration below or above those values at one time or different durations.

Differences of > 15mg/dl between interstitial and blood glucose concentrations. So these should not replace
blood sampling. Future will see improved accuracy of these devices now used for research.

No study has demonstrated improved outcomes following treatment of asymptomatic hypoglycemia, it is even
possible CGM could increase diagnostics and treatments that are not warranted.

Hay and Rozance Arch Dis Child Fetal 2018
Do you really know how many
times my blood glucose went
below 47mg/dl? YES! A LOT
CGM

Quadrigenta Septum Phobia profoundly
influenced neonatal care

(courtesy Win Tin )
FINDING the CRITICAL
LEVEL for GLUCOSE and
NEURODEVELOPMENTAL
OUTCOME
Children with Hypoglycemia and
their Later Development
(The CHYLD Study)

Hypothesis: The neuropsychological
development of 2 and 4.5 year old children
is related to the severity, duration, and
frequency of low glucose concentrations in
the neonatal period (n=614 @ Risk)

NEW ZEALAND
CHYLD
Children with Hypoglycaemia and their Later Development ,Courtesy Jane Harding
Key Findings From CHYLD @2y
At risk babies screened and treated with the aim of
keeping blood glucose concentrations >47 mg/dl:

1. There were long and undetected periods of
interstitial glucose concentrations ≤ 47mg/dl
2. High or unstable glucose concentrations were
associated with worse developmental outcomes.
“U shaped curves” morbidity @ low and high levels

CHYLD
McKinlay et al, NEJM 373: 2507, 2015 Children with Hypoglycaemia and their Later Development
Undetected Low Glucose
Concentrations
In at risk babies screened and treated with the aim of keeping blood
glucose concentrations > 47 mg/dl:
• 53% experienced blood glucose < 47mg/dl
• 23% had glucose concentrations <47mg/dl not detected on
intermittent blood testing.
• 25% of those treated had glucose concentrations < 47mg/dl for >5
hours in the first week

McKinlay et al, NEJM 373: 2507, 2015
CHYLD
Children with Hypoglycaemia and their Later Development
No Relationship Between Neonatal
Hypoglycemia and Neurodevelopmental
Impairment at Two Years

McKinlay et al, NEJM 373: 2507, 2015
CHYLD
Children with Hypoglycaemia and their Later Development
Undetected Hypoglycemia and
Outcome at 2 Years (CGM)

No events ≥1 Interstitial
Outcome RR (95%CI)
(N=108) episode (N=33)

Neurosensory impairment 42% 42% 1.01 (0.66, 1.54)

Processing difficulty 17% 17% 0.92 (0.38, 2.23)

McKinlay et al, NEJM 373: 2507, 2015
CHYLD
Children with Hypoglycaemia and their Later Development
Association of Neonatal Glycemia
with Neurodevelopment at 4.5 y
> 32 wks n=614 with at least one neonatal risk factor for
Hypoglycemia
• Blood and Masked interstitial measurements (CGM) up to 7 days

• NH =@ least one episode< 47, severe = <36, recurrent = > 3
episodes. Interstitial NH = < 47 for at least 10 minutes
Mckinlay et al Jama Peds 2017 CHYLD
RESULTS
• 477/604 were assessed (79%). 280 (58.7%) were exposed to
hypoglycemia
Hypoglycemia did not increase neurosensory impairment as
defined by visual impairment, deafness, CP or IQ > 1 SD below
mean

• Hypoglycemia was associated with increased risk of low executive
function,and lower visual motor function
• Highest risk in those exposed to severe, recurrent, or clinically
undetected (interstitial) hypoglycemia
Mckinlay et al Jama Peds 2017 CHYLD CHYLD
Children with Hypoglycaemia and their Later Development
Conclusions and Relevance
• NH was not associated with increase risk of combined
neurosensory impairment at 4.5 years

• NH was associated a dose dependent increased risk of
poor executive function and visual motor function, even if
not detected clinically.

• Will this influence later learning?
EXECUTIVE FUNCTION
• Collective capacity for problem solving, planning, attention control
and goal-directed behavior.
• Children have difficulty remembering and carrying out instructions,
staying focused, and planning and monitoring progress with a
specific task, which can affect not only daily activities but also
learning.
• Pre frontal cortex is responsible for proper devt of EF and
increased activation of this region is associated with better
academic functions and EF.
• Development of pre frontal cortex and EF is continuous from
childhood through adolescence and into early adulthood
Shah et al, Neonatology in press 2019
Neonatal Glycemia and
Neurodevelopmental Outcome: A
Systematic Review and Meta-analysis
• Eleven of 1665 studies reviewed were included.
• Early Childhood (2-5y) NH not associated with neurodevelopmental
impairment, but was associated with visual motor impairment and
executive dysfunction.
• Mid Childhood (6-11y) NH was associated with neurodevelopmental
impairment and low literacy and numeracy.
• No data for adolescents. ( Win Tin data not included)

Shah et al, Neonatology in press 2019
Conclusion Neonatal Glycemia and
Neurodevelopmental Outcome: A
Systematic Review and Meta-analysis
• Overall quality of evidence was low to very low.
• Authors suggest the review nevertheless suggests that neonatal
hypoglycemia may have important long-lasting adverse effects
on neurodevelopment.
• Carefully designed longer intervention trials are needed to
determine optimal management of neonates at risk of
hypoglycemia to improve long-term outcomes

Shah et al, Neonatology in press 2019
Neonatal Hypoglycemia (NH) : Is there a
neurodevelopmental impact in early
childhood ?
Single Center prospective cohort study @ least one risk factor
(>32 wks) N = 477 Developmental outcome at 2 years and 4.5 years. NZ

Infants grouped based on glucose oxidase : 1) NH consecutive glucose <
47mg/dl, 2) Severe NH consecutive < 36mg/dl and 3) Recurrent > 3 episodes
of hypoglycemia or CGM < 47 for greater than 10 minutes.

First screen 1-2hr of age then q3 to 4 first 24hrs and q6-8 the following 24hrs.
Up to 7 days or until no ongoing clinical concerns. Masked CGM 7days

Anchan et al, Journal of Perinatology 2019
Neonatal Hypoglycemia (NH) : Is there a
neurodevelopmental impact in childhood
Primary Outcome: Neurosensory impairment at 4yo, Visual
impairment, deafness, CP, Full Scale IQ, Visual motor integration,
executive function, movement assessment battery
RESULTS
No association between the presence of NH and neurosensory impairment
at 4.5 years of age ( 37.4% in children with history of NH vs 38.5% in
children with no history of NH) Not understood why so high in controls.
Risk was also not associated with the number of episodes of NH or minimum
blood glucose level
Lowest quintile for maximum blood glucose level in first 12 hours was
associated with impairment.
Anchan et al, Journal of Perinatology 2019
Neonatal Hypoglycemia (NH) : Is there a
neurodevelopmental impact in early childhood ?
RESULTS (cont)
Secondary outcomes children with exposure to NH did have a
statistically significant increase low executive function 10.6% vs
4.7% and low visual motor integration score 4.7% vs 1.6%.
Greatest risk those exposed to severe NH
NH only detected by CGM was associated with higher risk of low
executive function 12.5% vs 3.5%
Post hoc analysis showed Pts who developed impairment had a
steeper rise in CGM after NH.
Conundrum while NH can effect outcome, rapid resolution can
have adverse effects.
Anchan et al, Journal of Perinatology 2019
Screening and Management of Postnatal Glucose Homeostasis in Late Preterm
and Term SGA, IDM/LGA Infants (PEDS March 2011,reaffirm 2016)
[(LPT) Infants 34 – 36 6/7 weeks and SGA (screen 0-24 hrs); IDM and LGA > 34 weeks (screen 0 -12 hrs)]

Symptomatic and <40mg/dl IV Glucose

ASYMPTOMATIC
Birth to 4 hours of age 4 – 24 hours of Age
INITIAL FEED WITHIN 1 Hour Continue feeds q2-3 hours
Screen glucose 30 minutes after 1st feed Screen Glucose prior to each feed
Initial Screen <25mg/dl Screen <35mg/dl
Feed and check in 1 hour Feed and check in 1 hour
<25mg/dl 25 – 40mg/dl <35mg/dl 35 – 45m/dl

IV Glucose* Refeed/IV Glucose* IV Glucose* Refeed/IV Glucose*
as needed as needed

Target Glucose screen ≥45mg/dl prior to routine feeds
*Glucose dose = 200mg/kg (dextrose 10% at 2ml/kg) and/or IV infusion at 5 – 8mg/kg/min (80 – 100ml/kg/d)
Achieve plasma glucose 40 – 50mg/dl.

Symptoms of Hypoglycemia include: Irritability, tremors, jitteriness, exaggerated moro reflex, high-pitched cry,
seizures, lethargy, floppiness, cyanosis, apnea, poor feeding.
Dextrose Gel
GEL ADMINISTRATION @ALGH ( Provided by Cathy Bennet)

Repeat this process,
alternating sides until
entire dose has been
administered.

Insert 0.5 mls into right Massage for a few seconds
buccal cavity
Dextrose Gel for Neonatal Hypoglycemia (Sugar Babies Study)
RCT
RESULTS
Randomized double blind placebo controlled trial
(New Zealand) • 242/547 (47%) were hypoglycemic and then
• 35-42 wks,< 48 hours old @ risk 1:1 randomized
randomization
• Dextrose gel reduced treatment failure vs
• 40%dextrose gel (200mg/k) or placebo gel placebo 14% vs 29%
• Randomization stratified by maternal FINDINGS
diabetes and BW
• Treatment with dextrose gel is inexpensive
• Hypoglycemia < 47mg/dl and simple to administer. Dextrose gel more
• Treatment failure < 47 after 2 tx effective than feeding alone and should be
• Up to 6 doses over 48 hours considered for first line treatment to
manage hypoglycemia in LPT and Term in
first 48 hours after birth.

Harris DL et Al Lancet 2013
Outcome at 2 Years after Dextrose Gel Treatment
for Neonatal Hypoglycemia: F/U RCT

• Gel vs Placebo gel, N=184, Standard risk categories. First 48 hours
• Primary Outcome was Treatment failure which was defined as glucose
< 47mg/dl after two attempts with gel. Feedings encouraged.
• Glucose at one hour then q 4 first 24 hours.
• Next 24 hours q 6 to 8 hours

Harris J Ped 2016
Study Results
• High Rates of Neurosensory impairment (35%) both groups. Most were
mild processing difficulties. Multiple secondary growth and
developmental outcomes were also equivalent for both groups.

• Less treatment failure with Dextrose Gel, less NICU admissions NNT = 8

• Overlapping cohort (Mckinlay) treated to maintain > 47mg/dl was not
associated with increased risk of NDI.

Harris J of Ped 2016
Oral Dextrose for Treatment of Hypoglycemia
• Two trials N=312 Cochrane Weston et al 2016

1) No evidence of a difference between dextrose gel and placebo gel for major
neurosensory disability at 2 year follow-up. ( One trial n =184 quality of evidence very
low)
2) Dextrose gel vs placebo gel or no gel did not alter the need for IV treatment for
hypoglycemia.
3) One trial (n=237) dextrose gel treated infants less likely to be separated from
mothers for treatment of hypoglycemia and more likely to be exclusively breast fed
after discharge.

Conclusion: Oral dextrose gel should be considered first line treatment for infants with
neonatal hypoglycemia
Glucose Gel in Infants at Risk for Transitional
Neonatal Hypoglycemia
Nursery protocol adopted 200 mg/kg gel for at risk infants. Compared to year
before no gel ( n=421) and year 2 after the addition of gel (n=383)
RESULTS

NICU transfer for management of Neonatal Hypoglycemia fell
from 8.1% in Year 1 (34/421) to 3.7% in Year 2 (14/383)
57%reduction

1 gel dose 45%, 2 doses 30%, 3 doses 17%, 4 doses 8 %

Rate of exclusive breastfeeding increased from 6% in Year 1 to 19% in Year 2 with
gel.

Hospital charges for the study population decreased from $801,276 to $387, 668
pre-gel vs gel ,respectively.
Makker et al Am J
Peri 2018
What Happens to Blood Glucose after Oral
Treatment for Neonatal Hypoglycemia?
Harris et al J Ped 2017

• N=227, Blood glucose < 47mg/dl, 295 episodes NH
• Glucose Oxidase within 90 min after randomization ( Dextrose or placebo gel) plus
feeding with formula, expressed breast milk, or breast fed
RESULTS
• 1) Overall mean increase in blood glucose was 11.7 mg/dl
• 2) Gel vs Placebo +3.0mg/dl larger increase,Formula +3.8mg/dl vs other feeds
• 3) Increase in blood glucose not affected by breast feeding or expressed milk, but
breast feeding was associated with reduced requirement for repeated gel.

• Conclusion: Dextrose gel and breast feeding should be considered for first line oral
treatment of infants with hypoglycemia
Now Screening

Universal Screening
Association Between Transient Newborn Hypoglycemia
and Fourth-Grade Achievement Test Proficiency
A Population Based Study

Retrospective 1998 included all infants born @ University of Arkansas (1395 pairs)

At least 1 recorded glucose within first three hours of life was below cut off while next
value was above the cutoff.

< 35mg/dl (primary) , < 40mg/dl, <45mg/dl (secondary) cut offs

Student achievement scores done in 2008 from Arkansas Department of Education:
Literacy and Mathematics (predict HS graduation, college, long term success).

Kaiser et al JAMA PEDS 2015
Association Between Transient Newborn Hypoglycemia
and 4th grade Achievement Test Proficiency
• Transient hypoglycemia occurred in 6.4%, 10.3% and 19.3% of newborns with a
cutoff value of 35, 40 or 45 mg/dl.
• Hypoglycemia was associated with significant reductions on proficiency in literacy
and mathematic achievement tests
• (50% reduction in score)
Do These Data Justify Universal Screening?

• The key question is “would an intervention have prevented an adverse
outcome?”
• First low glucose concentration was detected at 1.5 hours
• A subsequent result after re-feeding was available in 1 hour and 10 minutes
• That means that more than 3 hours would have lapsed before the second result
was available
• It is unlikely any intervention after the first measurement was known would have
decreased the duration of hypoglycemia.
• Almost 20% < 40 mg /dl
Does Prophylactic Dextrose Gel after First Milk
Feeding Decrease NH and NICU admits
• N = 72 Gel,164 Controls. Risk groups <2500g or >4000g, LPT/IDM
• Quasi –Experimental Approach, ( when researchers available)
• Feed as soon after birth as possible (63-68% BF)
• Blood glucose 30 mins after gel
• Followed AAP guideline for glucose level and IV glucose
RESULTS (Gel vs Controls)
Glucose 52.1 ±17 vs 50.5 ±15 mg/dl
NICU Admission (IVF) 9.7% vs 14.6 % NO differences

Coors /Kaiser et al J Ped 2018