- Neonatal hypoglycemia or blood
glucose is quite common in the neonatal transition period, affecting
around 15 percent of babies and is a preventable cause of brain damage.
- Neonatal hypoglycemia might lead to
permanent neurodevelopmental effects in early childhood at around four and
a half years finds a prospective study.
- Further studies necessary to
determine whether threshold glucose levels for diagnosis and intervention
need to be re-evaluated to ensure optimal outcome of these children.
Recurrent and severe neonatal
hypoglycemia could cause learning and behavioral difficulties at school,
however with normal intelligence, according to a study conducted by an international research team led by
Distinguished Professor Jane Harding at the Liggins Institute, University of
Auckland, New Zealand.
findings of the study appear in the journal JAMA
, and form part of a major long-term study, dubbed the "CHYLD"
study (Children with Hypoglycaemia and their Later Development).
‘Neonatal hypoglycemia could lead to learning difficulties at school, and future studies should prioritize their focus on measures to prevent brain damage.’
of Early Diagnosis and Treatment of Neonatal HypoglycemiaNeonatal hypoglycemia
is a fairly common
occurrence and more importantly is a
preventable cause of brain damage
is diagnosed clinically by performing a heel-prick
and if glucose levels are found to be low (less than 47 mg/dl),
the baby is given dextrose gel
normal levels are restored. In fact, this treatment was pioneered by Prof.
Harding and her team in 2013.
there is no internationally accepted
value for neonatal blood glucose level that is considered unsafe
immediate intervention. Values vary
from less than <2.6 mmol/L
(most commonly used and followed
in this study), but authorities from other countries have recommended cut-offs as low as 1.4 mmol/L and as high as 3.3
team therefore embarked on this study to assess
the risk of neurodevelopmental defects
associated with neonatal
hypoglycemia in this prospective cohort study and to determine whether current criteria for diagnosis of neonatal
hypoglycemia have to be revisited
and standardized to achieve better
outcomes for these babies.
Assessing Neurodevelopmental Effects Of Neonatal
Hypoglycemia - The Study Design
of The Study - Neurodevelopmental Outcomes Associated With Neonatal
- The Children With Hypoglycemia and
Their Later Development (CHYLD) Study is a prospective cohort study conducted among moderate to late
preterm and term infants born at risk of hypoglycemia.
- It was done at a regional perinatal
center in Hamilton, New Zealand between the months of December 2006 to
November 2010. Follow-up periods were from September 2011 to June 2015.
- The study included 614 neonates born from 32 weeks' gestation with at least 1
risk factor for hypoglycemia, including preterm, small, large,
diabetic mother, or acute illness.
- Whole blood and masked interstitial
glucose concentrations were estimated for up to 7 days after birth.
- Neonatal hypoglycemia is defined as
at least 1 consecutive blood glucose level of less than 47 mg/dL, a severe
episode with levels <36 mg/dL, and recurrent episodes were said to
occur if there were three or more instances. Interstitial hypoglycemia was
defined as an interstitial glucose concentration less than 47 mg/dL for at
least 10 minutes.
- Neonates with hypoglycemia (blood
glucose concentration <47 mg/dL) were treated to maintain blood glucose
concentration at a minimum 47 mg/dL.
- Cognitive function, executive
function, motor function and visual function were then assessed at 4 ½
- Overall, 477 of 604 eligible
children (79.0%) were assessed. Their mean age at the time of assessment
was 4.5 years, and 228 (47.8%) were females.
- Infants exposed to neonatal
hypoglycemia (280 [58.7%]) did not have an increased risk of neurosensory
- However, neonatal hypoglycemia was
associated with higher risk of low executive function and visual motor
function with the greatest risk in children exposed to severe, recurrent,
including clinically undetected (interstitial episodes only)
The findings seem to suggest that neonatal hypoglycemia
may not be
associated with neurosensory impairment at 4 ½ years of age but could cause a dose-dependent increase in
the risk of poor executive function
(skills for problem-solving, planning, memory and
attention) and visual
(skills for fine
control of movement, and understanding what you see)
even though not detected clinically
episodes), which could affect learning at school.
Professor Harding. "At two years there was no relationship between blood sugar
levels and later brain development, but at age 4.5 years, it's clear that the
children who experienced low blood sugar levels were more likely to have
She goes on to add, "We don't know yet what these impairments mean for
the child in practical terms, but executive
function and visual motor integration are believed to be important for learning
at school, particularly for math and reading
of The Study and Future Plans
- The current study raises serious
doubts that neonatal hypoglycemic episodes could indeed cause problems at
school, with some of the episodes not detected clinically.
was especially concerning in our 4.5 year results was the four-fold increase in
risk of executive function difficulties in children who had experienced low
blood sugars that were not detected in routine testing," says the paper's lead
author, Dr Chris McKinlay, also from the Liggins Institute. "This is the first
time this has been shown."
- The team plans to enlarge upon the
current study and conduct further
tests at 9-10 years of age to see if these children have significant
math and reading difficulties and behavioral problems.
Professor Harding opines that if the 9-10 year studies throw up
significant neurodevelopmental outcomes
linked to neonatal hypoglycemia,
then an urgent rethink would become
essential to re-evaluate and establish standardized diagnostic threshold
glucose levels for neonatal hypoglycemia
- Moreover, if treated infants also
show neurodevelopmental impairments, this raises the possibility of brain
damage being already present even before dextrose treatment was given.
The findings therefore, of another
ongoing study that Prof Harding is heading become all the more significant. The
study plans to assess whether dextrose
gel could be routinely given to all neonates at risk
of hypoglycemia before
brain damage could occur.
- Nataliia Burakevych, PhD1; Arijit Chakraborty, PhD1,4; J. Geoffrey Chase, PhD5; Gregory D. Gamble, MSc1; Deborah L. Harris, Robert J. Jacobs, Yannan Jiang, Nabin Paudel, Ryan J. San Diego, Benjamin Thompson, Trecia A. Wouldes, Jane E. Harding. Association of Neonatal Glycemia With Neurodevelopmental Outcomes at 4.5 Years. JAMA Pediatrics (2017). doi:10.1001/jamapediatrics.2017.1579