The Journal of Maternal-Fetal & Neonatal Medicine

ISSN: 1476-7058 (Print) 1476-4954 (Online) Journal homepage: https://www.tandfonline.com/loi/ijmf20

Incidence of hypoglycemia in newborn infants

identified as at risk

Johanna Stark, Burkhard Simma & Anya Blassnig-Ezeh

To cite this article: Johanna Stark, Burkhard Simma & Anya Blassnig-Ezeh (2019): Incidence of
hypoglycemia in newborn infants identified as at risk, The Journal of Maternal-Fetal & Neonatal
Medicine, DOI: 10.1080/14767058.2019.1568985

To link to this article: https://doi.org/10.1080/14767058.2019.1568985

Published online: 27 Jan 2019.

Submit your article to this journal

View Crossmark data

Full Terms & Conditions of access and use can be found at

https://www.tandfonline.com/action/journalInformation?journalCode=ijmf20
THE JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE
https://doi.org/10.1080/14767058.2019.1568985

ORIGINAL ARTICLE

Incidence of hypoglycemia in newborn infants identified as at risk

Johanna Starka , Burkhard Simmab and Anya Blassnig-Ezehb
a
Krankenhaus Sankt Vinzenz Zams, Zams, Austria; bDepartment of Pediatrics and Adolescent Medicine, Landeskrankenhaus Feldkirch,
Feldkirch, Austria

ABSTRACT ARTICLE HISTORY

Background: Temporary low plasma glucose concentrations are common in healthy newborns. Received 17 July 2018
Although there is no uniform definition of neonatal hypoglycemia, there is a consensus in the Accepted 9 January 2019
current literature that plasma glucose concentrations should be measured in infants at risk.
KEYWORDS
Known risk groups for transient neonatal hypoglycemia include infants of diabetic mothers
Diabetes; glucose; neonate;
(IDM), large (LGA) or small (SGA) for gestational age and late preterm (LPT) infants. risk-group; screening
Objectives: The aim of this retrospective trial was to determine the incidence of hypoglycemia
and the impact of the application of a 2011 revised guideline in respect of additional feeding or
i.v. glucose administration, admission to a neonatal ward and the number of blood sam-
ples taken.
Methods: During the period 1 January 2015 to 31 January 2016, the plasma glucose concentra-
tions of all infants at risk were determined. They were screened over a period of 24 hours or
until plasma glucose concentration was >45 mg/dL on three occasions. Hypoglycemia was
defined as a plasma glucose concentration <40 mg/dL, regardless of the age of the infant.
Results: One hundred and thirty-six (13.6%) out of 1017 newborns were identified as at-risk
patients, 119 (87.5%) of whom were included in the final data evaluation. Ten study participants
had more than one risk factor and 32 (26.9%) newborns (male:female ¼ 1.1:1) had a total of 40
hypoglycemic episodes. Three (9.4%) out of these 32 newborns had to be transferred to the
neonatal ward for i.v. glucose treatment. The mean number of blood samples taken
was 7.6 ± 2.4.
Conclusions: The incidence of hypoglycemia in the studied infants at risk was 27%, and 19.7
blood samples had to be taken to detect one episode of low glucose concentration. Neonatal
hypoglycemia can be recognized and avoided in time, which justifies the establishment of a
standardized plasma glucose measurement protocol in newborn infants at risk.

BRIEF RATIONALE
Following a considerable number of sources, it is recommended that infants at risk be identified,
low plasma glucose concentrations prevented and, if necessary, the affected neonates cared for.
Our data show that the risk group for neonatal hypoglycemia comprised about one-tenth of all
infants at our nursery and hypoglycemia occurred in one-fourth. These results are in accordance
with the recommendations to implement this protocol as a screening tool in neonates.

Introduction and asymptomatic hypoglycemia suffer from clinically

Neonatal hypoglycemia is a common finding in new-
borns and a treatable risk factor for long-term neuro-
logic impairment. At birth plasma glucose levels
immediately fall to the lowest values in the first hours
of life and reach adult levels at two or three days of
age [1,2].
Although there are established associations
between prolonged symptomatic neonatal hypogly-
cemia and poor long-term neurocognitive function [3],
it is unknown whether children with milder
detected adverse neurodevelopmental outcomes [4,5].
Consequently, the clinical significance of temporary
low-plasma glucose concentrations remains a continu-
ing controversy, especially in newborns at risk, such as
infants of diabetic mothers (IDM), large or small for
gestational age infants (LGA and SGA, respectively)
and late preterms (LPTs) [6,7]. Following a consider-
able number of sources, it is recommended that
infants at risk be identified, low plasma glucose con-
centrations prevented and, if necessary, the affected
neonates cared for [8–12].

CONTACT Johanna Stark johanna.stark@hotmail.com Krankenhaus St. Vinzenz Zams, Sanatoriumstraße 43, Zams, Austria
ß 2019 Informa UK Limited, trading as Taylor & Francis Group
2 J. STARK ET AL.
Recently, the American Academy of Paediatrics
(AAP) [9] published a guideline for screening and
management of hypoglycemia in newborns at risk.
This guideline recommends taking a first blood
sample 30 min after the first feed and within 1 h after
delivery. All further measurements should be done
every 3–4 h right before feeding. If plasma glucose
concentration falls below 25 mg/dL in the first hour of
life or below 40 mg/dL thereafter, additional feeding
or i.v. glucose is recommended. The target glucose to
be achieved is defined as 45 mg/dL. Monitoring dur-
ation should be 12 h for IDM and LGA infants, and
24 h for SGA and LPT infants.
Hypothesis
The purpose of this retrospective cohort study is to
define the incidence of hypoglycemia in newborns
identified as being at risk and the consequences of
screening in respect to numbers of blood samples
taken, additional feeding or i.v. glucose administration
and leading to admission to the neonatal ward.
Materials and methods
Study design and participants
In this observational, anonymized and retrospective
study, we implemented the 2011 guidelines published
by the AAP [9]. In light of the results of a previous
investigation at our institution [13], we partially rede-
fined the at-risk groups and adapted the treatment
regimen. We restricted the definitions for LGA and
SGA infants to infants with birth weights greater than
the 97th percentile and smaller than the third percent-
ile. We screened all infants for 24 h or until there were
at least three glucose concentrations of 45 mg/dL.
Eligible participants were recruited from all
infants born between 1 January 2015 and 31 January
2016 (13 months) at the Academic Hospital,
Landeskrankenhaus Feldkirch, Austria. Newborns were
enrolled in the study if they were identified as being
at risk: IDM (type 1 or 2 diabetes, gestational diabetes
or impaired glucose tolerance in pregnancy), LPTs
(34 þ 0/7 to 36 þ 6/7-week gestation), small (birth-
weight <3rd percentile) or large (birthweight >97th
percentile) for gestational age infants. Exclusion crite-
ria were met if infants had to be admitted to the neo-
natal ward because of a disease other than
hypoglycemia or if infants suffered from serious con-
genital malformations (e.g. congenital heart defect,
cleft lip, and/or palate) or terminal conditions.
Procedures
All infants were breast or formula fed in the first
hour after birth and plasma glucose concentrations
were measured 30 min thereafter. If glucose was
<25 mg/dL, feeding had to be repeated immediately
and the glucose value was rechecked 1 h later. If glu-
cose values stayed <25 mg/dL i.v. glucose treatment
was started. Below 40 mg/dL, the consulting pediatri-
cian decided whether i.v. glucose was to be adminis-
tered or feeding repeated. Further plasma glucose
monitoring was performed every 2–3 h, before feeds.
Between 4 and 24 h of age, i.v. glucose administra-
tion was necessary if glucose values were twice con-
secutively below 35 mg/dL, despite repeated feeding.
Symptomatic infants and infants with recurrent plasma
glucose concentrations <40 mg/dL were admitted to
the neonatal ward for i.v. glucose infusion.
Capillary blood samples were taken by nursing staff
via heel-/finger-pricking and analyzed immediately. In
order to enhance comparability, all plasma glucose
concentrations were measured with a uniform blood
gas analyzer, Bayer Contour XTV (Bayer Vital GmbH,
R
Leverkusen, Germany), using the glucose-oxidase
method. This device calibrates results to plasma and
displays them as plasma values. It can read hematocrit
values between 0 and 70% and is therefore authorized
for neonatal blood samples.
We defined an episode of hypoglycemia as one or
more consecutive plasma glucose concentrations
of less than 40 mg/dL, independently of age. The
duration of a hypoglycemic episode was defined as
the time from the first measured plasma glucose
<40 mg/dL to the first measured plasma glucose
>40 mg/dL. Recurrent hypoglycemia was defined as a
further episode of hypoglycemia after successful treat-
ment within 24 h. Plasma glucose concentrations
<25 mg/dL within the first 4 h after birth and plasma
glucose concentrations of <35 mg/dL between 4 and
24 h of age were classified as severe hypoglycemia.
The study was approved by the local ethics com-
mittee (Ethikkommission des Landes Vorarlberg, EK-2-
1/2016-14).
Statistical analysis
Customized birth weight percentiles were calculated
using a growth calculator (www.peditools.org/fen-
ton2013). We calculated data using Excel 2016
(Microsoft, Redmond, WA). The analysis was performed
with IBM SPS Statistics 23 (IBM Corporation, Armonk,
North Castle, NY). Data were presented as numbers
(percentage), means (SD) or medians (range) and
 THE JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE 3

quartile. Comparisons between two groups were
performed using the two-sample T test. We analyzed
variables between more groups using the v2 test.
A p value <.05 was considered statistically significant.
Results
During the study period of 13 months, 1017 infants
were eligible, of whom 136 (13.4%) of them were
defined as at-risk infants and enrolled: 46 were IDM,
51 LPT, seven LGA, 10 SGA, and two were not relat-
able to a specific risk group due to incomplete docu-
mentation. An additional 17 infants belonged to two
at-risk groups and three infants had three risk factors.
We excluded 13 infants, who were admitted to the
neonatal ward (LPT n ¼ 13) and four infants who had
insufficient documentation. As a result, the study
population consisted of 119 out of 136 (87.5%) of the
136 infants at risk. Recruitment was between 78 and
100% in all at-risk groups, except the group where
newborns belonged to three risk factors (33%).
Of the 119 study participants, 32 (27%) infants
showed 40 episodes of hypoglycemia with a total of
46 low plasma glucose readings; 17 of the affected
infants were male and 15 were female. The incidence
was similar in all at-risk groups. Multiple risk factors
altered the incidence of hypoglycemia significantly.
Of the 102 infants with one risk factor 22 (22%) and of
the 17 infants with more risk factors, 10 (59%) became
hypoglycemic (p ¼ .001) (Table 1).
Overall, three (2.5%) of the 119 babies were admit-
ted to the neonatal ward for i.v. glucose treatment;
one was noted to be jittery when hypoglycemic and
two according to the protocol.
In all 119 participating newborns, the initial plasma
glucose measurement was performed at a median
(range) age of 97 (13–699) min after birth with a
median (range) first plasma glucose level of 54
(17–113) mg/dL. The median (range) number of taken
blood samples taken from each study participant was
seven (3–23).
Six (5%) infants at-risk showed severe hypogly-
cemia: four LPT, one IDM, one IDM þ LGA (Table 1).
Half of those severe episodes were determined within
9.75 h (range 0.5–14) and three-quarters (Q0,75) were
measured <13 h after birth. Six (5%) infants had recur-
rent episodes: three LPT, one IDM, one IDM þ LGA,
and one LPT þ SGA (Table 1).
Half of the hypoglycemic episodes occurred before
140 min after birth (range: 41–1820 min) (Figure 1),
and 26/32 (81%) were observed within the first three
measurements after birth. In three LPT infants, the first
hypoglycemic episode was detected after 12 h and in
one SGA infant after 24 h. One IDM infant had three
episodes, of which the last one was detected
after 12 h.
Plasma glucose values of all 119 study participants
within the first 12 h (60.15 ± 9.75) were significantly
lower than those between 12 and <24 h (63.4 ± 9.1,
p ¼ .0005), however not those 24 h
(63.9 ± 11.2, p ¼ .6237).
Hypoglycemic infants had a significant mean lower
birth weight as compared to nonhypoglycemic infants
(2758 ± 640 g versus 3168 ± 724 g, p ¼ .006) and
altogether, hypoglycemic infants were of lower gesta-
tional age than were nonhypoglycemic infants
(37.0 ± 1.8 versus 38.3 ± 2.0 weeks, p ¼ .003).
We found no significant differences in plasma glu-
cose concentrations between boys and girls. Our
results showed no further correlation between plasma
glucose concentration and umbilical cord pH, Apgar
scores at 1, 5, or 10 min and being an infant of type 1
or 2 diabetic mother or a mother with gestational dia-
betes or impaired glucose tolerance in pregnancy.
Discussion
In this study, we investigated the incidence of low
plasma glucose values (<40 mg/dL) in newborns at
risk, which made up 27% (32/119) of the cohort.
Implementing our protocol, only three (2.5%) out of
119 newborns at risk or three (9.5%) of 32 with a

Table 1. Demographic analysis.

All infants IDM LPT LGA SGA Multiple risk factors
Number of study participants, n 119 46 40 7 9 17
Hypoglycemia, n (%) 32 (27) 5 (11) 13 (33) 1 (14) 3 (33) 10 (59)
Severe hypoglycemia, n (%) 6 (5) 1 (2) 4 (10) 0 0 1 (6)
Recurrent hypoglycemia, n (%) 6 (5) 1 (2) 3 (8) 0 0 2 (12)
Hypoglycemic episodes, n 40 7 16 1 3 13
No. of hypoglycemic episodes per infant 1 (1–3) 1 (1–3) 1 (1–2) 1 1 1 (1–3)
Duration of hypoglycemic episodes, h 1 (0.25–6.5) 1 (1–2) 1 (0.5–6.5) 0.25 1.2 (1–1.4) 1.25 (1–3)
Mean age at first hypoglycemic episode, h 2.3 (0.6–30.3) 3.95 (1.7–6.3) 5.4 (0.7–14.0) 1.8 9.9 (1.2–30.3) 1.5 (0.6–10.6)
First hypoglycemic value, mg/dL 34 (17–39) 34.6 (31–38) 33.6 (17–37) 27 37.3 (36–39) 34.6 (29–38)
IDM: infants of diabetic mothers; LPT: late preterm; LGA: large for gestational age infants; SGA: small for gestational age infants.
Data are mean (range) and n (%).
4 J. STARK ET AL.
Figure 1. Graphic illustration of the first hypoglycemic episode in dependence on age (min), plasma glucose concentration
(mg/dL), and risk factors (IDM, LPT, LGA, SGA, multiple risk factors).
hypoglycemic episode had to be transferred to the
neonatal ward for i.v. glucose treatment and further
observation. This means that the majority of hypogly-
cemic infants can be treated successfully according to
the protocol and can remain in the nursery.
In the present study, each participant underwent a
mean number of 7.6 ± 2.4 blood measurements.
Overall, 119 infants had a total of 907 blood samples
taken, meaning that about 20 plasma glucose meas-
urements were necessary to detect one episode of
hypoglycemia. This shows a considerably improved
outcome as compared to our previous study [13].
Although the incidence of hypoglycemia was not
affected by the reason for being at risk, infants with
more risk factors were more likely to become hypogly-
cemic, which stands in contrast to the study by Harris
et al. [14].
Incidence
Although at-risk groups are similarly defined in all
published guidelines [8–12], results from different
studies are difficult to compare as the incidence of
hypoglycemic episodes depends on the determined
threshold as well as on the frequency of measure-
ments. In our cohort, neonatal hypoglycemia was
observed in roughly equal numbers as previously
reported [8,15,16]: 32 (27%) affected infants out of 119
were at risk (Table 1).
If we recalculate the data from this study with the
recommended threshold from the German [12], the
Swiss [11], and the AAP [9] guidelines, namely
<45 mg/dL instead of <40 mg/dL, the incidence in our
cohort would rise from 27 to 43% (51/119). Harris
et al. [14] used <47 mg/dL as a threshold, which gave
an incidence of 51% or exactly the same proportion as
if we had used this threshold in our patients.
Duration of monitoring
Current guidelines [9,10,17] recommend that IDM and
LGA infants be screened for a shorter period of time,
namely 12 h [9,10], and LPT and SGA infants for up to
either 24 h [9] or 36 h [10]. To simplify the handling of

an at any rate time-consuming and complex screening
process, we used the same study protocol for all
infants at risk and monitored them for a period
of 24 h.
Nevertheless, we observed half of the hypoglycemic
episodes within 2 h and 20 min after birth and most of
the episodes within the first few hours of life.
Following the AAP guidelines [9], our results show
that only two out of 40 hypoglycemic episodes would
have been missed. This confirms the recommendation
to discontinue the duration of monitoring depending
on the at-risk group.
Severe, recurrent, and long lasting
hypoglycemic episodes
Of the hypoglycemic infants, 19% (6/32) had severe
hypoglycemia and we observed these episodes up to
14 h after birth. Another 19% suffered from recurrent
hypoglycemic episodes. Two such infants – both LPT –
had severe as well as recurrent episodes. In accord-
ance with these results, Harris et al. [14] also showed
in a comparable study of 514 newborns, that approxi-
mately one-fifth of the infants with hypoglycemia
showed severe and one-fifth recurrent low plasma
glucose concentrations.
In the present study, half of the hypoglycemic
episodes lasted for 1 h and one-tenth for 3 h or even
longer. It is likely that these results are over- or
perhaps underestimated, since intermittent plasma
glucose monitoring, which is recommended by most
of the guidelines [9–12], is difficult and not precise.
These findings may be important as severe, recur-
rent and long-lasting neonatal hypoglycemia has been
linked with poor neurologic outcome [5,18–22].
Limitations and implications
The most important limitation of this study is the
retrospective and observational study design. Due to
the retrospective study design, unfortunately, parents
from affected neonates have not been asked for
authorization to investigate the neurologic outcome
after a preset time.
In addition, a small study population has only a lim-
ited significance.
Comparing the detection rate and the number of
neonates identified as at risk, there are still way too
many blood glucose measurements. For further quality
assurance, the at risk-groups will have to be read-
justed according to the results.
THE JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE 5
Due to the lacking evidence on chosen arbitrary
blood glucose concentration, thresholds defining neo-
natal hypoglycemia are difficult and will remain an
open discussion.
The 2017 published CHYLD study by McKinlay et al.
[5] demonstrates the necessity to determine optimal
screening and intervention thresholds as the poor
neurologic outcome and asymptomatic neonatal hypo-
glycemia has been put into context.
Summary
In summary, our data show that the risk group for
neonatal hypoglycemia comprised 12% of all infants
at our nursery and hypoglycemia occurs in one-fourth
(27%) of this cohort of newborns. Although each
infant received an average of seven blood samples,
the number of samples needed to detect one episode
of hypoglycemia was 20. Almost all infants with hypo-
glycemia, more than 80%, were able to stay at the
nursery due to the protocol.
Even though these results are in accordance with
the recommendations to implement this protocol as a
screening tool in newborn infants, we recommend fur-
ther adjustment regarding the at risk groups.
Acknowledgments
There exists no financial support or other benefits from com-
mercial sources for the work reported on this manuscript.
Disclosure statement
No potential conflict of interest was reported by the authors.
ORCID
Johanna Stark http://orcid.org/0000-0002-6223-7957
Burkhard Simma http://orcid.org/0000-0002-6965-2125
Anya Blassnig-Ezeh http://orcid.org/0000-0002-2668-2375
References
[1] Cornblath M, Reisner SH. Blood glucose in the neo-
nate and its clinical significance. N Engl J Med. 1965;
273:378–381.
[2] 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;167:238–245.
[3] Burns CM, Rutherford MA, Boardman JP, et al.
Patterns of cerebral injury and neurodevelopmental
6 J. STARK ET AL.
outcomes after symptomatic neonatal hypoglycemia.
Pediatrics. 2008;122:65–74.
[4] Boluyt N, van Kempen A, Offringa
Neurodevelopment after neonatal hypoglycemia: a
systematic review and design of an optimal future
study. Pediatrics. 2006;117:2231–2243.
[5] McKinlay CJD, Alsweiler JM, Anstice NS, et al. Association
of neonatal glycemia with neurodevelopmental
outcomes at 4.5 years. JAMA Pediatr. 2017;171:
972–983.
[6] Cornblath M, Hawdon JM, Williams AF, et al.
Controversies regarding definition of neonatal hypo-
glycemia: suggested operational thresholds.
Pediatrics. 2000;105:1141–1145.
[7] Koh TH, Eyre JA, Aynsley-Green A. Neonatal hypogly-
caemia – the controversy regarding definition. Arch
Dis Child. 1988;63:1386–1388.
[8] Hawdon J, Cheetham T, Schenk DJ, et al. Metabolic
and endocrine disorders. Vol. 5. In: Rennie J, Roberton
NRC, editors. Rennie & Roberton’s textbook of neonat-
ology. Edinburgh: Elsevier/Churchill Livingstone; 2012.
p. 849–867.
[9] Adamkin DH. Postnatal glucose homeostasis in late-
preterm and term infants. Pediatrics. 2011;127:
575–579.
[10] Aziz K, Dancey P. Screening guidelines for newborns
at risk for low blood glucose. Paediatr Child Health.
2004;9:723–729.
[11] Berger T, Das-Kundu S, Pfister R, et al. Betreuung von
Neugeborenen 34 0/7 SSW mit erho €htem
Hypoglyk€amierisiko oder Hypoglyk€amie im Geb€arsaal
und in der Wochenbettstation. Pediatr Ann. 2007;18:
15–17.
[12] Kattner E, Maier F, Gonser M, et al. Leitlinie zur
Betreuung von Neugeborenen diabetischer M€ utter.
M. Monatsschr Kinderheilkd. 2011;159:57–62.
[13] Jonas D, Dietz W, Simma B. Hypoglycemia in newborn
infants at risk. Klin Padiatr. 2014;226:287–291.
[14] Harris DL, Weston PJ, Harding JE. Incidence of neo-
natal hypoglycemia in babies identified as at risk.
J Pediatr. 2012;161:787–791.
[15] Sundercombe SL, Raynes-Greenow CH, Carberry AE,
et al. Audit of a clinical guideline for neonatal hypo-
glycaemia screening. J Paediatr Child Health. 2013;49:
833–838.
[16] Sexson WR. Incidence of neonatal hypoglycemia: a
matter of definition. J Pediatr. 1984;105:149–150.
[17] Holtrop PC. The frequency of hypoglycemia in full-
term large and small for gestational age newborns.
Am J Perinatol. 1993;10:150–154.
[18] Rozance PJ, Hay WW. Hypoglycemia in newborn
infants: features associated with adverse outcomes.
Neonatology. 2006;90:74–86.
[19] Anderson JM, Milner RD, Strich SJ. Effects of neonatal
hypoglycaemia on the nervous system: a pathological
study. J Neurol Neurosurg Psychiatry. 1967;30:
295–310.
[20] Lucas A, Morley R, Cole TJ. Adverse neurodevelop-
mental outcome of moderate neonatal hypogly-
caemia. BMJ. 1988;297:1304–1308.
[21] Duvanel CB, Fawer CL, Cotting J, et al. Long-term
effects of neonatal hypoglycemia on brain growth
and psychomotor development in small-for-gesta-
tional-age preterm infants. J Pediatr. 1999;134:
492–498.
[22] Caraballo RH, Sakr D, Mozzi M, et al. Symptomatic
occipital lobe epilepsy following neonatal hypogly-
cemia. Pediatr Neurol. 2004;31:24–29.