Original article
Hypoglycemia in term newborns with a birth weight
below the 10th percentile
Abdelwaheb Mejri MD1,2*, Veronique G Dorval MD1,2*, Anne Monique Nuyt MD1,2, Ana Carceller MD1
A Mejri, VG Dorval, AM Nuyt, A Carceller. Hypoglycemia in
term newborns with a birth weight below the 10th percentile.
Paediatr Child Health 2010;15(5):271-275.
BACKGROUND: Current recommendations suggest that routine
screening for hypoglycemia should be performed in all term newborns
with a birth weight (BW) below the 10th percentile. The impact of
updated growth curves on the incidence of hypoglycemia in
small-for-gestational-age (SGA) newborns has not been evaluated.
OBJECTIVES: To evaluate the occurrence and severity of hypoglycemia in term newborns with a BW between the 10th and fifth percentile, and below the fifth percentile, using recently updated growth
curves.
DESIGN: A one-year prospective cohort study.
METHODS: Inclusion criteria were gestational age of 37 weeks or
greater and BW below the 10th percentile. Neonatal hypoglycemia
was defined as a blood glucose level of less than 2.6 mmol/L measured
after 2 h of life. Blood glucose was measured routinely for all SGA
infants during the first 36 h of life.
RESULTS: A total of 187 SGA infants met the study criteria:
85 infants with a BW between the 10th and fifth percentile, and
102 infants with a BW below the fifth percentile. The characteristics of the study cohort were similar between BW groups.
Twenty-six per cent of the infants screened had at least one episode
of hypoglycemia: 22% of infants in the 10th to fifth percentile group
and 28% in the less than fifth percentile group. Hypoglycemia was
symptomatic in four infants, all of whom were below the fifth percentile for BW. The mean (± SD) lowest blood glucose level was
2.1±0.4 mmol/L (range 0.6 mmol/L to 2.5 mmol/L) in the 10th to
fifth percentile group and 2.0±0.5 mmol/L (range 0.8 mmol/L to
2.5 mmol/L) in the less than fifth percentile group (P=0.05).
CONCLUSION: The present study demonstrates a high incidence
of hypoglycemia among SGA infants with a BW below the 10th percentile using updated growth curves. There was no difference in the
incidence of hypoglycemia among SGA infants with a BW below the
fifth percentile versus those with a BW between the 10th and
fifth percentile.
L’hypoglycémie chez les nouveau-nés à terme
dont le poids de naissance est inférieur au
10e percentile
HISTORIQUE : Selon les recommandations actuelles, tous les nouveaunés à terme dont le poids de naissance (PN) est inférieur au 10e percentile
devraient subir un dépistage systématique de l’hypoglycémie. Les
répercussions des courbes de croissance récemment mises à jour sur
l’incidence de l’hypoglycémie chez les nouveau-nés petits par rapport à leur
âge gestationnel (PAG) n’ont pas été évaluées.
OBJECTIFS : Évaluer l’occurrence et la gravité de l’hypoglycémie chez
des nouveau-nés à terme dont le PN se situe entre le 10e et le 5e percentile
ainsi que sous le 5e percentile, au moyen des courbes de croissance
récemment mises à jour.
CONCEPTION : Étude prospective de cohorte d’un an
MÉTHODOLOGIE : Les critères d’inclusion étaient un âge gestationnel
d’au moins 37 semaines et un PN inférieur au 10e percentile.
L’hypoglycémie néonatale était définie par une glycémie inférieure à
2,6 mmol/L, mesurée après deux heures de vie. La glycémie était mesurée
systématiquement chez tous les nouveau-nés PAG pendant leurs
36 premières heures de vie.
RÉSULTATS : Au total, 187 nouveau-nés PAG respectaient les critères
de l’étude : 85 dont le PN se situait entre le 10e et le 5e percentile, et
102 dont le PN se situait sous le 5e percentile. Les caractéristiques de la
cohorte à l’étude étaient semblables entre les groupes de PN. Vingtsix pour cent de ceux ayant subi le test de dépistage avaient eu au moins un
épisode d’hypoglycémie, soit 22 % de ceux du groupe entre le 10e et le
5e percentile et 28 % de ceux du groupe inférieur au 5e percentile.
L’hypoglycémie était symptomatique chez quatre nouveau-nés, dont le PN
se situait sous le 5e percentile. La glycémie minimale moyenne (± ÉT)
équivalait à 2,1±0,4 mmol/L (plage de 0,6 mmol/L à 2,5 mmol/L) dans le
groupe du 10e au 5e percentile, et à 2,0±0,5 mmol/L (plage de 0,8 mmol/L
à 2,5 mmol/L) dans celui inférieur au 5e percentile (P=0,05).
CONCLUSION : La présente étude démontre une forte incidence
d’hypoglycémie chez les nouveau-nés PAG dont le PN est inférieur au
10e percentile d’après les courbes de croissance récemment mises à jour.
On ne remarquait pas de différences entre les nouveau-nés PAG dont le
PN se situait sous le 5e percentile et ceux dont le PN se situait entre le
10e et le 5e percentile.
Key Words: Full-term infants; Hypoglycemia; SGA
I
t has long been known that infants born with a low birth
weight (BW) for their gestational age are at risk of hypoglycemia even though its definition remains controversial (1-6).
Routine screening for low blood glucose is currently recommended for all term newborns with a BW below the
10th percentile (5,7). A few studies (8-10) have suggested
that persistent glucose levels of less then 2.6 mmol/L in
small-for-gestational-age (SGA) preterm newborns may have
long-term effects on their neurodevelopment. Because of this
evidence, current clinical practice guidelines recommend the
*Both authors contributed equally to this work
1Department of Pediatrics; 2Division of Neonatology and Research Center, CHU Sainte-Justine, Université de Montréal, Montreal, Quebec
Correspondence: Dr Ana Carceller, Department of Pediatrics, CHU Sainte-Justine, 3175 Côte Sainte-Catherine, Montreal, Quebec H3T 1C5.
Telephone 514-345-4788, fax 514-345-4822, e-mail [email protected]
Accepted for publication May 29, 2009
Paediatr Child Health Vol 15 No 5 May/June 2010
©2010 Pulsus Group Inc. All rights reserved
271
Mejri et al
use of 2.6 mmol/L for blood glucose concentration measured
after 2 h of life as the threshold value, below which intervention is warranted in a term newborn (7).
Recently updated growth curves have demonstrated a
considerable upward shift in the BW of North American
newborns. This increase in the average BW can be explained
by multiple sociodemographic factors (11-14) and may be a
reflection of increasing maternal obesity, reduction in serious malnutrition and improvement in antenatal obstetrical
care. Therefore, we hypothesized that the incidence of
hypoglycemia in the current newborn population has
decreased, especially in the ‘not so small’ infants such as
those with a BW between the 10th and fifth percentiles
relative to babies with a BW below the fifth percentile. The
aim of the present study was to compare the incidence and
severity of hypoglycemia in infants between the 10th and
fifth percentiles for BW with those below the fifth percentile, using the cut-off values from the recently updated
growth curves (12).
METHODS
A longitudinal prospective study of all full-term SGA
infants born at the Centre Hospitalier Universitaire SainteJustine (Montreal, Quebec) between July 1, 2005, and
June 30, 2006, was designed. Approval of the research
protocol was obtained from both the Scientific and the
Ethics Committees at the institution before the start of the
present study. Infants in the hospital nursery were already
routinely screened for neonatal hypoglycemia in accordance
with the guidelines published by the Canadian Paediatric
Society (7). Therefore, informed consent was not required
by the institution. Infants with chromosome anomalies,
congenital anomalies and congenital infection that could
cause growth restriction were excluded. In the centre,
mothers of SGA newborns are encouraged to breastfeed (if
this was their intent) or to offer formula within the first 2 h
after delivery. Infants with BW below the 10th percentile
are screened for hypoglycemia at 2 h of life, or sooner if
clinically indicated. Blood glucose measurements are subsequently performed every 3 h to 6 h before feedings for the
first 36 h of life. In all cases, screening was performed by
pricking the skin of the heel and collecting a drop of blood.
The sample was applied to a glucose test strip and analyzed
(SureStepPro Test Strip, SureStepFlexx, LifeScan Inc of
Johnson & Johnson Company, USA). All glucose test strip
values of less than 2.6 mmol/L were confirmed by a plasma
glucose concentration analyzer (Coulter Lx Series, Beckman
Coulter, USA) from capillary blood also obtained from a
heel prick. Hypoglycemic infants were immediately fed and
a blood sugar measurement was repeated 1 h after feeding.
An intravenous (IV) dextrose infusion was used only if
blood glucose values remained below 2.0 mmol/L after feeding, or between 2.0 mmol/L and 2.5 mmol/L on two or three
consecutive samples despite having given supplements of
breast milk or formula. Infants who were administered IV
fluids on admission to the nursery for reasons other than
hypoglycemia were excluded.
272
Study definitions
Neonatal hypoglycemia was defined as a plasma glucose
value of less than 2.6 mmol/L at or after 2 h of life as confirmed by the laboratory (7-10). During the first 2 h of life,
a blood glucose measurement greater than 1.8 mmol/L was
considered to be normal and was not verified by a laboratory
test. A laboratory-confirmed plasma glucose value of less
than 1.8 mmol/L was considered to be hypoglycemic.
Maternal diabetes included the diagnoses of gestational
diabetes, and type 1 and 2 diabetes. Gestational age was
calculated using the date of the last menstrual period or
from the ultrasound performed in the first trimester and/or
at 18 to 20 weeks of gestation. Ultrasound dating was used
in cases of more than one week discrepancy with last menstrual period. Infants were categorized as SGA if their BW
was below the 10th percentile using recently updated
growth curves (12). The decision to classify infants according to BW between the 10th and fifth percentile and BW
below the fifth percentile was arbitrary and because the
information was readily available to the investigators. The
choices of exclusive breastfeeding, formula feeding or mixed
feeding were recorded according to what the infant actually
received over the first 36 h of life.
Statistical analysis
Descriptive statistics were obtained for all variables. Mean
values between groups were compared using the Student’s
t test. χ2 tests were used to compare dichotomous data. A
logistic regression was used to identify whether covariates
were associated with an increased risk for hypoglycemia.
RESULTS
During the study period, 219 newborns were identified as
being SGA. Ten charts were excluded from the analysis
because of missing data. Twenty-two infants who required
IV dextrose infusions at birth for reasons other than hypoglycemia were also excluded from further analysis. Of the
187 remaining newborns, none met the exclusion criteria:
85 infants had a BW between the 10th and fifth percentile,
and 102 infants had a BW below the fifth percentile. The
characteristics of the two groups are shown in Table 1.
Significantly higher proportions of infants with BW below
the fifth percentile compared with those between the 10th
and fifth percentile had a head circumference less than the
third percentile and were exclusively formula fed. All
patients but one had an Apgar score of 7 or greater at 5 min.
Fifteen infants had blood glucose values between 1.8 mmol/L
and 2.6 mmol/L within the first 2 h of life (seven in the
10th to fifth percentile group, eight in the below fifth percentile group), which were not considered to be indicative
of hypoglycemia. Five of these patients had persistent episodes of hypoglycemia beyond the first 2 h of life. Therefore,
these patients were defined as having hypoglycemia and
were included in further analyses.
Incidence
Overall, 26% (n=48) of the infants screened experienced at
least one episode of hypoglycemia: 22% (n=19) in the 10th
Paediatr Child Health Vol 15 No 5 May/June 2010
Hypoglycemia in SGA
TAble 1
General characteristics of the population
TAble 3
Univariate analysis and risk factors for hypoglycemia
birth weight
Risk factor
10th–5th percentile,
n=85
<5th percentile,
n=102
Gestational age, mean ± SD,
weeks
39.2±1.3
39.3±1.1
Weight*, mean ± SD, g
2779±210
2548±254
2795 (2300–3165)
2598 (1535–2960)
Variables
Weight, median (range), g
Male sex
Head circumference <3rd
percentile* (14)
Hypoglycemia
Diabetes
52 (61)
55 (54)
7 (8)
23 (23)
19 (22)
29 (28)
5 (6)
4 (4)
Primiparous
61 (72)
63 (62)
Singleton
79 (93)
88 (86)
Caesarean
28 (33)
31 (30)
IV dextrose for hypoglycemia
Exclusive breastfeeding
Formula feeding*
Mixed (breast and formula)
feeding
Weight loss >10%
4 (5)
3 (3)
57 (67)
59 (58)
8 (9)
22 (22)
20 (24)
21 (21)
3 (4)
10 (10)
Values are given as n (%), unless indicated otherwise. *P<0.05 for the
10th to fifth percentile versus less than the fifth percentile. IV Intravenous
TAble 2
Characteristics of the population with and without
hypoglycemia
Variables
Weight, mean ± SD, g
Weight, median (range), g
Male sex
With hypoglycemia, Without hypoglycemia,
n=48
n=139
2639±257
2658±263
2668 (1985–3125)
2705 (1535–3165)
18 (38)
62 (45)
Head circumference <3rd
percentile* (14)
4 (8)
26 (19)
Diabetes
2 (4)
7 (5)
Primiparous
32 (67)
92 (66)
Singleton
42 (88)
125 (90)
Caesarean
12 (25)
47 (34)
IV dextrose
4 (8)
3 (2)
19 (40)
97 (70)
Exclusive breastfeeding*
8 (17)
22 (16)
Mixed (breast and
formula) feeding*
Formula feeding
21 (44)
20 (14)
Weight loss >10%
4 (8)
9 (7)
Values are given as n (%), unless indicated otherwise. *P<0.05 for the
10th to fifth percentile versus less than the fifth percentile. IV Intravenous
to fifth percentile group and 28% (n=29) in the less than
fifth percentile group. Characteristics of newborns with and
without episodes of hypoglycemia are shown in Table 2.
The proportion of infants who had a head circumference
below the third percentile was significantly lower among
those with hypoglycemia than those without hypoglycemia.
Infants with hypoglycemia were less likely to be exclusively
breastfed and a greater proportion received mixed (formula
and breast) feeding. Univariate analysis did not allow identification of any other specific risk factors for the development of hypoglycemia in the study cohort (Table 3). The
Paediatr Child Health Vol 15 No 5 May/June 2010
OR (95% CI)
Diabetes
0.82 (0.16–4.09)
Singleton
1.28 (0.46–3.53)
Gestational age
1.10 (0.84–1.44)
Mode of delivery
0.73 (0.43–1.22)
Male sex
0.75 (0.38–1.46)
Weight loss
0.93 (0.56–1.55)
Figure 1) Timing of the first episode of hypoglycemia. Opaque circle
represents newborns with birth weight between the 10th and fifth
percentile (median age of 7 h at the first episode of hypoglycemia).
Open circle represents newborns with birth weight below the fifth
percentile (median age of 4 h at the first episode of hypoglycemia)
number of infants presenting two or more episodes of hypoglycemia did not differ between BW groups (12 in the less
than fifth percentile group versus nine in the 10th to fifth
percentile group).
Timing
Fifty-six per cent (n=27) of the infants with hypoglycemia
had only one such episode (11 in the 10th to fifth percentile
group and 16 in the less than fifth percentile group; P not
significant). Of the 21 infants (44%) who had two or more
episodes of hypoglycemia, 10 had their first episode at 3 h or
less of life (three in the 10th to fifth percentile group and
seven in the less than fifth percentile group). The timing of
the first episode of hypoglycemia for each infant is shown in
Figure 1. The median time at which the first episode of
hypoglycemia occurred was 5.5 h (range 1 h to 48 h).
Overall, 15% of patients with hypoglycemia continued to
present episodes after 36 h of age.
Severity
The mean values of the lowest blood glucose measurements
recorded for each patient in the cohort were 2.1±0.4 mmol/L
(range 0.6 mmol/L to 2.5 mmol/L) in the 10th to fifth percentile group and 2.0±0.5 mmol/L (range 0.8 mmol/L to
2.5 mmol/L) in the less than fifth percentile group (P=0.05;
ie, not statistically significant). Overall, there were four
infants in the 10th to fifth percentile group versus eight
infants in the less than fifth percentile group with glucose
values of less than 1.8 mmol/L. Four patients were treated
with IV dextrose because of persistent hypoglycemia (n=2
273
Mejri et al
in each BW group); three of them required initiation of IV
therapy within the first 3 h of life.
Only four infants were noted to have manifested symptoms simultaneously with hypoglycemic episodes (jitteriness
and tachypnea). All four of these infants were in the group
with BW less than the fifth percentile. Two of these infants
had only one episode of hypoglycemia; one episode occurred
at 4 h of life and the other at 11 h of life. Both infants had a
blood sugar value of 2.5 mmol/L. The two other symptomatic infants had more than three episodes of hypoglycemia,
and their lowest blood sugar values were 1.8 mmol/L and
1.9 mmol/L. Only one of the four symptomatic infants
required IV dextrose for persistent hypoglycemia.
DISCUSSION
Twenty-six per cent of all SGA infants screened in our study
had at least one episode of hypoglycemia in the first 36 h of
life. This incidence is surprisingly high despite our use of
recently updated growth curves to identify infants at risk,
with higher weight cut-offs for the 10th percentile. We did
not observe a significant difference in the incidence of
hypoglycemia in the groups characterized by BW between
the fifth and 10th percentile versus those with BW less than
the fifth percentile. The results of our study do not support
our initial hypothesis that the upward shift in BW results in
a decrease in the incidence of hypoglycemia, particularly in
infants between the fifth and 10th percentile.
We also did not identify any statistically significant risk
factors for the development of hypoglycemia in SGA infants.
The majority of the infants in the study who had a head circumference below the third percentile (14) did not present
with hypoglycemia. This suggests that etiologies of more
‘symmetrical’ growth restriction decrease the risk of neonatal
hypoglycemia (such as constitutional SGA, environmental
toxins or infectious exposures with early perturbation of fetal
cell hyperplasia) or, alternatively, that more severe growth
restriction is associated with relative insulin resistance (15)
and, therefore, maintained normal glucose.
The difference in feeding patterns between BW groups
and between with versus without hypoglycemia groups probably reflects either the worry of the mother and health care
provider that the smaller infants (ie, BW below the fifth
percentile) would not receive enough nutrition solely from
breastfeeding, or a ‘treatment’ response to an episode of
hypoglycemia. We cannot exclude that a higher formula
intake over the first 36 h of life in this cohort of SGA infants
contributed to preventing episodes of hypoglycemia.
The rationale for the systematic screening of hypoglycemia in infants with a BW below the 10th percentile can
be questioned in light of our results. Given our surprisingly
high incidence, one might even be tempted to screen more
infants. Alternatively, considering that in appropriate-forgestational-age full-term healthy breastfed infants, incidence of blood glucose values of less than 2.6 mmol/L is not
infrequent and has been reported to be as high as 12% to
14% (16-19), we could postulate that the blood glucose
threshold of 2.6 mmol/L may be too high and not
274
discriminatory for truly clinically relevant hypoglycemia in
term (SGA) infants. In 1971, Lubchenco and Bard (20)
defined neonatal hypoglycemia as a blood glucose level of
less than 1.7 mmol/L and reported an incidence of 25% in
44 SGA newborns and 10% in 126 appropriate-forgestational-age newborns on samples obtained before the
first feed (20,21). By applying their threshold to our study,
the incidence of hypoglycemia in our current cohort of
SGA newborns decreases to 5.3%. The latter observation
would support our hypothesis that the infants labelled SGA
with the recent BW curves represent, in fact, a ‘healthier’
newborn population. In 1993, Holtrop (5) defined hypoglycemia as a serum glucose value of less than 1.9 mmol/L in
the first 3 h of life, less than 2.2 mmol/L at 3 h to 24 h of life
and less than 2.4 mmol/L after 24 h of life, and reported an
incidence of hypoglycemia in SGA infants of 14.7%. Using
Holtrop’s threshold value (5), the incidence in our group
would be similar at 18%. The nonunanimous definitions of
hypoglycemia and of the methods of assessment used in
each of these studies (22) hinder our ability to reliably compare our results.
The level at which hypoglycemia becomes clinically
important is not well understood (23), and the neurodevelopmental consequences of asymptomatic hypoglycemia in
term SGA infants are still unknown (24,25). Glucose is the
primary organic fuel for energy production, especially for
the brain. However, alternative substrates such as ketone
bodies, lactate, glycerol, B-hydroxybutarate and acetoacetate play an important role in glucose deprivation status;
they support brain metabolism and may, therefore, prevent
clinical manifestations in neonates (26-28). Because our
study does not provide follow-up data regarding the
neurodevelopmental outcomes of the infants studied, we
cannot add insight into a meaningful threshold for hypoglycemia. Our small cohort size has also limited our ability to
identify risk factors associated with the occurrence of hypoglycemia, which might have helped refine screening
criteria.
For obvious practical purposes, a lowest acceptable blood
glucose level needs to be agreed on for optimal management
of all patients in newborn nurseries and neonatal units. The
threshold of 2.6 mmol/L currently recommended in guidelines is heavily influenced by outcomes reported by Lucas
et al (8) and Duvanel et al (9) from cohorts of mostly symptomatic SGA preterm infants with hypoglycemia.
Conclusions drawn from a cohort of infants already at
increased risk of neurodevelopmental sequelae should be
extrapolated cautiously to a small but otherwise healthy and
asymptomatic term newborn population. Cornblath and
Ichord (29) suggest that a plasma glucose level of 2.6 mmol/L
should be an ‘operational threshold’, ie, an indication for
action but not diagnostic of a disease. Determining the relationship between operational, epidemiological and physiological thresholds for hypoglycemia and abnormal
neurological and developmental outcomes would require a
prospective, controlled longitudinal study of asymptomatic
term neonates.
Paediatr Child Health Vol 15 No 5 May/June 2010
Hypoglycemia in SGA
CONCLUSION
Our study shows a high percentage of SGA infants (26%)
presenting with blood glucose levels below the threshold of
2.6 mmol/L. We observed no difference in the incidence of
hypoglycemia in newborns with BW between the 10th and
fifth percentile compared with those with BW less than the
fifth percentile. Long-term neurodevelopmental studies of
these asymptomatic infants, along with measures of other
energy substrates, are necessary to refine our screening criteria for pathological hypoglycemia in newborns.
NOTE: Presented at the 83rd Annual Meeting of the Canadian
Paediatric Society, June 13 to 17, 2006, St John’s, Newfoundland
and Labrador; and the Pediatric Academic Societies’ Annual
Meeting in Toronto, Ontario, May 5 to 8, 2007.
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