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ARTICLE
New diagnostic criteria for gestational diabetes mellitus and their
impact on the number of diagnoses and pregnancy outcomes
Sarah H. Koning
1
&Jelmer J. van Zanden
2
&Klaas Hoogenberg
3
&Helen L. Lutgers
4
&
Alberdina W. Klomp
1
&Fleurisca J. Korteweg
5
&Aren J. van Loon
5
&
Bruce H. R. Wolffenbuttel
1
&Paul P. van den Berg
6
Received: 5 September 2017 /Accepted: 19 October 2017 /Published online: 22 November 2017
#The Author(s) 2017. This article is an open access publication
Abstract
Aims/hypothesis Detection and management of gestational di-
abetes mellitus (GDM) are crucial to reduce the risk of
pregnancy-related complications for both mother and child.
In 2013, the WHO adopted new diagnostic criteria for GDM
to improve pregnancy outcomes. However, the evidence
supporting these criteria is limited. Consequently, these new
criteria have not yet been endorsed in the Netherlands. The
aim of this study was to determine the impact of these criteria
on the number of GDM diagnoses and pregnancy outcomes.
Methods Data were available from 10,642 women who
underwent a 75 g OGTT because of risk factors or signs sug-
gestive of GDM. Women were treated if diagnosed with GDM
according to the WHO 1999 criteria. Data on pregnancy out-
comes were obtained from extensive chart reviews from 4,431
women and were compared between women with normal glu-
cose tolerance (NGT) and women classified into the following
groups: (1) GDM according to WHO 1999 criteria; (2) GDM
according to WHO 2013 criteria; (3) GDM according to
WHO 2013 fasting glucose threshold, but not WHO 1999
criteria; and (4) GDM according to WHO 1999 2 h plasma
glucose threshold (2HG), but not WHO 2013 criteria.
Results Applying the new WHO 2013 criteria would have
increased the number of diagnoses by 45% (32% vs 22%) in
this population of women at higher risk for GDM. In compar-
ison with women with NGT, women classified as having
GDM based only on the WHO 2013 threshold for fasting
glucose, who were not treated for GDM, were more likely to
have been obese (46.1% vs 28.1%, p< 0.001) and hyperten-
sive (3.3% vs 1.2%, p< 0.001) before pregnancy, and to have
had higher rates of gestational hypertension (7.8% vs 4.9%,
p= 0.003), planned Caesarean section (10.3% vs 6.5%, p=
0.001) and induction of labour (34.8% vs 28.0%, p=0.001).
In addition, their neonates were more likely to have had an
Apgar score <7 at 5 min (4.4% vs 2.6%, p=0.015) and to
have been admitted to the Neonatology Department (15.0% vs
11.1%, p= 0.004). The number of large for gestational age
(LGA) neonates was not significantly different between the
two groups. Women potentially missed owing to the higher
2HG threshold set by WHO 2013 had similar pregnancy out-
comes to women with NGT. These women were all treated for
GDM with diet and 20.5% received additional insulin.
Conclusions/interpretation Applying the WHO 2013 criteria
will have a major impact on the number of GDM diagnoses.
Using the fasting glucose threshold set by WHO 2013 iden-
tifies a group of women with an increased risk of adverse
outcomes compared with women with NGT. We therefore
support the use of a lower fasting glucose threshold in the
Electronic supplementary material The online version of this article
(https://doi.org/10.1007/s00125-017-4506-x) contains peer-reviewed but
unedited supplementary material, which is available to authorised users.
*Bruce H. R. Wolffenbuttel
bwo@umcg.nl
1
Department of Endocrinology, University of Groningen, University
Medical Center Groningen, HPC AA31, P.O. Box 30.001,
Hanzeplein 1, 9700 RB Groningen, the Netherlands
2
Laboratory of Clinical Chemistry, Certe, Medical Laboratory North,
Groningen, the Netherlands
3
Department of Internal Medicine, Martini Hospital, Groningen, the
Netherlands
4
Department of Internal Medicine, Medical Center Leeuwarden,
Leeuwarden, the Netherlands
5
Department of Obstetrics and Gynaecology, Martini Hospital,
Groningen, the Netherlands
6
Department of Obstetrics and Gynaecology, University of
Groningen, University Medical Center Groningen, Groningen, the
Netherlands
Diabetologia (2018) 61:800–809
https://doi.org/10.1007/s00125-017-4506-x
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
Dutch national guideline for GDM diagnosis. However,
adopting the WHO 2013 criteria with a higher 2HG threshold
would exclude women in whom treatment for GDM seems to
be effective.
Keywords Diagnosis .Diagnostic criteria .GDM .
Gestational diabetes mellitus .Pregnancy .Pregnancy
outcomes .WHO
Abbreviations
2HG 2 h plasma glucose
GDM Gestational diabetes mellitus
HAPO Hyperglycaemia and Adverse Pregnancy
Outcomes
IADPSG International Association of the Diabetes and
Pregnancy Study Groups
IFG Impaired fasting glucose
IGT Impaired glucose tolerance
IQR Interquartile range
LGA Large for gestational age
NGT Normal glucose tolerance
NICE National Institute for Health and Care Excellence
SGA Small for gestational age
UMCG University Medical Center Groningen
Introduction
Gestational diabetes mellitus (GDM) is associated with an
increased risk of pregnancy-related complications for both
mother and child [1,2]. International guidelines recommend
active screening for GDM since many of these risks can be
reduced by its detection and management [3,4]. However,
these guidelines lack uniformity in terms of their diagnostic
thresholds.
In 2010, the International Association of the Diabetes and
Pregnancy Study Groups (IADPSG) proposed more stringent
thresholds for diagnosing GDM that were based on the results
of the international prospective Hyperglycaemia and Adverse
Pregnancy Outcomes (HAPO) study [5,6]. This study dem-
onstrated a linear association between maternal glucose levels
at fasting and during an OGTT and the risk of adverse preg-
nancy outcomes such as increased birthweight, primary
Caesarean section and neonatal hypoglycaemia [6]. The
IADPSG diagnostic criteria (fasting plasma glucose
≥5.1 mmol/l; and/or 1 h plasma glucose ≥10.0 mmol/l; and/
or 2 h plasma glucose (2HG) ≥8.5 mmol/l) have now been
adopted by many guideline committees and expert groups,
including the WHO in 2013 [5,7].
However, evidence in support of applying the new criteria
to diagnose GDM to improve pregnancy outcomes is limited.
The optimal glucose thresholds to define GDM remain uncer-
tain and international consensus has not yet been reached [8,
9]. Applying the new criteria gives rise to more women being
diagnosed with GDM and the resulting cost increases and
medicalisation of pregnancy are causes for concern for
healthcare managers and caregivers [10,11]. Studies into clin-
ical outcomes and cost-effectiveness analyses are required to
better appraise the value of these new glucose thresholds. In
the Netherlands, the new WHO 2013 criteria have not yet
been endorsed. In their 2010 guideline ‘Diabetes and
Pregnancy’, the Dutch Society of Obstetrics and
Gynaecology instead recommends using the WHO 1999
criteria to diagnose GDM (fasting glucose ≥7.0 mmol/l and/
or 2HG ≥7.8 mmol/l) [12,13]. When compared with the new
WHO 2013 criteria, these use a much higher threshold for
fasting glucose and a lower threshold for 2HG.
The consequences of adopting the WHO 2013 thresholds
need to be evaluated in order to answer the following crucial
questions: Do the additional women diagnosed with GDM
using the new WHO 2013 fasting glucose criteria (fasting
glucose ≥5.1 but ≤6.9 mmol/l) indeed have unfavourable
pregnancy outcomes? What are the pregnancy outcomes of
the women who would be missed owing to the higher 2HG
threshold using the WHO 2013 criteria (i.e. women with 2HG
≥7.8 but ≤8.4 mmol/l)?
The aim of this study was therefore to evaluate the possible
impact on the number of GDM diagnoses and pregnancy out-
comes when applying the new WHO 2013 criteria instead of
the older WHO 1999 criteria.
Methods
Study design and population This study is a retrospective
evaluation of data on testing for GDM (in women with rele-
vant risk factors), pregnancy management and pregnancy out-
comes collected between January 2011 and September 2016
in the Groningen area by Certe; a regional primary- and sec-
ondary healthcare laboratory in the north of the Netherlands
and by the University Medical Center Groningen (UMCG); a
tertiary referral centre.
As previously described [14,15], pregnant women be-
tween 24 and 28 weeks of gestation were referred either by
their midwife (in primary care) or by their gynaecologist (in
secondary/tertiary care) for a 75 g OGTT if they had one or
more risk factors for GDM [13]. These risk factors were; a
pre-pregnancy body mass index (BMI) ≥30 kg/m
2
;havinga
first-degree relative with diabetes; having a previous neonate
weighing ≥4500 g at birth or a birthweight >95th percentile;
having a personal history of GDM, intrauterine fetal death or
polycystic ovary syndrome; and belonging to an ethnic risk
Diabetologia (2018) 61:800–809 801
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group (Asian, African-Caribbean, Middle Eastern i.e.
Moroccan and Egyptian).Universal testing is not recommend-
ed in the Dutch national guideline.
An OGTT was also recommended for women with
signs suggestive of GDM (e.g. fetal macrosomia or
polyhydramnios). Women were treated if diagnosed with
GDM according to the WHO 1999 criteria: fasting glu-
cose ≥7.0 mmol/l and/or 2HG value ≥7.8 mmol/l [12]. All
women were referred to a dietitian for dietary counselling
and received instructions for self-monitoring of blood glu-
cose values by a diabetes specialist nurse. If, after 1–
2 weeks, repeated measurements indicated a fasting glu-
cose level >5.3 mmol/l and/or 1 h postprandial plasma
glucose level >7.8 mmol/l, insulin therapy was started
[15].
The study was conducted in accordancewith the guidelines
of the Declaration of Helsinki and Good Clinical Practice, and
approved by the Medical Ethical Review Committee of the
UMCG. The data was analysed retrospectively and all require-
ments for patient anonymity are in agreement with the regu-
lations of the ethical committee of both hospitals for publica-
tion of patient data. According to this and the Dutch law
Medical Research with Human Subject, no informed consent
was deemed necessary.
GDM classification and outcomes On the basis of their
OGTT results, women were retrospectively assigned to the
following diagnostic groups:
1. normal glucose tolerance (fasting glucose <5.1 mmol/l
and 2HG <7.8 mmol/l), denoted as ‘NGT’;
2. GDM according to WHO 1999 criteria (fasting glucose
≥7.0 mmol/l and/or 2HG ≥7.8 mmol/l), denoted as ‘WHO
1999’;
3. GDM according to WHO 2013 criteria (fasting glucose
≥5.1 mmol/l and/or 2HG ≥8.5 mmol/l), denoted as ‘WHO
2013’.
We separately identified two further groups of women as
follows:
4. GDM according to new WHO 2013 fasting glucose
threshold, but do not meet WHO 1999 criteria (fasting
glucose ≥5.1 but ≤6.9 mmol/l and 2HG <7.8 mmol/l),
denoted as ‘WHO 2013 only fasting glucose’;
5. GDM according to WHO 1999 2HG threshold, but do not
meet WHO 2013 criteria (fasting glucose <5.1 mmol/l
and 2HG ≥7.8 but ≤8.4 mmol/l), denoted as ‘WHO
1999 only 2HG’.
It should be noted that the women with NGT underwent an
OGTT because they had risk factors for GDM or signs sug-
gestive of GDM (e.g. fetal macrosomia or polyhydramnios).
Approximately 85% of the women were tested based on
predefined risk factors for GDM. Since the women with
NGT are not representative of all pregnancies not affected
by GDM, neonatal outcomes regarding birthweight in the
general obstetric population in the Northern region of the
Netherlands (period 2011–2013) were obtained from the
Dutch Perinatal Registry and the Municipal Health Service
Groningen. The nature of this dataset unfortunately does not
allow exclusion of those screened for GDM.
The original OGTT dataset comprised 10,642 women with
GDM risk factors or signs suggestive of GDM. We were able
to retrospectively collect data on maternal characteristics and
pregnancy outcomes in a representative sample of women
(n= 4431) from written medical and obstetric records at
midwives’offices in primary care and at two hospitals; the
UMCG and the Martini Hospital Groningen (Fig. 1). All data
were incorporated in an anonymised database. An overview of
collected maternal and neonatal outcomes is given in ESM
Tab le 1.
Statistical analyses Continuous data are presented as mean ±
SD, or as median and interquartile range (IQR) in case of
skewed distribution. Categorical data are presented as num-
bers and percentages. Differences between groups were tested
NGT:
fasting glucose
<5.1 and
2HG <7.8
mmol/l
n=2851
GDM according to
WHO 2013 criteria:
fasting glucose ≥5.1
and 2HG ≥8.5 mmol/l
n=1346
GDM according to
WHO 1999 criteria:
fasting glucose
≥7.0 and 2HG ≥7.8
mmol/l
n=913
GDM according to
WHO 2013 only fasting
glucose criteria:
fasting glucose
≥5.1 but ≤6.9 and
2HG <7.8 mmol/l
n=667
GDM according to
WHO 1999 only 2HG
criteria:
fasting glucose
<5.1 and 2HG ≥7.8 but
≤8.4 mmol/l
n=234
GDM classification
groups
Pregnancy outcomes collected
in a representative sample
n=4431
OGTT data available
for period Jan 2011 – Sep 2016
n=10,642
Fig. 1 Flow chart of the study population
802 Diabetologia (2018) 61:800–809
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using the Student’sunpairedttest for continuous data, or the
Mann–Whitney Utest in case of skewed distribution. For
categorical data, a χ
2
test or Fisher’s exact test was used.
All pvalues are two-tailed, and pvalues <0.05 are consid-
ered statistically significant.
Results
Number of GDM diagnoses and maternal characteristics
OGTT data were collected from 10,642 pregnant women with
GDM risk factors or signs suggestive of GDM. In Table 1,
numbers of women with GDM are presented according to the
WHO 1999 criteria and WHO 2013 criteria. The number of
women with GDM in the total cohort was 22% when the
WHO 1999 criteria were applied and 32% when the WHO
2013 criteria were applied.
The characteristics of the women in the different GDM
classification groups are presented in Table 2. Characteristics
and pregnancy outcomes were collected for 4,431 women
who had singleton pregnancies. The fasting glucose, 2HG
values and age of these 4,431 women (fasting glucose 4.7 ±
0.6 mmol/l; 2HG 6.6 ± 1.6 mmol/l; age of the mother at
OGTT 30.6 ± 4.9 years) were similar to the values obtained
for the other 6,211 women (mean fasting glucose 4.8 ±
0.5 mmol/l; 2HG 6.6 ± 1.6 mmol/l; age of the mother at
OGTT 30.1 ± 4.9 years) who completed a 75 g OGTT.
Treatment for GDM was only given to women diagnosed
according to the WHO 1999 criteria, since the WHO 2013-
based GDM classification was only assigned retrospectively.
In comparison with women in the NGT group, women classi-
fied as having GDM (using the WHO 2013 criteria or WHO
1999 criteria) were older, had a higher pre-pregnancy BMI
andweremorelikelytobemultiparousandtohavechronic
hypertension.
A total of 667 women were retrospectively classified as
having GDM based only on the WHO 2013 fasting glucose
criteria. In comparison with women in the NGT group, these
women were older, had a higher pre-pregnancy BMI (29.1
[IQR 24.8–33.5] vs 25.2 [IQR 22.0–30.4] kg/m
2
,p<0.001),
were more likely to be obese (46.1% vs 28.1%, p<0.001),to
have smoked during pregnancy (13.2% vs 10.5%, p=0.05)
and to have chronic hypertension (3.3% vs 1.2%, p<0.001).
A total of 234 women were retrospectively classified as
having GDM based only on the WHO 1999 criteria for
2HG. These women were all treated for GDM, 79.5% with
diet only and 20.5% received additional insulin therapy. In
comparison with women with NGT, women in this group
were older, had a slightly higher pre-pregnancy BMI (26.4
[IQR 23.3–30.4] vs 25.2 [IQR 22.0–30.4] kg/m
2
,p=0.01),
were more likely to be overweight (33.9% vs 23.0%,
p< 0.001) and to have hypertension (3.0% vs 1.2%, p=0.02).
Pregnancy outcomes Maternal and neonatal outcomes ac-
cording to the different GDM classification groups are given
in Table 3. Compared with women in the NGT group, women
classified as having GDM (using the WHO 2013 criteria or
WHO 1999 criteria) were more likely to develop gestational
hypertension or preeclampsia and to have had a planned
Caesarean section delivery or induced labour.
Compared with women in the NGT group, women classi-
fied as having GDM based only on the WHO 2013 criteria for
fasting glucose were more likely to have gestational hyper-
tension (7.8% vs 4.9%, p= 0.003), to have a planned
Caesarean section (10.3% vs 6.5%, p= 0.001) and induced
labour (34.8% vs 28.0%, p=0.001).
Women classified as having GDM based only on the WHO
1999 criteria for 2HG were more likely to have induced labour
(62.8% vs 28.0%, p< 0.001) compared with women in the
NGT group. There were no significant differences in gesta-
tional hypertension, preeclampsia or mode of delivery be-
tween this group and women with NGT.
Neonates from mothers classified as having GDM
(using the WHO 2013 criteria or WHO 1999 criteria) had
a lower birthweight, a lower gestational age at delivery and
were less likely to have macrosomia compared with those
from mothers with NGT. However, the likelihood of these
neonates being born large for gestational age (LGA) [16]
Table 1 Number of GDM diag-
noses according to the WHO
1999 and WHO 2013 criteria
Criteria mmol/l WHO 1999
Fasting glucose ≥7.0
and/or 2HG ≥7.8
WHO 2013
Fasting glucose ≥5.1
and/or 2HG ≥8.5
Tot al cohort n= 10,642
Tot al GDM, n(%) 2326 (22) 3364 (32)
GDM based on elevated fasting glucose, but with 2HG
below the threshold, n(%)
14 (1) 2045 (61)
GDM based on the 2HG, but with fasting glucose
below the threshold, n(%)
2267 (97) 634 (19)
GDM based on both elevated fasting glucose and
elevated 2HG, n(%)
45 (2) 685 (20)
Abbreviations: 2HG, 2 h plasma glucose
Diabetologia (2018) 61:800–809 803
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Tab le 2 Maternal characteristics according to the GDM classification groups
NGT WHO 1999 WHO 2013 WHO 2013 only fasting glucose WHO 1999
only 2HG
Criteria (mmol/l) Fasting glucose <5.1 and
2HG <7.8
Fasting glucose ≥7.0 and/or
2HG ≥7.8
Fasting glucose ≥5.1 and/or
2HG ≥8.5
Fasting glucose ≥5.1-≤6.9 and
2HG <7.8
Fasting glucose <5.1 and
2HG ≥7.8-≤8.4
Characteristics N
a
N4431 2851 913 1346 667 234
Treated for GDM, n(%) Diet 0 524 (57.4) 338 (25.1) 0 186 (79.5)
Additional insulin therapy 0 389 (42.6) 341 (25.3) 0 48 (20.5)
Age (years) 4431 30.7 ± 4.9 32.1 ± 5.1*** 32.0 ± 5.2*** 31.6 ± 5.2*** 31.6 ± 4.5**
Pre-pregnancy BMI (kg/m
2
) 4196 25.2 (22.0–30.4) 27.7 (24.1–31.8)*** 28.7 (24.5–32.9)*** 29.1 (24.8–33.5)*** 26.4 (23.3–30.4)**
Pre-pregnancy BMI, n(%)
b
4196 *** *** *** ***
<25 kg/m
2
1311 (48.8) 285 (32.0) 366 (28.5) 167 (26.9) 86 (37.4)
25–30 kg/m
2
618 (23.0) 276 (30.9) 365 (28.4) 167 (26.9) 78 (33.9)
≥30 kg/m
2
755 (28.1) 331 (37.1) 551 (42.9) 286 (46.1) 66 (28.7)
Ethnicity, n(%)
b
4431 * * *
White 2211 (77.6) 719 (78.8) 1060 (78.8) 519 (77.8) 178 (76.1)
Asian 160 (5.6) 65 (7.1) 62 (4.6) 21 (3.1) 24 (10.3)
African-American 150 (5.3) 37 (4.1) 78 (5.8) 48 (7.2) 7 (3.0)
Mediterranean 207 (7.3) 68 (7.4) 95 (7.1) 47 (7.0) 20 (8.5)
Other 123 (4.3) 24 (2.6) 51 (3.8) 32 (4.8) 5 (2.1)
Nulliparous, n(%) 4431 1281 (44.9) 373 (40.9)* 523 (38.9)*** 250 (37.5)*** 100 (42.7)
Chronic hypertension, n(%) 4427 34 (1.2) 37 (4.1)*** 52 (3.9)*** 22 (3.3)*** 7 (3.0)*
Smoking during pregnancy, n(%) 4381 296 (10.5) 101 (11.1) 165 (12.4) 87 (13.2)* 23 (9.8)
Data are expressed as mean ± SD, median (IQR) or proportion of n(%)
pvalues are based on Student’s unpaired ttest (non-skewed continuous variables), Mann–Whitney Utest (skewed continuous variables), or χ
2
test/Fisher’sexacttest.*p<0.05, **p<0.01, ***p<0.001
compared with NGT group
a
Data with respect to pre-pregnancy BMI, chronic hypertension and smoking are missing in 235 (5.3%), 4 (0.09%) and 50 (1.1%) of the subjects, respectively
b
pvalues are for the complete categorical variable BMI and ethnicity, indicating changes in ethnic composition and BMI composition between groups
804 Diabetologia (2018) 61:800–809
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Tab le 3 Pregnancy outcomes according to the GDM classification groups
NGT WHO 1999 WHO 2013 WHO 2013 fasting
glucose only
WHO 1999 2HG only
Pregnancy outcomes General obstetric population
in the north of the Netherlands
Criteria
(mmol/l)
Fasting glucose <5.1
and 2HG <7.8
Fasting glucose ≥7.0
and/or 2HG ≥7.8
Fasting glucose ≥5.1
and/or 2HG ≥8.5
Fasting glucose ≥5.1-
≤6.9 and 2HG <7.8
Fasting glucose <5.1
and 2HG ≥7.8- ≤8.4
N
b
N29,562 4431 2851 913 1346 667 234
Treated for GDM, n0 913 679 0 234
Maternal
Gestational hypertension, n(%) 4427 139 (4.9) 62 (6.8)* 98 (7.3)** 52 (7.8)** 16 (6.9)
Preeclampsia, n(%) 4427 41 (1.4) 28 (3.1)** 35 (2.6)** 12 (1.8) 5 (2.1)
Induction of labour, n(%) 4405 793 (28.0) 587 (64.3)*** 670 (50.0)*** 230 (34.8)** 147 (62.8)***
Mode of delivery, n(%) 4410
Vaginal 2051 (72.3) 618 (67.7)** 904 (67.4)** 451 (68.1)* 165 (70.5)
Emergency CS 327 (11.5) 116 (12.7) 177 (13.2) 89 (13.4) 28 (12.0)
Planned CS 185 (6.5) 103 (11.3)*** 150 (11.2)*** 68 (10.3)** 21 (9.0)
Instrumental 272 (9.6) 76 (8.3) 110 (8.2) 54 (8.2) 20 (8.5)
Gestational age at delivery (weeks) 4431 39.7 (38.7–40.6) 38.3 (38.0–39.0)*** 38.7 (38.0–39.9)*** 39.6 (38.3–40.4)*** 38.6 (38.1–39.4)***
Neonatal
LGA, n(%) 3246 (11.0) 4430 514 (18.0) 167 (18.3) 271 (20.1) 140 (21.0) 36 (15.4)
Macrosomia, n(%) 4275 (14.5) 4431 595 (20.9) 108 (11.8)*** 226 (16.8)** 148 (22.2) 30 (12.8)**
Small for gestational age, n(%) 2364 (8.0) 4430 195 (6.8) 36 (3.9)** 69 (5.1)* 38 (5.7) 5 (2.1)**
Birthweight (g) 4431 3544 ± 579 3391 ± 550*** 3477 ± 590** 3580 ± 596 3437 ± 498**
Birth trauma, n(%) 4420 64 (2.3) 27 (3.0) 43 (3.2) 20 (3.0) 4 (1.7)
Hypoglycaemia, n(%)
a
4418 NA 38 (4.2)*** NA NA 4 (1.7)
Hyperbilirubinaemia, n(%)
a
4418 NA 24 (2.6)** NA NA 5 (2.1)
Stillbirth, n(%) 4431 10 (0.4) 2 (0.2) 6 (0.4) 4 (0.6) 0
Preterm delivery, n(%) 4431 146 (5.1) 57 (6.2) 92 (6.8)* 46 (6.9) 11 (4.7)
Respiratory support, n(%) 4418 116 (4.1) 34 (3.7) 51 (3.8) 27 (4.1) 10 (4.3)
Apgar score <7 at 5 min, n(%) 4414 74 (2.6) 30 (3.3) 57 (4.3)** 29 (4.4)* 2 (0.9)
Admission to neonatology, n(%) 4423 315 (11.1) 130 (14.2)* 206 (15.3)*** 100 (15.0)** 24 (10.3)
Data are expressed as mean ± SD, median (IQR) or proportion of n(%)
a
Data were collected in primary care (midwives) and secondary care (hospital). In primary care, neonatal hypoglycaemia and hyperbilirubinaemia were not reported and measured in all pregnancies.
Therefore we only report the percentages for the WHO 1999 group, as all these women delivered in secondary care
b
Data with respect to gestational hypertension, preeclampsia, induction of labour, mode
of delivery, birth trauma, hypoglycaemia, hyperbilirubinaemia, respiratory support, Apgar score and admission to the neonatology are missing in 4 (0.09%), 4 (0.09%), 26 (0.5%), 21 (0.5%), 11 (0.2%), 13
(0.3%), 13 (0.3%), 13 (0.3%), 17 (0.4%) and 8 (0.2%) of the subjects, respectively
pvalues are based on Student’s unpaired ttest (non-skewed continuous variables), Mann–Whitney Utest (skewed continuous variables), or χ
2
test/Fisher’sexacttest.*p<0.05, **p<0.01, ***p<0.001
compared with NGT group
Diabetologia (2018) 61:800–809 805
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did not differ significantly from that of neonates born to
women with NGT. The likelihood of these neonates being
born small for gestational age (SGA) [16]waslowerthan
that of neonates born to women with NGT.
Compared with neonates from mothers with NGT, neo-
nates from mothers classified as having GDM based only on
the WHO 2013 criteria for fasting glucose had similar
birthweight (3580 ± 596 g vs 3544 ± 579 g, p= 0.145), likeli-
hood of having macrosomia (22.2% vs 20.9%, p=0.452)or
being born LGA (21.0% vs 18.0%, p= 0.077). However,
these neonates were more likely to have had an Apgar score
<7 after 5 min (4.4% vs 2.6%, p= 0.015) and to have been
admitted to the neonatology department (15.0% vs 11.0%,
p= 0.004). None of the other neonatal outcomes showed sig-
nificant differences between these two groups.
Compared with neonates from mothers with NGT, neo-
nates from mothers classified as having GDM based only on
the WHO 1999 criteria for 2HG had a lower birthweight
(3437 ± 498 g vs 3544 ± 579 g, p= 0.01) and were less likely
to have macrosomia (12.8% vs 20.9%, p= 0.003). The likeli-
hood of these neonates being born LGA was similar to those
from mothers with NGT (15.4% vs 18.0%, p= 0.309).
However, 20.5% of the women in this group were treated with
insulin. None of the other neonatal outcomes showed signifi-
cant differences between these two groups.
When we compared the percentage of LGA neonates in our
data with those found in the general obstetric population in the
north of the Netherlands (11%), we found that all GDM clas-
sification groups as well as women with NGT had a higher
percentage of LGA neonates.
Discussion
This large retrospective cohort study to evaluate the pos-
sibleimpactofapplyingthenewWHO2013criteriadem-
onstrates that the number of GDM diagnoses would in-
crease by 45%, relative to the WHO 1999 criteria. We
also show that applying these new criteria indeed iden-
tifies a new group of women (with fasting glucose ≥5.1
but ≤6.9 mmol/l) who have unfavourable characteristics
and more adverse pregnancy outcomes when compared
either with women found to have NGT upon testing or
with the general obstetric population. Our results show
that women potentially missed owing to the higher 2HG
threshold (2HG ≥7.8 but ≤8.4 mmol/l) of the WHO 2013
criteria have similar pregnancy outcomes to women with
NGT. Our results also indicate that neonates from mothers
who are tested for GDM but are found to have NGT are
more likely to be born LGA or with macrosomia than
those born to mothers in the general obstetric population
in our region.
The number of gestational diabetes diagnoses and mater-
nal characteristics Several authors have expressed concerns
about the adoption of the WHO 2013 criteria, as this will
significantly increase the number of GDM diagnoses, and
impose a higher burden on healthcare provided by obstetri-
cians [10,11]. Studies have shown that implementing the new
WHO 2013 criteria will result in a two- to threefold increase in
the number of GDM diagnoses [9,11,17]. The increase from
22% to 32% observed in our cohort of women at higher risk of
GDM was mainly the result of an increase in the number of
women who would be diagnosed on the basis of an elevated
fasting glucose level. At the same time a number of women
would not be diagnosed due to the higher threshold for 2HG in
the WHO 2013 criteria.
The lower fasting glucose threshold in the WHO 2013
criteria identifies a group of women who are more likely than
those with NGT to be obese and hypertensive. Moreover, the
women classified as having GDM based only on the WHO
1999 criteria for 2HG were also more likely than women with
NGT to be overweight. It is known that impaired fasting glu-
cose (IFG; fasting glucose ≥5.6 and ≤6.9 mmol/l) and/or im-
paired glucose tolerance (IGT; 2HG ≥7.8 and ≤11.0 mmol/l)
are both predictors for the future development of type 2 dia-
betes [18]. IFG and IGT are associated with an unfavourable
metabolic profile, including obesity and hypertension. Both
groups successfully identify a group of high-risk women with
an adverse metabolic profile. These women are at increased
risk of developing complications during pregnancy.
Pregnancy outcomes Although uncertainty remains regard-
ing the optimal glucose threshold to define GDM,
hyperglycaemia during pregnancy is clearly associated with
an increased risk of adverse pregnancy outcomes [6]. Indeed,
women in this study classified as having GDM using any
criteria had higher rates of adverse maternal outcomes, includ-
ing hypertensive disorders during pregnancy, planned
Caesarean section and induced labour when compared with
women with NGT. Moreover, the neonates of mothers classi-
fied as having GDM by any criteria were likely to have been
admitted to the neonatology department.
Concerns have been raised about the ‘medicalisation’of
pregnancy should the new WHO 2013 criteria be implement-
ed [10]. Based on the WHO 1999 criteria currently applied in
the Netherlands, these women are not diagnosed with GDM
and are therefore not treated with diet and/or insulin.
However, our findings suggest that these women already have
higher intervention rates. We demonstrated that, in contrast to
women with NGT, women classified as having GDM based
only on the WHO 2013 criteria for fasting glucose had higher
rates of gestational hypertension, planned Caesarean section
and induced labour and their neonates were more likely to
have an Apgar score <7 at 5 min and to be admitted to the
neonatology department. A number of other studies have also
806 Diabetologia (2018) 61:800–809
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
shown that women reclassified as having gestational diabetes
using the new WHO 2013 criteria are at increased risk of
adverse pregnancy outcomes including gestational hyperten-
sion, Caesarean section, neonatal intensive care admission and
LGA neonates [19–22].
In terms of the likelihood of having an LGA neonate, we
found no significant differencesbetween the women classified
as having GDM based on the WHO 2013 threshold for fasting
glucose and women with NGT. However, the percentage of
women in this group having an LGA neonate was much
higher than for the general obstetric population (21% vs
11%). On the basis of these findings, it seems that women
classifiedwithGDMbasedonlyontheWHO2013criteriafor
fasting glucose should not be left untreated. This is supported
by the results of a study by Landon et al, 2009, suggesting that
early treatment in women with mild GDM reduces the per-
centage of women giving birth to LGA neonates by 7% [4].
Our study has also shown that implementing the new WHO
2013 criteria with a higher 2HG threshold may exclude a
group of women who now benefit from treatment. The women
classified as having GDM based only on the WHO 1999
criteria for 2HG had pregnancy outcomes similar to those of
women with NGT. A notable finding was that they had the
lowest rate of LGA neonates of all other diagnostic groups.
The only obstetric variable that differed in comparison with
the NGT group was the rate of induced labour, but it has to be
borne in mind that induction of labour at 38/39 weeks of
gestation is more likely to be recommended in women being
treated for GDM, especially those receiving insulin therapy.
All women classified as having GDM based on the WHO
1999 criteria were actively treated with diet and/or insulin.
These interventions normalised their glycaemic profile and
outcomes for this group [14,15]. Therefore, it is unclear
whether these women can be safely left untreated after
implementing the new WHO 2013 criteria. Indeed, Farrar
et al, 2015, showed that even women with a 2HG glucose
level ≥7.5 mmol/l are at increased risk of adverse outcomes
(i.e. birthweight >90th percentile, high infant adiposity, and
Caesarean section) [23]. These authors therefore recommend
using a 2HG glucose threshold even lower than those recom-
mended by both the WHO 1999 and WHO 2013 criteria.
A notable finding of our study is that the women who had
undergone an OGTT and were subsequently found to have
NGT also had a rate of LGA neonates higher than that of
the women receiving treatment after being diagnosed with
GDM based on the WHO 1999 criteria for 2HG (18.0% vs
15.4%). Although this finding was not statistically significant,
it was a large difference compared with the incidence of LGA
neonates in the general obstetric population (18% vs 11%).
This coincidental finding shows that even NGT women with-
out a positive diagnosis of GDM are at increased risk of giving
birth to an LGA neonate. This finding is in agreement with a
study by Meek et al, 2015, who demonstrated that women
diagnosed and treated for GDM according to the National
Institute for Health and Care Excellence (NICE) criteria in
the UK had lower rates of LGA neonates than women nega-
tive for GDM according to both the NICE and IADPSG/WHO
2013 criteria [21]. A possible explanation for this finding is
that these women were tested too early in pregnancy and were
therefore not diagnosed with GDM at this time. Some studies
have shown that the OGTT has a poor reproducibility, sug-
gesting that some women who first test negative for GDM can
test positive on a second test [24]. We therefore agree with the
suggestion made by Meek et al, 2015, that standard lifestyle
interventions (including dietary advice) given to women with
GDM might also benefit NGT women.
Strengths and limitations
A major strength of our study is the relatively large cohort of
laboratory results from 75 g OGTTs and the extensive and
detailed information regarding pregnancy outcomes in a sub-
set of 4431 women with singleton pregnancies. All women
with GDM were treated according to a detailed protocol in
two large hospitals [14,15]. Maternal and pregnancy outcome
data were collected manually from individuals’charts at their
midwives’offices. This study also has limitations that should
be noted. First, since universal testing for GDM is not current-
ly recommended in the Netherlands, only women with one or
more risk factors for GDM or signs suggestive of GDM, such
as macrosomia, were tested. The number of pregnancies af-
fected by GDM found in our study is therefore not a reflection
of the general obstetric population, and represents a selected
group of women at higher risk of GDM. Universal testing is
now recommended in several countries around the world.
However, literature regarding the best method of screening
(universal or risk-based) remains controversial [8]. Second,
the WHO 2013 criteria also recommend that the diagnosis of
GDM should include a 1 h plasma glucose of ≥10.0 mmol/l
following a 75 g OGTT. Since we did not have data for 1 h
glucose levels, the number of GDM diagnoses reported here
might be an underestimation. Third, all women diagnosed
according to the WHO 1999 criteria were offered treatment
for GDM. Finally, we have compared outcomes with those in
the general population in the north of the Netherlands between
2011 and 2013. Unfortunately data after 2013 have not yet
been made available from public datasets. Furthermore, this
dataset does not indicate which women were tested with an
OGTT.
Conclusions This large retrospective cohort study evaluat-
ed the possible impact on the number of GDM diagnoses
and pregnancy outcomes of applying the new WHO 2013
rather than the old WHO 1999 criteria. We demonstrated
that the number of GDM diagnoses would increase
Diabetologia (2018) 61:800–809 807
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
markedly if the WHO 2013 criteria were implemented.
Nevertheless, the WHO 2013 threshold for fasting glucose,
≥5.1 but ≤6.9 mmol/l, identifies a group of women with an
increased risk of pregnancy complications. We therefore
recommend that, to improve GDM outcomes, the fasting
glucose threshold in the Dutch national guideline needs to
be reduced. However, it remains unclear from our data
whether women with a 2HG ≥7.8 but ≤8.4 mmol/l can be
safely left untreated. Recent studies suggest that a 2HG
threshold of 7.5 mmol/l may be more appropriate. Future
studies should evaluate whether a stricter 2HG OGTT
threshold further improves pregnancy outcomes and
should also address pregnancy outcomes in women who
are tested but found to have NGT.
Acknowledgements The authors wish to thank the endocrinologists,
gynaecologists, diabetes specialist nurses, and dietitians of the
University Medical Center and Martini Hospital Groningen. Special
thanks are expressed to the participating midwife practices: De
Verloskundigenpraktijk van Groningen, Verloskundigenpraktijk
Hoogezand, Verloskundigenpraktijk La Vie, Verloskundigenpraktijk
New Life, Verloskundige Stadspraktijk, Verloskundigenpraktijk ‘t
Stroomdal, Verloskundigenpraktijk Veendam. We would also like to
thank H. Hepkema-Geerligs (customer relations manager Laboratory of
Clinical Chemistry, Certe, the Netherlands) and the students S. Klöppner
(University Medical Center Groningen) and J. van Amstel (University
Medical Center Groningen) for their contribution to the data collection.
Finally, we thank epidemiologist H. Groen (Department of
Epidemiology, University Medical Center Groningen), the Dutch
Perinatal Registry and the Municipal Health Service Groningen for pro-
viding the data on the reference population in the northern region of the
Netherlands.
Some of the data were presented as an abstract at the 53rd EASD
Annual Meeting in 2017.
Data availability The datasets generated during and/or analysed during
the current study are not publicly available. The dataset contains clinical
data which, because of the Dutch law for Personal Data Protection and
patient confidentiality, cannot be shared publicly. Patients did not sign
informed consent to release their data on an individual basis on the inter-
net, but data are available from the corresponding author on reasonable
request.
Funding Novo Nordisk Netherlands provided an unrestricted research
grant. The study sponsor was not involved in the designs of the study; the
collection, analysis and interpretation of data; writing the report; or the
decision to submit the report for publication.
Duality of interest The authors declare that there is no duality of inter-
est associated with this manuscript.
Contribution statement SHK and AWK analysedthe data and drafted
the manuscript. All authors qualify for authorship according to
International Committee of Medical Journal Editors criteria. They have
all contributed to the conception and design of the study, the interpretation
of the data, the critical revision of the article for important intellectual
content and the final approval of the version to be published. SHK and
BHRWare the guarantors of this work.
Open Access This article is distributed under the terms of the Creative
Commons Attribution 4.0 International License (http://
creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
distribution, and reproduction in any medium, provided you give appro-
priate credit to the original author(s) and the source, provide a link to the
Creative Commons license, and indicate if changes were made.
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