Adv Exp Med Biol - Advances in Internal Medicine

https://doi.org/10.1007/5584_2020_512
# Springer Nature Switzerland AG 2020

Gestational Diabetes Mellitus Screening

and Diagnosis

U. Yasemin Sert and A. Seval Ozgu-Erdinc

Abstract diagnosis methods of GDM accepted by dif-

ferent study groups will be discussed which
An ideal screening test for gestational diabetes will be followed by the evaluation of different
should be capable of identifying not only glycemic thresholds. Then the advantages and
women with the disease but also the women disadvantages of used methods will be
with a high risk of developing gestational dia- explained and the chapter will finish with an
betes mellitus (GDM). Screening and diagno- evaluation of the current international
sis are the main steps leading to the way of guidelines.
management. There is a lack of consensus
among healthcare professionals regarding the Keywords
screening methods worldwide. Different study
groups advocate a variety of screening 100-g Oral glucose tolerance test · 50-g
methods with the support of evidence-based glucose challenge test · 75-g Oral glucose
comprehensive data. Some of the tolerance test · Diagnosis · Fasting plasma
organizations suggest screening for high risk glucose · Gestational diabetes mellitus ·
or all pregnant women, while others prefer to Hemoglobin A1c · Postprandial glucose ·
offer definitive testing without screening. Random plasma glucose · Screening
Glycemic thresholds are also not standardized
to decide GDM among different guidelines.
Prevalence rates of GDM vary between 1 Introduction
populations and with the choice of glucose
thresholds for both screening and definitive Diabetes mellitus is defined as a metabolic dis-
tests. One-step or two-step methods have ease presented with the defect of the function of
been used for GDM diagnosis. However, glucose metabolism (American Diabetes A
screening includes selecting patients with his- 2013). Pregnancy is naturally associated with
torical risk factors, 50 g 1-h glucose challenge pancreatic β-cell hyperplasia, which results in
test, fasting plasma glucose, random plasma higher fasting and postprandial insulin levels
glucose, and hemoglobin A1c with different (Butte 2000). While during the first-trimester
cutoffs. In this chapter, screening and blood glucose levels decrease with increasing
insulin, hormones such as cortisol and estrogen
lead to insulin resistance, especially in the second
U. Y. Sert and A. S. Ozgu-Erdinc (*)
Ministry of Health-Ankara City Hospital, Universiteler and third trimesters (Carr and Gabbe 1998). In
Mahallesi Bilkent Cad, Ankara, Turkey addition to the hormonal changes, placental
 U. Y. Sert and A. S. Ozgu-Erdinc

tumor necrosis factor (TNF)-α, human placental et al. 2018; Haneda et al. 2018; Yang 2012;
lactogen (HPL), and growth hormone National Institute for Health and Care Excellence
(GH) impair glucose metabolism due to 2015; World Health Organization 2013;
pregnancy-associated insulin resistance Kleinwechter et al. 2014; Negrato et al. 2010;
(IR) (Barbour et al. 2007; Catalano et al. 1991). Hod et al. 2018; Mahmood 2018; Seshiah et al.
The problem can be characterized by the failure 2009; Blumer et al. 2013; Diabetes Association Of
of insulin secretion, activity, or both, which The Republic Of China T 2020; Moyer and Force
results in a diabetogenic state in pregnancy USPST 2014; Brown 2014; IDF GDM Model of
(Mumtaz 2000). Care 2015; RANZCOG 2017; Nankervis et al.
Gestational diabetes mellitus (GDM) is the 2014; Guidelines QC 2015; Guidelines H 2016;
most common metabolic disease of pregnancy, American Diabetes A 2020; Network SIG 2014).
which is associated with short- and long-term A disagreement is present even between
adverse outcomes for the mother and the off- obstetric and diabetes mellitus organizations of a
spring. The incidence depends on the population country (e.g., American Diabetes Association
and the diagnostic criteria (2.4–37.7%) (Simmons (ADA) and American College of Gynecology
2017; Ozgu-Erdinc et al. 2019a), and the preva- and Obstetrics (ACOG)) (Committee on Practice
lence is significantly increasing, mostly due to the B-O 2018; American Diabetes A 2020). The
obesity epidemic. Uncontrolled hyperglycemia is diversity of recommendations results in different
associated with serious/severe acute and chronic approaches, even within the same hospital, which
effects. The fetal adverse outcome increases if leads the clinicians to a complicated dilemma.
hyperglycemia which is associated with long Since this lack of consensus creates major
term effects on different organ systems occurs problems in addressing prevalence,
during the pregnancy (Fuller and Borgida 2014). complications, the efficacy of treatment, and
Langer et al. demonstrated that every 10 mg/dL follow-up of GDM, the need for consensus has
increase in fasting plasma glucose (FPG) is been repeatedly expressed by the experts. There is
associated with a 15% increase in both maternal a need for standardization to have global unifor-
and fetal adverse outcomes (Langer et al. 2005). mity for diagnosing GDM.
The risk of developing Diabetes mellitus
(DM) also increases among women with GDM
(Herath et al. 2017). As appropriate glycemic 2 History of GDM
control decreases the risk of GDM-related
complications, early diagnosis and treatment/ The first documented case of hyperglycemia in
management are very essential. pregnancy in literature was a 22-year-old
To prevent or decrease the fetal and maternal multigravida woman with a history of severe
risks of GDM, prediction, screening, diagnosis, fetal macrosomia and stillbirth in 1824.
management, and follow up strategies are essen- Bennewitz demonstrated that the women were
tial. However, there is currently no consensus on suffering from severe hyperglycemic symptoms
the definition, screening, diagnosis, and manage- in the pregnancy, while all of them were
ment strategies about GDM. Today nearly 30 dif- disappearing after the delivery (Hadden 1998).
ferent guidelines for screening and diagnosing This was the first observation of the existence of
GDM addressed by national and international dia- the hyperglycemic conditions and their unusual
betes organizations, healthcare societies, endo- effects on the newborn. Previously, the clinicians
crine groups, and obstetric associations (Agarwal had recognized that any degree of hyperglycemia
2018; Committee on Practice B-O 2018; Interna- from mild to severe resulted in poor perinatal
tional Association of D, Pregnancy Study Groups outcomes (Hoet and Lukens 1954). However,
Consensus P et al. 2010; Panel NC 2013; Diabetes the most crucial step for the definition of “hyper-
Canada Clinical Practice Guidelines Expert C glycemia in pregnancy” was an epidemiologic
Gestational Diabetes Mellitus Screening and Diagnosis

study performed with a two-step method follow- (IADPSG) in 2010 (International Association
ing an oral glucose tolerance test (OGTT) in 1964 of D, Pregnancy Study Groups Consensus P,
by O’Sullivan and Mahan (1964). New et al. 2010). WHO has also announced a recom-
approaches to plasma glucose measurement mendation concerning hyperglycemia during
revealed Carpenter and Coustan criteria based pregnancy in 2013 (World Health Organization
on this study (Carpenter and Coustan 1982). The 2013). WHO classified hyperglycemia during
US National Diabetes Data Group (NDDG) pregnancy as “diabetes mellitus in pregnancy”
(1979) and the World Health Organization and “GDM” and the International Federation of
(WHO) (1980) established that the 2-h 75-g Gynecology and Obstetrics (FIGO) endorsed this
OGTT should be the main diagnostic test for definition (Chi et al. 2018; Hod et al. 2015). ADA
glucose intolerance outside pregnancy. WHO introduced the definition of GDM as the diagnosis
issued a recommendation suggesting to use the of diabetes during the second or third trimester of
same criteria of non-pregnant people by using a pregnancy in 2018 (American Diabetes A 2018).
75 g oral glucose tolerance test, which was sub- Endocrine Society has suggested distinguishing
stantially weak for the prediction of perinatal hyperglycemia in terms of “pregnancy-
outcomes (Houshmand et al. 2013). In 1980, associated” and “antedated to pregnancy”
Freinkel N. demonstrated a study focusing on (Blumer et al. 2013). According to the
the effects of fuel metabolism of mother to fetus, recommendations, diabetes mellitus during preg-
and this was an important cornerstone leading nancy, whether symptomatic or not, carries a
The American Diabetes Association (ADA) to significant risk of adverse perinatal outcomes.
define GDM as “glucose intolerance with onset Management of diabetes mellitus during preg-
or first recognized during pregnancy” (Metzger nancy should be based on the microvascular and
and Coustan 1998). This step demonstrated the chronic effects of hyperglycemia, while GDM
need for different diagnostic methods and man- management targeted first and foremost perinatal
agement strategies for pregnant women different outcomes.
from the recommendation of WHO.

4 GDM Screening
3 Definition
The purpose of the screening should be to identify
Gestational diabetes mellitus (GDM) was histori-
GDM cases and asymptomatic pregnant women
cally defined as any glucose intolerance first
who are at risk of GDM progression. Screening is
recognized in the pregnancy by ADA and
indispensable for the prevention of obstetric
NDDG (Metzger and Coustan 1998). This defini-
outcomes and the future effects of GDM on sev-
tion also included unrecognized pre-existing dia-
eral organ systems (Committee on Practice
betes cases, insulin or only diet modification used
Bulletins—Obstetrics 2018).
for treatment, and whether or not condition
Controversies on GDM screening among vari-
persists after pregnancy. Studies showed that
ous guidelines mainly stem from the inclusion of
including such a wide range of glucose
different studies on the improvement of perinatal
abnormalities under one title might cause
outcomes (Houshmand et al. 2013). These
difficulties in management and postpartum
controversies related to the indication for screen-
follow-up strategies of the disease (Fuller and
ing (universal or selective-risk-factor based), the
Borgida 2014; National Diabetes Data Group
timing of screening (early or 24–28 weeks of
1979). The first determined hyperglycemia during
pregnancy/gestation), how to screen (one or
the pregnancy was assessed as “overt diabetes” or
two-step), and criteria for diagnosis (not
“gestational diabetes” by The International Asso-
standardized).
ciation of Diabetes and Pregnancy Study Groups
 U. Y. Sert and A. S. Ozgu-Erdinc

4.1 Indications for Screening listed in Table 1 (Committee on Practice B-O

2018; American Diabetes A 2020; Lee et al.
4.1.1 Risk Factor-Based Screening or 2018; Mirghani Dirar and Doupis 2017). Both
Universal Screening? ADA and ACOG recommend using these factors
Guidelines that are based on recent reviews have to screen GDM (Committee on Practice B-O
no consensus on performing universal screening 2018; American Diabetes A 2020). These factors
or risk-based screening. ADA defines the women are quite decisive for increased risk of GDM;
at low risk as younger than 25 years, not a mem- however, diagnostic accuracy is limited for one
ber of an ethnic group, body mass index (BMI) factor alone (Griffin et al. 2000; van Leeuwen
<25 kg/m2, no history of previous abnormal glu- et al. 2010). Some authors suggest improving
cose tolerance or adverse obstetric outcome, and the diagnostic accuracy of risk factors by adding
no known history of glucose metabolism some risk indicators such as FPG and some bio-
abnormalities in the first degree relatives. ADA chemical markers (Nanda et al. 2011; Savvidou
recommends not to screen these women since et al. 2010). Risk factors such as BMI have
screening provides no additional benefit (Ameri- variations between different ethnic groups, and
can Diabetes A 2020). Risk factors defined for this appears to be a limitation of adopting all the
GDM development by different study groups are risk factors universally (Shah et al. 2011). There

Table 1 Risk factors for GDM prediction

Previous history of gestational diabetes mellitus
Previously elevated blood glucose levels, pre-diabetes/impaired glucose metabolism
Maternal age 25-35-40 years
Family history of diabetes mellitus (first-degree relative with diabetes or a sister with gestational diabetes mellitus)
Body mass index 25–30 kg/m2
Previous macrosomia (baby with birth weight >4500g or >90th centile) or polyhydramnios.
Signs of insulin resistance such as Polycystic ovary syndrome (PCOS) and Acanthosis nigricans
Medications: corticosteroids, antipsychotics
History of congenital anomalies
Pregnancy-induced hypertension (PIH)
History of stillbirth
History of abortion
Multiparity 2
History of preterm delivery
History of neonatal death
Current smoking
Current drinking
Excessive weight gain in the index pregnancy
Minority ethnic family origin with a high prevalence of diabetes. (Latino, Native American, Caribbean, Chinese, Asian,
Indian subcontinent, Aboriginal, Torres Strait Islander, Pacific Islander, Maori, Middle Eastern, non-white African)
History of PAOD (Peripheral Arterial Occlusive Disease), CVD (cerebral vascular disease).
Hypertension (>140/90 mmHg or on therapy for hypertension)
HDL cholesterol level <35 mg/dL (0.90 mmol/L) and/or a triglyceride level >250 mg/dL (2.82 mmol/L)
A sister with hyperglycemia in pregnancy
Physical inactivity
Short stature
Multifetal pregnancy
Vitamin D deficiency
Maternal history of low birth weight
HbA1c 5.7%
Gestational Diabetes Mellitus Screening and Diagnosis

are several risk factors with several cutoffs in the development of GDM (Bhattacharya 2004). On
literature. Some of the studies endorse the contrary, one study from Israel that included
population-based risk factor assessment and sig- 6129 pregnant women demonstrated a significant
nificant effect of life-style modifications (physical association between FPG and developing GDM
activity, diet, alcohol, and smoking) on develop- (the group with FPG: 100–105 mg/dL
ing GDM (Caliskan et al. 2004; Gobl et al. 2012; and < 75 mg/dL have GDM prevalence of
Zhang et al. 2014). 11.7% and 1% respectively) (Riskin-Mashiah
The main concern about the risk-based selec- et al. 2009). Although this study reveals that
tive screening regarding historical or clinical GDM prevalence is low among pregnant women
factors is missing the majority of GDM cases with FPG < 75 mg/dL, GDM diagnosis would be
(Lavin 1985). In one study, GDM was found in missed nearly 9% of pregnant women (Riskin-
1.45% of women with risk-based screening, while Mashiah et al. 2009). Most of the studies have
it increased to 2.7% in the same population with shown that pre-conception FPG could be used to
universal screening, which demonstrates that risk- predict GDM and in the first trimester with differ-
based screening has missed half of the GDM ent thresholds (Ozgu-Erdinc et al. 2019b; Li et al.
cases (Griffin et al. 2000). For this reason, most 2019). FPG, high sensitive C-reactive protein
of the experts prefer universal screening. (hs-CRP), SHBG, tissue plasminogen activator
(tPA), TNF-α, leptin, adiponectin, placental pro-
tein 13, endoglin, and lipids were identified as the
4.2 When to the Screen? predictors of GDM when combined with risk
factors in the first trimester of pregnancy in the
4.2.1 Pre-conceptual Prediction of GDM literature (Savvidou et al. 2010; Ozgu-Erdinc
In a recent study, it is postulated that GDM can be et al. 2015; Yeral et al. 2014; Kansu-Celik et al.
predicted before conception by using the first 2019a; Huhn et al. 2018). Many biomarkers have
degree relatives with type 2 diabetes mellitus, been identified for the prediction of GDM during
FPG, fasting insulin, androstenedione, and sex the first trimester (Table 2) (Kansu-Celik et al.
hormone-binding globulin (SHBG) levels 2019a; Huhn et al. 2018; Kansu-Celik et al.
(Bidhendi Yarandi et al. 2019). Although these 2019b; Yang et al. 2017; Ravnsborg et al. 2016;
factors can predict GDM, it is not suitable to Nevalainen et al. 2016; Powe 2017; Donovan
screen all the women with these factors before et al. 2018; Tu et al. 2017; Yoffe et al. 2019;
conception. Wang et al. 2018; Zhu et al. 2019; Mertoglu
et al. 2019; Arslan et al. 2019; Gan et al. 2019).
4.2.2 First-Trimester Screening It is possible to identify 75% of pregnancies in
Prediction of GDM during the first trimester is which GDM will develop, by a combination of
unclear and also controversial because different maternal factors, biomarkers, and obstetric his-
guidelines suggest different screening methods tory (Plasencia et al. 2011).
and follow-up strategies by using various cutoff Although pregnancy is associated with
values (Agarwal 2016). In the first trimester, FPG hyperinsulinemia and IR, the level of maternal
physiologically tends to decline (Mills et al. hormones such as cortisol and estrogen, reach
1998). Regardless of this anticipated decline, it the peak effect between 26–33 weeks of gestation
is still possible to miss the risky/high-risk patients (Carr and Gabbe 1998; Kuhl and Holst 1976).
by using the cut-off values of the third trimester of Women who are not able to normalize the glucose
pregnancy (<92 mg/dL) (McIntyre et al. 2016; level with this increment of insulin develop
Ozgu-Erdinc et al. 2015). hyperglycemia (Plows et al. 2018). This condition
The study of Bhattacharya demonstrated that constitutes the basis for screening between
fasting plasma glucose evaluated during the first 24–28 weeks of pregnancy. Performing the test
trimester of pregnancy cannot be used as an effi- too early can lead to missing the cases due to the
cient diagnostic test for the prediction of later increase of IR from the first to the third trimester,
 U. Y. Sert and A. S. Ozgu-Erdinc

Table 2 List of tested biomarkers for early GDM screening

Glycemic related markers: Glucose
Hemoglobin A1c
Fructosamine
C-peptide
1.5 Anhydroglucitol
Glycosylated fibronectin
Osteocalcin
Fetuin-A
Insulin resistance markers Fasting insulin and related indices
Sex-hormone binding globulin
Growth factors and their binding proteins: Insulin-like growth factor-1 and 2,
Insulin-like growth factor-binding protein-1,2,3 and 5
Lipid related markers: High-density lipoprotein
Low-density lipoprotein
Triglycerides
Plasma phospholipid fatty acids
Apolipoprotein E, M, D, L1, AIV
Pregnancy-related/Placenta derived markers: Placental growth factor
Soluble FMS-like tyrosine kinase
Pregnancy-associated plasma protein-A
Placental exosomes
Follistatin-like 3
Soluble endoglin
Human placental protein 13
Placental lactogen
Adipocytokines: Adiponectin
Leptin
Visfatin
Resistin
Retinol binding protein-4
Chemerin
Vaspin
Adipocyte fatty acid-binding protein (Fatty Acid-Binding Protein 4)
Neutrophil gelatinase-associated lipocalin
Lipocalin-2
Hormones: Placental lactogen
Free β-Human chorionic gonadotropin
Inhibin A, Activin A
Testosterone
Dehydroepiandrosterone sulfate
Thyroid-stimulating hormone
Thyroxin
Natriuretic peptides (Atrial, brain)
Nucleic acids: Micro RNAs
Genetic variants
Omics based biomarkers
Inflammation related markers: High sensitive C-reactive protein
Tumor necrosis factor-α
Interleukin-6
(continued)
Gestational Diabetes Mellitus Screening and Diagnosis

Table 2 (continued)
Others: Soluble (pro)renin
Alanine aminotransferase
Ferritin
Hemoglobin
Serum iron concentration
Soluble human leukocyte antigen
Coagulation factor IX
Fibrinogen alpha-chains
Plasminogen activator (inhibitor)
Afamin
α2-macroglobulin
Haptoglobin β chain
Clustering α chain
Serum Amino Acids (Arginine, Glycine)
Acylcarnitines (3-hydroxy-isovalerylcarnitine)

while late screening may result in losing the specific OGTT thresholds for early detection of
chance of implementing preventive measures. GDM (Jokelainen et al. 2020) and as stated in
The clinicians need to be vigilant to identify preg- ADA GDM screening and diagnostic criteria used
nant women who will develop diabetes mellitus in the either one or two-step approach were not
before the first trimester. All the women should be obtained from the data of the first trimester, there-
assessed at the initial visit for overt diabetes and fore the diagnosis of GDM in this period by these
should be screened if the suspicion of GDM arises tests is not evidence based (McIntyre et al. 2016)
due to the risk factors. GDM screening should be and research is needed (American Diabetes A
repeated during 24–28 weeks of gestation if the 2020).
pregnant women have risk factors and GDM were First-trimester universal screening for GDM is
not addressed during the first prenatal visit evalu- not internationally recommended currently since
ation (International Association of D, Pregnancy randomized controlled trials evaluating the poten-
Study Groups Consensus P et al. 2010; Gupta tial benefits and harms of early detection and
et al. 2015). subsequent treatment are lacking (Committee on
IADPSG, which is based on Hyperglycemia Practice Bulletins—Obstetrics 2018).
and Adverse Pregnancy Outcome (HAPO) study, Recommendations of guidelines for trimester-
recommends the first-trimester screening with a based prediction of GDM are listed in Table 3.
75-g OGTT for GDM screening and to make the
diagnosis of GDM if FPG  92 mg/dL (Interna-
4.2.3 24–28 Weeks Screening
tional Association of D, Pregnancy Study Groups
The diabetogenic effect of pregnancy appears
Consensus P et al. 2010). However, ADA
more pronounced at 24–28 weeks of pregnancy.
suggests evaluating high-risk women at the initial
Most of the guidelines recommend universal
visit with FPG, hemoglobin A1c (HbA1c), or
screening at 24–28 weeks of gestation with or
random plasma glucose (RPG) (American Diabe-
without the first-trimester screening. (Table 4)
tes A 2020). If FPG ranges from 92 mg/dL to
(Yang 2012; Nankervis et al. 2014; Kuo and Li
126 mg/dL, it must be accepted as pre-diabetes
2019; Li-zhen et al. 2019). International Diabetes
(impaired glucose tolerance), and the patients
Federation (IDF) and Diabetes in Pregnancy
should be encouraged to have life-style changes
Study group in India (DIPSI) recommend repeat
to prevent GDM or type-2 DM due to the lack of
screening at 32–34 weeks of gestation (IDF GDM
evidence-based studies (American Diabetes A
Model of Care 2015; Seshiah et al. 2006).
2020). A recent study suggested gestational-age
 U. Y. Sert and A. S. Ozgu-Erdinc

Table 3 First trimester/early gestational diabetes screening according to the guidelines

Diagnostic
Threshold threshold
Target Target Diagnostic mg/dL
Guideline population diagnose Screening method mg/dL (mmol/L) method (mmol/L)
NICE Risk- GDM 75-g OGTT FPG 100
(RCOG) based (5.6)
2015 2-h 140
(7.8)
WHO 2013/ Universal Overt DM 75-g OGTT at Overt DM
EBCOG- GDM any time of the FPG 126
EAPM- gestation (7)
FIGO 2018 2-h 200
(11.1)
RPG 200
(11.1)
GDM
a
FPG 92
(5.1)
1-h 180
(10)
2-h 153
(8.5)
ADIPS 2014 Risk- Overt DM Moderate risk Not clear 75-g OGTT a
FPG 92
based factors RPG, (5.1)
RANZCOG GDM FPG, OGTT 1-h 180
2017 (if indicated) (10)
One high risk or 2-h 153
two moderate (8.5)
risks: 75-g
OGTT
GDA/GAGO Risk- Overt DM RPG FPG 92 (5.1) 75-g OGTT a
FPG 92
2014 based (repeat FPG) (5.1)
FPG 1-h 180
(10)
RPG: 140–199 2-h 153
(7.8–11.05) (8.5)
(OGTT)
RPG 200 (11.1)
(Overt DM)
IADPSG Risk- Overt DM FPG FPG Overt DM
2010/IDF/ based
FIGO 2015 Universal GDM RPG RPG FPG 126
(IDF, (7)
FIGO) HbA1c HbA1c HbA1c
6.5%
75g OGTT (high- RPG 200
risk ethnic groups) (11.1)
(FIGO) GDM
FPG
92–126
(5.1–7)
FPG<92
(5.1) 75-g
OGTT
(24–28 GW)
(continued)
Gestational Diabetes Mellitus Screening and Diagnosis

Table 3 (continued)
Diagnostic
Threshold threshold
Target Target Diagnostic mg/dL
Guideline population diagnose Screening method mg/dL (mmol/L) method (mmol/L)
JDS 2016 Risk- Overt DM FPG FPG FPG 126
based (7)
RPG RPG HbA1c
6.5%
75 g OGTT 75-g OGTT RPG 200
(11.1)
HbA1c HbA1c 75-g OGTT
2-h 200
(11.1)
DIPSI 2009 Universal Overt DM – – 75-g OGTT in Overt DM
the first 2-h 200
trimester (11.1)
(Irrespective
of fasting
state)
BSD 2010 Universal Overt DM FPG IGT: 75-g OGTT a
FPG  92
(5.1)
FPG 85 (4.7) 1-h 180
(10)
Overt DM 2-h 153
(8.5)
FPG 126 If negative,
(Simmons 2017) repeat at
24–28 GW
Queensland Risk- GDM HbA1c GDM
2015 based Diabetes 75-g OGTT HbA1c
in 5.9–6.5%
pregnancy FPG
92–124
(5.1–6.9)
1-h180
(10)
2-h
153–200
(8.5–11)
DIP
FPG 126
(Simmons
2017)
2-h 200
(11.1)
RPG 200
(11.1)
HbA1c
6.5%
(continued)
 U. Y. Sert and A. S. Ozgu-Erdinc

Table 3 (continued)
Diagnostic
Threshold threshold
Target Target Diagnostic mg/dL
Guideline population diagnose Screening method mg/dL (mmol/L) method (mmol/L)
MOH of Risk- GDM – 75-g OGTT a
FPG 92
China 2012 based (5.1)
1-h 180
(10)
2-h 153
(8.5)
If negative,
repeat at
24–28 GW
DAROC Universal Overt DM – FPG Overt DM
2018 (type1,2 HbA1c (type1,2 or
or other) other)
FPG mg/dL
(mmol/L)
126
(7.0)
HbA1c
6.5%
HKCOG Risk- Overt DM – 75-g OGTT GDM
2016 based (type1,2 FPG FPG 92
or other) (5.1)
GDM HbA1c Overt DM
FPG 126
(7.0)
75-g OGTT
2-h 200
(11.1)
RPG 200
(11.1)
HbA1c
6.5%
CDA 2018 Risk- Overt DM FPG NA – –
based (type1,2 HbA1c
or other) 50-g GCT
75-g OGTT
SIGN 2017 Risk- Overt DM FPG Overt DM FPG Overt DM
based (type1,2 2-h PPG FPG 126 (7.0) HbA1c FPG 126
or other) (7.0)
HbA1c HbA1c 6.5% PPG HbA1c
6.5%
IGT 2-h PPG 200 2-h PPG
(11.1) 200 (11.1)
IGT
FPG:92–124
(5.1–6.9)
(continued)
Gestational Diabetes Mellitus Screening and Diagnosis

Table 3 (continued)
Diagnostic
Threshold threshold
Target Target Diagnostic mg/dL
Guideline population diagnose Screening method mg/dL (mmol/L) method (mmol/L)
2-h PPG:
140–200 (7.8–11)
HbA1c: 6–6.4%
a
IGT should be
evaluated with
75-g OGTT at
24–28 GW
ACOG 2018/ Risk- Overt DM 75-g OGTT NA 75-g OGTT a
FPG 92
NIH 2015 based (type1,2 (5.1)
or other) 50-g GCT or 1-h 180
(10)
HbA1c (not alone) 100-g OGTT 2-h 153
(8.5)
or
GDM b
FPG 95
(5.3)
1-h 180
(10)
2-h 155
(8.6)
3-h 140
(7.8)
NZSSD Universal Overt DM HbA1c Overt DM Overt DM
2014 (type 1,2 HbA1c  6.7% HbA1c
or other) 6.7%
GDM GDM
GDM If HbA1c:
5.9–6.6%, apply
2-h 75-g OGTT at
24–28 GW
Endocrine Universal Overt DM FPG – FPG Overt DM
Society of (type 1,2 RPG RPG FPG 126
USA 2013 or other) (7.0)
-HbA1c HbA1c RPG 200
(11.1)
GDM 2-h 75-g OGTT HbA1c
before 13 GW 6.5%
(8–14 h fasting) GDM
FPG:
92–125
(5.1–6.9)
RPG: NA
HbA1c: NA
(continued)
 U. Y. Sert and A. S. Ozgu-Erdinc

Table 3 (continued)
Diagnostic
Threshold threshold
Target Target Diagnostic mg/dL
Guideline population diagnose Screening method mg/dL (mmol/L) method (mmol/L)
ADA 2020 Risk- Overt DM FPG – FPG FPG 126
based (7.0)
HbA1c HbA1c 75-g OGTT
75-g OGTT, 2-h 75-g OGTT, 2-h 200
value 2-h value (11.1)
RPG 200
(11.1)
HbA1c
6.5%
ACOG The American College of Obstetricians and Gynecologists, ADA American Diabetes Organization, ADIPS
Australian Diabetes in Pregnancy Society, BSD Brazilian Society of Diabetes, CDA Canadian Diabetes Association,
DAROC The diabetes association of republic of China, DIPSI Diabetes in Pregnancy Study group in India, EAPM
European Association of Perinatal Medicine, EASD European Association for the Study of Diabetes, EBCOG the
European Board and College of Obstetrics and Gynecology, DGGT Decreased gestational glucose tolerance, DIP
Diabetes in pregnancy, FIGO International Federation of Gynecology and Obstetrics, FPG Fasting plasma glucose,
GAGO German Association of Gynecologists and obstetricians, GCT Glucose challenge test, GDA German diabetes
Association, GDM Gestational diabetes mellitus,, GW Gestational week, HbA1c Hemoglobin A1c, HKCOG Hong Kong
College of Obstetricians and Gynecologists, IADPSG The International Association of the Diabetes and Pregnancy study
groups, IDF International Diabetes Federation, JDS Japan Diabetes Society, MOH The Ministry of Health, NA Not
applicable, NICE National Institute for Health and Care Excellence, NIH National Institutes of Health, NZSSD
New Zealand Society for the Study of Diabetes, OGTT Oral glucose tolerance test, RANZCOG The Royal Australian
and New Zealand College of Obstetricians and Gynecologists, RCOG Royal College of Obstetricians and Gynecologists,
RPG Random plasma glucose, SIGN Scottish Intercollegiate Guidelines Network, UPSTF The U.S. Preventive Services
Task Force, USA The United States of America, WHO World Health Organization
a
A diagnosis requires that one or more thresholds be met or exceeded
b
A diagnosis requires that two or more thresholds be met or exceeded

4.2.4 Screening and Diagnostic Criteria maternal worsening on developing retinopathy

There is no consensus on screening and diagnosis and nephropathy. The majority of the guidelines
of GDM in the world. The lack of uniformity, as a recommend screening overt diabetes during the
consequence of different guidelines, leads first prenatal visit, particularly for high-risk
clinicians to evaluate the goals and weaknesses patients due to the metabolic disturbance on glu-
and strength of the methods, especially before cose metabolism during the pregnancy (Panel NC
implementing them to their clinical practice. 2013; Blumer et al. 2013; Committee on Practice
These methods might be risk-based or universal Bulletins—Obstetrics 2018; American Diabetes
and either with a one-step or two-step procedure. A 2019; WHO 2014).
Since each method acknowledges different stud- Overt diabetes detected in early pregnancy is
ies performed in various populations, the method diagnosed with the same cutoff plasma levels of
of choice should be decided based on the popula- diabetes of non-pregnant people. The thresholds
tion characteristics, the prevalence of diabetes are FPG  126 mg/dL (7.0 mmol/L);
mellitus and obesity, access to healthcare RPG  200 mg/dL (11.1 mmol/L); or
services, and patients’ adherence to follow-up. HbA1c  6.5% (47 mmol/mol) (International
Association of D, Pregnancy Study Groups Con-
4.2.5 Universal Testing During the First sensus P et al. 2010). WHO recommended that
Trimester HbA1c has no diagnostic accuracy for diabetes in
Deteriorated blood glucose levels due to overt pregnancy (World Health Organization 2013).
diabetes cause congenital fetal defects and Screening and treatment before 24 weeks of
Gestational Diabetes Mellitus Screening and Diagnosis

Table 4 International guidelines for the diagnosis and screening of GDM between 24–28 gestational weeks
Diagnostic
Threshold threshold
Target Diagnosing mg/dL
Guideline population Screening method mG/dL (mmol/L) method (mmol/L)
NICE (RCOG) Universal 75-g OGTT FPG 100
2015 (5.6)
2-h 140
(7.8)
WHO 2013/ Universal 75-g OGTT at any time 75-g OGTT at a
FPG 92
EBCOG-EAPM- Risk- of the gestation any time of the (5.1)
FIGO2018 based gestation 1-h 180
(10)
2-h 153
(8.5)
ADIPS 2014 Universal 75-g OGTT at a
FPG  92
RANZCOG 24–28 weeks (5.1)
2017 gestation 1-h 180
(10)
2-h 153
(8.5)
GDA/GAGO Universal 50-g GCT non-fasting 50-g GCT 135 50 + 75-g OGTT a
FPG 92
2014 (24–28 GW) (7.5) (5.1)
or 1-h 180
(10)
50-g GCT 2-h 153
(8.5)
or
50-g GCT
201
(11.1)
IADPSG 2010/ Universal 75-g OGTT at a
FPG 92
IDF/FIGO 2015 24–28 weeks (5.1)
gestation 1-h 180
(10)
2-h 153
(8.5)
JDS 2016 Risk- FPG FPG Overt DM
based RPG RPG FPG 126
(7)
75-g OGTT 75-g OGTT HbA1c
6.5%
HbA1c HbA1c RPG 200
(11.1)
75-g OGTT
2-h 200
(11.1)
a
GDM
FPG 92
(5.1)
1-h 180
(10)
2-h 153
(8.5)
(continued)
 U. Y. Sert and A. S. Ozgu-Erdinc

Table 4 (continued)
Diagnostic
Threshold threshold
Target Diagnosing mg/dL
Guideline population Screening method mG/dL (mmol/L) method (mmol/L)
DIPSI 2009 Universal 75-g OGTT (24–28 GW) GDM 2-h 140 75-g OGTT GDM 2-h
(irrespective of fasting (7.7) (24–28 GW) 140 (7.7)
state) Overt DM 200 (irrespective of Overt DM
(11.1) fasting state 200 (11.1)
DGGT 120 (6.6) DGGT 120
(6.6)
a
BSD 2010 Universal FPG IGT:FPG mg/dL 75-g OGTT FPG mg/dL
(mmol/L)  (24–28 GW) (mmol/L)
85 (4.7) 92 (5.1)
Overt DM:FPG -1-h Value,
mg/dL (mmol/L)  mg/dL
126 (Simmons (mmol/L)
2017) 180 (10)
-2-h Value,
mg/dL
(mmol/L)
153 (8.5)
QUEENSLAND Universal 75-g OGTT (24–28 GW) – 75-g OGTT at a
FPG 92
2015 24–28 weeks (5.1)
gestation 1-h 180
(10)
2-h 153
(8.5)
MOH OF Universal 75-g OGTT (24–28 GW) – 75-g OGTT a
FPG 92
CHINA 2012 (24–28 GW) (5.1)
1-h 180
(10)
2-h 153
(8.5)
DAROC 2018 Universal 50-g GCT non-fasting 50-g GCT mg/dL 50 + 100-g b
FPG 95
(24–28 GW) (mmol/L) 130/140 OGTT (5.3)
(7.2/7.8) 1-h 180
(10)
or 2-h 155
(8.6)
3-h 140
(7.8)
75-g OGTT or
a
FPG 92
(5.1)
1-h 180
(10)
2-h 153
(8.5)
KCOG 2016 Universal – – 75-g OGTT a
FPG 92
(5.1)
1-h 180
(10)
2-h 153
(8.5)
(continued)
Gestational Diabetes Mellitus Screening and Diagnosis

Table 4 (continued)
Diagnostic
Threshold threshold
Target Diagnosing mg/dL
Guideline population Screening method mG/dL (mmol/L) method (mmol/L)
UPSTF 2014 Universal 50-g GCT non-fasting 50-g GCT mg/dL 50 + 100-g b
FPG 95
(24–28 GW) (mmol/L) 130/135/ OGTT (5.3)
140 (7.2/7.5/7.8) or 1-h 180
(10)
2-h 155
(8.6)
3-h 140
(7.8)
50 + 75-g OGTT a
FPG 92
(5.1)
1-h 180
(10)
2-h 153
(8.5)
CDA 2018 Universal 50-g GCT 50-gGCT mg/dL 75-g OGTT a
FPG 95
(mmol/L) 140 (5.3)
or (7.8) 1-h 190
(10.6)
75-g OGTT (24–28 GW) 2-h 162
(9)
IGN 2017 Risk- FPG (low risk) 75-g – FPG a
FPG 92
based OGTT (high risk) (5.1)
75-g OGTT 1-h 180
(10)
2-h 153
(8.5)
ACOG 2018/ Universal 50-g GCT 50-g GCT 100-g OGTT at b
FPG  95
NIH 2015 130/135/140 (7.2/ 24–28 GW (5.3)
7.5/7.8) 1-h 180
(10)
2-h 155
(8.6)
3-h 140
(7.8)
NZSSD 2014 Universal If HbA1c: 5.9–6.6% 50-g GCT mg/dL 2-h 75-g OGTT FPG 99
(at first trimester), apply (mmol/L) 140–200 (24–28 GW) (5.5)
2-h 75-g OGTT (24–28 (7.8–11) 2-h 162
GW) (9)
If HbA1c: or
5.9–6.6% (at first 50-g GCT
trimester) 200
Others or (11.1)
50-g GCT 50-g GCT
140–200
(7.8–11) (24–28
GW)
(continued)
 U. Y. Sert and A. S. Ozgu-Erdinc

Table 4 (continued)
Diagnostic
Threshold threshold
Target Diagnosing mg/dL
Guideline population Screening method mG/dL (mmol/L) method (mmol/L)
Endocrine Universal – – 2-h 75-g OGTT Overt DM
Society of USA (24–28 GW) (type1,2 or
2013 other):
(8–14 h fasting) FPG 126
(7.0
1-h NA
2-h 200
(11.1)
a
GDM
FPG 92–125
(5.1–6.9)
1-h 180
(10.0)
2-h 153–199
(8.5–11.0)
ADA 2020 Universal 75-g OGTT a
FPG  92
(5.1)
or 1-h 180
(10)
50 + 100-g 2-h 153
OGTT (8.5)
b
FPG  95
(5.3)
1-h 180
(10)
2-h 155
(8.6)
3-h 140
(7.8)
ACOG The American College of Obstetricians and Gynecologists, ADA American Diabetes Organization, ADIPS
Australian Diabetes in Pregnancy Society, BSD Brazilian Society of Diabetes, CDA Canadian Diabetes Association,
DAROC The diabetes association of republic of China, DIPSI Diabetes in Pregnancy Study group in India, EAPM
European Association of Perinatal Medicine, EASD European Association for the Study of Diabetes, EBCOG the
European Board and College of Obstetrics and Gynecology, DGGT Decreased gestational glucose tolerance, FIGO
International Federation of Gynecology and Obstetrics, FPG Fasting plasma glucose, GAGO German Association of
Gynecologists and obstetricians, GCT Glucose challenge test, GDA German diabetes Association, GDM Gestational
diabetes mellitus, GW Gestational week, HbA1c Hemoglobin A1c, HKCOG Hong Kong College of Obstetricians and
Gynecologists, IADPSG The International Association of the Diabetes and Pregnancy study groups, IDF International
Diabetes Federation, JDS Japan Diabetes Society, MOH The Ministry of Health, NA Not applicable, NICE National
Institute for Health and Care Excellence, NIH National Institutes of Health, NZSSD New Zealand Society for the Study of
Diabetes, OGTT Oral glucose tolerance test, RANZCOG The Royal Australian and New Zealand College of Obstetricians
and Gynecologists, RCOG Royal College of Obstetricians and Gynecologists, RPG Random plasma glucose, SIGN
Scottish Intercollegiate Guidelines Network, UPSTF The U.S. Preventive Services Task Force, USA The United States of
America, WHO World Health Organization
a
A diagnosis requires that one or more thresholds be met or exceeded
b
A diagnosis requires that two or more thresholds be met or exceeded
Gestational Diabetes Mellitus Screening and Diagnosis

gestation have no additional benefit for GDM measurement model by using glucose oxidase
according to National Institutes of Health (NIH), and hexokinase combined with new plasma
United States (US) Preventive Services Task values and Carpenter Coustan criteria emerged
Force, Committee of Practice Bulletins, and rec- (Carpenter and Coustan 1982).
ommend performing risk factor-based screening In the two-step approach, which is endorsed by
in the first trimester (Panel NC 2013; Donovan ACOG and NIH, a 50-g glucose challenge test
et al. 2013). (GCT) irrespective of last meal is followed by a
IADPSG recommends diagnosing women 100-g, fasting 3-h OGTT if required according to
with FPG  92 mg/dL (5.1 mmol/L) at any time GCT results. The screening thresholds for 50-g
during pregnancy as GDM (International Associ- GCT vary in different study groups and generally
ation of D, Pregnancy Study Groups Consensus P either 7.8 mmol/L (140 mg/dL) or 7.2 mmol/L
et al. 2010). This recommendation is debatable (130 mg/dL) on the 50-g, 1-h oral GCT is accept-
due to the fact that the same cutoff value is used to able to assume that screening was positive
diagnose GDM in later pregnancy with a 75-g (Benhalima et al. 2018). GDM diagnosis is
OGTT. Pregnancy is associated with changes in made if two or more plasma glucose levels equals
glucose levels, and the same cutoffs with late or exceeds with 100-g OGTT performed while
pregnancy may result in diagnosing GDM more FPG  95 mg/dL (5.5 mmol/L), 1-h plasma
often than it is actually present (Carr and Gabbe glucose180 mg/dL (10 mmol/L), 2-h plasma
1998). A study from China examined 17,186 glucose155 mg/dL (8.6 mmol/L) and 3-h
pregnant women in the first prenatal visit and plasma glucose140 mg/dL (7.8 mmol/L) (Rani
24–28 weeks of gestation and recommended to and Begum 2016). The patients who had positive
use FPG between 6.10 and 7.00 mmol/L GCT results but did not meet the thresholds for
(110–126 mg/dL) for the diagnosis of GDM dur- GDM diagnosis were identified as impaired glu-
ing the first trimester, which is higher than cose tolerance (IGT), and this condition is
IADPSG recommendation (Zhu et al. 2013). thought to indicate deteriorated glucose regu-
IADPSG recommendation on overt diabetes is latory capacity, which might progress to DM in
endorsed by most of the clinicians; however, uni- the future (Retnakaran et al. 2008).
versal screening needs to be performed at
24–28 weeks of gestation according to the avail- 4.2.7 75-g OGTT and One Step
able evidence (Donovan et al. 2013; Long and Screening
Cundy 2013). The first prenatal visit should be WHO recommended using 75-g OGTT for the
essential for the detection of overt diabetes and diagnosis of GDM with the same thresholds of
risky patients (Blumer et al. 2013). non-pregnant people in their first recommenda-
tion (Gupta et al. 2015). This approach was
4.2.6 100-g OGTT and Two-Step criticized for ignoring the physiological changes
Screening in glucose metabolism peculiar to pregnancy,
O’Sullivan and Mahan introduced the diagnostic which resulted in new recommendations in
criteria of GDM, which was based on blood glu- 1999 and lastly in 2013. WHO decreased the
cose testing before and every 3 h after 100-g oral cutoff value of FPG from 7.8 mmol/L (140 mg/
glucose intake in 1964 (Hoet and Lukens 1954). dL) to 5.1 mmol/L (92 mg/dL) for pregnant
In one study included 752 pregnant women, two women with new updates (Chi et al. 2018).
abnormal values were accepted as significant for These criteria, which were changed by WHO,
GDM diagnosis (Houshmand et al. 2013). primarily considered the effects of the metabolic
In 1979, NDDG suggested converting the changes during pregnancy on prenatal outcomes
whole-body glucose cutoffs to plasma values (Houshmand et al. 2013). The current IADPSG
(approximately 14% higher) (National Diabetes criteria for the diagnosis of GDM were devised
Data Group 1979). The new glucose according to the HAPO study, which focused on
 U. Y. Sert and A. S. Ozgu-Erdinc

adverse perinatal outcomes (McIntyre et al. Cheung 2009). In a systemic review, 50-g GCT
2015; Group HSCR et al. 2008). HAPO study was compared with OGTT (75-g or 100-g) to
became a cornerstone for threshold values that estimate the accuracy of GCT for GDM diagnosis
are able to predict adverse perinatal outcomes (van Leeuwen et al. 2012). The sensitivity and
such as large for gestational age (LGA), primary specificity to predict GDM were 0.74 and 0.85,
cesarean section, neonatal hypoglycemia, and respectively. The study concluded that the
birth trauma. One study showed a linear associa- two-step screening implemented with GCT
tion between glycemic values and adverse preg- followed by OGTT misses 26% of actual GDM
nancy outcomes (Group HSCR et al. 2008). cases, which will result in a delay in initiating the
Therefore, IADPSG criteria have been endorsed treatment (van Leeuwen et al. 2012). Another
by several groups including, WHO, ADA, and concern about the two-step method is that several
The Endocrine Society of the USA (Blumer et al. studies showed that many pregnant women did
2013; American Diabetes A 2020; WHO 2014). not proceed with the diagnostic test after the GCT
IADPSG recommends a FPG level of 5.1 mmol/ application. The missing rate is 10% in Toronto
L (92 mg/dL), a 1-h level of 10.0 mmol/L while it increases to 23% in New Zealand (Sermer
(180 mg/dL) or 2-h value of 8.5 mmol/L et al. 1995; Sievenpiper et al. 2012).
(153 mg/dL) for GDM diagnosis after 75-g oral The fasting time also affects the results of
glucose load after overnight fasting of 8–14 h GCT. The metabolic capacity of pregnant
(WHO 2014). women is considered to be better when tested in
the afternoon. This also suggests that the time of
4.2.8 Advantages and Disadvantages OGTT might cause GDM over-, or delayed- diag-
of One-Step and Two-Step nosis. Hence, it would affect fetal and maternal
Methods outcomes (Goldberg et al. 2012). According to
Two-Step Method Arguments opposing the the study of Hancerliogullari et al. fasting dura-
two-step method dominate among the study tion of >6.5 h resulted in 2.7 times more unneces-
groups. The main concerns about implementing sary 100-g OGTT, which is also another
the method are the lack of existence of studies to disadvantage of the method (Hancerliogullari
decide the cutoffs, how to incorporate GCT with et al. 2018).
OGTT, and why two abnormal values needed In contrast, the GCT method is advantageous
(McIntyre et al. 2015; Akgol et al. 2019). in (1) fever false-positive rates, (2) avoiding
The two-step screening implies an inevitable OGTT in more than 75% of women (Brown and
delay in the diagnosis of GDM (Moses and Wyckoff 2017) (Table 5).

Table 5 Advantages and disadvantages of one-step and two-step screenings

Two-step One-step
Method A 50-g GCT followed by a 100-g, 3-h OGTT. Those who 75-or 100-g OGTT is done in all
screen positive are followed up by an oral 100-g glucose patients, without the preliminary step
tolerance test by GCT
Advantages Fewer false positives Simple to follow
Avoids OGTT in more than 75% of the women Easily diagnosed
Less missing follow up
Disadvantages Higher missed diagnosis Poor reproducibility
Delay in initiating treatment even in those who test All women need to come in a fasting
positive state
It requires patients to make two visits for testing
GCT results differ according to the time applied
Abbreviations: GDM gestational diabetes mellitus, GCT glucose challenge test, OGTT oral glucose tolerance test
Gestational Diabetes Mellitus Screening and Diagnosis

One-Step Method Not only the prevalence of 4.2.9 Role of FPG and Postprandial
GDM will increase from 10.6% to 35.5% with Plasma Glucose (PPG)
the one-step approach by using the IADPSG for Screening GDM
criterion but also pregnancy outcome and cost- In the literature, the ideal biomarker to predict
effectiveness will be improved (Duran et al. GDM was studied by several investigators. Espe-
2014). The debate is about whether the increase cially diagnostic accuracy of using FPG and PPG
allows identifying missed cases or results in was evaluated in different studies to be used
over-diagnosis and over-treatment of healthy instead of the glucose load (Bhattacharya 2004;
pregnancies (McIntyre et al. 2014, 2015; Long Powe 2017; Senanayake et al. 2006; Kansu-Celik
2011). et al. 2019c). In the first trimester, FPG physio-
Weak association of the primary adverse logically tends to decline (Ozgu-Erdinc et al.
outcomes with the glycemic levels is the main 2019b; Yeral et al. 2014). Regardless of this
obstacle for adopting the IADPSG criteria univer- anticipated decline, it is possible to miss out the
sally (Akgol and Budak 2019; Ayhan et al. 2016). risky/high-risk patients by using the cut-off
Although the association with secondary values of the third trimester of pregnancy
outcomes such as shoulder dystocia, premature (<92 mg/dL) (McIntyre et al. 2016).
delivery, and preeclampsia is significant, these First-trimester FPG values between 79 mg/dL
complications are not frequent (Long and Cundy and 92 mg/dL have sensitivity and specificity rang-
2013; Group HSCR et al. 2008). ing between 55% and 88% to predict GDM in the
Australian Carbohydrate Intolerance Study in rest of the pregnancy according to the previous
Pregnant Women (ACHOIS) demonstrated and studies (Riskin-Mashiah et al. 2009; Yeral et al.
other studies showed that diagnosis of GDM 2014; Kansu-Celik et al. 2019a; Sacks et al. 2003;
results in increased cesarean section rate, earlier Reichelt et al. 1998). The study of Zhu et al.
delivery, increased interventions, and more fre- demonstrated that FPG between 110 mg/dL and
quent neonatal intensive care unit management/ 126 mg/dL should be considered and treated as
need (Long and Cundy 2013; Ryan 2011; GDM to improve pregnancy outcomes; However,
Crowther et al. 2005). Lower diagnostic levels nutritional and exercise advice will be enough
will cause lower glucose targets achieved with when the FPG level is between 92 mg/dL and
diet or glucose-lowering therapies, which can 110 mg/dL (Zhu et al. 2013). ADA also
lead to hypoglycemic conditions and fetal growth recommends nutrition and exercise advice for the
abnormalities (Crowther et al. 2005). women whose FPG is between 92 mg/dL and
Arguments favoring IADPSG criteria accused 110 mg/dL without diagnosing as GDM (Ameri-
the experts criticizing the one-step method and can Diabetes A 2020). HAPO study also
NIH report for ignoring the increased prevalence recommended that FPG >95 mg/dL is correlated
of pre-diabetes and undiagnosed type 2 diabetes with fetal macrosomia at 24–28 weeks of gestation
of childbearing aged young women (Panel NC (Group HSCR et al. 2008). Increasing FPG is not
2013; McIntyre 2013). The National Health and only associated with increasing GDM risk but also
Nutrition Examination Survey (NHANES) is a predicts the need for treatment (Alunni et al. 2015).
program of studies designed to assess the health Although Senanayake et al. demonstrated that
and nutritional status of adults and children in the postprandial glucose level could be used to predict
US. This program showed that about 30% of GDM with lower sensitivity than FPG
women in the reproductive period have IGT (Senanayake et al. 2006), most of the studies do
(McIntyre 2013; Shin et al. 2015). These not recommend the use of the 2-h PPG level
alterations of glucose metabolism will undoubt- instead of GCT (Agarwal 2018; Bhattacharya
edly reflect GDM prevalence. It is clear that low- 2004). Huddleson et al. advocated that the PPG
ering the thresholds is the only way to reduce the level is not necessary if FPG is within the normal
number of missed cases (McIntyre 2013). range (Huddleston et al. 1993).
 U. Y. Sert and A. S. Ozgu-Erdinc

4.2.10 Role of HbA1c biochemical markers can support early detection

for Screening GDM of high-risk patients. Table 4 demonstrates the
The cutoff values for the healthy population are different approaches to GDM screening and diag-
well defined for HbA1c, while it needs to be nosis among different guidelines and countries.
evaluated for pregnant women (Rafat and
Ahmad 2012). Although HAPO study
demonstrated that the association between glu- 5.1 Overt Diabetes
cose level and the adverse perinatal outcome is
more significant than with HbA1c, several studies IADPSG recommends screening for overt diabe-
claimed that 40–60% of pregnant women could tes at first prenatal visit or universal screening of
be avoided from OGTT by using different cutoffs high-risk women and leaves the decision to the
of HbA1c (Rajput et al. 2012; Lowe et al. 2012; clinicians. WHO endorses the recommendations
Yerebasmaz et al. 2014). There is no consensus of IADPSG (WHO 2014). The Endocrine Society
on change in the level of HbA1c during the preg- recommends screening using the same criteria
nancy; some studies showed an increase, used for non-pregnant people (Blumer et al.
decrease, and no change in HbA1c level during 2013). ADA, ACOG, NIH, and ADIPS suggested
trimesters (Rafat and Ahmad 2012; Davies and screening before 24 weeks of gestation if only
Welborn 1980; Pollak et al. 1979; McFarland risk factors were determined (Panel NC 2013;
et al. 1981). HbA1c should not be considered as Nankervis et al. 2014; American Diabetes A
an acceptable alternative for screening and 2020; Committee on Practice Bulletins—Obstet-
diagnosing GDM. rics 2018).

5 Conclusion 5.2 One-Step Versus Two-Step

and Recommendations Testing

The main reason for the diagnostic dilemma ACOG and NIH still advocated the use of
between different guidelines is a large number two-step testing for the screening and diagnosis
of procedures and glucose thresholds suggested of GDM (Panel NC 2013; Committee on Practice
for the diagnosis of glucose metabolism disorders Bulletins—Obstetrics 2018). WHO, ADIPS, and
in the pregnancy (Table 4). HAPO study and Endocrine Society support the criteria of
concomitant IADPSG criteria became a corner- IADPSG (Blumer et al. 2013; WHO 2014). The
stone for the screening and diagnosis of GDM current recommendations of ADA point out the
(Group HSCR et al. 2008). The Endocrine Soci- need for further researches to build a uniformity
ety of the USA, Australasian Diabetes in Preg- among the health professionals and suggest leav-
nancy Society (ADIPS) and WHO endorsed the ing the decision about one-step or two-step to the
criteria of IADPSG, while ACOG and NIH clinicians (American Diabetes A 2020). IADPSG
recommended a two-step approach (Committee strongly recommended not using HbA1c for
on Practice B-O 2018; Panel NC 2013; World GDM screening, and all other guidelines have
Health Organization 2013; Blumer et al. 2013; endorsed this. HbA1c can be used to rule out
Nankervis et al. 2014). ADA recommended overt diabetes in early pregnancy (International
using either the one-step or two-step approach Association of D, Pregnancy Study Groups Con-
for the diagnosis of GDM (Table 4) (American sensus P et al. 2010).
Diabetes A 2020). GDM is currently diagnosed The optimal screening method is still contro-
between 24 and 28 weeks of pregnancy, while the versial. Women with high plasma glucose levels
combination of maternal risk factors and are detected more sensitively with a 75-g OGTT
Gestational Diabetes Mellitus Screening and Diagnosis

and correlated with adverse pregnancy outcomes. Arslan E, Gorkem U, Togrul C (2019) Is there an associa-
However, the increasing rate of GDM diagnosis tion between kisspeptin levels and gestational diabetes
mellitus? Gynecol Obstet Reprod Med 25(1):1–5
and lack of studies demonstrating that treatment Ayhan S, Alt{nkaya SÖ, Güngör T, Özcan U (2016) Prog-
of women labeled as GDM improved prenatal nosis of pregnancies with different degrees of glucose
outcomes are the major obstacles in the way of intolerance. Gynecol Obstet Reprod Med 19(2):76–81
creating a universal approach. Further researches Barbour LA, McCurdy CE, Hernandez TL, Kirwan JP,
Catalano PM, Friedman JE (2007) Cellular
are needed to be able to generalize the diagnostic mechanisms for insulin resistance in normal pregnancy
methods. and gestational diabetes. Diabetes Care 30(Suppl 2):
Despite numerous research, multiple interna- S112–S119
tional conferences, and major trials, GDM Benhalima K, Van Crombrugge P, Moyson C,
Verhaeghe J, Vandeginste S, Verlaenen H et al
remains a complex and contentious obstetrical (2018) The sensitivity and specificity of the glucose
and public health problem that deserves to be challenge test in a universal two-step screening strat-
carefully discussed and studied. The lack of con- egy for gestational diabetes mellitus using the 2013
sensus and a single acceptable, evidence-based World Health Organization Criteria. Diabetes Care 41
(7):e111–e1e2
guideline confuses the health care providers. A Bhattacharya SM (2004) Fasting or two-hour postprandial
simple, easy to follow, and validated recommen- plasma glucose levels in early months of pregnancy as
dation is essential for GDM screening and screening tools for gestational diabetes mellitus devel-
diagnosis. oping in later months of pregnancy. J Obstet Gynaecol
Res 30(4):333–336
Bidhendi Yarandi R, Behboudi-Gandevani S, Amiri M,
Ramezani TF (2019) Metformin therapy before con-
ception versus throughout the pregnancy and risk of
References gestational diabetes mellitus in women with polycystic
ovary syndrome: a systemic review, meta-analysis and
Agarwal MM (2016) Gestational diabetes mellitus: screen- meta-regression. Diabetol Metab Syndr 11:58
ing with fasting plasma glucose. World J Diabetes 7 Blumer I, Hadar E, Hadden DR, Jovanovic L, Mestman
(14):279–289 JH, Murad MH et al (2013) Diabetes and pregnancy:
Agarwal MM (2018) Consensus in gestational diabetes an endocrine society clinical practice guideline. J Clin
MELLITUS: looking for the Holy Grail. J Clin Med Endocrinol Metab 98(11):4227–4249
7(6):123 Brown J (2014) Screening, diagnosis and management of
Akgol S, Budak MS (2019) Obstetric and neonatal gestational Diabetes in New Zealand: a clinical prac-
outcomes of pregnancies with mild gestational hyper- tice guideline. Ministry of Health, Wellington. http://
glycemia diagnosed at gestational diabetes mellitus www.health.govt.nz/publication/screening-diagnosis-and-
screening. Gynecol Obstet Reprod Med 25(3):138–141 management-gestational-0
Akgol S, Obut M, Bagl{ İ, Kahveci B, Budak MS (2019) Brown FM, Wyckoff J (2017) Application of one-step
An evaluation of the effect of a one or two-step gesta- IADPSG versus two-step diagnostic criteria for gesta-
tional diabetes mellitus screening program on obstetric tional diabetes in the real world: impact on health
and neonatal outcomes in pregnancies. Gynecol Obstet services, clinical care, and outcomes. Curr Diab Rep
Reprod Med 25(2):62–66 17(10):85
Alunni ML, Roeder HA, Moore TR, Ramos GA (2015) Butte NF (2000) Carbohydrate and lipid metabolism in
First trimester gestational diabetes screening – change pregnancy: normal compared with gestational diabetes
in incidence and pharmacotherapy need. Diabetes Res mellitus. Am J Clin Nutr 71(5 Suppl):1256S–1261S
Clin Pract 109(1):135–140 Caliskan E, Kayikcioglu F, Ozturk N, Koc S, Haberal A
American Diabetes A (2013) Diagnosis and classification (2004) A population-based risk factor scoring will
of diabetes mellitus. Diabetes Care 36(Suppl 1):S67– decrease unnecessary testing for the diagnosis of ges-
S74 tational diabetes mellitus. Acta Obstet Gynecol Scand
American Diabetes A (2018) 13. Management of diabetes 83(6):524–530
in pregnancy: standards of medical care in diabetes- Carpenter MW, Coustan DR (1982) Criteria for screening
2018. Diabetes Care 41(Suppl 1):S137–SS43 tests for gestational diabetes. Am J Obstet Gynecol 144
American Diabetes A (2019) 14. Management of diabetes (7):768–773
in pregnancy: standards of medical care in diabetes- Carr DB, Gabbe S (1998) Gestational diabetes: detection,
2019. Diabetes Care 42(Suppl 1):S165–SS72 management, and implications. Clin Diabetes 16
American Diabetes A (2020) 14. Management of diabetes (1):4–12
in pregnancy: standards of medical care in diabetes- Catalano PM, Tyzbir ED, Roman NM, Amini SB, Sims
2020. Diabetes Care 43(Suppl 1):S183–SS92 EA (1991) Longitudinal changes in insulin release and
 U. Y. Sert and A. S. Ozgu-Erdinc

insulin resistance in nonobese pregnant women. Am J Goldberg RJ, Ye C, Sermer M, Connelly PW, Hanley AJ,
Obstet Gynecol 165(6 Pt 1):1667–1672 Zinman B et al (2012) Circadian variation in the
Chi C, Loy SL, Chan SY, Choong C, Cai S, Soh SE et al response to the glucose challenge test in pregnancy:
(2018) Impact of adopting the 2013 World Health implications for screening for gestational diabetes
Organization criteria for diagnosis of gestational dia- mellitus. Diabetes Care 35(7):1578–1584
betes in a multi-ethnic Asian cohort: a prospective Griffin ME, Coffey M, Johnson H, Scanlon P, Foley M,
study. BMC Pregnancy Childbirth 18(1):69 Stronge J et al (2000) Universal vs. risk factor-based
Committee on Practice B-O (2018) ACOG practice bulle- screening for gestational diabetes mellitus: detection
tin no. 190: gestational diabetes mellitus. Obstet rates, gestation at diagnosis and outcome. Diabet Med
Gynecol 131(2):e49–e64 17(1):26–32
Committee on Practice Bulletins—Obstetrics (2018) Group HSCR, Metzger BE, Lowe LP, Dyer AR, Trimble
ACOG practice bulletin no. 190 summary: gestational ER, Chaovarindr U et al (2008) Hyperglycemia and
diabetes mellitus. Obstet Gynecol 131(2):406–408 adverse pregnancy outcomes. N Engl J Med 358
Crowther CA, Hiller JE, Moss JR, McPhee AJ, Jeffries (19):1991–2002
WS, Robinson JS et al (2005) Effect of treatment of Guidelines H (2016) Guidelines for the management of
gestational diabetes mellitus on pregnancy outcomes. gestational diabetes mellitus. The Hong Kong College
N Engl J Med 352(24):2477–2486 of Obstetricians and Gynaecologists
Davies D, Welborn T (1980) Glycosylated haemoglobin in Guidelines QC (2015) Gestational diabetes mellitus.
pregnancy. Aust N Z J Obstet Gynaecol 20(3):147–150 Queensland Health, Queensland
Diabetes Association Of The Republic Of China T (2020) Gupta Y, Kalra B, Baruah MP, Singla R, Kalra S (2015)
Executive summary of the DAROC clinical practice Updated guidelines on screening for gestational diabe-
guidelines for diabetes care- 2018. J Formos Med tes. Int J Women's Health 7:539–550
Assoc 119(2):577–586 Hadden DR (1998) A historical perspective on gestational
Diabetes Canada Clinical Practice Guidelines Expert C, diabetes. Diabetes Care 21(Suppl 2):B3–B4
Feig DS, Berger H, Donovan L, Godbout A, Kader T Hancerliogullari N, Celik HK, Karakaya BK, Tokmak A,
et al (2018) Diabetes and pregnancy. Can J Diabetes 42 Tasci Y, Erkaya S et al (2018) Effect of prolonged
(Suppl 1):S255–SS82 fasting duration on 50 gram oral glucose challenge
Donovan L, Hartling L, Muise M, Guthrie A, test in the diagnosis of gestational diabetes mellitus.
Vandermeer B, Dryden DM (2013) Screening tests Horm Metab Res 50(9):671–674
for gestational diabetes: a systematic review for the Haneda M, Noda M, Origasa H, Noto H, Yabe D, Fujita Y
U.S. Preventive Services Task Force. Ann Intern Med et al (2018) Japanese clinical practice guideline for
159(2):115–122 diabetes 2016. J Diabetes Investig 9(3):657–697
Donovan BM, Nidey NL, Jasper EA, Robinson JG, Herath H, Herath R, Wickremasinghe R (2017) Gesta-
Bao W, Saftlas AF et al (2018) First trimester prenatal tional diabetes mellitus and risk of type 2 diabetes
screening biomarkers and gestational diabetes mellitus: 10 years after the index pregnancy in Sri Lankan
a systematic review and meta-analysis. PLoS One 13 Women-A community based retrospective cohort
(7):e0201319 study. PLoS One 12(6):e0179647
Duran A, Saenz S, Torrejon MJ, Bordiu E, Del Valle L, Hod M, Kapur A, Sacks DA, Hadar E, Agarwal M, Di
Galindo M et al (2014) Introduction of IADPSG Renzo GC et al (2015) The International Federation of
criteria for the screening and diagnosis of gestational Gynecology and Obstetrics (FIGO) initiative on gesta-
diabetes mellitus results in improved pregnancy tional diabetes mellitus: a pragmatic guide for diagno-
outcomes at a lower cost in a large cohort of pregnant sis, management, and care. Int J Gynaecol Obstet 131
women: the St. Carlos Gestational Diabetes Study. (Suppl 3):S173–S211
Diabetes Care 37(9):2442–2450 Hod M, Pretty M, Mahmood T, Figo E, Ebcog (2018) Joint
Fuller KP, Borgida AF (2014) Gestational diabetes position statement on universal screening for GDM in
mellitus screening using the one-step versus two-step Europe by FIGO, EBCOG and EAPM. Eur J Obstet
method in a high-risk practice. Clin Diabetes 32 Gynecol Reprod Biol 228:329–330
(4):148–150 Hoet JP, Lukens FD (1954) Carbohydrate metabolism
Gan WZ, Ramachandran V, Lim CSY, Koh RY (2019) during pregnancy. Diabetes 3(1):1–12
Omics-based biomarkers in the diagnosis of diabetes. Houshmand A, Jensen DM, Mathiesen ER, Damm P
J Basic Clin Physiol Pharmacol. https://doi.org/10. (2013) Evolution of diagnostic criteria for gestational
1515/jbcpp-2019-0120 diabetes mellitus. Acta Obstet Gynecol Scand 92
Gobl CS, Bozkurt L, Rivic P, Schernthaner G, (7):739–745
Weitgasser R, Pacini G et al (2012) A two-step screen- Huddleston JF, Cramer MK, Vroon DH (1993) A rationale
ing algorithm including fasting plasma glucose mea- for omitting two-hour postprandial glucose
surement and a risk estimation model is an accurate determinations in gestational diabetes. Am J Obstet
strategy for detecting gestational diabetes mellitus. Gynecol 169(2 Pt 1):257–262; discussion 62-4
Diabetologia 55(12):3173–3181 Huhn EA, Rossi SW, Hoesli I, Gobl CS (2018)
Controversies in screening and diagnostic criteria for
Gestational Diabetes Mellitus Screening and Diagnosis

gestational diabetes in early and late pregnancy. Front Li P, Lin S, Li L, Cui J, Zhou S, Fan J (2019) First-
Endocrinol (Lausanne) 9:696 trimester fasting plasma glucose as a predictor of ges-
IDF GDM Model of Care (2015) Implementation protocol. tational diabetes mellitus and the association with
Guidelines for healthcare professionals. International adverse pregnancy outcomes. Pak J Med Sci 35
Diabetes Federation, pp 7–9 (1):95–100
International Association of D, Pregnancy Study Groups Li-zhen L, Yun X, Xiao-Dong Z, Shu-bin H, Zi-lian W,
Consensus P, Metzger BE, Gabbe SG, Persson B, Sandra DA et al (2019) Evaluation of guidelines on the
Buchanan TA et al (2010) International association of screening and diagnosis of gestational diabetes
diabetes and pregnancy study groups mellitus: systematic review. BMJ Open 9(5):e023014
recommendations on the diagnosis and classification Long H (2011) Diagnosing gestational diabetes: can expert
of hyperglycemia in pregnancy. Diabetes Care 33 opinions replace scientific evidence? Diabetologia 54
(3):676–682 (9):2211–2213
Jokelainen M, Stach-Lempinen B, Rono K, Nenonen A, Long H, Cundy T (2013) Establishing consensus in the
Kautiainen H, Teramo K et al (2020) Oral glucose diagnosis of gestational diabetes following HAPO:
tolerance test results in early pregnancy: a Finnish where do we stand? Curr Diab Rep 13(1):43–50
population-based cohort study. Diabetes Res Clin Lowe LP, Metzger BE, Dyer AR, Lowe J, McCance DR,
Pract 162:108077 Lappin TR et al (2012) Hyperglycemia and Adverse
Kansu-Celik H, Ozgu-Erdinc AS, Kisa B, Findik RB, Pregnancy Outcome (HAPO) Study: associations of
Yilmaz C, Tasci Y (2019a) Prediction of gestational maternal A1C and glucose with pregnancy outcomes.
diabetes mellitus in the first trimester: comparison of Diabetes Care 35(3):574–580
maternal fetuin-A, N-terminal proatrial natriuretic pep- Mahmood T (2018) Paris consensus on gestational diabe-
tide, high-sensitivity C-reactive protein, and fasting tes mellitus screening 2018. Eur J Obstet Gynecol
glucose levels. Arch Endocrinol Metab 63(2):121–127 Reprod Biol 227:75–76
Kansu-Celik H, Ozgu-Erdinc AS, Kisa B, Eldem S, McFarland KF, Catalano EW, Keil JE, McFarland DE
Hancerliogullari N, Engin-Ustun Y (2019b) Maternal (1981) Glycosylated hemoglobin in diabetic and non-
serum glycosylated hemoglobin and fasting plasma diabetic pregnancies. South Med J 74(4):410–412
glucose predicts gestational diabetes at the first trimes- McIntyre HD (2013) Diagnosing gestational diabetes
ter in Turkish women with a low-risk pregnancy and its mellitus: rationed or rationally related to risk? Diabetes
relationship with fetal birth weight; a retrospective Care 36(10):2879–2880
cohort study. J Matern Fetal Neonatal Med 1–211:1–8 McIntyre HD, Metzger BE, Coustan DR, Dyer AR,
Kansu-Celik H, Ozgu-Erdinc AS, Kisa-Karakaya B, Hadden DR, Hod M et al (2014) Counterpoint:
Tasci Y, Erkaya S (2019c) Fasting and post-prandial establishing consensus in the diagnosis of GDM fol-
plasma glucose screening for gestational diabetes lowing the HAPO study. Curr Diab Rep 14(6):497
mellitus. East Mediterr Health J 25(4):282–289 McIntyre HD, Colagiuri S, Roglic G, Hod M (2015) Diag-
Kleinwechter H, Schafer-Graf U, Buhrer C, Hoesli I, nosis of GDM: a suggested consensus. Best Pract Res
Kainer F, Kautzky-Willer A et al (2014) Gestational Clin Obstet Gynaecol 29(2):194–205
Diabetes Mellitus (GDM) diagnosis, therapy and McIntyre HD, Sacks DA, Barbour LA, Feig DS, Catalano
follow-up care: practice guideline of the German Dia- PM, Damm P et al (2016) Issues with the diagnosis and
betes Association (DDG) and the German Association classification of hyperglycemia in early pregnancy.
for Gynaecologyand Obstetrics (DGGG). Exp Clin Diabetes Care 39(1):53–54
Endocrinol Diabetes 122(7):395–405 Mertoglu C, Gunay M, Gungor M, Kulhan M, Kulhan NG
Kuhl C, Holst JJ (1976) Plasma glucagon and the insulin: (2019) A study of inflammatory markers in gestational
glucagon ratio in gestational diabetes. Diabetes 25 diabetes mellitus. Gynecol Obstet Reprod Med 25
(1):16–23 (1):7–11
Kuo C-H, Li H-Y (2019) Diagnostic strategies for gesta- Metzger BE, Coustan DR (1998) Summary and
tional diabetes mellitus: review of current evidence. recommendations of the Fourth International
Curr Diab Rep 19(12):155 Workshop-Conference on Gestational Diabetes
Langer O, Yogev Y, Most O, Xenakis EM (2005) Gesta- Mellitus. The Organizing Committee. Diabetes Care
tional diabetes: the consequences of not treating. Am J 21(Suppl 2):B161–B167
Obstet Gynecol 192(4):989–997 Mills JL, Jovanovic L, Knopp R, Aarons J, Conley M,
Lavin JP Jr (1985) Screening of high-risk and general Park E et al (1998) Physiological reduction in fasting
populations for gestational diabetes. Clin Appl Cost plasma glucose concentration in the first trimester of
Anal Diabetes 34(Suppl 2):24–27 normal pregnancy: the diabetes in early pregnancy
Lee KW, Ching SM, Ramachandran V, Yee A, Hoo FK, study. Metab Clin Exp 47(9):1140–1144
Chia YC et al (2018) Prevalence and risk factors of Mirghani Dirar A, Doupis J (2017) Gestational diabetes
gestational diabetes mellitus in Asia: a systematic from A to Z. World J Diabetes 8(12):489–511
review and meta-analysis. BMC Pregnancy Childbirth Moses RG, Cheung NW (2009) Point: universal screening
18(1):494 for gestational diabetes mellitus. Diabetes Care 32
(7):1349–1351
 U. Y. Sert and A. S. Ozgu-Erdinc

Moyer VA, Force USPST (2014) Screening for gestational Panel NC (2013) National Institutes of Health consensus
diabetes mellitus: U.S. Preventive Services Task Force development conference statement: diagnosing gesta-
recommendation statement. Ann Intern Med 160 tional diabetes mellitus, March 4–6, 2013. Obstet
(6):414–420 Gynecol 122(2 Pt 1):358–369
Mumtaz M (2000) Gestational diabetes mellitus. Malays J Plasencia W, Garcia R, Pereira S, Akolekar R, Nicolaides
Med Sci 7(1):4–9 KH (2011) Criteria for screening and diagnosis of
Nanda S, Savvidou M, Syngelaki A, Akolekar R, gestational diabetes mellitus in the first trimester of
Nicolaides KH (2011) Prediction of gestational diabe- pregnancy. Fetal Diagn Ther 30(2):108–115
tes mellitus by maternal factors and biomarkers at 11 to Plows JF, Stanley JL, Baker PN, Reynolds CM, Vickers
13 weeks. Prenat Diagn 31(2):135–141 MH (2018) The pathophysiology of gestational diabe-
Nankervis A MH, Moses R, Ross GP, Callaway L, tes mellitus. Int J Mol Sci 19(11):3342
Porter C, Jeffries W, Boorman C, De Vries B, Pollak A, Widness JA, Schwartz R (1979) ‘Minor
McElduff A for the Australasian Diabetes in Pregnancy Hemoglobins’: an alternative approach for evaluating
Society (2014) ADIPS consensus guidelines for the glucose control in pregnancy. Neonatology 36
testing and diagnosis of gestational diabetes mellitus (3–4):185–192
in Australia 2014. Available from: http://adips.org/ Powe CE (2017) Early pregnancy biochemical predictors
downloads/ADIPSConsensusGuidelinesGDM-03.05. of gestational diabetes mellitus. Curr Diab Rep 17
13VersionACCEPTEDFINAL.pdf (2):12
National Diabetes Data Group (1979) Classification and Rafat D, Ahmad J (2012) HbA1c in pregnancy. Diabetes
diagnosis of diabetes mellitus and other categories of Metab Syndr 6(1):59–64
glucose intolerance. Diabetes 28(12):1039–1057 Rajput R, Yogesh Y, Rajput M, Nanda S (2012) Utility of
National Institute for Health and Care Excellence (2015) HbA1c for diagnosis of gestational diabetes mellitus.
Diabetes in pregnancy: management of diabetes and its Diabetes Res Clin Pract 98(1):104–107
complications from preconception to the postnatal Rani PR, Begum J (2016) Screening and diagnosis of
period. National Institute for Health and Care Excel- gestational diabetes mellitus, where do we stand. J
lence: Clinical Guidelines, London Clin Diagn Res 10(4):QE01–QE04
Negrato CA, Montenegro RM Jr, Mattar R, Zajdenverg L, RANZCOG (2017) Diagnosis of Gestational Diabetes
Francisco RP, Pereira BG et al (2010) Dysglycemias in Mellitus (GDM) and diabetes mellitus in pregnancy.
pregnancy: from diagnosis to treatment. Brazilian con- In: RANZCOG (ed). Available from: https://ranzcog.
sensus statement. Diabetol Metab Syndr 2:27 edu.au/RANZCOG_SITE
Network SIG (2014) Management of diabetes: a national Ravnsborg T, Andersen LL, Trabjerg ND, Rasmussen
clinical guideline. Scottish Intercollegiate Guidelines LM, Jensen DM, Overgaard M (2016) First-trimester
Network, Edinburgh multimarker prediction of gestational diabetes mellitus
Nevalainen J, Sairanen M, Appelblom H, Gissler M, using targeted mass spectrometry. Diabetologia 59
Timonen S, Ryynanen M (2016) First-trimester mater- (5):970–979
nal serum amino acids and acylcarnitines are signifi- Reichelt AJ, Spichler ER, Branchtein L, Nucci LB, Franco
cant predictors of gestational diabetes. Rev Diabet Stud LJ, Schmidt MI (1998) Fasting plasma glucose is a
13(4):236–245 useful test for the detection of gestational diabetes.
O’Sullivan JB, Mahan CM (1964) Criteria for the Oral Brazilian Study of Gestational Diabetes (EBDG)
glucose tolerance test in pregnancy. Diabetes Working Group. Diabetes Care 21(8):1246–1249
13:278–285 Retnakaran R, Qi Y, Sermer M, Connelly PW, Hanley AJ,
Ozgu-Erdinc AS, Yilmaz S, Yeral MI, Seckin KD, Zinman B (2008) Glucose intolerance in pregnancy
Erkaya S, Danisman AN (2015) Prediction of gesta- and future risk of pre-diabetes or diabetes. Diabetes
tional diabetes mellitus in the first trimester: compari- Care 31(10):2026–2031
son of C-reactive protein, fasting plasma glucose, Riskin-Mashiah S, Younes G, Damti A, Auslender R
insulin and insulin sensitivity indices. J Matern Fetal (2009) First-trimester fasting hyperglycemia and
Neonatal Med 28(16):1957–1962 adverse pregnancy outcomes. Diabetes Care 32
Ozgu-Erdinc AS, Sert UY, Buyuk GN, Engin-Ustun Y (9):1639–1643
(2019a) Prevalence of gestational diabetes mellitus Ryan EA (2011) Diagnosing gestational diabetes.
and results of the screening tests at a tertiary referral Diabetologia 54(3):480–486
center: a cross-sectional study. Diabetes Metab Syndr Sacks DA, Chen W, Wolde-Tsadik G, Buchanan TA
13(1):74–77 (2003) Fasting plasma glucose test at the first prenatal
Ozgu-Erdinc AS, Sert UY, Kansu-Celik H, Moraloglu visit as a screen for gestational diabetes. Obstet
Tekin O, Engin-Ustun Y (2019b) Prediction of gesta- Gynecol 101(6):1197–1203
tional diabetes mellitus in the first trimester by fasting Savvidou M, Nelson SM, Makgoba M, Messow CM,
plasma glucose which cutoff is better? Arch Physiol Sattar N, Nicolaides K (2010) First-trimester prediction
Biochem 28(16):1–5 of gestational diabetes mellitus: examining the poten-
tial of combining maternal characteristics and labora-
tory measures. Diabetes 59(12):3017–3022
Gestational Diabetes Mellitus Screening and Diagnosis

Senanayake H, Seneviratne S, Ariyaratne H, Wijeratne S WHO (1980) WHO expert committee on diabetes
(2006) Screening for gestational diabetes mellitus in mellitus: second report. World Health Organ Tech
Southern Asian women. J Obstet Gynaecol Res 32 Rep Ser 646:1–80
(3):286–291 WHO (2014) Diagnostic criteria and classification of
Sermer M, Naylor CD, Gare DJ, Kenshole AB, Ritchie hyperglycaemia first detected in pregnancy: a World
JW, Farine D et al (1995) Impact of increasing carbo- Health Organization Guideline. Diabetes Res Clin
hydrate intolerance on maternal-fetal outcomes in 3637 Pract 103(3):341–363
women without gestational diabetes. The Toronto World Health Organization (2013) Diagnostic criteria and
Tri-Hospital Gestational Diabetes Project. Am J Obstet classification of hyperglycaemia first detected in preg-
Gynecol 173(1):146–156 nancy. WHO guidelines approved by the guidelines
Seshiah V, Das AK, Balaji V, Joshi SR, Parikh MN, Gupta review committee. World Health Organization,
S et al (2006) Gestational diabetes mellitus – Geneva
guidelines. J Assoc Physicians India 54:622–628 Yang HX (2012) Diagnostic criteria for gestational diabe-
Seshiah V, Sahay BK, Das AK, Shah S, Banerjee S, Rao tes mellitus (WS 331-2011). Chin Med J 125
PV et al (2009) Gestational diabetes mellitus – Indian (7):1212–1213
guidelines. J Indian Med Assoc 107(11):799–802, 4–6 Yang X, Quan X, Lan Y, Ye J, Wei Q, Yin X et al (2017)
Shah A, Stotland NE, Cheng YW, Ramos GA, Caughey Serum chemerin level during the first trimester of
AB (2011) The association between body mass index pregnancy and the risk of gestational diabetes mellitus.
and gestational diabetes mellitus varies by race/ethnic- Gynecol Endocrinol 33(10):770–773
ity. Am J Perinatol 28(7):515–520 Yeral MI, Ozgu-Erdinc AS, Uygur D, Seckin KD, Karsli
Shin D, Lee KW, Song WO (2015) Dietary patterns during MF, Danisman AN (2014) Prediction of gestational
pregnancy are associated with risk of gestational dia- diabetes mellitus in the first trimester, comparison of
betes mellitus. Nutrients 7(11):9369–9382 fasting plasma glucose, two-step and one-step
Sievenpiper JL, McDonald SD, Grey V, Don-Wauchope methods: a prospective randomized controlled trial.
AC (2012) Missed follow-up opportunities using a Endocrine 46(3):512–518
two-step screening approach for gestational diabetes. Yerebasmaz N, Aldemir O, As{ltürk Ş, Esinler D,
Diabetes Res Clin Pract 96(2):e43–e46 Karahanoğlu E, Kandemir Ö et al (2014) Is HbA1c
Simmons D (2017) Epidemiology of diabetes in preg- predictive for screening and diagnosis of gestational
nancy. A Practical Manual of Diabetes in pregnancy, diabetes mellitus? Gynecol Obstet Reprod Med 20
(second edition, chapter 1), pp 1–16 (2):88–91
Tu WJ, Guo M, Shi XD, Cai Y, Liu Q, Fu CW (2017) Yoffe L, Polsky A, Gilam A, Raff C, Mecacci F, Ognibene
First-trimester serum fatty acid-binding protein 4 and A et al (2019) Early diagnosis of gestational diabetes
subsequent gestational diabetes mellitus. Obstet mellitus using circulating microRNAs. Eur J
Gynecol 130(5):1011–1016 Endocrinol/European Federation of Endocrine
van Leeuwen M, Opmeer BC, Zweers EJ, van Societies 181(5):565–577
Ballegooie E, ter Brugge HG, de Valk HW et al Zhang C, Tobias DK, Chavarro JE, Bao W, Wang D, Ley
(2010) Estimating the risk of gestational diabetes SH et al (2014) Adherence to healthy lifestyle and risk
mellitus: a clinical prediction model based on patient of gestational diabetes mellitus: prospective cohort
characteristics and medical history. BJOG 117 study. BMJ 349:g5450
(1):69–75 Zhu WW, Yang HX, Wei YM, Yan J, Wang ZL, Li XL
van Leeuwen M, Louwerse MD, Opmeer BC, Limpens J, et al (2013) Evaluation of the value of fasting plasma
Serlie MJ, Reitsma JB et al (2012) Glucose challenge glucose in the first prenatal visit to diagnose gestational
test for detecting gestational diabetes mellitus: a sys- diabetes mellitus in China. Diabetes Care 36
tematic review. BJOG 119(4):393–401 (3):586–590
Wang C, Lin L, Su R, Zhu W, Wei Y, Yan J et al (2018) Zhu B, Liang C, Xia X, Huang K, Yan S, Hao J et al
Hemoglobin levels during the first trimester of preg- (2019) Iron-related factors in early pregnancy and
nancy are associated with the risk of gestational diabe- subsequent risk of gestational diabetes mellitus: the
tes mellitus, pre-eclampsia and preterm birth in Ma’anshan Birth Cohort (MABC) Study. Biol Trace
Chinese women: a retrospective study. BMC Preg- Elem Res 191(1):45–53
nancy Childbirth 18(1):263