Screening and subsequent management for gestational diabetes for improving maternal and infant health

Article (PDF Available)inCochrane database of systematic reviews (Online) 7(7):CD007222 · July 2010with22 Reads
DOI: 10.1002/14651858.CD007222.pub2 · Source: PubMed
Abstract
Gestational diabetes mellitus (GDM) is a form of diabetes that can develop during pregnancy, usually toward the end of the second trimester. Having GDM increases the risk of complications during the rest of the pregnancy. Women with GDM are more likely to develop pre-eclampsia (a combination of high blood pressure and protein in the urine) and require a caesarean section. For the baby, potential problems include the baby growing larger than it normally would, causing difficulties with birth. The baby can also have low blood sugar levels after birth. Although GDM usually resolves following birth, both mother and child are at risk of developing type 2 diabetes in the future. There is strong evidence that treatment of GDM is beneficial and improves health outcomes. It may therefore help if pregnant women are screened to identify as many as possible of those who do have GDM before they have symptoms, such as excessive thirst, frequent urination or fatigue. The two main approaches to screening approaches are 'universal' where all women undergo a screening test for GDM; and a selective approach where only those women at high risk are screened. The main risk factors are maternal age, high body mass index, family history and cigarette smoking. The different screening strategies used around the world to identify women with GDM include identifying women based on their risk factors, a blood sugar test one hour after a 50 g glucose drink, and random blood sugar measurements. It is however unclear whether screening for GDM leads to better health outcomes and if so, which screening strategy is the most appropriate. This review of four trials involving 3972 women found that there is little high-quality evidence on the effects of screening for GDM on health outcomes for mothers and their babies. Further research is required to see which recommendations for screening practices for gestational diabetes are most appropriate.
Screening and subsequent management for gestational
diabetes for improving m a ternal an d infant health (Review)
Tieu J, McPhee AJ, Crowther CA, Middleton P
This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library
2014, Issue 2
http://www.thecochranelibrary.com
Screening and subsequent management for gestational diabetes for improving maternal and infant health (Review)
Copyright © 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
T A B L E O F C O N T E N T S
1HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
6OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
6METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
10RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Figure 1. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
Figure 2. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
16DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
17AUTHORS’ CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
17ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
18REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
22CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
31DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 1.1. Comparison 1 Risk factor versus universal screening, Outcome 1 Diagnosis of gestational diabetes. . . 33
Analysis 1.2. Comparison 1 Risk factor versus universal screening, Outcome 2 Gestational age at birth. . . . . . 33
Analysis 2.1. Comparison 2 Glucose monomer versus glucose polymer, Outcome 1 Diagnosis of gestational diabetes. 34
Analysis 2.2. Comparison 2 Glucose monomer versus glucose polymer, Outcome 2 Positive screen for gestational diabetes. 34
Analysis 2.3. Comparison 2 Glucose monomer versus glucose polymer, Outcome 3 Symptoms. . . . . . . . . 35
Analysis 2.4. Comparison 2 Glucose monomer versus glucose polymer, Outcome 4 Taste. . . . . . . . . . . 37
Analysis 3.1. Comparison 3 Glucose monomer versus candy bar, Outcome 1 Diagnosis of gestational diabetes. . . 37
Analysis 3.2. Comparison 3 Glucose monomer versus candy bar, Outcome 2 Positive screen for gestational diabetes. . 38
Analysis 3.3. Comparison 3 Glucose monomer versus candy bar, Outcome 3 Taste. . . . . . . . . . . . . 38
Analysis 3.4. Comparison 3 Glucose monomer versus candy bar, Outcome 4 Symptoms. . . . . . . . . . . 39
Analysis 4.1. Comparison 4 Glucose polymer versus candy bar, Outcome 1 Diagnosis of gestational diabetes. . . . 40
Analysis 4.2. Comparison 4 Glucose polymer versus candy bar, Outcome 2 Positive screen for gestational diabetes. . 40
Analysis 4.3. Comparison 4 Glucose polymer versus candy bar, Outcome 3 Taste. . . . . . . . . . . . . 41
Analysis 4.4. Comparison 4 Glucose polymer versus candy bar, Outcome 4 Symptoms. . . . . . . . . . . . 41
Analysis 5.1. Comparison 5 Glucose versus food, Outcome 1 Positive screen for gestational diabetes. . . . . . . 43
Analysis 5.2. Comparison 5 Glucose versus food, Outcome 2 Any symptom. . . . . . . . . . . . . . . 43
43FEEDBACK . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
44WHAT’S N EW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
44HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
44CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
45DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
45SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
45DIFFERENCES BETWEEN PROTOCOL AND REVIEW . . . . . . . . . . . . . . . . . . . . .
45INDEX TERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
iScreening and subsequent management for gestational diabetes for improving maternal and infant health (Review)
Copyright © 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
[Intervention Review]
Screening and subsequent m a nagement for gestational
diabetes for improving m a ternal an d infant health
Joanna Tieu
1
, Andrew J McPhee
2
, Caroline A Crowther
1, 3
, Philippa Middleton
4
1
ARCH: Australian Research Centre for Health of Women and Babies, Robinson Research Institute, Discipline of Obstetrics and
Gynaecology, The University of Adelaide, Adelaide, Australia.
2
Neonatal Medicine, Womens and Childrens Hospital, North Adelaide,
Australia.
3
Liggins Institute, The University of Auckland, Auckland, New Zealand.
4
Womens and Childrens Research Institute, The
University of Adelaide, Adelaide, Australia
Contact address: Joanna Tieu, ARCH: Australian Research Centre for Health of Women and Babies, Robinson Research Institute,
Discipline of Obstetrics and Gynaecology, The University of Adelaide, Womens and Childrens Hospital, 1st floor, Queen Victoria
Building, 72 King William Road, Adelaide, South Australia, 5006, Australia.
joanna.tieu@gmail.com. joanna.tieu@mh.org.au.
Editorial group: Cochrane Pregnancy and Chil dbirth Group.
Publication status and date: Edited (no change to conclusions), comment added to review, published in Issue 4, 2015.
Review content assessed as up-to-date: 1 December 2013.
Citation: Tieu J, McPhee AJ, Crowther CA, Middleton P. Screening and subsequent management for gestational diabetes
for improving maternal and infant health. Cochrane Database of Systematic Reviews 2014, Issue 2. Art. No.: CD007222. DOI:
10.1002/14651858.CD007222.pub3.
Copyright © 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
A B S T R A C T
Background
Gestational diabetes mellitus (GDM) is a form of diabetes that occurs in pregnancy. Although GDM usually resolves following birth, it
is associated with significant morbidities for mother and baby both perinatally and in the long term. There is strong evidence to support
treatment for GDM. However, there is little consensus on whethe r or not screening for GDM will improve maternal and infant health
and if so, the most appropriate protocol to follow.
Objectives
To assess the effects of different methods of screening for GDM and maternal and infant outcomes.
Search methods
We search ed the Cochrane Pregnancy and Ch ildbirth Groups Trials Register (1 December 2013).
Selection criteria
Randomised and quasi-randomised trials e valuating the effects of different methods of screening for GDM.
Data co llection and analysis
Two review authors independently conducted data extraction and quality assessment. We resolved disagreements through discussion
or through a third author.
Main results
We included four trials involving 3972 women in the review. One quasi-randomised trial compared risk factor screening with universal
or routine screening by 50 g oral glucose challenge testing. Women in the universal screening group were more likely to be diagnosed
with GDM (one trial, 3152 women, risk ratio (RR) 0.44, 95% confidence inter val (CI) 0.26 to 0.75). This trial did not report on the
1Screening and subsequent management for gestational diabetes for improving maternal and infant health (Review)
Copyright © 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
other primary outcomes of the review (positive screen for GDM, mode of birth, large-for-gestational age, or macrosomia). Considering
secondary outcomes, infants of mothers in the risk factor screening group were born marginally e arlier than infants of mothers in the
routine screening group (one trial, 3152 women, mean difference (MD) -0.15 weeks, 95% CI -0.27 to -0.03).
The remaining three trials evaluated different methods of administering a 50 g glucose load. Two small trials compared glucose monomer
with glucose polymer testing, with one of these trials including a candy bar group. One trial compared a glucose solution with food. No
differences in diagnosis of GDM were found between each comparison. However, in one trial significantly more women in the glucose
monomer group screened positive for GDM than women in the candy bar group (80 women, RR 3.49, 95% CI 1.05 to 11.57). The
three trials did not report on the primary review outcomes of mode of birth , large-for-gestational age or macrosomia. Overall, women
drinking the glucose monomer experienced fewer side effects from testing than women drinking the glucose polymer (two tr ials, 151
women, RR 2.80, 95% CI 1.10 to 7.13). However, we observed substantial heterogeneity between the trials for this result (I² = 61%).
Authors conclusions
There was insufficient evidence to determine if screening for gestational diabetes, or what types of screening, can improve maternal and
infant health outcomes.
P L A I N L A N G U A G E S U M M A R Y
Screening for gestational diabetes and subsequent management for improving maternal and infant health
Gestational diabetes mellitus (GDM) is a form of diabetes that can develop during pregnancy. Having GDM increases the risk of
complications during the rest of the pregnancy for the mother and her baby. Women with GDM are more likely to develop pre-
eclampsia (high blood pressure and protein in the urine) and require a caesarean section. For the baby, potential problems include the
baby growing larger than it normally would, causing difficulties with birth. The baby can also have low blood sugar levels after birth.
Although GDM usually resolves following birth, both mother and child are at risk of developing type II diabetes in the future. There
is strong evidence that treating GDM is beneficial and improves health outcomes.
It may therefore he lp if pregnant women are screened to identify as many as possible of th ose who do have GDM before they have
symptoms, such as excessive thirst or urination, or fatigue. The two main approaches to screening are ’universal where all women
undergo a screening test for GDM; and selective’ where only those women at ’high risk are screened. The main risk factors are maternal
age, high body mass index, family history and cigarette smoking. The diffe rent screening strategies used around the world to identify
women with GDM include identifying women based on their risk factors, a blood sugar te st one hour after a 50 g glucose drink, and
random blood sugar measurements. It is however unclear whether screening for GDM leads to better health outcomes and if so, which
screening strategy is the most appropriate.
This review included four trials involving 3972 women and their babies, and found that there is little high-quality evidence on the
effects of screening for GDM on h ealth outcomes for mothers and their babies. One trial compared risk factor screening with universal
screening, and three trials evaluated different methods of administering a 50 g glucose load (the glucose load is used during the screening
test). In one trial, women who were in the universal screening group were more likely to be diagnosed with GDM compared with
women in the high-risk screening group. However, this trial was not of high quality. Fe w other differences between groups were shown
in any of the trials. Further research is required to see which recommendations for screening practices for GDM are most appropriate.
B A C K G R O U N D
Description of the condition
Gestational diabetes mellitus
Gestational diabetes mellitus (GDM) is defined as carbohydrate
intolerance of var yin g degrees of severity with onset or firs t recognition
during pregnancy (
Metzger 1998). GDM therefore includes type
2Screening and subsequent management for gestational diabetes for improving maternal and infant health (Review)
Copyright © 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
I or type II diabetes previously undetected or with first presenta-
tion during pregnancy. GDM typically resolves following birth.
However, these women are at risk for type II diabetes in the future
(
Kim 2002).
Epidemiology
GDM affects up to 14% of pregnant women ever y year and
accounts for 90% of pregnancies affected by diabetes mellitus
(
Coustan 1995; Setji 2005). There is growing concern over the
increasing prevalence of GDM and its effects for individual moth-
ers and infants and its impact on public health (
Ferrara 2007;
Hunt 2007; Metzger 2007). GDM is associated with numerous
risk factors. Maternal age and body mass index (BMI) are among
the most common risk factors (
Di Cianni 2003; O’Sullivan 1973).
Specific ethnicities are also at higher risk of developing GDM,
namely Hispanic, black, Native American, South or East Asian,
Pacific Islander and Indigenous Australian (
Kjos 2005). These eth-
nicities are similar to those at high risk of type II diabetes mellitus,
with suggestions that parallels may be drawn between these two
forms of diabetes (
Ben-Haroush 2004; Kuhl 1998). Other risk
factors include previous birth of a large baby, a family history of
diabetes mellitus, weight gain and cigarette smoking (
Davey 2001;
Di Cianni 2003; O’Sullivan 1973; Solomon 1997).
Aetiology/pathophysiology
Normally, insulin is released by pancreatic beta cells in response
to increasing blood glucose levels to achieve euglycaemia (normal
blood glucose levels). This system can be disrupted in two ways. A
problem with the release of insulin from beta cells can occur, such
as in type I or insulin de pendent diabetes mellitus. Alternatively,
insulin may not act as effectively in promoting glucose uptake.
This is known as insulin resistance, and is seen in the development
of ty pe II or non insulin dependent diabetes mellitus and GDM.
Placental hormones such as progesterone, cortisol, prolactin and
human placental lactogen released mid-pregnancy contribute to
decreased insulin action in pregnancy (
Kuhl 1998). Physiologi-
cally, this ensures sufficient nutrient transport to the fetus as it de-
velops, and promotes growth (
Setji 2005). In a normal pregnancy,
the action of the se placental hormones is adequately compensated
by increasing insulin release, creating an equilibrium between in-
sulin supply and insulin demand.
In pregnant women with abnormal glucose intolerance, the in-
sulin resistance of pregnancy is not adequately compensated for,
resulting in carbohydrate or glucose intolerance. It is suggested
that women who develop GDM may also have an underlying
insulin resistance, such as high maternal adiposity, or beta cell
dysfunction that potentiates the insulin resistance of pregnancy
(
Buchanan 2005; Kuhl 1998; Richardson 2007). Recent theo-
ries relating to the pathogenesis of GDM include inflammation
(
Richardson 2007).
These effects culminate in a disruption of the action of insulin in
maintaining glucose levels, resulting in maternal hyperglycaemia
(high blood glucose). Glucose is transferred, via the placenta, to
the fetus. Maternal hyperglycaemia therefore stimulates a fetal hy-
perinsulinaemia to counter the excess placental glucose transfer.
There is strong evidence confirming the continuum of risk as-
sociated with increasing carbohydrate intolerance (
Dodd 2007;
HAPO 2008; Sermer 1995). The point at which this increasing
carbohydrate intolerance becomes pathological remains uncertain.
Clinical features
Infant
Excess insulin due to maternal h yperglycaemia acts in two ways on
the fetus. Firstly, insulin promotes fat deposition due to the state
of nutrient excess (
Pedersen 1954; Whitelaw 1977). Secondly, in-
sulin acts as a growth factor, stimulating further growth of the in-
fant in utero (
Hunt 2007). Thus, fetal hyperinsulinaemia results in
excessive growth of the fetus, leading to one of the major perinatal
concerns in GDM, macrosomia (birthweight greater than 4000 g).
Macrosomia may lead tobirth trauma including shoulder dystocia,
nerve palsies and fractures (Dodd 2007; Metzger 1998). GDM is
associated with respiratory distress syndrome, neonatal hypogly-
caemia (low blood glucose), hyperbilirubinaemia (high bilirubin
levels), polycythaemia (excess red blood cel ls), and hypocalcaemia
(low calcium) (
ADA 2003; Metzger 1998). In utero exposure to
hyperglycaemia has long lasting effects on the infant, increasing
their risk of future obesity and type II diabetes mellitus (
Pettitt
1985
; Silverman 1998).
Maternal
With the implementation of screening protocols, GDM is usu-
ally diagnosed before it becomes symptomatic during pregnancy.
However, where GDM is undetected, the pregnant woman may
experience polyuria (increased urinary frequency), polydipsia (ex-
cessive thirst) or fatigue. Macrosomia in utero or polyhydramnios
(excess amniotic fluid volume) may also indicate GDM.
In the mother, evidence supports an association between GDM
and increased rates of caesarean delivery and pre-eclampsia
(
ACOG 2001). As with their infants, the consequences of GDM
for the mother extend beyond the perinatal period. There are
strong links between GDM and future development of type II
diabetes mellitus. Within 10 years of developing GDM, half the
women develop type II diabetes mellitus (Kim 2002).
Diagnosis of GDM
Although diagnostic criteria vary (
ACOG 2001; ADA 2003;
Berger 2002; IADPSG 2010; NICE 2008; Oats 2004;
RANZCOG 2008; WHO 1999), the oral glucose tolerance test
3Screening and subsequent management for gestational diabetes for improving maternal and infant health (Review)
Copyright © 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
(OGTT) is considered the gold standard for diagnosis of GDM
(
Scott 2002). Minor degrees of abnormal carbohydrate tolerance,
such as one abnormal value on OGTT or positive oral glucose
challenge test (OGCT) with normal OGTT are also associated
with similar outcomes to GDM. This is in line with the increasing
awareness of the continuum of risk associated with increasing car-
bohydrate intolerance (Dodd 2007; HAPO 2008; Sermer 1995).
Management of GDM
The importance of management for women with GDM has
been widely accepted and is evaluated by several Cochrane re-
views (
Alwan 2009; Boulvain 2001; Ceysens 2006) and the treat-
ment of GDM is widely supported (
ADA 2003; Crowther 2005;
Hoffman 1998; Metzger 1998; O’Sullivan 1966). Treatment fo-
cuses on reducing the hyperglycaemia driving the complications
of GDM (
Metzger 1998). In general, management includes any
or all of: nutritional therapy, exercise, blood glucose monitoring
and insulin therapy. The results from two large, multi-centred
randomised controlled trials provide strong support for the treat-
ment of women with mild GDM (
Crowther 2005; Landon 2009).
Crowther and colleagues reported reduced infant morbidity in
those treated for GDM in addition to suggesting that maternal
quality of life was improved by treatment. Landon and colleagues
showed treatment for GDM reduced the risks of fetal overgrowth,
shoulder dystocia and pre-eclampsia.
Medical nutrition therapy
The American Diabetes Association and Australasian Diabetes in
Pregnancy Society, in line with other governing bodies, recom-
mend nutrition therapy in the treatment of GDM (
ADA 2003;
ADA 2007; Hoffman 1998). Both guidelines focus on managing
carbohydrate intake for blood glucose maintenance.
Exercise
Exercise is ofte n used in conjunction with dietary therapy to main-
tain normal glucose levels. The Cochrane review Exercise in dia-
betic pregnancy found that there was insufficient evidence to make
a recommendation (
Ceysens 2006). However, there is growing
consensus on the safety of moderate exercise in pregnancy and its
benefits in the treatment of GDM.
Blood glucose monitoring
Blood glucose monitoring is often recommended (
ACOG
2001
; Hoffman 1998). Postprandial hyperglycaemia monitoring
demonstrates a closer association with rates of fetal macrosomia
and obviously correlates with peaks of blood glucose (
Hoffman
1998
). Blood glucose monitoring provides the health professional
with a representation of glycaemic control while providing th e
woman with fe edback on her management progress.
Insulin/oral hypoglycaemic agents
Where the maternal h yperglycaemia cannot be managed by di-
etary or exercise advice and blood glucose levels remain elevated,
insulin is added for greater control (
Metzger 1998). The methods
for administering insulin are discussed in the Cochrane review
’Continuous subcutaneous insulin infusion versus multiple daily in-
jections of insulin for pregnant women with diabetes (
Farrar 2007).
Oral hypoglycaemics such as glyburide (
Langer 2000) and met-
formin (
Rowan 2008) have been suggested as alternatives to in-
sulin therapy.
Birth
The Cochrane review Elective delivery in diabetic pregnant women
suggested that induction of labour at 38 to 39 weeks may be
suitable for diabetic women treated with insulin (
Boulvain 2001).
Following pregnancy
It is recommended that women whose pregnancies were affected
by GDM receive an OGTT between six and 12 weeks postpartum
to detect diabetes (
ACOG 2009; Berger 2002; Hoffman 1998;
Metzger 2007; Oats 2004; RANZCOG 2008). Because of the
high risk of future diabetes, these women are often advised to be
retested on a regular basis (
Hoffman 1998; Metzger 2007; Oats
2004; RANZCOG 2008).
Description of the intervention
Screening
A screening tool establishes the risk of disease in an otherwise well
person (
NSC 2007). Ordinarily, the presentation of symptoms
prompts testing for disease. However, screening aims to identify
the illness earlier, before symptoms arise. Identification of an illness
by screening allows for earlier management, which may result in
better health outcomes. While screening can be beneficial, it can
also cause unnecessary anxiety due to the testing process itself.
This is further complicated by the occurrence of false positives,
where screening has suggested an increased risk for the disease but
the diagnostic test does not show evidence of the disease.
An accepted screeningprocess must first meet certain criteria (
NSC
2003). In addition to the illness being an important health prob-
lem, the screening process must benefit the individual. This in-
cludes the acceptability of the screening process clinically, socially
and ethically and the availability of an effective treatment. These
benefits must outweigh any possible harms such as discomfort
from any testing and costs of administering the screening process.
Fr om an economic perspective, the screening process must also be
cost effective.
4Screening and subsequent management for gestational diabetes for improving maternal and infant health (Review)
Copyright © 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Screening does not always involve a clinical test, and may include,
for example, a series of history questions. Furthermore, it is im-
portant to distinguish screening from diagnostic procedures which
provide a diagnosis in an already symptomatic or high-risk indi-
vidual. It is important to distinguish between a screening and di-
agnostic test. While a screening test will identify those at risk for
a disease, diagnostic tests are generally designed to give a defini-
tive yes or no. Diagnostic tests are also often more complex and
expensive than screening tests.
While screening tools will identify those at risk of an illness, it is
the subsequent management of the result that ultimately affects
health outcomes. ’Screening can be used to refer to an individual
screening tool or to a screening program, protocol or guideline,
which includes the screening tool and subsequent management
such as diagnostic testing and treatment of any illness identified.
By identifying individuals at high and low risk of a particular ill-
ness, a screening tool therefore identifies those who require diag-
nostic testing and those who do not. It therefore follows that the
implementation of a screening program, which includes a combi-
nation of screening tool, subsequent diagnostic testing and man-
agement, is able to affect health outcome.
Screening for GDM
Whether to screen for GDM, and which methods to use, remain
controversial. This is compounded by the lack of clearly defined,
universally accepted screening criteria, and the uncertainty as to
the severity of glucose intolerance at which treatment is beneficial.
Even with screening protocols in place, GDM is diagnosed at the
end of th e second trimester or early third trimester based on phys-
iology. This leaves little time for management of GDM. Without
screening, the diagnosis of GDM, and therefore treatment, is po-
tentially delayed.
Screening for GDM is ofte n implemented de spite the uncertainty
of its utility. A wide variety of strategies h ave been employed in
screening for GDM that provide varying degrees of sensitivity and
specificity. Universal or routine screening, usually where all women
are offered a 50 g OGCT, and risk factor screening (by womens
history) are the most commonly used methods and combinations
of these and other methods have been used to form various screen-
ing protocols (
ACOG 2001; Gabbe 2004; Metzger 2007; Mires
1999
; Rumbold 2001).
The OGCT was originally proposed by O’Sullivan and colleagues
to provide a more sensitive screening process than risk factor
screening (
O’Sullivan 1973). An OGCT involves a 50 g glucose
drink and a blood glucose measurement after one hour. While
the predefined risk factors used vary between centres and coun-
tries, they commonly include maternal age, BMI, ethnicity, pre-
vious GDM and family history of diabetes mellitus (
ADA 2003;
Berger 2002; Hoffman 1998; Metzger 2007; USPSTF 2008).
Other methods used to screen for GDM include urine testing
for glucosuria, fructosamine testing, random plasma glucose me a-
surements, fasting plasma glucose measurements and HbA
1
c (a
measure of how well blood glucose has been controlled over the
previous two to th ree months) (
Scott 2002).
The variation in screening protocols is reflected in surveys con-
ducted around the world. In a UK survey of obstetric units in 1996,
it was found that 89% screened for GDM, with 81% of those units
using risk factor based screening (
Mires 1999). There was a lack
of consensus on the appropriate screening method (
Mires 1999).
In a similar Australian survey of obstetric practice conducted in
1999, it was found that 87% of the obstetric population was being
screened for GDM. Again there was no strong consensus on how
to screen (Rumbold 2001). An American survey in 2004 found
that 95.2% of obstetricians screening for GDM adopted a uni-
versal one-hour 50 g OGCT (
Gabbe 2004). This diversity in pre-
ferred screening protocols may reflect a number of factors, such as
the cost of screening, the expected prevalence of GDM and test
accuracy, in addition to the lack of definitive evidence in favour
of a particular screening protocol.
A largely accepted time for screening is the end of the second
trimester, ranging between 24 to 28 weeks gestation (
ACOG
2001
; Hoffman 1998; Metzger 2007; Oats 2004; RANZCOG
2008
). This value reflects a balance between having adequate time
to manage GDM and the ability to detect the development of
carbohydrate intolerance (
ACOG 2001; Brody 2003). There is
little evidence on the benefits and detriments of screening prior to
24 weeks gestation (
USPSTF 2008).
The negative impact of screeningfor GDM also needs to be consid-
ered. The importance of identification of GDM should be weighed
against any discomfort experienced by the woman and anxiety
from testing. While the 50 g OGCT is considered to be a quick
and simple test, it is unpleasant to drink and is associated with side
effects such as dizziness, headaches, nausea and vomiting, and re-
quires a blood test. For many women, the inconvenience of testing
can be significant. Screening by any meth od can create anxiety for
the mother, including women identified as having risk factors for
GDM, those identified through routine OGCT and those with
elevated random blood glucose levels. In particular, a false positive
result has bee n associated with a decline in womens perception of
health (
Kerbel 1997; Rumbold 2002). It also follows that with the
introduction of screening, that more women are offered diagnostic
testing, usually an OGTT, which requires them to fast overnight,
drink a higher glucose load, requires more blood tests and can take
up to three hours to complete.
An evaluation of cost is imperative with any screening procedure.
While screening processes may affect detection, management and
therefore improve maternal and infant health, this must also be
weighed against the cost of screening all pregnant women, any
subsequent diagnostic tests and treatment for additional women
diagnosed with GDM.
Why it is important to do this review
5Screening and subsequent management for gestational diabetes for improving maternal and infant health (Review)
Copyright © 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Many believe that the incidence of GDM, the adverse outcomes
arising from GDM and the benefits of treatment suggest a need for
some screening process. However, high-quality evidence demon-
strating the effectiveness of screening on detection of GDM and
subsequent maternal and infant health is required for screening to
be implemented (
NSC 2003). Whether a screening protocol ade-
quately identifies those at risk of GDM, and whether this knowl-
edge improves the he alth outcomes for women with GDM and
their babies through subsequent management of a screening result,
are important factors to consider when recommending a screening
process. It is also equally important that a recommended screening
protocol does not harm women without GDM. Moreover, given
the lack of consensus on a method for screening, an evaluation of
the different screening protocols on the detection of GDM and
subsequent maternal and infant health is required.
This review updates a previously published Cochrane review on
screening and subsequent management for GDM for improving
maternal and infant health (
Tieu 2010). The previous review in-
cluded four randomised trials and found that there was insuffi-
cient e vidence to determine if screening for GDM, or what types
of screening, can improve maternal and infant h ealth outcomes;
and concluded that high-quality, large trials are required in this
area.
This review update therefore aims to evaluate the current evidence
regarding the effects of screening for GDM as an intervention on
maternal and infant health. The evaluation of test performance of
individual screening methods is not included in the scope of th is
review. The strategies for diagnosis of GDM have been evaluated
in a separate Cochrane review ’Alternative strategies for glucose tol-
erance testing to diagnose gestational diabetes and impaired glucose
tolerance during pregnancy (
Farrar 2011). The Cochrane review
’Treatments for gestational diabetes (
Alwan 2009) assesses manage-
ment after diagnosis of GDM or impaired glucose tolerance and
therefore is looking at a later stage in the pathways of care and
management than this review which addresses the process from
screening onwards
O B J E C T I V E S
To assess the effects of different methods of screening for gesta-
tional diabetes mellitus on maternal and infant outcomes.
M E T H O D S
Criteria for considering studies for t his review
Types o f studies
Randomised controlled trials, quasi-randomised controlled trials
and cluster-randomised trials. We planned to exclude cross-over
trials. We planned to include studies published as abstracts pro-
vided there was sufficient information to allow us to assess study
eligibility and risk of bias. If sufficient information was not avail-
able, the study would await assessment pending the publication
of the full trial report, or the provision of further information by
trial authors.
Types o f participants
Pregnant women, excluding women who have already been di-
agnosed with GDM in this pregnancy or who have pre-existing
diabetes mellitus.
Types o f interventions
Any individual screening tool or screening program, protocol or
guideline for GDM compared with the absence of screening; or
any individual screening tool or screening program, protocol or
guideline for GDM with another.
Types o f outcome measures
Primary outcomes
Maternal
Perinatal
1. Diagnosis of GDM*;
2. positive screen for GDM*;
3. mode of birth (normal vaginal birth, operative vaginal
birth, caesarean section).
Offspring
Neonatal
1. Large-for-gestational age (birthweight greater than or equal
to 90th percentile);
2. macrosomia (greater than 4000 g or greater than 4500 g).
* as defined by author(s)
6Screening and subsequent management for gestational diabetes for improving maternal and infant health (Review)
Copyright © 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Secondary outcom es
Maternal
Perinatal
1. Pre-eclampsia;
2. induction of labour;
3. perineal trauma;
4. weight gain in pregnancy;
5. augmentation of labour;
6. insulin or oral hypoglycaemic agent required to treat GDM;
7. women who screen positive and are not subsequently
diagnosed with GDM;
8. placental abruption;
9. postpartum haemorrhage*;
10. postpartum infection*;
11. womens sense of well-being and quality of life*.
Long term
1. Development of type II diabetes mellitus;
2. GDM in subsequent pregnancy;
3. development of type I diabetes mellitus;
4. impaired glucose tolerance*;
5. insulin sensitivity*;
6. body mass index (BMI);
7. BMI greater than 25;
8. BMI greater than 30;
9. womens se nse of well-being and quality of life*.
Offspring
Neonatal
1. Stillbirths;
2. death of l iveborn infants prior to hospital discharge;
3. infant death (up to one year of life);
4. shoulder dystocia;
5. bone fractures;
6. nerve palsy;
7. birthweight;
8. birth centile;
9. ponderal index;
10. gestational age at birth;
11. preterm birth (less th an 37 weeks gestation);
12. respiratory distress syndrome;
13. hypoglycaemia requiring treatment;
14. hyperbilirubinaemia requiring treatment;
15. five minute Apgar score less than seven;
16. five minute Apgar score less than four.
Childhood
1. BMI;
2. BMI greater than 25;
3. BMI greater than 30;
4. weight;
5. height;
6. fat mass/fat-free mass;
7. skinfold thickness measurements;
8. blood pressure;
9. impaired glucose tolerance*;
10. type I diabetes;
11. type II diabetes;
12. insulin sensitivity*;
13. dyslipidaemia.
Adulthood
1. BMI;
2. BMI greater than 25;
3. BMI greater than 30;
4. weight;
5. height;
6. fat mass/fat-free mass;
7. skinfold thickness measurements;
8. blood pressure;
9. impaired glucose tolerance*;
10. type I diabetes;
11. type II diabetes;
12. insulin sensitivity*;
13. dyslipidaemia;
14. educational achievement.
Acceptability of testing
1. Adverse effects of testing (e.g. nausea, vomiting);
2. womens acceptance of screening protocol*.
Costs
1. Cost of screening each woman;
2. number of hospital visits/antenatal visits for mother;
3. dietitian visits;
4. medical physician visits;
5. length of postnatal stay (mother);
6. length of postnatal stay (baby);
7. cost of maternal care;
7Screening and subsequent management for gestational diabetes for improving maternal and infant health (Review)
Copyright © 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
8. cost of offspring care.
* as defined by author(s)
Search meth ods for identification of studies
Electronic searches
We contacted the Trials Search Co-ordinator to search the
Cochrane Pregnancy and Childbirth Groups Trials Register (1
December 2013).
The Cochrane Pregnancy and Childbirth Groups Trials Register
is maintained by the Trials Search Co-ordinator and contains trials
identified from:
1. quarterly searches of the Cochrane Central Register of
Controlled Trials (CENTRAL);
2. weekly searches of MEDLINE;
3. weekly searches of Embase;
4. handsearches of 30 journals and the proceedings of major
conferences;
5. weekly current awareness ale rts for a further 44 journals
plus monthly BioMed Central email alerts.
Details of the search strategies for CENTRAL, MEDLINE and
Embase, the list of handsearched journals and conference pro-
ceedings, and the list of journals reviewed via the current aware-
ness service can be found in the ‘Specialized Register’ section
within the editorial information about the
Cochrane Pregnancy
and Childbir th Group
.
Trials identified through the searching activities described above
are each assigned to a review topic (or topics). The Tr ials Search
Co-ordinator searches the register for each review using the topic
list rather than keywords.
We did not apply any language restrictions.
Data collection and analysis
For methods used in the previous version, please see
Tieu 2010.
For this update, the following methods were used.
Selection of studies
Two review authors independently assessed for inclusion all the
potential studies we identified as a result of the search strategy. We
resolved any disagreement through discussion or, if required, we
consulted a third review author.
Data extraction and management
We designed a form to extract data. For eligible studies, two re-
view authors extracted the data using the agreed form. We resolved
discrepancies through discussion or, if required, we consulted a
third review author. We entered data into Review Manager soft-
ware (
RevMan 2012) and checked for accuracy.
When information regarding any of the above was unclear, we
attempted to contact authors of the original reports to provide
further details.
Assessment of risk of bias in included studies
Two review authors independently assessed risk of bias for each
study using the criteria outlined in the Cochrane Handbook for
Systematic Reviews of Interventions (
Higgins 2011). We resolved
any disagreement by discussion or by involving a third author.
(1) Random sequence generation (checking for possible
selection bias)
We described for each included study the methods used to generate
the allocation sequence in sufficient detail to allow an assessment
of whe ther it should produce comparable groups.
We assessed the methods as:
low risk of bias (any truly random process, e.g. random
number table; computer random number generator);
high risk of bias (any non-random process, e.g. odd or even
date of birth; hospital or clinic record number);
unclear risk of bias.
(2) Allocation concealment (checking for possible selection
bias)
We described f or e ach included study the method used to conceal
the allocation sequence and determined whether intervention al-
location could have been foreseen in advance of, or during recruit-
ment, or changed after assignment.
We assessed the methods as:
low risk of bias (e.g. tel ephone or central randomisation;
consecutively numbered sealed opaque envelopes);
high risk of bias (open random allocation; unsealed or non-
opaque envelopes, alternation; date of bir th);
unclear risk of bias.
(3.1) Blinding of participants and personnel (checking for
possible performance bias)
We described for each included study, the methods, if any, used to
blind study participants and personnel from knowledge of which
intervention a participant received. We considered studies to be
at a low r isk of bias if th ey were blinded, or if we judged that the
lack of blinding would be unlikely to affect results. We assessed
blinding separately for different outcomes or classes of outcomes.
We assessed the methods as:
low, high or unclear risk of bias for participants;
low, high or unclear risk of bias for personnel.
8Screening and subsequent management for gestational diabetes for improving maternal and infant health (Review)
Copyright © 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
(3.2) Blinding of outcome assessment (checking for possible
detection bias)
We described f or each included study the methods used, if any, to
blind outcome assessors fr om knowledge of which intervention a
participant received. We assessed blinding separately for different
outcomes or classes of outcomes.
We assessed methods used to blind outcome assessment as:
low, high or unclear risk of bias.
(4) Incomplete outcome data (checking for possible attrition
bias due to the amount, nature and handling of incomplete
outcome data)
We described for each included study and for each outcome or
class of outcomes, the completeness of data including attrition
and exclusions from the analysis. We stated whether attrition and
exclusions were reported, the numbers included in the analysis at
each stage (compared with the total randomised participants), rea-
sons f or attrition or exclusion where reported, and whether miss-
ing data were balanced across groups or were related to outcomes.
Where sufficient information was reported or was supplied by the
trial authors, we included missing data in the analyses which we
undertook.
We assessed the methods as:
low risk of bias (e.g. where there were no missing data or
where reasons for missing data were balanced across groups);
high risk of bias (e.g. numbers or reasons for missing data
imbalanced across groups; ’as treated’ analysis done with
substantial departure of intervention received fr om that assigned
at randomisation);
unclear risk of bias.
(5) Sele ctive reporting bias (checking for reporting bias)
We described for each included study how the possibility of se-
lective outcome reporting bias was examined by us and what we
found.
We assessed the methods as:
low risk of bias (where it was clear that all of the study’s pre-
specified outcomes and all expected outcomes of interest to the
review had been reported);
high risk of bias (where not all the studys pre-specified
outcomes had been reported; one or more reported primary
outcomes were not pre-specified; outcomes of interest were
reported incompletely and so could not be used; study failed to
include results of a key outcome that would have been expected
to have been reported);
unclear risk of bias.
(6) Other sources of bias (checking for bias due to problems
not covered by (1) to (5) above)
We described for each included study any important concerns we
had about othe r possible sources of bias. We assessed whether each
study was free of other problems that could put it at risk of bias:
low risk of other bias;
high risk of other bias;
unclear whether there is risk of other bias.
(7) Overall risk of bias
We made explicit judgements about whether studies were at a
high risk of bias, according to the criteria given in the Cochrane
Handbook for Systematic Reviews of Interventions (
Higgins 2011).
With reference to (1) to (6) above, we assessed the likely magnitude
and direction of the bias and whether we considered it is likely
to impact on the findings. We planned to explore the impact of
the level of bias through undertaking se nsitivity analyses - see
Sensitivity analysis.
Measures of treatment effect
Dichotomous data
For dichotomous data, we presented results as risk ratio with 95%
confidence intervals.
Continuous data
For continuous data, we used the mean difference when outcomes
were measured in the same way between trials. If necessary, we
would have used the standardised mean difference to combine
trials that measured the same outcome, but used different methods.
Unit of analysis issues
Cluster-randomised trials
We planned to include cluster-randomised trials in the analyses
along with individually-randomised trials. We planned to adjust
their sample sizes using the methods described in the Handbook
using an estimate of the intracluster correlation co-efficient (ICC)
derived from the trial (if possible), from a similar trial or from a
study of a similar population. If we had used ICCs from other
sources, we planned to report this and conduct sensitivity analyses
to investigate the effect of variation in the ICC. If we had identified
both cluster-randomised trials and individually-randomised tri-
als, we planned to synthesise the relevant information. We would
have considered it reasonable to combine the results from both if
there was little heterogeneity between the study designs and the
interaction between the effect of intervention and the choice of
randomisation unit was considered to be unlikely.
9Screening and subsequent management for gestational diabetes for improving maternal and infant health (Review)
Copyright © 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
We planned to also acknowledge heterogeneity in the randomisa-
tion unit and perform a sensitivity analysis to investigate the ef-
fects of the randomisation unit.
Cross-over trials
We considered cross-over trials inappropriate for this research
question.
Dealing with missing data
For included studies, we noted levels of attrition. We planned to
explore the impact of including studies with high levels of missing
data in the overall assessment of treatment eff ect by using sensi-
tivity analysis.
For all outcomes, we carried out analyses, as far as possible, on
an intention-to-treat basis, i.e. we attempted to include all partic-
ipants randomised to each group in the analyses, and all partici-
pants were analysed in th e group to which th ey were allocated, re-
gardless of whether or not they received the allocated intervention.
The denominator for each outcome in each trial was the number
randomised minus any participants whose outcomes were known
to be missing.
Assessment of heterogeneity
We assessed statistical heterogeneity in each meta-analysis using
the Tau², and Chi² statistics. We regarded he terogeneity as sub-
stantial where the was greater than 30% and either the Tau² was
greater than zero, or there was a low P value (less than 0.10) in the
Chi² test for heterogeneity.
Assessment of reporting biases
In future updates of this review, if there are 10 or more studies
in the meta-analysis, we will investigate reporting biases (such as
publication bias) using funnel plots. We will assess funnel plot
asymmetry visually. If asymmetry is suggested by a visual assess-
ment, we will perform exploratory analyses to investigate it.
Data synthesis
We carried out statistical analysis using the Review Manager soft-
ware (
RevMan 2011). We used fixed-effect meta-analysis for com-
bining data where it was reasonable to assume that studies were
estimating the same underlying treatment effect: i.e. where tri-
als were e xamining the same intervention, and the trials popula-
tions and methods were judged sufficiently similar. Where there
was clinical heterogeneity sufficient to expect that the underlying
treatment effects differed between trials, or where substantial sta-
tistical heterogeneity was detected, we used random-effects meta-
analysis to produce an overall summary, if an average treatment
effect across trials was considered clinically meaningful. The ran-
dom-effects summary was treated as the average range of possible
treatment effects and we have discussed the clinical implications of
treatment effects differing between trials. If the average treatment
effect was not clinically meaningful, we would not have combined
trials.
Where we have used random-effects analyses, we have presented
the results as the average treatment effect with its 95% confidence
interval, and the estimates of Tau² and
Subgroup analysis and investigation of heterogeneity
If we had identified substantial h eterogeneity, we planned to in-
vestigate it using subgroup analyses and sensitivity analyses. We
planned to consider whether an overall summary was meaningful,
and if it was, use random-effects analysis to produce it.
We planned an assessment of trials comparing any screening proto-
col with none, with data analysed separately for different methods
of screening. We analysed trials comparing one method of screen-
ing with another, with data from different comparisons analysed
separately.
We planned to carry out the following subgroup analyses for pri-
mary outcomes:
high risk f or GDM (variously defined) (we will explore risk
factors individually if sufficient data become available);
gestational age at screening (less than 24 weeks, 24 to 30
weeks, 30 weeks or more);
number of stages in the screening protocol;
type of management protocol.
There were insufficient data to conduct subgroup analyses.
We planned to assess subgroup differences by interaction tests
available in within RevMan (
RevMan 2012). We planned to report
the results of the subgroup analysis quoting the Chi² statistic and
P value, and the interaction test value.
Sensitivity an alysis
We planned to carry out se nsitivity analysis to explore the effect
of trial quality assessed by concealment of allocation, by excluding
studies with clearly inadequate allocation of concealment (rated
high risk of bias).
We planned to then carry out sensitivity analysis to explore the
effect of trial quality on primary outcomes. This would have in-
volved analysis based on an assessment of selection bias and at-
trition bias. We planned to exclude studies of poor quality in the
analysis (those rating unclear or high risk) in order to assess for
any substantive difference in the overall result.
There were insufficient data to conduct sensitivity analyses.
R E S U L T S
10Screening and s ubs equent management for gestational diabetes for improving maternal and infant health (Review)
Copyright © 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Description of studies
Results of the search
The updated search of the Cochrane Pregnancy and Childbirth
Groups Trials Register identified three studies (one which was
awaiting assessment in the previous version of this review). We
have excluded the three studies, and have therefore not included
any new trials in this update.
In the previous version of this review, the search identified 31 trials
to be considered for inclusion. Following application of eligibility
criteria, we included four of these trials in this review (Bergus
1992
; Griffin 2000; Martinez Collado 2003; Murphy 1994); we
excluded 25, and one remains awaiting classification (
Bebbington
1999
).
Included studies
One quasi-randomised study compared the ef fect of screening by
risk factors and universal (routine) screening by a 50 g oral glucose
challenge test (OGCT) on health outcomes (Griffin 2000). Three
studies compared screening by different glucose loading methods
(
Bergus 1992; Martinez Collado 2003; Murphy 1994). Of the
four studies,
Griffin 2000 was the largest study with 3742 women
enrolled in the study.
Murphy 1994 recruited 124 women, Bergus
1992
enrolled 76 women into the study and Martinez Collado
2003 included 30 women.
Participants
All studies included pregnant women in Western societies.
Bergus
1992
and Murphy 1994 were conducted in the United States,
while Griffin 2000 took place in Ireland and Martinez Collado
2003
recruited women in Mexico. In all studies, women were re-
cruited from obstetric clinics. Gestational age at entry was spec-
ified in
Bergus 1992 and Martinez Collado 2003, where women
were between 24 and 28 weeks gestation.
Murphy 1994 screened
women routinely at 24 to 28 weeks’ gestation and also screened
women at their first antenatal visit if they were found to have one
of the following risk factors for GDM: past history of glucose in-
tolerance, first-degree relative with diabetes mel litus, age greater
than 35 years, previous baby with macrosomia, habitual abortion,
unexplained stillbirth, congenital anomalies, current pregnancy
with glycosuria, hypertension, suspected large-for-gestational-age
fetus, polyhydramnios or obesity.
Martinez Collado 2003 included
women with a high-risk pregnancy, although a description of
’high risk’ was not reported. This trial excluded women with dia-
betes, previously diagnosed GDM and those treated with steroids
or tocolytics. No other exclusion criter ia were listed for the studies.
Baseline characteristics of the participants by treatment group were
compared in two studies (
Griffin 2000; Murphy 1994). In Murphy
1994
, there was an imbalance in age and parity at screening with
participants in the candy bar group being younger and having
a lower parity than those in the d-glucose group. No baseline
imbalances were reported between women in the candy bar group
and the polymer group. Participants in the risk factor group and
universal group in
Griffin 2000 were similar with respect to age,
weight at 36 weeks, BMI, gestational age at delivery, parity and
prevalence of risk factors for GDM.
Interventions
Risk factor versus universal (routine) screening
Griffin 2000 compared risk factor screening with universal (rou-
tine) screening. Participants in the risk factor group of
Griffin
2000
were screened on the basis of historical and current risk fac-
tors, including having a first-degree relative with diabetes melli-
tus, weighing more than 100 kg in the current pregnancy, having
a previous baby greater than 4.5 kg, previous unexplained still-
birth or intrauterine death, previous major malformation, previ-
ous GDM, glycosuria in second fasting urine sample, macrosomia
in the current pregnancy and polyhydramnios in the current preg-
nancy. Women received glucose testing by a 100 g oral glucose tol-
erance test (OGTT) at 32 weeks’ gestation where they were found
to have any of the risk factors listed.
The universal screening group used a 50 g OGCT at 26 to 28
weeks gestation. A one-hour plasma glucose of greater than or
equal to 7.8 mmol/L was considered positive. A positive screening
test was an indication for a full 100 g OGTT using the National
Diabetes Data Group criteria for diagnosis. The 50 g O GCT was
repeated in those with a negative OGCT and with risk factors for
GDM four to six weeks after the initial O GCT.
Women who were diagnosed with GDM were treated by stan-
dard diabetes management, maintaining otherwise similar antena-
tal care for both groups.
Griffin 2000 referred women for obstetric
and endocrinology review fortnightly and weekly after 36 weeks
gestation, with treatment including diabetic diet and insulin as
required.
Glucose method
Bergus 1992, Martinez Collado 2003 and Murphy 1994 com-
pared different methods of glucose loading as screening tests for
GDM. Both
Bergus 1992 and Murph y 1994 assessed solutions of
glucose monomer (d-glucose) and glucose polymer. Murphy 1994
included an additional group where participants ate 50 g choco-
late bars in place of a glucose drink. In both studies, all women
underwent a glucose toler ance test within three to seven days of
their 50 g challenge test. Both used a 100 g OGT T by O’Sullivan
criteria to diagnose GDM.
Martinez Collado 2003 compared a 50
g glucose solution with a food mix, w hich included 50 g of glucose,
and did not report on further testing to diagnose GDM. It is not
11Screening and s ubs equent management for gestational diabetes for improving maternal and infant health (Review)
Copyright © 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
reported whethe r the glucose solution was a glucose monomer or
polymer.
Outcomes
Griffin 2000 reported clinical measures of maternal health out-
come and infant health outcome and size.
Bergus 1992, Martinez
Collado 2003
and Murphy 1994 focused primarily on the effi-
ciency of the methods by which glucose was administered, report-
ing on diagnosis of GDM, glucose levels following testing and
the adverse effects of the different me thods.
Murphy 1994 re-
ported side effects only where they were rated moderate to severe
by women on a five-point scale.
Excluded studies
Eighteen studies identified by the literature search assessed strate-
gies for diagnosis of GDM rather than screening (
Berkus 1995;
Brustman 1995; Buhling 2004; Cheng 1992; Court 1984; Court
1985
; Duenas-Garcia 2011; Fung 1993; Harlass 1991; Jones
1993
; Meltzer 2010; Olarinoye 2004; Saijan 2011; Sammarco
1993
; Soonthornpun 2003; Stavrianos 2004; Weiss 1998; Zhang
1995
). One study was not randomised (Dornhorst 2000). Seven
of the trials identified were cross-over studies (
Eslamian 2007;
Eslamian 2008; Helton 1989; Hidar 2001; Lamar 1999a; Lamar
1999b
; Soonthornpun 2008) and two studies included women
who had already undergone diagnostic testing for GDM (
Kjos
2001
; Lewis 1993).
Risk of bias in included studies
Please see
Figure 1 and Figure 2 for summaries of all ’Risk of bias
assessments.
Figure 1. Methodological quality graph: review authors’ judgements about each method ological quality
item presented as percentages across all included studies.
12Screening and s ubs equent management for gestational diabetes for improving maternal and infant health (Review)
Copyright © 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Figure 2. Methodological quality summary: review author s’ judgements about each methodological quality
item for each included study.
13Screening and s ubs equent management for gestational diabetes for improving maternal and infant health (Review)
Copyright © 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Allocation
The generation of randomisation sequence was specified only by
Bergus 1992. Bergus 1992 used consecutive numbers from a ran-
dom number table to allocate participants to study group while
Griffin 2000 was quasi-randomised, allocating women to study
group by the day of their clinic visit. While reported as randomised
controlled trials,
Martinez Collado 2003 and Murphy 1994 did
not specify the method of allocation of participants.
None of the studies reported allocation concealment.
Blinding
Bergus 1992 describes a double-blind design’, but did not specifi-
cally state who was blinded.
Griffin 2000, Martinez Collado 2003
and Murphy 1994 did not report on blinding of participants, clin-
icians or outcome assessors.
Incomplete outcome data
Ten out of 76 women (13%) did not complete the symptom ques-
tionnaire in
Bergus 1992 and it is reported that their baseline char-
acteristics were comparable to those who were followed up. Griffin
2000
reported that 590, or 31%, of the women in the universal
screening group did not consent to glucose challenge testing and
were excluded from analysis. No participants in the risk factor
screening group were lost to follow-up. Routine care in this centre
was risk factor screening, which contributes to the differential loss
to follow-up rate. There were no significant differences between
those who consented to glucose challenge testing and those who
did not in
Griffin 2000. Sixteen women in Murphy 1994 were lost
to follow-up. However, no comparison of baseline characteristics
of those lost to follow-up and those who remained in the study
was made and it is unclear which groups these women were fr om.
It is al so uncertain as to how many women in
Murphy 1994 were
being screened in their first trimester or at 24 to 28 weeks gesta-
tion.
Selective reporting
Outcome data in
Griffin 2000 was analysed primarily by GDM
diagnosis rather than by original group allocation by day of visit,
which affects the ability to interpret results of pre-specified out-
comes. Although a comparison of baseline characteristics between
women who were able or unable to complete the symptom ques-
tionnaire was made,
Bergus 1992 did not report the baseline char-
acteristics of participants by inter vention group.
Murphy 1994
only reported side effects of testing where women had rated the ir
symptoms as moderate or severe, equivalent to a three to five out
of a possible five. Mild symptoms were unreported.
Other potential sources of bias
Analysis of
Griffin 2000 was based on diagnosis of GDM rather
than original group allocation by day of visit. Because no baseline
comparison of the intervention groups was made in
Bergus 1992
and Martinez Collado 2003, it is uncertain whether or not baseline
imbalances are present.
Overall risk of bias
In general, assessment of the included studies for methodological
quality revealed a moderate to high risk of bias, which is likely
to have affected the results of the review (
Figure 1; Figure 2) by
making the results of trials less certain. Most studies were unclear
or did not adequately report on sequence generation, allocation
concealment and blinding. Missing data affected the assessment of
incomplete outcome data, and selective reporting and other biases
were also likely.
Effects of interventions
We included four studies (
Bergus 1992; Griffin 2000; Martinez
Collado 2003
; Murphy 1994), with data available from 3382 of
the 3972 women randomised. One study compared risk factor
screening with routine screening (
Griffin 2000) and three trials
compared the method of glucose administration at screening (
Bergus 1992; Martinez Collado 2003; Murphy 1994).
Risk factor versus routine screening
Primary outcomes
Significantly more women were diagnosed with GDM in the uni-
versal screening group than in the risk factor screening group
(
Griffin 2000). Thirty-five women were diagnosed with GDM in
the routine screening group compared with 22 in the risk factor
group (one trial, 3152 women, risk ratio (RR) 0.44, 95% confi-
dence interval (CI) 0.26 to 0.75) (
Analysis 1.1).
The
Griffin 2000 tr ial did not report on the other primary out-
comes including: positive screen for GDM, mode of birth, large-
for-gestational age and macrosomia.
Secondary outcom es
Infants of mothers in the risk factor screening group were born
significantly earlier than infants of mothers in the routine screening
group (one trial, 3152 women, mean difference (MD) -0.15 weeks,
95% CI -0.27 to -0.03) (
Analysis 1.2).
The remaining data from this trial were reported according to
diagnosis of GDM and we have been in correspondence with th e
14Screening and s ubs equent management for gestational diabetes for improving maternal and infant health (Review)
Copyright © 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
authors of this paper for additional data. Therefore, we have not
been able to report data on any of the reviews other secondary
outcomes f rom this trial.
Glucose monomer versus glucose po lymer
Primary outcomes
Two studies,
Bergus 1992 and Murph y 1994, compared a glucose
monomer (d-glucose) with a glucose polymer drink for screening
for GDM.
No women were diagnosed with GDM in either group in
Bergus
1992
. Three women in the glucose monomer group and two
women in the glucose polymer group were diagnosed with GDM
in
Murphy 1994. There was no significant difference in GDM di-
agnosis between groups overall (two trials, 161 women, RR 1.61,
95% CI 0.28 to 9.15) (
Analysis 2.1). Numbers of women screen-
ing positive also showed no significant differences between groups
in one trial (85 women, RR 2.36, 95% CI 0.90 to 6.21) (
Analysis
2.2).
These trials did not report on the other primary outcomes includ-
ing: mode of birth, large-for-gestational age and macrosomia.
Secondary outcom es
Both trials reported a number of side effects from the method
of glucose administration. Although not pre-specified, any symp-
tom, sick, tired, taste and bloating were included as me asures of
acceptability of testing. Women in the glucose monomer group
were significantly more likely to experience ’any symptom than
those in the glucose poly mer group (two trials, 151 women, RR
2.80, 95% CI 1.10 to 7.13). There was significant heterogeneity
in this result, with an value of 61%, and thus a random-effects
meta-analysis was used (
Analysis 2.3). Nausea was experienced sig-
nificantly more often by women in the glucose monomer group
than glucose polymer (two tr ials, 151 women, RR 2.62, 95% CI
1.01 to 6.79). No statistically significant differences were found
for all other measures of acceptability of testing, including: dizzi-
ness and abdominal discomfort (both trials); bloating (Murphy
1994
); headache, vomiting, sickness and tiredness (Bergus 1992);
or taste (
Murphy 1994) (Analysis 2.4).
Neither study reported on additional maternal or infant secondary
review outcomes.
Glucose monomer versus candy bar
Primary outcomes
Murphy 1994 included a third group of women, who consumed a
chocolate bar as an alternative to the two types of glucose drinks.
There was no significant difference in diagnosis of GDM between
the candy bar and glucose monomer groups, with three women
diagnosed with GDM in the glucose monomer group, compared
with none in the candy bar group (one trial, 80 women, RR 6.67,
95% CI 0.36 to 125.02) (
Analysis 3.1). However, significantly
more women in the monomer group screened positive for GDM
(RR 3.49, 95% CI 1.05 to 11.57) (
Analysis 3.2).
This trial did not report on the other primary outcomes including:
mode of birth, large-for-gestational age and macrosomia.
Secondary outcom es
The candy bar was given the highest rating for taste significantly
more often than glucose monomer (one trial, 80 women, RR 0.35,
95% CI 0.17 to 0.74) (
Analysis 3.3). No significant differences
were seen overall (RR 1.90, 95% CI 0.97 to 3.72) or for each
individual symptom of dizziness, nausea, abdominal discomfort
and bloating (
Analysis 3.4).
No other maternal or infant secondary review outcomes were re-
ported by this trial.
Glucose polymer versus candy bar
Primary outcomes
No significant difference was found in diagnosis of GDM between
the two groups (glucose polymer versus candy bar) (one trial, 83
women, RR 4.44, 95% CI 0.22 to 89.84) (
Analysis 4.1) or for
screening positive (RR 1.48, 95% CI 0.38 to 5.78) (
Analysis 4.2).
This trial did not report on the other primary outcomes including:
mode of birth, large-for-gestational age and macrosomia.
Secondary outcom es
Again, the candy bar was preferred for taste significantly more
often than the glucose polymer drink (one trial, 83 women, RR
0.42, 95% CI 0.22 to 0.82) (
Analysis 4.3 ). Other measures of
acceptability of testing were not significantly different between the
two groups (RR 0.39, 95% CI 0.13 to 1.18) (
Analysis 4.4).
No other maternal or infant secondary review outcomes were re-
ported by this trial.
Glucose solution versus food
Primary outcomes
In one trial (
Martinez Collado 2003), there was no significant
difference in having a positive screening test for GDM between
the two glucose solution and food mix groups (30 women, RR
7.00, 95% CI 0.39 to 124.83) (
Analysis 5.1).
15Screening and s ubs equent management for gestational diabetes for improving maternal and infant health (Review)
Copyright © 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
This trial did not report on the other primary outcomes including:
diagnosis of GDM, mode of birth, large-for-gestational age and
macrosomia.
Secondary outcom es
Women receiving the glucose solution were more likely to expe-
rience a side effect of the screening, including nausea, vomiting,
migraine, diarrhoea and feeling sick, than those receiving the food
mix (80% versus 7% for ’any symptom’, one trial, 30 women, RR
12.00, 95% CI 1.78 to 81.06) (
Analysis 5.2).
No other maternal or infant secondary review outcomes were re-
ported by this trial.
There were insufficient data to perform subgroup analyses or sen-
sitivity analyses for all comparisons of the review.
D I S C U S S I O N
Gestational diabetes mellitus (GDM) is widely accepted as a seri-
ous health issue, associated with serious maternal and infant mor-
bidity. Recent, high-quality evidence exists to suggest that treat-
ment of GDM is beneficial (
Crowther 2005; Landon 2009). The
variation in screening practices and guidelines, both in national
surveys and worldwide, further demonstrates the need for large,
high-quality trials evaluating the effect of screening for GDM
(
ACOG 2001; A DA 2003; CDA 2008; Gabbe 2004; Hanna
2008
; Mires 1999; NICE 2008; Oats 2004; RANZCOG 2008;
Rumbold 2001). Despite its use, this review found little evidence
on the effect of screening on maternal and infant health out-
comes. This is consistent with other reviews on screening for GDM
(
Hillier 2008; Hollander 2007; NICE 2008; Scott 2002).
We included four trials evaluating various methods of screening
for GDM, which can be considered in two categories.
Griffin 2000
evaluated different screening protocols. Bergus 1992, Martinez
Collado 2003
and Murphy 1994 compared different types of glu-
cose for a 50 g OGCT.
Griffin 2000 was a large quasi-randomised trial comparing uni-
versal screening by 50 g OGCT with risk factor screening and re-
ported on diagnosis of GDM, positive screening f or GDM and ges-
tational age at birth. Of the 1299 women in the universal screening
group who completed an OGCT, 366 were referred for an oral glu-
cose tolerance test (OGTT). By comparison, fewer women (249
of the 1853 women in the risk factor group) were referred for an
OGTT. Unsurprisingly, with more women offered diagnostic test-
ing for GDM in the universal screening group, more women were
diagnosed with GDM. It is, however, difficult to interpret how
these increases in diagnoses and subsequent management translate
to clinical maternal and infant health outcomes in the review. The
marginal reduction seen in gestational age at birth is likely a result
of the large sample size rather than a clinically relevant difference.
The trial reported on the remaining health outcome data with
women reorganised into three groups, those who were not diag-
nosed with GDM, women who were diagnosed with GDM from
the universal screening group and those diagnosed with GDM in
the risk factor screening group.
While more women received glucose testing in the universal
screeninggroup, compared to those in the risk factor group, Griffin
2000 did not report on womens views on the two forms of screen-
ing. In addition to side e ffects of receiving a glucose load, prac-
tical issues for testing and the anxiety from screening and false
positive results, the anxiety created by receiving an abnormal re-
sult on screening compared with receiving information on back-
ground risk of GDM is also important in sel ecting an appropriate
screening protocol. Womens views on their health status and the
screening pr otocol would be further affected by whether or not
they are subsequently diagnosed and managed for GDM. Given
that some screening protocols will result in more women being
diagnosed with GDM than others, this may influence womens
views on their health status.
Furthermore, although management of diagnosed GDM improves
maternal and infant health outcomes, the diagnosis of GDM may
also be associated with increased intervention or monitoring such
as induction of labour and neonatal intensive care unit admission
(
Alwan 2009). Therefore, with various protocols for screening,
the subsequent management of women with a positive or negative
screening result as part of these protocols may impact on maternal
and infant health. Large studies are required to address these issues
and given that only a proportion of women are subsequently di-
agnosed with GDM, these trials require sufficient power for sub-
group analyses by diagnosis of GDM are meaningful.
Interestingly, women in the risk factor group with risk factors for
GDM received an oral glucose tolerance test at 32 weeks. Women
in the universal screening group underwent a glucose challenge
test at 26 to 28 weeks gestation and were referred for subsequent
OGTT if this was positive. Further to this, if glucose testing was
negative, repeat screening was performed where the woman had
risk factors for GDM. The risk factor group is therefore more
likely to be diagnosed at a later stage in pregnancy than those in
the universal screening group. It is unclear, however, if the timing
of glucose testing has affected health outcomes.
The trials (
Bergus 1992; Martinez Collado 2003; Murphy 1994)
evaluating different types of glucose for the challenge te st were
primarily interested in the side effects and number of women
diagnosed by different forms of glucose. Therefore, unlike
Griffin
2000
, the women in these trials were all offered the same diagnostic
testing pathway regardless of the screening result. Although no
health outcome data were included in th e review, data on health
outcome would be unlikely to be affected by the screening test
because the women received the same subsequent management.
Bergus 1992 and Murphy 1994 included a comparison of glu-
16Screening and s ubs equent management for gestational diabetes for improving maternal and infant health (Review)
Copyright © 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
cose monomer (d-glucose) and glucose polymer. Overall, fewer
side effects were reported by women receiving a glucose polymer
drink than glucose monomer. There was, however, significant het-
erogeneity in this result, with a stronger eff ect seen in
Murphy
1994
than Bergus 1992. This may be e xpl ained by the different
approaches taken by the trials, with
Murphy 1994 only reporting
side effects where they were rated moderate to severe. Bergus 1992
however used a binary approach. The differences in data presenta-
tion therefore limit interpretationof these outcomes. Maternal and
infant health outcomes were not recorded by the trials. Although
not statistically significant, the glucose polymer group generally
reported fewer side effects in the moderate to severe range than
the candy bar group.
Interpretation of the results of this arm of the review are, how-
ever, limited by the number of participants in each trial. Although
women were screened at 24 to 28 weeks’ gestation in the trials,
Murphy 1994 also included women in their first trimester with risk
factors for GDM and
Martinez Collado 2003 included women
with a ’high-risk pregnancy. Both trials used a 100 g OGTT for
diagnosis of GDM.
The results of this review were limited by the number of partici-
pants and methodological quality of the trials, which, overall, was
assessed to be moderate to low. Therefore, the results of this review
are to be interpreted with caution. Bergus 1992, Martinez Collado
2003
and Murphy 1994 included a total of 230 women and were
both primarily interested in the side effects and numbers of women
diagnosed by different forms of glucose. As a consequence, most
of the maternal and infant health outcomes included in this re-
view were not reported by these trials. While
Griffin 2000 was a
large quasi-randomised trial enrolling 3792 women, the format of
outcome reporting precluded the outcome data of interest for this
review from being included.
The trials included in this review were conducted in the United
States, Ireland and Mexico. Geographical location, socio-eco-
nomic circumstances and ethnicity are important factors that can
alter the most appropriate method of screening with regard to fea-
sibility and practicality. Compliance is probably not only related
to side effects, as investigated by
Bergus 1992, Martinez Collado
2003
and Murphy 1994, but also the requirements f or the screen-
ing protocol. For e xample, the inconvenience posed by a one-hour
50 g OGCT should be considered against random capillary blood
glucose testing or risk f actor screening. This emphasises the need
for future research to report not only on subsequent management
and maternal and infant health outcomes, but also on the accept-
ability of and adherence to particular screening pr otocols.
One trial (
Bebbington 1999) published as an abstract, and await-
ing assessment, also compared universal and selected screening in
2401 women with no reported risk factors for GDM. In abstract
form, there were insufficient data to include results in the review.
The abstract reports no significant difference in birthweight and
the incidence of macrosomia between the two groups.
A U T H O R S C O N C L U S I O N S
Implications for practice
There was insufficient evidence from this review to determine the
effects of screening for GDM and its subsequent management,
or the comparative effects of different protocols f or screening.
Although women who were routinely screened by 50 g glucose
challenge testing were more likely to be diagnosed with GDM
than those screened by their risk factors, effe cts of subsequent
management on health outcome are unclear.
Implications for research
Large, high-quality trials are required to evaluate the effects of
screening and subsequent management of GDM. As only a pro-
portion of women will be subsequently diagnosed with GDM in
these trials, a large number of participants is required for sufficient
power to de tect statistically significant differences and subgroup
analyses by diagnosis. Future studies should assess the value of
screening compared with no screening in addition to comparing
different types of screening tools. The 50 g oral glucose challenge
test and screening tools that are more easily implemented such
as risk f actor screening, glucosuria and the use of capillary blood
glucose testing need to be evaluated as part of screening protocols.
Furthermore, assessment of the optimal gestational age for screen-
ing is required. Trials should include data on health outcomes for
mother and baby, acceptability of the screening protocol and cost
effectiveness.
A C K N O W L E D G E M E N T S
We thank Emily Bain, Australian Research Centre for Health of
Women and Babies, The University of Adelaide, for her support
for updating this review.
We thank Dr George Bergus for contributing extra information
and clarification on
Bergus 1992. We also acknowledge the efforts
of Dr Richard Firth and Dr Michael Bebbington in locating extra
data.
The National Institute for Health Research (NIHR) is the largest
single funder of the Cochrane Pregnancy and Childbirth Group.
The views and opinions expressed therein are those of the authors
and do not necessarily reflect those of the NIHR, NHS or the
Department of Health.
17Screening and s ubs equent management for gestational diabetes for improving maternal and infant health (Review)
Copyright © 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
R E F E R E N C E S
References to studies included in this review
Bergus 1992 {published data only}
Bergus GR, Murphy NJ. Screening for gestational diabetes
mellitus: comparison of a glucose polymer and a glucose
monomer test beverage. Journal of the Ameri can Board of
Family Practice 1992;5(3):241–7.
Griffin 2 000 {published data only}
Griffin ME, Coffey M , Johnson H, Scanlon P, Foley M,
Stronge J, et al. Universal vs. risk factor-based screening for
gestational diabetes mellitus: detection rates, gestation at
diagnosis and outcome. Diabetic Medicine 2000;17:26–32.
Martinez Collado 2003 {published data only}
Martinez Collado JH, Alvarado Gay FJ, Danel Beltran JA,
Gonzalez Martinez E. Glucose screening test in pregnant
women. A comparison between the traditional glucose load
and diet [Tamiz de glucosa en emabarazadas. Comparacion
de la carga tradicional contra la dieta]. Medicina Interna de
Mexico 2003;19(5):286–8.
Murphy 1994 {published data only}
Murphy NJ, Meyer BA, Hogard ME. Carbohydrate sources
for gestational diabetes screening. A comparison. Journal of
Reproductive Medicine 1994;39:977–81.
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Berkus 1995 {published data only}
Berkus MD, Langer O. Glucose tolerance test periodicity:
the effect of glucose loading. Obstetrics & Gynecology 1995;
85:423–7.
Brustman 1995 {published data only}
Brustman LE, G ela BD, Moore M, Reilly KD, Langer O.
Variations in oral glucose tolerance tests: the 100- versus
75-g controversy. Journal of the Association for Academic
Minority Physicians 1995;6(2):70–2.
Buhling 2004 {published data only}
Buhling KJ, Elsner E, Wolf C, Harder T, Engel B, Wascher
C, et al. No influence of high- and low-carbohydrate diet
on the oral glucose tolerance test in pregnancy. Clinical
Biochemistr y 2004;37(4):323–7.
Cheng 1992 {published data only}
Cheng LC, Salmon YM, Chen C. A double-blind,
randomised, cross-over study comparing the 50g OGTT
and the 75g OGTT for pregnant women in the third
trimester. Annals of the Academy of Medicine, Singapore
1992;21(6):769–72.
Court 1984 {published data only}
Court DJ, Stone PR, Killip M. Comparison of glucose and
a glucose polymer for testing oral carbohydrate tolerance in
pregnancy. Obstetrics & Gynecology 1984;64(2):251–5.
Court 1985 {published data only}
Court DJ, Mann SL, Stone PR, Goldsbury SM, Dixon-
McIvor D, Baker JR. Comparison of glucose polymer and
glucose for screening and tolerance tests in pregnancy.
Obstetrics & Gynecology 1985;66(4):491–9.
Dornhorst 2000 {published data only}
Dornhorst A, Frost G. Jelly-beans, only a colourful
distraction from gestational glucose-challenge tests. Lancet
2000;355(9205):674.
Duenas-Garcia 2011 {published data only}
Duenas-Garcia OF, Ramirez-Torres A, Diaz-Sotomayor
M, Rico-Olvera H. Perinatal outcomes of patients with
gestational diabetes diagnosed by three different methods
[Resultados perinatales de pacientes con diabetes gestacional
diagnosticada con tres metodos diferentes]. Ginecologia y
Obstetricia de Mexico 2011;79(7):411–8.
Eslamian 2007 {published data only}
Eslamian L, Ramezani S. Breakfast as a screening test for
gestational diabetes. International Journal of Gynecology &
Obstetrics 2007;96(1):34–5.
Eslamian 2008 {published data only}
Eslamian L, Ramezani Z. Evaluation of a breakfast screening
test for the detection of gestational diabetes. Acta Medica
Iranica 2008;46(1):43–6.
Fung 1993 {published data only}
Fung H, Baldwin S, Rogers M. The influence of a glucose
load on subsequent carbohydrate metabolism in pregnancy.
Australian and New Zealand Journal of Obstetrics and
Gynaecology 1993;33(2):118–21.
Harlass 1991 {published data only}
Harlass FE, McClure GB, Read JA, Brady K. Use of a
standard preparatory diet for the oral glucose tolerance test.
Is it necessar y?. Journal of Reproductive Medicine 1991;36:
147–50.
Helton 1 989 {published data only}
Helton DG, Marin RW, Martin JN, Meeks GR, Morrison
JC. Detection of glucose intolerance