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Epidemiologic context of diabetes in pregnancy

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PRACTICE POINTS

• The prevalence of all forms of diabetes in pregnancy, namely
Type 1, Type 2, and gestational diabetes mellitus (GDM),
ranges from below 2% to over 20%, although variations in
defi nition, screening, and diagnostic criteria of GDM make
comparisons diffi cult.
• The prevalence of Type 2 diabetes, GDM, and probably Type
1 diabetes in pregnancy is increasing and varies signifi cantly
between ethnic groups and between locations.
• The prevalence of some risk factors for GDM and Type 2
diabetes in pregnancy (e.g. obesity) is increasing.
• Adverse pregnancy outcomes are generally increased 2 – 7 - fold
in women with pre - existing diabetes and are similar for Type
1 and Type 2 diabetes.
• There is good evidence that intervention for diabetes in
pregnancy can reduce adverse pregnancy outcomes: it has
been estimated that for every US$1 invested in diabetes in
pregnancy, there is a saving of US$3 – 4 on downstream
health costs.
• The health, social, and economic impacts of intergenerational
transmission of diabetes are unknown.

BACKGROUND

Historically, the study of diabetes in pregnancy has
focused on either women with Type 1 diabetes, whose
poor obstetric outcomes once led to an editorial entitled
“ They give birth astride the grave ” 1 or GDM, an entity
which remains contentious, 2,3 with variable approaches
to defi nition, screening, and diagnosis. 4 The current
epidemic of obesity and diabetes among children,
adolescents, and non - pregnant adults 5 has changed
the situation, leading to growing numbers with Type 2
diabetes in pregnancy and GDM (including undiagnosed
Type 2 diabetes). 6 – 8 In parallel, our understanding of the
impact of diabetes in pregnancy for future generations, 9
and our increasing ability to reduce pregnancy complications,
10 and postpone, if not prevent, diabetes after
GDM, 11 have emphasized the epidemiologic and public
health importance of diabetes in pregnancy.

OUTCOMES FROM DIABETES
IN PREGNANCY

That there is no common unique pathognomonic complication
of diabetes in pregnancy, combined with the
apparent continuous relationship between glucose and
fetal macrosomia, has resulted in a lack of consensus on
the diagnosis of GDM. While diabetes in pregnancy is
associated with increased obstetric risk compared with
normal pregnancy, the overall contribution of diabetes to
most obstetric and neonatal complications on a population
basis is actually relatively low, with the largest impact
being on shoulder dystocia (through GDM). Table 1.1
shows examples of odds ratios for each obstetric and
neonatal complication by diabetes type and the proportion
that diabetes in pregnancy contributes on a population
basis. 12 – 15
Apart from malformations, which are likely to have
resulted from preconceptional or periconceptional
hyperglycemia, improvements in obstetric practice have
led to major reductions in adverse outcomes. Avoidance
of such outcomes may dictate the need for complex
obstetric decision - making, with the inevitable increase in
fetal monitoring (see chapter 12 ) and which is strongly
infl uenced by the preconceptional and antenatal management
of hyperglycemia (see chapters 8 and 10 ). The
importance of other metabolic factors, such as obesity 16 – 19
and hypertriglyceridemia, 20 in pregnancy are also now
increasingly being recognized.







The long - term implications of diabetes in pregnancy
for the offspring, particularly obesity and Type 2 diabetes,
are discussed in chapter 25 . While there is early
evidence that optimal management of diabetes during
pregnancy may reduce excess adiposity in the offspring
(and hopefully, ergo, subsequent diabetes), 21 this urgently
requires confi rmation. As yet there is no evidence that
poorer neurodevelopmental outcomes, which may be
associated with GDM, are amenable to change. 22
Such analyses can be confounded by the associations
between socioeconomic status and both GDM and
achievement.

DIAGNOSIS OF GESTATIONAL DIABETES MELLITUS

While it is generally accepted that severe hyperglycemia
in pregnancy is associated with adverse maternal fetal
outcome, the signifi cance of lesser degrees of hyperglycemia,
along with the lack of common pathognomonic
sequelae, and the apparent continuum between glucose
and, for example, fetal macrosomia 24 have fuelled the lack
of consensus on the optimal glycemic threshold for diagnosis
of hyperglycemia in pregnancy. This is discussed in
chapter 6 , but essentially involves deriving a glycemic
threshold above which the benefi ts of intervention outweigh
any harm and are cost - effective.
Outside of pregnancy, the 75 - g 2 - hour oral glucose
tolerance test (OGTT) is used. Diabetes and prediabetes
are defi ned by their association with macrovascular and
microvascular complications, the clinical appearance of
the latter (retinopathy) being largely unique to diabetes.
As a result, diabetes in non - pregnant adults has a globally
agreed defi nition, as does impaired glucose tolerance (IGT) (Table 1.2 ). There remains disagreement between the World Health Organization (WHO) and the American
Diabetes Association (ADA) defi nition of impaired
fasting glucose (Table 1.2 ). As GDM is defi ned as
carbohydrate/glucose intolerance fi rst identifi ed/with
new onset in pregnancy, intuitively it would be thought
that by defi nition, the criteria for diagnosis of GDM
would include a fasting glucose of greater than or equal
5.6 or 6.1 mmol/L ( ≥ 101– 110 mg/d L) (ADA or WHO)
and/or a 2 - hour glucose greater than or equal to
7.8 mmol/L (140 mg/dL ), with potentially some modifi -
cation should pregnancy outcomes be quantitatively
worse below these cut - off points. This is discussed more
fully in chapter 6 .
There have been multiple attempts to defi ne the glycemic
thresholds for fetal and maternal outcomes (i.e.
diagnostic criteria) for GDM (Table 1.2 ). These have traditionally
been based upon a fasting blood glucose test,
50 – 100 - g glucose load, 4 followed by 1 – 3 hours of blood
glucose testing, and involving interpretation of the results
either singly or in combination.
A global move to standardize the diagnostic criteria
was the rationale for the Hyperglycaemia and Adverse
Pregnancy Outcomes (HAPO) study, a large study among
25 000 women across continents and, importantly,
involving many ethnic groups. 24 Of importance is the fact
that this study showed that the impact of hyperglycemia
for maternal/fetal outcome was applicable to all ethnic
groups 24 and independent of maternal obesity, a recognized
risk factor per se for large babies. 16 – 19 Further analysis
of data from the HAPO study will address the
important question of whether different glycemic thresholds
are needed to predict a greater risk of glucose - sensitive
adverse outcomes.




PREVALENCE OF PREGESTATIONAL DIABETES IN PREGNANCY

The prevalence of Type 1 and Type 2 diabetes in pregnancy
would be expected to refl ect the rates of diabetes
in the background population. 25,26 However, the standard
fertility ratio (SFR) is low in Type 1 diabetes (0.80, 95%
CI 0.77 – 0.82), and is particularly low among women with
retinopathy, nephropathy, neuropathy, or cardiovascular
complications (0.63, 0.54, 0.50, and 0.34, respectively). 27
While fertility rates in Type 2 diabetes have not been
reported, they would also be expected to be low (particularly
in view of the additional associated obesity, polycystic
ovarian syndrome [PCOS], and vascular disease).
The incidence of Type 1 and the prevalence of Type 2
diabetes has been increasing over time, 28 with a reduction
in the age at diagnosis of Type 2 diabetes. Both of these
factors predict an increasing number of women with
pregestational diabetes. However, the more rapid increase
in Type 2 diabetes in pregnancy has resulted in some
diabetes clinics now seeing a predominance of Type 2 over
Type 1 diabetes, which has been accentuated further by
ethnicity. In the US, the ratio of women with Type 1 to
Type 2 diabetes has shifted from 3 : 1 to 1 : 2 between 1980
and 1995. 28 This may be partly due to changes in the population
(e.g. in Birmingham, UK the ratio of Type 1 to Type
2 diabetes was 1 : 2 in South Asians but 11 : 1 in Europeans
29 ). Meanwhile, there have been other important
changes. Women with diabetes in pregnancy are now
expected to survive. The perinatal mortality for pregnancies
complicated by Type 1 diabetes has also dropped from
40% to much nearer the background rate . 23,28 In Type 2
diabetes, the evolving evidence suggests that perinatal
mortality and the frequency of congenital malformations
are similar to those of Type 1 diabetes, 23 including in those
women diagnosed with GDM but found to have Type
2 diabetes postnatally. 6,29 While these trends are more
often seen in women of non - European descent, it is likely
that a similar picture will be seen in all groups eventually.
To date there are few reports of the prevalence of
monogenetic forms of diabetes or secondary diabetes in
pregnancy. Glucokinase mutations are present in up to
5 – 6% of women with GDM and up to 80% of women
with persisting fasting hyperglycemia outside pregnancy,
a small glucose increment during the OGTT, and a family
history of diabetes. 30 Cystic fi brosis is associated with a
doubling in the prevalence of diabetes outside of pregnancy,
with a further increase during pregnancy (e.g.
from 9.3% at baseline to 20.6% during pregnancy, and
14.4% at follow - up).
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