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Pregnancy
and diabetes
This guideline was supported by an unrestricted educational grant from Eli Lilly
and Company. This company had no involvement in the writing, review and
approval of the manuscript.
Citation
IDF Clinical Guidelines Task Force.
Global Guideline on Pregnancy and Diabetes.
Brussels: International Diabetes Federation, 2009.
Contents
1. Introduction .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ............................................ 4 6. Recommendations for Standard Care ................... 18
Pre-pregnancy counselling ............................................................... 18
2. Gestational diabetes mellitus (GDM) ......................... 5 At first prenatal visit ................................................................................ 19
2.1 Defining the condition .. . . . . . . . . . . . . . ................................................... 5
Frequency of subsequent visits .. .............................................. 20
2.2 Diagnosis of GDM . . . . . . . . . . . . . . . . . . . . . . . . . . . ................................................... 5
Ongoing management of diabetes
2.3 Rationale for treating GDM .................................................. 5 during pregnancy ............................................. .............................................. 20
Management of gestational diabetes ................................ 21
3. Before pregnancy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ............................................ 6
After delivery ....................................................... .............................................. 22
3.1 G
eneral issues for different groups
of women .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ................................................... 6 Breastfeeding . ..................................................................................................... 22
3.2 Review of medications .. . . . . . . . . . . . . . ................................................... 7 Follow-up within 6 weeks . ................ .............................................. 22
3.3 Pre-conception glycaemic control ............................... 8
7. Implementation ...................................................................................... 23
4. During pregnancy .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ............................................ 9
8. Evaluation . ...................................................................................................... 23
4.1 Testing of all or some women for GDM ............. 9
4.2 Testing for GDM – a two-stage or
9. References ...................................................................................................... 24
one-stage procedure? .. . . . . . . . . . . . . . . . . . ............................................... 10
4.3 Management during pregnancy ..................................... 10
Women already known to have diabetes (sometimes There are theoretical problems potentially associated with
called ‘pre-gestational diabetes’ in this context) need to the use of ARBs in pregnancy, but only very limited data on
consider how the effects of their pregnancy may impact this topic. Calcium channel blockers have the potential to
on the diabetes, and on any of their diabetes-associated cause fetal hypoxia and should be used cautiously if at all.
problems. Hypoglycaemia is more likely to occur in preg-
nancy, especially in the first trimester, as a greater effort is For statins, congenital malformations have been reported
made to attain and maintain glycaemic control. A variable and there is concern that decreased cholesterol synthesis
dietary intake associated with morning sickness may also may affect fetal development [29], but evidence on use in
increase this tendency towards hypoglycaemia. Women pregnancy is very limited. Data on the use of fibrates and
with established diabetic complications, such as retinopa- niacin are also limited.
thy or nephropathy, may experience a worsening during
the pregnancy. These aspects should ideally be assessed These medications need to be stopped as part of pre-
prior to any pregnancy and/or at such intervals during the conception planning or as soon as a pregnancy is recog-
pregnancy as clinically indicated. nized. Sufficient blood pressure control should be secured
by using methyldopa or labetalol.
3.2 Review of medications
Women with diabetes or previous GDM may be taking In common with other women during pregnancy, women
medications contra-indicated in pregnancy.These include, with diabetes need to ensure there is an adequate intake
but are not limited to, angiotensin converting enzyme of folic acid.
(ACE) inhibitors, angiotensin-II receptor blockers (ARBs),
calcium channel blockers and lipid lowering agents. Women with type 2 diabetes who are taking either met-
formin and/or glyburide (glibenclamide) need to have the
In a large cohort study of pregnancy which excluded women potential advantages and disadvantages of these medica-
with diabetes, first-trimester exposure to ACE inhibitors tions outlined and to continue with them if it is in their
was associated with an increased risk of major congenital best interests to do so.
malformations compared to the use of other anti-hyperten-
sive agents [26]. If ACE inhibitors were being used to treat
diabetic nephropathy prior to pregnancy, then a significant
deterioration in proteinuria can be anticipated during the
course of the pregnancy following discontinuation [27,28].
This aspect will need to be considered when offering advice.
3.3 Pre-conception glycaemic control before meals and <8.5 mmol/l (<153 mg/dl) after meals.
Women with diabetes have increased risk of an early Women with an elevated HbA1c value above 8.0% should
miscarriage and are at increased risk of having a baby be discouraged from becoming pregnant until their control
with malformations. Both of these risks are associated can be improved. There are currently no equivalent data
with less than optimal glycaemic control around the time about glucose levels.
of conception and in the first trimester. The extent of
the risk is difficult to quantify, but risks appear to be ap- Women with diabetes without pre-conception planning, or
proximately equivalent for women with type 1 diabetes with an unexpected pregnancy, should have their glycaemic
and type 2 diabetes. Women with type 2 diabetes appear control assessed as soon as practical, and advice on risk
to have a lesser uptake of pre-conception counselling [30]. should be offered on the basis of this result.
4. During pregnancy suggested for reducing the number of women requiring test-
ing [44], but this was considered unlikely to be practical [45].
4.1 Testing of all or some women for GDM
There is continuing debate about whether all pregnant
There is general consensus that testing should be done
women should be tested, or whether testing should be
at an early stage of pregnancy if risk factors are present,
done if risk factors are present, or not done if risk factors
but only poor evidence that interventions initiated at this
are absent. There is general agreement about the major
early stage are helpful.
risk factors for GDM. These include but are not limited
to increasing maternal age and weight, previous GDM or
There is insufficient evidence to come to a definitive
a macrosomic infant, family history of diabetes among
opinion on the advantages of selective testing. However,
first-degree relatives, and being from an ethnic background
selective testing could be considered:
with a high prevalence of diabetes.While there is no doubt
(a) if there was evidence to show that this process de-
that women with some or all of these risk factors are
tected the vast majority of women in the population
more likely to develop GDM, the reality is that any woman
being considered;
can develop this problem. An RCT found that risk-based
(b) if there was evidence that the process of selection
screening compared with universal screening missed about
based on risk factors could be conducted with ac-
half the women with GDM (1.45% vs 2.7%) [40].
curacy;
(c) if women in the population being considered and not
An earlier observational study of Caucasian women where
being tested had a more benign outcome to their
all were tested with an OGTT found that the prevalence of
undiagnosed GDM;
GDM among women with no risk factors was 2.8%. Excluding
(d) if it was deemed cost-effective, or was the only option,
this low-risk group of women would still require 80% of
within a particular healthcare arrangement.
the women to be tested and would miss 10% of all cases
of GDM [41]. Testing women according to the older age-
The limited evidence so far [46] indicates that a sorting
based American College of Obstetricians and Gynecologists
system cannot be conducted in an efficient manner, and
(ACOG) criteria would miss one-third of cases and result in
that women with GDM without risk factors appear to
minimal cost savings [42]. A later retrospective study found
be no different from women with GDM and risk factors.
that testing according to risk factors would require 90% of the
population to be tested [43].A complicated scheme has been
4.2 Testing for GDM – a two-stage or one-stage One study has found that management based on 1-h
procedure? rather than 2-h glucose levels resulted in better obstetric
A definitive diagnosis of GDM is currently made on the outcomes [51]. Women prefer, and are more likely to be
result of an OGTT. Currently, a two-stage diagnostic compliant with, testing 1 h after a meal [52]. For glucose
procedure is conducted in some parts of the world. A tolerant women there was a positive correlation between
two-stage procedure involves a non-fasting glucose chal- the 1 h postprandial glucose level and the fetal abdominal
lenge test (GCT) followed by a formal OGTT for women circumference [53]. Women with type 1 diabetes, who
who have a positive result. The GCT will inevitably miss have an LGA infant, are more likely to have an elevated
some women with GDM. In addition, there has been little HbA1c than those who do not have an LGA infant [54].
systematic examination of: The level of HbA1c in the third trimester has a strong
(a) how many women who are positive on a GCT fail to correlation with macrosomia but lacks some sensitivity.
return for the definitive OGTT; A possible explanation is that the postprandial glucose
(b) w hether a two-stage procedure delays the diagnosis excursions are more important in pregnancy, and this
and treatment of GDM, and what the effect of such is not always being reflected in the HbA1c level [55]. In
a possible delay might be. one study, women with type 1 diabetes who were tightly
controlled, based on fasting and postprandial glucose goals,
A one-stage definitive procedure is preferred, but a two- had no LGA babies [56].
stage procedure will continue to suit many healthcare
arrangements. Potential adoption of a lower glucose load Continuous glucose monitoring can add an extra dimen-
(75 g) and a shorter duration of the testing procedure sion to self-monitoring and may highlight areas of both
may lead to a reconsideration about the need for a two- unexpected hypoglycaemia and hyperglycaemia [57,58].
stage procedure.
Whenever it is possible, pregnant women with diabetes
4.3 Management during pregnancy should be encouraged to self-monitor blood glucose levels
4.3.1 Monitoring glucose levels both fasting and postprandial, preferably 1 h after a meal.
There is strong evidence of a relationship between el- The target glucose levels should be as low as possible
evated maternal glucose levels and macrosomia [15,47,48]. compatible with patient comfort and safety. The conclu-
Clinical studies where women were randomized to test sions of the Fifth International Workshop-Conference
either before or after meals have found that treatment on Gestational Diabetes Mellitus [59], in the absence of
decisions based on the postprandial glucose levels resulted specific evidence, referred to ‘upper boundary’ treatment
in fewer complications, particularly macrosomia [49,50]. targets for capillary blood glucose levels: fasting 90 to 99
10
mg/dl (5.0 to 5.5 mmol/l), 1 h after starting a meal <140 may provide clarification and help with treatment. However,
mg/dl (<7.8 mmol/l) or 2 h after starting a meal <120 to the routine measurement of HbA1c currently has only a
127 mg/dl (<6.7 to 7.1 mmol/l).The National Institute for minimal role in the management of women with GDM.
Health and Clinical Excellence (NICE) recommendations
for self testing in pregnancy are to have a fasting glucose 4.3.2 Lifestyle management
between 3.5 and 5.9 mmol/l (63 and 106 mg/dl) and a 1-h 4.3.2.1 Nutrition
postprandial glucose <7.8 mmol/l (<140 mg/dl) [2]. The All women in all pregnancies should ideally have advice
updated Canadian Diabetes Association (CDA) guideline about the macronutrient and micronutrient intake most
recommends plasma glucose target values during pregnancy suitable for achieving the best possible pregnancy outcome.
as follows: fasting and preprandial 3.8 to 5.2 mmol/l; 1-h Women with diabetes require an extra dimension to
postprandial 5.5 to 7.7 mmol/l; 2-h postprandial 5.0 to this advice.Women with pre-existing diabetes have most
6.6 mmol/l [3]. likely had previous nutritional advice that will need to
be revised and reviewed during pregnancy. Women who
Action points (arbitrary) for treatment adjustment should develop GDM will most likely require this advice for the
be easy to remember and therefore may need to be first time, often towards the end of pregnancy. In some
rounded differently depending on which system of units respects the nutrition management advice offered during
is being used. Exact translation from one system to the pregnancy, especially with regard to intake of macronutri-
other would imply a precision that does not exist. For ents (fats, for instance), may differ slightly from the advice
rounding in the SI, this might mean a fasting glucose ≥5.5 that is applicable before and after the pregnancy. All such
mmol/l, a 1-h postprandial glucose of ≥8.0 mmol/l or a 2-h advice should be individualized and culturally sensitive,
postprandial glucose level of ≥7.0 mmol/l. Alternatively, it and should be administered by a healthcare professional,
might be a fasting glucose ≥100 mg/dl, 1-h postprandial of ideally someone with specific expertise in medical nutri-
≥140 mg/dl or a 2-h postprandial of ≥120 mg/dl. tion therapy (MNT).
The HbA1c level should ideally be measured at regular Women with pre-existing insulin-treated diabetes should
intervals (4 to 8 weeks), or at such intervals as can be have the type, quality and quantity of their carbohydrate
managed, for all women with previously diagnosed diabetes, food matched to their insulin type and dose. Quite significant
as an ancillary aid to self-monitoring of blood glucose. For changes may be necessary as efforts are made to improve
women with gestational diabetes, in whom it is suspected control, either before pregnancy or after conception is
that they may have developed either type 1 diabetes or confirmed.Women with intermediate hyperglycaemia (IGT
type 2 diabetes while pregnant, an HbA1c measurement or IFG) and women with type 2 diabetes who are changing
11
from tablets or electing to be treated with insulin, if diet sumed, particularly with respect to the use of foods with
alone is inadequate, will also need careful advice about a low glycaemic index (GI), can reduce the postprandial
their carbohydrate choices. The same observations about glucose excursions. For women with GDM, postprandial
carbohydrate regulation apply to women diagnosed with glucose elevations are associated with adverse pregnancy
GDM [60,61]. outcomes [49,69]. In normal pregnancies, a low GI diet
will result in a reduced rate of LGA babies [70,71]. For
There may be an involuntary decrease in energy intake at women with GDM, a low GI diet can reduce the rate
the beginning of the pregnancy related to nausea. Later of insulin use, with no compromise of obstetric and
in pregnancy the total energy requirements are likely to fetal outcomes [72].
increase. For those women who are insulin treated, there
is likely to be an increase in the total dose of insulin dur- 4.3.2.2 Exercise
ing the pregnancy related to the physiological decrease in A moderate amount of exercise is beneficial for most people
insulin sensitivity. Thus the dietary carbohydrate content most of the time, and pregnancy is no exception.The ‘expert
and distribution will need to be changing to fulfil nutritional opinion’ of ACOG was that a minimum of 30 minutes ex-
requirements and as the insulin dose and type are changed. ercise on most days of the week was recommended during
a normal pregnancy [73]. There is no indication that this
It is possible that maternal obesity could be associated opinion, with common sense precautions, would be any
with an increased risk of fetal abnormalities [62,63]. different for pregnant women with diabetes. Women who
Weight loss diets are in general not recommended during were exercising before pregnancy should be encouraged to
the course of a pregnancy. However, at least for women continue this during the pregnancy though the extent and
with GDM who are considerably overweight, reducing type of exercise may need to be modified. For women with
energy intake by no more than 30% of habitual intake GDM, exercise can be seen as a useful adjunct to treatment
[64] is not associated with ketosis and does not cause [3,64,74]. Exercises that effectively avoid excessive abdominal
harm [65,66]. muscular contraction are preferred [59].
The proportion of energy intake derived from carbohy- Women who exercise regularly are probably less likely
drates will vary depending on the traditional diet and the to develop GDM, although this reduced rate appears
availability of alternative sources of energy. Regulating to be related to the habitual amount of exercise rather
and potentially reducing the carbohydrate intake is an than exercise started in the year before the pregnancy
effective strategy for helping to control glucose levels [75]. An exercise programme may be an alternative to
[67,68]. Changing the nature of the carbohydrates con- the use of insulin in women with GDM who have not
12
responded to diet alone [76,77]. This may come about rapid action for mealtime use or a longer duration of
due to the increased insulin sensitivity associated with action for basal use.
exercise therapy [78,79].
Human insulin was shown to achieve improved pregnancy
Advice on exercise should be tailored to the previous and infant outcomes compared with highly purified animal
exercise habits of the individual. If they were previously insulins [81]. Commencing in 1999, the safety and ef-
sedentary, then arm exercises may be a good starting point. ficacy of the rapid-acting analogue insulin lispro has been
Inactivity can be expected to result in a further reduction demonstrated in pregnancy in pre-existing diabetes and
in insulin sensitivity. GDM [82,83], and it was found not to cross the placenta
[84].The second rapid-acting analogue, insulin aspart, has
In summary, exercise may be useful for preventing GDM also been shown to be safe and effective in pregnancy in
and also for improving insulin sensitivity. This is based type 1 diabetes [85,86] and GDM [87]. The use of these
on limited and diverse clinical studies as well as expert two analogues has been the subject of a systematic review
opinion. The prescription of exercise during pregnancy is [88].There are currently no data regarding the rapid-acting
hindered by lack of evidence regarding the type, frequency analogue insulin glulisine in pregnancy.
and intensity [80].
For the long-acting insulin analogues, there is limited
4.3.3 Insulin use during pregnancy experience in pregnancy with insulin glargine [89-92] but
Insulin has been used in pregnancy since 1922. It is es- no data so far for insulin detemir, although a trial is now
sential for women with type 1 diabetes and is still widely under way.
considered the drug of choice for women with either
type 2 diabetes or GDM who are not meeting treatment The decision about which type of insulin and which insulin
goals with lifestyle modification and/or oral glucose- regimen to start or continue during pregnancy should be
lowering agents. The clinical experience with insulin taken after informed discussion.The more limited clinical
use is vast, but the availability of clinical trial evidence is experience and therefore the theoretical possibility of
limited. The longer an insulin has been used, the greater as yet unknown risks associated with the newer insulin
is the collective clinical experience but not necessarily analogues needs to be balanced against patient preference
the clinical trial evidence. Highly purified animal insulins and overall glycaemic control and stability.
have been largely replaced by human insulin preparations.
These in turn are now being replaced in some markets
by insulin analogues, modified to produce either a more
13
14
4.3.4.7 Conclusion
The clinical experience with insulin therapy is vast and with-
out problem and it remains the agent of choice whenever
possible.There also does not appear to be any clear harm
with respect to pregnancy outcomes from using either
15
5. After pregnancy type 1 diabetic women have a reduced basal insulin need
during lactation [107].
5.1 Breastfeeding
Unless there is a specific contra-indication or concern,
Transfer of metformin to human milk is minimal, at <0.4%
breastfeeding is the preferred option for all women. This
of the maternal concentration [108-110].There is concern
general recommendation is also applicable to women
that sulfonylureas may cause hypoglycaemia in the baby.
whose pregnancy was affected by pre-existing or ges-
Data on sulfonylureas are inadequate, but are discussed
tational diabetes. However, it should be noted that it is
in the report of a very small study in which glibenclamide
possible for breastfeeding to have an influence on mater-
(glyburide) and glipizide could not be detected in the
nal glycaemic control, and maternal diabetes may in turn
breast milk of nursing mothers [111].
influence the composition of breast milk.
16
If further pregnancies are planned, then a repeat OGTT risk reduction in the troglitazone treated group compared
prior to conception or at least in the first trimester is with placebo [114].This beneficial effect was substantiated
desirable. If no abnormality is present, then testing should in the follow-on Pioglitazone in Prevention of Diabetes
be repeated at the usual time and with the usual indica- (PIPOD) study when pioglitazone was substituted [115].
tions during pregnancy.
The second study was the Diabetes Prevention Program
If no further pregnancies are planned, the long-term (DPP), where women with previous GDM were included
follow-up arrangements will depend heavily on the per- [116]. This study demonstrated a significant reduction in
ceived risk of developing type 2 diabetes. In a high-risk type 2 diabetes for both lifestyle modification and met-
group there should be an annual OGTT. In a low-risk formin therapy compared with placebo. A subsequent
group there could be fasting glucose every two to three sub-group analysis of the results found that, for women
years and an OGTT only if this level is ≥5.5 mmol/l with previous GDM, lifestyle modification and metformin
(100 mg/dl). were equally effective [117].
17
Pre-pregnancy counselling
F or all fertile women of child-bearing age with diabetes, identify possibility of
pregnancy by direct questioning on every relevant occasion. Provide contraceptive
advice where appropriate.
iscuss the advantages and theoretical risks of oral glucose-lowering agents and start
D
insulin where appropriate.
iscuss choice of insulin, with possible risks of the most recently introduced insulin
D
analogues to be balanced against individual preference and overall glycaemic control.
18
ssess established diabetes complications, especially of the eyes and kidneys; discuss
A
and manage identified problems.
F or women with diabetes who may have missed pre-pregnancy counselling, determine
HbA1c as soon as practical, and offer advice on risk on the basis of the result.
F or women who are at high risk of diabetes because of previous GDM, provide
healthy lifestyle advice and offer an OGTT as soon as practical. If the result is normal,
then offer again at 26 to 28 weeks of gestation. A one-stage definitive procedure is
preferred.
F or all other women (unless a selective process based on risk factors is deemed
more appropriate), advise that they will be offered testing for GDM at 26 to 28
weeks of gestation.
19
Offer general instruction about nutrition and specific advice about carbohydrate
intake, which wherever possible should include foods with a low glycaemic index.
If insulin is being used, then the choice, quantity and distribution of carbohydrate will
need to be coordinated with the amount, type and distribution of the varying insulin
requirements of pregnancy.
Encourage physical activity, tailoring advice to the previous exercise habits of the
individual. Explain that exercise can counter the decline in insulin sensitivity that
occurs during pregnancy and that resting will have the opposite effect.
Glucose control
HbA1c as an ancillary aid to self-monitoring. Aim for an HbA1c <6.0%, or lower
Use
if safe and acceptable.
20
If at all possible, self-monitoring of blood glucose (SMBG) should be done frequently.
For women with pre-existing diabetes this will relate to their previous pattern of
testing and the type of insulin regimen they are using.
Monitor blood pressure and advise/treat accordingly, avoiding ACE inhibitors and ARBs.
Instruct in self-monitoring of blood glucose (to be used four times daily, fasting and
1 h after each meal), and advise on lifestyle modification.
If agreed glucose control targets are not met within 1 to 2 weeks of initiation of
lifestyle management, offer glucose-lowering medication. Insulin has been, and is likely
to remain, the treatment of choice but there is now adequate evidence to consider
the use of metformin and glibenclamide (glyburide) as treatment options for women
who have been informed of the possible risks. Combination therapy has not been
specifically studied.
21
After delivery
nticipate changed insulin requirements (immediate reduction), and thus the need for more
A
frequent glucose monitoring, if continuing insulin postpartum and during breastfeeding.
Breastfeeding
E ncourage breastfeeding (nutritional and immunological benefits to the baby). Advise
women with type 1 diabetes or type 2 diabetes that self-monitoring should continue
and good glycaemic control should be maintained during this period.
Insulin requirements drop immediately after delivery, and a dose adjustment will be
needed to allow for the eating patterns of the breastfeeding mother.
eview medications, taking into consideration the potential risks associated with
R
any transfer into the milk. Metformin and possibly glibenclamide (glyburide) may be
used. Statins should be avoided, and consideration should be given to the choice of
anti-hypertensive agents.
22
7. Implementation 8. Evaluation
Implementation of these recommendations will require Delivery weight of the infant and achieved maternal HbA1c
liaison between healthcare professionals involved in dia- each trimester may be useful surrogate outcomes for
betes, obstetric and neonatal care, such that joint proto- quality assurance. Structural review should be of the exist-
cols can be devised for pregnancy and post-pregnancy ence of joint management protocols addressing the above
management. Local decisions will be required as to means recommendations, and appropriate availability of staff.
of testing for GDM and whether a selective or universal
approach will be used.
23
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