Ch36 Pregnanدرحاب Cy

Canadian Diabetes Association Clinical Practice Guidelines

Pregnancy

Chapter 36

David Thompson, Howard Berger,

Denice Feig, Robert Gagnon, Tina Kader,

Erin Keely, Sharon Kozak, Edmond Ryan,

Mathew Sermer, Christina Vinokuroff

guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.caCopyright © 2013 Canadian Diabetes Association

In collaboration with …


Diabetes in Pregnancy: 2 Categories

Pregestational diabetes Gestational diabetes

Pregnancy in pre-existing diabetes

• Type 1 diabetes • Type 2 diabetes

Diabetes diagnosed in pregnancy


Diabetes in Pregnancy: Consider Phases


1. Preconception counseling 1. Screening

2. Glycemic control during pregnancy


3. Management in labour 3. Management in labour

4. Postpartum considerations 4. Postpartum considerations


Dysglycemia in Pregnancy can Result in Adverse Pregnancy Outcome

• Elevated glucose levels can have adverse effects on the fetus– 1st trimester ↑ fetal malformations– 2nd and 3rd trimester: ↑ risk of macrosomia and

metabolic complications


Risk of Fetal Anomaly Relative to Periconceptional A1C

Guerin A et al. Diabetes Care 2007;30:1-6.

Glycemic control pre-conception = essential


Need a Preconception Checklist for Women with Pre-existing Diabetes

1. Attain a preconception A1C of ≤7.0% (if safe)

2. Assess for and manage any complications

3. Switch to insulin if on oral agents

4. Folic Acid 5 mg/d: 3 months pre-conception to 12 weeks post-conception

5. Discontinue potential embryopathic meds: Ace-inhibitors/ARB (prior to or upon detection of pregnancy) Statin therapy

2013


Table 1: Comparison of ARB pharmacokinetics

Drug Trade NameBiological half-life [h]

Protein binding [%]

Bioavailability [%]

Renal/hepatic clearance [%]

Food effectDaily dosage

[mg]

Losartan Cozaar 6-9 h 98.7% 33% 10%/90% Minimal 50–100 mg

EXP 3174 6–9 h 99.8% – 50%/50% – –

Candesartan

Atacand 9h >99% 15% 60%/40% No 4–32 mg

Valsartan Diovan 6 h 95% 25% 30%/70% No 80–320 mg

Irbesartan Avapro 11–15 h 90–95% 70% 1%/99% No 150–300 mg

Telmisartan

Micardis 24 h >99% 42–58% 1%/99% No 40–80 mg

Eprosartan

Teveten 5 h 98% 13% 30%/70% No 400–800 mg

Olmesartan

Benicar/Olmetec 14–16 h >99% 29% 40%/60% No 10–40 mg

Azilsartan Edarbi 11 h >99% 60% 55%/42% No 40–80 mg

http://en.wikipedia.org/wiki/Clearance_(medicine)

http://en.wikipedia.org/wiki/Losartan

http://en.wikipedia.org/wiki/Candesartan

http://en.wikipedia.org/wiki/Candesartan

http://en.wikipedia.org/wiki/Valsartan

http://en.wikipedia.org/wiki/Irbesartan

http://en.wikipedia.org/wiki/Telmisartan

http://en.wikipedia.org/wiki/Telmisartan

http://en.wikipedia.org/wiki/Eprosartan

http://en.wikipedia.org/wiki/Eprosartan

http://en.wikipedia.org/wiki/Olmesartan

http://en.wikipedia.org/wiki/Olmesartan

http://en.wikipedia.org/wiki/Azilsartan


• ACE inhibitors can be divided into three groups based on their molecular structure:• Sulfhydryl-containing agents[edit]• Captopril (trade name Capoten), the first ACE inhibitor• Zofenopril• Dicarboxylate-containing agents[edit]• This is the largest group, including:• Enalapril (Vasotec/Renitec)• Ramipril (Altace/Prilace/Ramace/Ramiwin/Triatec/Tritace)• Quinapril (Accupril)• Perindopril (Coversyl/Aceon/Perindo)• Lisinopril (Listril/Lopril/Novatec/Prinivil/Zestril)• Benazepril (Lotensin)• Imidapril (Tanatril)• Trandolapril (Mavik/Odrik/Gopten)• Cilazapril (Inhibace)• Phosphonate-containing agents[edit]• Fosinopril (Fositen/Monopril) is the only member of this group• Naturally occurring[edit]• Casokinins and lactokinins, breakdown products of casein and whey, occur naturally after ingestion of milk products, especially

cultured milk. Their role in blood pressure control is uncertain.[24]

• The lactotripeptides Val-Pro-Pro and Ile-Pro-Pro produced by the probiotic Lactobacillus helveticus or derived from casein have been shown to have ACE-inhibiting and antihypertensive functions

http://en.wikipedia.org/w/index.php?title=ACE_inhibitor&action=edit&section=8

http://en.wikipedia.org/wiki/Captopril

http://en.wikipedia.org/wiki/Zofenopril


http://en.wikipedia.org/wiki/Enalapril

http://en.wikipedia.org/wiki/Ramipril

http://en.wikipedia.org/wiki/Quinapril

http://en.wikipedia.org/wiki/Perindopril

http://en.wikipedia.org/wiki/Lisinopril

http://en.wikipedia.org/wiki/Benazepril

http://en.wikipedia.org/wiki/Imidapril

http://en.wikipedia.org/wiki/Trandolapril

http://en.wikipedia.org/wiki/Cilazapril


http://en.wikipedia.org/wiki/Fosinopril


http://en.wikipedia.org/wiki/Kinin

http://en.wikipedia.org/wiki/Casein

http://en.wikipedia.org/wiki/Whey

http://en.wikipedia.org/wiki/Milk

http://en.wikipedia.org/wiki/Cultured_milk

http://en.wikipedia.org/wiki/ACE_inhibitor#cite_note-FitzGerald2004-24

http://en.wikipedia.org/wiki/Lactotripeptides

http://en.wikipedia.org/wiki/Probiotic

http://en.wikipedia.org/wiki/Lactobacillus_helveticus

http://en.wikipedia.org/wiki/Lactobacillus_helveticus

http://en.wikipedia.org/wiki/Casein


Preconception Counseling for Pregestational Diabetes

• Advise reproductive age women with diabetes about

reliable birth control– NOTE: Metformin in PCOS may improve fertility need to

warn about possible pregnancy

– Metformin safe for ovulation induction in PCOS

• Achieving a healthy weight is essential – obesity

associated with adverse pregnancy outcomes


• Metformin is safe in pregnancy and women with gestational diabetes treated with metformin have less weight gain during pregnancy than those treated with insulin. Babies born to women treated with metformin have been found to develop less visceral fat, making them less prone to insulin resistance in later life.

http://en.wikipedia.org/wiki/Gestational_diabetes


Screen for Complications: Pre-pregnancy and Intrapartum

Screening for:

1. Retinopathy: Need ophthalmological evaluation

2. Nephropathy: Assess creatinine + urine

microalbumin / creatinine ratio (ACR)– Women with microalbuminuria or overt nephropathy are at

↑ risk for hypertension and preeclampsia


Recommendations 1-2: Preconception Care

1. All women of reproductive age with type 1 or type 2

diabetes should receive advice on reliable birth control,

the importance of glycemic control prior to pregnancy,

impact of BMI on pregnancy outcomes, need for folic

acid and the need to stop potentially embyropathic

drugs prior to pregnancy [Grade D, Level 4].

2. Women with type 2 diabetes and irregular

menses/PCOS who are started on metformin or a

should be advised that fertility may improve and be

warned about possible pregnancy [Grade D, Consensus].

2013


Recommendation 3: Preconception Care

3. Before attempting to become pregnant, women

with type 1 or type 2 diabetes should:

a) Receive preconception counseling that

includes optimal diabetes management and

nutrition, preferably in consultation with an

interdisciplinary pregnancy team to optimize

maternal and neonatal outcomes [Grade C, Level 3]


Recommendation 3: Preconception Care (continued)

b) Strive to attain a preconception A1C of ≤7.0% (or

A1C as close to normal as can safely be achieved)

to decrease the risk of:

– Spontaneous abortion [Grade C, Level 3]

– Congenital anomalies [Grade C, Level 3]

– Pre-eclampsia [Grade C, Level 3]

– Progression of retinopathy in pregnancy [Grade A, level

1 for type 1 diabetes (23); Grade D, Consensus for type 2 diabetes]


c) Supplement their diet with multivitamins containing 5

mg of folic acid at least 3 months pre-conception

and continuing until at least 12 weeks post-

conception [Grade D, Level 4]. Supplementation should

continue with a multivitamin containing 0.4-1.0 mg

of folic acid from 12 weeks postconception

through to 6 weeks postpartum or as long as

breastfeeding continues [Grade D, Consensus].



d) Discontinue medications that are potentially

embryopathic, including any from the following

classes:

• ACE inhibitors and ARBs prior to conception

or upon detection of pregnancy [Grade C, Level 3]

• Statins [Grade D, Level 4]

2013



4. Women with type 2 diabetes who are planning a

pregnancy should switch from non-insulin

antihyperglycemic agents to insulin for glycemic

control [Grade D, Consensus].

Women with pregestational diabetes who also

have PCOS may continue metformin for

ovulation induction [Grade D, Consensus].

Recommendation 4: Preconception Care


Recommendations 5 and 6: Preconception and Complications

5. Women should undergo an ophthalmological

evaluation by an eye care specialist [Grade A, Level 1, for

type 1; Grade D, Level 4 for type 2].

6. Women should be screened for chronic kidney

disease prior to pregnancy [Grade D level 4 for type 1 diabetes

Grade D, consensus for type 2 diabetes]. Women with

microalbuminuria or overt nephropathy are at

increased risk for the development of HTN and

preeclampsia [Grade A level 1]; and should be followed

closely for these conditions [Grade D, Consensus]


Need Optimal Glycemic Control in Pregnancy for Pre-existing Diabetes

• Individualized insulin therapy with close monitoring– Bolus insulin: May use aspart or lispro instead of regular

insulin– Basal insulin: May use detemir or glargine as alternative to

NPH • Encourage patients to SMBG pre- and postprandially

Target glucose values

Fasting PG <5.3 mmol/L

1h postprandial PG <7.8 mmol/L



• Maternal blood glucose levels should be kept

between 4.0 -7.0 mmol/L ↓ neonatal hypoglycemia

• Women should receive adequate glucose during

labour in order to meet the high energy requirements– IV Dextrose + IV insulin protocols may be helpful

Glucose Management During Labour and Delivery

2013


Postpartum care for pre-existing diabetes

1. Adjust insulin at risk of hypoglycemia

2. Encourage women to breastfeed

3. Metformin and glyburide may be used during breast-

feeding no long term data but appears safe

4. Screen for postpartum thyroiditis in T1DM

check TSH at 6-8 weeks postpartum


Recommendation 7: Management in Pregnancy for Pregestational Diabetes

7. Pregnant women with type 1 or type 2 diabetes

should:

a) Receive an individualized insulin regimen and

glycemic targets typically using intensive insulin

therapy [Grade A, Level 1B for type 1; Grade A, Level 1 for type 2]

b) Strive for target glucose values [Grade D consensus]:

• Fasting PG below 5.3 mmol/L

• 1h postprandial below 7.8 mmol/L

• 2h postprandial below 6.7 mmol/L


Recommendation 7: Management in Pregnancy for Pre-gestational Diabetes (continued)

c) Be prepared to raise these targets if need be

because of the increased risk of severe

hypoglycemia during pregnancy [Grade D, Consensus]

d) Perform SMBG, both pre- and postprandially

to achieve glycemic targets and improve

pregnancy outcomes [Grade C, Level 3]

2013


8. Women with pregestational diabetes may use

aspart or lispro in pregnancy instead of regular

insulin to improve glycemic control and reduce

hypoglycemia [Grade C level 2 for aspart , Grade C, Level 3 for lispro].

9. Detemir [Grade C, Level 2] or glargine [Grade C, Level 3 ] may

be used in women with pregestational diabetes as

an alternative to NPH.

Recommendations 8-9: Management in Pregnancy for Pre-gestational Diabetes

2013

2013


10.Women should be closely monitored during labour

and delivery and maternal blood glucose levels

should be kept between 4.0 and 7.0 mmol/L in

order to minimize the risk of neonatal hypoglycemia [Grade D, Consensus]

11. Women should receive adequate glucose during

labour in order to meet the high energy requirements [Grade D, Consensus]

Recommendation 10 and 11: Intrapartum Glucose Management

2013

2013


Recommendations 12 and 13: Postpartum Glucose Management

12.Women with pregestational diabetes should be

carefully monitored postpartum as they have a

high risk of hypoglycemia [Grade D, Consensus].

13.Metformin and glyburide may be used during

breast-feeding [Grade C, Level 3 for metformin; Grade D, Level 4 for

glyburide].

2013

2013


Recommendation 14 and 15: Postpartum Glucose Management

14.Women with type 1 diabetes in pregnancy should

be screened for postpartum thyroiditis with a TSH

test at 6-8 weeks postpartum [Grade D, Consensus].

15.All women should be encouraged to breast-feed,

since this may reduce offspring obesity, especially in

the setting of maternal obesity [Grade C level 3-]




1. Preconception counseling 1. Screening & diagnosis






Gestational Diabetes (GDM) Diagnosis• Universal screening for GDM @ 24-28 weeks

Gestational Age (GA)• Screen earlier if risk factors for GDM:

Previous GDM BMI ≥30 kg/m2

Prediabetes Polycystic ovarian syndrome

High risk population (Aboriginal, Hispanic, South Asian, Asian, African)

Current fetal macrosomia or polyhydramnios

Age ≥35 years History of macrosomic infant

Corticosteroid use Acanthosis nigricans


Why Diagnose and Treat GDM?

• Macrosomia• Shoulder dystocia and

nerve injury• Neonatal hypoglycemia• Preterm delivery• Hyperbilirubinemia

• Caesarian section• Offspring obesity (?)• Offspring diabetes (?)


HAPO: Incidence of Adverse Outcomes Increases Along Continuum

Metzger BE, et al. Hyperglycemia and Adverse Pregnancy Outcomes. NEJM 2008;358(19):1991-2002.


Benefits of Treatment of GDM


Benefits of Treatment of GDM

Horvath K et al. BMJ 2010;340:c1935


Are there clear threshold glucose levels

above which the risk of adverse neonatal

or maternal outcomes increases?

Diagnosis of GDM


Diabetes Care 2010;22:676-682

IADPSG


HAPO: Incidence of Adverse Outcomes Increases Along Continuum – No Threshold

Metzger BE, et al. HAPO. NEJM 2008;358(19):1991-2002.


Are there clear threshold glucose levels

above which the risk of adverse neonatal

or maternal outcomes increases?

NO


Glucose measure with a 75 g OGTT

Glucose threshold (mmol/L)

Proportion of HAPO cohort above threshold (%)

Fasting plasma glucose (FPG)

5.1 8.3

1-h plasma glucose 10.0 14.0


IADPSG Consensus Threshold Values for Diagnosis of GDM (≥1 Value is Diagnostic)

Based on odds ratio (OR) of 1.75 for primary outcomeOGTT = Oral Glucose Tolerance TestHAPO = Hyperglycemia and Adverse Pregnancy Outcomes studyIADPSG. Diabetes Care 2010;22:676-682


Threshold glucose levels (mmol/L) after a 75g OGTT

OR 1.75 OR 2.0

Fasting plasma glucose

5.1 5.3



% of cohort that met ≥ 1 threshold above

16.1% 8.8%

Odds Ratio (OR) of 1.75 vs. 2.0 for Primary Outcome in HAPO

OGTT = Oral Glucose Tolerance TestHAPO = Hyperglycemia and Adverse Pregnancy Outcomes studyIADPSG. Diabetes Care 2010;22:676-682


HAPO: Incidence of Adverse Outcomes for Glucose Categories (OR 1.75 or 2.0 )

Metzger BE, et al. HAPO. NEJM 2008;358(19):1991-2002.


Remains a Controversial Topic …


Considerations for the CDA Adopting the IADPSG Thresholds

• How can we select an odds ratio threshold in the

absence of a true threshold in the data?

• What is the impact on the patient and workload of

increasing the prevalence of GDM?

• Do we have sufficient evidence with respect to

treatment benefit at the various thresholds to make

an informed decision?

• In the absence of clear benefit, should the diagnostic

criteria be changed from 2008?


2013 CDA Diagnostic Criteria for GDM

PREFERRED APPROACH (2 steps)

1. 50 gram glucose challenge test

2. 75 gram oral glucose tolerance test

– Using thresholds of OR 2.0

ALTERNATIVE APPROACH (1 step)

1. 75 gram oral glucose tolerance test

– Using thresholds of OR 1.75

2013


2013 GDM Diagnosis: Two Approaches2013


2013 GDM Diagnosis: Preferred Approach 2013


2013 GDM Diagnosis: Preferred Approach2013


2013 GDM diagnosis: Alternative Approach 2013


Recommendations 16-17: Diagnosis of GDM

16.All pregnant women should be screened for GDM

at 24-28 weeks of gestation [Grade C, Level 3].

17. If there is a high risk of GDM based on multiple

clinical factors, screening should be offered at any

stage in the pregnancy [Grade D, Consensus]. If the initial

screening is performed before 24 weeks of

gestation and is negative, rescreen between 24-28

weeks of gestation. (see next slide)


Recommendation 17: Risk Factors for GDM (continued)

• Age ≥35 years

• Previous GDM

• Prediabetes

• High risk population – Aboriginal, Hispanic, South

Asian, Asian, African

• BMI ≥30 kg/m2

• Polycystic ovarian

syndrome

• Acanthosis nigricans

• Corticosteroid use

• History of macrosomic

infant

• Current fetal macrosomia

or polyhydramnios [Grade D, Consensus]


Recommendation 18: Diagnosis of GDM

18.The preferred approach for the screening and

diagnosis of GDM is the following [Grade D, Consensus]:

a) Screening for GDM should be conducted using the 50 g

glucose challenge test (GCT) administered in the non-

fasting state with plasma glucose measured one hour later

[Grade D, Level 4]. A plasma glucose value ≥7.8 mmol/L at

one hour will be considered a positive screen and will be

an indication to proceed to the 75 gram OGTT [Grade C, Level

2]. A plasma glucose value >11.1 mmol/L can be

considered to be diagnostic of gestational diabetes and

does not require a 75 gram OGTT for confirmation [Grade C,

Level 3].

2013


Recommendation 18: Diagnosis of GDM (continued)

b) If the GCT screen is positive, a 75 gram OGTT

should be performed as the diagnostic test for

GDM using the following criteria: >1 of the

following values: – Fasting >5.3 mmol/L,

– 1h >10.6 mmol/L,

– 2h >9.0 mmol/L [Grade B, Level 1]

2013


Recommendation 19: Diagnosis of GDM

19.An alternative approach that may be used to screen

and diagnose GDM is the one-step approach [Grade D,

Consensus]:

a) A 75 gram OGTT should be performed (with no

prior screening 50g GCT) as the diagnostic test for

GDM using the following criteria [Grade D, Consensus]:

≥1 of the following values: – Fasting > 5.1 mmol/L, – 1h > 10.0 mmol/L, – 2h > 8.5 mmol/L [Grade B, Level 1 (4)]

2013


Diabetes in Pregnancy: Consider PhasesPregestational diabetes Gestational diabetes

1. Preconception counseling 1. Screening & diagnosis






GDM: Glycemic Management During Pregnancy

• Perform SMBG, both fasting and postprandially• Glycemic Targets during pregnancy:

• Receive nutrition counseling– Moderate carbohydrate restriction: 3 meals + 3 snacks – Targets not met within 2 weeks start insulin – Avoid hypocaloric diet weight loss + ketosis

Target glucose values

Fasting PG <5.3 mmol/L




Pre-Pregnancy BMI Recommended range of total weight gain

(Kg)

Recommended range of total weight gain

(lb)

BMI <18.5 12.5 – 18.0 28 – 40

BMI 18.5 - 24.9 11.5 – 16.0 25 – 35

BMI 25.0 - 29.9 7.0 – 11.5 15 – 23

BMI > or = 30 5.0 – 9.0 11 – 20

Recommended rate of weight gain and total weight gain for singleton Pregnancies according to pre-pregnancy BMI

IOM Guidelines for Gestational Weight Gain

Institute of Medicine. Weight gain during pregnancy: reexamining the guidelines. Consensus Report. May 2009. The National Academies Press. Washington, DC.


What About Insulin Analogues and Oral Agents Among Patients with GDM?

• May use rapid-acting analog insulin for postprandial

glucose control – no difference in perinatal outcomes

• May use glyburide or metformin for women who

are non-adherent to or who refuse insulin– Likely safe BUT it is OFF-Label no long-term data, need

discussion with patient


GDM: Glycemic Management During Labour and Delivery

• Keep maternal blood glucose l between 4.0 and 7.0

mmol/L reduce risk of neonatal hypoglycemia

• Women should receive adequate glucose during

labour in order to meet the high energy requirements

2013


Postpartum GDM Management Checklist

1. Encourage Breastfeeding

2. 75g OGTT between 6 weeks - 6 months

postpartum to detect prediabetes or diabetes

3. Discuss increased long-term risk of diabetes –

Importance of returning to pre-pregnancy weight


Recommendation 20: Management During Pregnancy (GDM)

20.Women with GDM should:

a. Strive for target glucose values: – Fasting PG below 5.3 mmol/L [Grade B, Level 2]

– 1h postprandial below 7.8 mmol/L [Grade B, Level 2]

– 2h postprandial below 6.7 mmol/L [Grade B, Level 2]

b. Perform SMBG, both fasting and postprandially to

achieve glycemic targets and improve pregnancy

outcomes [Grade B, Level 2]

c. Avoid ketosis during pregnancy [Grade C, Level 3]



21.Receive nutrition counseling from a registered

dietitian during pregnancy [Grade C, Level 3] and

postpartum [Grade D, Consensus]. Recommendations for

weight gain during pregnancy should be based on

pregravid BMI [Grade D, Consensus].


Recommendation 22 and 24: Management During Pregnancy (GDM)

22. If women with GDM do not achieve glycemic targets

within 2 weeks from nutritional therapy alone,

insulin therapy should be initiated [Grade D, Consensus].

23. Insulin therapy in the form of multiple injections

should be used [Grade A, Level 1].

24.Rapid-acting bolus analog insulin may be used

over regular insulin for postprandial glucose control

although perinatal outcomes are similar [Grade B, Level 2].

2013



25.For women who are non-adherent to or who refuse

insulin, glyburide [Grade B, Level 2] or metformin [Grade B,

Level 2] may be used as alternative agents for

glycemic control. Use of oral agents in pregnancy is

off-label and this should be discussed with the

patient [Grade D, Consensus].


Recommendation 26: Intrapartum Management (GDM)

26.Women should be closely monitored during labour

and delivery and maternal blood glucose levels

should be kept between 4.0 and 7.0 mmol/L in

order to minimize the risk of neonatal hypoglycemia. [Grade D, Consensus]

27.Women should receive adequate glucose during

labour in order to meet the high energy requirements [Grade D, Consensus].

2013

2013


Recommendation 28: Postpartum (GDM)

28.Women with GDM should be encouraged to

breastfeed immediately after delivery in order to

avoid neonatal hypoglycemia [Grade D, Level 4] and to

continue for at least three months postpartum in

order to prevent childhood obesity [Grade C, Level 3] and

reduce risk of maternal hyperglycemia [Grade C, Level 3].

29.Women should be screened with a 75g OGTT

between 6 weeks and 6 months postpartum to

detect prediabetes and diabetes [Grade D, Consensus].

2013


CDA Clinical Practice Guidelines

http://guidelines.diabetes.ca – for professionals

1-800-BANTING (226-8464)

http://diabetes.ca – for patients

http://guidelines.diabetes.ca/

http://diabetes.ca/

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