This is the current release of the guideline.

Congenital abnormalities associated with pre-existing and gestational diabetes mellitus (GDM)

Counseling
Prevention
Risk Assessment
Screening

Endocrinology
Family Practice
Internal Medicine
Obstetrics and Gynecology

Advanced Practice Nurses
Physician Assistants
Physicians

• To review the teratogenesis associated with pre-existing gestational diabetes
• To provide guidelines to optimize prevention and diagnosis of fetal abnormalities in women with diabetes
• To identify areas specific to fetal abnormalities and diabetes requiring further research

Women with pre-existing and gestational diabetes who become or are attempting to become pregnant

1. Pre-conception recognition of women at high risk
2. Offer biochemical and ultrasonic screening, detailed evaluation of fetal cardiac structures
3. Obtain family history
4. Pre-conception counseling by multidisciplinary team that reviews risks and encourages planned pregnancy
5. Maintain euglycemia before and during pregnancy
6. Pre-conception and first trimester folic acid supplementation

• Structural congenital abnormalities
• Chromosomal abnormalities
• Perinatal and infant mortality and morbidity

Hand-searches of Published Literature (Primary Sources)
Hand-searches of Published Literature (Secondary Sources)
Searches of Electronic Databases

The Cochrane Library and Medline were searched for English-language articles, published from 1990 to February 2005, relating to pre-existing and gestational diabetes and fetal abnormalities. Search terms included pregnancy, diabetes mellitus, pre-existing diabetes, pregestational diabetes, type 1 diabetes, type 2 diabetes, insulin dependent diabetes, gestational diabetes, impaired glucose tolerance, congenital anomalies, malformations, and stillbirth. Additional publications were identified from the bibliographies of these articles as well as the Science Citation Index. All study types were reviewed. Randomized controlled trials were considered evidence of the highest quality, followed by cohort studies. Key studies and supporting data for each recommendation are summarized with evaluative comments and referenced.

Not stated

Weighting According to a Rating Scheme (Scheme Given)

Quality of Evidence Assessment*

I: Evidence obtained from at least one properly designed randomized controlled trial.

II-1: Evidence obtained from well-designed controlled trials without randomization.

II-2: Evidence obtained from well-designed cohort (prospective or retrospective) or case–control analytic studies, preferably from more than one center or research group.

II-3: Evidence obtained from comparisons between times or places with or without the intervention. Dramatic results in uncontrolled experiments (such as the results of treatment with penicillin in the 1940s) could also be included in this category

III: Opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees.

* Adapted from the Evaluation of Evidence criteria described in the Canadian Task Force on Preventive Health Care.

Systematic Review

Not stated

Expert Consensus

Not stated

Classification of Recommendations*

A.   There is good evidence to recommend the clinical preventive action

B.   There is fair evidence to recommend the clinical preventive action

C.   The existing evidence is conflicting and does not allow to make a recommendation for or against use of the clinical preventive action; however, other factors may influence decision-making

D.   There is fair evidence to recommend against the clinical preventive action

E.   There is good evidence to recommend against the clinical preventive action

I.   There is insufficient evidence (in quantity or quality) to make a recommendation; however, other factors may influence decision-making

*Adapted from the Classification of Recommendations criteria described in the Canadian Task Force on Preventive Health Care.

A formal cost analysis was not performed and published cost analyses were not reviewed.

Internal Peer Review

This guideline has been reviewed by the Genetics Committee and the Maternal Fetal Medicine Committee, and approved by the Executive and Council of the Society of Obstetricians and Gynaecologists of Canada (SOGC).

The quality of evidence (I-III) and classification of recommendations (A-E, I) are defined at the end of the "Major Recommendations."

Pathophysiology

1. Experimental studies suggest that hyperglycemia is the major teratogen in diabetic pregnancies, but other diabetes-related factors may also affect fetal outcomes. Further research using animal models is required to clarify the teratogenic factors associated with pre-existing and gestational diabetes. (II-3C)

Pre-Existing Diabetes

2. Prospective and retrospective cohort studies have demonstrated an increased risk of congenital abnormalities with pre-existing diabetes (see Table 2 in the original guideline document for specific malformations). Further studies that include outcomes from first and second trimester pregnancy terminations, account for potential confounding variables, and use appropriate control groups are required. (II-2A)

Gestational Diabetes

3. Prospective and retrospective cohort studies have demonstrated an increased risk of congenital abnormalities with gestational diabetes. This observation is probably related to the inclusion of women with unrecognized type 2 diabetes. Clarification of the relationship between gestational diabetes and congenital abnormalities by studies that include outcomes from first and second trimester pregnancy terminations, account for potential confounding variables, and use appropriate control groups are required. (II-2A)
4. In some women, type 2 diabetes may be identified for the first time in pregnancy. Pre-conception recognition of women at high risk for type 2 diabetes and optimal glycemic control may reduce the risk of congenital anomalies. (II-2A)

Medications

5. Second generation sulfonylureas have not been associated with congenital abnormalities in human studies. The use of biguanides may be associated with other adverse perinatal outcomes. The use of other oral antihyperglycemic agents is not recommended in pregnancy. (II-2A)

Effect of Obesity

6. The risk of congenital abnormalities is increased in the offspring of obese women with diabetes. A healthy diet and regular exercise may help optimize pre-pregnancy weight and reduce the risk of congenital anomalies. (II-2A)

Prenatal Diagnosis

7. Accurate determination of gestational age is required in women with diabetes. Given the increased risk of congenital abnormalities, they should be offered appropriate biochemical and ultrasonographic screening and a detailed evaluation of fetal cardiac structures. (II-2A)

Pre-Conception Counseling

8. Women with diabetes should be offered pre-conception counselling with a multidisciplinary team to optimize general health and glycemic control and to review the risks of congenital anomalies. (II-2A)
9. A careful history should be obtained to identify other factors, such as a positive family history or advanced maternal age, that may further increase the risk of congenital structural or chromosomal abnormalities. (II-2A)
10. Pregnancy in women with diabetes should be planned. Good contraceptive advice and pre-pregnancy counselling are essential. Euglycemia should be maintained before and during pregnancy. (II-2A)
11. All women with diabetes should be counselled regarding intake of foods high in folic acid, folate-fortified foods, and appropriate folic acid supplementation of 4 to 5 mg per day pre-conceptionally and in the first 12 weeks of gestation. (II-2A)
12. A substantial number of women with diabetes do not access pre-conception care programs. Strategies are needed to improve access to such programs and to maximize interventions associated with improved pregnancy outcomes, such as folic acid use. (II-2A)

Definitions

Quality of Evidence Assessment*

I: Evidence obtained from at least one properly designed randomized controlled trial.

II-1: Evidence obtained from well-designed controlled trials without randomization.

II-2: Evidence obtained from well-designed cohort (prospective or retrospective) or case–control analytic studies, preferably from more than one center or research group.

II-3: Evidence obtained from comparisons between times or places with or without the intervention. Dramatic results in uncontrolled experiments (such as the results of treatment with penicillin in the 1940s) could also be included in this category

III: Opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees.

Classification of Recommendations **

A.   There is good evidence to recommend the clinical preventive action

B.   There is fair evidence to recommend the clinical preventive action

C.   The existing evidence is conflicting and does not allow to make a recommendation for or against use of the clinical preventive action; however, other factors may influence decision-making

D.   There is fair evidence to recommend against the clinical preventive action

E.   There is good evidence to recommend against the clinical preventive action

I.   There is insufficient evidence (in quantity or quality) to make a recommendation; however, other factors may influence decision-making

*The quality of evidence reported in these guidelines has been adapted from The Evaluation of Evidence criteria described in the Canadian Task Force on Preventive Health Care.

**Recommendations included in these guidelines have been adapted from the Classification of Recommendations criteria described in the Canadian Task Force on Preventive Health Care.

None provided

The type of supporting evidence is identified and graded for each recommendation (see "Major Recommendations").

• Appropriate counseling and prevention of fetal abnormalities in women with pre-existing or gestational diabetes
• Increased awareness of fetal abnormalities associated with pre-existing and gestational diabetes

• First generation sulfonylureas (such as chlorpropamide) have been shown to cross the placenta; however, the newer second generation sulfonylureas (such as glyburide) may not cross the placenta, and less fetal exposure may occur.
• Biguanides cross the placenta, and although they do not appear teratogenic, they have been associated with other adverse perinatal outcomes such as gestational hypertension and increased perinatal mortality when used for treatment in diabetic pregnancies.

This document reflects emerging clinical and scientific advances on the date issued and is subject to change. The information should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be reproduced in any form without prior written permission of the Society of Obstetricians and Gynaecologists of Canada (SOGC).

An implementation strategy was not provided.

Staying Healthy

Effectiveness
Patient-centeredness

Not applicable: The guideline was not adapted from another source.

2007 Nov

Society of Obstetricians and Gynaecologists of Canada - Medical Specialty Society

Society of Obstetricians and Gynaecologists of Canada

Society of Obstetricians and Gynaecologists of Canada Genetics Committee
Society of Obstetricians and Gynaecologists of Canada Maternal Fetal Medicine Committee

Principal Authors: Victoria M. Allen, MD, MSc, FRCSC, Halifax NS; B. Anthony Armson, MD, MSc, FRCSC, Halifax NS

Genetics Committee Members: R. Douglas Wilson (Chair), MD, MSc, FRCSC, Philadelphia PA; Victoria M. Allen, MD, MSc, FRCSC, Halifax NS; Claire Blight, RN, Halifax, NS; Alain Gagnon, MD, FRCSC, Vancouver B.C.; Jo-Ann Johnson, MD, FRCSC, Calgary AB; Sylvie Langlois, MD, FRCPC, Vancouver B.C.; Anne Summers, MD, FRCPC, Toronto ON; Philip Wyatt, MD, PhD, North York ON

Maternal Fetal Medicine Committee Members: Dan Farine (Chair), MD, FRCSC, Toronto ON; B. Anthony Armson, MD, MSc, FRCSC, Halifax NS; Joan Crane, MD, FRCSC, St. John's NL; Marie-France Delisle, MD, FRCSC, Vancouver B.C.; Lisa Keenan-Lindsay, RN, Toronto ON; Valerie Morin, MD, FRCSC, Montreal QC; Carol Ellison Schneider, MD, FRCSC, Winnipeg MB; John Van Aerde, MD, FRCPC, Edmonton AB

Not stated

This is the current release of the guideline.

None available

None available

This NGC summary was completed by ECRI Institute on March 9, 2009. The information was verified by the guideline developer on March 25, 2009.

This NGC summary is based on the original guideline, which is subject to the guideline developer's copyright restrictions.