Teratogenicity associated with pre-existing and gestational diabetes.J Obstet Gynaecol Can. 2007 Nov; 29(11):927-934.JO
To review the teratogenesis associated with pre-existing and gestational diabetes, to provide guidelines to optimize prevention and diagnosis of fetal abnormalities in women with diabetes, and to identify areas specific to fetal abnormalities and diabetes requiring further research.
Increased awareness of fetal abnormalities associated with pre-existing and gestational diabetes.
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, 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.
The evidence collected was reviewed by the Genetics and Maternal Fetal Medicine Committees of the Society of Obstetricians and Gynaecologists of Canada (SOGC) and quantified using the criteria and classifications of the Canadian Task Force on Preventive Health Care.
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) 2. Prospective and retrospective cohort studies have demonstrated an increased risk of congenital abnormalities with pre-existing diabetes. 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) 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) 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) 6. The risk of congenital anomalies 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) 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) 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) VALIDATION: These guidelines have been reviewed by the Genetics Committee and the Maternal Fetal Medicine Committee of the SOGC. Final approval has been given by the Executive and Council of the Society of Obstetricians and Gynaecologists of Canada.