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Diabetes

 

Maternal diabetes can develop during pregnancy, affect how a body's cells use sugar, and cause high blood sugar levels that can affect a pregnancy and a baby's health. When poorly controlled, it is a well-known, established teratogen, a factor that causes an embryo or fetus to develop abnormally. It causes heart defects but also other major birth defects, 1-10, i.e. infants with two or more major malformations, or three or more minor malformations. With good blood sugar control, including monitoring and controlling blood sugar levels starting before becoming pregnant, diabetes-related malformations can be minimized and possibly eliminated. Because some women have diabetes but do not know it, screening for unrecognized diabetes before conception is important for detecting and controlling diabetes and its teratogenic effects in pregnancy.

Maternal diabetes has been associated with a wide range of congenital heart defects. Specific types of heart defects consistently associated with maternal diabetes include laterality defects (heterotaxy) and several conotruncal defects. Less consistently, but still associated with maternal diabetes are left ventricular outflow obstructive defects and septal defects1-6, 9, 11. Cardiomyopathy also occurs but typically resolves over time.

The frequency of diabetes among women of childbearing age varies by country, age, and other factors. According to one estimate, diabetes affects approximately 2% or 1.85 million women of childbearing age in the United States. Including diabetes management as part of a preconception plan could decrease the risk for pregnancy loss and congenital malformation for approximately 113,000 births per year15. Rates of diabetes are not only high, but rising in both developed and developing countries16, 17. Of additional concern is that many women could have unrecognized or undiagnosed diabetes. One study estimates that in the United States, for every two women of childbearing age diagnosed with diabetes, there is another one with undiagnosed diabetes18.

Strategies fo​​r Prevention:

Even without considering the overall effect on women's health, these three elements -- strong evidence for causation, high relative risk for disease, and comparatively high and rising frequency in the population – combine to make diabetes a clear priority for prevention. Additionally, findings show that it is possible to reduce considerably the risk of diabetes-related malformations in pregnancy through careful monitoring and controlling of blood sugar levels before a woman becomes pregnant15, 19, 20. In practice, however, many affected pregnancies continue to occur8, 15, 21, highlighting the challenges of implementing optimal preconceptional control22.

Some findings suggest that birth defect risk may be lower among diabetic women who also took a folic acid-containing multivitamin supplement from before conception2. If confirmed, taking such a supplement could represent an additional prevention strategy for diabetes-associated birth defects. In summary, maternal diabetes is an established, serious risk for heart defects, and an achievable priority target for prevention efforts.

Selected R​​eferences:

1. Becerra JE, Khoury MJ, Cordero JF, Erickson JD. Diabetes mellitus during pregnancy and the risks for specific birth defects: a population-based case-control study. Pediatrics 1990;85(1):1-9.

2. Correa A, Botto L, Liu Y, Mulinare J, Erickson JD. Do multivitamin supplements attenuate the risk for diabetes-associated birth defects? Pediatrics 2003;111(5 Part 2):1146-51.
3. Correa A, Gilboa SM, Besser LM, Botto LD, Moore CA, Hobbs CA, et al. Diabetes mellitus and birth defects. Am J Obstet Gynecol 2008;199(3):237 e1-9.

4. Ferencz C, Loffredo CA, Correa-Villasenor A, Wilson PD. Genetic and environmental risk factors of major congenital heart disease: the Baltimore-Washington Infant Study 1981-1989. Mount Kisco, NY: Futura Publishing Company, Inc.; 1997.

5. Lisowski LA, Verheijen PM, Copel JA, Kleinman CS, Wassink S, Visser GH, et al. Congenital heart disease in pregnancies complicated by maternal diabetes mellitus. An international clinical collaboration, literature review, and meta-analysis. Herz 2010;35(1):19-26.

6. Loffredo CA. Epidemiology of cardiovascular malformations: prevalence and risk factors. Am J Med Genet 2000;97(4):319-25.

7. Moore LL, Singer MR, Bradlee ML, Rothman KJ, Milunsky A. A prospective study of the risk of congenital defects associated with maternal obesity and diabetes mellitus. Epidemiology 2000;11(6):689-94.

8. Ray JG, O'Brien TE, Chan WS. Preconception care and the risk of congenital anomalies in the offspring of women with diabetes mellitus: a meta-analysis. Qjm 2001;94(8):435-44.

9. Wren C, Birrell G, Hawthorne G. Cardiovascular malformations in infants of diabetic mothers. Heart 2003;89(10):1217-20.

10. Kousseff BG. Diabetic embryopathy. Curr Opin Pediatr 1999;11(4):348-52.

11. Rowland TW, Hubbell JP, Jr., Nadas AS. Congenital heart disease in infants of diabetic mothers. J Pediatr 1973;83(5):815-20.

12. Aberg A, Westbom L, Kallen B. Congenital malformations among infants whose mothers had gestational diabetes or preexisting diabetes. Early Hum Dev 2001;61(2):85-95.

13. Martinez-Frias ML, Bermejo E, Rodriguez-Pinilla E, Prieto L, Frias JL. Epidemiological analysis of outcomes of pregnancy in gestational diabetic mothers. Am J Med Genet 1998;78(2):140-5.

14. Sheffield JS, Butler-Koster EL, Casey BM, McIntire DD, Leveno KJ. Maternal diabetes mellitus and infant malformations. Obstet Gynecol 2002;100(5 Pt 1):925-30.

15. Johnson K, Posner SF, Biermann J, Cordero JF, Atrash HK, Parker CS, et al. Recommendations to Improve Preconception Health and Health Care --- United States. MMWR 2006(55(RR06)):1-23.

16. Harris MI, Flegal KM, Cowie CC, Eberhardt MS, Goldstein DE, Little RR, et al. Prevalence of diabetes, impaired fasting glucose, and impaired glucose tolerance in U.S. adults. The Third National Health and Nutrition Examination Survey, 1988-1994. Diabetes Care 1998;21(4):518-24.

17. Mokdad AH, Ford ES, Bowman BA, Dietz WH, Vinicor F, Bales VS, et al. Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001. Jama 2003;289(1):76-9.

18. Cowie CC, Rust KF, Byrd-Holt DD, Eberhardt MS, Flegal KM, Engelgau MM, et al. Prevalence of diabetes and impaired fasting glucose in adults in the U.S. population: National Health And Nutrition Examination Survey 1999-2002. Diabetes Care 2006;29(6):1263-8.

19. Cousins L. Etiology and prevention of congenital anomalies among infants of overt diabetic women. Clin Obstet Gynecol 1991;34(3):481-93.

20. Suhonen L, Hiilesmaa V, Teramo K. Glycaemic control during early pregnancy and fetal malformations in women with type I diabetes mellitus. Diabetologia 2000;43(1):79-82.

21. Holing EV, Beyer CS, Brown ZA, Connell FA. Why don't women with diabetes plan their pregnancies? Diabetes Care 1998;21(6):889-95.

22. Kitzmiller JL, Wallerstein R, Correa A, Kwan S. Preconception care for women with diabetes and prevention of major congenital malformations. Birth Defects Res A Clin Mol Teratol 2010;88(10):791-803.

(1. Inkster M, Fahey TP, Donnan PT, et al. 2006. Poor glycated hemoglobin control and adverse pregnancy outcomes in type 1 and type 2 diabetes: systematic review of observational studies. BMC Pregnancy and Childbirth 6:30. doi:10.1186/1471–2393-6–30. 2. Ray JG, O'Brien TE, Chan WS: Preconception care and the risk of congenital anomalies in the offspring of women with diabetes mellitus: a meta-analysis. QJM 2001, 94: 435- 444. 3. Wahabi HA, Alzeidan RA, Bawazeer GA, Alansari LA, Esmaeil SA. Preconception care for diabetic women for improving maternal and fetal outcomes: a systematic review and meta-analysis. BMC Pregnancy and Childbirth 2010, 10:63 doi:10.1186/1471-2393-10-63).​

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