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Volume 6, No. 10, October 2008
Abstract of the Month
Diabetes mellitus and birth defects
OBJECTIVE: The purpose
of this study was to examine associations between diabetes mellitus and 39 birth
defects.
STUDY DESIGN: This was a multicenter case-control study of mothers of infants
who were born with (n = 13,030) and without (n = 4895) birth defects in the National
Birth Defects Prevention Study (1997-2003).
RESULTS: Pregestational diabetes mellitus (PGDM) was associated significantly
with noncardiac defects (isolated, 7/23 defects; multiples, 13/23 defects) and
cardiac defects (isolated, 11/16 defects; multiples, 8/16 defects). Adjusted
odds ratios for PGDM and all isolated and multiple defects were 3.17 (95% CI,
2.20-4.99) and 8.62 (95% CI, 5.27-14.10), respectively. Gestational diabetes
mellitus (GDM) was associated with fewer noncardiac defects (isolated, 3/23 defects;
multiples, 3/23 defects) and cardiac defects (isolated, 3/16 defects; multiples,
2/16 defects). Odds ratios between GDM and all isolated and multiple defects
were 1.42 (95% CI, 1.17-1.73) and 1.50 (95% CI, 1.13-2.00), respectively. These
associations were limited generally to offspring of women with prepregnancy body
mass index >/=25 kg/m(2).
CONCLUSION: PGDM was associated with a wide range of birth defects; GDM was associated
with a limited group of birth defects.
Correa A, Gilboa SM, Besser LM, Botto LD, Moore CA, Hobbs CA, Cleves MA, Riehle-Colarusso TJ, Waller DK, Reece EA. Diabetes mellitus and birth defects. Am J Obstet Gynecol. 2008 Sep;199(3):237.e1-9. Epub 2008 Jul 31. http://www.ncbi.nlm.nih.gov/pubmed/18674752
OB/GYN CCC Editorial comment:
The National Birth Defects Prevention Study is a population-based case-control study utilizing data from 10 United States birth defect surveillance systems. The authors of this paper used data from this national surveillance program to examine the associations of pregestational diabetes mellitus (PGDM) and gestational diabetes (GDM) with a broad range of birth defects. The association of maternal obesity/BMI with birth defects was also assessed.
4895 controls and 13,030 cases were included in the final analysis. The prevalence of PGDM was 0.5% in the control subjects and 2.2% for the case subjects; the rates for GDM were 3.7% (controls) and 5.1% (cases). For those with PGDM, the association of diabetes with both isolated and multiple birth defects persisted, irrespective of BMI. In the setting of PGDM, the odds of an isolated anomaly increased by a factor of 3.2 and of multiple anomalies by 8.6. For those with gestational diabetes, an increased risk was noted only for those with a pre-pregnancy BMI >25 kg/m2 (GDM odds ratio isolated defects = 1.4, multiple defects = 1.5).
The authors noted that PGDM was associated with approximately 50% of the birth defect categories that were analyzed. Particular associations were noted with central nervous system defects, limb deficiencies, renal agenesis, hypospadias, orofacial clefts, and heart defects.
Notably, this study does not include information on the degree of glucose control achieved by the mothers of the control and case infants. It is well-known that the risk of fetal anomalies increases with increasing glucose levels and that A1C levels early in pregnancy (during organogenesis) correlate with risks of both miscarriage and fetal anomaly. This study is important because it quantifies the increased risk for those with PGDM and also confirms that GDM in the setting of maternal obesity is associated with a modest increase in risk as well.
This information highlights the need to identify pre-conceptually women with potential glucose control problems and assist them in achieving optimal control prior to pregnancy. Many women who have glucose intolerance or GDM in one pregnancy will go on to have PGDM with a subsequent pregnancy; these women merit special attention during pregnancy and also vigorous postpartum follow-up. In pregnancy many women are motivated to make dramatic lifestyle changes for the health of their baby; success in maintaining these changes after delivery is less common. Yet the postpartum period is a unique opportunity as this is also the pre-conceptual period for any subsequent pregnancy. Our efforts must combine the use of medical therapies, when necessary, with sustained lifestyle modification to reduce the risk of diabetes to both maternal health and to the health of future pregnancies.
Other efforts at preventing birth defects through targeted intervention have met with varying success. Folic acid fortification of food has resulted in a 20 – 30% decrease in the rates of neural tube defects (spina bifida and anencephaly) in the U.S1. Efforts to decrease rates of fetal alcohol spectrum disorders (FASD) have not been as clearly successful. For FASD, the data is limited and increased rates of diagnosis (likely due to heightened awareness amongst pediatric healthcare providers) have obscured any clear decrease in overall incidence2. FASD interventions have relied primarily on public health messaging about the dangers of alcohol. Actual resources for women to address alcoholism and binge drinking have not been as forthcoming. As the rates of diabetes and obesity continue to increase dramatically nationally, positive and truly effective public health messaging about the importance of optimal glucose control and achieving a healthy body weight prior to pregnancy merits careful attention. These population-based efforts must be paired with individual systems of support that improve access to medical care for women with diabetes and pre-diabetes and develop living environments that foster healthy food choices and exercise. These interventions are vital to both child health and maternal health.
1Centers for Disease Control. Folic Acid and Prevention of Spina Bifida and Anencephaly 10 Years After the U.S. Public Health Service Recommendation. September 13, 2002 / 51(RR13);1-3. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5730a1.htm?s_cid=mm5730a1_e
2Centers for Disease Control. Tracking Fetal Alcohol Syndrome. Fetal Alcohol Spectrum Disorders. http://www.cdc.gov/ncbddd/fas/fassurv.htm
Resources from the March of Dimes:
For Health Care Professionals:
http://www.marchofdimes.com/professionals/14332_1197.asp
For Patients:
Gestational Diabetes:
http://www.marchofdimes.com/pnhec/188_1025.asp
Pre-existing Diabetes:
http://www.marchofdimes.com/pnhec/188_1064.asp
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OB/GYN
Jean Howe, MD, MPH is the Obstetrics and Gynecology Chief Clinical Consultant (OB/GYN C.C.C.). Dr. Howe is very interested in establishing a dialogue and/or networking with anyone involved in women's health or maternal child health, especially as it applies to American Indian and Alaska Native women and also indigenous peoples around the world. Please don't hesitate to contact her by e-mail (jean.howe@ihs.gov) or phone at (928) 674-7422.
