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son JD: Diabetes mellitus during preg- nancy and the risk for specific birth ... Obstet Gynecol 102:203–213,. 2003. 5. Wilson RD, Davies G, Desilets V, Reid GJ,.

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OBSERVATIONS What Dose of Folic Acid Should Be Used for Pregnant Diabetic Women?

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t is well established that folate requirements increase during pregnancy and that supplementing 0.4 mg folic acid/ day to the general pregnant population is beneficial in terms of reducing the risk of neural tube defects (NTDs). Offspring of women with pregestational diabetes mellitus have an increased risk of congenital anomalies, including NTDs (1). In animal models, folic acid supplementation reduces glucose-induced congenital anomalies with a threshold effect (2). In humans, the protection afforded by folic acid supplementation against diabetesassociated birth defects is not clear: multivitamin supplements have been reported to reduce the risk of congenital anomalies, but the composition of the supplements was unknown and the benefit probably included that of overall prepregnancy care (3). In recent years, several academic societies (4,5) have recommended high doses of folic acid (4 –5 mg/day) to diabetic pregnant women, based on their risk of congenital malformations. As folic acid–tolerable upper intake level is 1 mg/day, the aforementioned

DIABETES CARE, VOLUME 30, NUMBER 7, JULY 2007

recommendations should be considered in the pharmacological range. High doses of folic acid can aggravate B12 vitamin deficiency and promote neoplasia (6), with diabetic women being at high risk (7). On the other hand, most diabetic women, even when planning pregnancy, do not take any folic acid supplement (8). We suggest that large efforts be made to ensure that, as one of the interventions of comprehensive prepregnancy care, diabetic women receive at least the folic acid dose recommended for the general population. When using high doses, we must take into account that they are in the pharmacological range, that there is no evidence of their benefit as a primary prevention strategy in diabetic pregnancy, and that side effects are potentially serious.

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ISMAEL CAPEL, MD1 ROSA CORCOY, MD, PHD1,2 From the 1Department of Endocrinology and Nutrition, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; and 2CIBER Bioengineering, Biomaterials and Nanotechnology, Instituto de Salud Carlos III, Madrid, Spain. Address correspondence to Ismael Capel, Department of Endocrinology and Nutrition, Hospital de la Santa Creu i Sant Pau, Sant Antoni M. Claret, 16708025, Barcelona, Spain. E-mail: [email protected] es. DOI: 10.2337/dc07-0200 © 2007 by the American Diabetes Association. ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●

References 1. Becerra JE, Khoury Mj, Cordero JF, Erickson JD: Diabetes mellitus during pregnancy and the risk for specific birth

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defects: a population-based case-control study. Pediatrics 85:1–9, 1990 Wentzel P, Ga¨reskog M, Eriksson UJ: Folic acid supplementation disminishes diabetes- and glucose-induced dysmorphogenesis in rat embryos in vivo and in vitro. Diabetes 54:546 –547, 2005 Correa A, Botto L, Liu Y, Mulinare J, Erikson JD: Do multivitamin supplements attenuate the risk for diabetes-associated birth deffects? Pediatrics 111:1146 –1151, 2003 ACOG Committee on Practice Bulletins: ACOG practice bulletin: clinical management guidelines for obstetrician-gynecologists: number 44, July 2003 (replaces committee opinion number 252, March 2001). Obstet Gynecol 102:203–213, 2003 Wilson RD, Davies G, Desilets V, Reid GJ, Summers A, Wyatt P, Young D, Genetics Committee and Executive and Council of the Society of Obstetricians and Gynaecologists of Canada: The use of folic acid for the prevention of neural tube defects and other congenital anomalies. J Obstet Gynaecol Can 25:959 –973, 2003 Kim YI: Will mandatory folic acid fortification prevent or promote cancer? Am J Clin Nutr 80:1123–1138, 2004 Rapp K, Schroeder J, Klenk J, Ulmer H, Concin H, Diem G, Oberaigner W, Weiland SK: Fasting blood glucose and cancer risk in a cohort of more than 140,000 adults in Austria. Diabetologia 49:945– 952, 2006 Roland JM, Murphy HR, Ball V, Northcote-Wrightt J, Temple RC: The pregnancies of women with type 2 diabetes: poor outcomes but opportunities for improvement. Diabet Med 22:1774 –1777, 2005

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