PRATIQUE CLINIQUE

Motherisk Update

Multivitamin supplements for pregnant women

New insights

Eric Ahn  Alejandro A. Nava-Ocampo, MD, MSC  Gideon Koren, MD, FRCPC

Prenatal multivitamins are recommended before and during pregnancy to prevent iron-deficiency anemia and neural tube defects (NTDs).1-3 A range of prenatal supplements are available; most meet the required dietary allowance for pregnant women.

Some patients have very low tolerance of iron because they have morning sickness, which is experienced by 50% to 80% of pregnant women.4 A new twice-a-day prenatal multivitamin supplement (PregVit®) might be an appropriate alternative for women unable to tolerate the side effects of ingesting iron at high doses. The morning tablet contains 35 mg of iron, almost 50% less than is in most prenatal multivitamins. Calcium is provided in the night tablet so that it does not interfere with the absorption of iron, which is why the lower dose of iron is adequate.5,6 A recent study at the Motherisk program showed that patients absorbed similar amounts of iron from PregVit® and another widely used prenatal supplement.

Even today, following folate fortification of flour, about half of Canadian women have folate levels below the protective 900 nM and thus are at increased risk of having babies with NTDs.7 Folic acid supplementation is especially important before closure of the neural tube at approximately 28 days’ gestation (iron becomes more important during the second and third trimesters). Folic acid might be beneficial throughout the first trimester in preventing other malformations also.8

Women who have a family history of NTDs, insulin-dependent diabetes mellitus, or epilepsy, or are currently taking valproic acid, carbamazepine, or antifolates (eg, sulfonamides) are at intermediate-to-high risk of having babies with NTDs. These women need 4 mg to 5 mg of folic acid daily starting before they become pregnant.

New and potentially important findings were recently reported in an analysis of all published folic acid dose-level studies. Results demonstrated that to achieve the needed serum concentration of 900 nM, 5 mg of folic acid are required daily. This dose, rather than the previously recommended 0.4 to 1.0 mg dose, could prevent 85% of folate-dependent NTDs.9 The main concern with this high dose of folic acid is that it could mask vitamin B12–deficiency pernicious anemia. Making a general recommendation for higher folate supplementation must await in-depth analysis of the effects of the “low folate” fortification instituted in the United States and Canada in 1997-1998.

Finally, prenatal multivitamins contain iron and calcium, both of which are potent inhibitors of absorption of levothyroxine.10,11 A recent study found that doses of levothyroxine do not need to be modified if prenatal multivitamins are taken 4 hours after ingestion of levothyroxine.12 Concomitant ingestion of iron causes marked decreases in the bioavailability of a variety of drugs (Table 1).13 The major mechanism of these drug interactions is the formation of iron-drug complexes.

References

1. Beaton GH. Iron needs during pregnancy: do we need to rethink our targets? Am J Clin Nutr 2000;72(Suppl 1):265-71S.
2. MRC Vitamin Study Research Group. Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. Lancet 1991;338:131-7.
3. Czeizel AE, Dudas I. Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation. N Engl J Med 1992;327:1832-5.
4. Koren G, Boskovic R, Hard M, Maltepe C, Navioz Y, Einarson A. Motherisk-PUQE (pregnancy-unique quantification of emesis and nausea) scoring system for nausea and vomiting of pregnancy. Am J Obstet Gynecol 2002;186(Suppl 5):S228-31.
5. Bendich A. Calcium supplementation and iron status of females. Nutrition 2001;17:46-51.
6. Zijp IM, Korver O, Tijburg LB. Effect of tea and other dietary factors on iron absorption. Crit Rev Food Sci Nutr 2000;40:371-98.
7. Kapur B, Soldin OP, Koren G. Potential prevention of neural tube defects by assessment of women of childbearing age through monitoring of folate. Ther Drug Monit 2002;24:628-30.
8. French AE, Grant R, Weitzman S, Ray JG, Vermeulen MJ, Sung L, et al. Folic acid food fortification is associated with a decline in neuroblastoma. Clin Pharmacol Ther 2003;74:288-94.
9. Wald NJ, Law MR, Morris JK, Wald DS. Quantifying the effect of folic acid. Lancet 2001;358:2069-73.
10. Campbell NR, Hasinoff BB, Stalts H, Rao B, Wong NC. Ferrous sulfate reduces thyroxine efficacy in patients with hypothyroidism. Ann Intern Med 1992;117:1010-3.
11. Singh N, Singh PN, Hershman JM. Effect of calcium carbonate on the absorption of levothyroxine. JAMA 2000;283:2822-5.
12. Chopra IJ, Baber K. Treatment of primary hypothyroidism during pregnancy: is there an increase in thyroxine dose requirement in pregnancy? Metabolism 2003;52:122-8.
13. Campbell NR, Hasinoff BB. Iron supplements: a common cause of drug interactions. Br J Clin Pharmacol 1991;31:251-5.

Motherisk questions are prepared by the Motherisk Team at the Hospital for Sick Children in Toronto, Ont. Dr Nava-Ocampo and Dr Soldin are members and Dr Koren is Director of the Motherisk Program. Dr Koren, a Senior Scientist at the Canadian Institutes for Health Research, is supported by the Research Leadership for Better Pharmacotherapy during Pregnancy and Lactation and, in part, by a grant from the Canadian Institutes for Health Research.

Do you have questions about the safety of drugs, chemicals, radiation, or infections in women who are pregnant or breastfeeding? We invite you to submit them to the Motherisk Program by fax at (416) 813-7562; they will be addressed in future Motherisk Updates.

Published Motherisk Updates are available on the College of Family Physicians of Canada website ( www.cfpc.ca ). Some articles are published in The Motherisk Newsletter and on the Motherisk website ( www.motherisk.org) also.