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LETTERS: W J Huttly, N J Wald, and J C Walters Folic acid supplementation before pregnancy remains inadequate BMJ 1999; 319: 1499 [Full text]

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Think conception at the time of contraception!

James Andrew McSherry   (9 December 1999)

Dr.

Fabio Parazzini   (29 January 2000)

Think conception at the time of contraception! 9 December 1999
James Andrew McSherry, Professor of Family Medicine The University of Western Ontario, London, Canada Send response to journal: Re: Think conception at the time of contraception!	The case for pre-conceptual folic acid supplementation seems unanswerable as a means of reducing the numbers of children with neural tube defects. There's no doubt that a population-based strategy would be the most effective approach to the problem, but it seems to take an enormous amount of time for a government to make up its mind on something that could be seen by some as basically tampering with food. There is another way of dealing with at least a piece of this problem. If 28-day oral contraceptive packages were altered to contain 21 OC active tablets and 7 folic acid tablets instead of an inert filler, and women seeking contraceptive advice were at least given the option of subsequently stopping oral contraception in good folic acid status, wouldn't that do something to help resolve an impasse? Let's think conception at the time we think contraception! James Andrew McSherry.
Dr. 29 January 2000
Fabio Parazzini, Head, Analytical Epidemiology Unit Istituto di Ricerche Farmacologiche "Mario Negri" Send response to journal: Re: Dr.	Periconceptional folic acid supplements in Italy: evidence based clinical practice is possible? EDITOR - Although the optimal dosage, timing, and vehicle for folic acid have not been established, the most convincing trials1,2 support the recommendation that all women planning or at risk of pregnancy take a daily multivitamin supplement containing 0.4-0.8mg of folic acid, beginning at least 1 month before conception and continuing through the first trimester for primary prevention of neural tube defects (NTDs). Despite this consistent evidence and following recommendation, in Italy no folate strategy to prevent NTDs has been developed. The lack of any national campaign addressed to support and maintain the periconceptional supplementation is mirrored in clinical practice, that not appear in agreement with scientific evidence. We do not know surveys among Italian women in reproductive age to assess the extent of use of supplements before conception. The only available information derived from an international co-operative study on drug use in pregnancy3, that enrolled over 5000 Italian women giving birth in 64 hospitals in 1989-90, before the publication of the Medical Research Council and the Hungarian trials. About 11-12% of Italian women took haematological and/or nutritional supplements in the first trimester, of which only a part was folic acid. More recent data between 1994 and 1997 derived from 1061 women who gave birth at term to healthy infants interviewed as controls in the framework of a case control study on the risk factors for obstetric conditions4: only 6% of them declared to have used multivitamin supplements during pregnancy, without any important difference on reproductive age, reproductive history or socioeconomic status. T he scientific evidence do not seem to have changed the attitude of Italian women on periconceptional folic acid supplementation. Moreover it is likely that, although a part of Italian pregnant women take supplements, most do not begin before conception but only after, and most of them after the fifth week of pregnancy, which may well offer little or no protection since neural tube closure is 26-27 days after conception. Furthermore, in the Italian market there is an high availability of multivitamin supplements containing too low doses of folic acid for primary prevention (0.1-0.3mg) and more than 25 formulations of folic acid containing up to 15mg of metabolically active form, that are widely promoted by manufacturers among gynaecologists. This raises some concerns about the cost and the safety of high doses of folic acid in pregnancy and reproductive age. Although no adverse effects of folic acid at doses of 4mg per day were noted in the Medical Research Council study, the size of the trial was not large enough to eliminate the chance of a low-frequency toxic effect. Folic acid supplements administered to pregnant women have not been found to cause long-term developmental, neurologic or major behaviour disorders in children but worries, fussiness, and fearfulness were highly significantly overrepresented5. Considering that an increase of intake to 1.0mg of folic acid per day would give just a 5% additional reduction in the total NTD rate6, the current guidelines of 0.4 mg per day of folic acid may therefore be near optimal, particularly given the concern that too high an intake of folic acid may result in a masking of vitamin B12 deficiency. Although a note of caution should be addressed in that the Medical Research Council and the Hungarian trials were performed in areas with higher prevalence of NTDs than Italy, this does not justify the lack of active effort to support and maintain these recommendations also in Italy. Given the efforts directed towards antenatal screening for congenital abnormalities, it is disappointing that recommendations aimed at the level of primary prevention have received such low priority. *Renata Bortolus, Fabio Parazzini, Antonio Addis *Analytical Epidemiology Unit and Laboratory for Mother-Child Health and CRIF-Regional Drug Information Centre, Istituto di Ricerche Farmacologiche Mario Negri, 20157 Milan, Italy 1 MRC Vitamin Study Research Group. Prevention of neural tube defects: results of the MRC Vitamin Study. Lancet 1991; 338: 131-37. 2 Czeizel AE, Dudas I. Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation. N Engl J Med 1992; 327: 1832-35. 3 Collaborative group on drug use in pregnancy (C.G.D.U.P.). Medication during pregnancy: an intercontinental cooperative study. Int J Gynecol Obstet 1992; 39: 185-96. 4 Parazzini F, Chatenoud L, Di Cintio E, Mezzopane R, Surace M, Zanconato G, Fedele L, Benzi G. Coffee consumption and risk of hospitalized miscarriage before 12 weeks of gestation. Hum Reprod 1998; 13: 2286-91. 5 Holmes-Siedle M, Dennis J, Lindenbaum RH, Galliard A. Long term effects of periconceptional multivitamin supplements for prevention of neural tube defects: a seven to 10 year follow up. Arch Dis Child 1992; 67: 1436-41. 6 Daly LE, Kirke PN, Molloy A, Weir DG, Scott JM. Folate levels and neural tube defects. Implications for prevention. JAMA 1995; 274: 1698- 702.