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Alcohol and Substance

Periconception folic acid supplementation

Gideon Koren, MD, FRCPC

May, 1997



Many of my pregnant patients come to see me only after they have found out they are pregnant. I understand this is too late to prevent spina bifida. What should I do?


Motherisk has just created an information pamphlet on folic acid. We advise all primary physicians caring for women of reproductive age in Canada to give their patients this pamphlet. It can be ordered and received by fax (416) 813-7562.

Neural tube defects (NTDs) result from failure of the neural tube to close during early embryogenesis (between 21 and 27 days of gestation2) and are the most common serious congenital neurologic malformations seen in humans. Of all NTDs, 50% are spina bifida cystica (myelomeningocele, meningocele, encephalocele), and about 40% are anencephalies.2

The causative role of folate deficiency in NTDs has been suspected for more than 25 years.3 Two recent multicentre studies demonstrated this role through prospective, randomized, placebo-controlled trials.3,4

A recent study by Motherisk5 showed that women who gave birth to children with NTDs knew very little about the role of folic acid. Also, it has been shown that more than 25% of pharmacists in the Toronto area are unaware of the importance of periconception folic acid supplementation and, consequently do not recommend or advise folic acid supplementation to their female customers.6 These data suggest that 4 years after the role of folate deficiency in causing NTDs7 was established, the message was still not getting to women and primary health care professionals.

In a recent pilot study, we evaluated current awareness among family physicians in Toronto of the role of folate supplementation in prevention of NTDs.8 Because almost all women in Ontario see their family physicians first when planning pregnancy, the role of these health professionals in delivering this information is crucial. Two groups of family physicians were interviewed regarding the advice they give to female patients planning pregnancies. Confidentiality was strictly maintained, and the questionnaires were answered anonymously.

Randomly selected family physicians

A random sample of 35 physicians responded to the questionnaire: 19 men and 16 women. They had been in practice for 6 to 42 years. (Because it was a pilot study, this was a convenience sample to detect large trends in knowledge). In at least one of the scenarios, 20 (57%) physicians mentioned folic acid as one of the issues to discuss. Fifteen (43%) did not mention folic acid supplementation as a topic for discussion with women of childbearing age, with women actually planning pregnancies, or with women in the first trimester of pregnancy.

Only 14.3% knew the correct timing of folate supplementation (ie, periconception). Physicians who mentioned folate in their responses had been in practice for significantly less time than their counterparts who did not mention folate (mean was 13.5 ± 7.0 years vs 19.4 ± 11.7 years, P = 0.05).

Motherisk-recruited physicians

Thirty-six physicians were interviewed by telephone: 16 men and 20 women. Time in practice varied from 1 to 25 years (8.4 ± 5.7 years). This sample differed significantly from the random sample by being in practice, on average, only half as long (8.4 ± 5.7 years vs 16.2 ± 9.5 years, P < 0.001). In this group, only five physicians (14%) were correct in terms of both timing and dosages of folic acid supplements. Another nine (25%) understood the importance of periconception folate supplementation, but mistakenly suggested initiation of folate treatment to an already pregnant mother or did not know either the correct dose or the need to increase dose in women with increased risk of delivering a child with an NTD (eg, previous NTD delivery, taking anticonvulsants).8


Canadian mothers continue to have little awareness of the benefits of periconception folate supplementation even after giving birth to children with spina bifida.4 These findings can be explained, in part, by our present data, which show that only a small fraction of a randomly selected group of primary caregivers provide this crucial information to their patients. Among physicians who did mention folic acid, up to 40% incorrectly recommended it to an already pregnant woman and two (10%) thought that folate should be recommended only to pregnant women. Only 17% of all contacted physicians recommended folate to any woman of childbearing age. Even among primary caregivers who contacted Motherisk about drug safety during pregnancy and who presumably represent a group with higher awareness of reproductive issues, only 14% had correct knowledge of the appropriate dosages and timing for folate supplements for preventing NTDs (Table 1).

Table 1. Physicians' responses to questionnaire on folic acid

Mentioned folic acid at least once
20 (57.1)
30 (83.3)
Knew correct timing for supplementation
5 (14.3)
5 (14.0)
Not significant

*16.2 ± 9.5 years in practice, P < 0.01
8.4 ± 5.7 years in practice, P < 0.01

The obvious role of primary care physicians in advising their patients about the need for folate supplements cannot be overemphasized. Because this is one of very few congenital birth defects that can be prevented at a primary level, it will be very difficult for physicians to defend not counseling women who seek advice while planning pregnancy and who end up giving birth to children with NTDs. Although this pilot study might not be generalizable to all Canadian or even Ontario physicians, it highlights the issue of not informing women of the possibility of preventing NTDs.


  1. Pellegrini E, Koren G. The Motherisk program. In: Koren G, editor. Maternal-fetal toxicology. A clinician's guide. New York: Marcel Dekker; 1994. P. 707-26.
  2. Chitayat D, Hodgkinson K. Neural tube defects: embryology inheritance and prenatal diagnosis. In: Koren G, editor. Folic acid and the prevention of neural tube defects. Toronto: Motherisk Program; 1995. P. 1-29.
  3. MRC Vitamin Study Research Group. Prevention of neural tube defects. Lancet 1991; 338: 131-7.
  4. 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.
  5. Forman R, Chou S, Perelman V, Einarson A, Koren G. Folic acid consumption by women giving birth to children with neural tube defects. Clin Invest Med, In press.
  6. Jacobson S, McArthur C, Joshi P, Forman R, Koren G. Availability of folic acid and knowledge about prophylactic use: a survey of urban pharmacies. In: Koren G, editor. Folic acid and the prevention of neural tube defects. Toronto: Motherisk Program; 1995. P. 151-4.
  7. Daly LE, Kirke PN, Molloy A, Weir DG, Scott JM. Folate levels and neural tube defects: implications for prevention. JAMA 1995; 274: 1698-702.
  8. Perelman V, Signal N, Einarson A, Kennedy D, Koren G. Knowledge and practice by Canadian family physicians regarding periconceptional folic acid supplementation for the prevention of neural tube defects. Can J Clin Pharmacol 1996; 3: 145-8.
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