1. Michiel Van den Hof Dalhousie University Halifax, Nova Scotia

2. History of Folate Research 1976-1991 - Numerous small studies suggesting benefit of folic acid supplementation 1991 -“Landmark” paper on benefit of folic acid supplementation to reduce the recurrence of NTDs* * MRC Vitamin Study Research Group: Lancet 1991

3. History of Folate Research 1992 -Research shows that folic acid supplementation reduces open NTDs in low-risk women* * Czeizel AE, Dudas I: N Engl J Med 1992

4. History of Folate Research 1991 - 1994 - Canadian recommendations about folic acid supplementation issued: -Health Canada -SOGC -Canadian Task Force on the Periodic Health Examination

5. Incidence of ONTD’S per 1000 births in Nova Scotia

6. Total Incidence of ONTD’S per 1000 Pregnancies 2.512.49 2.57 2.65 2.11

7. History of Folate Research 1993 - 1999 - < 45% of pregnant women taking folic acid before conception

8. History of Folate Research March 1996 - US-FDA orders all enriched grain products to be fortified (.14/100gm) starting January 1, 1998

9. History of Folate Research November 1, 1998 -Health Canada endorses similar fortification

10. Questions? Did recommendations for folic acid supplementation work? Did the “small” amount of fortification work?

11. Folic Acid Supplementation/Fortification Methods: Nova Scotia Perinatal Database plus Nova Scotia Fetal Anomaly Database combined have information on all births and birth defects that occur in this province.

12. Folic Acid Supplementation/Fortification Open neural tube defects: -spina bifida -anencephaly -other

13. Folic Acid Supplementation/Fortification Pre-supplementation1991-1994 Post-supplementation but pre-fortification1994-1997 Pre-fortification1991-1997 Post-fortification1998-2000

14. Folic Acid Supplementation/Fortification Risks for Folic Acid Fortification: Delay diagnosis of vitamin B12 deficiency which may result in neurologic effects.

15. Folic Acid Supplementation/Fortification Spina Total Anencephaly* Bifida** NTDs*** Pre-supplementation 1.00 1.44 2.55 1991-1994 Post-supplementation.82 1.60 2.61 Pre-fortification 1995-1997 *RR0.82,95%CI 0.51-1.32; p=0.49 **RR1.11,95%CI 0.79-1.60; p=0.64 ***RR1.02,95%CI 0.77-1.35; p=0.87

16. Incidence of ONTD’S per 1000 Pregnancies 2.55 2.61

17. Folic Acid Supplementation/Fortification Spina Total Anencephaly* Bifida** NTDs*** Pre-fortification.93 1.52 2.58 1991-1997 Post-fortification.38.62 1.17 * RR 0.41, 95% CI 0.22-0.77; p=0.004 ** RR 0.40, 95% CI 0.25-0.67; p<0.001 ***RR 0.46, 95% CI 0.32-0.66; p<0.001

18. Incidence of ONTD’S per 1000 Pregnancies 1.16 2.57

19. Folic Acid Supplementation/Fortification With the introduction of folic acid fortification, there was a 59% reduction in anencephaly 59% reduction in spina bifida and a54% reduction in all NTDs. Calculated reduction ~ 20%

20. Folic Acid Supplementation/Fortification Can prevention be further reduced? Chinese study suggested ~.6/1000 in both high and low-risk population. Thus, further reduction may be possible, 1.0 .6 (40%).

21. Incidence of Anencephaly and Spina Bifida per 1000 Pregnancies in Nova Scotia