# Presentation: 492329

## Michiel Van den Hof

- Dalhousie University
- Halifax, Nova Scotia

## History of Folate Research

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

## 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**

## History of Folate Research

**1991 - 1994**
**	****- Canadian recommendations about folic acid ****	****	****  supplementation issued:**
**	****	****-****	****Health Canada**
**	****	****-****	****SOGC**
**	****	****-****	****Canadian Task Force on the ****	****	****	****	****Periodic Health Examination**

## Incidence of ONTD’S per 1000 births in Nova Scotia

## Total Incidence of ONTD’S per 1000 Pregnancies

- 2.51

- 2.49

- 2.57

- 2.65

- 2.11

## History of Folate Research

**1993 - 1999**
**	****- < 45% of pregnant women taking folic acid ****	****   before conception**

## History of Folate Research

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

## History of Folate Research

**November 1, 1998**
**	****-****	****Health Canada endorses similar ****	****	****	****fortification**

## Questions?

**Did recommendations for folic acid supplementation work?**
**Did the “small” amount of fortification work?**

## 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.**

## Folic Acid Supplementation/Fortification

**Open neural tube defects:**
**	****	****-****	****spina bifida**
**	****	****-****	****anencephaly**
**	****	****-****	****other**

## Folic Acid Supplementation/Fortification

**	****Pre-supplementation****	****	****1991-1994**
**	****Post-supplementation****	****	**** **
**	****	****but pre-fortification****	****1994-1997**
**	****Pre-fortification****	****	****	****1991-1997**
**	****Post-fortification****	****	****	****1998-2000                    **

## Folic Acid Supplementation/Fortification

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

## 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**

## Incidence of ONTD’S per 1000 Pregnancies

- 2.55

- 2.61

## 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**

## Incidence of ONTD’S per 1000 Pregnancies

- 1.16

- 2.57

## Folic Acid Supplementation/Fortification

**With the introduction of folic acid fortification, there was a ****	****59% reduction in anencephaly**
**	****	****59% reduction in spina bifida**
**       ****and a****	****54% reduction in all  NTDs.**
**Calculated reduction ~ 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%).**

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