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Folic acid supplementation and fortification in Nova Scotia

Michiel Van den HofDalhousie UniversityHalifax, Nova Scotia

History of Folate History of Folate ResearchResearch

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


1992 -Research shows that folic acid supplementation reduces open NTDs in low-risk women*

*Czeizel AE, Dudas I: N Engl J Med 1992


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

1.5 1.411.2

1.06

0.46

0

0.2

0.4

0.6

0.8

1

1.2

1.4

1.6

1991 1992 1993 1994 1995

Livebirths/stillbirths

Total Incidence of ONTD’S per 1000 Total Incidence of ONTD’S per 1000 PregnanciesPregnancies

1.5

1.01

1.41

1.08

1.2

1.37

1.06

1.59

0.46

1.65

0

0.5

1

1.5

2

2.5

3

1991 1992 1993 1994 1995

Pregnancyterminations

Livebirths/stillbirths

2.51 2.49 2.57 2.65

2.11


1993 - 1999

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


March 1996

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


November 1, 1998

- Health Canada endorses similar fortification

Questions?Questions?

Did recommendations for folic acid supplementation work?

Did the “small” amount of fortification work?

Folic Acid Folic Acid Supplementation/FortificationSupplementation/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.


Open neural tube defects:

- spina bifida

- anencephaly

- other


Pre-supplementation 1991-1994

Post-supplementation

but pre-fortification 1994-1997

Pre-fortification 1991-1997

Post-fortification 1998-2000

Folic Acid Folic Acid Supplementation/FortificatSupplementation/Fortificat

ionion

Risks for Folic Acid Fortification:

Delay diagnosis of vitamin B12 deficiency which may result in neurologic effects.

Folic Acid Folic Acid Supplementation/FortificatioSupplementation/Fortificatio

nn 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 Incidence of ONTD’S per 1000 PregnanciesPregnancies

1.3

1.25

0.82

1.79

0

0.5

1

1.5

2

2.5

3

1991-1994 1995-1997


Livebirths/ stillbirths

2.552.61


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 Incidence of ONTD’S per 1000 PregnanciesPregnancies

1.1

1.47

0.29

0.87

0

0.5

1

1.5

2

2.5

3

1991-1997 1998-2002


Livebirths/ stillbirths

1.16

2.57


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%


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 Incidence of Anencephaly and Spina Bifida per 1000 Pregnancies in Nova Scotia1000 Pregnancies in Nova Scotia

1.44

1

0.11

1.6

0.82

0.19

0.56

0.460.15

0

0.5

1

1.5

2

2.5

3

1991-1994 1995-1997 1998-2002

OtherAnencephalySpina bifida