UNSW Embryology

Abnormal Development - Folic Acid and Neural Tube Defects

© Dr Mark Hill (2008)

Acknowledgements

Introduction

In 2001, the Australian estimated birth prevalence of neural tube defects was 0.5 per 1,000 births (National Perinatal Statistics Unit).

Folic Acid	Fruits

Research over the last 20 years has suggested a relationship between maternal diet and the birth of an affected infant, and recent evidence has confirmed that folic acid, a water soluble vitamin, found in many fruits (particularly oranges, berries and bananas), leafy green vegetables, cereals and legumes, may prevent the majority of neural tube defects.

In the U.S.A. the Food and Drug Administration in 1996 authorized that all enriched cereal grain products be fortified with folic acid, with optional fortification beginning in March 1996 and mandatory fortification in January 1998. (More? USA Data)

The March of Dimes Folic Acid Campaign (a major US charity group) has as one of its major objectives to reduce neural tube defects by 30% by 2001 using community programs, professional education, and mass media information.

Page Links: Introduction | Recent Articles | Australian Statistics | USA Statistics | Folic Acid | WWW Links | References | Glossary

See also: Spina Bifida | Neural Abnormalities notes

Some Recent Findings

Eichholzer M, Tonz O, Zimmermann R. Folic acid: a public-health challenge. Lancet. 2006 Apr 22;367(9519):1352-61. "... In the USA, Canada, and Chile, mandatory fortification of flour substantially improved folate and homocysteine status, and neural tube defects rates fell by between 31% and 78%. Nevertheless, many countries do not choose mandatory folic acid fortification, in part because expected additional health benefits are not yet scientifically proven in clinical trials, in part because of feared health risks, and because of the issue of freedom of choice. Thus, additional creative public-health approaches need to be developed to prevent neural tube defects and improve the folate status of the general population."

Padmanabhan R. Etiology, pathogenesis and prevention of neural tube defects. Congenit Anom (Kyoto). 2006 Jun;46(2):55-67.

Tamura T, Picciano MF. Folate and human reproduction. Am J Clin Nutr. 2006 May;83(5):993-1016.

Wen SW, Walker M. An exploration of health effects of folic acid in pregnancy beyond reducing neural tube defects. J Obstet Gynaecol Can. 2005 Jan;27(1):13-9.

Gonzalez MJ, et al. [See Related Articles] Folate supplementation and neural tube defects: a review of a public health issue. P R Health Sci J. 1997 Dec;16(4):387-93. Review.

Australian Statistics

• Women who have one infant with a neural tube defect have a significantly increased risk of recurrence
  • 40-50 per thousand compared with 2 per thousand for all births.
• A randomised controlled trial conducted by the Medical Research Council of the United Kingdom demonstrated a 72% reduction in risk of recurrence by periconceptional (ie before and after conception) folic acid supplementation (4mg daily).
• Other epidemiological research, including work done in Australia, suggests that primary occurrences of neural tube defects may also be prevented by folic acid either as a supplement or in the diet.
• This has been confirmed in a randomised controlled trial from Hungary, which found that a multivitamin supplement containing 0.8mg folic acid was effective in reducing the occurrence of neural tube defects in first births.

(Data excerpt from NHMRC Publication)

USA Statistics

In the U.S.A. the Food and Drug Administration in 1996 authorized that all enriched cereal grain products be fortified with folic acid, with optional fortification beginning in March 1996 and mandatory fortification in January 1998. The data below shows the subsequent changes in anencephaly and spina bifida rate over that period.

Data: CDC Trends in Spina Bifida and Anencephalus in the United States, 1991-2005

Folic Acid

Formula: C₁₉H₁₉N₇O₆

Alternate Names: Folic acid, Folate, Pteroylglutamic acid

(Data from KEGG)

Folate Biosynthesis
(click image for full size or get original Map)

WWW Links

• See also the NHMRC Publication Dietary Folic Acid and Neural Tube Defects
• National Perinatal Statistics Unit
• Australian Journal of Nutrition and Dietetics
• Australian Nutrition Foundation
• CSIRO Human Nutrition
• Food, Nutrition & Health Information - Centre for Advanced Food Research
• Office of Dietary Supplements, National Institutes of Health (USA)Dietary Supplement Fact Sheet: Folate
• Foodwatch
• Healthy Eating, Healthy Living
• AIS Sport Nutrition - information from the Australian Institute of Sport. Supplies nutrition research, a question-and-answer section, publications, and other resources.
• America's Eating Habits - a report from the U.S. Department of Agriculture's economic research service. Covers dietary recommendations, health claims in food advertising, reality about cholesterol, and various other topics. 
• British Nutrition Foundation - an organization that works with academic, private, and public groups on nutrition. Includes nutrition education, facts, news, and publications. 
• Center for Food Safety & Applied Nutrition - a repository of links relevant to all manner of food issues, including food safety. Emphasizes FDA regulations and related research programs. 
• Nutrition.gov - a collection of information and links to other sites on food safety, food programs, and federally funded research centers.
• Nutrition.org - site of the American Society for Nutritional Sciences. Features an encyclopedia that summarizes food sources, diet recommendations, and deficiencies for a number of macro- and micronutrients.
• Nutrition Navigator - a guide to nutrition websites reviewed and rated by Tufts University nutritionists. Supplies news and sections arranged by topic.
  • Antioxidants Research Laboratory
  • Genetics Laboratory
  • Jean Mayer United States Department of Agriculture Human Nutrition Research Center on Aging
• U.S. Department of Agriculture
  • Beltsville Human Nutrition Research Center
  • Food Surveys Research Group
  • The Food Guide Pyramid: A Guide to Daily Food Choices
• Children's Nutrition Research Center
• Facts about the DASH Diet
• Healthfinder Kids
  • Nutrition
• Interactive Healthy Eating Index
• National Dairy Council
• Nutrition Explorations
  • The Food Guide Pyramid

Australian NHMRC

The Australian NHMRC (1988) recommends neonates be assessed for follow-up care under the following conditions.

(see the NHMRC WWW Page)

• Birthweight less than 1500g or gestational age less than 32 weeks
• Small-for-gestational-age neonates
• Perinatal asphyxia
• Apgar score less than 3 at 5 minutes
• clinical evidence of neurological dysfunction
• delay in onset of spontaneous respiration for more than 5 minutes and requiring mechanical ventilation
• Clinical evidence of central nervous system abnormalities ie., seizures, hypotonia
• Hyperbilirubinaemia of greater than 350umol/l in full term neonates
• Genetic, dysmorphic or metabolic disorders or a family history of serious genetic disorder
• Perinatal or serious neonatal infection including children of mothers who are HIV positive
• Psychosocial problems eg., infants of drug-addicted or alcoholic mothers.

For Normal Childhood Development see Publications (or NHMRC WWW Page)

References

Reviews

Eichholzer M, Tonz O, Zimmermann R. Folic acid: a public-health challenge. Lancet. 2006 Apr 22;367(9519):1352-61.

Padmanabhan R. Etiology, pathogenesis and prevention of neural tube defects. Congenit Anom (Kyoto). 2006 Jun;46(2):55-67.

Tamura T, Picciano MF. Folate and human reproduction. Am J Clin Nutr. 2006 May;83(5):993-1016.

Wen SW, Walker M. An exploration of health effects of folic acid in pregnancy beyond reducing neural tube defects. J Obstet Gynaecol Can. 2005 Jan;27(1):13-9.

Gonzalez MJ, et al. [See Related Articles] Folate supplementation and neural tube defects: a review of a public health issue. P R Health Sci J. 1997 Dec;16(4):387-93. Review.

Articles

I have included an earlier (1999) search list of selected review articles from PubMed Medline 1969-99. Also selected a few abstracts from reviews.

Glossary of Terms

A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Y | Z

Where to Next?

You should look at normal development. Development Notes

Alternatively, go on to look at Systematic Development of organs and tissues.

Quick Links

Development Notes ----------------- Menstrual Cycle Week 1 Week 2 Week 3 Week 4 Placenta Serial Images Genes/DNA Molecular Dev Abnormal Dev Postnatal Dev Notes Index

System Notes ----------------- Heart/Cardiovascular Respiratory Coelomic cavity Gastrointestinal Tract Head and Neck Neural Neural Crest Eye Ear Nose Endocrine Urogenital Musculoskeletal Integumentary

Finally

For those wanting to see dynamic processes of development (and have a reasonably quick connection) then the Movies pages are good for watching changes occur.

Movies ----------------- Embryo Growth Carnegie Stages Ultrasound Images Stage 13/14 Embryo Stage 22 Embryo Heart Septation Neural Neural Crest Other Embryos Larsen Movies

Other Embryos

The study of human development has relied extensively on studying the process in other model animals. For those wanting to see the process of development in other species then the other embryos pages are a good start.

Other Embryos ----------------- Chicken Fly Frog Mouse Rabbit Rat Worm Zebrafish Guinea Pig

UNSW Embryology ISBN: 978 0 7334 2609 4

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