Abnormal Development - Folic Acid and Neural Tube Defects: Difference between revisions

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* '''Association between maternal use of folic acid supplements and risk of autism spectrum disorders in children'''<ref name=PMID23403681><pubmed>23403681 </pubmed></ref> "To examine the association between maternal use of prenatal folic acid supplements and subsequent risk of autism spectrum disorders (ASDs) (autistic disorder, Asperger syndrome, pervasive developmental disorder-not otherwise specified [PDD-NOS]) in children. The study sample of 85,176 children was derived from the population-based, prospective Norwegian Mother and Child Cohort Study (MoBa). The children were born in 2002-2008; by the end of follow-up on March 31, 2012, the age range was 3.3 through 10.2 years (mean, 6.4 years). The exposure of primary interest was use of folic acid from 4 weeks before to 8 weeks after the start of pregnancy, defined as the first day of the last menstrual period before conception. Relative risks of ASDs were estimated by odds ratios (ORs) with 95% CIs in a logistic regression analysis. Analyses were adjusted for maternal education level, year of birth, and parity. ...Use of prenatal folic acid supplements around the time of conception was associated with a lower risk of autistic disorder in the MoBa cohort. Although these findings cannot establish causality, they do support prenatal folic acid supplementation."
* '''Association between maternal use of folic acid supplements and risk of autism spectrum disorders in children'''<ref name=PMID23403681><pubmed>23403681 </pubmed>| [http://jama.jamanetwork.com/article.aspx?articleid=1570279 JAMA]</ref> "To examine the association between maternal use of prenatal folic acid supplements and subsequent risk of autism spectrum disorders (ASDs) (autistic disorder, Asperger syndrome, pervasive developmental disorder-not otherwise specified [PDD-NOS]) in children. The study sample of 85,176 children was derived from the population-based, prospective Norwegian Mother and Child Cohort Study (MoBa). The children were born in 2002-2008; by the end of follow-up on March 31, 2012, the age range was 3.3 through 10.2 years (mean, 6.4 years). The exposure of primary interest was use of folic acid from 4 weeks before to 8 weeks after the start of pregnancy, defined as the first day of the last menstrual period before conception. Relative risks of ASDs were estimated by odds ratios (ORs) with 95% CIs in a logistic regression analysis. Analyses were adjusted for maternal education level, year of birth, and parity. ...Use of prenatal folic acid supplements around the time of conception was associated with a lower risk of autistic disorder in the MoBa cohort. Although these findings cannot establish causality, they do support prenatal folic acid supplementation."


* '''Disruption of the folate pathway in zebrafish causes developmental defects'''<ref><pubmed>22480165</pubmed></ref> "Our studies demonstrate that human and zebrafish utilize similar one-carbon pathways. Our data indicate that folate metabolism is essential for early zebrafish development. Zebrafish studies of the folate pathway and its deficiencies could provide insight into the underlying etiology of human birth defects and the natural role of folate in development."
* '''Disruption of the folate pathway in zebrafish causes developmental defects'''<ref><pubmed>22480165</pubmed></ref> "Our studies demonstrate that human and zebrafish utilize similar one-carbon pathways. Our data indicate that folate metabolism is essential for early zebrafish development. Zebrafish studies of the folate pathway and its deficiencies could provide insight into the underlying etiology of human birth defects and the natural role of folate in development."

Revision as of 15:52, 15 February 2013

Introduction

In 2001, the Australian estimated birth prevalence of neural tube defects was 0.5 per 1,000 births (National Perinatal Statistics Unit). Low maternal dietary folic acid (folate) has been shown to be associated with the development of neural tube defects. In September 2009, mandatory folic acid fortification of bread flour was introduced in Australia.

Research over the last 20 years had suggested a relationship between maternal diet and the birth of an affected infant. Recent evidence has confirmed that folic acid, a water soluble vitamin (vitamin B9) found in many fruits (particularly oranges, berries and bananas), leafy green vegetables, cereals and legumes, may prevent the majority of neural tube defects.

Folatefruit.jpg
Folate.jpg
Fruits
Folic Acid

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 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.

Links: Nutrition | Neural System - Abnormalities | Axial Skeleton Abnormalities
Environmental Links: Introduction | low folic acid | iodine deficiency | Nutrition | Drugs | Australian Drug Categories | USA Drug Categories | thalidomide | herbal drugs | Illegal Drugs | smoking | Fetal Alcohol Syndrome | TORCH | viral infection | bacterial infection | fungal infection | zoonotic infection | toxoplasmosis | Malaria | maternal diabetes | maternal hypertension | maternal hyperthermia | Maternal Inflammation | Maternal Obesity | hypoxia | biological toxins | chemicals | heavy metals | air pollution | radiation | Prenatal Diagnosis | Neonatal Diagnosis | International Classification of Diseases | Fetal Origins Hypothesis

Some Recent Findings

  • Association between maternal use of folic acid supplements and risk of autism spectrum disorders in children[1] "To examine the association between maternal use of prenatal folic acid supplements and subsequent risk of autism spectrum disorders (ASDs) (autistic disorder, Asperger syndrome, pervasive developmental disorder-not otherwise specified [PDD-NOS]) in children. The study sample of 85,176 children was derived from the population-based, prospective Norwegian Mother and Child Cohort Study (MoBa). The children were born in 2002-2008; by the end of follow-up on March 31, 2012, the age range was 3.3 through 10.2 years (mean, 6.4 years). The exposure of primary interest was use of folic acid from 4 weeks before to 8 weeks after the start of pregnancy, defined as the first day of the last menstrual period before conception. Relative risks of ASDs were estimated by odds ratios (ORs) with 95% CIs in a logistic regression analysis. Analyses were adjusted for maternal education level, year of birth, and parity. ...Use of prenatal folic acid supplements around the time of conception was associated with a lower risk of autistic disorder in the MoBa cohort. Although these findings cannot establish causality, they do support prenatal folic acid supplementation."
  • Disruption of the folate pathway in zebrafish causes developmental defects[2] "Our studies demonstrate that human and zebrafish utilize similar one-carbon pathways. Our data indicate that folate metabolism is essential for early zebrafish development. Zebrafish studies of the folate pathway and its deficiencies could provide insight into the underlying etiology of human birth defects and the natural role of folate in development."
  • Periconceptional bread intakes indicate New Zealand's proposed mandatory folic acid fortification program may be outdated[3] "In September 2009, a folic acid fortification mandate (135 μg/100 g bread) was to be implemented in New Zealand. However, due to political and manufacturer objection, fortification was deferred until May 2012. Based on estimates of bread consumption derived from a 1997 nationally representative survey, this program was intended to deliver a mean additional intake of 140 μg folic acid/d to women of childbearing age. ...This study provides insight on the ability of a fortification policy to benefit the groups at highest risk of poor folate intakes in a population. However, bread consumption among the target group of childbearing women appears to have declined since the data used in previous dietary modeling were collected. Thus, it seems prudent to re-model dietary folic acid intakes based on more recent national survey data prior to the implementation of a mandatory folic acid fortification policy."
  • Australian Institute of Health and Welfare Neural tube defects in Australia: prevalence before mandatory folic acid fortification [4] 19 Dec 2011 "The purpose of compiling this national report is to provide baseline prevalence of NTD, before implementation of mandatory folic acid fortification of bread flour in September 2009."

References

Neural Tube Defect Classification

Neural tube defects comprise three distinct conditions: anencephaly, spina bifida and encephalocele.

Anencephaly

  • A congenital anomaly characterised by the total or partial absence of the cranial vault, the covering skin and the brain.
  • Remaining brain tissue may be very much reduced in size.
  • Craniorachischisis and iniencephaly are included.
  • Acephaly, the absence of the head observed in amorphous acardiac twins, is excluded.
  • ICD codes: ICD-9-BPA codes: 740.00–740.29 or ICD-10-AM codes: Q00.0–Q00.2.

Spina bifida

  • A congenital anomaly characterised by a failure in the closure of the spinal column.
  • Characterised by herniation or exposure of the spinal cord and/or meninges through the incompletely closed spine.
  • This excludes spina bifida occulta and sacrococcygeal teratoma without dysraphism.
  • ICD codes: ICD-9-BPA codes: 741.00–741.99 or ICD-10-AM codes: Q05.0–Q05.9.

Encephalocele

  • A congenital anomaly characterised by herniation of the brain and/or meninges through a defect in the skull.
  • ICD codes: ICD-9-BPA codes: 742.00–742.09 or ICD-10-AM codes: Q01.0–Q01.2, Q01.8, Q01.9.

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)


Before mandatory folic acid fortification was introduced:

  • mean dietary folic acid intakes for women aged 16–44 years (the target population) in Australia was 108 micrograms (μg) of folic acid per day and in New Zealand was 62 μg of folic acid per day, well below the recommended 400 μg per day.
  • there were 149 pregnancies affected by NTDs in 2005 in Australia (rate of 13.3 per 10,000 births) in the three states that provide the most accurate baseline of NTD incidence (South Australia, Western Australia and Victoria), and 63 pregnancies affected by NTDs in 2003 in New Zealand (rate of 11.2 per 10,000 births).

Before mandatory iodine fortification was introduced:

  • large proportions of the Australian and New Zealand population had inadequate iodine intakes.
  • national surveys measuring median urinary iodine concentration (MUIC) in schoolchildren, an indicator of overall population status, confirmed mild iodine deficiency in both countries.
    • The concentration was 96 μg per litre in Australia, and 66 μg per litre in New Zealand, less than the 100–200 μg per litre considered optimal.

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.

USA spina bifida rates.jpg

USA anencephaly rates.jpg

Data CDC Report[5]

Folic Acid

Formula: C19H19N7O6

Alternate Names: Folic acid, Folate, Pteroylglutamic acid


Folate Biosynthesis.jpg

(Data from KEGG)

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

Folate Supplementation and Other Abnormalities

A recent study of periconceptional folate supplementation using the Cochrane Pregnancy and Childbirth Group's Trials Register (July 2010) identified no statistically significant evidence of any effects on prevention of cleft palate, cleft lip, congenital cardiovascular defects, miscarriages or any other birth defects.[6]


References

  1. <pubmed>23403681 </pubmed>| JAMA
  2. <pubmed>22480165</pubmed>
  3. <pubmed>22333513</pubmed>
  4. AIHW National Perinatal Statistics Unit 2011. Neural tube defects in Australia: prevalence before mandatory folic acid fortification. Cat. no. PER 53. Canberra: AIHW. http://www.aihw.gov.au/publication-detail/?id=10737420864
  5. CDC Trends in Spina Bifida and Anencephalus in the United States, 1991-2005
  6. <pubmed>20927767</pubmed>

Reviews

<pubmed></pubmed> <pubmed>23119003</pubmed> <pubmed>16631914</pubmed> <pubmed>16685040</pubmed> <pubmed>15937577</pubmed>

Articles

<pubmed></pubmed> <pubmed>11887752</pubmed> <pubmed>7474275</pubmed> <pubmed>68194</pubmed> <pubmed>1015847</pubmed>

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Cite this page: Hill, M.A. (2024, March 28) Embryology Abnormal Development - Folic Acid and Neural Tube Defects. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Abnormal_Development_-_Folic_Acid_and_Neural_Tube_Defects

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