Skip to main content

Main menu

  • Home
  • Content
    • Current issue
    • Past issues
    • Early releases
    • Collections
    • Sections
    • Blog
    • Infographics & illustrations
    • Podcasts
    • COVID-19 articles
    • Obituary notices
  • Authors & Reviewers
    • Overview for authors
    • Submission guidelines
    • Submit a manuscript
    • Forms
    • Editorial process
    • Editorial policies
    • Peer review process
    • Publication fees
    • Reprint requests
    • Open access
    • Patient engagement
  • Physicians & Subscribers
    • Benefits for Canadian physicians
    • CPD Credits for CMA Members
    • Subscribe to CMAJ Print
    • Subscription prices
    • Obituary notices
  • Alerts
    • Email alerts
    • RSS
  • JAMC
    • À propos
    • Numéro en cours
    • Archives
    • Sections
    • Abonnement
    • Alertes
    • Trousse média 2023
    • Avis de décès
  • CMAJ JOURNALS
    • CMAJ Open
    • CJS
    • JAMC
    • JPN

User menu

Search

  • Advanced search
CMAJ
  • CMAJ JOURNALS
    • CMAJ Open
    • CJS
    • JAMC
    • JPN
CMAJ

Advanced Search

  • Home
  • Content
    • Current issue
    • Past issues
    • Early releases
    • Collections
    • Sections
    • Blog
    • Infographics & illustrations
    • Podcasts
    • COVID-19 articles
    • Obituary notices
  • Authors & Reviewers
    • Overview for authors
    • Submission guidelines
    • Submit a manuscript
    • Forms
    • Editorial process
    • Editorial policies
    • Peer review process
    • Publication fees
    • Reprint requests
    • Open access
    • Patient engagement
  • Physicians & Subscribers
    • Benefits for Canadian physicians
    • CPD Credits for CMA Members
    • Subscribe to CMAJ Print
    • Subscription prices
    • Obituary notices
  • Alerts
    • Email alerts
    • RSS
  • JAMC
    • À propos
    • Numéro en cours
    • Archives
    • Sections
    • Abonnement
    • Alertes
    • Trousse média 2023
    • Avis de décès
  • Visit CMAJ on Facebook
  • Follow CMAJ on Twitter
  • Follow CMAJ on Instagram
  • Listen to CMAJ podcasts
Research article

Folate and vitamin B12 status of women in Newfoundland at their first prenatal visit

James D. House, Sandra B. March, Sam Ratnam, Elizabeth Ives, John T. Brosnan and James K. Friel
CMAJ May 30, 2000 162 (11) 1557-1559;
James D. House
From *the Department of Animal Science, University of Manitoba, Winnipeg, Man.; †the Provincial Public Health Laboratory, St. John's, Nfld.; ‡Community Medicine and §the Department of Biochemistry, Memorial University of Newfoundland, St. John's, Nfld.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sandra B. March
From *the Department of Animal Science, University of Manitoba, Winnipeg, Man.; †the Provincial Public Health Laboratory, St. John's, Nfld.; ‡Community Medicine and §the Department of Biochemistry, Memorial University of Newfoundland, St. John's, Nfld.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sam Ratnam
From *the Department of Animal Science, University of Manitoba, Winnipeg, Man.; †the Provincial Public Health Laboratory, St. John's, Nfld.; ‡Community Medicine and §the Department of Biochemistry, Memorial University of Newfoundland, St. John's, Nfld.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Elizabeth Ives
From *the Department of Animal Science, University of Manitoba, Winnipeg, Man.; †the Provincial Public Health Laboratory, St. John's, Nfld.; ‡Community Medicine and §the Department of Biochemistry, Memorial University of Newfoundland, St. John's, Nfld.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
John T. Brosnan
From *the Department of Animal Science, University of Manitoba, Winnipeg, Man.; †the Provincial Public Health Laboratory, St. John's, Nfld.; ‡Community Medicine and §the Department of Biochemistry, Memorial University of Newfoundland, St. John's, Nfld.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
James K. Friel
From *the Department of Animal Science, University of Manitoba, Winnipeg, Man.; †the Provincial Public Health Laboratory, St. John's, Nfld.; ‡Community Medicine and §the Department of Biochemistry, Memorial University of Newfoundland, St. John's, Nfld.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Tables
  • Responses
  • Metrics
  • PDF
Loading

Abstract

Background: Newfoundland has one of the highest rates of neural tube defects in North America. Given the association between low maternal folic acid levels and neural tube defects, a cross-sectional study was conducted to obtain baseline data on the folate and vitamin B12 status of a sample of women in Newfoundland who were pregnant.

Methods: Blood samples were collected between August 1996 and July 1997 from 1424 pregnant women in Newfoundland during the first prenatal visit (at approximately 16 weeks' gestation); this represented approximately 25% of the women in Newfoundland who were pregnant during this period. The samples were analysed for serum folate, vitamin B12, red blood cell folate and homocysteine.

Results: Median values for serum folate, red blood cell folate and serum vitamin B12 were 25 nmol/L, 650 nmol/L and 180 pmol/L, respectively. On the basis of the interpretive criteria used for red blood cell folate status, 157 (11.0%) of the 1424 women were deficient (< 340 nmol/L) and a further 180 (12.6%) were classified as indeterminate (340-420 nmol/L). Serum homocysteine levels, measured in subsets of the red blood cell folate status groups, supported the inadequate folate status. Serum vitamin B12 levels of 621 (43.6%) women were classified as deficient or marginal; however, the validity of the interpretive criteria for pregnant women is questionable.

Interpretation: A large proportion of pregnant women surveyed in Newfoundland in 1997 had low red blood cell folate level

In Newfoundland the incidence of neural tube defects, including anencephaly and spina bifida cystica, is one of the highest in North America, with 3.2 neural tube defects per 1000 births documented between 1976 and 1991.1

Maternal folate status and folic acid intake at the time of conception are strongly implicated in the etiology of neural tube defects. Several case-control studies documented significantly decreased relative risks of occurrence2,3 and recurrence4 of neural tube defect births for women who consumed folic acid supplements during the periconceptional period. Kirke and colleagues5 showed that plasma and red blood cell folate levels were significantly lower in women who gave birth to a child with a neural tube defect. In Newfoundland 64% of a sample of mothers who gave birth to children with neural tube defects had folate intakes below the national recommended levels (168 μg/d),6 compared with 27% of mothers who gave birth to healthy babies.7 These findings suggest that poor maternal folate status may be associated with the high incidence of neural tube defects in Newfoundland.

We assessed the folate levels of women in Newfoundland at their first prenatal visit to establish baseline data prior to the implementation of cereal grain fortification with folic acid. In addition, given the association between low serum vitamin B12 and increased risk for neural tube defects,5 we also assessed serum B12 concentrations.

Methods

An anonymous cross-sectional survey of patients was conducted from August 1996 to July 1997, and blood samples were collected from 1424 women in Newfoundland (25% of all pregnancies) at their first prenatal visit. For each subject blood was collected and frozen, and samples (linked by identification numbers) were shipped to the Public Health Laboratory in St. John's, Nfld., for the preparation of sera and red blood cell lysates. Folate concentrations in sera and red blood cell lysates were determined using the IMx Folate System (Abbott Laboratories, Abbott Park, Ill.), and vitamin B12 concentrations in sera were determined using the IMx B12 System (Abbott Laboratories). Samples were classified with respect to folate and vitamin B12 status as deficient (serum folate < 6 nmol/L, red blood cell folate < 340 nmol/L, serum vitamin B12 < 130 pmol/L); indeterminate (6-7 nmol/L, 340-420 nmol/L, 130-160 pmol/L, respectively); or normal (>> 7 nmol/L, >> 420 nmol/L, >> 160 pmol/L, respectively) based on criteria established by the manufacturer. Serum homocysteine concentrations, a further biochemical indicator of cellular folate status, were evaluated for a subset of 370 samples, comprising equal numbers of samples from the red blood cell folate status groups, using reverse-phase high-performance liquid chromatography with fluorescence detection.8 Significant differences (p < 0.05) between log-transformed variables were determined by 1-way ANOVA, and differences between groups were assessed by the Neuman-Keuls procedure.9,10

Ethics approval for the study was obtained from the Human Investigation Committee, Memorial University of Newfoundland.

Results

Median values for serum folate, red blood cell folate and serum vitamin B12 were 25 nmol/L, 650 nmol/L and 180 pmol/L, respectively (Table 1). On the basis of the interpretive criteria, 157 (11.0%) of the 1424 women were deficient (< 340 nmol/L) in red blood cell folate, and a further 180 (12.6 %) were classified as indeterminate (340-420 nmol/L) (Table 2). Serum homocysteine levels measured in subsets of the red blood cell folate status groups supported the inadequate folate status; homocysteine levels for the red blood cell folate-deficient group were 11.9 ± 0.5 μM, the indeterminate group, 10.3 ± 0.7 μM, and for the normal group, 8.2 ± 0.6 μM.

View this table:
  • View inline
  • View popup
  • Download powerpoint

Table 2.

View this table:
  • View inline
  • View popup
  • Download powerpoint

Table 1.

Interpretation

On the basis of serum folate levels less than 4% of the women in our sample were deficient or at risk for becoming deficient in folate. Using the less conservative criteria of Bailey and colleagues11 (i.e., < 7 nmol/L = deficient, 7-13 nmol/L = marginal), 2.4% and 23.3% of the women sampled would be categorized as deficient or of marginal status, respectively. Despite the lack of consensus concerning the limits for normal and deficient levels for serum folate during pregnancy,12,13,14,15 it is generally agreed that serum folate is more reflective of recent folate intake and that levels normally decline with advancing pregnancy.16,17 However, red blood cell folate concentration is independent of parity and plasma-volume expansion and is therefore more stable throughout pregnancy.16 Given the long half-life of red blood cells, red blood cell folate concentration at the first prenatal clinic (16 weeks' gestation) should better reflect the folate status of pregnant women at the time of neural tube closure (21 days' gestation); using criteria similar to those used by other groups11,13 27% of the women in our sample had either deficient or marginal systemic folate stores. Serum homocysteine concentrations, which were inversely correlated with the folate concentrations, confirmed the depleted systemic folate stores.

According to category limits (i.e., deficient, indeterminate and normal) that were based on samples from women who were not pregnant, 43.6% of the women in our study were of deficient or indeterminate status for serum vitamin B12. Although serum vitamin B12 levels are known to decline with advancing pregnancy,18,19,20 there may not be any other reliable marker for B12 deficiency.21 Benjamin and colleagues22 set their limit for deficiency at 100 pg/mL (approx. 70 pmol/L), which would result in less than 5% of the women in our study classified as deficient in vitamin B12. Clearly, further work is required to define appropriate interpretive criteria for serum vitamin B12 status in pregnant subjects, perhaps by linking serum B12 levels to other indices of B12 status, such as methylmalonic acid.23 Although serum homocysteine concentration has also been used as an index of vitamin B12 status,23,24 our regression analysis yielded no significant relationship between serum B12 status and serum homocysteine concentrations.

Unfortunately, we were unable to correlate the low folate levels with other relevant patient variables (e.g., dietary preferences, multivitamin usage, socioeconomic status or gravidity) because blood samples were given anonymously. Nevertheless, the fact that 27% of the pregnant women presented with deficient or indeterminate red blood cell folate levels is a serious public health concern that should be addressed.

Footnotes

  • This article has been peer reviewed.

    We thank all participating hospitals and the women who took part in the study. We also thank Claude Mercer and Allison MacDonald for data analysis and Marian Crowley for collecting rates of neural tube defect occurrence.

    This study was supported by the Janeway Research Foundation, the Medical Research Council of Canada and the Canadian Diabetic Association.

    Competing interests: None declared.

    Reprint requests to: Dr. James K. Friel, Department of Biochemistry, Memorial University of Newfoundland, St. John's NF A1B 3X9; fax 709 737-2422; [email protected]

References

  1. 1.↵
    Frecker ME. Neural tube defects in Newfoundland. J Epidemiol Community Health 1994;48:100.
    OpenUrl
  2. 2.↵
    Czeizel AE, Dudas I. Prevention of the first occurrence of neural tube defects by periconceptional vitamin supplementation. N Engl J Med 1992;327:1832-5.
    OpenUrlCrossRefPubMed
  3. 3.↵
    Werler MM, Shapiro S, Mitchell AA. Periconceptional folic acid exposure and risk of occurent neural tube defects. JAMA 1993;269:1257-61.
    OpenUrlCrossRefPubMed
  4. 4.↵
    Medical Research Council Vitamin Study Research Group. Prevention of neural tube defects: Results of the Medical Research Council Vitamin Study. Lancet 1991;338:131-7.
    OpenUrlCrossRefPubMed
  5. 5.↵
    Kirke PN, Molloy AN, Daly LE, Burke H, Weir DG, Scott JM. Maternal plasma folate and vitamin B12 and independent risk factors for neural tube defects. Q J Med 1993;86:703-8.
    OpenUrlAbstract/FREE Full Text
  6. 6.↵
    Health and Welfare Canada. Nutrition recommendations. The Report of the Scientific Review Committee. Ottawa: Minister of Supply and Services; 1990.
  7. 7.↵
    Friel JK, Frecker M, Fraser FC. Nutritional patterns of mothers of children with neural tube defects in Newfoundland. Am J Med Genet 1995;55:195-9.
    OpenUrlCrossRefPubMed
  8. 8.↵
    Vester B, Rasmussen K. High performance liquid chromatography method for rapid and accurate determination of homocysteine in plasma and serum. Eur J Clin Chem Clin Biochem 1991;29:549-54.
    OpenUrlPubMed
  9. 9.↵
    SAS Institute. SAS/STAT user's guide. vol 6. 4th ed. Cary (NC): SAS Institute; 1989.
  10. 10.↵
    Zar JH. Biostatistical analysis. 2nd ed. Englewood Cliffs (NJ): Prentice-Hall; 1941.
  11. 11.↵
    Bailey LB, Mahan CS, Dimperio D. Folacin and iron status in low-income pregnant adolescents and mature women. Am J Clin Nutr 1980;33:1997-2001.
    OpenUrlFREE Full Text
  12. 12.↵
    Huber AM, Wallins LL, DeRusso P. Folate nutriture during pregnancy. J Am Diet Assoc 1988;88:791-5.
    OpenUrlPubMed
  13. 13.↵
    Lehti KK. Iron, folic acid, and zinc intakes and status of low socioeconomic pregnant and lactating Amazonian women. Eur J Clin Nutr 1989;43:505-13.
    OpenUrlPubMed
  14. 14.↵
    Nutrition Canada. Nutrition: a national priority; a report by Nutrition Canada to the Department of National Health and Welfare. Ottawa: Information Canada; 1973.
  15. 15.↵
    O'Connor DL. Folate status during pregnancy and lactation. In: Allen L, King J, LÖnnerdal B, editors. Nutrient regulation during pregnancy, lactation, and infant growth. New York: Plenum Press; 1994. p. 157-72.
  16. 16.↵
    Ek J, Magnus EM. Plasma and red blood cell folate during normal pregnancies. Acta Obstet Gynecol Scand 1981;60:247-51.
    OpenUrlCrossRefPubMed
  17. 17.↵
    Hall MH, Pirani BB, Campbell D. The cause of the fall in serum folate in normal pregnancy. Br J Obstet Gynaecol 1976;83:132-6.
    OpenUrlCrossRefPubMed
  18. 18.↵
    Ball EW, Giles C. Folic acid and vitamin B12 levels in pregnancy and their relation to megaloblastic anaemia. J Clin Pathol 1964;17:165-74.
    OpenUrlAbstract/FREE Full Text
  19. 19.↵
    Green R, Colman N, Metz J. Comparison of results of micro biologic and radio isotopic assays for serum vitamin B12 during pregnancy. Am J Obstet Gynecol 1975;122:21-4.
    OpenUrlPubMed
  20. 20.↵
    Zamorano AF, Arnalich F, Sanchez Casas E, Sicilia A, Solis C, Vazquez JJ, et al. Levels of iron, vitamin B12, folic acid and their binding proteins during pregnancy. Acta Haematol 1985;74:92-6.
    OpenUrlCrossRefPubMed
  21. 21.↵
    Metz J, McGrath K, Bennett M, Hyland K, Bottiglieri T. Biochemical indices of vitamin B12 nutrition in pregnant patients with subnormal serum vitamin B12 levels. Am J Hematol 1995;48:251-5.
    OpenUrlCrossRefPubMed
  22. 22.↵
    Benjamin F, Bassen FA, Meyer LM. Serum levels of folic acid, vitamin B12 and iron in anemia of pregnancy. Am J Obstet Gynecol 1966;96:310-5.
    OpenUrlPubMed
  23. 23.↵
    Pardo J, Peled Y, Bar J, Hod M, Sela BA, Ben Rafael Z, et al. Evaluation of low serum B12 in the nonanaemic pregnant patient. Hum Reprod 2000;15:224-6.
    OpenUrlAbstract/FREE Full Text
  24. 24.↵
    Stabler SP, Lindenbaum J, Allen RH. The use of homocysteine and other metabolites in the specific diagnosis of vitamin B12 deficiency. J Nutr 1996;126:1266S-72S.
    OpenUrl
PreviousNext
Back to top

In this issue

CMAJ
Vol. 162, Issue 11
30 May 2000
  • Table of Contents
  • Index by author

Article tools

Respond to this article
Print
Download PDF
Article Alerts
To sign up for email alerts or to access your current email alerts, enter your email address below:
Email Article

Thank you for your interest in spreading the word on CMAJ.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Folate and vitamin B12 status of women in Newfoundland at their first prenatal visit
(Your Name) has sent you a message from CMAJ
(Your Name) thought you would like to see the CMAJ web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Folate and vitamin B12 status of women in Newfoundland at their first prenatal visit
James D. House, Sandra B. March, Sam Ratnam, Elizabeth Ives, John T. Brosnan, James K. Friel
CMAJ May 2000, 162 (11) 1557-1559;

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
‍ Request Permissions
Share
Folate and vitamin B12 status of women in Newfoundland at their first prenatal visit
James D. House, Sandra B. March, Sam Ratnam, Elizabeth Ives, John T. Brosnan, James K. Friel
CMAJ May 2000, 162 (11) 1557-1559;
Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like

Jump to section

  • Article
    • Abstract
    • Methods
    • Results
    • Interpretation
    • Footnotes
    • References
  • Figures & Tables
  • Responses
  • Metrics
  • PDF

Related Articles

  • No related articles found.
  • PubMed
  • Google Scholar

Cited By...

  • Prevalence of vitamin B-12 insufficiency during pregnancy and its effect on offspring birth weight: a systematic review and meta-analysis
  • One-Third of Pregnant and Lactating Women May Not Be Meeting Their Folate Requirements from Diet Alone Based on Mandated Levels of Folic Acid Fortification
  • Folic acid supplementation: more work is needed
  • Folic acid supplementation: more work is needed
  • Folic acid: the opportunity that still exists
  • Google Scholar

More in this TOC Section

  • Falsely elevated point-of-care lactate measurement after ingestion of ethylene glycol
  • Severe necrotizing pancreatitis following combined hepatitis A and B vaccination
  • Can hockey playoffs harm your hearing?
Show more Research article

Similar Articles

 

View Latest Classified Ads

Content

  • Current issue
  • Past issues
  • Collections
  • Sections
  • Blog
  • Podcasts
  • Alerts
  • RSS
  • Early releases

Information for

  • Advertisers
  • Authors
  • Reviewers
  • CMA Members
  • CPD credits
  • Media
  • Reprint requests
  • Subscribers

About

  • General Information
  • Journal staff
  • Editorial Board
  • Advisory Panels
  • Governance Council
  • Journal Oversight
  • Careers
  • Contact
  • Copyright and Permissions
CMAJ Group

Copyright 2023, CMA Impact Inc. or its licensors. All rights reserved. ISSN 1488-2329 (e) 0820-3946 (p)

All editorial matter in CMAJ represents the opinions of the authors and not necessarily those of the Canadian Medical Association or its subsidiaries.

To receive any of these resources in an accessible format, please contact us at CMAJ Group, 500-1410 Blair Towers Place, Ottawa ON, K1J 9B9; p: 1-888-855-2555; e: [email protected]

CMA Civility, Accessibility, Privacy

 

Powered by HighWire