{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T19:07:53Z","timestamp":1787771273978,"version":"build-2784847793"},"reference-count":45,"publisher":"Elsevier BV","issue":"5","license":[{"start":{"date-parts":[[2019,5,1]],"date-time":"2019-05-01T00:00:00Z","timestamp":1556668800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,1,31]],"date-time":"2023-01-31T00:00:00Z","timestamp":1675123200000},"content-version":"vor","delay-in-days":1371,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["The American Journal of Clinical Nutrition"],"published-print":{"date-parts":[[2019,5]]},"DOI":"10.1093\/ajcn\/nqz027","type":"journal-article","created":{"date-parts":[[2019,2,7]],"date-time":"2019-02-07T15:28:31Z","timestamp":1549553311000},"page":"1452-1461","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":98,"title":["Defining the plasma folate concentration associated with the red blood cell folate concentration threshold for optimal neural tube defects prevention: a population-based, randomized trial of folic acid supplementation"],"prefix":"10.1016","volume":"109","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7391-4581","authenticated-orcid":false,"given":"Meng-Yu","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles E","family":"Rose","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan Ping","family":"Qi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer L","family":"Williams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorraine F","family":"Yeung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7162-5046","authenticated-orcid":false,"given":"Robert J","family":"Berry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Hao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5776-5010","authenticated-orcid":false,"given":"Michael J","family":"Cannon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6997-5955","authenticated-orcid":false,"given":"Krista S","family":"Crider","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1093\/ajcn\/nqz027_bib1","doi-asserted-by":"crossref","first-page":"1636s","DOI":"10.3945\/jn.114.206599","article-title":"Biomarkers of nutrition for development\u2014folate review","volume":"145","author":"Bailey","year":"2015","journal-title":"J Nutr"},{"key":"10.1093\/ajcn\/nqz027_bib2","doi-asserted-by":"crossref","first-page":"S101","DOI":"10.1177\/15648265080292S114","article-title":"Effects of folate and vitamin B12 deficiencies during pregnancy on fetal, infant, and child development","volume":"29","author":"Molloy","year":"2008","journal-title":"Food Nutr Bull"},{"key":"10.1093\/ajcn\/nqz027_bib3","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1093\/jn\/129.4.779","article-title":"Folate metabolism and requirements","volume":"129","author":"Bailey","year":"1999","journal-title":"J Nutr"},{"key":"10.1093\/ajcn\/nqz027_bib4","article-title":"Dietary reference intakes for thiamin, riboflavin, niacin, vitamin B6, folate, vitamin B12, pantothenic acid, biotin, and choline","year":"1998","journal-title":"Dietary reference intakes for thiamin, riboflavin, niacin, vitamin B6, folate, vitamin B12, pantothenic acid, biotin, and choline"},{"key":"10.1093\/ajcn\/nqz027_bib5","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1056\/NEJM199911113412001","article-title":"Prevention of neural-tube defects with folic acid in China","volume":"341","author":"Berry","year":"1999","journal-title":"N Engl J Med"},{"key":"10.1093\/ajcn\/nqz027_bib6","doi-asserted-by":"crossref","first-page":"1832","DOI":"10.1056\/NEJM199212243272602","article-title":"Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation","volume":"327","author":"Czeizel","year":"1992","journal-title":"N Engl J Med"},{"key":"10.1093\/ajcn\/nqz027_bib7","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/0140-6736(91)90133-A","article-title":"Prevention of neural tube defects: results of the Medical Research Council Vitamin Study","volume":"338","year":"1991","journal-title":"Lancet"},{"key":"10.1093\/ajcn\/nqz027_bib8","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1001\/jama.2016.19438","article-title":"Folic acid supplementation for the prevention of neural tube defects: US Preventive Services Task Force recommendation statement","volume":"317","author":"Bibbins-Domingo","year":"2017","journal-title":"JAMA"},{"key":"10.1093\/ajcn\/nqz027_bib9","series-title":"WHO recommendations on antenatal care for a positive pregnancy experience","year":"2016"},{"key":"10.1093\/ajcn\/nqz027_bib10","first-page":"980","article-title":"CDC Grand Rounds: additional opportunities to prevent neural tube defects with folic acid fortification","volume":"59","year":"2010","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"10.1093\/ajcn\/nqz027_bib11","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1056\/NEJMoa067103","article-title":"Reduction in neural-tube defects after folic acid fortification in Canada","volume":"357","author":"DeWals","year":"2007","journal-title":"N Engl J Med"},{"key":"10.1093\/ajcn\/nqz027_bib12","doi-asserted-by":"crossref","first-page":"1885","DOI":"10.1002\/ajmg.a.35430","article-title":"Wheat flour fortification with folic acid: changes in neural tube defects rates in Chile","volume":"158a","author":"Cortes","year":"2012","journal-title":"Am J Med Genet A"},{"key":"10.1093\/ajcn\/nqz027_bib13","doi-asserted-by":"crossref","first-page":"S40","DOI":"10.1111\/j.1753-4887.2004.tb00073.x","article-title":"The Costa Rican experience: reduction of neural tube defects following food fortification programs","volume":"62","author":"Chen","year":"2004","journal-title":"Nutr Rev"},{"key":"10.1093\/ajcn\/nqz027_bib14","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1002\/bdra.20442","article-title":"Decline in the prevalence of neural tube defects following folic acid fortification and its cost\u2013benefit in South Africa","volume":"82","author":"Sayed","year":"2008","journal-title":"Birth Defects Res A Clin Mol Teratol"},{"key":"10.1093\/ajcn\/nqz027_bib15","first-page":"1","article-title":"Updated estimates of neural tube defects prevented by mandatory folic acid fortification\u2014United States, 1995\u20132011","volume":"64","author":"Williams","year":"2015","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"10.1093\/ajcn\/nqz027_bib16","article-title":"Guideline: optimal serum and red blood cell folate concentrations in women of reproductive age for prevention of neural tube defects","year":"2015","journal-title":"Guideline: optimal serum and red blood cell folate concentrations in women of reproductive age for prevention of neural tube defects"},{"key":"10.1093\/ajcn\/nqz027_bib17","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.3945\/ajcn.116.138529","article-title":"Applying inappropriate cutoffs leads to misinterpretation of folate status in the US population","volume":"104","author":"Pfeiffer","year":"2016","journal-title":"Am J Clin Nutr"},{"key":"10.1093\/ajcn\/nqz027_bib18","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1002\/bdra.23378","article-title":"U.S. women of childbearing age who are at possible increased risk of a neural tube defect-affected pregnancy due to suboptimal red blood cell folate concentrations: National Health and Nutrition Examination Survey 2007 to 2012","volume":"103","author":"Tinker","year":"2015","journal-title":"Birth Defects Res A Clin Mol Teratol"},{"key":"10.1093\/ajcn\/nqz027_bib19","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1002\/bdra.23499","article-title":"Red blood cell folate insufficiency among nonpregnant women of childbearing age in Guatemala 2009 to 2010: prevalence and predicted neural tube defects risk","volume":"106","author":"Rosenthal","year":"2016","journal-title":"Birth Defects Res A Clin Mol Teratol"},{"key":"10.1093\/ajcn\/nqz027_bib20","doi-asserted-by":"crossref","first-page":"64","DOI":"10.3945\/ajcn.2009.28401","article-title":"Folic acid source, usual intake, and folate and vitamin B-12 status in US adults: National Health and Nutrition Examination Survey (NHANES) 2003\u20132006","volume":"91","author":"Yang","year":"2010","journal-title":"Am J Clin Nutr"},{"key":"10.1093\/ajcn\/nqz027_bib21","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.3945\/ajcn.115.107151","article-title":"Impact of voluntary fortification and supplement use on dietary intakes and biomarker status of folate and vitamin B-12 in Irish adults","volume":"101","author":"Hopkins","year":"2015","journal-title":"Am J Clin Nutr"},{"key":"10.1093\/ajcn\/nqz027_bib22","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1111\/j.1365-2141.1975.tb01844.x","article-title":"Folate deficiency in the alcoholic\u2014its relationship to clinical and haematological abnormalities, liver disease and folate stores","volume":"29","author":"Wu","year":"1975","journal-title":"Br J Haematol"},{"key":"10.1093\/ajcn\/nqz027_bib23","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.3945\/ajcn.110.004671","article-title":"MTHFR 677C\u2192T genotype is associated with folate and homocysteine concentrations in a large, population-based, double-blind trial of folic acid supplementation","volume":"93","author":"Crider","year":"2011","journal-title":"Am J Clin Nutr"},{"key":"10.1093\/ajcn\/nqz027_bib24","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1093\/ajcn\/88.2.448","article-title":"Folate status and homocysteine response to folic acid doses and withdrawal among young Chinese women in a large-scale randomized double-blind trial","volume":"88","author":"Hao","year":"2008","journal-title":"Am J Clin Nutr"},{"key":"10.1093\/ajcn\/nqz027_bib25","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/S0076-6879(97)81007-5","article-title":"Microbiological assay for serum, plasma, and red cell folate using cryopreserved, microtiter plate method","volume":"281","author":"Molloy","year":"1997","journal-title":"Methods Enzymol"},{"key":"10.1093\/ajcn\/nqz027_bib26","doi-asserted-by":"crossref","first-page":"693S","DOI":"10.3945\/ajcn.2008.26947A","article-title":"How common is vitamin B-12 deficiency?","volume":"89","author":"Allen","year":"2009","journal-title":"Am J Clin Nutr"},{"key":"10.1093\/ajcn\/nqz027_bib27","first-page":"421","article-title":"Optimal serum and red blood cell folate concentrations in women of reproductive age for prevention of neural tube defects: World Health Organization guidelines","volume":"64","author":"Cordero","year":"2015","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"10.1093\/ajcn\/nqz027_bib28","first-page":"703","article-title":"Maternal plasma folate and vitamin B12 are independent risk factors for neural tube defects","volume":"86","author":"Kirke","year":"1993","journal-title":"Q J Med"},{"key":"10.1093\/ajcn\/nqz027_bib29","doi-asserted-by":"crossref","first-page":"1698","DOI":"10.1001\/jama.1995.03530210052030","article-title":"Folate levels and neural tube defects: implications for prevention","volume":"274","author":"Daly","year":"1995","journal-title":"JAMA"},{"key":"10.1093\/ajcn\/nqz027_bib30","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1111\/j.1471-0528.1976.tb00794.x","article-title":"The cause of the fall in serum folate in normal pregnancy","volume":"83","author":"Hall","year":"1976","journal-title":"BJOG"},{"key":"10.1093\/ajcn\/nqz027_bib31","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.3945\/ajcn.114.099994","article-title":"Assessing the association between the methylenetetrahydrofolate reductase (MTHFR) 677C>T polymorphism and blood folate concentrations: a systematic review and meta-analysis of trials and observational studies","volume":"101","author":"Tsang","year":"2015","journal-title":"Am J Clin Nutr"},{"key":"10.1093\/ajcn\/nqz027_bib32","doi-asserted-by":"crossref","first-page":"e59570","DOI":"10.1371\/journal.pone.0059570","article-title":"Genetic variants in the folate pathway and the risk of neural tube defects: a meta-analysis of the published literature","volume":"8","author":"Zhang","year":"2013","journal-title":"PLoS One"},{"key":"10.1093\/ajcn\/nqz027_bib33","doi-asserted-by":"crossref","first-page":"g4554","DOI":"10.1136\/bmj.g4554","article-title":"Population red blood cell folate concentrations for prevention of neural tube defects: Bayesian model","volume":"349","author":"Crider","year":"2014","journal-title":"BMJ"},{"key":"10.1093\/ajcn\/nqz027_bib34","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1007\/s10654-004-2253-z","article-title":"Body mass index and serum folate in childbearing age women","volume":"19","author":"Mojtabai","year":"2004","journal-title":"Eur J Epidemiol"},{"key":"10.1093\/ajcn\/nqz027_bib35","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1002\/bdra.23024","article-title":"Does obesity modify the association of supplemental folic acid with folate status among nonpregnant women of childbearing age in the United States?","volume":"94","author":"Tinker","year":"2012","journal-title":"Birth Defects Res A Clin Mol Teratol"},{"key":"10.1093\/ajcn\/nqz027_bib36","doi-asserted-by":"crossref","first-page":"1608","DOI":"10.1038\/ijo.2013.41","article-title":"Obesity affects short-term folate pharmacokinetics in women of childbearing age","volume":"37","author":"daSilva","year":"2013","journal-title":"Int J Obes"},{"key":"10.1093\/ajcn\/nqz027_bib37","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1097\/FTD.0b013e318219407a","article-title":"A comparison of folic acid pharmacokinetics in obese and nonobese women of childbearing age","volume":"33","author":"Stern","year":"2011","journal-title":"Ther Drug Monit"},{"key":"10.1093\/ajcn\/nqz027_bib38","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.4239\/wjd.v6.i10.1158","article-title":"Vitamin paradox in obesity: deficiency or excess?","volume":"6","author":"Zhou","year":"2015","journal-title":"World J Diabetes"},{"key":"10.1093\/ajcn\/nqz027_bib39","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1146\/annurev.nu.05.070185.000555","article-title":"Vitamin B12\u2013folate interrelationships","volume":"5","author":"Shane","year":"1985","journal-title":"Annu Rev Nutr"},{"key":"10.1093\/ajcn\/nqz027_bib40","doi-asserted-by":"crossref","first-page":"163","DOI":"10.3177\/jnsv.33.163","article-title":"Effect of long-term supplementation of folate on folate status in plasma and erythrocytes","volume":"33","author":"Heseker","year":"1987","journal-title":"J Nutr Sci Vitaminol"},{"key":"10.1093\/ajcn\/nqz027_bib41","doi-asserted-by":"crossref","first-page":"1414","DOI":"10.1093\/ajcn\/86.5.1414","article-title":"Calculation of red blood cell folate steady state conditions and elimination kinetics after daily supplementation with various folate forms and doses in women of childbearing age","volume":"86","author":"Pietrzik","year":"2007","journal-title":"Am J Clin Nutr"},{"key":"10.1093\/ajcn\/nqz027_bib42","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1093\/ajcn\/84.1.156","article-title":"Red blood cell folate concentrations increase more after supplementation with [6S]-5-methyltetrahydrofolate than with folic acid in women of childbearing age","volume":"84","author":"Lamers","year":"2006","journal-title":"Am J Clin Nutr"},{"key":"10.1093\/ajcn\/nqz027_bib43","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1024\/0300-9831.79.2.61","article-title":"Supplementation with a multivitamin containing 800 microg of folic acid shortens the time to reach the preventive red blood cell folate concentration in healthy women","volume":"79","author":"Bramswig","year":"2009","journal-title":"Int J Vitam Nutr Res"},{"key":"10.1093\/ajcn\/nqz027_bib44","doi-asserted-by":"crossref","first-page":"844","DOI":"10.3945\/ajcn.2008.26878","article-title":"Steady state folate concentrations achieved with 5 compared with 1.1 mg folic acid supplementation among women of childbearing age","volume":"89","author":"Nguyen","year":"2009","journal-title":"Am J Clin Nutr"},{"key":"10.1093\/ajcn\/nqz027_bib45","doi-asserted-by":"crossref","first-page":"136","DOI":"10.3945\/ajcn.110.004549","article-title":"Long-term effect of low-dose folic acid intake: potential effect of mandatory fortification on the prevention of neural tube defects","volume":"94","author":"Houghton","year":"2011","journal-title":"Am J Clin Nutr"}],"container-title":["The American Journal of Clinical Nutrition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0002916522032002?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0002916522032002?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/academic.oup.com\/ajcn\/advance-article-pdf\/doi\/10.1093\/ajcn\/nqz027\/28492542\/nqz027.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/ajcn\/article-pdf\/109\/5\/1452\/28888071\/nqz027.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,27]],"date-time":"2023-05-27T07:57:31Z","timestamp":1685174251000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0002916522032002"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5]]},"references-count":45,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2019,5]]}},"alternative-id":["S0002916522032002"],"URL":"https:\/\/doi.org\/10.1093\/ajcn\/nqz027","relation":{},"ISSN":["0002-9165"],"issn-type":[{"value":"0002-9165","type":"print"}],"subject":[],"published":{"date-parts":[[2019,5]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Defining the plasma folate concentration associated with the red blood cell folate concentration threshold for optimal neural tube defects prevention: a population-based, randomized trial of folic acid supplementation","name":"articletitle","label":"Article Title"},{"value":"The American Journal of Clinical Nutrition","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1093\/ajcn\/nqz027","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Copyright \u00a9 2019 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}]}}