{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:28:38Z","timestamp":1785421718140,"version":"3.56.0"},"reference-count":43,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:00:00Z","timestamp":1783555200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key Research and Development Program, Ministry of Science and Technology of the People\u2019s Republic of China","award":["2025YFC2511501"],"award-info":[{"award-number":["2025YFC2511501"]}]},{"award":["2025YFC2511501"],"award-info":[{"award-number":["2025YFC2511501"]}],"id":[{"id":"https:\/\/ror.org\/027s68j25","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Key Project of the Regional Innovation and Development Joint Fund, National Natural Science Foundation of China","award":["U23A20420"],"award-info":[{"award-number":["U23A20420"]}]},{"award":["U23A20420"],"award-info":[{"award-number":["U23A20420"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Open Project Fund from Key Laboratory of Coal Environmental Pathogenicity and Prevention (Shanxi Medical University), Ministry of Education, China","award":["MEKLCEPP\/SXMU-202503"],"award-info":[{"award-number":["MEKLCEPP\/SXMU-202503"]}]},{"name":"Open Project Fund from Department of Obstetrics and Gynecology, Peking University Third Hospital","award":["BYSYSZKF2025003"],"award-info":[{"award-number":["BYSYSZKF2025003"]}]},{"DOI":"10.13039\/501100012226","name":"Clinical Medicine Plus X\u2014Young Scholars Project, Peking University, the Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["PKU2025PKULCXQ010"],"award-info":[{"award-number":["PKU2025PKULCXQ010"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: Folate plays a key role in one-carbon metabolism and may influence reproductive function, but evidence regarding its association with fecundability remains inconsistent. This study examined the association of folic acid (FA) supplementation, dietary folate intake, and folate status with time to pregnancy (TTP) among women planning to conceive. Methods: This study is a secondary analysis of a prospective cohort study included women enrolled during premarital health examinations in two counties in Shanxi Province (2009\u20132012). Folate-related exposures were assessed at baseline and included FA supplementation, dietary folate intake, and red blood cell (RBC) folate concentrations. Discrete-time proportional hazards model was used to estimate fecundability ratios (FRs) and 95% confidence intervals (CIs). Results: A total of 1475 women without a history of previous pregnancy were included, among whom 24 (1.6%) reported FA supplementation at baseline. Higher intake of several food groups was associated with increased RBC folate concentrations. In separate models, only seafood intake (1\u20133 times per week) was significantly associated with higher fecundability (FR: 1.23, 95% CI: 1.04, 1.44). In joint models, FA supplementation was associated with higher fecundability at 6 months (FR: 2.07, 95% CI: 1.01, 3.77), 12 months (FR: 1.91, 95% CI: 1.00, 3.30), and 24 months (FR: 1.91, 95% CI: 1.00, 3.30). Conclusions: Preconception FA supplementation showed a potential positive association with fecundability when considered alongside dietary intake and folate status, although the evidence was limited by the low use of supplementation. Further studies are needed to clarify the role of folate in human fecundability.<\/jats:p>","DOI":"10.3390\/nu18142238","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T11:55:32Z","timestamp":1783598132000},"page":"2238","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Preconception Folate Status, Dietary Intake, Supplementation, and Time to Pregnancy Among Women in a Premarital Health Examination Cohort"],"prefix":"10.3390","volume":"18","author":[{"given":"Lirong","family":"Nie","sequence":"first","affiliation":[{"name":"Institute of Reproductive and Child Health, National Health Commission Key Laboratory of Reproductive Health, School of Public Health, Peking University, Beijing 100191, China"},{"name":"Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Tian","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China"},{"name":"State Key Laboratory of Female Fertility Promotion, Peking University, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqian","family":"Jia","sequence":"additional","affiliation":[{"name":"Institute of Reproductive and Child Health, National Health Commission Key Laboratory of Reproductive Health, School of Public Health, Peking University, Beijing 100191, China"},{"name":"Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China"},{"name":"State Key Laboratory of Female Fertility Promotion, Peking University, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyue","family":"Lin","sequence":"additional","affiliation":[{"name":"Institute of Reproductive and Child Health, National Health Commission Key Laboratory of Reproductive Health, School of Public Health, Peking University, Beijing 100191, China"},{"name":"Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingzhang","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Reproductive and Child Health, National Health Commission Key Laboratory of Reproductive Health, School of Public Health, Peking University, Beijing 100191, China"},{"name":"Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuwei","family":"Wu","sequence":"additional","affiliation":[{"name":"Institute of Reproductive and Child Health, National Health Commission Key Laboratory of Reproductive Health, School of Public Health, Peking University, Beijing 100191, China"},{"name":"Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yali","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Reproductive and Child Health, National Health Commission Key Laboratory of Reproductive Health, School of Public Health, Peking University, Beijing 100191, China"},{"name":"Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China"},{"name":"State Key Laboratory of Female Fertility Promotion, Peking University, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Reproductive and Child Health, National Health Commission Key Laboratory of Reproductive Health, School of Public Health, Peking University, Beijing 100191, China"},{"name":"Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China"},{"name":"State Key Laboratory of Female Fertility Promotion, Peking University, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianting","family":"Li","sequence":"additional","affiliation":[{"name":"Shanxi Key Laboratory of Birth Defect and Cell Regeneration, Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan 030001, China"},{"name":"Key Laboratory of Coal Environmental Pathogenicity and Prevention, Ministry of Education, Shanxi Medical University, Taiyuan 030001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7570-3809","authenticated-orcid":false,"given":"Zhiwen","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Reproductive and Child Health, National Health Commission Key Laboratory of Reproductive Health, School of Public Health, Peking University, Beijing 100191, China"},{"name":"Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China"},{"name":"State Key Laboratory of Female Fertility Promotion, Peking University, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhizhen","family":"Liu","sequence":"additional","affiliation":[{"name":"Shanxi Key Laboratory of Birth Defect and Cell Regeneration, Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan 030001, China"},{"name":"Key Laboratory of Coal Environmental Pathogenicity and Prevention, Ministry of Education, Shanxi Medical University, Taiyuan 030001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5844-8973","authenticated-orcid":false,"given":"Jufen","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Reproductive and Child Health, National Health Commission Key Laboratory of Reproductive Health, School of Public Health, Peking University, Beijing 100191, China"},{"name":"Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China"},{"name":"State Key Laboratory of Female Fertility Promotion, Peking University, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1093\/humupd\/dmv016","article-title":"Infertility around the globe: New thinking on gender, reproductive technologies and global movements in the 21st century","volume":"21","author":"Inhorn","year":"2015","journal-title":"Hum. Reprod. Update"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1186\/s12978-022-01450-6","article-title":"The current situation and future directions for the study on time-to-pregnancy: A scoping review","volume":"19","author":"Hong","year":"2022","journal-title":"Reprod. Health"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2331","DOI":"10.1093\/humrep\/deab107","article-title":"Trends in time-to-pregnancy in the USA: 2002 to 2017","volume":"36","author":"Eisenberg","year":"2021","journal-title":"Hum. Reprod."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1958","DOI":"10.1016\/j.fertnstert.2013.02.040","article-title":"Volitional determinants and age-related decline in fecundability: A general population prospective cohort study in Denmark","volume":"99","author":"Rothman","year":"2013","journal-title":"Fertil. Steril."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1097\/EDE.0b013e31816334ad","article-title":"Time trends in human fecundability in Sweden","volume":"19","author":"Scheike","year":"2008","journal-title":"Epidemiology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"22251","DOI":"10.1007\/s11356-020-08754-9","article-title":"Occupational exposure to pesticides and associated health effects among greenhouse farm workers","volume":"27","author":"Amoatey","year":"2020","journal-title":"Environ. Sci. Pollut. Res. Int."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e023996","DOI":"10.1136\/bmjopen-2018-023996","article-title":"Fecundability among Danish women with a history of miscarriage: A prospective cohort study","volume":"9","author":"Wildenschild","year":"2019","journal-title":"BMJ Open"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1093\/humrep\/dex001","article-title":"Couples\u2019 body composition and time-to-pregnancy","volume":"32","author":"Sundaram","year":"2017","journal-title":"Hum. Reprod."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e12985","DOI":"10.1111\/mcn.12985","article-title":"Thinness and fecundability: Time to pregnancy after adolescent marriage in rural Bangladesh","volume":"16","author":"Hur","year":"2020","journal-title":"Matern. Child Nutr."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1093\/humrep\/dey372","article-title":"Prospective study of cigarette smoking and fecundability","volume":"34","author":"Wesselink","year":"2019","journal-title":"Hum. Reprod."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1186\/s12978-025-02106-x","article-title":"Sleep behaviors and time-to-pregnancy: Results from a Guangzhou City cohort","volume":"22","author":"Zhang","year":"2025","journal-title":"Reprod. Health"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/j.fertnstert.2023.11.022","article-title":"Association between job control and time to pregnancy in a preconception cohort","volume":"121","author":"Sabbath","year":"2024","journal-title":"Fertil. Steril."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1111\/1471-0528.15647","article-title":"Metabolic syndrome and time to pregnancy: A retrospective study of nulliparous women","volume":"126","author":"Grieger","year":"2019","journal-title":"Bjog"},{"key":"ref_14","first-page":"Cd007807","article-title":"Antioxidants for female subfertility","volume":"8","author":"Showell","year":"2020","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1016\/j.fertnstert.2013.11.008","article-title":"Female dietary antioxidant intake and time to pregnancy among couples treated for unexplained infertility","volume":"101","author":"Ruder","year":"2014","journal-title":"Fertil. Steril."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"S213","DOI":"10.1016\/S0020-7292(15)30023-0","article-title":"The International Federation of Gynecology and Obstetrics (FIGO) recommendations on adolescent, preconception, and maternal nutrition: \u201cThink Nutrition First\u201d","volume":"131","author":"Hanson","year":"2015","journal-title":"Int. J. Gynaecol. Obstet."},{"key":"ref_17","first-page":"Cd007950","article-title":"Effects and safety of periconceptional oral folate supplementation for preventing birth defects","volume":"2015","year":"2015","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_18","unstructured":"World Health Organization (2026, June 05). Periconceptional Folic Acid Supplementation to Prevent Neural Tube Defects. Available online: https:\/\/www.who.int\/tools\/elena\/interventions\/folate-periconceptional\/."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1093\/humupd\/dmt041","article-title":"The periconceptional period, reproduction and long-term health of offspring: The importance of one-carbon metabolism","volume":"19","author":"Twigt","year":"2013","journal-title":"Hum. Reprod. Update"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3540","DOI":"10.1210\/jc.2018-00855","article-title":"First trimester urinary bisphenol and phthalate concentrations and time to pregnancy: A population-based cohort analysis","volume":"103","author":"Philips","year":"2018","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Ku, C.W., Ku, C.O., Tay, L.P.C., Xing, H.K., Cheung, Y.B., Godfrey, K.M., Colega, M.T., Teo, C., Tan, K.M.L., and Chong, Y.S. (2022). Dietary supplement intake and fecundability in a Singapore preconception cohort study. Nutrients, 14.","DOI":"10.3390\/nu14235110"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1038\/ejcn.2015.94","article-title":"Folic acid supplementation and fecundability: A Danish prospective cohort study","volume":"70","author":"Cueto","year":"2016","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"51.e1","DOI":"10.1016\/j.ajog.2019.02.039","article-title":"Preconception folate status and reproductive outcomes among a prospective cohort of folate-replete women","volume":"221","author":"DeVilbiss","year":"2019","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1080\/17520363.2024.2394386","article-title":"Exploring the correlation between homocysteine, red blood cell folate and MTHFRC677T genotypes with female infertility","volume":"18","author":"You","year":"2024","journal-title":"Biomark. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1002\/bdr2.1040","article-title":"Plasma folate levels and associated factors in women planning to become pregnant in a population with high prevalence of neural tube defects","volume":"109","author":"Ma","year":"2017","journal-title":"Birth Defects Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1017\/S1368980007246786","article-title":"Comparison of blood folate levels among pregnant Chinese women in areas with high and low prevalence of neural tube defects","volume":"10","author":"Ren","year":"2007","journal-title":"Public Health Nutr."},{"key":"ref_27","unstructured":"World Health Organization (2026, April 10). Serum and Red Blood Cell Folate Concentrations for Assessing Folate Status in Populations. Available online: http:\/\/apps.who.int\/iris\/bitstream\/10665\/162114\/1\/WHO_NMH_NHD_EPG_15.01.pdf?ua=1."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e2255001","DOI":"10.1001\/jamanetworkopen.2022.55001","article-title":"Modifiable risk factor score and fecundability in a preconception cohort in Singapore","volume":"6","author":"Loy","year":"2023","journal-title":"JAMA Netw. Open"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.fertnstert.2021.09.037","article-title":"Folate intake and ovarian reserve among women attending a fertility center","volume":"117","author":"Kadir","year":"2022","journal-title":"Fertil. Steril."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1097\/AOG.0000000000000477","article-title":"Dietary folate and reproductive success among women undergoing assisted reproduction","volume":"124","author":"Gaskins","year":"2014","journal-title":"Obstet. Gynecol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1111\/j.1753-4887.2009.00266.x","article-title":"Folate-mediated one-carbon metabolism and its effect on female fertility and pregnancy viability","volume":"68","author":"Laanpere","year":"2010","journal-title":"Nutr. Rev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1093\/humupd\/dmp025","article-title":"Role of micronutrients in the periconceptional period","volume":"16","author":"Cetin","year":"2010","journal-title":"Hum. Reprod. Update"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1095\/biolreprod.103.015800","article-title":"Homocysteine induces trophoblast cell death with apoptotic features","volume":"69","author":"Maggiano","year":"2003","journal-title":"Biol. Reprod."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2372","DOI":"10.1093\/advances\/nmab068","article-title":"Female fertility and the nutritional approach: The most essential aspects","volume":"12","author":"Skoracka","year":"2021","journal-title":"Adv. Nutr."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1007\/s43032-021-00467-9","article-title":"Folate Levels and Pregnancy Rate in Women Undergoing Assisted Reproductive Techniques: A Systematic Review and Meta-analysis","volume":"29","author":"Paffoni","year":"2022","journal-title":"Reprod. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1016\/S0140-6736(01)05969-4","article-title":"Folic acid supplements during pregnancy and risk of miscarriage","volume":"358","author":"Gindler","year":"2001","journal-title":"Lancet"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1016\/j.rbmo.2014.01.017","article-title":"Folic acid supplementation and IVF pregnancy outcome in women with unexplained infertility","volume":"28","author":"Murto","year":"2014","journal-title":"Reprod. Biomed. Online"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1111\/aogs.12522","article-title":"Folic acid supplementation and methylenetetrahydrofolate reductase (MTHFR) gene variations in relation to in vitro fertilization pregnancy outcome","volume":"94","author":"Murto","year":"2015","journal-title":"Acta Obstet. Gynecol. Scand."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1016\/S0140-6736(06)68651-0","article-title":"Effect of B vitamins and genetics on success of in-vitro fertilisation: Prospective cohort study","volume":"367","author":"Haggarty","year":"2006","journal-title":"Lancet"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1093\/humrep\/deac002","article-title":"Dietary folate intake and fecundability in two preconception cohorts","volume":"37","author":"Cueto","year":"2022","journal-title":"Hum. Reprod."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1017\/S1368980013000864","article-title":"The folate status of reproductive-aged women in a randomised trial of a folate-fortified oral contraceptive: Dietary and blood assessments","volume":"17","author":"Aydemir","year":"2014","journal-title":"Public Health Nutr."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1496","DOI":"10.1093\/jn\/nxac050","article-title":"RBC folate and serum folate, vitamin b-12, and homocysteine in Chinese couples prepregnancy in the Shanghai preconception cohort","volume":"152","author":"Li","year":"2022","journal-title":"J. Nutr."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e70119","DOI":"10.1002\/ajhb.70119","article-title":"The Fertility Effects of the C677T Mutation in the methylenetetrahydrofolate reductase gene: A cross-site systematic review and meta-analysis","volume":"37","author":"MacLean","year":"2025","journal-title":"Am. J. Hum. Biol."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/14\/2238\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T12:12:18Z","timestamp":1783599138000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/14\/2238"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,9]]},"references-count":43,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["nu18142238"],"URL":"https:\/\/doi.org\/10.3390\/nu18142238","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,9]]}}}