{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T05:23:54Z","timestamp":1787203434205,"version":"build-2736575974"},"reference-count":45,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009609","name":"Hospital Infantil de M\u00e9xico Federico G\u00f3mez","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100009609","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/00nzavp26","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: Congenital heart defects (CHDs) are among the most common congenital anomalies worldwide, and maternal nutrition during early pregnancy may influence their development. Although previous studies have mainly evaluated individual B-complex vitamins, the contribution of their combined dietary intake to CHD risk remains poorly understood. This study investigated the association between maternal dietary B-complex vitamin intake and the risk of complex CHDs in a Mexican case\u2013control study. Methods: Maternal dietary intake during pregnancy was assessed using a validated food frequency questionnaire, and nutrient intakes were energy-adjusted. Principal component analysis was used to construct a B-Complex Index based on the combined intake of vitamins B1, B2, B3, B6, and B12. Associations were evaluated using multivariable logistic regression adjusted for maternal age, total energy intake, multivitamin supplementation during pregnancy, and periconceptional folic acid supplementation. Results: Mothers of children with complex CHDs had significantly lower dietary intakes of B-complex vitamins than control mothers. The B-Complex Index was independently associated with lower odds of complex CHDs (adjusted OR = 0.707, 95% CI: 0.586\u20130.843; p = 0.0001). Conclusions: These findings suggest that evaluating the overall maternal dietary pattern of selected B-complex vitamins may provide complementary information regarding the nutritional environment relevant to early cardiac development. Prospective studies integrating dietary assessment, biomarkers, and genetic susceptibility are warranted to confirm these findings and further elucidate the underlying biological mechanisms.<\/jats:p>","DOI":"10.3390\/nu18162693","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T10:22:52Z","timestamp":1787048572000},"page":"2693","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Maternal Dietary B-Complex Vitamin Pattern and Risk of Complex Congenital Heart Defects in a Mexican Population"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5473-6772","authenticated-orcid":false,"given":"Jenny","family":"Vilchis-Gil","sequence":"first","affiliation":[{"name":"Unidad de Investigaci\u00f3n Epidemiol\u00f3gica en Endocrinolog\u00eda y Nutrici\u00f3n, Hospital Infantil de M\u00e9xico Federico G\u00f3mez, Mexico City 06720, Mexico"},{"name":"Facultad de Medicina, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Mexico City 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1099-0431","authenticated-orcid":false,"given":"Aaron M.","family":"G\u00f3mez-Jim\u00e9nez","sequence":"additional","affiliation":[{"name":"Departamento de Matem\u00e1ticas, Facultad de Ciencias, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Mexico City 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda E.","family":"Santill\u00e1n-Orgas","sequence":"additional","affiliation":[{"name":"Departamento de Neonatolog\u00eda, Hospital Infantil de M\u00e9xico Federico G\u00f3mez, Mexico City 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bego\u00f1a","family":"Segura-Stanford","sequence":"additional","affiliation":[{"name":"Departamento de Cardiolog\u00eda, Hospital Infantil de M\u00e9xico Federico G\u00f3mez, Mexico City 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7680-0835","authenticated-orcid":false,"given":"I\u00f1aki","family":"Navarro-Castellanos","sequence":"additional","affiliation":[{"name":"Departamento de Cardiolog\u00eda, Hospital Infantil de M\u00e9xico Federico G\u00f3mez, Mexico City 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline","family":"Gomez-Lopez","sequence":"additional","affiliation":[{"name":"Hospital Militar de Especialidades de la Mujer y Neonatolog\u00eda, Secretar\u00eda de la Defensa Nacional, Mexico City 11200, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mari C","family":"Mor\u00e1n-Espinosa","sequence":"additional","affiliation":[{"name":"Laboratorio de Investigaci\u00f3n en Patog\u00e9nesis Molecular, Hospital Infantil de M\u00e9xico Federico G\u00f3mez, Mexico City 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier T.","family":"Granados-Riveron","sequence":"additional","affiliation":[{"name":"Laboratorio de Investigaci\u00f3n en Patog\u00e9nesis Molecular, Hospital Infantil de M\u00e9xico Federico G\u00f3mez, Mexico City 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8018-7749","authenticated-orcid":false,"given":"Roc\u00edo","family":"Sanchez-Urbina","sequence":"additional","affiliation":[{"name":"Laboratorio de Investigaci\u00f3n en Cardiogen\u00e9tica, Hospital Infantil de M\u00e9xico Federico G\u00f3mez, Mexico City 06720, Mexico"},{"name":"Escuela Superior de Medicina, Instituto Polit\u00e9cnico Nacional, Mexico City 11340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1016\/0002-9149(78)90635-5","article-title":"Congenital heart disease in a cohort of 19,502 births with long-term follow-up","volume":"42","author":"Hoffman","year":"1978","journal-title":"Am. J. Cardiol."},{"key":"ref_2","first-page":"150","article-title":"La regionalizacion de la atencion de cardiopatias congenitas: Una meta pendiente","volume":"89","year":"2019","journal-title":"Arch. Cardiol. Mex."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/S0022-3476(05)81842-6","article-title":"Cardiovascular abnormalities in infants prenatally exposed to cocaine","volume":"118","author":"Lipshultz","year":"1991","journal-title":"J. Pediatr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2995","DOI":"10.1161\/CIRCULATIONAHA.106.183216","article-title":"Noninherited risk factors and congenital cardiovascular defects: Current knowledge: A scientific statement from the American Heart Association Council on Cardiovascular Disease in the Young: Endorsed by the American Academy of Pediatrics","volume":"115","author":"Jenkins","year":"2007","journal-title":"Circulation"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1588","DOI":"10.1001\/jama.2015.12505","article-title":"Association Between Preeclampsia and Congenital Heart Defects","volume":"314","author":"Auger","year":"2015","journal-title":"JAMA"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1159\/000506804","article-title":"There is a Strong Association between Early Preeclampsia and Congenital Heart Defects: A Large Population-Based, Retrospective Study","volume":"86","author":"Liu","year":"2021","journal-title":"Gynecol. Obstet. Investig."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.arcmed.2018.06.001","article-title":"Maternal Obesity as a Risk Factor for the Development of Total Anomalous Pulmonary Venous Connection in Their Offspring","volume":"49","author":"Blanco","year":"2018","journal-title":"Arch. Med. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.jacc.2018.10.050","article-title":"Maternal Overweight and Obesity and Risk of Congenital Heart Defects","volume":"73","author":"Persson","year":"2019","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1016\/j.contraception.2009.06.006","article-title":"Effect of interpregnancy interval on adverse perinatal outcomes--a national study","volume":"80","author":"Gordon","year":"2009","journal-title":"Contraception"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1002\/bdra.23507","article-title":"Is advanced maternal age a risk factor for congenital heart disease?","volume":"106","author":"Best","year":"2016","journal-title":"Birth Defects Res. Part A Clin. Mol. Teratol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"564.e1","DOI":"10.1016\/j.ajog.2014.02.002","article-title":"Relationship between interpregnancy interval and congenital anomalies","volume":"210","author":"Chen","year":"2014","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1016\/j.ajog.2014.02.003","article-title":"Interpregnancy interval and congenital anomalies","volume":"210","author":"Dolan","year":"2014","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1146\/annurev.nutr.19.1.217","article-title":"Homocysteine metabolism","volume":"19","author":"Selhub","year":"1999","journal-title":"Annu. Rev. Nutr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"15227","DOI":"10.1073\/pnas.93.26.15227","article-title":"Homocysteine induces congenital defects of the heart and neural tube: Effect of folic acid","volume":"93","author":"Rosenquist","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_15","first-page":"52","article-title":"Amino acids and the regulation of methyl balance in humans","volume":"10","author":"Brosnan","year":"2007","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"727","DOI":"10.2174\/1389203720666190125110150","article-title":"Epigenetic Mechanisms of Maternal Dietary Protein and Amino Acids Affecting Growth and Development of Offspring","volume":"20","author":"Wu","year":"2019","journal-title":"Curr. Protein Pept. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1017\/S0029665124004865","article-title":"B-vitamins and one-carbon metabolism during pregnancy: Health impacts and challenges","volume":"84","author":"Pentieva","year":"2025","journal-title":"Proc. Nutr. Soc."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.cbi.2006.04.014","article-title":"Mitochondrial function and toxicity: Role of the B vitamin family on mitochondrial energy metabolism","volume":"163","author":"Depeint","year":"2006","journal-title":"Chem. Biol. Interact."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1111\/cns.13207","article-title":"B Vitamins in the nervous system: Current knowledge of the biochemical modes of action and synergies of thiamine, pyridoxine, and cobalamin","volume":"26","year":"2020","journal-title":"CNS Neurosci. Ther."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1016\/j.tem.2021.05.011","article-title":"One carbon metabolism and early development: A diet-dependent destiny","volume":"32","author":"Korsmo","year":"2021","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e13474","DOI":"10.1111\/mcn.13474","article-title":"Molecular nutrition in life course perspective: Pinpointing metabolic pathways to target during periconception","volume":"20","author":"Ostojic","year":"2024","journal-title":"Matern. Child Nutr."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1016\/S0022-3476(99)70102-2","article-title":"Congenital heart defects and maternal derangement of homocysteine metabolism","volume":"135","author":"Kapusta","year":"1999","journal-title":"J. Pediatr."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.1111\/j.1471-0528.2006.01109.x","article-title":"Maternal hyperhomocysteinaemia is a risk factor for congenital heart disease","volume":"113","author":"Verlinde","year":"2006","journal-title":"BJOG"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1002\/bdrc.20098","article-title":"Effects of oxidative stress on embryonic development","volume":"81","author":"Dennery","year":"2007","journal-title":"Birth Defects Res. Part C Embryo Today"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1007\/s00726-003-0026-8","article-title":"Homocysteine and oxidative stress","volume":"25","author":"Perna","year":"2003","journal-title":"Amino Acids"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1038\/s41430-020-00804-2","article-title":"Maternal B-vitamin intake and B-vitamin supplementation during pregnancy in relation to neonatal congenital heart defects: A case-control study with propensity score matching","volume":"75","author":"Zhang","year":"2021","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1017\/S0007114520001816","article-title":"Maternal intake of one-carbon metabolism-related B vitamins and anorectal malformations in the Japan Environment and Children\u2019s Study","volume":"124","author":"Michikawa","year":"2020","journal-title":"Br. J. Nutr."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1016\/j.jacc.2025.09.006","article-title":"2025 ACC\/AHA\/HRS\/ISACHD\/SCAI Guideline for the Management of Adults with Congenital Heart Disease: A Report of the American College of Cardiology\/American Heart Association Joint Committee on Clinical Practice Guidelines","volume":"87","author":"Gurvitz","year":"2026","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_29","first-page":"237","article-title":"Validity and reproducibility of a food frequency questionnaire to estimate folate intake in a Mexican population","volume":"53","year":"2011","journal-title":"Salud Publica Mex."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1214\/aoms\/1177730491","article-title":"On a test of whether one of two random variables is stochastically larger than the other","volume":"18","author":"Mann","year":"1947","journal-title":"Ann. Math. Stat."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1002\/(SICI)1521-4036(200001)42:1<17::AID-BIMJ17>3.0.CO;2-U","article-title":"The Nonparametric Behrens-Fisher Problem: Asymptotic Theory and a Small-Sample Approximation","volume":"42","author":"Brunner","year":"2000","journal-title":"Biom. J."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Hosmer, D.W., Lemeshow, S., and Sturdivant, R.X. (2013). Applied Logistic Regression, John Wiley & Sons.","DOI":"10.1002\/9781118548387"},{"key":"ref_33","unstructured":"Hartig, F. (2026, August 16). DHARMa: Residual Diagnostics for Hierarchical (Multi-Level\/Mixed) Regression Models. R Package Version 0.4.6. Available online: https:\/\/CRAN.R-project.org\/package=DHARMa."},{"key":"ref_34","unstructured":"Team, R.C. (2020). R: A Language and Environment for Statistical Computing, R Foundation for Statistical Computing."},{"key":"ref_35","unstructured":"Gastwirth, J.L.G., Hui, Y.R., Lyubchich, W.L.W., Miao, V., and Noguchi, W. (2020). Lawstat: Tools for Biostatistics, Public Policy, and Law, R Package."},{"key":"ref_36","unstructured":"Kassambara, A., and Mundt, F. (2020). Factoextra: Extract and Visualize the Results of Multivariate Data Analyses, R Package."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Wickham, H. (2016). Data Analysis, in Ggplot2: Elegant Graphics for Data Analysis, Springer.","DOI":"10.1007\/978-3-319-24277-4_9"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.jpeds.2021.09.004","article-title":"Maternal Periconceptional Folic Acid Supplementation and Risk for Fetal Congenital Heart Defects","volume":"240","author":"Wang","year":"2022","journal-title":"J. Pediatr."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"260","DOI":"10.7150\/ijms.102843","article-title":"Association between maternal folic acid and\/or multivitamin supplementation time and fetal congenital heart disease: Based on the China birth cohort study","volume":"22","author":"Wang","year":"2025","journal-title":"Int. J. Med. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Kolmaga, A., Trafalska, E., Gaszy\u0144ska, E., Murlewska, J., Witkowski, S., Sylwestrzak, O., Soko\u0142owski, \u0141., Respondek-Liberska, M., and Strzelecka, I. (2024). Folic Acid and Selected Risk Factors for Fetal Heart Defects-Preliminary Study Results. Nutrients, 16.","DOI":"10.3390\/nu16173024"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Chen, L., Yang, T., Wang, T., Sun, M., and Qin, J. (2023). Relationships between Maternal Folic Acid Supplementation and GATA4 Gene Polymorphisms in Patients with Non-Chromosomal Congenital Heart Disease: A Hospital-Based Case-Control Study in China. Nutrients, 15.","DOI":"10.3390\/nu15204478"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1186\/s41043-024-00699-w","article-title":"Association of maternal folic acid supplementation and offspring MTRR gene polymorphism with congenital heart disease: A hospital-based case-control study in Han population","volume":"43","author":"Li","year":"2024","journal-title":"J. Health Popul. Nutr."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Liu, H., Ou, J., Chen, Y., Chen, Q., Luo, M., Wang, T., and Qin, J. (2023). Association of Maternal Folate Intake and Offspring MTHFD1 and MTHFD2 Genes with Congenital Heart Disease. Nutrients, 15.","DOI":"10.3390\/nu15163502"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1007\/s00246-012-0380-y","article-title":"Polymorphism 677C \u2192 T MTHFR gene in Mexican mothers of children with complex congenital heart disease","volume":"34","year":"2013","journal-title":"Pediatr. Cardiol."},{"key":"ref_45","first-page":"158","article-title":"Methylenetetrahydrofolate reductase gene 677CT polymorphism and isolated congenital heart disease in a Mexican population","volume":"65","year":"2012","journal-title":"Rev. Esp. Cardiol."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/16\/2693\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T04:32:59Z","timestamp":1787200379000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/16\/2693"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,18]]},"references-count":45,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["nu18162693"],"URL":"https:\/\/doi.org\/10.3390\/nu18162693","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,18]]}}}