{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T15:58:49Z","timestamp":1772639929091,"version":"3.50.1"},"reference-count":50,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2020,6,4]],"date-time":"2020-06-04T00:00:00Z","timestamp":1591228800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Small-for-gestational-age (SGA) is associated with significant perinatal morbidity and mortality. Our aim was to investigate gene-nutrient interactions between maternal one-carbon single nucleotide polymorphisms (SNPs) and folic acid supplement (FAS) use, and their association with SGA. Nulliparous New Zealand women with singleton pregnancy were recruited as part of the Screening for Pregnancy Endpoints prospective cohort study. Data on FAS use was collected via face-to-face interview at 15 weeks\u2019 gestation; participants were followed prospectively and birth outcome data collected within 72 h of delivery. Participants were genotyped for MTHFR 677, MTHFR 1298, MTHFD1 1958, MTR 2756, MTRR 66 and TCN2 776 SNPs. Genotype data for at least one SNP was available for 1873 (93%) of eligible participants. Analysis showed a significant SNP-FAS interaction for MTHFR 1298 (p = 0.020), MTHFR 677 (p = 0.019) and TCN2 776 (p = 0.017) in relation to SGA: MTHFR 1298 CC variant non-FAS users had an increased likelihood [Odds Ratio (OR) = 2.91 (95% Confidence Interval (CI) = 1.52, 5.60] compared with wild-type (MTHFR 1298 AA) FAS users. MTHFR 677 variant allele carrier (MTHFR 677 CT + MTHFR 677 TT) non-FAS users had an increased likelihood [OR = 1.87 (95% CI = 1.21, 2.88)] compared to wild-type (MTHFR 677 CC) FAS users. TCN2 776 variant (TCN2 776 GG) non-FAS users had an increased likelihood [OR = 2.16 (95% CI = 1.26, 3.71)] compared with wild type homozygote + heterozygote (TCN2 776 CC + TCN2 776 CG) FAS users. No significant interactions were observed for MTHFD1 1958, MTR 2756 or MTRR 66 (p &gt; 0.05). We observed an overall pattern of FAS attenuating differences in the likelihood of SGA seen between genotype groups in FAS non-users. Future research should focus on how intake of other one-carbon nutrients might mediate these gene-nutrient interactions.<\/jats:p>","DOI":"10.3390\/nu12061677","type":"journal-article","created":{"date-parts":[[2020,6,5]],"date-time":"2020-06-05T03:32:21Z","timestamp":1591327941000},"page":"1677","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["The Effect of Interactions between Folic Acid Supplementation and One Carbon Metabolism Gene Variants on Small-for-Gestational-Age Births in the Screening for Pregnancy Endpoints (SCOPE) Cohort Study"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3765-1387","authenticated-orcid":false,"given":"Rhodi E.","family":"Bulloch","sequence":"first","affiliation":[{"name":"Discipline of Nutrition and Dietetics, The University of Auckland, Auckland 1010, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1062-3909","authenticated-orcid":false,"given":"Clare R.","family":"Wall","sequence":"additional","affiliation":[{"name":"Discipline of Nutrition and Dietetics, The University of Auckland, Auckland 1010, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lesley M. E.","family":"McCowan","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, The University of Auckland, Auckland 1010, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1718-9332","authenticated-orcid":false,"given":"Rennae S.","family":"Taylor","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, The University of Auckland, Auckland 1010, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9250-2192","authenticated-orcid":false,"given":"Claire T.","family":"Roberts","sequence":"additional","affiliation":[{"name":"Robinson Research Institute, Adelaide Medical School, University of Adelaide, Adelaide 5005, Australia"},{"name":"Flinders Health and Medical Research Institute, Flinders University, Bedford Park 5042, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6944-381X","authenticated-orcid":false,"given":"John M. D.","family":"Thompson","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, The University of Auckland, Auckland 1010, New Zealand"},{"name":"Department of Paediatrics, Child and Youth Health, The University of Auckland, Auckland 1010, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1210\/er.2018-00083","article-title":"Children born small for gestational age: Differential diagnosis, molecular genetic evaluation, and implications","volume":"39","author":"Finken","year":"2018","journal-title":"Endocr. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"McCowan, L.M., Thompson, J.M., Taylor, R.S., Baker, P.N., North, R.A., Poston, L., Roberts, C.T., Simpson, N.A., Walker, J.J., and Myers, J. (2017). 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