{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T12:07:40Z","timestamp":1789992460926,"version":"4.0.1"},"reference-count":37,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2015,6,8]],"date-time":"2015-06-08T00:00:00Z","timestamp":1433721600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2015,6,8]],"date-time":"2015-06-08T00:00:00Z","timestamp":1433721600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We investigated the association between maternal zinc level during pregnancy and the risks of low birth weight (LBW) and small for gestational age (SGA) infants in a large population-based birth cohort study. In this study, 3187 pregnant women were recruited. For serum zinc level, 2940 pregnant women were sufficient (\u226556\u2009\u03bcg\/dL) and 247 deficient (&lt;56\u2009\u03bcg\/dL). Of interest, 7.3% newborns were with LBW among subjects with low zinc level (<jats:italic>RR<\/jats:italic>: 3.48; 95% <jats:italic>CI<\/jats:italic>: 2.03, 5.96; <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001). Adjusted <jats:italic>RR<\/jats:italic> for LBW was 3.41 (95% <jats:italic>CI<\/jats:italic>: 1.97, 5.91; <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001) among subjects with low zinc level. Moreover, 15.0% newborns were with SGA among subjects with low zinc level (<jats:italic>RR<\/jats:italic>: 1.98; 95% <jats:italic>CI<\/jats:italic>: 1.36, 2.88; <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001). Adjusted <jats:italic>RR<\/jats:italic> for SGA was 1.93 (95% <jats:italic>CI<\/jats:italic>: 1.32, 2.82; <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001) among subjects with low zinc level. A nested case-control study within above cohort showed that maternal serum zinc level was lower in SGA cases as compared with controls. By contrast, maternal serum C-reactive protein, TNF-\u03b1 and IL-8 levels were significantly higher in SGA cases than that of controls. Moreover, nuclear NF-\u03baB p65 was significantly up-regulated in placentas of SGA cases as compared with controls. Taken together, maternal zinc deficiency during pregnancy elevates the risks of LBW and SGA infants.<\/jats:p>","DOI":"10.1038\/srep11262","type":"journal-article","created":{"date-parts":[[2015,6,8]],"date-time":"2015-06-08T15:35:46Z","timestamp":1433777746000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":103,"title":["Maternal zinc deficiency during pregnancy elevates the risks of fetal growth restriction: a population-based birth cohort study"],"prefix":"10.1038","volume":"5","author":[{"given":"Hua","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-Fang","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-Hu","family":"Hao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan-Hua","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pu-Yu","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan-Yuan","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang-Biao","family":"Tao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"De-Xiang","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,6,8]]},"reference":[{"key":"BFsrep11262_CR1","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1210\/er.2006-0039","volume":"28","author":"P Saenger","year":"2007","unstructured":"Saenger, P., Czernichow, P., Hughes, I. & Reiter, E. O. Small for gestational age: short stature and beyond. Endocr Rev. 28, 219\u2013251 (2007).","journal-title":"Endocr Rev."},{"key":"BFsrep11262_CR2","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1097\/MOP.0b013e328326773b","volume":"21","author":"LA Joss-Moore","year":"2009","unstructured":"Joss-Moore, L. A. & Lane, R. H. The developmental origins of adult disease. Curr Opin Pediatr. 21, 230\u2013234 (2009).","journal-title":"Curr Opin Pediatr."},{"key":"BFsrep11262_CR3","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1136\/bmj.298.6673.564","volume":"298","author":"DJ Barker","year":"1989","unstructured":"Barker, D. J., Osmond, C., Golding, J., Kuh, D. & Wadsworth, M. E. Growth in utero, blood pressure in childhood and adult life and mortality from cardiovascular disease. BMJ. 298, 564\u2013567 (1989).","journal-title":"BMJ"},{"key":"BFsrep11262_CR4","doi-asserted-by":"publisher","first-page":"938","DOI":"10.1016\/0140-6736(93)91224-A","volume":"341","author":"DJ Barker","year":"1993","unstructured":"Barker, D. J. et al. Fetal nutrition and cardiovascular disease in adult life. Lancet. 341, 938\u2013941 (1993).","journal-title":"Lancet."},{"key":"BFsrep11262_CR5","doi-asserted-by":"publisher","first-page":"4448","DOI":"10.1210\/jc.2009-1079","volume":"94","author":"C Brufani","year":"2009","unstructured":"Brufani, C. et al. Obese children with low birth weight demonstrate impaired beta-cell function during oral glucose tolerance test. J Clin Endocrinol Metab. 94, 4448\u20134452 (2009).","journal-title":"J Clin Endocrinol Metab."},{"key":"BFsrep11262_CR6","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1016\/j.schres.2010.12.007","volume":"126","author":"CH Liao","year":"2011","unstructured":"Liao, C. H. et al. Schizophrenia patients at higher risk of diabetes, hypertension and hyperlipidemia: a population-based study. Schizophr Res. 126, 110\u2013116 (2011).","journal-title":"Schizophr Res."},{"key":"BFsrep11262_CR7","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/S0065-2776(08)00003-5","volume":"97","author":"T Hirano","year":"2008","unstructured":"Hirano, T. et al. Roles of zinc and zinc signaling in immunity: zinc as an intracellular signaling molecule. Adv Immunol. 97, 149\u2013176 (2008).","journal-title":"Adv Immunol."},{"key":"BFsrep11262_CR8","doi-asserted-by":"publisher","first-page":"788","DOI":"10.1111\/j.1471-0528.1984.tb04851.x","volume":"91","author":"PK Buamah","year":"1984","unstructured":"Buamah, P. K., Russell, M., Bates, G., Ward, A. M. & Skillen, A. W. Maternal zinc status: a determination of central nervous system malformation. Br J Obstet Gynaecol. 91, 788\u2013790 (1984).","journal-title":"Br J Obstet Gynaecol."},{"key":"BFsrep11262_CR9","first-page":"156","volume":"9","author":"KK Lehti","year":"1993","unstructured":"Lehti, K. K. Stillbirth rates and folic acid and zinc status in low-socioeconomic pregnant women of Brazilian Amazon. Nutrition. 9, 156\u2013158 (1993).","journal-title":"Nutrition"},{"key":"BFsrep11262_CR10","doi-asserted-by":"publisher","first-page":"1115","DOI":"10.1093\/oxfordjournals.aje.a116615","volume":"137","author":"TO Scholl","year":"1993","unstructured":"Scholl, T. O., Hediger, M. L., Schall, J. I., Fischer, R. L. & Khoo, C. S. Low zinc intake during pregnancy: its association with preterm and very preterm delivery. Am J Epidemiol. 137, 1115\u20131124 (1993).","journal-title":"Am J Epidemiol."},{"key":"BFsrep11262_CR11","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1530\/jrf.0.1020253","volume":"102","author":"TW Graham","year":"1994","unstructured":"Graham, T. W. et al. Serum zinc and copper concentrations in relation to spontaneous abortion in cows: implications for human fetal loss. J Reprod Fertil. 102, 253\u2013262 (1994).","journal-title":"J Reprod Fertil."},{"key":"BFsrep11262_CR12","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1024\/0300-9831\/a000141","volume":"83","author":"EP Prawirohartono","year":"2013","unstructured":"Prawirohartono, E. P., Nystrom, L., Nurdiati, D. S., Hakimi, M. & Lind, T. The impact of prenatal vitamin A and zinc supplementation on birth size and neonatal survival - a double-blind, randomized controlled trial in a rural area of Indonesia. Int J Vitam Nutr Res. 83, 14\u201325 (2013).","journal-title":"Int J Vitam Nutr Res."},{"key":"BFsrep11262_CR13","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1186\/1756-0500-7-265","volume":"7","author":"B Piso","year":"2014","unstructured":"Piso, B., Zechmeister-Koss, I. & Winkler, R. Antenatal interventions to reduce preterm birth: an overview of Cochrane Systematic Reviews. BMC Res Notes. 7, 265 (2014).","journal-title":"BMC Res Notes"},{"key":"BFsrep11262_CR14","first-page":"CD000230","volume":"7","author":"R Mori","year":"2012","unstructured":"Mori, R. et al. Zinc supplementation for improving pregnancy and infant outcome. Cochrane Database Syst Rev. 7, CD000230 (2012).","journal-title":"Cochrane Database Syst Rev."},{"key":"BFsrep11262_CR15","first-page":"CD000230","volume":"2","author":"E Ota","year":"2015","unstructured":"Ota, E. et al. Zinc supplementation for improving pregnancy and infant outcome. Cochrane Database Syst Rev. 2, CD000230 (2015).","journal-title":"Cochrane Database Syst Rev."},{"key":"BFsrep11262_CR16","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1042\/cs0680395","volume":"68","author":"K Simmer","year":"1985","unstructured":"Simmer, K. & Thompson, R. P. Maternal zinc and intrauterine growth retardation. Clin Sci (Lond). 68, 395\u2013399 (1985).","journal-title":"Clin Sci (Lond)"},{"key":"BFsrep11262_CR17","doi-asserted-by":"publisher","first-page":"678","DOI":"10.1093\/ajcn\/51.4.678","volume":"51","author":"YH Neggers","year":"1990","unstructured":"Neggers, Y. H. et al. A positive association between maternal serum zinc concentration and birth weight. Am J Clin Nutr. 51, 678\u2013684 (1990).","journal-title":"Am J Clin Nutr."},{"key":"BFsrep11262_CR18","doi-asserted-by":"publisher","first-page":"756","DOI":"10.1093\/ajcn\/78.4.756","volume":"78","author":"C Hotz","year":"2003","unstructured":"Hotz, C., Peerson, J. M. & Brown, K. H. Suggested lower cutoffs of serum zinc concentrations for assessing zinc status: reanalysis of the second National Health and Nutrition Examination Survey data (1976-1980). Am J Clin Nutr. 78, 756\u2013764 (2003).","journal-title":"Am J Clin Nutr."},{"key":"BFsrep11262_CR19","doi-asserted-by":"publisher","first-page":"1027","DOI":"10.3945\/ajcn.2009.28089","volume":"91","author":"CR Cole","year":"2010","unstructured":"Cole, C. R. et al. Zinc and iron deficiency and their interrelations in low-income African American and Hispanic children in Atlanta. Am J Clin Nutr. 91, 1027\u20131034 (2010).","journal-title":"Am J Clin Nutr."},{"key":"BFsrep11262_CR20","doi-asserted-by":"publisher","first-page":"898","DOI":"10.1186\/1471-2458-11-898","volume":"11","author":"S Gebremedhin","year":"2011","unstructured":"Gebremedhin, S., Enquselassie, F. & Umeta, M. Prevalence of prenatal zinc deficiency and its association with socio-demographic, dietary and health care related factors in rural Sidama, Southern Ethiopia: a cross-sectional study. BMC Public Health. 11, 898 (2011).","journal-title":"BMC Public Health."},{"key":"BFsrep11262_CR21","doi-asserted-by":"publisher","first-page":"1057","DOI":"10.1038\/ejcn.2010.118","volume":"64","author":"J Arnaud","year":"2010","unstructured":"Arnaud, J. et al. Determinants of serum zinc concentrations in a population of French middle-age subjects (SU.VI.MAX cohort). Eur J Clin Nutr. 64, 1057\u20131064 (2010).","journal-title":"Eur J Clin Nutr."},{"key":"BFsrep11262_CR22","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1093\/ajcn\/71.1.109","volume":"71","author":"T Tamura","year":"2000","unstructured":"Tamura, T., Goldenberg, R. L., Johnston, K. E. & DuBard, M. Maternal plasma zinc concentrations and pregnancy outcome. Am J Clin Nutr. 71, 109\u2013113 (2000).","journal-title":"Am J Clin Nutr."},{"key":"BFsrep11262_CR23","doi-asserted-by":"publisher","first-page":"702","DOI":"10.1093\/ajcn\/67.4.702","volume":"67","author":"RS Gibson","year":"1998","unstructured":"Gibson, R. S. & Huddle, J. M. Suboptimal zinc status in pregnant Malawian women: its association with low intakes of poorly available zinc, frequent reproductive cycling and malaria. Am J Clin Nutr. 67, 702\u2013709 (1998).","journal-title":"Am J Clin Nutr."},{"key":"BFsrep11262_CR24","doi-asserted-by":"publisher","first-page":"e50213","DOI":"10.1371\/journal.pone.0050213","volume":"7","author":"S Gebremedhin","year":"2012","unstructured":"Gebremedhin, S., Enquselassie, F. & Umeta, M. Independent and joint effects of prenatal Zinc and Vitamin A Deficiencies on birthweight in rural Sidama, Southern Ethiopia: prospective cohort study. PLoS One. 7, e50213 (2012).","journal-title":"PLoS One."},{"key":"BFsrep11262_CR25","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1111\/j.1740-8709.2012.00430.x","volume":"10","author":"HD Mistry","year":"2014","unstructured":"Mistry, H. D. et al. Maternal selenium, copper and zinc concentrations in pregnancy associated with small-for-gestational-age infants. Matern Child Nutr. 10, 327\u2013334 (2014).","journal-title":"Matern Child Nutr."},{"key":"BFsrep11262_CR26","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1146\/annurev-nutr-080508-141119","volume":"29","author":"H Haase","year":"2009","unstructured":"Haase, H. & Rink, L. Functional significance of zinc-related signaling pathways in immune cells. Annu Rev Nutr. 29, 133\u2013152 (2009).","journal-title":"Annu Rev Nutr."},{"key":"BFsrep11262_CR27","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1002\/bdra.10035","volume":"67","author":"LC Carey","year":"2003","unstructured":"Carey, L. C., Berbee, P. L., Coyle, P., Philcox, J. C. & Rofe, A. M. Zinc treatment prevents lipopolysaccharide-induced teratogenicity in mice. Birth Defects Res A Clin Mol Teratol. 67, 240\u2013245 (2003).","journal-title":"Birth Defects Res A Clin Mol Teratol."},{"key":"BFsrep11262_CR28","doi-asserted-by":"publisher","first-page":"454","DOI":"10.4049\/jimmunol.1103579","volume":"189","author":"YH Chen","year":"2012","unstructured":"Chen, Y. H. et al. Zinc supplementation during pregnancy protects against lipopolysaccharide-induced fetal growth restriction and demise through its anti-inflammatory effect. J Immunol. 189, 454\u2013463 (2012).","journal-title":"J Immunol."},{"key":"BFsrep11262_CR29","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1038\/jp.2010.53","volume":"31","author":"G Amarilyo","year":"2011","unstructured":"Amarilyo, G. et al. Increased cord serum inflammatory markers in small-for-gestational-age neonates. J Perinatol. 31, 30\u201332 (2011).","journal-title":"J Perinatol."},{"key":"BFsrep11262_CR30","doi-asserted-by":"publisher","first-page":"114","DOI":"10.3109\/15513815.2013.879239","volume":"33","author":"U Lausten-Thomsen","year":"2014","unstructured":"Lausten-Thomsen, U., Olsen, M., Greisen, G. & Schmiegelow, K. Inflammatory markers in umbilical cord blood from small-for-gestational-age newborns. Fetal Pediatr Pathol. 33, 114\u2013118 (2014).","journal-title":"Fetal Pediatr Pathol."},{"key":"BFsrep11262_CR31","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1093\/ajcn\/88.1.147","volume":"88","author":"M van Eijsden","year":"2008","unstructured":"van Eijsden, M., Smits, L. J., van der Wal, M. F. & Bonsel, G. J. Association between short interpregnancy intervals and term birth weight: the role of folate depletion. Am J Clin Nutr. 88, 147\u2013153 (2008).","journal-title":"Am J Clin Nutr."},{"key":"BFsrep11262_CR32","doi-asserted-by":"publisher","first-page":"1450","DOI":"10.3945\/ajcn.112.056382","volume":"98","author":"P Dwarkanath","year":"2013","unstructured":"Dwarkanath, P. et al. High folate and low vitamin B-12 intakes during pregnancy are associated with small-for-gestational age infants in South Indian women: a prospective observational cohort study. Am J Clin Nutr. 98, 1450\u20131458 (2013).","journal-title":"Am J Clin Nutr."},{"key":"BFsrep11262_CR33","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1093\/aje\/kwm071","volume":"166","author":"JM Catov","year":"2007","unstructured":"Catov, J. M., Bodnar, L. M., Ness, R. B., Markovic, N. & Roberts, J. M. Association of periconceptional multivitamin use and risk of preterm or small-for-gestational-age births. Am J Epidemiol. 166, 296\u2013303 (2007).","journal-title":"Am J Epidemiol."},{"key":"BFsrep11262_CR34","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1017\/S0007114509288994","volume":"102","author":"S Timmermans","year":"2009","unstructured":"Timmermans, S., Jaddoe, V. W., Hofman, A., Steegers-Theunissen, R. P. & Steegers, E. A. Periconception folic acid supplementation, fetal growth and the risks of low birth weight and preterm birth: the Generation R Study. Br J Nutr. 102, 777\u2013785 (2009).","journal-title":"Br J Nutr."},{"key":"BFsrep11262_CR35","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1093\/ije\/dys085","volume":"42","author":"FB Tao","year":"2013","unstructured":"Tao, F. B. et al. Cohort Profile: the China-Anhui Birth Cohort Study. Int J Epidemiol. 42, 709\u2013721 (2013).","journal-title":"Int J Epidemiol."},{"key":"BFsrep11262_CR36","doi-asserted-by":"publisher","first-page":"e1001292","DOI":"10.1371\/journal.pmed.1001292","volume":"9","author":"T Marchant","year":"2012","unstructured":"Marchant, T. et al. Neonatal mortality risk associated with preterm birth in East Africa, adjusted by weight for gestational age: individual participant level meta-analysis. PLoS Med. 9, e1001292 (2012).","journal-title":"PLoS Med."},{"key":"BFsrep11262_CR37","first-page":"241","volume":"28","author":"A Stahlavska","year":"1973","unstructured":"Stahlavska, A., Slansky, V. & Benediktova, B. The use of spectrum analytical methods in drug analysis. 3. Determination of iron using atomic absorption spectrophotometry. Pharmazie. 28, 241\u2013242 (1973).","journal-title":"Pharmazie."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep11262.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep11262","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep11262.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T18:12:53Z","timestamp":1672942373000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep11262"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,6,8]]},"references-count":37,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2015,9,1]]}},"alternative-id":["BFsrep11262"],"URL":"https:\/\/doi.org\/10.1038\/srep11262","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,6,8]]},"assertion":[{"value":"2 October 2014","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 May 2015","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 June 2015","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"11262"}}