{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T16:32:23Z","timestamp":1792427543728,"version":"4.5.0"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,8,3]],"date-time":"2022-08-03T00:00:00Z","timestamp":1659484800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Public Health"],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Previous studies have found that exposure to heavy metals increased the incidence of congenital heart defects (CHDs). However, there is a paucity of information about the connection between exposure to titanium and CHDs. This study sought to examine the relationship between prenatal titanium exposure and the risk of CHDs in offspring.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We looked back on a birth cohort study that was carried out in our hospital between 2010 and 2012. The associations between titanium exposure and the risk of CHDs were analyzed by using logistic regression analysis to investigate titanium concentrations in maternal whole blood and fetal umbilical cord blood.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 97 case groups and 194 control groups were included for a nested case-control study. The [P<jats:sub>50<\/jats:sub> (P<jats:sub>25<\/jats:sub>, P<jats:sub>75<\/jats:sub>)] of titanium were 371.91 (188.85, 659.15) \u03bcg\/L and 370.43 (264.86, 459.76) \u03bcg\/L in serum titanium levels in pregnant women and in umbilical cord serum titanium content in the CHDs group, respectively. There was a moderate positive correlation between the concentration of titanium in pregnant women's blood and that in umbilical cord blood. A higher concentrations of maternal blood titanium level was associated with a greater risk of CHDs (OR 2.706, 95% CI 1.547\u20134.734), the multiple CHDs (OR 2.382, 95% CI 1.219\u20134.655), atrial septal defects (OR 2.367, 95% CI 1.215\u20134.609), and patent ductus arteriosus (OR 2.412, 95% CI 1.336\u20134.357). Dramatically higher concentrations of umbilical cord blood levels had an increased risk of CHDs and different heart defects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Titanium can cross the placental barrier and the occurrence of CHDs may be related to titanium exposure.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fpubh.2022.946439","type":"journal-article","created":{"date-parts":[[2022,8,3]],"date-time":"2022-08-03T04:49:11Z","timestamp":1659502151000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":17,"title":["Relationship between maternal exposure to heavy metal titanium and offspring congenital heart defects in Lanzhou, China: A nested case-control study"],"prefix":"10.3389","volume":"10","author":[{"given":"Jianhao","family":"Sun","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baohong","family":"Mao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenzhen","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinjuan","family":"Jiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanxia","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongli","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuejing","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohui","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoying","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongmei","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojuan","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Yi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,8,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e20593","DOI":"10.1097\/MD.0000000000020593","article-title":"Incidence and mortality trend of congenital heart disease at the global, regional, and national level, 1990-2017","volume":"99","author":"Wu","year":"2020","journal-title":"Medicine."},{"key":"B2","doi-asserted-by":"publisher","first-page":"943","DOI":"10.1038\/nature06801","article-title":"The developmental genetics of congenital heart disease","volume":"451","author":"Bruneau","year":"2008","journal-title":"Nature."},{"key":"B3","doi-asserted-by":"publisher","first-page":"nzaa166","DOI":"10.1093\/cdn\/nzaa166","article-title":"Exploring the role of maternal nutritional epigenetics in congenital heart disease","volume":"4","author":"Joshi","year":"2020","journal-title":"Curr Dev Nutr."},{"key":"B4","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1080\/15563650.2017.1343479","article-title":"Barium exposure increases the risk of congenital heart defects occurrence in offspring","volume":"56","author":"Zhang","year":"2018","journal-title":"Clin Toxicol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"e15352","DOI":"10.1097\/MD.0000000000015352","article-title":"Metal nickel exposure increase the risk of congenital heart defects occurrence in offspring a case-control study in China","volume":"98","author":"Zhang","year":"2019","journal-title":"Medicine."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1110","DOI":"10.3390\/nano10061110","article-title":"Titanium dioxide nanoparticles in food and personal care products-what do we know about their safety?","volume":"10","author":"Musial","year":"2020","journal-title":"Nanomaterials."},{"key":"B7","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1038\/s41370-019-0161-2","article-title":"Weight of epidemiological evidence for titanium dioxide risk assessment: current state and further needs","volume":"30","author":"Canu","year":"2020","journal-title":"J Expo Sci Environ Epidemiol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"111632","DOI":"10.1016\/j.ecoenv.2020.111632","article-title":"Environmental titanium exposure and reproductive health: Risk of low birth weight associated with maternal titanium exposure from a nested case-control study in northern China","volume":"208","author":"Jin","year":"2021","journal-title":"Ecotoxicol Environ Saf"},{"key":"B9","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1007\/s12668-021-00836-3","article-title":"Toxicological consequences of titanium dioxide nanoparticles (TiO 2 NPs) and their jeopardy to human population","volume":"11","author":"Shabbir","year":"2021","journal-title":"Bionanoscience."},{"key":"B10","doi-asserted-by":"publisher","first-page":"103204","DOI":"10.1016\/j.etap.2019.103204","article-title":"Evaluation of cytogenotoxicity and oxidative stress parameters in male Swiss mice co-exposed to titanium dioxide and zinc oxide nanoparticles","volume":"70","author":"Fadoju","year":"2019","journal-title":"Environ Toxicol Pharmacol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1080\/17435390.2018.1425502","article-title":"Cardiopulmonary effects induced by occupational exposure to titanium dioxide nanoparticles","volume":"12","author":"Zhao","year":"2018","journal-title":"Nanotoxicology."},{"key":"B12","doi-asserted-by":"publisher","first-page":"110911","DOI":"10.1016\/j.ecoenv.2020.110911","article-title":"A key moment for TiO2: Prenatal exposure to TiO2 nanoparticles may inhibit the development of offspring","volume":"202","author":"Wu","year":"2020","journal-title":"Ecotoxicol Environ Saf"},{"key":"B13","doi-asserted-by":"publisher","first-page":"11767","DOI":"10.1021\/acs.jafc.8b02952","article-title":"Nano-TiO2 inhibits development of the central nervous system and its mechanism in offspring mice","volume":"66","author":"Hong","year":"2018","journal-title":"J Agric Food Chem."},{"key":"B14","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/j.ecoenv.2015.03.012","article-title":"Efficacy of the hatching event in assessing the embryo toxicity of the nano-sized TiO2 particles in zebrafish: a comparison between two different classes of hatching-derived variables","volume":"116","author":"Samaee","year":"2015","journal-title":"Ecotoxicol Environ Saf."},{"key":"B15","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1016\/j.chemosphere.2010.12.069","article-title":"Disruption of zebrafish (Danio rerio) reproduction upon chronic exposure to TiO2 nanoparticles","volume":"83","author":"Wang","year":"2011","journal-title":"Chemosphere."},{"key":"B16","doi-asserted-by":"publisher","first-page":"6197","DOI":"10.2147\/IJN.S143598","article-title":"Maternal exposure to nanosized titanium dioxide suppresses embryonic development in mice","volume":"12","author":"Hong","year":"2017","journal-title":"Int J Nanomedicine."},{"key":"B17","doi-asserted-by":"publisher","first-page":"e59378","DOI":"10.1371\/journal.pone.0059378","article-title":"Nanosized TiO2-induced reproductive system dysfunction and its mechanism in female mice","volume":"8","author":"Zhao","year":"2013","journal-title":"PLoS ONE."},{"key":"B18","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1007\/s12011-019-01706-6","article-title":"Effects of titanium dioxide nanoparticles exposure on human health-a review","volume":"193","author":"Baranowska-Wojcik","year":"2020","journal-title":"Biol Trace Elem Res."},{"key":"B19","doi-asserted-by":"publisher","first-page":"917","DOI":"10.1016\/j.envpol.2018.01.046","article-title":"Associations of multiple plasma metals with incident type 2 diabetes in Chinese adults: the Dongfeng-Tongji cohort","volume":"237","author":"Yuan","year":"2018","journal-title":"Environ Pollut."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1216","DOI":"10.1136\/gutjnl-2015-310297","article-title":"Titanium dioxide nanoparticles exacerbate DSS-induced colitis: role of the NLRP3 inflammasome","volume":"66","author":"Ruiz","year":"2017","journal-title":"Gut."},{"key":"B21","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/j.reprotox.2016.10.006","article-title":"Association between titanium and silver concentrations in maternal hair and risk of neural tube defects in offspring: a case-control study in north China","volume":"66","author":"Li","year":"2016","journal-title":"Reprod Toxicol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1007\/s12011-014-0057-x","article-title":"Levels of heavy metals and trace elements in umbilical cord blood and the risk of adverse pregnancy outcomes: a population-based study","volume":"160","author":"Zheng","year":"2014","journal-title":"Biol Trace Elem Res."},{"key":"B23","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1093\/aje\/kwu092","article-title":"Passive smoking and preterm birth in urban China","volume":"180","author":"Qiu","year":"2014","journal-title":"Am J Epidemiol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"e0187996","DOI":"10.1371\/journal.pone.0187996","article-title":"Maternal folic acid supplementation and dietary folate intake and congenital heart defects","volume":"12","author":"Mao","year":"2017","journal-title":"PLoS ONE."},{"key":"B25","doi-asserted-by":"publisher","first-page":"691364","DOI":"10.3389\/fimmu.2021.691364","article-title":"The relationship between preoperative systemic immune inflammation index and prognostic nutritional index and the prognosis of patients with alveolar hydatid disease","volume":"12","author":"Ren","year":"2021","journal-title":"Front Immunol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/j.jes.2018.11.004","article-title":"Heavy metals in maternal and cord blood in Beijing and their efficiency of placental transfer","volume":"80","author":"Li","year":"2019","journal-title":"J Environ Sci."},{"key":"B27","doi-asserted-by":"publisher","first-page":"109755","DOI":"10.1016\/j.ecoenv.2019.109755","article-title":"A pilot study of mothers and infants reveals fetal sex differences in the placental transfer efficiency of heavy metals","volume":"186","author":"Li","year":"2019","journal-title":"Ecotoxicol Environ Saf"},{"key":"B28","doi-asserted-by":"publisher","first-page":"5520","DOI":"10.1039\/C8AN00824H","article-title":"Analysis of soluble or titanium dioxide derived titanium levels in human whole blood: consensus from an inter-laboratory comparison","volume":"143","author":"Koller","year":"2018","journal-title":"Analyst."},{"key":"B29","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1186\/s12989-020-00381-z","article-title":"Basal Ti level in the human placenta and meconium and evidence of a materno-foetal transfer of food-grade TiOnanoparticles in an ex vivo placental perfusion model","volume":"17","author":"Guillard","year":"2020","journal-title":"Part Fibre Toxicol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"777","DOI":"10.2147\/IJN.S152400","article-title":"Gestational exposure to titanium dioxide nanoparticles impairs the placentation through dysregulation of vascularization, proliferation and apoptosis in mice","volume":"13","author":"Zhang","year":"2018","journal-title":"Int J Nanomedicine."},{"key":"B31","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.taap.2019.01.024","article-title":"Maternal titanium dioxide nanomaterial inhalation exposure compromises placental hemodynamics","volume":"367","author":"Abukabda","year":"2019","journal-title":"Toxicol Appl Pharmacol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"109439","DOI":"10.1016\/j.ecoenv.2019.109439","article-title":"Size-dependent maternal-fetal transfer and fetal developmental toxicity of ZnO nanoparticles after oral exposures in pregnant mice","volume":"182","author":"Teng","year":"2019","journal-title":"Ecotoxicol Environ Saf"},{"key":"B33","doi-asserted-by":"publisher","first-page":"3273","DOI":"10.1039\/C8BM00856F","article-title":"miR-96-5p and miR-101-3p as potential intervention targets to rescue TiO2 NP-induced autophagy and migration impairment of human trophoblastic cells","volume":"6","author":"Mao","year":"2018","journal-title":"Biomater Sci."},{"key":"B34","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1186\/s12989-019-0310-8","article-title":"ROS promote epigenetic remodeling and cardiac dysfunction in offspring following maternal engineered nanomaterial (ENM) exposure","volume":"16","author":"Kunovac","year":"2019","journal-title":"Part Fibre Toxicol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"e13485","DOI":"10.14814\/phy2.13485","article-title":"Linking metabolic and contractile dysfunction in aged cardiac myocytes","volume":"5","author":"Barton","year":"2017","journal-title":"Physiol. Rep."},{"key":"B36","doi-asserted-by":"publisher","first-page":"H446","DOI":"10.1152\/ajpheart.00634.2016","article-title":"Maternal-engineered nanomaterial exposure disrupts progeny cardiac function and bioenergetics","volume":"312","author":"Hathaway","year":"2017","journal-title":"Am J Physiol Heart Circ Physiol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"1800190","DOI":"10.1002\/smll.201800190","article-title":"Quantitative proteomics study reveals changes in the molecular landscape of human embryonic stem cells with impaired stem cell differentiation upon exposure to titanium dioxide nanoparticles","volume":"14","author":"Pan","year":"2018","journal-title":"Small."}],"container-title":["Frontiers in Public Health"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpubh.2022.946439\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,8,3]],"date-time":"2022-08-03T04:49:13Z","timestamp":1659502153000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpubh.2022.946439\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,3]]},"references-count":37,"alternative-id":["10.3389\/fpubh.2022.946439"],"URL":"https:\/\/doi.org\/10.3389\/fpubh.2022.946439","relation":{},"ISSN":["2296-2565"],"issn-type":[{"value":"2296-2565","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,3]]},"article-number":"946439"}}