{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T06:42:08Z","timestamp":1776062528317,"version":"3.50.1"},"reference-count":67,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T00:00:00Z","timestamp":1776038400000},"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. Pediatr."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Copper is an essential micronutrient critical for fetal neurodevelopment, haematopoiesis, angiogenesis, and immune function, with maternal transfer\u2014particularly in the third trimester\u2014playing a key role in establishing fetal copper stores. Disruption of this process, due to genetic defects or micronutrient imbalance, can lead to significant neonatal complications.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This review examines the potential role of excessive maternal zinc supplementation as an underrecognized environmental modifier in Menkes disease (MD), an X-linked disorder caused by mutations in the ATP7A copper transporter. We hypothesize that in fetuses with ATP7A dysfunction, elevated maternal zinc intake may further impair copper absorption and placental transfer through competitive antagonism, thereby exacerbating fetal copper deficiency and influencing disease severity or onset.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Evidence<\/jats:title>\n                    <jats:p>Limited clinical data in pregnant women demonstrate that zinc supplementation can reduce maternal and fetal copper levels, supported by consistent findings from animal models and case reports indicating disrupted copper homeostasis. However, no large-scale or disease-specific studies have evaluated this interaction in relation to Menkes disease or neonatal outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Given the widespread use of zinc supplementation, particularly during the COVID-19 era, its impact on fetal copper status in genetically susceptible populations warrants urgent investigation. Targeted retrospective analyses and well-designed prospective studies are needed to validate this hypothesis. A re-evaluation of prenatal micronutrient strategies with emphasis on trace element balance may improve risk stratification and optimize maternal\u2013fetal health outcomes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fped.2026.1734361","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T05:43:27Z","timestamp":1776059007000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Could excessive zinc supplementation during pregnancy cause menkes disease? A hypothesis worth investigating"],"prefix":"10.3389","volume":"14","author":[{"given":"Uma Maheshwari","family":"Mugundan","sequence":"first","affiliation":[{"name":"Department of Pharmacy Practice, SRM College of Pharmacy, Faculty of Medicine and Health Sciences, SRM Institute of Science and Technology, Kattankulathur","place":["Chengalpattu, Tamil Nadu, India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Venkatesan","family":"Saravanan","sequence":"additional","affiliation":[{"name":"School of Pharmacy, SBV Chennai, Sri Balaji Vidyapeeth (Deemed to be University)","place":["Pondicherry, India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muhasaparur Ganesan","family":"Rajanandh","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice, SRM College of Pharmacy, Faculty of Medicine and Health Sciences, SRM Institute of Science and Technology, Kattankulathur","place":["Chengalpattu, Tamil Nadu, 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