{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T18:17:21Z","timestamp":1790619441508,"version":"4.1.0"},"reference-count":27,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"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":["Pediatr Res"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Our previous preclinical rodent studies demonstrated the safety and efficacy of citrate-functionalized tri-manganese tetroxide (C-Mn\n                      <jats:sub>3<\/jats:sub>\n                      O\n                      <jats:sub>4<\/jats:sub>\n                      ) nanoparticles to reverse severe neonatal hyperbilirubinemia (SHB).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>Primary objective was to evaluate whether a single oral dose of the nanodrug could reduce neonatal mortality due to SHB and secondarily reduce the need for exchange transfusion (ExTx).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The nanodrug was administered to neonates (gestational age \u226535 weeks) admitted for SHB undergoing phototherapy (per AAP-guidelines) and deemed risk for ABE following parental consent. Clinical outcomes, including neonatal mortality, ExTx use and phototherapy duration were compared to a cohort managed after the experimental drug\u2019s use was paused.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In 207\/216 eligible neonates, 170 received nanodrug (Phase I) and 37 did not (Phase II). Mortality was 1.2% vs. 16.2%, respectively; 94% reduction (OR\u2009=\u20090.06). ExTx was needed in 17.1% vs. 81.1% (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001). Phototherapy duration was shorter: mean\u2009=\u200918.0\u2009\u00b1\u20099.8\u2009h vs 57.4\u2009\u00b1\u200920.7\u2009h; difference \u221239.4\u2009h (95% CI: \u221245.2 to -33.6; HR\u2009=\u200912.9;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001), with treated neonates 13-fold more likely to discontinue therapy at any given point-of-time. No significant clinical adverse events were reported.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and relevance<\/jats:title>\n                    <jats:p>\n                      Pilot observations suggest prescriptive adjunctive-use of C-Mn\n                      <jats:sub>3<\/jats:sub>\n                      O\n                      <jats:sub>4<\/jats:sub>\n                      NPs reduced neonatal mortality, decreased ExTx need among neonates with SHB and augmented phototherapy efficacy by shortening its duration.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Impact<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Citrate-functionalized manganese oxide nanoparticles augments phototherapy by reducing frequency of neonatal mortality, exchange transfusions, and phototherapy duration in SHB neonates at-risk for acute bilirubin encephalopathy.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>This experimental chemical agent is the only drug since tin-mesoporphyrin to demonstrate clinical efficacy to reverse hyperbilirubinemia in human neonates.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Successful implementation of this agent, when proven through randomized controlled trials, could alleviate current treatment gaps for SHB in resource-constrained communities.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1038\/s41390-026-05144-8","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T09:36:52Z","timestamp":1780393012000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Citrate-functionalized manganese oxide nanoparticles in neonates \u226535 weeks gestation at risk of acute bilirubin encephalopathy: a phase 1 observational trial"],"prefix":"10.1038","author":[{"given":"Asim K.","family":"Mallick","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tithi","family":"Dutta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodosi","family":"Hauli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anisha","family":"Mallick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6470-4099","authenticated-orcid":false,"given":"Aniruddha","family":"Adhikari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinod K.","family":"Bhutani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,2]]},"reference":[{"key":"5144_CR1","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1038\/s41372-023-01862-7","volume":"44","author":"VK Bhutani","year":"2024","unstructured":"Bhutani, V. 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