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Identification of the neuroprotective component with target plasma concentrations could lead to neonatal treatment with greater efficacy and accessibility.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>\n                      This is a prospective observational cohort study, in three tertiary Australian centres. Participants are preterm infants, irrespective of antenatal MgSO\n                      <jats:sub>4<\/jats:sub>\n                      exposure, born in 2013\u20132020 at 24\n                      <jats:sup>+0<\/jats:sup>\n                      to 31\n                      <jats:sup>+6<\/jats:sup>\n                      weeks gestation, and followed up to 2 years corrected age (CA) (to September 2023). 1595 participants are required (allowing for 17% deaths\/loss to follow-up) to detect a clinically significant reduction (30% relative risk reduction) in CP when sulfate concentration at 7 days of age is 1 SD above the mean.\n                    <\/jats:p>\n                    <jats:p>A blood sample is collected on day 7 of age for plasma sulfate and magnesium measurement. In a subset of participants multiple blood and urine samples are collected for pharmacokinetic studies, between days 1\u201328, and in a further subset mother\/infant blood is screened for genetic variants of sulfate transporter genes.<\/jats:p>\n                    <jats:p>The primary outcome is CP. Surviving infants are assessed for high risk of CP at 12\u201314 weeks CA according to Prechtl\u2019s Method to assess General Movements. Follow-up at 2 years CA includes assessments for CP, cognitive, language and motor development, and social\/behavioural difficulties.<\/jats:p>\n                    <jats:p>Multivariate analyses will examine the association between day 7 plasma sulfate\/magnesium concentrations with adverse neurodevelopmental outcomes. A population pharmacokinetic model for sulfate in the preterm infant will be created using non-linear mixed-effects modelling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>The study has been approved by Mater Misericordiae Ltd Human Research Ethics Committee (HREC\/14\/MHS\/188). Results will be disseminated in peer-reviewed journal publications, and provided to the funding bodies. Using consumer input, a summary will be prepared for participants and consumer groups.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2023-076130","type":"journal-article","created":{"date-parts":[[2023,7,14]],"date-time":"2023-07-14T11:20:23Z","timestamp":1689333623000},"page":"e076130","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":7,"title":["SuPreme Study: a protocol to study the neuroprotective potential of sulfate among very\/extremely preterm infants"],"prefix":"10.1136","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3950-8907","authenticated-orcid":false,"given":"Elizabeth M","family":"Hurrion","sequence":"first","affiliation":[{"name":"Department of Newborn Services, Mater Mothers' Hospital, Brisbane, Queensland, Australia"},{"name":"Mater Research Institute The University of Queensland, South Brisbane, Queensland, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadia","family":"Badawi","sequence":"additional","affiliation":[{"name":"Cerebral Palsy Alliance, The University of Sydney, Sydney, New South Wales, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roslyn N","family":"Boyd","sequence":"additional","affiliation":[{"name":"Queensland Cerebral Palsy and Rehabilitation Research Centre, The University of Queensland, Saint Lucia, Queensland, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3670-0845","authenticated-orcid":false,"given":"Catherine","family":"Morgan","sequence":"additional","affiliation":[{"name":"Cerebral Palsy Alliance, The University of Sydney, Sydney, New South Wales, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristen","family":"Gibbons","sequence":"additional","affiliation":[{"name":"Child Health Research Centre, Mater Research Institute The University of Queensland, South Brisbane, Queensland, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefanie","family":"Hennig","sequence":"additional","affiliation":[{"name":"School of Clinical Sciences, Queensland University of Technology Faculty of Health, Kelvin Grove, Queensland, Australia"},{"name":"Integrated Drug Development, Certara Strategic Consulting, Certara LP, Princeton, New Jersey, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pieter","family":"Koorts","sequence":"additional","affiliation":[{"name":"Grantley Stable Neonatal Unit, Royal Brisbane and Women's Hospital, Herston, Queensland, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manbir","family":"Chauhan","sequence":"additional","affiliation":[{"name":"Department of Newborn Care, Gold Coast University Hospital, Southport, Queensland, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francis","family":"Bowling","sequence":"additional","affiliation":[{"name":"Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vicki","family":"Flenady","sequence":"additional","affiliation":[{"name":"Mater Research Institute The University of Queensland, South Brisbane, Queensland, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0832-4811","authenticated-orcid":false,"given":"Sailesh","family":"Kumar","sequence":"additional","affiliation":[{"name":"Mater Research Institute The University of Queensland, South Brisbane, Queensland, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7318-4985","authenticated-orcid":false,"given":"Paul A","family":"Dawson","sequence":"additional","affiliation":[{"name":"Mater Research Institute The University of Queensland, South Brisbane, Queensland, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2023,7,14]]},"reference":[{"key":"2025121220185711000_13.7.e076130.1","unstructured":"March of Dimes, PMNCH, Save the Children, WHO . 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