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Research Article: SuPreme Study: a protocol to study the neuroprotective potential of sulfate among very/extremely preterm infants

Date Published: 2023-07-14

Abstract:
Introduction Antenatal maternal magnesium sulfate (MgSO 4 ) administration is a proven efficacious neuroprotective treatment reducing the risk of cerebral palsy (CP) among infants born preterm. Identification of the neuroprotective component with target plasma concentrations could lead to neonatal treatment with greater efficacy and accessibility. Methods and analysis This is a prospective observational cohort study, in three tertiary Australian centres. Participants are preterm infants, irrespective of antenatal MgSO 4 exposure, born in 2013–2020 at 24 +0 to 31 +6 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. 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 1–28, and in a further subset mother/infant blood is screened for genetic variants of sulfate transporter genes. The primary outcome is CP. Surviving infants are assessed for high risk of CP at 12–14 weeks CA according to Prechtl’s Method to assess General Movements. Follow-up at 2 years CA includes assessments for CP, cognitive, language and motor development, and social/behavioural difficulties. 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. Ethics and dissemination 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.

Introduction:
More than 1 in 10 births are preterm (<37 weeks gestation), 1 with survivors at considerable risk of life-long disabilities, including cerebral palsy (CP), intellectual impairment, social/behavioural difficulties and educational disadvantage. 2 3 The family, health and broader societal costs are estimated at >$26 billion per annum in the USA alone. 4 CP is a permanent condition of motor dysfunction, is the most common physical disability in childhood, and almost 50% of cases are due to preterm birth. 5 CP…

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