The neuroprotective benefit of antenatal magnesium sulphate (MgSO4) for preterm infants is currently attributed to the magnesium content. Even though the mechanism is not fully understood, the potential contribution of sulphate has not been considered. This is relevant to very/extremely preterm infants that lack the capacity to generate sulphate. In our initial study, we showed that preterm infants (<30 wk) rapidly become sulphate deficient, and that antenatal MgSO4 administration can mitigate this deficiency.
Since sulphate is important for modulating brain development, we proposed that sulphate deficiency in preterm babies is detrimental to normal neurodevelopment. This is currently being investigated in a prospective observational study recruiting 1,505 preterm infants (<32 wk), and correlating plasma sulphate level at 1 week of age with developmental outcomes at 12 and 14 weeks CA (General Movements) and at 2 years CA (assessed by Bayley III). If sulphate neuroprotection is proven then neonatal sulphate supplementation (in place of antenatal magnesium sulphate) may prove a simple and effective, low-cost, low-risk intervention universally available to all preterm infants to improve their chances of a normal neurodevelopmental outcome.
The next phase of our research will involve a preclinical animal study to test the hypothesis that maintaining circulating sulphate levels in the preterm animal (pig) model will provide neuroprotective benefits. In 2016, we are generating pilot data to determine whether the preterm pig becomes sulphate deficient, as well as investigating the genetics and physiology of sulphate biology in the pregnant sow. The overarching aim of the preclinical animal study is to apply sulphate intervention to preterm pigs and assess potential benefits for neurodevelopmental outcomes. This study brings together a transdisciplinary team of biomedical and clinical investigators to address health issues in preterm infants using a world-first preclinical animal model of the very/extremely preterm human infant.