SuPreme study: Neuroprotective role of sulphate among preterm babies

Chief Investigators: A/Prof Paul Dawson (MRI-UQ), Prof N Badawi (CP Alliance), Prof R Boyd, A/Prof V Flenady (MRI-UQ), Dr E Hurrion (MMH), Prof F Bowling (MRI-UQ), Dr P Koorts (RBWH), Prof S Kumar (MRI-UQ).

Associate Investigators: Dr C Morgan, A/Prof K Gibbons, Dr M Beckmann, Prof P Colditz, Dr S McIntyre, Ms V de Ryck.

Funding:  NHMRC Project grant ($720k, 2015-2019).

Rationale: Preterm birth places >4000 infants each year at increased risk of life-long adverse health outcomes, including CP and cognitive delay. Animal studies propose the neuroprotective role of sulphate in preterm babies.

Methods: Plasma sulphate levels will be measured in 1,324 preterm infants (<32 wks GA), to test if sulphate levels in 1 week old infants inversely correlate with adverse neurodevelopment outcome at 12 weeks of age using GMs, and 24 months C.A. on Bayley III.

Sample size: Based on CP rates of survivors (7%) at < 32wks GA, and Cochrane risk reduction effect of antenatal MgSu on CP74, 93, a clinically significant reduction in CP at 24 months C.A. (7% to 5.25%, corresponds to a 30% relative reduction, OR 0.74 when sulphate level is increased by 1SD above the mean), with 80% power, p<0.05, then n=1,324 required.

New knowledge: The neuroprotective effect of MgSu may be conferred by the Su rather than the Mg. If antenatal MgSu could be replaced by neonatal supplementation this would have significant health-cost implications and avoid any complications of delaying delivery to administer MgSu.

Update: To date, our study has recruited more than 450 preterm infants (born less than 32 weeks gestation) at the Mater Mothers’ Hospital and the Royal Brisbane Women’s Hospital, with an additional 1000 infants to be recruited over the coming 2 years. We have shown that by one week of age, preterm infants become deficient in sulphate. Since sulfate is important for modulating brain development, we propose that sulfate deficiency is detrimental to normal neurodevelopment. In late 2017, our study will commence assessing clinical outcomes in 2 year old children to determine whether sulphate deficiency after birth correlates with adverse neurodevelopment. If our hypothesis is proven, then neonatal sulfate supplementation 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.