Poster Presentation & Flash Talk 46th Annual Meeting of the Fetal and Neonatal Physiological Society 2019

Preterm infants are susceptible to oxidative stress arising before birth in response to intrauterine inflammation or postnatally from hypoxia/hyperoxia and pro-inflammatory exposures including sepsis and mechanical ventilation. Oxidative stress contributes to adverse preterm outcomes such as impaired neurodevelopment (e.g. cerebral palsy, intellectual disability), bronchopulmonary dysplasia and necrotising enterocolitis. Serial oxidative stress testing is potentially useful for tracking the contribution of oxidative stress to preterm infant morbidity and mortality. However, current oxidative stress measures are unsuitable for serial sampling, or are insufficiently sensitive. We have developed a highly sensitive blood-based biomarker of oxidative stress (albumin thiol oxidation) measurable from micro-samples (<10 uL), or from dried blood spot cards facilitating sample collection and storage at room temperature. We hypothesised that this biomarker will identify differences in oxidative stress in extreme preterm fetal lambs exposed to intra-amniotic lipopolysaccharide with or without prior tissue creatine loading for protection against oxidative stress.

Fetal lambs were instrumented at 90 d gestation with venous, arterial and intra-amniotic catheters. Creatine (6 mg/kg/h) or saline was infused intravenously from day 94. Intra-amniotic lipopolysaccharide (1 mg; E. coli O55:B5) or saline was administered on day 104 creating 4 study groups (n): Sal/Sal (11); Creat/Sal (8); Sal/LPS (11); Creat/LPS (10). Fetuses were delivered and euthanased immediately following blood collection on day 111.

Albumin thiol oxidation was 2.5 fold higher in LPS challenged lambs compared to control (saline). Lambs treated with creatine exhibited 2 fold lower albumin thiol oxidation compared to LPS challenged lambs.

Albumin thiol oxidation appears to be a sensitive biomarker of oxidative stress in the preterm fetal lamb and indicate that fetal creatine loading is effective in protecting the fetus from oxidative stress following in utero exposure to LPS.