Umbilical cord blood pTau217 and BD-tau are associated with markers of neonatal hypoxia: a prospective cohort study

ObjectiveCurrent methods for early detection of hypoxic-ischemic encephalopathy (HIE) are limited by lack of specificity, cost, and time constraints. Blood tau protein concentrations reflect neuropathology in adults. This study examines tau as a potential HIE biomarker in neonates by relating cord blood levels to short-term fetomaternal outcomes. We aimed to examine 1) association of BD-tau with non-reassuring fetal status; 2) correlations between cord blood tau and other hypoxia biomarkers; 3) associations between tau levels and risk factors for fetomaternal morbidity; 4) associations between tau levels and short-term fetomaternal outcome. Methods107 maternal participants were prospectively recruited at Royal Prince Alfred Hospital--a large Australian tertiary referral centre. Simoa analysis detected umbilical cord blood pTau217 and brain-derived (BD)-tau levels. ResultsOf 509 deliveries, cord blood was analysed in 107/110 recruited maternal participants. BD-tau correlated with non-reassuring fetal status (OR=3.0;95%CI=1.6- 5.7;p=0.001), though not when adjusting for mode of delivery and gestational age. BD-tau was higher in vaginal deliveries, and positively associated with pTau217, NfL, and lactate (p<0.001), and negatively associated with pH and base excess. pTau217 was higher in preterm neonates and was associated with neurofilament light chain (Spearmans rho=0.44,p<0.001). BD-tau and pTau217 were associated with maternal hypertension and placental abnormalities. ConclusionsCord blood BD-tau correlates with surrogate markers of fetal hypoxia, whilst pTau217 may represent a marker of neurodevelopment. Further studies could explore whether these findings translate to clinical use of tau as an HIE biomarker. FundingUS National Institutes of Health (grant:R01AG063849-01).