Is salivary uric acid, a putative biomarker of pre-eclampsia, of maternal, placental, or fetal origin?

Objectives: Increased salivary uric acid (sUA) represents a potential biomarker predictive of pre-eclampsia (PE), but its origin is unclear. The study explores whether sUA levels reflect maternal or feto-placental physiological stress and whether sUA levels in these cases correlate with amniotic fluid (fetal origin), maternal blood (maternal origin), or cord blood (fetal vs placental origin). Study design: Pregnant women (n = 39) undergoing amniotomy or caesarean section after 34 gestational weeks were designated into three groups of either maternal, feto-placental, or no signs of physiological stress: women (n = 15) in the established first phase of active labour and without any signs of fetal growth restriction (FGR) or PE were assigned to the maternal stress group, women (n = 6) with an ultrasound-based diagnosis of FGR, with or without PE, were assigned to the fetoplacental stress group, and women (n = 18) not yet in active labour and without any signs of FGR or PE, were assigned to the control group. Uric acid levels in corresponding samples of amniotic fluid, saliva, maternal blood, and cord blood were compared between groups and between body compartments within each group. Results: The feto-placental stress group showed increased UA levels in saliva (median, interquartile range [IQR]: 0.47 [0.38] mmol/L, P = 0.023) and maternal blood (0.42 [0.13] mmol/L, P = 0.032), but no differences in amniotic fluid or cord blood compared with the other groups. Within the control and maternal stress group, sUA levels were lower compared with maternal blood (0.20 [0.08] vs 0.25 [0.08] mmol/L, P-control = 0.018; 0.20 [0.06] vs 0.26 [0.08] mmol/L, P-maternal = 0.001) and highest in amniotic fluid (control group (0.49 [0.18] mmol/L): P-maternal,P-blood = 0.001, P-umbilical,P-artery = <0.001, P-umbilical,P-vein = <0.001, P-saliva = <0.001) (maternal stress group (0.56 [0.23] mmol/L): P-maternal,P-blood = 0.021, P-umbilical,P-artery = 0.006, P-umbilical,P-vein = 0.004, P-saliva = 0.003). Levels did not differ between compartments in the feto-placental stress group. Conclusions: Salivary and maternal blood UA levels were increased in the feto-placental stress group with salivary levels increasing more than blood levels compared with the maternal stress and control groups, whilst UA in amniotic fluid were not different between the groups, suggesting a placental origin and potential use of sUA as a biomarker of placental dysfunction, including FGR and severe PE.