Urinary inflammatory profiling as a candidate for non-invasive antenatal monitoring of villitis of unknown — ASN Events
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  3. Urinary inflammatory profiling as a candidate for non-invasive antenatal monitoring of villitis of unknown

Urinary inflammatory profiling as a candidate for non-invasive antenatal monitoring of villitis of unknown (#510)

Christine Cox 1 , Ashley Williams 1 , Min-Tz Weng 2 , Kathryn Steadman 2 , Elizabeth Burmeister 1 2 3 , Angela Ratsch 1 2 3 , Georgia Kafer 1
  1. School of Health, University of the Sunshine Coast, Moreton Bay, QLD, Australia
  2. The University of Queensland, St Lucia, Queensland, Australia 
  3. Research Services, Wide Bay Hospital and Health Service, Fraser Coast, Queensland, Australia

1.Introduction

Villitis of Unknown Etiology (VUE) is a recurrent inflammatory lesion where maternal T cells inappropriately target the placental chorionic villi in the absence of any defined infection. VUE results in villous destruction and is linked to adverse outcomes including fetal growth restriction, recurrent pregnancy loss and stillbirth. Currently, VUE can only be diagnosed retrospectively on histology.  In a co-designed study with an Aboriginal and Torres Strait Islander cohort, gestational tobacco, nicotine and cannabis (TNC) exposure was associated with increased inflammatory pathology, including a high incidence of VUE. A scoping review (Cox et al. under consideration) identified candidate inflammatory markers associated with VUE including 8-OHdG, 3-NT, ICAM1, TNFa, IL-6 and IL-8, and these markers were piloted in urine collected across gestation in an attempt at retrospectively diagnosing VUE antenatally.

 

2.Methods

Placentas collected at delivery (n=59) were assessed histologically and graded as absent, low or high-grade VUE. Paired urine samples from second and third trimesters (n=34) were stratified into healthy controls, TNC-exposed controls and low/high grade VUE. Urinary markers were quantified by ELISA (per manufacturer instructions), interpolated from standard curves and normalised to urinary creatine.  

 

3.Results

All candidate markers were detectable in urine. Urinary L-6 and IL-8 trended upwards from the second to the third trimester in high-grade VUE, unlike low-grade VUE. Paired analysis revealed significant differences in IL-6 levels between healthy controls, exposed controls and high-grade VUE in the second trimester (p=0.0270 (Kruskal-Wallis, Dunn’s post-hoc). Urinary 3-NT showed descending (non-significant) median gradient across healthy, exposed, low-grade and high-grade VUE, with clustering of diseased and non-diseased groups.

 

4.Conclusion

Preliminary urinary testing demonstrates both signal detectability and potential analyte pathway specificity. Although no single marker discriminated VUE consistently, coherent analyte gradients and directionality across multiple analytes support urinary profiling as a candidate, minimally invasive modality for longitudinal inflammatory monitoring in pregnancy.