1171 Steroidogenic enzyme activity is predictive of spontaneous preterm delivery

Abstract

To assess the association between enzymatic activity in the steroid metabolism pathway and timing of spontaneous preterm delivery. A cohort of women who delivered preterm were selected from an academic pregnancy biobank and divided into late preterm (34-36 weeks, latePTD) and extreme to moderate preterm (20-33 weeks, earlyPTD) spontaneous delivery groups. Plasma specimens were obtained prospectively from subjects in the second trimester (Epoch 1) and third trimester (Epoch 2). Enzymatic activity within the steroid metabolism pathway was estimated by calculation of the ratio of substrate and primary products quantified using ultraperformance liquid chromatography tandem mass spectrometry (UPLC/MS-MS). Nine steroid pairs were identified to estimate the activity of six key enzymes involved in steroidogenesis (Table). Comparison of enzymatic activity between earlyPTD and latePTD groups was conducted using the Mann-Whitney U test. Area under the receiver operating characteristic curve (AUROC) was utilized to assess the potential for enzymatic activity to predict early PTD. All analysis was performed using IBM SPSS Statistics. Specimens were obtained from 47 unique subjects across Epoch 1 (31 samples) and Epoch 2 (33 samples). There was no difference in the gestational age at sample acquisition between earlyPTD and latePTD groups in either Epoch 1 (15.2±4.6 vs. 16.0±3.5 weeks, p=0.47) or Epoch 2 (30.1±3.8 vs. 29.1±2.2 weeks, p=0.46). As expected, the gestational age at delivery was significantly different (29.3 ± 3.5 vs. 34.5 ±0.5 weeks; p<0.001). Of the six enzymes assessed, a significant difference in activity between earlyPTD and latePTD groups was only found for 21-hydroxylase (p=0.03) and 20a-HSD (p=0.04) in Epoch 1. None of the enzyme activities were significantly different between groups in Epoch 2. The area under the ROC curve (AUROC) demonstrated similar predictive potential for both 21-hydroxylase (AUROC 0.74, p=0.03) and 20a-HSD (AUROC 0.74, p=0.04). The steroidogenic enzymes 21-hydroxylase and 20α-HSD may influence the propensity for early preterm delivery.