113: Exposure to 17-alpha hydroxyprogesterone caproate (17P) influences expression of maternal serum proteins in progesterone signaling pathways

We sought to further investigate mechanisms of action of 17P by examining maternal serum proteomic profiles in the presence and absence of 17P exposure. Nested cohort from the prospective Proteomic Assessment of Preterm Risk (PAPR) study [designed to develop a clinical test for spontaneous preterm birth (SPTB) prediction] conducted at 11 US centers 2011-2013. Enrolled women who received 17P were compared to those in the PAPR validation cohort (enriched for SPTB; 2 term:1 SPTB) who did not receive 17P. Maternal blood was collected 170/7 -286/7 weeks gestation, serum was extracted and processed by a proteomic workflow, and proteins were evaluated in each sample by multiple reaction monitoring mass spectrometry. Proteomic biomarkers with p<0.05 were considered potential candidates and were further analyzed using Ingenuity® pathway analysis. 384 women met inclusion criteria; 141 (37%) were on 17P, initiated at a mean 16.6 +/- 2.1 wks. As expected, women exposed to 17P were more likely to have ≥1 prior PTB (99% vs. 12%, p<0.001), less likely to have had a prior term delivery (45% vs. 81%, p<0.001). They were also more likely black race (36% vs. 23%, p=0.009). Despite these differences (and due to the selection of 17P-unexposed from PAPR), PTB rates <37 weeks (36% vs. 33%, p=0.67), <34 weeks (13% vs. 9%, p=0.18), and <28 weeks (2% vs. 2%, p=0.57) were similar between 17P-exposed and unexposed women. Maternal serum was collected at a mean 22.6 weeks in 17P-exposed vs. 22.5 weeks in 17P-unexposed pregnancies (p=0.75). For women on 17P, this was at a median 5.9 weeks (IQR 3.6-8.1 weeks) after 17P initiation. Sixteen differentially expressed proteins were identified between 17P-exposed and unexposed women; 14/16 proteins were aggregated in progesterone signaling pathways (Figure). The remaining 2 proteins are APOC3 (involved in lipid signaling & metabolism) and PGRP2 (involved in immune response). Women exposed to 17P for PTB prevention have distinct changes in their mid-trimester protein expression profiles. Future mechanistic studies should investigate the implications of these progesterone signaling pathway alterations among women exposed to 17P during pregnancy to elucidate whether aberrant responses result in variable clinical outcomes.