692 - Placental Signaling Factors Linking Early-Onset Preeclampsia to Risk of Necrotizing Enterocolitis in a High-Risk Preterm Patient Population

Publication Number: 1669.692

Julia Katz, Boston Children's Hospital, Brookline, MA, United States; Diya Pamidimukkla, Boston University School of Medicine, Boston, MA, United States; Rachel Pfau, Boston University School of Medicine, Boston, MA, United States; Kendra Lujan, Boston University School of Medicine, Jamaica Plain, MA, United States; Andrew Parsons, Lucile Packard Children's Hospital Stanford, Palo Alto, CA, United States; Elizabeth Taglauer, Boston University School of Medicine, Boston, MA, United States

Background: Necrotizing enterocolitis (NEC) is a leading cause of morbidity and mortality in preterm neonates. Preeclampsia (PE) has been proposed as a risk factor for NEC, but it remains unclear whether this reflects PE's association with preterm delivery or a distinct PE-driven placental contribution to NEC pathogenesis.

Objective: First, to examine NEC risk among preterm infants born to a high-risk pregnant population at Boston Medical Center (BMC). Next, to determine whether the placental secreted proteins ("secretome") in this population differ between pregnancies delivered from preeclampsia (PE) versus spontaneous preterm labor (PTL). Finally, to identify secreted placental factors that may contribute to the risk of NEC pathogenesis among infants of PE pregnancies (Fig. 1).

Design/Methods: We conducted a 5-year retrospective chart review of infants born at 24-32 weeks' gestation at BMC. We then collected placental tissues at BMC from deliveries at 26-32 weeks' gestation, comparing PE and PTL pregnancies (n=3 each). Placental tissues were cultured in trans-well systems to capture secreted proteins in conditioned media, which underwent proteomic profiling via mass spectrometry. To also distinguish PE-specific pathways from gestational hypertension (GHTN), we compared spatial transcriptomics (SpTr) on placental tissues from PE vs GHTN pregnancies (n=1 each). Targets of interest were cross-referenced in proteomic and transcriptomic datasets by evaluating for soluble signaling factors with significant upregulation in PE vs PTL samples (FDR adjusted p < 0.05, absolute fold change >2).

Results: Preterm infants from PE pregnancies had a significantly higher risk of NEC compared with those from PTL pregnancies (OR 3.7, 95% CI 1.34-10.91). Combined proteomic and transcriptomic analyses identified several soluble factors of interest upregulated in PE placentas (Table 1). These included soluble endoglin (sEng), an inhibitor of TGF-β signaling, tissue factor pathway inhibitor-2 (TFPI-2), a serine protease inhibitor, and inhibin subunit beta A (INHBA), an inflammatory mediator.

Conclusion(s): Placental tissues from this pilot study in our high-risk NEC preterm population showed upregulation of several anti-angiogenic, immunomodulation, and repair-disrupting factors. As these pathways have ties with NEC pathogenesis, this placental signaling analysis converges on shared pathways that may prime the preterm intestine for injury. Our findings highlight PE as a key area for ongoing studies on NEC pathogenesis.

Figure 1
Figure 1 Study Design NEC PAS PRIME abstract.jpegStudy design

Table 1. Selected Human Placental Signaling Factors Upregulated in Preeclamptic Placental Tissues with Potential to Prime the Preterm Intestine for Injury