327 - Chorioamnionitis-induced fetal breathing movement inhibition is not restored by Ibuprofen.

Sunday, April 30, 2023

3:30 PM – 6:00 PM ET

Poster Number: 327
Publication Number: 327.345

Robert Galinsky, Hudson Institute of Medical Research, MELBOURNE, Victoria, Australia; Nhi T. Tran, The Hudson Institute of Medical Research, Melbourne, Victoria, Australia; Sharmony B. Kelly, The Hudson Institute/Monash University, Melbourne, Victoria, Australia; Graeme Polglase, Hudson Institute of Medical Research, Melbourne, Victoria, Australia

Presenting Author(s)

Graeme Polglase, PhD (he/him/his)

Associate DIrector
Hudson Institute of Medical Research
Melbourne, Victoria, Australia

Background: Preterm infants exposed to chorioamnionitis during pregnancy are at increased risk of apnoea after birth. We have previously shown in late preterm fetal sheep that lipopolysaccharide (LPS) exposure inhibits fetal breathing movements (FBM) and was associated with increased prostaglandin E2 (PGE₂) within plasma and the brainstem respiratory centres.

Objective: We hypothesised that inhibiting increases of PGE₂ with Ibuprofen, a non-steroidal PGE2 inhibitor, would prevent FBM inhibition.

Design/Methods: Fetal sheep (~125 days gestation (dGA)) were sterilely instrumented with tracheal, arterial and venous catheters to measure FBM, heart rate, blood pressure, blood gases and administer interventions. At ~130 dGA, fetuses received saline or escalating doses of LPS (300ng, 600ng, 1.2ug i.v.) over 3 days, with each LPS event followed by saline or 5mg/kg/d ibuprofen. FBMs were assessed using LabChart. PGE₂ expression in brainstem respiratory centres was assessed by immunohistochemistry. PGE₂ levels in cerebrospinal fluid (CSF) and plasma were assessed by ELISA.

Results: LPS significantly increased plasma PGE₂ levels and transiently inhibited FBMs. This coincided with a significant increase in PaCO₂ and reduction in PaO₂.
Ibuprofen treatment following LPS administration significantly reduced circulating PGE₂ levels and PGE₂ levels in the brainstem respiratory centre (RTN/pFRG and Raphe nuclei) but not in the CSF and pre-BötC and Hypoglossal nucleus (XII). Despite the reductions in PGE₂, Ibuprofen treatment did not restore fetal breathing movement inhibition induced by LPS.

Conclusion(s): Our data suggests FBM inhibition is not exclusively driven by high PGE₂ levels, challenging our current understanding. Further investigation elucidating the mechanisms and pathways underlying respiratory depression following chorioamnionitis in preterm newborns are needed to develop treatment strategies.