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ORIGINAL RESEARCH article

Front. Med.

Sec. Obstetrics and Gynecology

Volume 12 - 2025 | doi: 10.3389/fmed.2025.1667607

Fetal heart and surroundings: umbilical cord traction triggers sympathetic heart rate surge in fetal lambs in the artificial womb

Provisionally accepted
Maria Antonietta  CastaldiMaria Antonietta Castaldi1,2*Salvatore Giovanni  CastaldiSalvatore Giovanni Castaldi1Maria Silena  MosqueraMaria Silena Mosquera2,3Grace  HwangGrace Hwang2Marina  HeffelfingerMarina Heffelfinger2Aaron  WeilersteinAaron Weilerstein2Marcus  G DaveyMarcus G Davey4Alan  W FlakeAlan W Flake2
  • 1University of Salerno, Fisciano, Italy
  • 2The Children's Hospital of Philadelphia, Philadelphia, United States
  • 3Westchester Medical Center, Valhalla, United States
  • 4Vitara Biomedical Inc., 19103, United States

The final, formatted version of the article will be published soon.

Objective: to investigate whether umbilical cord traction triggers a unique umbilico-neuro-cardio reflex via sympathetic autonomic nervous system (ANS) activation, potentially explaining fetal heart rate (FHR) increases such as the double mountain peak sign and unexplained tachycardia outside labor. Design: Experimental physiological study using the EXTrauterine Environment for Neonatal Development (EXTEND) system. Setting: Controlled laboratory environment at The Children's Hospital of Philadelphia with fetal lambs supported by the EXTEND system. Population or Sample: Twenty-nine experiments were performed on three fetal lambs: 5 ANS-immature (<110 days gestational age) and 24 ANS-mature (>110 days GA), including subgroups for pharmacological intervention. Methods: Umbilical cord traction was performed in 20 experiments (5 ANS-immature, 15 ANS-mature). To investigate autonomic modulation, nine ANS-mature experiments included administration of either periumbilical capsaicin or intravenous propranolol. FHR changes were measured, and norepinephrine levels were sampled before and after interventions. Main Outcome Measures: Change in FHR (bpm) and circulating norepinephrine concentrations in response to umbilical cord traction and pharmacologic modulation. Results: Cord traction significantly increased FHR in ANS-mature lambs (mean +42 bpm, p < .001), but not in ANS-immature lambs (mean +1 bpm, p = .770). Capsaicin also elevated FHR and norepinephrine, while propranolol inhibited both responses. Conclusions: Umbilical cord traction appears to activate an umbilico-neuro-cardiac reflex through sympathetic ANS pathways in ANS-mature fetuses. This mechanism may underlie clinical CTG features such as the double mountain peak sign and fetal tachycardia outside of labor.

Keywords: fetal heart rate, Tachycardia, Cardiotocography, Artificial womb, Mechanical activation, sheep (ovine), Sympathetic Nervous System

Received: 16 Jul 2025; Accepted: 24 Sep 2025.

Copyright: © 2025 Castaldi, Castaldi, Mosquera, Hwang, Heffelfinger, Weilerstein, Davey and Flake. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Maria Antonietta Castaldi, mantocastaldi@msn.com

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