Nitric oxide donor increases umbilical vein blood flow and fetal oxygenation in fetal growth restriction. A pilot study

Daniele Farsetti; Francesca Pometti; Barbara Vasapollo; Gian Paolo Novelli; Sara Nardini; Benedetta Lupoli; Christoph Lees; Herbert Valensise

doi:10.1016/j.placenta.2024.04.014

Nitric oxide donor increases umbilical vein blood flow and fetal oxygenation in fetal growth restriction. A pilot study

Placenta. 2024 May 3:151:59-66. doi: 10.1016/j.placenta.2024.04.014. Online ahead of print.

Authors

Daniele Farsetti¹, Francesca Pometti², Barbara Vasapollo³, Gian Paolo Novelli⁴, Sara Nardini², Benedetta Lupoli², Christoph Lees⁵, Herbert Valensise³

Affiliations

¹ Department of Surgical Sciences, University of Rome Tor Vergata, Rome, Italy; Department of Obstetrics and Gynecology, Policlinico Casilino, Rome, Italy. Electronic address: dan.farsetti@gmail.com.
² Department of Surgical Sciences, University of Rome Tor Vergata, Rome, Italy.
³ Department of Surgical Sciences, University of Rome Tor Vergata, Rome, Italy; Department of Obstetrics and Gynecology, Policlinico Casilino, Rome, Italy.
⁴ Department of Integrated Care Processes, Fondazione PTV Policlinico Tor Vergata, Rome, Italy.
⁵ Centre for Fetal Care, Department of Obstetrics and Gynecology, Queen Charlotte's and Chelsea Hospital, Imperial College London, London, United Kingdom.

PMID: 38718734
DOI: 10.1016/j.placenta.2024.04.014

Abstract

Introduction: To evaluate the maternal and fetal hemodynamic effects of treatment with a nitric oxide donor and oral fluid in pregnancies complicated by fetal growth restriction.

Methods: 30 normotensive participants with early fetal growth restriction were enrolled. 15 participants were treated until delivery with transdermal glyceryl trinitrate and oral fluid intake (Treated group), and 15 comprised the untreated group. All women underwent non-invasive assessment of fetal and maternal hemodynamics and repeat evaluation 2 weeks later.

Results: In the treated group, maternal hemodynamics improved significantly after two weeks of therapy compared to untreated participants. Fetal hemodynamics in the treated group showed an increase in umbilical vein diameter by 18.87 % (p < 0.01), in umbilical vein blood flow by 48.16 % (p < 0.01) and in umbilical vein blood flow corrected for estimated fetal weight by 30.03 % (p < 0.01). In the untreated group, the characteristics of the umbilical vein were unchanged compared to baseline. At the same time, the cerebro-placental ratio increased in the treated group, while it was reduced in the untreated group, compared to baseline values. The treated group showed a higher birthweight centile (p = 0.03) and a lower preeclampsia rate (p = 0.04) compared to the untreated group.

Discussion: The combined therapeutic approach with nitric oxide donor and oral fluid intake in fetal growth restriction improves maternal hemodynamics, which becomes more hyperdynamic (volume-dominant). At the same time, in the fetal circuit, umbilical vein flow increased and fetal brain sparing improved. Although a modest sample size, there was less preeclampsia and a higher birthweight suggesting beneficial maternal and fetal characteristics of treatment.

Keywords: Cardiac output; Fetal growth restriction; Maternal hemodynamics; Nitric oxide donors; Systemic vascular resistance; Umbilical vein flow.