Acute maternal hyperoxygenation protocol: consensus opinion from the Fetal Heart Society

Acute maternal hyperoxygenation (MH) testing leverages two aspects of fetal cardiovascular physiology: (1) the normally high fetal pulmonary vascular resistance (PVR); and (2) changes in PVR upon exposure to increased fetal oxygen tension1, 2. Normal fetal PVR is high relative to systemic vascular resistance, directing the blood ejected from the right ventricle preferentially across the ductus arteriosus, with a small proportion entering the pulmonary arteries (PAs)1. By extension, a modest amount of left atrial filling is via the pulmonary veins. After delivery, mechanical expansion of the lungs and increased oxygen levels result in a rapid drop in PVR1. Exposure of the fetus to acute MH also results in a reduction in PVR, although less drastic than that at delivery. This response has been demonstrated in the second trimester3, but tends to become more prevalent2, albeit remaining variable4, 5, in the third trimester. Acute MH response is reflected by a decrease in pulsatility index (PI) in the PA branches (Figure 1) and increased pulmonary venous flow as assessed by Doppler on fetal echocardiography (FE). A 10–20% drop in branch PA-PI is considered reactive4, 6-8. The presence or absence of fetal pulmonary vascular reactivity is useful information. Some literature suggests that a lack of pulmonary vascular reactivity in certain cardiac and non-cardiac defects may signal poor postnatal outcome and, by extension, indicate the need for urgent postnatal resuscitation6, 7, 9, 10. However, given the reported variability in pulmonary vascular reactivity in the third trimester of healthy pregnancies4, 5, lack of reactivity in high-risk fetuses should be interpreted with caution. Fetuses demonstrating reactive PVR experience acute cardiovascular changes similar to postnatal circulatory shifts, including increased pulmonary blood flow, increased left-sided filling and changes in foramen ovale geometry. This simulation might predict unfavorable changes that may occur postnatally, such as profound hypoxemia due to persistent pulmonary hypertension, restrictive atrial septum in hypoplastic left heart syndrome (HLHS) or d-transposition of the great arteries (d-TGA), and increased venous obstruction in total anomalous pulmonary venous connection (TAPVC)7, 10, 11. In summary, acute MH testing may be useful to understand fetal pulmonary vascular reactivity and to mimic postnatal redistribution of blood flow and associated changes in anatomy and/or physiology. Despite the safety7, 12-14 and potential of acute MH testing in predicting postnatal hemodynamic instability with certain congenital cardiac and non-cardiac defects, this test remains underutilized secondary to the absence of a published standardized protocol and limited guidance regarding test interpretation. To address this, the Program Leaders Committee at the Fetal Heart Society formed a writing group of experts to develop an acute MH testing protocol. This document represents a consensus opinion on the various facets of acute MH testing, including timing, oxygen administration, FE assessments and test interpretation, providing a framework for fetal cardiac centers interested in implementing acute MH for clinical testing. For those fetal cardiac centers already conducting the test, it offers a standardized approach to foster collaborative learning and research in the field. Under the sponsorship of the Fetal Heart Society, a benchmarking survey aimed at elucidating current trends in fetal cardiology programs was carried out in 2023. Among the inquiries in this survey, one query focused on whether acute MH testing was performed at the surveyed site. Following the survey findings to this query, we assembled a panel of clinicians and researchers spanning the USA, Canada and the UK to collaborate on formulating a consensus protocol on acute MH testing. Group discussions were held to define objectives, and subsequently, the document underwent numerous iterations and was reviewed meticulously by all members until a consensus was achieved. Use of PWD is recommended Recovery phase after removing oxygen for 5 min (optional): FE assessment in the recovery phase is not required routinely; however, this is strongly recommended if concerning findings develop during acute MH, such as new or worsening tricuspid regurgitation, ductal constriction, new arrhythmia, foramen ovale closure and/or decrease in cardiac function. We present a consensus opinion on a standardized approach to conducting acute MH testing in both clinical and research settings. We provide indications, an image library and a basic guide to interpreting acute MH test results, based on the available literature. Additionally, we pinpoint knowledge gaps to serve as a compass for future research endeavors. This publication was developed with the support of the Fetal Heart Society sponsoring institutions. Without their contributions, the evolution of the Fetal Heart Society and this and ongoing research would not be possible. A full listing of sponsoring institutions can be found at www.fetalheartsociety.org. L. Freud, Division of Paediatric Cardiology, Department of Paediatrics, The Hospital for Sick Children, Toronto, ON, Canada M. Geiger, Division of Pediatric Cardiology, Mount Sinai Hospital, Icahn School of Medicine at Mount Sinai, New York, NY, USA L. K. Hornberger, Fetal and Neonatal Cardiology Program, Division of Cardiology, Department of Pediatrics, Stollery Children's Hospital, Edmonton, AB, Canada J. Johnson, Johns Hopkins All Children's Hospital, St Petersburg, FL, USA A. McBrien, Fetal and Neonatal Cardiology Program, Division of Cardiology, Department of Pediatrics, Stollery Children's Hospital, Edmonton, AB, Canada S. A. Morris, Division of Cardiology, Department of Pediatrics, Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA S. Peyvandi, Division of Pediatric Cardiology, Department of Pediatrics, University of California San Francisco, San Francisco, CA, USA J. Pruetz, Division of Pediatric Cardiology, Department of Pediatrics, Children's Hospital Los Angeles, Los Angeles, CA, USA D. Schidlow, Department of Cardiology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA T. A. Tacy, Division of Cardiology, Department of Pediatrics, Stanford University, Palo Alto, CA, USA T. V. Vigneswaran, Department of Congenital Heart Disease, Evelina London Children's Hospital, Guy's & St Thomas' NHS Trust, London, UK Data sharing not applicable - no new data generated. Figure S1 Fetal Heart Society patient information leaflet for maternal hyperoxygenation. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.