To Treat or Not to Treat – That is the Question!

What if your newborn has a patent ductus arteriosus?

Some might ask, what is a ductus arteriosus?

During fetal development, a patent ductus arteriosus (PDA, see Figure) is important for diverting well-oxygenated blood returning from the placenta past the fluid-filled lungs and directly into the systemic circulation in order to perfuse organs.

Blood Flow with Patent Ductus Arteriousus

A patent ductus arteriosus allows for diverting aortic blood to flow into the lungs and thus pressurize the pulmonary circulation as well as allow for deoxygenated blood to enter into the aortic arch if the flow is reversed. Very low birth weight infants are prone to this condition and choice of appropriate treatment is in question. Image provided by Blausen.com.(4)

In full-term newborns, the PDA closes within two days of birth by means of vasoconstriction and anatomic remodeling.(1) Or it doesn’t. In 65% of premature infants born at 30 weeks’ gestation or less, the PDA fails to close within the first 7 days.(2, 3) Therefore, the pulmonary and systemic circulations remain connected. Consequently, blood is shunted away from the general systemic circulation to the lungs and can lead to severe flow-related problems such as central nervous system ischemia and hemorrhage, necrotizing enterocolitis, and renal failure. Such a Patent Ductus Arteriosus (PDA) leads to the ultimate question of to treat or not to treat? The two schools of thought in neonatology are watchful waiting, treating with nonsteroidal anti-inflammatory drugs (NSAID) or an invasive procedure to close the ductus.

Possible concerns are multifactorial. Intervention risks side effects from medications and procedural complications. Watchful waiting risks diminished blood and oxygen supply to the brain and abdominal organs. Quantifying blood flow and oxygen supply in these fragile humans is nearly impossible, especially since most of them are actually very low birth weight babies (VLBW, i.e. <1,500 grams). They are tiny.

In rare cases, clinicians use MRI to image and quantify PDA and carotid flow. That, however, requires specialized facilities in which the neonates can remain in their protective incubators while being in the magnet.

Imagine you could use ultrasound to assess not only the PDA but also the blood flow to the brain and the abdomen. Ultrasound is the ideal modality as it is non-ionizing, can be used at the bedside and is already a part of neonatal care. Yet, assessing blood flow quantitatively using 2D pulsed-wave ultrasound has been a challenge in and of itself. It not only requires user-selected angle correction as well as lumen diameter measurements but also neglects flow outside of the 2D image plane. Others may use simple velocity measurements or surrogate markers, but those do not represent flow.

A possible solution has been proposed by our group at the University of Michigan (UM). It is using 3D ultrasound to employ Gauss’ Theorem to quantify flow. While high-frequency ultrasound is excellent for VLBW babies, imaging a 1-mm diameter PDA lumen may still be a challenge. The UM team has previously shown the benefits of 3D color flow for quantification of blood flow. We hypothesize that even a PDA lumen could be assessed accurately, despite its challenging diameter. In addition, if successful, clinicians should be able to measure flow in the PDA within 6 seconds after obtaining a cross-sectional color flow image of the PDA with minimal to no user dependence. This presupposes a 2D matrix array capable of recording 5 color flow volumes per second.

In an American Society of Echocardiography (ASE) and AIUM co-sponsored investigation (E21 and EER funding), we will assess the effects of PDAs before and after treatment. Baseline blood flow for cardiac output, total brain blood flow, blood flow to the small intestines, and renal blood flow will be determined in full-term healthy neonates. An inter- and intraoperator variability study will be employed to warrant scientific rigor and target an end-organ flow estimation with <10% variation for test-retest and <10% between operators. Blood flow measurements in VLBW cohorts scheduled for intervention will yield estimates before and after intervention and thus provide insight in the predictive value for this method.

The ultimate goal is that 3D ultrasound will help caregivers to determine if adequate flow to end organs exists and if intervention is required. Furthermore, stable and unstable VLBW cohorts can possibly be differentiated by their flow to end organs and through the PDA. Thus, answering the question of whether to treat or not to treat.

Principle Investigators: Oliver D. Kripfgans, Ph.D. and Jonathan M. Rubin, M.D., Ph.D.
Co-Investigators: Gary Weiner, M.D. and Marjorie C. Treadwell, M.D.

References:

  1. Deshpande P, Baczynski M, McNamara PJ, Jain A. Patent ductus arteriosus: The physiology of transition. Semin Fetal Neonatal Med 2018;23(4):225–231. doi: 10.1016/j.siny.2018.05.001
  2. Clyman RI, Couto J, Murphy GM. Patent ductus arteriosus: are current neonatal treatment options better or worse than no treatment at all? Semin Perinatol 2012;36(2):123–129. doi: 10.1053/j.semperi.2011.09.022
  3. Egbe A, Uppu S, Stroustrup A, Lee S, Ho D, Srivastava S. Incidences and sociodemographics of specific congenital heart diseases in the United States of America: an evaluation of hospital discharge diagnoses. Pediatr Cardiol 2014;35(6):975–982. doi: 10.1007/s00246-014-0884-8
  4. Blausen.com staff (2014). “Medical gallery of Blausen Medical 2014”. WikiJournal of Medicine 1 (2). DOI:10.15347/wjm/2014.010. ISSN 2002-4436.

 

Oliver D. Kripfgans, PhD, FAIUM, is a Research Associate Professor in the Department of Radiology at the University of Michigan. Jonathan Rubin, MD, PhD, FAIUM, is a Professor Emeritus in the Department of Radiology at the University of Michigan.

 

Comment below, or, AIUM members, continue the conversation on Connect, the AIUM’s online community to share your experience.

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