The Journal of Maternal-Fetal and Neonatal Medicine, 2011; 24(S(1)): 15-16

Copyright © 2011 Informa UK, Ltd.

ISSN 1476-7058 print/ISSN 1476-4954 online
DOI: 10.3109/14767058.2011.607564

review Article

Patent ductus arteriosus: patho-physiology, hemodynamic

effects and clinical complications
Giovanbattista Capozzi & Giuseppe Santoro

Paediatric Cardiology Unit, Second University of Naples, Monaldi Hospital, Naples, Italy
J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by Florida International University on 08/21/14

closure is just functional due to transient vasoconstriction of pari-

During fetal life, patent arterial duct diverts placental oxygen-
etal muscular fibers, but fibrous transformation of all wall layers
ated blood from the pulmonary artery into the aorta by-passing
causes irreversible occlusion of ductal lumen in a few days [2].
lungs. After birth, decrease of prostacyclins and prostaglandins
This process may be delayed, or even completely fail, in preterm
concentration usually causes arterial duct closure. This process
infants. In addition, several studies showed an inverse relationship
may be delayed, or may even completely fail in preterm infants
between the chance of persistent ductal patency and gestational
with arterial duct still remaining patent. If that happens, blood
age and neonate weight, with a rate of nearly 30% in very low birth
flow by-pass of the systemic circulation through the arterial
weight (VLBW) and up to 60% in extremely low birth weight
duct results in pulmonary overflow and systemic hypoperfusion.
(ELBW) [3]. This phenomenon is deemed to be due to both higher
When pulmonary flow is 50% higher than systemic flow, a hemo-
sensitivity to prostaglandin E2 and lesser sensitivity to vasocon-
dynamic “paradox” results, with an increase of left ventricular
strictor effect of oxygen of the vascular tissues of preterm infants.
output without a subsequent increase of systemic output.
In the case of persistent ductal patency, the post-neonatal
Cardiac overload support neuro-humoral effects (activation of
hemodynamic changes result in pulmonary overflow and systemic
sympathetic nervous system and renin-angiotensin system) that
hypoperfusion, the amount of which strictly depends on pulmo-
finally promote heart failure. Moreover, increased pulmonary
For personal use only.

nary/systemic vascular resistance ratio [4]. Liable measure of this

blood flow can cause vascular congestion and pulmonary edema.
However, the most dangerous effect is cerebral under-perfusion
due to diastolic reverse-flow and resulting in cerebral hypoxia. At
last, blood flow decreases through the abdominal aorta, reducing
perfusion of liver, gut and kidneys and may cause hepatic failure,
renal insufficiency and necrotizing enterocolitis. Conclusions
Large patent arterial duct may cause life-threatening multi-organ
effects. In pre-term infant early diagnosis and timely effective
treatment are cornerstones in the prevention of cerebral damage
and long-term multi-organ failure.
Keywords:  patent ductus arteriosus, preterm infant,
clinical complication
Introduction
During fetal life, patent arterial duct is crucial to survival acting
both as a by-pass circuit from lung circulation and as a conduit
to deliver oxygenated blood from placental circulation to lower-
body organs.
After birth, arterial duct closure ensues in a few hours due to
decrease of circulatory and local vasodilator mediators (mainly
prostacyclins and prostaglandins) caused by placental removal
and increased lung clearance [1]. In addition, profound hemo-
dynamic and blood gas changes caused by activation of respira-
tion further contribute to this process. Indeed, both reduction
of pulmonary vascular resistance secondary to expansion of the
lungs and increase of peripheral vascular resistance due to exclu-
sion of the placenta from systemic circulation, tend to force the
blood flow toward the pulmonary circulation thereby increasing
the oxygen content of arterial blood. At the beginning, ductal
circulatory unbalance is the ratio between pulmonary blood flow
(Qp) and systemic blood flow (Qs). Without ductal shunt, the
pulmonary and systemic flows are identical, because pulmonary
and systemic circulation are in series (Qp/Qs = 1). In the presence
of patent arterial duct, pulmonary flow exceeds systemic flow
so that the Qp/Qs is higher than 1. Significant hemodynamic
changes affecting several organs or systems occur when the Qp/
Qs is higher than 1.5. In this setting, timely diagnosis and proper
treatment of significant patent arterial ducts may significantly
reduce morbidity and mortality of this subset of patients [4].
Hemodynamic effects and clinical complications
Cardiovascular effect
Hemodynamic changes caused by persistent connection between
pulmonary and systemic circulation result in paradoxical reduc-
tion of systemic flow despite increased cardiac output. Indeed,
decreased pulmonary vascular resistance and increased systemic
vascular resistance picture rapidly occurring in preterm infant,
causes massive pulmonary overflow and increases pulmonary
venous return and hence, progressively increasing left ventricular
output. However, this high performance of the systemic ventricle
is not paralleled by increase of effective systemic cardiac output,
because the blood flow by-passes the systemic circulation through
the arterial duct. This hemodynamic “paradox” promotes neuro-
humoral changes that tend to worsen the cardiac overload and
promote heart failure and damage of vital systems [4].
Neuro-humoral effect
Sympathetic nervous system and renin-angiotensin system are
particularly active in patients with significant systemic pulmo-
nary shunt, as was confirmed by tight association between Qp/Qs,

Correspondence: Giovanbattista Capozzi, Paediatric Cardiology Unit, Second University of Naples, Monaldi Hospital, Naples, Italy. E-mail: giovanbattista.
capozzi@fastwebnet.it
15
 16  G. Capozzi & G. Santoro
activation of the renin-angiotensin system, increased aldosterone
plasma concentrations and heart failure [5]. In addition, cardiac
overload activates specific receptors that release the B-type natri-
uretic peptide (BNP) which has vasodilator and diuretic effect.
Finally, recent studies also confirmed the direct relationship
between BNP levels and the systemic pulmonary shunt volume in
preterm infants [6,7].
Pulmonary effect
Increase of pulmonary blood flow causes vascular congestion
and increased pulmonary pressure, resulting in leakage of fluids
into the interstitial space and pulmonary edema [8]. In addition,
increased flow and pressure may also be a risk factor for life-
threatening pulmonary bleeding. Potential for complications, as
well as severity of patho-physiologic effects, depend on amount
J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by Florida International University on 08/21/14
and duration of the shunt. Finally, large arterial ducts also cause
broncho-pulmonary dysplasia, although interventional studies
failed to document any effect of treatment in decreasing the inci-
dence of bronchopulmonary dysplasia in preterm infants.
Cerebral flow effect
The paradox of systemic circulation, “steal” results in reduced perfu-
sion of vital organs. In this setting, the most dangerous effect is
cerebral under-perfusion due to diastolic reverse-flow and resulting
cerebral hypoxia [9]. This occurs in the presence of PDA with
moderate shunt and can be assessed by pulsed-Doppler examination
of cerebral blood flow showing inversion of the blood flow direction
during diastole. Cerebral hypo-perfusion and poor cerebral oxygen-
ation by themselves increase the intra-ventricular bleeding risk.
For personal use only.
Visceral flow effect
As for cerebral circulation, arterial duct “steal” might result in
decrease of blood flow into the abdominal aorta and hence hypo-
perfusion of liver, gut and kidney. This phenomenon may cause
hepatic failure, renal insufficiency and/or activation of compensa-
tory mechanisms (see Neurohumoral changes), as well as results
in, increased risk of necrotizing enterocolitis [10].
Conclusions
Large patent arterial duct may cause life-threatening multi-organ
effects in pre-term infants. In this very frail subset of patients, early
diagnosis and timely effective treatment are cornerstones in the
prevention of long-term multi-organ failure. Two-dimensional,
color-Doppler echocardiography is a key contributor to early diag-
nosis, although this method must be complemented by several
others (abdominal visceral and cerebral flow; chest x-ray for enlarged
cardiac shadow; BNP and NT-pro-BNP values; etc.), which overall,
contribute to the proper and timely indication for treatment.
Declaration of interest: The authors report no conflicts of
interest. The authors alone are responsible for the content and
writing of the paper.
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The Journal of Maternal-Fetal and Neonatal Medicine