SYMPOSIUM: NEONATOLOGY
A clinical and
echocardiographic
approach to evaluation of
patent ductus arteriosus
in preterm infants
Kunal Babla
Sandeep Shetty
Anay Kulkarni
Abstract
The ductus arteriosus provides a physiological right-to-left shunt in
fetal life, before closing early in the postnatal period. In extremely pre-
term infants, it commonly does not close and remains as a patent duc-
tus arteriosus, and can have significant effects on the haemodynamic
status of the baby. There is no clear definition for haemodynamically
significant patent ductus arteriosus in preterm infants and debate per-
sists regarding the benefits of medical or surgical intervention to close
patent ductus arteriosus. Echocardiography remains the current gold
standard diagnostic approach. There are several echocardiographic
parameters that can be used to assess patent ductus arteriosus in pre-
term infants, each with their own strengths and limitations. Owing to
these limitations, there is no single echocardiographic parameter
that allows us to define a haemodynamically significant patent ductus
arteriosus. We therefore recommend an approach that encompasses
clinical assessment, and echocardiographic assessment of duct char-
acteristics, pulmonary overcirculation and systemic hypoperfusion.
Combining these assessments and interpreting them in the context
of the baby’s cardiac anatomy and clinical status will allow clinicians
to make a more objective and informed judgement regarding the hae-
modynamic significance of a patent ductus arteriosus in preterm
infants.
Keywords echocardiography; heart disease; patent ductus arterio-
sus; PDA; preterm
Introduction
In fetal life, the ductus arteriosus (DA) serves to allow blood to
pass from the pulmonary artery to aorta and bypass the fluid-filled
Kunal Babla BSc (Hons) MBBS MSc MRCPCH MAcadMEd, Senior Clinical
Fellow in Paediatric Cardiology and ST8 Trainee in Neonatal
Medicine, Royal Brompton Hospital, London, UK. Conflicts of
interest: none declared.
Sandeep Shetty MBBS DCH DNB (Paediatrics) FRCPCH (UK) MDres
Consultant Neonatologist, St George’s University Hospital, London,
UK. Conflicts of interest: none declared.
Anay Kulkarni MBBS DCH DNB (Paediatrics) FRCPCH (UK) Consultant
Neonatologist, St George’s University Hospital, London, UK.
Conflicts of interest: none declared.
PAEDIATRICS AND CHILD HEALTH 30:4
lungs, which do not participate in gas exchange. After birth, when
the lungs are filled with air, pulmonary vascular resistance falls,
allowing blood to circulate through the lungs. This removes the
physiological need for the DA, which closes through a number of
mechanisms. The DA usually begins shunting from left-to-right,
then closes functionally in the first two to three days, but can
take longer than three weeks to close anatomically.
In some babies, particularly preterm babies, this process of
closure often does not occur, resulting in a patent ductus arte-
riosus (PDA). The persistence of a PDA occurs as a result of a
number of factors, often related to gestational age. This includes
immaturity of the musculature within the ductal wall, persistence
of high levels of circulating prostaglandins, high sensitivity of the
preterm duct to vasodilators such as prostaglandins and nitric
oxide, thrombocytopenia, impaired platelet function and adrenal
insufficiency. In addition, conditions such as hypoxia and sepsis
can further promote persistence of PDA.
The prevalence of PDA falls as gestational age increases, with
up to 56% of infants born under 28 weeks’ gestation affected.
Other authors have reported rates as high as 90% in infants born
at under 24 weeks’ gestation.
While it is outside the scope of this paper to discuss the ad-
vantages and disadvantages of medical or surgical treatment, we
will provide a summary of the strengths and limitations of clin-
ical, echocardiographic and biochemical methods used to define
haemodynamically significant PDA (hsPDA), and a concise
summary of how to apply them in clinical practice.
Pathophysiology associated with a haemodynamically
significant PDA
The left-to-right shunt associated with hsPDA results in increased
pulmonary circulation and therefore, an increased return of blood
to the left side of the heart. This increased pulmonary circulation
can result in breathlessness, hypoxia and radiographic features of
pulmonary plethora. The increased return of blood to the left side
of the heart can result in left-sided volume overload and dilata-
tion of the left atrium and ventricle. Concurrently, the left-to-right
shunt can give features of ‘ductal steal’ resulting in low systemic
diastolic pressures and wide pulse pressures.
It is postulated that hsPDA is associated with a number of adverse
outcomes in preterm infants. These include intraventricular hae-
morrhage, bronchopulmonary dysplasia, necrotising enterocolitis
and mortality. There is therefore considerable interest in treatment
methods, and defining which babies require treatment for hsPDA.
Bedside assessment
Clinical signs are generally less reliable than echocardiographic
findings. Our recommendation would be that these should not be
relied upon for diagnostic purposes. Echocardiography remains
the gold standard for diagnosing the presence of a PDA. How-
ever, given that not all practitioners will readily have access to
echocardiography, we will discuss the strengths and limitations
of key clinical findings as part of this review, and have sum-
marised them in Table 1.
PDA characteristically presents with tachypnoea, tachycardia,
bounding pulses, a wide pulse pressure and a systolic murmur.
Given the likely clinical status and coexisting problems (e.g.,
sepsis, respiratory distress syndrome) of a preterm infant,
129 Ó 2020 Published by Elsevier Ltd.
 SYMPOSIUM: NEONATOLOGY

A summary of the sensitivity and specificity of a range of clinical and echocardiographic parameters, including commonly
used cut off values for defining hsPDA. Note that sensitivity and specificity figures may vary between studies and timing
of echocardiography.
Parameter Timing after birth Cut-off value Sensitivity Specificity
for hsPDA (%) (%)

Clinical/ Murmur Daily from day 1 to day 7 21e79 86e100

radiographic Pulses Daily from day 1 to day 7 31e71 61e86
parameters Pulses 3e7 days 43 74
Increased cardiothoracic ratio 3e7 days 8 94
Duct and shunt PDA Diameter <31 hours
1.5 mm 81 85
characteristics PDA Diameter 12e48 hours
1.5 mm 94 73
PDA:Left Pulmonary 4 days
0.5 78 80
Artery diameter
PDA:Left Pulmonary 3 days
0.5 92 55
Artery diameter
PDA Diameter:weight 12e48 hours >1.5 mm/kg 94 73
Pulsatile flow pattern 24 hours 91 59
Pulsatile flow pattern Daily for 7 days 93 100
Pulsatile flow pattern 3 days 67 78
Growing pattern Daily for 7 days 64 81
Vmax:Vmin First 48 hours >1.9 88 90
1/2 SDT 7 days <90 ms 63 100
Pulmonary LA:Ao <31 hours
1.5 29 91
overcirculation E/A ratio 3 days >1 10 6
Left ventricular output <31 hours
300 ml/kg/min 26 92
Systemic Descending aorta diastolic flow <31 hours Absent/ 68 85
hypoperfusion retrograde

Table 1

tachypnoea and tachycardia are non-specific findings in the
context of PDA. Heart rate was found to be higher in infants with
hsPDA but still within the normal range, and therefore unlikely
to be of significant clinical value in determining the presence of
a PDA.
Murmurs
The presence of a murmur was found to be of greater sensitivity
by day seven in comparison to day three (79% vs 31%). The
specificity of the sign remained relatively high at 86e94%. The
results suggest that the presence of a murmur is most likely to be
due to PDA, however the absence of one does not exclude the
presence of a PDA. However, it should be considered that mur-
murs could be produced by other congenital defects, most
commonly a patent foramen ovale or ventricular septal defect.
Pulse volume
Increased pulse volumes do not have sufficient clinical accuracy
to be relied on as an isolated marker for hsPDA. They have been
found to have sensitivities of 43e71% with a specificity of 61
e86% in two studies. When combined with the presence of a
murmur the positive predictive value of increased pulse volume
for hsPDA was found to be 77%.
Blood pressure
Systolic and mean blood pressure have been found to be higher
in infants with a closed duct in comparison to those with the
haemodynamically insignificant PDA, and in turn, hsPDA.
However, the measured blood pressures have all been within the
expected normal range. Diastolic blood pressure has been found
to correlate slightly better with the presence of a hsPDA, most
likely representing the ductal steal phenomenon as described
above. The classically described wide pulse pressure in the
presence of hsPDA does not have strong diagnostic value. Studies
have shown that the pulse pressure in the first week of life in
extreme preterm infants does not differ significantly between
those with hsPDA and those without.
Chest radiograph
Chest x-rays will be helpful in the detection of pulmonary plethora
and to help exclude other causes of tachypnoea and the need for
respiratory support, such as pneumothorax or consolidation. A
cardiothoracic ratio better than 60% has been shown to be highly
specific for the presence of hsPDA (94%) but has very low
sensitivity (8%). Chest x-rays are therefore unlikely to be helpful
in the diagnosis of PDA, but will help investigate other pathology.
Echocardiographic evaluation of hsPDA
As discussed above, echocardiography remains the gold standard
investigation for diagnosis and evaluation of hsPDA in preterm
infants. Prior to evaluating hsPDA, normal cardiac anatomy
should be demonstrated. There are three main components to
echocardiographic evaluation of hsPDA: duct and shunt

PAEDIATRICS AND CHILD HEALTH 30:4 130 Ó 2020 Published by Elsevier Ltd.
 SYMPOSIUM: NEONATOLOGY
characteristics, pulmonary overcirculation and systemic hypo-
perfusion. Using these three components, we will examine the
strengths and limitations of each individual parameter to evalu-
ation of hsPDA. These are summarised in Table 1.
Duct and shunt characteristics
Within the characteristics of the duct, we include three main
features: the patency, the size and the direction of the shunt
through the duct.
Patency of the duct: the PDA can be visualised on echocardi-
ography through a number of different echo windows. Current
consensus is that the preferred window to obtain a clear 2D
image is through a left-sided high parasternal “ductal view”. This
classically allows the PDA to be visualised leaving the descend-
ing aorta and entering the main pulmonary artery adjacent to the
left pulmonary artery, as illustrated in Figure 1.
Using colour Doppler can help to show flow through the
duct and therefore demonstrate its patency. Most commonly,
the PDA will show as red colour flow (in contrast to the blue
flow of the pulmonary arteries), representing a left-to-right
shunt. A right-to-left shunt will show as blue flow through
the PDA. This can be easily overlooked and care should be
taken to ensure that a right-to-left shunt is not missed, as this
could be representative of a duct-dependent cardiac lesion or
pulmonary hypertension.
Ductal diameter: ductal diameter is one of the most commonly
used parameters to define an hsPDA. The most commonly used
absolute value to define hsPDA is >1.5mm. PDA diameter should
be measured in end-systole at the pulmonary end, or the nar-
rowest part of the PDA. We recommend measuring duct diameter
in 2D imaging as the use of colour Doppler can result in
Figure 1 Echocardiographic images of a patent ductus arteriosus (PDA) demonstrating a left to right shunt. The PDA inserts into the pulmonary
artery (PA) at point A, emerging from the aorta (Ao) at point B. Blue flow signifies normal forward flow through the pulmonary artery. Red flow
signifies flow from the aorta to the pulmonary artery via the PDA.
PAEDIATRICS AND CHILD HEALTH 30:4
overestimation of PDA diameter. Studies have shown significant
inter- and intra-observer variability when measuring PDA
diameter both in 2D and on colour Doppler imaging.
PDA diameter can be indexed against LPA diameter (cut-off
value 0.5) or bodyweight (1.4mm/kg), offering an element of
standardisation for patient size, but carries the same inherent
limitations as described above with regards to PDA diameter.
Assessment of flow direction and character: as described
above, simple inspection of the colour Doppler over the PDA can
give an impression of the direction of the shunt. However, given
the high heart rate in preterm infants, right-to-left shunting in
diastole can be easily missed using this approach. Continuous
wave (CW) Doppler through the PDA is a more objective
approach to defining the direction and characteristics of the
shunt.
Doppler flow patterns through the PDA been characterised as
non-restrictive (left-to-right) restrictive (left-to-right), bidirec-
tional, and right-to-left. These are illustrated in Figure 2. Non-
restrictive shunts can be objectively defined as having a high
systolic to diastolic velocity gradient (Vmax:Vmin
2.0),
whereas restrictive shunts have a low gradient (Vmax:Vmin
<2.0). A pulsatile, non-restrictive left-to-right Doppler pattern is
most sensitive (93.5%) and specific (100%) for predicting the
development of hsPDA, whereas a growing pattern (bidirectional
with right-to-left shunt
30% of the cycle) has less sensitivity
(64.5%) and specificity (81%).
In addition, measuring the half-systolic decay time (1/2SDT)
can be derived by measuring the time taken to halve peak sys-
tolic velocity across a PDA on CW Doppler. A 1/2SDT (on day
seven of life) of <90ms showed 62.5% sensitivity and 100%
specificity for hsPDA.
131 Ó 2020 Published by Elsevier Ltd.
 SYMPOSIUM: NEONATOLOGY
Figure 2 Doppler flow profiles for ductal flow measured from a left-sided high parasternal view.
Pulmonary overcirculation
In the presence of a left-to-right shunt via a PDA, left ventricular
output represents the total pulmonary venous return, and
therefore parameters measuring left ventricular output, volume
and pressure loading can be used as surrogates for the degree of
shunting at a ductal level. One should consider that the presence
of a shunt via a patent foramen ovale (PFO) can impact mea-
surements of volume and pressure in the left atrium and
ventricle.
Left ventricular output: left ventricular output can be derived by
measuring the velocity-time integral (stroke distance) from a
pulsed-wave Doppler of flow at the aortic valve and measuring
the size of the aortic annulus. The measurements are applied to
the equation:
Blood flow (ml/kg/min) ¼ (pr2 (cm2)  VTI (cm)  HR (bpm))/
body weight (kg)
where r is the radius of the aortic annulus, to calculate blood flow.
A calculated output of greater than 300e400 ml/kg/min has been
associated with the presence of hsPDA. This approach has been
shown to have errors of up to 28% in comparison to gold
standard measurement techniques, as small errors in recording
Doppler profiles, measurement of VTI and aortic annulus radius
can lead to clinically significant errors in the final value.
Calculating a ratio of left ventricular output to superior vena
cava flow has not been found to provide additional benefit to the
assessment of hsPDA.
Left heart volume loading: Left atrium to aortic root ratio
(LA:Ao): left atrium to aortic root ratio is a popular parameter,
and has been shown to be higher in babies with hsPDA. It can be
measured in the parasternal long axis view, using M-mode, with
the cursor placed perpendicular to the aorta at the level of the
aortic valve. The most commonly applied cut-off value for
determining an hsPDA is
1.5. The sensitivity and specificity of
LA:Ao is variable across the literature at 29e89% and 29e91%
respectively, with relatively poor repeatability between
observers.
PAEDIATRICS AND CHILD HEALTH 30:4
Left ventricular end diastolic diameter (LVEDD): LVEDD can
be measured in the parasternal long axis view, using M-mode
with the cursor placed through the tips of the mitral valve leaf-
lets, and then standardised by calculating z-scores. LVEDD can
be helpful for reviewing left ventricular volume loading over
time.
Pulmonary vein d wave velocity: using a high parasternal
view with colour Doppler, the pulmonary veins can be visualised
entering the left atrium. Using pulsed-wave Doppler on the lower
pulmonary veins can provide a flow profile (systolic, diastolic
and atrial contraction components) of pulmonary venous return
to the left side of the heart. A diastolic velocity of
0.5 m/s has
been associated with the presence of hsPDA. This approach has
the advantage that it is not affected by shunting at the atrial level.
There is however, currently limited evidence for the use of this
parameter for defining hsPDA.
Left pulmonary artery diastolic velocity: the presence of and
exclusively left-to-right shunt through an hsPDA is likely to cause
forward flow in diastole in the left pulmonary artery. This can be
quantified using pulsed-wave Doppler in high parasternal short
axis view and measuring the mean and end-diastolic velocity. A
suggested end-diastolic flow velocity cut-off value for a large
shunt is 0.5 m/s or higher. Though there is some evidence for its
use in the literature, its accuracy has been calibrated against
LVO/SVC flow ratio, which carries its own limitations, as
described earlier.
Left side pressure loading: left-sided pressure loading can be
investigated by interrogating the flow of blood from the left
atrium to left ventricle, by taking an apical 4-chamber view, and
measuring a pulsed-wave Doppler just below the mitral valve
annulus. The recorded Doppler profile will delineate the flow of
blood into the left ventricle during diastole due to passive filling
of the ventricle (E wave) and active filling caused by atrial
contraction (A wave) (Figure 3).
Mitral valve E/A ratio: mitral valve E/A ratio gives an
objective measure of left ventricular filling by early passive filling
versus active filling. Preterm infants have relatively impaired
diastolic ventricular relaxation, meaning the E/A ratio is usually
132 Ó 2020 Published by Elsevier Ltd.
 SYMPOSIUM: NEONATOLOGY

Figure 3 Doppler flow profiles of mitral inflow in diastole. In this

example, A wave is larger than E wave (E/A ratio <1). IVRT: Isovolumic
relaxation time.

<1 (E wave smaller than A wave). In the presence of the sig-

nificant left-to-right shunt through an hsPDA, atrial pressure will
increase, meaning that the proportion of early diastolic filling will
be increased in comparison to normal. This may lead to the E/A
ratio becoming >1 (E wave larger than A wave), representing an
hsPDA. Care should be taken when interpreting this in the
presence of a left-to-right shunt through a PFO, which may act to
offload pressure in the left atrium, and therefore give a falsely
low E/A ratio.
Isovolumic relaxation time (IVRT): following closure of the
aortic valve, there is a short period of time before the mitral
valve opens, during which the left ventricle relaxes. This is the
IVRT. In the presence of a significant atrial pressure load, atrial
pressure will exceed to that in the left ventricle, and force the
mitral valve open sooner, thereby reducing the IVRT. This can
be measured using the same Doppler profile as that used to Figure 4 Doppler profiles of flow in abdominal aorta or coeliac axis.
measure the E/A ratio. An IVRT of less than 30e40ms has been
associated with hsPDA. Care should be taken to ensure that the
Doppler profile is as clear as possible to ensure accuracy in Biochemical assessment of hsPDA
measuring the IVRT. In addition to echocardiographic assessments, blood markers
have also been used to assess the significance of the PDA. Brain
Systemic hypoperfusion
Natriuretic Peptide (BNP) has been used as a marker of left atrial
In addition to echocardiographic assessment for systemic hypo-
stretch. High BNP levels have been shown to be associated with
perfusion, one should consider assessing end-organ perfusion.
hsPDA, and have been shown to fall in the presence of the
This includes assessing urine output, GI tract function, and
closing or closed PDA.
monitoring lactate levels.
Although not a direct assessment for hsPDA, one should
Echocardiographic assessment can be performed by check-
consider performing basic renal function, full blood count and
ing flow in the abdominal aorta, coeliac axis or in the middle
liver function tests when considering medical treatment such as
cerebral artery. Normally, there is forward flow in diastole in
ibuprofen or paracetamol. Thrombocytopenia may reduce the
post-ductal arteries. In the presence of hsPDA, diastolic flow
chance of successful closure of the duct. One should also ensure
may be absent or reversed, as illustrated in Figure 4. Recording
that renal function is adequate before and during a course of non-
a pulsed-wave Doppler profile in any of these arteries will give
steroidal anti-inflammatory therapy, and that liver function is
an objective assessment of flow direction. Care should be taken
monitored if using paracetamol.
to ensure that the angle of insonation is as low as possible
(ideally less than 20 ) to minimise errors in the Doppler profile Combined echocardiographic parameters
recorded. One should ensure normal aortic valve function, as it As demonstrated in Table 1 and in the text above, each indi-
is also possible to see reversed aortic flow in the presence of vidual parameter for the assessment of hsPDA has its own
severe aortic regurgitation. Interpretation of Doppler profile in strengths and limitations. We would therefore recommend the
the middle cerebral artery may be more difficult in the presence use of several parameters in combination in order to build a
of a significant intraventricular haemorrhage in a preterm clearer picture of the haemodynamic effect of the PDA. A scoring
infant. system has suggested in the literature, and includes clinical

PAEDIATRICS AND CHILD HEALTH 30:4 133 Ó 2020 Published by Elsevier Ltd.
 SYMPOSIUM: NEONATOLOGY

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