Spontaneous Closure of Patent Ductus

Arteriosus in Infants ≤1500 g

Jana Semberova, MD, PhD,​a,​b Jan Sirc, MD, PhD,​b,​c Jan Miletin, MD, FRCPI, FJFICMI,​a,​b,​c,​d Jachym Kucera, MD,​b Ivan Berka, MD,​b
Sylva Sebkova, MD,​b Sinead O’Sullivan, BMBS,​a Orla Franklin, MB, DCH, MRCPCI, MRCPCH,​e Zbynek Stranak, MD, PhDb,​c

OBJECTIVES: Patent ductus arteriosus (PDA) remains a challenging issue in very low birth abstract

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weight (VLBW) infants, and its management varies widely. Our aim in this study was
to document the natural course of ductus arteriosus in a cohort of VLBW infants who
underwent conservative PDA management with no medical or surgical intervention.
METHODS: A retrospective cohort study conducted in 2 European level-3 neonatal units.

RESULTS: A total of 368 VLBW infants were born within the study period. Two hundred and
ninety-seven infants were free of congenital malformations or heart defects and survived to
hospital discharge. Out of those, 280 infants received truly conservative PDA management.
In 237 (85%) of nontreated infants, the PDA closed before hospital discharge. The Kaplan-
Meier model was used to document the incidence proportion of PDA closure over time for
different gestational age groups. The median time to ductal closure was 71, 13, 8, and 6
days in <26+0, 26+0 to 27+6, 28+0 to 29+6, and ≥30 weeks, respectively. For different birth
weight groups, the median was 48, 22, 9, and 8 days in infants weighing <750, 750 to 999,
1000 to 1249, and 1250 to 1500 g, respectively. No statistically significant relationship was
found between PDA closure before hospital discharge and neonatal morbidities.
CONCLUSIONS: The likelihood of PDA spontaneous closure in VLBW infants is extremely high.
We provide in our findings a platform for future placebo-controlled trials focused on the
smallest and youngest infants.

aDepartment of Neonatology, Coombe Women and Infants Hospital, Dublin, Ireland; bInstitute for the Care What’s Known on This Subject: The management
of Mother and Child, Prague, Czech Republic; cThird Faculty of Medicine, Charles University, Prague, Czech of patent ductus arteriosus in very low birth weight
Republic; dUCD School of Medicine and Medical Sciences, Dublin, Ireland; and eDepartment of Paediatric
Cardiology, Our Lady’s Children’s Hospital Crumlin, Dublin, Ireland
infants remains controversial. Spontaneous closure
occurs frequently, and therefore many infants
Dr Semberova designed the study, contributed substantially to the echocardiography, might receive unnecessary treatment. Data from
demographic, and outcome data acquisition and analysis, and drafted the initial manuscript; small cohort studies suggest that noninterventional
Dr Sirc designed the study, contributed substantially to the echocardiography, demographic, and management is a feasible option.
outcome data acquisition and analysis, and reviewed and revised the manuscript; Dr Miletin
conceptualized and designed the study, contributed to data collection and analysis, and reviewed What This Study Adds: Spontaneous closure of
and revised the manuscript critically for important intellectual content; Dr Kucera contributed ductus arteriosus is extremely prevalent in very low
substantially to the study concept and design and echocardiography data acquisition and birth weight infants. Infants born before 26 weeks
analysis, and reviewed and revised the manuscript critically for important intellectual content; and <750 g have significantly higher rates of patent
Drs Berka and Sebkova contributed substantially to the echocardiography and demographic ductus arteriosus at hospital discharge. Future
data acquisition and critically reviewed and revised the manuscript; Dr O’Sullivan contributed
studies should focus on this population.
substantially to the demographic and outcome data collection (particularly the postdischarge
outcomes) and analysis and reviewed the manuscript; Dr Franklin contributed substantially to
the study design, supervised the echocardiography data collection, and reviewed and revised
the manuscript; Dr Stranak supervised the conduct of the study, contributed substantially to the
study design, coordinated the data analysis, and reviewed and revised the manuscript critically
for important intellectual content; and all authors approved the final manuscript as submitted To cite: Semberova J, Sirc J, Miletin J, et al. Spontaneous
and agree to be accountable for all aspects of the work. Closure of Patent Ductus Arteriosus in Infants ≤1500 g.
DOI: https://​doi.​org/​10.​1542/​peds.​2016-​4258 Pediatrics. 2017;140(2):e20164258

PEDIATRICS Volume 140, number 2, August 2017:e20164258 Article

Patent ductus arteriosus (PDA) is uncertain at the moment. regards to ventilation, nutrition,
is a common issue in preterm Also, spontaneous PDA closure hemodynamic management, and
neonates. It has been associated occurs in a significant number of indications for hospital discharge.
with an increased risk of short- and premature infants.‍15,​16
‍ Therefore, The units also share the same
long-term complications, mainly a noninterventional, conservative conservative approach to PDA, with
bronchopulmonary dysplasia approach to PDA management a high threshold for treatment.
(BPD), chronic lung disease (CLD), seems to be one of the options.‍17,​18
All VLBW infants without congenital
and necrotizing enterocolitis Until further evidence for treatment
malformations or chromosomal
(NEC).‍1 However, the causality of type, timing, and initiation criteria is
anomalies were eligible. Infants with
this relationship has never been available, we have adopted such an
congenital heart disease other than
established.‍2 Practices in PDA approach with a high threshold for
PDA and/or patent foramen ovale

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management vary greatly among any type of treatment and regular
were excluded, as well as infants with
institutions,​‍3 ranging widely from point-of-care echocardiography
acquired heart disease not related to
universal prophylactic treatment (ECHO) follow-up.
PDA (such as infectious endocarditis,
through selective treatment on
Our aim is to present the data myocardial infarction, and twin-to-
the basis of different criteria to no
on the “natural” course of PDA twin transfusion syndrome) and
treatment at all.
before hospital discharge in a infants with incomplete inpatient
Despite the physiologic plausibility large retrospective cohort of very follow-up. Infants who died during
of PDA adverse effects (such as low birth weight (VLBW) infants the study period were excluded from
pulmonary overcirculation and with a birth weight (BW) ≤1500 g the primary analysis.
systemic hypoperfusion), researchers who underwent conservative PDA
on PDA medical treatment have management. A secondary outcome Functional ECHO and PDA Treatment
failed to show a significant decrease of this study is the comparison Targeted ECHO was performed
in PDA-associated complications of selected neonatal morbidities within the first week of life followed
or any long-term benefit apart between patients with closed and by serial examinations in 1 to 2
from the PDA closure itself.‍4–‍ 6‍ permanent PDA. weekly intervals until documented
The only beneficial treatment ductal closure or hospital discharge.
strategy seems to be prophylactic All the clinicians performing the
indomethacin, which decreases the Methods point-of-care ECHO assessment
rate of intraventricular hemorrhage underwent appropriate training and
Study Design
(IVH) and severe early pulmonary were experienced with the technique.
hemorrhage, although this also has We have retrospectively analyzed In both centers, the ultrasound
not translated into the improvement data from a routine serial-targeted assessment was performed by using
of long-term outcomes.‍7,​8 Such an ECHO follow-up of VLBW infants a Phillips CX50 Ultrasound System
approach exposes a large number of admitted to 2 European level-3 with S8-3 broadband sector array
infants to unnecessary medication NICUs: the Institute for the Care of or S12-4 sector array transducer
and carries the risk of adverse effects, Mother and Child, Prague, Czech (Phillips, Andover, MA).
especially if given together with Republic (center 1), and the Coombe
The first ECHO examination focused
steroids.‍9–‍ 11
‍ Surgical PDA ligation Women and Infants University
not only on the ductal parameters but
does not carry any long-term benefits Hospital, Dublin, Ireland (center 2).
also on the heart anatomy. Follow-up
either,​‍2 and it has been associated PDA-targeted point-of-care ECHO
scans were focused mainly on the
with adverse outcomes.12,​13 ‍ Early follow-up had been in place in both
PDA presence and the parameters of
targeted treatment according to units before the start of the data
ductal significance, which included
echocardiographic criteria within collection. Data from the period of
diameter, flow pattern, maximum and
the first hours of life seems to be a February 2012–June 2013 in center
minimum flow velocities, left atrium-
promising approach. This method 1 and June 2013–June 2014 in center
to-aorta ratio, presence of mitral
reduces pulmonary hemorrhages and 2 were analyzed. The respective
insufficiency, flow in the abdominal
trends toward IVH reduction without research ethics committees approved
aorta or celiac artery, and end-
exposing the entire population to the the use of the data in each institution.
diastolic flow in the left pulmonary
treatment.‍14 Informed consent was not required
artery.‍19,​20
‍ Ductal closure was
because of the retrospective nature
Evidence exists that some infants defined as an absence of identifiable
of the study.
might theoretically benefit from PDA flow in the ductus arteriosus (DA) by
closure‍14; however, the indication Participating units have similar using color Doppler. DA closure was
and mode of such treatment policies and philosophies with always reaffirmed after 2 weeks. All

2 Semberova et al
of the parameters were recorded into Outcomes group) were eligible for analysis. The
the infant’s documentation and were mean weight and GA in the study
The primary outcome was the
available for clinical decisions. For group were 1112 ± 269 g and 29 ±
documentation of the time of the
the purpose of this article, only the 2 weeks, respectively. Forty-eight
closure or permanent patency of
information on ductal patency was percent were boys, 42% were from
the PDA in a large cohort of VLBW
used. multiple pregnancies, 17% were
infants who did not receive medical
small for GA, and 89% were partially
or surgical treatment and therefore
The decision to treat and the or fully exposed to ANSs.
document the “natural history” of
mode of therapy remained at the PDA. The secondary outcome was the
discretion of the attending physician PDA-Treated Patients
comparison of the demographics and
and were based on the clinical the outcomes of infants who achieved Out of the 297 infants in the study

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and echocardiographic features spontaneous PDA closure during the group, 17 infants received PDA
attributable to the PDA. hospital stay with those who did not. treatment, 14 received medical
treatment, 1 had PDA ligation
Statistical Analysis performed later, and 3 additional
Data Collection
infants were selected for PDA ligation
Data were analyzed by using a
without previous medical therapy.
The following demographic Mann–Whitney U test, a χ2, or a
PDA closed in 6 infants receiving
information was collected for every Fisher’s exact test as appropriate.
medical treatment, but remained
infant: gestation at birth, BW, sex, The incidence proportion of ductal
open in another 7 infants.
antenatal steroid (ANS) exposure, patency was analyzed with the
multiple gestation, and documented Kaplan-Meier model for different Conservative PDA Management
intrauterine growth restriction gestational age (GA) and weight
(IUGR) (BW <10th percentile). groups. The Bonferroni correction Two hundred and eighty infants
Clinical outcome data included was used for multiple comparisons continued to be managed in a truly
survival to hospital discharge, PDA among the groups. We used forward conservative manner. In 237 (85%)
medical treatment, surgical ligation stepwise Cox regression to examine of them, PDA closed before hospital
or catheter device closure, BPD variables predictive of PDA patency; discharge. The Kaplan-Meier model
(defined as oxygen requirement at the tested variables were GA, BW, revealed the incidence proportion of
36 weeks postmenstrual age), IVH sex, multiple pregnancy, ANS, and PDA closure over time for different
grades III and IV, periventricular IUGR. Cox regression is a method GAs. For this group, the median (95%
leucomalacia (PVL), NEC grades ≥IIb, for investigating the effect of several confidence interval [CI]) was 71 (51–
and retinopathy of prematurity (ROP) variables on the time it takes for a 91) days in <26+0 GA, 13 (0–34) days
stages ≥III. The diagnoses were specified event to happen (in our in 26+0 to 27+6 GA, 8 (7–9) days in
defined according to the Vermont study, PDA patency at discharge 28+0 to 29+6 GA, and 6 (4–8) days in
Oxford Network.‍21 The definition from the hospital). The hazard ≥30 GA. For BW groups, the median
of early- and late-onset sepsis was ratio yielded from Cox regression (95% CI) was 48 (9–87) days in <750
based on the criteria proposed by is then expressing the ratio of g; 22 (6–38) days in 750 to 999 g; 9
Chiesa et al,​‍22 which is that neonates hazard (probability) rates that are (6–12) days in 1000 to 1249 g; and
with positive blood culture results 1 U apart (eg, 1 gestational week). 8 (7–9) days in 1250 to 1500 g (‍Figs
and clinical signs of infection, and/or Infants who received medical or 2 and ‍3). A statistically significant
neonates with negative blood culture surgical treatment were not included difference was found between the
results, clinical signs of infection, and in the Kaplan-Meier model or in medians of ductal closure among
a positive laboratory sepsis screen the regression analysis. Statistical infants born <27+6 and >28+0 GA
were considered as having sepsis. analysis was executed by using the and among infants <1250 g and
IBM SPSS Statistics 24.0.0.0 software >1250 g (‍Table 1).
Clinical data on infants discharged (IBM Corp, Armonk, NY). Forward stepwise Cox regression
from the hospital with an open PDA revealed that the GA was the only
focused on further management, significant predictor of ductus
Results
which included ligation, device closure (P < .0001, hazard ratio
closure, and a follow-up plan. In total, 368 VLBW infants were born 1.28, 95% CI 1.20–1.36) when all
The data were gathered up to 12 within the study periods; 242 in variables in the model were used.
months of age and sourced from the center 1 and 126 in center 2. Seventy- However, because GA and BW were
infant’s general practitioner and/or one infants were excluded (‍Fig 1). significantly correlating and collinear
cardiologist. Data on 297 VLBW infants (study (r2 = 0.54, P < .0001), we tested

PEDIATRICS Volume 140, number 2, August 2017 3

for GA and BW separately with the
following additional tested variables:
sex, multiple pregnancy, ANSs, and
IUGR. Without including GA, BW
became a statistically significant
predictor of the ductus closure
(P < .0001, hazard ratio 1.002, 95% CI
1.001–1.002). In the model excluding
the BW, GA was the only statistically
significant predictor of the ductus
closure (P < .0001, hazard ratio 1.29,

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95% CI 1.21–1.38), as expected. Sex,
multiple pregnancy, ANSs, and IUGR
were not statistically significant
predictors in either model.

Comparison of Infants With Closed

and Open PDA at Hospital Discharge
In conducting the univariate analysis,
we found no statistically significant
difference in severe neonatal
morbidities (BPD, IVH grades III and
IV, PVL, NEC grades ≥IIb, and ROP
stages ≥III) between the infants who
achieved spontaneous PDA closure
and those whose PDA remained
open in the truly conservative group
(‍Table 2).
However, when infants who
underwent treatment were included
in the comparison, a statistically
significant difference was found not
only between the GA and the BW but
also in the incidence of severe IVH:
2 (1%) infants in the PDA closure
group vs 4 infants (8%) in the PDA
FIGURE 1
nonclosure group (P = .008). Overall number of eligible infants identified with subsequent flowchart of the study.

Follow-up After Hospital Discharge

cardiac failure. Only 2 infants of them after 1 year postdischarge.
Spontaneous PDA closure occurred underwent artificial postdischarge Overall, PDA was closed in 261
in 24 (56%) out of 43 patients closure, 1 by surgical ligation infants (93%) at the age of 12
discharged from the hospital and 1 by percutaneous catheter months.
with ductus patency without device closure. In 11 infants, PDA
previous medical treatment. Six Neonatal Mortality
remained open but nonsignificant
patients were lost to outpatient
1 year after hospital discharge.
follow-up. We cross-checked data The overall mortality among infants
Seven infants were discharged from
for these 6 patients with the only eligible for the study was 9% (33 out
cardiothoracic or cardiac center in the hospital with open PDA after of 368). Seven patients died because
each country (Our Ladies Children’s failed medical treatment. Out of of serious congenital malformations.
Hospital, Crumlin, Dublin, Ireland, those, 2 experienced spontaneous Twenty-six remaining infants died
and University Hospital Motol, postdischarge closure, 1 underwent before hospital discharge; 19 died
Prague, Czech Republic), and surgical ligation, and 1 underwent within the first 7 days, and 7 died
none of them underwent surgical percutaneous catheter device later. The mean weight and GA were
intervention or presented with closure; PDA remained open in 3 significantly lower than the study

4 Semberova et al
 patients. Pulmonary hemorrhage
occurred in 4 infants, and in 1 infant
it was stated to be the main cause of
death. Ten out of 19 infants who died
before 7 days of age had a point-of-
care ECHO done, and all of them had
documented PDA. None of them was
medically treated. Out of 7 infants
who died after day 7, 3 of them had
NEC stated as the cause of death. Six
out of these 7 infants died with open

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PDA, and 2 of them were previously
medically treated for the same
without any positive result.
The overall results of the infants
eligible for the study in comparison
with the data from the Vermont
Oxford Network are available in
‍Table 3.

FIGURE 2
Prevalence of ductal patency stratified by BW over time before hospital discharge. The horizontal line Discussion
represents 50% closure. The plus sign signifies censored patients who were discharged from the
hospital before closure.
The data represent the true “natural
history” of PDA derived from a robust
retrospective cohort of VLBW infants
who underwent noninterventional,
conservative management. The
likelihood of spontaneous closure
before hospital discharge is age- and
weight-dependent as documented in
the Kaplan-Meier figures. Although
the rate of spontaneous closure
differs significantly among some
of the weight and GA categories,
spontaneous closure before hospital
discharge occurs in the majority
of even the youngest and smallest
infants, specifically those with a GA
<26 weeks’ gestation (68%) and a
BW <750 g (76%).
We have excluded the deceased
infants from the analysis. However,
out of 26 infants who died, 16 had a
recorded cause of death that could
FIGURE 3
Prevalence of ductal patency stratified by GA over time before hospital discharge. The horizontal line be potentially related to PDA: IVH
represents 50% closure. The plus sign signifies censored patients who were discharged from the (n = 7), NEC (n = 5), and pulmonary
hospital before closure. hemorrhage either associated with
IVH or alone (n = 4). Ten infants who
group (789 ± 256 g and 25.5 ± 2 However, the main cause of death died before 7 days of age had point-
weeks, respectively, P < .0001). The was early- or late-onset infection of-care ECHO done, and all of them
incidence of IVH and NEC was also in 10 infants followed by severe had documented PDA; none of them
significantly higher in comparison IVH (which influenced further were medically treated for PDA. We
with survivors (52% vs 2% and management of already critically ill could speculate that the outcome
26% vs 1%, respectively, P < .0001). infants) in 7 patients and NEC in 5 of some deceased infants could be

PEDIATRICS Volume 140, number 2, August 2017 5

influenced by early PDA treatment. TABLE 1 Comparison of Spontaneous DA Closure Time Among Different BW and GA Groups (Statistical
However, the criteria for such Significance P < .05)
treatment remain currently unclear. N = 280 Time to Ductal Closure (d), Pairwise Comparison Adjusted P Value for
Median (95% CI) Between the Groups, P, Multiple Comparisons
There were no differences in Mantel-Cox Log Rank Test (Bonferroni Correction)
IQR [Q1, Q3]
morbidities in nontreated infants.
The absence of a statistically SE of the Median
(Kaplan-Meier)
significant difference between the
groups may just be a consequence of ≤750 ga 48 (9–87) — —
[8, 94] .700b >.999b
a sample size insufficient to detect 20 .058c .347c
differences in those low-incidence <.001d <.001d
morbidities, but it may also be that 751–1000 gb 22 (6–38) .700a >.999a

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as morbidity rates have declined [7, NA] — —
in recent years, these conditions 8 .042c .255c
<.001d <.001d
may have become dissociated from 1001–1250 gc 9 (6–12) .058a .347a
historical risk indicators such as [3, 44] .042b .255b
PDA. When including the treated 2 — —
infants in our study group in the <.001d .002d
univariate analysis, a significant 1251–1500 gd 8 (7–9) <.001a <.001a
[3, 12] <.001b <.001b
difference in the incidence of severe 1 <.001c .002c
IVH becomes apparent between the — —
infants whose PDA closed and those <26+0 GAe 71 (51–91) — —
whose remained open until hospital [18, NA] .028f .169f
discharge. We suppose that the 10 <.001g <.001g
<.001h <.001h
failed treatment itself has no causal 26+0–27+6 GAf 13 (0–34) .028e .169e
relationship to the severe IVH because [6, NA] — —
no infant received early treatment; all 11 .001g .003g
treatments were administered beyond <.001h <.001h
day 3 of life. This result could reflect 28+0–29+6 GAg 8 (7–9) <.001e <.001e
[5, 17] .001f .003f
the fact that the overall “sickest” 1 — —
infants would have persistent PDA .027h .164h
despite treatment. >30 GAh 9 (4–8) <.001e <.001e
[2, 11] <.001f <.001f
Our data are in agreement with 1 .027g .164g
other published studies presenting — —
conservative PDA management.‍17,​18 ‍ P value is a result of comparison of the BW and GA groups labeled a, b, c, d and e, f, g, h, respectively. NA, not applicable
The mean closure date in our group (because Q3 was outside of the inpatient stay); IQR, interquartile range; Q1, 25th percentile; Q3, 75th percentile.
of infants <26 weeks GA occurred
TABLE 2 Comparison of Demographics and Clinical Outcomes of VLBW Infants With and Without
later than in the cohort recently
Spontaneous PDA Closure Before Hospital Discharge
presented by Sung et al,​‍18 and the rate
of infants discharged from the hospital PDA Closure Group PDA Nonclosure Group P
(n = 237) (n = 43)
with open PDA was higher in our
group (32% and 5%, respectively). GA, wk, mean ± SD 29.2 ± 2.3 27.5 ± 2.0 .0001
Birth wt, g, mean ± SD 1145 ± 264 1004 ± 239 .001
This difference could probably ANSs, n (%) 215 (91) 37 (86) .404
be explained by different fluid Multiple pregnancy, n (%) 99 (42) 19 (45) .867
management. Sung et al‍18 practiced Sex: M/F 50, 50 44, 56 .510
significant fluid restriction with an IUGR, n (%) 41 (17) 6 (14) .665
average fluid intake of 107 ± 20 to Severe IVH (grade III and IV), n (%) 2 (1) 2 (5) .113
PVL, n (%) 4 (2) 1 (2) .573
115 ± 21 mL/kg per day between BPD, n (%) 24 (10) 8 (19) .123
days 7 and 28. In our study, fluid NEC grade ≥IIb, n (%) 2 (1) 1 (2) .395
restriction was not routinely applied ROP stage ≥III, n (%) 4 (2) 0 (0) >.999
and diuretics were not used in either Infants with natural course of DA only, n = 280.
participating center. However, the rate
of CLD in infants of GA 23 to 26 weeks The overall mortality and the rate large databases, including centers
was similar in both cohorts (34.5% in of significant neonatal morbidities with different PDA management
our cohort as compared with 38%).18 in our cohort compare favorably to policies. The results of this large

6 Semberova et al
TABLE 3 Comparison of the Neonatal Outcomes of All the Infants Eligible for the Study (BW ≤1500 g) is inversely related to GA and BW.
Including Deaths and Congenital Anomalies to the Vermont-Oxford Network (BW 401–1500 g The results support the existing data
or GA From 22 Weeks, 0 Days to 29 Weeks, 6 Days) on the feasibility of conservative
Eligible Infants (n = 368) Vermont-Oxford Network 2013 (n management without an increase in
= 60 562) neonatal morbidity and mortality.
Mortality (%) [Q1, Q3] 9.0 14.6 [9.0, 18.4] However, it is physiologically
CLD (%) [Q1, Q3] 14.6 24.5 [10.5, 30.7] plausible that some infants might
Severe IVH (grade III and IV) (%) [Q1, Q3] 5.0 8.1 [3.5, 10.6] benefit from PDA treatment. The
PVL (%) [Q1, Q3] 2.4 2.9 [0.0, 4.1]
NEC ≥IIb (%) [Q1, Q3] 3.6 4.6 [0.0, 6.5] criteria for which infants will benefit
Severe ROP (stage ≥III) (%) [Q1, Q3] 2.4 6.2 [0.0, 8.3] from the treatment are not currently
defined. Such criteria could be

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determined through randomised
cohort of infants who underwent and then regularly in 1 to 2 weekly controlled trials and our data on
truly noninterventional management intervals, the days differ among infants managed conservatively
might encourage further placebo- the infants. The decision to treat provides a platform for future
controlled studies by demonstrating was not uniform and sometimes placebo-controlled research, as it has
the relative safety of the conservative difficult to retrospectively demonstrated the safety of the use of
approach. elucidate. The parameters of PDA a placebo arm for such trials.
echocardiographic or clinical
Spontaneous PDA closure
significance were not accounted
postdischarge in early infancy is
for in the data analysis. Also, Abbreviations
frequently documented,​‍23 and
the hospital discharge policy
our results are in agreement. In ANS: antenatal steroid
might differ significantly among
circumstances where cardiology feels BPD: bronchopulmonary
institutions. We have therefore
that invasive closure is indicated, the dysplasia
calculated the rate of PDA closure
occlusive device appears to be the BW: birth weight
at 36 weeks postmenstrual age.
modality of choice, as it is a much CI: confidence interval
The total closure rate in the truly
less invasive procedure than surgical CLD: chronic lung disease
conservative group of 280 infants
ligation. Because a late medical DA: ductus arteriosus
at 36 weeks postmenstrual age was
PDA treatment is less effective‍6 and ECHO: echocardiography
83% as opposed to 85% at hospital
indications for late PDA treatment GA: gestational age
discharge.
are unclear, it might be beneficial to IUGR: intrauterine growth
await early infancy before a closure restriction
decision. Conclusions IVH: intraventricular
hemorrhage
The results need to be interpreted Spontaneous closure of the PDA
NEC: necrotizing enterocolitis
cautiously because of the is likely in VLBW infants, as
PDA: patent ductus arteriosus
retrospective nature of this demonstrated in a large cohort
PVL: periventricular
study. We acknowledge other of infants who underwent truly
leucomalacia
obvious limitations. Although the noninterventional, conservative PDA
ROP: retinopathy of prematurity
echocardiographic studies were management. The rate of permanent
VLBW: very low birth weight
conducted in the first week of life ductal patency at hospital discharge

Accepted for publication Apr 25, 2017

Address correspondence to Jan Miletin, MD, FRCPI, FJFICMI, Department of Neonatology, Coombe Women and Infants University Hospital, Cork St, Dublin 8, Ireland.
E-mail: [email protected]
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).
Copyright © 2017 by the American Academy of Pediatrics
FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.
FUNDING: Supported by the HIP trial, the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement 260777.
POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.
COMPANION PAPER: A companion to this article can be found online at www.​pediatrics.​org/​cgi/​doi/​10.​1542/​peds.​2017-​0566.

PEDIATRICS Volume 140, number 2, August 2017 7

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