Echocardiographic detection of pulmonary hypertension in extremely low birth weight infants with bronchopulmonary dysplasia requiring prolonged positive pressure ventilation

Article (PDF Available)inJournal of perinatology: official journal of the California Perinatal Association 31(10):635-40 · February 2011with32 Reads
DOI: 10.1038/jp.2010.213 · Source: PubMed
Abstract
The goal of this study was to delineate the epidemiology of echocardiographically diagnosed pulmonary hypertension (PH) in extremely low birth weight (ELBW) infants with bronchopulmonary dysplasia (BPD) requiring prolonged positive pressure ventilation (PPV), and to determine the independent relationship between PH and mortality in these patients. Our retrospective cohort included ELBW infants, with BPD requiring prolonged PPV, hospitalized in Cincinnati, Ohio during 2003-2009, as recorded in the National Institute of Child Health and Human Development Neonatal Research Network Database. Following chart review, a logistic regression model was constructed to understand the contribution of PH to mortality in infants with BPD requiring prolonged PPV. We identified 216 patients (19%) with BPD requiring prolonged PPV among 1156 ELBW infants. Of these patients, 41% received echocardiography after 4 weeks of life, with 37% showing evidence of PH. Logistic regression analysis demonstrated that infants with BPD requiring prolonged PPV, with PH detectable by echocardiogram, were four times more likely to die (adjusted odds ratio): 4.6, 95% confidence interval: 1.3-16.5) when compared with infants with BPD requiring prolonged PPV without echocardiographic evidence of PH. Pulmonary hypertension appears to be an important, independent determinant of death in infants with BPD requiring prolonged PPV.

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Available from: David E Jones, Mar 15, 2016
ORIGINAL ARTICLE
Echocardiographic detection of pulmonary hypertension in
extremely low birth weight infants with bronchopulmonary
dysplasia requiring prolonged positive pressure ventilation
JL Slaughter
1,3
, T Pakrashi
2
, DE Jones
1
, AP South
1
and TA Shah
1
1
The Perinatal Institute, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA and
2
Department of Obstetrics
and Gynecology, University of Cincinnati Academic Medical Center, Cincinnati, OH, USA
Objective: The goal of this study was to delineate the epidemiology of
echocardiographically diagnosed pulmonary hypertension (PH) in
extremely low birth weight (ELBW) infants with bronchopulmonary
dysplasia (BPD) requiring prolonged positive pressure ventilation (PPV),
and to determine the independent relationship between PH and mortality in
these patients.
Study Design: Our retrospective cohort included ELBW infants, with
BPD requiring prolonged PPV, hospitalized in Cincinnati, Ohio during
2003–2009, as recorded in the National Institute of Child Health and
Human Development Neonatal Research Network Database. Following
chart review, a logistic regression model was constructed to understand
the contribution of PH to mortality in infants with BPD requiring
prolonged PPV.
Result: We identified 216 patients (19%) with BPD requiring prolonged
PPV among 1156 ELBW infants. Of these patients, 41% received
echocardiography after 4 weeks of life, with 37% showing evidence of PH.
Logistic regression analysis demonstrated that infants with BPD requiring
prolonged PPV, with PH detectable by echocardiogram, were four times
more likely to die (adjusted odds ratio): 4.6, 95% confidence interval:
1.3– 16.5) when compared with infants with BPD requiring prolonged
PPV without echocardiographic evidence of PH.
Conclusion: Pulmonary hypertension appears to be an important,
independent determinant of death in infants with BPD requiring
prolonged PPV.
Journal of Perinatology (2011) 31, 635640; doi:10.1038/jp.2010.213;
published online 10 February 2011
Keywords: pulmonary hypertension; bronchopulmonary dysplasia;
echocardiogram; extremely low birth weight infant; neonatal
Introduction
Innovations in neonatal care have led to increased survival rates
for extremely low birth weight (ELBW) infants (birth weight
<1000 g). As survival improves, morbidities among survivors have
changed.
1
Even though bronchopulmonary dysplasia (BPD) is the
most common complication among premature infants, advances in
neonatal care that include antenatal glucocorticoids, surfactant
treatment and gentle ventilation strategies have changed the
pathological features and clinical course of BPD. Historically,
oxygen toxicity and ventilator-induced injury, resulting in
inflammation, fibrosis and smooth muscle hypertrophy in the
airways characterized BPD in premature infants.
2
In the surfactant
era, the pathology of BPD is likely due to disruption in the normal
sequence of lung development in ELBW infants.
3
This ‘new’ BPD is
characterized by decreased numbers and volume of alveoli, and
deficiencies in the number and size of intra-acinar pulmonary
arteries. These changes are responsible for a significant reduction
in the total cross-sectional area of the pulmonary vascular bed.
4
This reduction in the vascular cross-sectional area and alveolar
hypoxia results in structural remodeling of the pulmonary
vasculature, abnormal vasoreactivity and subsequent development
of pulmonary hypertension (PH).
3,4
Although the mechanisms responsible for elevated pulmonary
vascular resistance and altered reactivity remain incompletely
understood, the development of PH is a recognized and sometimes
serious complication of severe BPD that can contribute significantly
to the morbidity and mortality rates of preterm infants.
4,5
Persistent
echocardiographic evidence of PH beyond the first few months of
life has been associated with up to 40% mortality in infants with
BPD.
6
However, the true prevalence of PH in BPD and the rate of
BPD mortality attributable to PH are unknown.
7
Diagnosis of
pulmonary vascular disease in this population is difficult and
requires a high degree of suspicion because the symptoms of PH
may be subtle and masked by the signs of BPD itself, even in
patients with significantly elevated pulmonary artery pressures.
8
Epidemiological research of PH is increasingly needed, as the
rate of BPD in the ELBW population has stabilized
2,9,10
and clinical
Received 7 September 2010; revised 7 December 2010; accepted 8 December 2010; published
online 10 February 2011
Correspondence: Dr TA Shah, The Perinatal Institute, Cincinnati Children’s Hospital Medical
Center, 3333 Burnet Avenue, Division of Neonatology, ML 7009, Cincinnati, OH 45229, USA.
E-mail: tushar.shah@cchmc.org
3
Present address: Division of Neonatology, Department of Pediatrics at Nationwide Children’s
Hospital and The Ohio State University, Columbus, Ohio, USA
Journal of Perinatology (2011) 31, 635– 640
r
2011 Nature America, Inc. All rights reserved. 0743-8346/11
www.nature.com/jp
attention has become increasingly focused upon the
late-pulmonary outcomes of BPD survivors.
11
If PH were found to
be highly prevalent and associated with increased mortality in
ELBW infants with severe cases of BPD, closer echocardiographic
surveillance for PH might be warranted. Early detection of PH by
echocardiogram could prompt more thorough diagnostic testing
via cardiac catheterization and provide prognostic information to
influence the use of targeted interventions such as vasodilator
therapies.
8
Patients with documented PH might also benefit both
from increased monitoring during periods of perioperative stress
and acute illness, and from closer follow-up upon discharge.
Our objectives were to delineate the epidemiology of
echocardiographically diagnosed PH in ELBW infants with BPD
requiring prolonged positive pressure ventilation (PPV), including
the determination of the minimum prevalence of PH in our cohort,
and to test the hypothesis that PH is an important determinant of
death in ELBW infants with BPD requiring prolonged PPV.
Methods
Subjects and definitions
The National Institute of Child Health and Human Development
Neonatal Research Network Database was utilized to identify ELBW
infants with BPD requiring PPV at 28 days of age who were born
during 20032009, and cared for in any of three Level III
Neonatal Intensive Care Units (Cincinnati Children’s Hospital
Medical Center, Good Samaritan Hospital, University of Cincinnati
Hospital) that serve the tri-state region of Northern Kentucky,
South-eastern Indiana and South-western Ohio. During the study
period, these hospitals served as the tertiary care referral centers
for all infants born at a gestational age of <32 weeks within the
tri-state region.
Bronchopulmonary dysplasia was defined as receiving
supplemental oxygen at 36 weeks post-menstrual age. Infants with
BPD were defined as requiring prolonged PPV if they were on
continued respiratory support at 28 days post-natal age by one of
the following modalities: mechanical ventilation, continuous
positive airway pressure (CPAP) or nasal cannula flow >2 l min
1
.
Infants were considered to have PH if an echocardiogram was
performed after 30 days post-natal age that demonstrated elevated
pulmonary artery pressure (pulmonary artery pressure >50%
systemic or evidence of right ventricular failure consistent with PH)
as determined by a pediatric cardiologist at Cincinnati Children’s
Hospital Medical Center. Presence of right ventricular hypertrophy,
tricuspid regurgitation jet, right to left shunt and/or septal
flattening were recorded when present in the setting of PH. Infants
with known structural lung, airway, pulmonary vascular or major
cardiac anomalies at birth were excluded. The overall outcome
was death due to any reason during the neonatal intensive care
unit stay in the cohort of ELBW infants with BPD requiring
prolonged PPV.
This study was approved by the institutional review boards of
Cincinnati Children’s Hospital Medical Center, the Good Samaritan
Hospital of Cincinnati and the University of Cincinnati. Waivers of
informed consent were granted from each institution.
Data sources
Data were obtained from two sources, the National Institute of
Child Health and Human Development Neonatal Network Database
and chart review. The National Institute of Child Health and
Human Development Neonatal Network Database is a registry of
very low birth weight infants (birth weight <1500 g), who were
born between 22 0/7 and 28 6/7 weeks (<29 weeks), inclusive
gestational age, and/or between 401 and 1500 g, inclusive birth
weight. Infants qualified for inclusion in the very low birth weight
registry when they were admitted to a network center within 14
days of birth or were live-born, but died in the delivery room.
Research nurses collected demographic, perinatal and infant data
at each participating center using common definitions developed
by investigators and described in previous publications.
12,13
Cincinnati Children’s Hospital Medical Center, the University of
Cincinnati Hospital and Good Samaritan Hospital are participating
centers in the database. Records were reviewed from these three
institutions to identify all ELBW infants (birth weight <1000 g) in
the tri-state region during 20032009 with BPD and PPV at
28 days of age. Infant demographic information extracted included
birth weight, gestational age, surfactant administration, patent
ductus arteriosus (PDA) and its treatment, duration of mechanical
ventilation, diuretic usage, intraventricular hemorrhage and its
grade, necrotizing enterocolitis (NEC) and its severity, any surgical
procedures and late-onset sepsis.
Patients that met our inclusion requirements were linked to
identifiers for chart review at the respective hospitals. The chart
review was conducted to collect information regarding
echocardiographic results, treatment for PH and autopsy results.
Echocardiograms were ordered at physician discretion as clinically
warranted, and may or may not have been obtained with the goal
of assessing for PH. Treatment for PH was defined as the use of
nitric oxide and/or sildenafil at greater than 2 months of age. All
autopsy results were reviewed when available.
Database variables
Antenatal steroids were defined as administration of any
corticosteroid to accelerate fetal lung maturity in the concurrent
pregnancy. Estimated gestational age, in completed weeks, was
determined by best obstetric estimate using last menstrual period,
standard obstetric parameters and ultrasonography. When there
was a 2-week range of gestational age among obstetric estimates,
the lowest estimate was used. When there was a 3-week range of
several existing estimates, the median gestational age estimate was
used. Data were also collected on diagnoses (including PDA),
treatments, and in-hospital morbidities until death, discharge or
Echocardiogram and pulmonary hypertension in BPD
JL Slaughter et al
636
Journal of Perinatology
120 days; after 120 days or if the patient was transferred, then data
were collected regarding death or discharge to home. Surfactant
treatment was defined as one or more doses of any surfactant
during hospitalization. Intraventricular hemorrhage was reported
according to the classification of Papile et al.
14
Late-onset sepsis
was defined as a positive blood or cerebral spinal fluid culture
obtained in the presence of compatible clinical signs of septicemia
occurring after 72 h of age. Data regarding NEC were collected for
infants who survived >12 h and was defined as modified Bell’s
classification stage IIA or greater.
15
Surgery for NEC was at the
discretion of each individual network center and included any
surgical intervention (drain, laparotomy or both).
Statistical analysis
SAS V9.2 (Cary, NC, USA) was used to analyze the data. Unadjusted
(crude) associations between group status for the hypothesis
(PH vs no PH) and neonatal characteristics were explored through
bivariable analysis using w
2
, Fisher’s exact, Wilcoxon or T-test
where appropriate. A multiple logistic regression model was
constructed for our hypothesis to understand the independent
relationship between PH and death while controlling for other
covariates and confounders. A stepwise approach was taken to
determine which variables remained in the final multivariable
model. Variables were included in the regression models that were
found to be significantly related to the outcome at the P<0.05 level
in unadjusted analysis and remained in the final model if they
were significant at P<0.05. The Hosmer Lemeshow test was
conducted to determine the model’s goodness of fit.
Results
A total of 1156 ELBW infants were evaluated (Figure 1), with 341
(29.4%) having BPD. Out of these, 216 infants with BPD required
prolonged PPV, defined as ventilation, CPAP, or >2 l nasal
cannula flow at >28 days of life. Overall, 16 infants were excluded
due to known structural lung, airway or major cardiac anomalies
at birth. Additionally, 10 infants were excluded because their
medical records could not be traced. All 190 included infants met
the conventional criteria for BPD, oxygen requirement at 28 days of
life and the NIH consensus definition of severe BPD.
2
Of patients
with BPD on prolonged PPV that met inclusion criteria, 78/190
(41%) had echocardiography after 4 weeks of life, with 29/78
(37%) showing evidence of PH. There was a 2.8-fold increase
(unadjusted odds ratio) in mortality in infants with BPD requiring
prolonged PPV when PH was present (38 vs 14%).
Clinical characteristics of all infants with BPD requiring
prolonged PPV are summarized in Table 1 by echocardiogram
status. Infants with a lower birth weight and longer duration of
respiratory support (mechanical ventilation, CPAP or oxygen
therapy) were more likely to undergo echocardiography after
30 days of life. In addition, infants who had an echocardiogram
were more likely to have persistent patency of the ductus arteriosus.
Gender, race, oxygen status at discharge, surgery for PDA and
incidence of NEC were not different between those who did and
those did not have an echocardiogram performed. However, infants
who had an echocardiogram had a significantly higher incidence
of death.
Among infants with BPD requiring prolonged PPV who had an
echocardiogram, birth weight, gestational age, gender, race,
incidence of major complications during the neonatal intensive
care unit stay (NEC, surgery for PDA) and duration of mechanical
ventilation were not different between those with and those without
PH. Infants with PH spent less days on average on CPAP when
compared with infants without PH (Table 2). The unadjusted
incidence of death was greater in the PH group.
Multiple logistic regression modeling demonstrated that infants
with BPD requiring prolonged PPV who developed PH were more
likely to die (adjusted odds ratio: 4.6, 95% confidence interval:
1.316.5) when compared with infants with BPD requiring
prolonged PPV who did not develop PH after controlling for NEC,
sepsis, severe intraventricular hemorrhage, birth weight and PDA
(Table 3) (HosmerLemeshow test, P¼0.14).
Autopsy results were only available for 6 of the 28 ELBW infants
with BPD requiring prolonged PPV that died. One infant had
evidence of BPD with severe PH, right ventricular hypertrophy and
hepatosplenomegaly.
Tot a l EL BW I n fa nts
2003-2009
1156
BPD with prolonged
PPV
216 (18.8%)
Excluded
26
Final Cohort
190
Echo >30 Days
78 (41%)
No Echo >30 days
112 (59%)
PH
29 (37%)
No PH
49 (63%)
Death
10(9%)
Death
7 (14%)
Death
11 (38%)
Figure 1 Flow of extremely low birth weight infants (<1000 g) from inclusion
into the cohort of infants with bronchopulmonary dysplasia on prolonged positive
pressure ventilation to the measured outcome: survival vs death.
Echocardiogram and pulmonary hypertension in BPD
JL Slaughter et al
637
Journal of Perinatology
Five patients (17%) who were diagnosed with PH by
echocardiogram at >30 days of age, received vasodilator therapy.
All were treated with nitric oxide. In addition, three also received
sildenafil. No patients were treated with sildenafil in isolation.
Despite intervention, all five patients whose PH was treated with
vasodilators died.
Discussion
When we retrospectively used the results of echocardiograms
obtained at greater than 30 days of age in our regional cohort
of ELBW infants with BPD requiring prolonged PPV, PH was
detected in 37%. This demonstrated that, at a minimum, 15%
(29/190) of our total population of ELBW infants with BPD requiring
prolonged PPV with ventilation, CPAP or >2 l nasal cannula flow at
28 days of life suffered from co-existing PH. When confounders
were controlled for, the presence of PH on echocardiogram led to a
nearly fivefold increase in the odds of death. These findings indicate
that PH is prevalent within the subsection of the ELBW
population with BPD on prolonged PPV, and that it appears to be an
important risk factor for death in these infants.
Previous research has shown that PH develops in some infants
with BPD and that it can contribute to BPD-associated morbidity
and mortality.
4,5
However, there is a paucity of evidence regarding
appropriate clinical surveillance for PH in BPD patients, and the
prevalence of PH in these infants remains unknown.
5,7,16
Very few studies have estimated the minimum prevalence of PH
within a population of patients with BPD.
7,16
An et al.
7
recently
used echocardiograms to evaluate a group of 116 very low birth
weight infants and observed a 25% prevalence of PH in patients
with BPD. However, their study differed from ours in that the BPD
severity within their cohort ranged from mild (breathing room air)
to severe, and birth weights ranged from 430 to 1560 g.
7
We
Table 1 Characteristics of extremely low birth weight infants with
bronchopulmonary dysplasia on prolonged positive pressure ventilation
(N¼190)
Characteristics No echo
(N¼112)
Echo
(N¼78)
P-value
Birth weight
a
779±122 734±133 0.016
b
Gestational age
a
25±1.3 25±1.5 0.006
c
Female, n(%) 58 (52) 36 (46) 0.409
Caucasian, n(%) 32 (29) 18 (23) 0.398
Antenatal antibiotics, n(%) 65 (58) 51 (65) 0.343
Antenatal steroids, n(%) 92 (82) 67 (86) 0.577
Surfactant, n(%) 85 (76) 64 (82) 0.470
PDA>30 days, n(%) 13 (12) 40 (51) <0.0001
Surgery for PDA, n(%) 13 (12) 15 (19) 0.704
NEC, n(%) 17 (15) 18 (23) 0.167
Severe IVH, n(%) 2 (2) 10 (13) 0.004
d
Discharged home on oxygen, n(%) 32 (29) 20 (26) 0.147
Death, n(%) 10 (9) 18 (23) 0.006
Days on oxygen
a
81±35 113±62 <0.0001
c
Days on mechanical ventilation
a
20±19.7 39±21.9 <0.0001
c
Days on CPAP
a
25±17.5 15±16.8 <0.0001
c
Abbreviations: CPAP, continuous positive pressure ventilation; Echo, echocardiogram;
intraventricular hemorrhage, IVH; NEC, necrotizing enterocolitis; PDA, patent ductus
arteriosus.
a
Mean±s.d.
w
2
-test used for statistical analysis unless otherwise noted:
b
T-test.
c
Wilcoxon analysis.
d
Fischer’s ExactFtwo-sided probability.
Table 2 Characteristics of the infants who received an echocardiogram after
30 days of life according to pulmonary hypertension status (N¼78)
Characteristics No PH
(N¼49)
PH
(N¼29)
P-value
Birth weight
a
733±144.19 735±114.93 0.959
b
Gestational age
a
25±1.43 25±1.50 0.801
c
Female, n(%) 21 (43) 15 (52) 0.448
Caucasian, n(%) 11 (22) 7 (24) 0.864
Antenatal antibiotics, n(%) 33 (67) 18 (62) 0.636
Antenatal steroids, n(%) 46 (94) 21 (72) 0.058
Surfactant, n(%) 38 (78) 26 (90) 0.231
PDA>30 days, n(%) 23 (47) 17 (59) 0.281
Surgery for PDA, n(%) 10 (20) 5 (17) 0.695
NEC, n(%) 12 (24) 6 (21) 0.700
Severe IVH, n(%) 5 (10) 5 (17) 0.369
Death, n(%) 7 (14) 11 (38) 0.019
Discharged home on oxygen, n(%) 13 (27) 7 (24) 0.633
Days on oxygen
a
113±66.56 113±56.00 0.610
c
Days on mechanical ventilation
a
36±22.30 42.69±21.20 0.257
c
Days on CPAP
a
19±17.58 8.07±12.50 0.003
c
Abbreviations: CPAP, continuous positive airway pressure; IVH, intraventricular
hemorrhage; NEC, necrotizing enterocolitis; PDA, patent ductus arteriosus; PH,
pulmonary hypertension.
a
Mean±s.d.
w
2
-test used for statistical analysis unless otherwise noted:
b
T-test.
c
Wilcoxon analysis.
Table 3 Adjusted odds ratios and 95% confidence intervals for death vs
covariates in multivariate logistic regression
Risk factor PH vs no PH
a
adjusted OR (95% CI)
Pulmonary hypertension 4.6 (1.316.5)
Birth weight 0.9 (0.9– 1)
Necrotizing enterocolitis 1.3 (0.3– 5.4)
Sepsis 1.3 (0.4– 4.4)
Patent ductus arteriosus 0.4 (0.1–1.4)
Severe intraventricular hemorrhage 3.1 (0.5– 17.5)
Abbreviations: CI, confidence interval; OR, odds ratio; PH, pulmonary hypertension.
a
Model comparing infants with echocardiographic evidence of pulmonary hypertension
with infants with no echocardiographic evidence of pulmonary hypertension.
Echocardiogram and pulmonary hypertension in BPD
JL Slaughter et al
638
Journal of Perinatology
restricted our cohort to ELBW infants with BPD that required
prolonged PPV, because these infants on considerable respiratory
support at 28 days of life are at the highest risk of developing PH
because of a striking decrease in normal alveolar septation and
microvascular development.
17,18
To our knowledge, our
investigation was the first to review echocardiogram results to
determine the minimum frequency of PH within a multi-year,
regional cohort of ELBW infants with BPD requiring prolonged
PPV, and to directly investigate the independent relationship
between PH and death in this highly vulnerable population. An
absolute frequency cannot be determined because only 41% of these
infants underwent echocardiography.
In our study, infants with PH were less likely to have received
antenatal steroids. Antenatal steroids may have a vital role in the
regulation of vascular endothelial growth factor receptors that are
instrumental in pulmonary angiogenesis and lung growth through
nitric oxide-dependent mechanisms.
19,20
Disruption of vascular
endothelial growth factor signaling because of premature birth
impairs lung growth and sets the stage for late PH.
19– 21
Lack of
antenatal steroids has also been associated with decreased
likelihood of closure of the ductus arteriosus.
22
Although not
statistically significant, infants with PH in our study were also more
likely to have a prolonged PDA. Prolonged PDA has been associated
with BPD and PH.
23
Physiologically, PH may be a protective
mechanism in neonates with prolonged PDA to prevent pulmonary
overcirculation and consequent congestive heart failure. The
relationship between the lack of antenatal steroids, prolonged PDA
and PH in premature infants needs to be studied.
Echocardiograms, commonly available and non-invasive, are
limited in their ability to differentiate severity of PH as compared
with the gold standard of cardiac catheterization.
5,8
Despite this
limitation, they are still considered the best method to screen BPD
patients for PH at the population level
18
and often correctly identify
infants with PH.
8,24
Recent technological advances such as
myocardial tissue Doppler might increase the sensitivity of this
important tool.
25
The retrospective nature of our study imposed several
limitations. As the use of echocardiography was selective, we were
only able to determine a minimal estimate of PH in ELBW with
BPD requiring prolonged PPV. It was also impossible for us to
determine the efficacy of vasodilators in these patients. All of the
patients in our cohort who had their PH treated with the
vasodilators, sildenafil and nitric oxide, died. However, our chart
review indicated that vasodilators were usually started only in those
patients with the most severe clinical courses. Experience with PH
therapies, such as intravenous epoprostenol, endothelin receptor
blockers, aerosolized prostacyclin analogues, inhaled nitric oxide,
sildenafil and other agents, is limited in the population of BPD
patients.
26,27
Moreover, the long-term consequences of these
potential therapies are unknown. Even though it is likely that
echocardiograms tend to be ordered on the sickest infants, PH
remains an important contributor to mortality even after
controlling for the most prevalent causes of death in the neonatal
intensive care unit.
In conclusion, our findings indicate that PH is prevalent and an
important determinant of mortality in the ELBW population with
BPD requiring prolonged PPV, and that it appears to be an
important and overlooked risk factor for death in these highly
vulnerable infants. Utilization of echocardiography as a
surveillance tool for PH in infants with BPD, as suggested by
experts in the field
28,29
may increase the likelihood of early PH
diagnosis. Prospective studies of PH prevalence and treatment in
BPD patients are needed to develop a screening strategy for PH in
this high-risk group.
Conflict of interest
The authors declare no conflict of interest.
Acknowledgments
This work was unfunded.
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Echocardiogram and pulmonary hypertension in BPD
JL Slaughter et al
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Journal of Perinatology
    • "This co-morbidity in the BPD population is associated with increased morbidity and mortality when compared to infants with BPD without PH.[10] PH is associated with a mortality rate ranging from 14% to 38% in these same studies.[4][5][6][7][8][9]Infants with PH and BPD have been shown to spend an additional 2.2 months in the hospital compared to infants with BPD alone, resulting in at least an additional $198,000 in health care costs.[11] "
    [Show abstract] [Hide abstract] ABSTRACT: Background Pulmonary hypertension (PH) is a significant cause of morbidity in preterm infants, but no screening guidelines exist. We sought to identify risk factors and clinical outcomes associated with PH in preterm infants to develop a PH risk score. Methods Retrospective analysis of two separate populations of preterm infants (NICU cohort n = 230; Clinic registry n = 580). Results 8.3% of the NICU cohort had PH after 4 weeks of age, while 14.8% of the clinic registry had PH after 2 months of age. Lower birth weights and longer initial hospitalizations were associated with PH in both populations (p<0.001 for all tests). Using adjusted logistic regression, patent ductus arteriosus (PDA) requiring ligation was associated with PH in both the NICU cohort (OR: 3.19; p = 0.024) and the clinic registry (OR: 2.67; p<0.001). Risk factors (birth weight ≤780 grams, home supplemental oxygen use, and PDA ligation) identified in the clinic registry (training dataset) were validated in the NICU cohort with 0–1 factors present were associated with ≤1.5% probability of having PH, any 2 factors with a 25% probability, and all 3 factors with a 40% probability. Conclusions Lower birth weight, PDA ligation, and respiratory support were associated with PH in both populations. A PH risk score based on clinical indicators from the training dataset predicted PH in the validation set. This risk score could help focus resources to preterm infants at higher risk for PH. Further work is needed to determine whether earlier or more aggressive management of ductal lesions could alter PH outcomes.
    Full-text · Article · Oct 2016
    • "In our study, none of the infants with BPD had echocardiographic signs of PHT. Previous studies have reported a prevalence of PHT in infants with BPD ranging from 25% to 37% [15,16]. PHT associated with BPD has been related to the degree of severity of BPD, a low birth weight, long-term ventilation care, oxygen supplementation, aggressive ventilator settings, infections and PDA [15,17,18]. "
    [Show abstract] [Hide abstract] ABSTRACT: Objective : To characterize the incidence of pulmonary hypertension in a cohort of patients with bronchopulmonary dysplasia [BPD] and to correlate echocardiographic markers of pulmonary artery pressure [PAP] with prolonged oxygen supplementation, blood oxygen saturation [SpO 2 ], pH and pCO 2. Study design: We prospectively studied 29 infants admitted to a level 3 Neonatal Intensive Care unit [NICU] between February 2006 and August 2007. Neonates born at less than 28 weeks of gestation and requiring oxygen supplementation at 34-36 weeks of postmenstrual age were included. Echocardiographic estimation of pulmonary arterial pressure [PAP] was done with interventricle septal motion, tricuspid regurgitation jet velocity, right ventricular pre-ejection period/ejection time ratio [RVPEP/RVET] and right ventricular acceleration time/ejection time ratio [RVAT/RVET] at weeks 0, 1, 4 and 6 of study. These echocardiographic measurements were assessed for correlation with duration of oxygen therapy, SpO 2 , pH and pCO 2. Results: Twenty-nine patients were enrolled at a mean postmenstrual age of 35 weeks and 3 days [±6 days [SD]]. BPD was moderate in 62% and severe in 38%. Twenty-four patients required prolonged oxygen therapy [oxygen needed past 44 weeks postmenstrual age]. RVPEP/RVET ratio was 0.21 in these patients compared to 0.13 [p=0.02] in those that did not require prolonged oxygen therapy. RVPEP/RVET ratio correlated with low pH [p=0.02] and high pCO 2 [p=0.04]. It did not correlate with SpO 2 levels. Conclusion: In infants with BPD, the RVPEP/RVET ratio at 34-42 weeks of postmenstrual age was higher in infants requiring prolonged oxygen therapy, and correlated with pH and pCO 2. This RVPEP/RVET ratio could help with early identification of patients that will require prolonged oxygen therapy.
    Full-text · Article · Nov 2015 · Journal of Pediatrics
    • "hypoxia; nitric oxide; nitric oxide synthase; preterm infant Bronchopulmonary dysplasia (BPD) is the most common pediatric chronic lung disease [1]. Pulmonary hypertension (PH) is a complication of BPD, with a prevalence estimated between 25–37%234. PH is associated with an increase in morbidity and mortality [5, 6]. Currently, not only is it difficult to diagnose PH in BPD but there are no clinical tests for predicting which BPD patients will develop PH. "
    [Show abstract] [Hide abstract] ABSTRACT: Objective: To test the hypothesis that levels of the endogenous inhibitor of nitric oxide production, asymmetric dimethylarginine (ADMA), would be greater in preterm infants with bronchopulmonary dysplasia (BPD)-associated pulmonary hypertension (PH) than in infants with BPD alone. Study design: A case-control study of 23 patients with both BPD and PH (cases) and 95 patients with BPD but no evidence of PH (controls). Levels of ADMA were compared between cases and controls by t test. Results: Patients with both BPD and PH had greater plasma levels of ADMA than patients with BPD alone (P = .04). In samples drawn before 28 days of life, greater levels of ADMA were again found in cases compared with controls (P = .02). The plasma arginine-to-ADMA ratio was lower in cases than in controls (P = .03), suggesting a greater likelihood of inhibition of nitric oxide production in patients with both BPD and PH than in patients with BPD alone. Conclusion: In this neonatal BPD cohort, ADMA levels are increased in patients with BPD who develop PH. We speculate that ADMA may be both a biomarker and a potential therapeutic target for preterm infants with BPD-associated PH.
    Full-text · Article · Oct 2014
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