Risk Factors for Pulmonary Artery Hypertension in Preterm Infants with Moderate or Severe Bronchopulmonary Dysplasia

Kim, Do Hyun; Kim, Han Suk; Choi, Chang Won; Kim, Ee Kyung; Kim, Beyong Il; Choi, Jung Hwan

doi:10.1159/000327891

Cited by 151 publications

(153 citation statements)

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“…A recent study by Mirza and coworkers described a lower incidence of PH (8% at 10-14 d of age and 4% at 36 wk PMA), but the criteria for PH diagnosis in that study was more similar to our alternate criteria-1 (41), which achieved similar rates of PH in our cohort (Figure 2). Higher death rates in preterm infants with BPD and PH compared with those without PH have been reported as well (24,40,42). Factors associated with late PH in these studies include lower birthweight and longer periods of respiratory support.…”

Section: Discussionmentioning

confidence: 82%

Early Pulmonary Vascular Disease in Preterm Infants at Risk for Bronchopulmonary Dysplasia

Mourani¹,

Sontag

Younoszai

et al. 2015

Am J Respir Crit Care Med

361

473

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Rationale: Pulmonary hypertension (PH) is associated with poor outcomes among preterm infants with bronchopulmonary dysplasia (BPD), but whether early signs of pulmonary vascular disease are associated with the subsequent development of BPD or PH at 36 weeks post-menstrual age (PMA) is unknown.Objectives: To prospectively evaluate the relationship of early echocardiogram signs of pulmonary vascular disease in preterm infants to the subsequent development of BPD and late PH (at 36 wk PMA).Methods: Prospectively enrolled preterm infants with birthweights 500-1,250 g underwent echocardiogram evaluations at 7 days of age (early) and 36 weeks PMA (late). Clinical and echocardiographic data were analyzed to identify early risk factors for BPD and late PH. Measurements and Main Results:A total of 277 preterm infants completed echocardiogram and BPD assessments at 36 weeks PMA. The median gestational age at birth and birthweight of the infants were 27 weeks and 909 g, respectively. Early PH was identified in 42% of infants, and 14% were diagnosed with late PH. Early PH was a risk factor for increased BPD severity (relative risk, 1.12; 95% confidence interval, 1.03-1.23) and late PH (relative risk, 2.85; 95% confidence interval, 1.28-6.33). Infants with late PH had greater duration of oxygen therapy and increased mortality in the first year of life (P , 0.05).Conclusions: Early pulmonary vascular disease is associated with the development of BPD and with late PH in preterm infants. Echocardiograms at 7 days of age may be a useful tool to identify infants at high risk for BPD and PH.Keywords: bronchopulmonary dysplasia; pulmonary vascular disease; pulmonary hypertension; echocardiography; prematurity At a Glance CommentaryScientific Knowledge on the Subject: Preterm infants remain at high risk for late respiratory morbidity and mortality caused by the development of bronchopulmonary dysplasia (BPD) and pulmonary hypertension (PH). Early injury to the developing lung can impair angiogenesis and alveolarization and result in simplification of distal lung airspace and the clinical manifestations of BPD and PH. However, whether early signs of pulmonary vascular disease are indicative of the subsequent development of BPD or PH at 36 weeks postmenstrual age (PMA) has not been well established.What This Study Adds to the Field: This paper presents a longitudinal study identifying echocardiogram-derived risk factors at 7 days of age for the subsequent development of both BPD and PH. We also describe the incidence of PH at 36 weeks PMA and its relationship to BPD severity.

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Section: Discussionmentioning

confidence: 82%

Early Pulmonary Vascular Disease in Preterm Infants at Risk for Bronchopulmonary Dysplasia

Mourani¹,

Sontag

Younoszai

et al. 2015

Am J Respir Crit Care Med

361

473

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“…Bronchopulmonary dysplasia (BPD) is associated with pulmonary hypertension (PH), [1][2][3] with BPD-PH occurring in 30% to 45% of infants with moderate to severe BPD. 1,3,4 Mortality rates in infants with BPD-PH are 4-fold greater than in infants without PH, with the majority of deaths linked directly to PH.…”

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confidence: 99%

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confidence: 99%

“…1,3,4 Mortality rates in infants with BPD-PH are 4-fold greater than in infants without PH, with the majority of deaths linked directly to PH. 3,5 Supplemental oxygen is the mainstay of therapy for patients with BPD-PH. [6][7][8] However, survival rates of infants with BPD-PH treated by using supplemental oxygen are 61% and 52% at 1 and 2 years of age, respectively.…”

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confidence: 99%

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Sildenafil Treatment of Infants With Bronchopulmonary Dysplasia–Associated Pulmonary Hypertension

Backes

Reagan

Smith

et al. 2016

Hospital Pediatrics

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OBJECTIVE: This study had 2 goals: (1) to identify clinical and demographic characteristics associated with sildenafil exposure for infants with bronchopulmonary dysplasia (BPD)-associated pulmonary hypertension (PH); and (2) to characterize hospital-specific treatment frequency, age at first administration, and length of sildenafil treatment. METHODS: This retrospective cohort study used data from the Pediatric Health Information System to determine variables associated with sildenafil exposure and between-hospital variations in sildenafil utilization patterns. The study included infants with BPD-PH who were discharged between January 1, 2006, and December 31, 2013. RESULTS: Within 36 US pediatric hospitals, 3720 infants were diagnosed with BPD, of whom 598 (16%) also had a diagnosis of PH (BPD-PH). Among infants with BPD-PH, 104 infants (17%) received sildenafil. The odds for sildenafil treatment among infants born between 25 and 26 weeks’ gestational age (GA) and <24 weeks’ GA, respectively, were 2.26 (95% confidence interval [CI]: 1.20–4.24) and 3.21 (95% CI: 1.66–6.21) times those of infants born at 27 to 28 weeks’ GA. Severity of BPD correlated with sildenafil exposure, with adjusted odds ratios (ORs) for moderate BPD (OR: 3.03 [95% CI: 1.03–8.93]) and severe BPD (OR: 7.56 [95% CI: 2.50–22.88]), compared with mild BPD. Greater rates of sildenafil exposure were observed among small for GA neonates (OR: 2.32 [95% CI: 1.21–4.46]). The proportion of infants with BPD-PH exposed to sildenafil varied according to hospital (median: 15%; 25th–75th percentile: 0%–25%), as did the median duration of therapy (52 days; 25th–75th percentile: 28–109 days). CONCLUSIONS: The odds of sildenafil treatment were greatest among the most premature infants with severe forms of BPD. The frequency and duration of sildenafil exposure varied markedly according to institution. Patient-centered trials for infants with BPD-PH are needed to develop evidence-based practices.

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“…PAH is common in infants with BPD, with an estimated incidence of 18%-25% of preterm infants, [79][80][81] and is associated with high mortality (30%-40%), especially if sustained beyond the first months of life. [82][83][84][85] Although long-term studies of BPD have primarily focused on late abnormalities of airway function, PVD can also persist into childhood and adult life. 79,[86][87][88][89] Tepper and colleagues 88 have reported that infants with even mild BPD have decreased diffusion capacity when corrected for lung volume, in comparison with age-matched term controls, suggesting that BPD infants may have decreased alveolar surface area available for gas exchange.…”

Section: Pvd In Bpdmentioning

confidence: 99%

The Robyn Barst Memorial Lecture: Differences between the Fetal, Newborn, and Adult Pulmonary Circulations: Relevance for Age‐Specific Therapies (2013 Grover Conference Series)

et al. 2014

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Pulmonary arterial hypertension (PAH) contributes to poor outcomes in diverse diseases in newborns, infants, and children. Many aspects of pediatric PAH parallel the pathophysiology and disease courses observed in adult patients; however, critical maturational differences exist that contribute to distinct outcomes and therapeutic responses in children. In comparison with adult PAH, disruption of lung vascular growth and development, or angiogenesis, plays an especially prominent role in the pathobiology of pediatric PAH. In children, abnormalities of lung vascular development have consequences well beyond the adverse hemodynamic effects of PAH alone. The developing endothelium also plays critical roles in development of the distal airspace, establishing lung surface area for gas exchange and maintenance of lung structure throughout postnatal life through angiocrine signaling. Impaired functional and structural adaptations of the pulmonary circulation during the transition from fetal to postnatal life contribute significantly to poor outcomes in such disorders as persistent pulmonary hypertension of the newborn, congenital diaphragmatic hernia, bronchopulmonary dysplasia, Down syndrome, and forms of congenital heart disease. In addition, several studies support the hypothesis that early perinatal events that alter lung vascular growth or function may set the stage for increased susceptibility to PAH in adult patients ("fetal programming"). Thus, insights into basic mechanisms underlying unique features of the developing pulmonary circulation, especially as related to preservation of endothelial survival and function, may provide unique therapeutic windows and distinct strategies to improve short-and long-term outcomes of children with PAH.Keywords: pulmonary vascular development, angiogenesis, alveolarization, persistent pulmonary hypertension of the newborn, congenital diaphragmatic hernia, bronchopulmonary dysplasia, Down syndrome, pediatric pulmonary hypertension. Pulmonary arterial hypertension (PAH) is a devastating and progressive disease that is characterized by abnormalities of vascular tone and reactivity, vessel wall structure, growth, and thrombosis. 1 Mechanisms contributing to PAH and its progression are complex and remain incompletely understood. Insights into vascular biology over the past few decades have led to remarkable improvements in the clinical course, outcomes, and survival in adults with PAH, yet relatively few studies have been performed in children. As in adults, PAH contributes to poor outcomes in diverse cardiac, pulmonary, and systemic diseases in newborns, infants, and children (Table 1). 2 There is a clear need to define the natural history of pediatric PAH in diverse settings; to develop new strategies to identify at-risk patients early in their course; and to establish novel approaches to better diagnose, evaluate, and treat children with PAH. 3,4 Despite many similarities between pediatric and adult PAH, critical differences exist that currently limit our clinical appr...

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Risk Factors for Pulmonary Artery Hypertension in Preterm Infants with Moderate or Severe Bronchopulmonary Dysplasia

Cited by 151 publications

References 55 publications

Early Pulmonary Vascular Disease in Preterm Infants at Risk for Bronchopulmonary Dysplasia

Early Pulmonary Vascular Disease in Preterm Infants at Risk for Bronchopulmonary Dysplasia

Sildenafil Treatment of Infants With Bronchopulmonary Dysplasia–Associated Pulmonary Hypertension

The Robyn Barst Memorial Lecture: Differences between the Fetal, Newborn, and Adult Pulmonary Circulations: Relevance for Age‐Specific Therapies (2013 Grover Conference Series)

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