Pulmonary Hypertension in Extremely Preterm Infants

Study Overview
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Brief Summary
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Extremely preterm infants are at risk for developing bronchopulmonary dysplasia (BPD) and associated chronic pulmonary hypertension (PH), a consequence of altered pulmonary vasculature. This condition occurs in about 25% of babies with BPD, and the association grows with increasing BPD severity. Other risk factors have been described as well. Morbidity and mortality associated with prematurity and/or BPD increase significantly in the presence of PH. Thus, international guidelines encourage the use of standardized screening protocols for this condition. However, several questions regarding these recommendations are left unanswered, such as a clear definition for PH in this population. The research aim is to prospectively evaluate prevalence, risk factors and clinical course of PH in these children. The investigators aim to identify at-risk infants early on and ultimately improve survival making use of an early targeted intervention.

Official Title
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Pulmonary Hypertension in Extremely Preterm Infants - A Prospective Cohort Study

Conditions
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Bronchopulmonary Dysplasia, Pulmonary Hypertension, Premature Birth

Intervention / Treatment
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* Diagnostic Test: Echocardiography
* Diagnostic Test: NT-proBNP


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Preterm infants with Gestational age <28 0/7 weeks Birth weight <1000 grams Exclusion Criteria: Major congenital malformations Structural airway or lung disease Congenital heart disease Lack of parental consent

Ages Eligible for Study
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Maximum Age: 2 Weeks

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Screening
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Extremely preterm newborns<br>All extremely preterm newborns in Flanders will be included, it is a single arm study | Diagnostic Test: Echocardiography<br>* There will be screened for pulmonary hypertension by means of serial echocardiographies during the study period<br>Diagnostic Test: NT-proBNP<br>* At 36 weeks postmenstrual age there will be screened for pulmonary hypertension by means of an NT-proBNP measurement in a blood sample<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Presence of pulmonary hypertension | Pulmonary hypertension will be defined as one or more of the following echocardiographic findings: Presence of a cardiac shunt with bidirectional or right-to-left flow Estimated right ventricular systolic pressure (RVSP) >40 mmHg RVSP/systemic systolic blood pressure (SBP) ratio >0.5 Presence of ventricular septal wall flattening | 3-10 days of life (time depending on the timing of the first echocardiography) | 
| Presence of pulmonary hypertension | Pulmonary hypertension will be defined as one or more of the following echocardiographic findings: Presence of a cardiac shunt with bidirectional or right-to-left flow Estimated right ventricular systolic pressure (RVSP) >40 mmHg RVSP/systemic systolic blood pressure (SBP) ratio >0.5 Presence of ventricular septal wall flattening | at 28 days of life | 
| Presence of pulmonary hypertension | Pulmonary hypertension will be defined as one or more of the following echocardiographic findings: Presence of a cardiac shunt with bidirectional or right-to-left flow Estimated right ventricular systolic pressure (RVSP) >40 mmHg RVSP/systemic systolic blood pressure (SBP) ratio >0.5 Presence of ventricular septal wall flattening | at 36 weeks PMA | 
| Presence of pulmonary hypertension | Pulmonary hypertension will be defined as one or more of the following echocardiographic findings: Presence of a cardiac shunt with bidirectional or right-to-left flow Estimated right ventricular systolic pressure (RVSP) >40 mmHg RVSP/systemic systolic blood pressure (SBP) ratio >0.5 Presence of ventricular septal wall flattening | at 6 months of age | 
| Presence of pulmonary hypertension | Pulmonary hypertension will be defined as one or more of the following echocardiographic findings: Presence of a cardiac shunt with bidirectional or right-to-left flow Estimated right ventricular systolic pressure (RVSP) >40 mmHg RVSP/systemic systolic blood pressure (SBP) ratio >0.5 Presence of ventricular septal wall flattening | at 12 months of age | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Presence of bronchopulmonary dysplasia | Assessment of supplemental oxygen | at 28 days of life | 
| Presence of bronchopulmonary dysplasia | Classification of BPD with an oxygen reduction test | at 36 weeks PMA | 
| Birth weight | Birth weight in grams | at birth | 
| Gestational age | Gestational age in weeks | at birth | 
| Small for gestational age | Birth weight <P3 | at birth | 
| Oligohydramnios | Presence of oligohydramnios during pregnancy | at birth | 
| Maternal hypertensive disorders | Presence of maternal hypertensive disorders during pregnancy (pre-eclampsia, hypertension, HELLP) | at birth | 
| ROP | Presence of retinopathy of prematurity | at 36 weeks | 
| NEC | Presence of necrotizing enterocolitis | at 36 weeks | 
| PDA | Presence of patent ductus arteriosus | at 36 weeks | 
| Sepsis | Presence of sepsis | up to discharge from the NICU, an average of 16 weeks | 
| VAP | Presence of ventilator associated pneumonia | at 36 weeks |