BOPP Study (B-NP and Occult Pulmonary Hypertension in Preterms)

Background

Infants born at less than 28 weeks gestation have an underdeveloped cardiorespiratory system and are at risk of respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD), cardiac insufficiency and pulmonary hypertension. Normal alveolar development is dependent upon the normal development of the pulmonary vascular bed through complex signalling pathways. Infants born at the extremes of prematurity have the normal pattern of alveolar and pulmonary vascular development disrupted. It is believed that the reduction in total cross-sectional area of the pulmonary vascular bed, coupled with recurrent intermittent hypoxia experienced by those born at extremely low gestational age, leads to abnormal remodelling of the pulmonary vasculature with persisting increased pulmonary vascular tone and vasoreactivity that lasts beyond infancy.

Retrospective studies have shown pulmonary hypertension occurs in 25-37% of patients with BPD. Infants with BPD requiring prolonged ventilation who have echocardiographically demonstrated pulmonary hypertension are four times more likely to die than those without demonstrable pulmonary hypertension. There have been no prospective studies documenting prevalence of pulmonary hypertension complicating BPD to date. In addition the long term effects of this disrupted path of cardiorespiratory development are yet to be established.

Cardiac catheterisation is the gold standard test for measuring pulmonary pressures but it is invasive and only available at specialist units necessitating a risky transport of a fragile neonate to access this service. We do not currently have a good screening test to identify premature infants with pulmonary hypertension. B-type (or brain) natriuretic peptide (BNP) is released from the myocardium in response to pressure and volume loading. BNP levels have been shown to be elevated in adults, children and term born infants with pulmonary hypertension. Reference values are available for BNP and N-Terminal proBNP in neonates.Serial NTpBNP has the potential to give longitudinal data reflecting the evolution of pulmonary hypertension.

NTpBNP levels has the potential to stratify extremely low gestational age neonates into low, intermediate and high risk categories for the development of pulmonary hypertension secondary to chronic lung disease. This would allow clinicians to identify those infants in need of further investigation with echocardiography and cardiac catheterisation. It may also help to identify infants who may benefit from medications that lower pulmonary pressures such as sildenifil. It could also facilitate further study into the optimum management of oxygen saturation targeting in this vulnerable group of infants.

We hypothesise that NTpBNP levels in extremely low gestational age neonates increase with increasing severity of lung disease and that those with the highest NTpBNP levels have the highest risk of recurrent hypoxemia.

We also hypothesise that those with the highest late NT-pBNP levels will demonstrate more cardiac dysfunction, in particular right ventricular dysfunction with raised pulmonary artery pressure in the most severely affected.

Study aims

1. Determine the range of NTpBNP levels in infants born at <30 weeks gestation at days 3, 10, 28 and at 36 weeks post conceptual age.
2. Correlate the NTpBNP levels with severity of BPD as scored by the NICHD workshop scale and with documented hypoxemia as recorded by Massimo continuous pulse oximeter.
3. Correlate the NTpBNP levels with currently used echocardiographic measures of pulmonary artery pressure.
4. Add to the body of knowledge regarding late cardiac function as shown by echocardiography in neonates born at extremely low gestational age by studying some novel echocardiographic parameters.

Participants

• Infants born at < 30 weeks gestation and cared for in Christchurch Neonatal Intensive Care Unit.

Exclusion criteria

• known structural airway or lung anomalies
• congenital anomalies of the pulmonary arteries or pulmonary veins
• major systemic vessel-to-PA collateral vessels
• congenital heart disease (except those with patent ductus arteriosus, patent foramen ovale or atrial septal defect)
• severe liver disease
• persistent pulmonary hypertension of the newborn

References

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Contacts

Principal Investigator

Dr Sarah Harris
Christchurch Women's Hospital
2 Riccarton Avenue, Christchurch Central
Christchurch 8011
Email sarah.harris@otago.ac.nz

Associate Professor Nicola Austin
Neonatal Paediatrician
Christchurch Women's Hospital
2 Riccarton Avenue, Christchurch Central
Christchurch 8011

Funding body

• Freemasons New Zealand Fellowships in Paediatrics and Child Health
• Maurice & Phyllis Paykel Trust