Pulmonary hypertension (PH) occurs when the pressure in the vessels in the lung is abnormally high. Chronic pulmonary hypertension is an extremely rare life-limiting condition due to a wide range of heterogeneous conditions that can lead to a wide range of treatment strategies. The term neonatal pulmonary hypertension includes any baby first diagnosed at less than three months of age, corrected for prematurity. In contrast to children and adults with PH there are very few treatments approved for newborns with the condition and more research needs to be done to find medicines that can be used to treat these babies. Currently there exists no agreed set of outcomes specific for neonatal PH, which limits meaningful comparisons of different treatments across studies.
In simple terms, PH makes it more difficult for blood to flow through lung vessels, and the heart must work harder to pump blood around the body. This can cause strain on the heart. About one in every 500 babies develop PH and it can happen for lots of different reasons. The lung blood vessels can be underdeveloped or fail to open properly after birth because of complications during pregnancy and labour, infections, and lung malformations. It is also common in babies born prematurely, especially those who need extra support with their breathing for a long time. The heterogeneity of causes of PH in the newborn makes it a difficult disease to diagnose and manage. Unfortunately, having PH is a serious and life-threatening condition, and can lead to babies dying prematurely or having long-term symptoms.
Existing commonly used trial outcomes in both paediatric and adult PH, such as six-minute walk-test or invasive haemodynamic assessment, can not be applied to babies with PH [1]. This study proposes to construct a core outcome set (COS) for neonatal PH through identification of existing outcome measures used in clinical trials of babies diagnoses with neonatal PH and through engagement of stake holders including clinicians, nurses, allied health professionals, academics, and parents/guardians of current and former babies with neonatal PH.
Our work will follow methodology used on development of the recently published neonatal COS that covers outcomes encountered for all infants receiving neonatal care but is not disease specific [2]. We acknowledge the limitations of applying the neonatal COS to this population of patients. For example the presence and severity of chronic lung disease (CLD) is an outcome in the neonatal COS, reflecting a measure of general neonatal care for the developing lung in terms of growth, maturation, reduced trauma from ventilation strategies, or respiratory infection/inflammation. In the context of neonatal PH as a disease entity, CLD if present is either an aetiology for that phenotype or a disease co-morbidity rather than an outcome. Due to the chronic persistence of PH in some babies we anticipate that longer-term cardio-respiratory outcomes will be candidates for the NeoPH COS, which are not included in the neonatal COS. Moreover, given the rarity and heterogeneity of neonatal PH the outcomes specific to its management are not covered by the existing neonatal COS and hence should be addressed by a disease-specific COS.
Aim:
To agree a core outcome set in neonatal PH developed using consensus methodology involving clinicians, nurses, allied health professionals, academics, and parents/guardians.
Objectives:
1. To identify, review and explore outcomes that are relevant to parents or guardians of any current or former neonate or young infant diagnosed with PH less than 3 months of age, corrected for prematurity.
2. To determine which outcomes are recorded in clinical trials, observational studies and qualitative studies of neonates and infants with PH diagnosed less than 3 months of age, corrected for prematurity.
3. Through consensus methodology to confirm a final core outcome set in neonatal PH.
References
[1] Marius M Hoeper, Ronald J Oudiz, Andrew Peacock, et al. End points and clinical trial designs in pulmonary arterial hypertension: Clinical and regulatory perspectives. JACC. 2004; 43(12):48-55.
[2] Webbe JWH, Duffy JMN, Afonso E, Al-Muzaffar I, Brunton G, Greenough A, et al. Core outcomes in neonatology: development of a core outcome set for neonatal research. Arch Dis Child Fetal Neonatal Ed. 2020 Jul;105(4):425–31.
Chief Investigator and supervisor to Dr Cara Morgan:
Dr Nim Subhedar
Consultant Neonatologist
Liverpool Women’s NHS Foundation Trust
Qualitative study Principal Investigator:
Dr Kerry Woolfall
University of Liverpool
Qualitative study main contact and Co-investigator:
Dr Cara Morgan
Neonatal Research Fellow
Liverpool Women’s NHS Foundation Trust
Co-investigator and supervisor to Dr Cara Morgan:
Professor Chris Gale
Study Co-ordinator:
Katrina Reilly
Liverpool Women’s NHS Foundation Trust
Disease Category: Neonatal care
Disease Name: Pulmonary hypertension
Age Range: 0 - 0
Sex: Either
Nature of Intervention: Any
- Clinical experts
- Consumers (caregivers)
- Patient/ support group representatives
- Researchers
- Service providers
- COS for clinical trials or clinical research
- COS for practice
- Consensus meeting
- Delphi process
- Interview
- Literature review
We will use a mixed methods study design including interviews with parents/guardians of current or former patients, scoping review of the literature, Delphi survey and stakeholder consensus meeting.