Efo/persistent Fetal Circulation Syndrome

1. Disease Summary:

Persistent fetal circulation syndrome (PFCS), also known as persistent pulmonary hypertension of the newborn (PPHN), is a serious neonatal condition characterized by the failure of normal circulatory transition at birth. This results in sustained elevated pulmonary vascular resistance (PVR) and right-to-left shunting of blood through the ductus arteriosus and foramen ovale, leading to severe hypoxemia. PPHN can occur in term and preterm infants and is often associated with other conditions such as congenital diaphragmatic hernia, meconium aspiration syndrome, and respiratory distress syndrome. The condition can lead to significant morbidity and mortality if not adequately managed.

2. Global Prevalence and Disease Burden:

PPHN has an estimated prevalence of approximately 0.4 to 6.8 per 1000 live births in developed countries. The mortality rate associated with PPHN can range from 10% to as high as 50%, depending on the underlying causes and the effectiveness of treatment (Durward & Macrae, 2022, PMID: 36031529). Survivors often face long-term complications, including chronic lung disease, neurodevelopmental impairments, and other significant health issues, which can lead to increased healthcare costs and a substantial economic burden on families and healthcare systems.

3. Unmet Medical Need:

Despite advancements in the management of PPHN, several unmet medical needs persist:

Limited Treatment Options: Current first-line therapies, such as inhaled nitric oxide (iNO), are not universally available, especially in low- and middle-income countries (LMICs), where access to effective treatments is limited (Galis et al., 2024, PMID: 38745027). The high cost and scarcity of iNO hinder its use in many settings.
Inadequate Long-term Outcome Data: Most studies focus on short-term outcomes, such as changes in oxygenation and blood pressure, rather than long-term morbidity and mortality (Galis et al., 2024, PMID: 38745027). There is a critical need for large-scale, prospective studies that evaluate long-term outcomes, including neurodevelopmental impacts and quality of life for survivors.
Lack of Effective Alternatives: While milrinone has been suggested as a potential treatment, evidence supporting its efficacy remains limited, and there is a need for randomized controlled trials to establish its role in PPHN management (Galis et al., 2024, PMID: 38745027).
Variability in Management Practices: There is significant variability in treatment protocols across different neonatal intensive care units (NICUs), leading to inconsistent care and outcomes for infants with PPHN (Durward & Macrae, 2022, PMID: 36031529).

4. Current Treatment Options:

Current management strategies for PPHN include:

Inhaled Nitric Oxide (iNO): This is the first-line therapy for PPHN in high-income countries. It acts as a selective pulmonary vasodilator, improving oxygenation in approximately 60-70% of patients and reducing the need for ECMO (Lai et al., 2018, PMID: 28923474).
Extracorporeal Membrane Oxygenation (ECMO): This is used for severe cases where conventional therapies fail. However, ECMO is resource-intensive and associated with significant risks, including bleeding and infection.
Milrinone: This medication is being explored as an adjunct therapy for PPHN, but evidence for its effectiveness is still emerging, and it is not yet established as a standard treatment (Galis et al., 2024, PMID: 38745027).
Supportive Care: This includes optimizing ventilatory support, maintaining adequate systemic blood pressure, and treating underlying conditions contributing to PPHN.

5. Current Clinical Trials:

Ongoing clinical trials are investigating various aspects of PPHN management, including:

Milrinone as Monotherapy: Trials are needed to evaluate the efficacy of milrinone in LMICs where iNO is not available (Galis et al., 2024, PMID: 38745027).
Prostanoids and Their Analogues: Research is being conducted to assess the safety and efficacy of prostanoids in treating PPHN, with a focus on long-term outcomes (Shivanna et al., 2019, PMID: 31573068).

6. Additional Context:

The economic impact of PPHN is significant, as affected infants often require prolonged hospitalization, specialized care, and follow-up for long-term complications. The burden on healthcare systems can be substantial, particularly in regions with limited resources. Addressing the unmet medical needs in PPHN management is crucial for improving outcomes and reducing the long-term economic burden associated with this condition.