Introduction

Persistent Pulmonary Hypertension of the Newborn (PPHN) is a life-threatening condition characterised by elevated pulmonary vascular resistance (PVR) after birth. The pulmonary arterial pressure exceeds the systemic arterial pressure, resulting in right-to-left shunting of blood.¹ As a result, persistent hypoxia (low oxygen) and cyanosis (bluish skin) are observed in newborns due to decreased pulmonary blood flow.

Prevalence (existing cases) and incidence (new cases) of PPHN

PPHN is a critical condition in the newborn baby period, with new cases recorded in about 2 per 1000 live births and an estimated death rate ranging from 7.6% to 10.7% due to its complications.² It most often occurs in infants born during 34 to 37 weeks of gestation (late preterm). 

Causes of PPHN

Before we discuss the functional changes that occur in PPHN, we need to understand the normal gas exchange that takes place in the lungs of a newborn and how functional changes during the fetus-infant period can lead to PPHN.

Along with the first cry, the newborn completes their first breath, marking the success of the fetal to neonatal transition. The major functional changes in breathing and blood flow have now occurred. During the initial stage of the first breath, lung liquid is cleared, and some air remains in the lungs at the end of exhalation, allowing lung gas exchange to begin. This triggers a significant decrease in PVR, consequently increasing blood flow to the lungs and cardiac venous return.³ 

On the contrary, in PPHN, the PVR is elevated, resulting in decreased blood flow and low blood oxygen levels. If this condition persists or worsens, it may further damage heart function.⁴

There are several causes associated with PPHN, which can be classified into intrinsic and extrinsic factors:⁵

Intrinsic factors (newborn-related conditions):

• Lung parenchymal conditions, such as meconium aspiration syndrome, pneumonia, and acute respiratory distress syndrome in the newborn
• Congenital anomalies (present at birth) such as pulmonary hypoplasia (incomplete development of lung tissues) and transposition of the great arteries

Extrinsic factors (maternal-related conditions)

• Low amniotic fluid
• Gestational diabetes or diabetes history
• Gestational age 
• Obesity 
• Smoking 

Interestingly, the distribution patterns of the disease show deep links with ethnicity. It appears that Hispanic or Latino ethnicity is more protective against PPHN, but African or African-American ethnicity constitutes a high-risk population for developing PPHN.²

Signs and symptoms of PPHN? 

Midwives and doctors can identify symptoms of PHNN at birth. Most PPHN babies show breathing distress symptoms such as:

• Rapid breath 
• Rapid heart rate 
• Cyanosis
• Grunting or moaning within 24 hours after birth
• Abnormal appearance, such as retraction of skin under the ribs when breathing 

Babies with PPHN will require intensive care, and healthcare professionals will monitor oxygen saturation to measure the oxygen levels in their blood.

Diagnosis of PPHN?

Doctors will perform a clinical examination of the baby after birth. Infants with PPHN may exhibit a noticeable heave in the area in front of their heart, a symptom clinically referred to as a parasternal heave. These babies may also have a loud heart sound or murmurs around the chest area. Additionally, some infants may present with differential cyanosis (blue skin or lips) due to anoxia (lack of oxygen in the blood).

According to the Nationwide Children's Hospital, the evaluations of babies with suspected PPHN include: 

• Echocardiogram (echo scan): This painless test uses ultrasound (sound waves) to take a picture of the heart and blood vessels. It will show how the blood flows through the body
• Heart and lung monitoring⁶
• Standard blood tests: These tests help determine whether the baby has an infection. The results depend on changes in the number of blood cells and levels of blood sugar and blood pH
• Chest x-ray: It is used to visualise the lungs and determine if the baby has an enlarged heart

Treatment of PPHN 

The main goal of treating PPHN is to increase the oxygen flow to the baby's organs, thereby preventing serious complications or long-term health issues. The choice of treatment depends on the severity of PPHN and other factors such as the baby's age and general health condition.

Here are the common ways to manage PPHN suggested by NHS:

Supportive measures

These measures are important for successful management. Care should be taken to maintain normal body temperature, correct bodily processes such as blood sugar levels, and provide appropriate nutritional support.

Pharmacological interventions 

• Inhaled nitric oxide: It is the preferred first-line treatment for most PPHN cases as it decreases PVR in infants
• Inotropic agents: Dopamine and milrinone are commonly used medications to increase systemic blood pressure

Non-pharmacological approach

Also known as oxygen therapy. This treatment aims to improve the oxygenation in the lungs, achieve adequate lung volume, and reduce PVR resistance in infants. A high-frequency ventilator is usually used to facilitate the oxygen flow in the blood.

Long-term complications and developmental outcomes

The complications of infants presenting with PPHN depend on their individual conditions and the treatments they have received. However, some patients may experience significant long-term effects regardless of the treatment methods used.⁷ These complications can include hearing deficits, stroke, seizure, hypoxemia, heart failure, kidney failure, and lung diseases. Moreover, these complications may not be diagnosed in early childhood, which increases the likelihood of both physical and mental disabilities later in life.

Impact on Families

PPHN can be heartbreaking news for the parents. According to the National Institute of Health and Care Research, about 40% of parents have experienced anxiety or post-traumatic stress when their newborn baby needs intensive care.

If you are experiencing high levels of stress and anxiety, several resources are available to offer support to families:

• BLISS is a UK charity offering support and advice to anyone with a premature or sick baby
• The Pulmonary Hypertension Association is an American growing community of families with children affected by PH

FAQs

How long does it take to recover from PPHN?

Recovery time varies depending on the severity of the condition. It can take weeks or even months to recover from PPHN. In some cases, children may need to be transferred to the intensive care unit if their condition worsens.

What is the survival rate for infants with PPHN?

The overall survival rate for PPHN ranges from 10 to 50%.

How can I prevent PPHN? 

Unfortunately, healthcare researchers haven't yet found a way to prevent PPHN in newborns. However, you can reduce the risk during pregnancy by:

• Avoiding certain medications
• Controlling your weight and diabetes
• refraining from alcohol intake
• Avoiding smoking

Summary

PPHN is a condition that manifests at birth and can be identified within several hours after an infant is born. Infants with PPHN often exhibit abnormal blood oxygen levels, irregular breathing, an elevated heart rate, and a noticeable heave around the chest area. Additionally, their skin may appear blue. PPHN is a serious condition for infants, associated with high morbidity and mortality rates. Furthermore, some patients may only develop long-term complications later in childhood. Inhaled nitric oxide is currently the first-line therapy for PPHN. Providing supportive care for all family members is crucial in managing this condition.