Bronchopulmonary dysplasia

Bronchopulmonary dysplasia also known as arrest of lung development, evolving chronic lung disease, neonatal chronic lung disease or respiratory insufficiency, is a serious lung condition that affects newborns. Bronchopulmonary dysplasia mostly affects premature newborns (infants born early whose lungs were not fully developed at birth) who need high levels of oxygen therapy, which is oxygen given through nasal prongs, a mask, or a breathing tube, for a long period. Bronchopulmonary dysplasia can also occur in very ill infants who were on a breathing machine (ventilator). Despite significant advances in preterm infant care in the past few decades, including the development of surfactant as well as newer and gentler modes of ventilation, the prevalence of bronchopulmonary dysplasia continues to remain high ¹. These new strategies have allowed the survival of very low birth weight infants and resulted in a change in the characteristics of bronchopulmonary dysplasia. Jobe ² coined the term “new bronchopulmonary dysplasia” in 1999 to describe the chronic lung disease in preterm infants at that time. This “new bronchopulmonary dysplasia” demonstrated much less airway damage and alveolar septal fibrosis when compared to “old bronchopulmonary dysplasia” which was characterized by dysmorphic microvasculature and alveolar simplification.

The highest observed rate of bronchopulmonary dysplasia is in infants born at a lower gestational age and lower birth weight ³. The data from the neonatal research network reports the incidence of bronchopulmonary dysplasia in very low birth weight infants (birth weight less than 1500 grams) to be 40 to 68% depending on the definition of bronchopulmonary dysplasia used. This incidence was found to be inversely proportional to the gestational age of the infant ⁴. The other demographic risk factors associated with bronchopulmonary dysplasia include male sex, low birth weight, white race, impaired growth for gestational age and family history of asthma ³.

Most newborns who develop bronchopulmonary dysplasia are born more than 10 weeks before their due dates, weigh less than 2 pounds at birth, and have breathing problems. Infections that occur before or shortly after birth also can contribute to bronchopulmonary dysplasia.

Most babies who develop bronchopulmonary dysplasia are born with respiratory distress syndrome. Respiratory distress syndrome is a breathing disorder that mostly affects premature newborns. If premature newborns still require oxygen therapy by the time they reach 36 weeks gestation, they are diagnosed with bronchopulmonary dysplasia.

Some newborns may need long-term oxygen or breathing support from nasal continuous positive airway pressure machines, ventilators, and medicines like bronchodilators. They may continue to have breathing problems throughout childhood and even into adulthood.

As children who have bronchopulmonary dysplasia grow, their parents can help reduce the risk of bronchopulmonary dysplasia complications. Parents can encourage healthy eating habits and good nutrition. They also can avoid cigarette smoke and other lung irritants.

Bronchopulmonary dysplasia causes

Bronchopulmonary dysplasia is a type of neonatal respiratory disease that develops as a result of a newborn’s lungs not developing normally while the baby is growing in the womb or not developing fully if the baby was born premature. These babies’ lungs are fragile and can be easily irritated or inflamed after birth. Ventilation, high levels of oxygen, or infections can also damage premature newborns’ lungs.

Bronchopulmonary dysplasia is a multifactorial pathology that is influenced by a variety of prenatal and postnatal factors affecting the mother and infant. The various prenatal risk factors that influence the development of bronchopulmonary dysplasia include ⁵:

• Lack of antenatal steroids
• Maternal smoking
• Pregnancy-induced hypertension/preeclampsia
• Hypoxia
• Maternal infection, including chorioamnionitis
• Genetic susceptibility
• Congenital anomalies causing pulmonary hypoplasia

Similarly, various postnatal factors predispose premature infants to develop bronchopulmonary dysplasia including:

• Lung immaturity
• Poor nutrition
• Need for mechanical ventilation. Newborns who have breathing problems or cannot breathe on their own may need ventilator support. Ventilators are machines that use pressure to blow air into the airways and lungs. Although ventilator support can help premature newborns survive, the machine’s pressure might irritate and harm the babies’ lungs. For this reason, doctors only recommend ventilator support when necessary.
• Oxygen injury. Newborns who have breathing problems might need oxygen therapy. This treatment helps the newborns’ organs get enough oxygen to work well. However, high levels of oxygen may inflame the lining of the lungs and injure the airways. Also, high levels of oxygen can slow lung development in premature newborns.
• Infections or sepsis. Infections may inflame the lungs. As a result, the airways narrow, which makes it harder for premature newborns to breathe. Lung infections also increase the babies’ need for extra oxygen and breathing support.

Risk factors for bronchopulmonary dysplasia

Risk factors for bronchopulmonary dysplasia include:

• Congenital heart disease (problem with the heart’s structure and function that is present at birth)
• Prematurity, usually in infants born before 32 weeks gestation
• Severe respiratory or lung infection

The more premature a newborn is and the lower his or her birth weight, the greater the risk of bronchopulmonary dysplasia. Most newborns who develop bronchopulmonary dysplasia are born more than 10 weeks before their due dates, weigh less than 2 pounds at birth, and have breathing problems. Infections that occur before or shortly after birth also can contribute to bronchopulmonary dysplasia.

The number of babies who have bronchopulmonary dysplasia is higher now than in the past. This is because of advances in care that help more premature newborns survive.

Many babies who develop bronchopulmonary dysplasia are born with serious respiratory distress syndrome. However, some babies who have mild respiratory distress syndrome or do not have respiratory distress syndrome also develop bronchopulmonary dysplasia.

Studies show that genetic factors may also play a role in causing bronchopulmonary dysplasia, but more studies are needed.

Bronchopulmonary dysplasia prevention

Taking steps to ensure a healthy pregnancy might prevent your newborn from being born before his or her lungs have fully developed. These steps include:

• Following a healthy eating plan
• Managing any medical conditions you have
• Not smoking and avoiding tobacco smoke, alcohol, and illegal drugs
• Preventing infections
• Seeing your doctor regularly during your pregnancy

Your doctor may give you injections of a corticosteroid medicine if he or she thinks you may give birth too early. This medicine can speed up development of the lungs, brain, and kidneys in your baby and surfactant production. Usually, within about 24 hours of your taking this medicine, the baby’s lungs start making enough surfactant. This will reduce the newborn’s risk of respiratory distress syndrome, which can lead to bronchopulmonary dysplasia.

Bronchopulmonary dysplasia symptoms

Bronchopulmonary dysplasia symptoms may include any of the following:

• Bluish skin color (cyanosis)
• Cough
• Rapid breathing
• Shortness of breath

Many babies who develop bronchopulmonary dysplasia are born with serious respiratory distress syndrome. A first sign of bronchopulmonary dysplasia is when premature newborns—usually those born more than 10 weeks early—still need oxygen therapy by the time they reach 36 weeks gestation.

Newborns who have severe bronchopulmonary dysplasia may have trouble feeding, which can lead to delayed growth. These babies also may develop:

• Pulmonary hypertension, which is increased pressure in the pulmonary arteries. These arteries carry blood from the heart to the lungs to pick up oxygen.
• Cor pulmonale, which is failure of the right side of the heart. Ongoing high blood pressure in the pulmonary arteries and the lower right chamber of the heart causes this condition.

Bronchopulmonary dysplasia complications

Babies who have had bronchopulmonary dysplasia are at greater risk for repeated respiratory infections, such as pneumonia, bronchiolitis, and respiratory syncytial virus (RSV) that require a hospital stay.

Other possible complications in babies who have had bronchopulmonary dysplasia are:

• Systemic hypertension
• Poor neurodevelopmental outcome
• Pulmonary hypertension (high blood pressure in the arteries of the lungs)
• Left ventricular hypertrophy and left ventricular dysfunction
• Developmental problems
• Poor growth
• Long-term lung and breathing problems

Bronchopulmonary dysplasia diagnosis

Newborns who are born early, usually more than 10 weeks before their due dates and still need oxygen therapy by the time they reach their original due dates are diagnosed with bronchopulmonary dysplasia. The diagnosis of bronchopulmonary dysplasia is made clinically based on the gestational age, postmenstrual age, oxygen exposure and oxygen requirement at 36 weeks postmenstrual age. In 2001, the National Institute of Child Health and Human Development workshop proposed the current definition where infants born at less than or equal to 32 weeks gestational age with 28 days of oxygen exposure get diagnosed with mild, moderate or severe bronchopulmonary dysplasia at 36 weeks postmenstrual age based on their respiratory support at that time ⁶. This definition still has many deficiencies and does not adequately predict respiratory outcomes; hence in 2016, the National Institute of Child Health and Human Development workshop on bronchopulmonary dysplasia proposed a revision of this definition. The suggested refinement suggests utilizing radiographic confirmation and accounts for the newer modes of non-invasive ventilation ⁷. Although this new definition classifies bronchopulmonary dysplasia further, it does not address the primary limitation of utilizing the treatment modality as the primary factor defining the disease and its severity ⁸.

Bronchopulmonary dysplasia can be mild, moderate, or severe. The diagnosis depends on how much extra oxygen a baby needs at the time of the original due date. It also depends on how long the baby needs oxygen therapy.

To help confirm a diagnosis of bronchopulmonary dysplasia, doctors may recommend tests, such as:

• Chest X-ray to show large areas of air and signs of inflammation or infection in the lung seen in severe cases of bronchopulmonary dysplasia. A chest X-ray also can detect problems, such as a collapsed lung, and show whether the lungs are not developing normally.
• Blood tests to see whether a newborn has enough oxygen in the blood. Blood tests also can help determine whether an infection is causing the newborn’s breathing problems.
• Echocardiography (echo) to rule out heart defects or pulmonary hypertension as the cause of the newborn’s breathing problems.

Bronchopulmonary dysplasia treatment

The main aim in the management of infants with bronchopulmonary dysplasia is to support them while lung growth occurs, limit further injury to the lungs, optimize lung function and detect complications associated with bronchopulmonary dysplasia. Once doctors diagnose bronchopulmonary dysplasia, some or all of the treatments used for respiratory distress syndrome will continue in the neonatal intensive care unit (NICU).

Treatment of bronchopulmonary dysplasia usually includes breathing support with a nasal continuous positive airway pressure (NCPAP) machine or a ventilator, other supportive treatments, and other procedures and treatments. The various measures employed in the care of these infants are:

• Nutrition: Infants with bronchopulmonary dysplasia need an increased amount of energy to promote lung growth and repair. Their nutritional need maybe up to 140 to 150 Kcal/Kg/day and protein intake from 3.5 to 4 g/kg/day ⁹. Breast milk is preferable to formula. Commercial milk fortifiers can be used to fortify the mother’s milk or donor breast milk to higher calories ¹⁰. Intramuscular supplementation of vitamin A started within a few days of birth and administered three times a week for 4 weeks has been shown to decrease the risk of bronchopulmonary dysplasia by 7% ¹¹.
• Fluid restriction: Based on the severity of their lung disease, infants are restricted to a total fluid volume of 120 to 150 ml/kg/day. Restriction of fluid intake allows for improved pulmonary function by preventing pulmonary edema and improving gas exchange. Although frequently followed, there is insufficient data to support this practice ¹².
• Minimize ventilator-associated lung injury: Newborns who have bronchopulmonary dysplasia often need breathing support, or oxygen therapy, until their lungs start making enough surfactant. Non-invasive ventilation is the preferred mode of ventilation wherever feasible. Until recently, a mechanical ventilator usually was used. The ventilator was connected to a breathing tube that ran through the newborn’s mouth or nose into the windpipe. Today, more and more newborns are receiving breathing support from nasal continuous positive airway pressure (NCPAP). Nasal continuous positive airway pressure gently pushes air into the baby’s lungs through prongs placed in the newborn’s nostrils. If mechanical ventilation is necessary, care should be taken to limit barotrauma and volutrauma. Early extubation has been shown to lower the rates of bronchopulmonary dysplasia ¹³.
• Minimize oxygen associated injury: Exposure to hyperoxia is one of the most critical factors in the pathogenesis of bronchopulmonary dysplasia. There is significant controversy regarding SpO target ranges. One approach attempts to target SpO of 88-94% with a lower alarm limit of 88% and a higher alarm limit of 96% ¹⁴.
• Pharmacological interventions:
  • Corticosteroids: Systemic corticosteroids have been used in bronchopulmonary dysplasia to improve lung function, reduce inflammation and reduce the need for mechanical ventilation. However, concerns about long term neurodevelopmental outcomes have led to recommendations to restrict their use to infants with severe bronchopulmonary dysplasia who remain ventilator dependent with high oxygen needs ¹⁵. Despite many clinical trials, it is unclear as to which corticosteroid provides the most benefit and at the optimal dose. Notwithstanding the variable evidence, low dose dexamethasone and hydrocortisone continue to be used in practice in the treatment of bronchopulmonary dysplasia ¹⁶. The current data does not demonstrate support for the routine use of inhaled corticosteroids to prevent bronchopulmonary dysplasia ¹⁷.
  • Diuretics: Thiazides and loop diuretics are the most commonly used diuretics in the setting to improve short term pulmonary mechanics of bronchopulmonary dysplasia. These agents are most commonly used in infants who are ventilator dependent with increasing requirement of positive end-expiratory pressure despite fluid restriction. A systemic review of available literature does not show any improvement in long term clinical outcome in infants with established or developing bronchopulmonary dysplasia ¹⁸.
  • Bronchodilators: Administration of beta-2 agonists can decrease airway resistance and improve compliance. However, their routine use is not recommended in bronchopulmonary dysplasia as it has not been shown to improve long term outcomes. Their use should be restricted to manage acute episodes of bronchoconstriction in older infants who remain ventilator dependent ¹⁹.

Other procedures and treatments

Newborns who have bronchopulmonary dysplasia may spend several weeks or months in the hospital. This allows them to get the care they need, which may include:

• Tracheostomy to provide long-term ventilator support. A tracheostomy is a surgically made hole. It goes through the front of the neck and into the trachea, or windpipe. Your child’s doctor will put the breathing tube from the ventilator through the hole. A tracheostomy can allow your baby to interact more with you and the NICU staff, start talking, and develop other skills.
• Physical therapy to help strengthen your child’s muscles and clear mucus out of the lungs.

At home

Infants with bronchopulmonary dysplasia may need oxygen therapy for weeks to months after leaving the hospital. Follow your health care provider’s instructions to ensure your baby gets enough nutrition during recovery. Your baby may need tube feedings or special formulas.

It is very important to prevent your baby from getting colds and other infections, such as respiratory syncytial virus (RSV). RSV can cause a severe lung infection, especially in a baby with bronchopulmonary dysplasia.

A simple way to help prevent respiratory syncytial virus (RSV) infection is to wash your hands often. Follow these measures:

• Wash your hands with warm water and soap before touching your baby. Tell others to wash their hands, too, before touching your baby.
• Ask others to avoid contact with your baby if they have a cold or fever, or ask them to wear a mask.
• Be aware that kissing your baby can spread respiratory syncytial virus (RSV).
• Try to keep young children away from your baby. RSV (respiratory syncytial virus) is very common among young children and spreads easily from child-to-child.
• DO NOT smoke inside your house, car, or anywhere near your baby. Exposure to tobacco smoke increases the risk of RSV illness.

Parents of babies with bronchopulmonary dysplasia should avoid crowds during outbreaks of RSV. Outbreaks are often reported by local news media.

Your baby’s provider may prescribe the medicine palivizumab (Synagis) to prevent RSV infection in your baby. Follow instructions on how to give your baby this medicine.

Bronchopulmonary dysplasia prognosis

Bronchopulmonary dysplasia is a chronic illness that persists beyond discharge from the hospital and into adulthood. Infants with bronchopulmonary dysplasia have a 50% chance of readmission to the hospital during their first year of life. They have an increased risk of developing reactive airway disease, asthma, emphysema, and respiratory syncytial virus (RSV) bronchiolitis. Bronchopulmonary dysplasia also affects their growth and neurodevelopmental outcome. Very low birth weight infants (birth weight less than 1000g) with bronchopulmonary dysplasia are more likely to have delays in fine and gross motor skills, and language ²⁰.

Infants with bronchopulmonary dysplasia are at high risk for cardiopulmonary sequelae like pulmonary hypertension, cor pulmonale, and systemic hypertension. A recent meta-analysis reported an accumulative estimated prevalence of pulmonary hypertension in bronchopulmonary dysplasia to be 20% and can be as high as 40% in severe bronchopulmonary dysplasia. A newer, prospective study showed that bronchopulmonary dysplasia-associated pulmonary hypertension (bronchopulmonary dysplasia-pulmonary hypertension) affects at least 8 to 25% of extremely low birth weight (birth weight less than 1000g) infants. Retrospective studies demonstrate a 2-year morbidity rate of 26 to 47% in patients with bronchopulmonary dysplasia-pulmonary hypertension ²¹.

Living with bronchopulmonary dysplasia

After your baby leaves the hospital, he or she will likely need follow-up care. It is important to follow your child’s treatment plan and get regular care. It is also important to take care of your mental health as you care for your baby at home.

Receive routine follow-up care

Your child will likely continue on all or some of the treatments that were started at the hospital, including:

• Medicines, such as bronchodilators, steroids, and diuretics.
• Oxygen therapy or breathing support from nasal continuous positive airway pressure (NCPAP) or a ventilator.
• Extra nutrition and calories, which may be given through a feeding tube.
• Preventive treatment with a medicine called palivizumab for severe RSV (respiratory syncytial virus). This common virus leads to mild, cold-like symptoms in adults and older, healthy children. However, in newborns—especially those in high-risk groups—respiratory syncytial virus can lead to severe breathing problems.

Your child also should have regular checkups with and timely vaccinations from a pediatrician, a doctor who specializes in treating children. If your child needs oxygen therapy or a ventilator at home, a pulmonary specialist might be involved in his or her care.

Ongoing health issues and developmental delays

Newborns who have bronchopulmonary dysplasia may have health problems even after they leave the hospital. These include:

• Delayed growth during their first two years. Children who survive bronchopulmonary dysplasia usually are smaller than other children of the same age.
• Increased risk for infections, such as colds and the flu. If these children develop respiratory infections, they may need to be treated in a hospital.
• Lung problems throughout childhood and even into adulthood. These problems can include underdeveloped lungs and asthma.
• Need for ongoing oxygen therapy or breathing support from nasal continuous positive airway pressure (NCPAP) or a ventilator. A pulmonary specialist may help with your child’s long-term care and make treatment recommendations.
• Trouble swallowing. This may put them at risk for getting food stuck in their airways. This condition is called aspiration, and it can cause infection. Children who have bronchopulmonary dysplasia may need help from a specialist to learn how to swallow correctly.

Babies who have very severe bronchopulmonary dysplasia also may develop other problems, such as:

• Apnea. This is a condition in which breathing stops for short periods.
• Poor coordination and muscle tone.
• Delayed speech and problems with vision and hearing.
• Learning problems.
• Gastroesophageal reflux disease (GERD). This is a condition in which the stomach contents back up into the esophagus during or after a feeding. The esophagus is the passage leading from the mouth to the stomach. GERD may lead to aspiration.

The risk of these complications increases in newborns who are very small at birth.

Prevent complications over your child’s lifetime

You can take steps to help manage your child’s bronchopulmonary dysplasia and help him or her recover.

• Try to prevent infection. Wash your hands often, and discourage visits from family and friends who are sick. Keep your baby away from large daycare centers and crowds to avoid colds, the flu, and other infections.
• Do not smoke in your home. Keep your baby away from cigarette smoke, dust, pollution, and other lung irritants.
• Make sure that your baby and your other children get their childhood vaccines and other treatments recommended by their doctors.
• Call your child’s doctor if you see any signs of respiratory infection. These may include irritability, fever, stuffy nose, cough, changes in breathing patterns, and wheezing.

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