Respiratory Disorders in The Newborn

Development of the Lung

The development of the lung involves two main aspects:

• Alveolar Development

  The respiratory system's formation begins as an embryonic bud from the foregut, which then divides and branches into various phases:

  1. Embryonic phase (through week 5): In this phase, the proximal airway begins to develop. Anomalies at this stage can lead to conditions like agenesis or tracheoesophageal fistula (TOF).
  2. Pseudoglandular Phase (week 5-16): This phase focuses on the development of the lower conducting airway and marks the closure of the diaphragm.
  3. Canalicular Phase (week 17-24): During this stage, gas exchange acini, specifically the respiratory bronchioles, start to form, with capillaries closely associated.
  4. Terminal Sac Phase (Week 24-37): Further development of the acini occurs in this phase, with capillary invasion becoming more extensive.
  5. Alveolar Phase (Week 37 – 3 years): This phase continues the proliferation and development of alveoli, critical for gas exchange.

• Vascular Development

  Alongside alveolar development, the vascular system of the lung undergoes changes, including:

  • An increase in the length and diameter of pulmonary arteries.
  • Muscularization of fetal pulmonary arteries, which is essential for proper blood flow and oxygen exchange.

The respiratory system plays a vital role in oxygen (O2) transport and delivery to tissues, and its normal physiology involves several key factors:

• Oxygen Transport in Blood

  Oxygen is carried in the blood through chemical binding with hemoglobin (Hb) and, to a lesser extent, in physical solution.

  The binding of O2 to Hb is typically expressed as a percentage saturation, known as SaO2 (arterial oxygen saturation).

• Determinants of Oxygen Delivery

  Oxygen delivery to tissues is influenced by several factors, including:

  • Cardiac Output: The volume of blood pumped by the heart per minute.
  • Total Hemoglobin Concentration: The amount of hemoglobin available to bind with oxygen.
  • Arterial PO2 (Partial Pressure of Oxygen): The oxygen pressure in arterial blood.
  • Hemoglobin Affinity for Oxygen: How readily hemoglobin binds with oxygen.

• Transition from Fetal to Postnatal Life

  Before birth, the lung is a fluid-filled organ, receiving approximately 10-15% of the total cardiac output.

  Within the first minutes of life, a significant portion of the fluid is absorbed, and the lungs fill with air, leading to an eight to tenfold increase in blood flow.

  The process of fluid reabsorption is facilitated by various mechanisms:

  • During passage through the vaginal canal, mechanical squeezing helps expel fluid from the lungs.
  • During labor, increased production of β-agonists results in ultrafiltration of fluid into the pulmonary system.
  • Increased surfactant synthesis and release help maintain surface tension, preventing the leakage of fluid back into the alveoli.

Elements of Normal Respiration and Causes of Respiratory Distress

Normal respiration is a complex process that depends on several essential elements:

• Stable Ribcage (Non-compliant)

  Providing a stable ribcage is crucial for normal respiration.

• Compliant Lungs (Gas Exchange Surface)

  The lungs must be compliant, allowing efficient gas exchange at their surfaces.

• Patent Air Passages (Conduction of Gases)

  Air passages must be patent and unobstructed to facilitate the conduction of gases.

• Mature and Well-Coordinated High Centre Control

  High-level control centers in the central nervous system must be mature and well-coordinated. These centers monitor and adjust the respiratory strategy.

• Peripheral Mechanical and Chemical Sensors

  Peripheral sensors, both mechanical and chemical, play a crucial role in regulating respiration.

• Adequate Pulmonary Circulation

  Efficient pulmonary circulation is necessary to support the respiratory process.

Respiratory distress can occur when there is interference with any of these essential mechanisms, leading to impaired breathing and oxygen exchange.

Respiratory difficulties in newborns often result from changes in normal respiration due to various factors:

• Inadequate Oxygen Supply

  Inadequate oxygen supply to tissues.

• Disorders of Acid-Base Balance

  Disorders affecting acid-base balance.

• Local and Central Effects

  Local or central effects on normal respiratory mechanisms, often caused by various local or systemic problems.

These factors can lead to critical conditions such as hypoxemia, acidosis (with or without hypercapnea), and postpartum asphyxia, endangering the baby's life due to insufficient tissue oxygenation and abnormal biochemical conditions.

The primary goals of therapy for newborns with respiratory diseases are as follows:

1. Ensure Adequate Oxygenation
2. Correct Acid-Base Imbalances
3. Identify the Underlying Cause
4. Administer Adequate Calories
5. Monitor the Patient's Condition

Effective treatment and care are essential to optimize the respiratory health of newborns and ensure their well-being.

• Cyanosis

  Bluish discoloration of the mucous membranes and extremities.

• Grunting

  Expiratory sound during breathing.

• Retraction

  Chest wall in-drawing, indicating increased effort during breathing.

• Tachypnea

  Rapid breathing characterized by a high respiratory rate.

• Apnea

  Cessation of breathing, temporary stoppage of respiratory efforts.

• Shock

  Severe hypotension or decreased tissue perfusion, often associated with respiratory distress.

Pulmonary Causes

• Lungs:

  • Difficult Transition
  • Transient Tachypnea of the Newborn
  • Aspiration Syndromes:
  • Meconium
  • Amniotic Fluid
  • Tracheoesophageal Fistula (TOF)
  • Feeding-related
  • Respiratory Distress Syndrome
  • Pneumonia
  • Pneumothorax
  • Pulmonary Hypoplasia / Diaphragmatic Hernia
  • Pulmonary Hemorrhage

Upper Airway Obstruction

• Choanal Atresia
• Laryngo/Tracheomalacia
• Laryngeal Web

Rib Cage Causes

• Rib Cage Deformity
• Fractured Rib

Diaphragm Causes

• Paralysis in Association with Upper Brachial Plexus
• Eventration

Extra Pulmonary Causes

• Vascular:

  • Persistent Fetal Circulation
  • Congenital Heart Defects (CHDs)
  • Polycythemia
  • Anemia

• Metabolic:

  • Acidosis
  • Hypothermia

• Neuromuscular:

  • Cerebral Edema
  • Phrenic Nerve Damage
  • Drugs (e.g., Theophylline Toxicity)

Difficult Transition is a common cause of respiratory distress in newborns, typically presenting at birth with the following characteristics:

• Onset: Presents at birth
• Features: Frothy secretions from the mouth and continuous sneezing
• Treatment: Some cases may require oxygen supplementation
• Resolution: Most infants typically normalize within four hours of age

Contributory factors to Difficult Transition include:

• Inadequate Suction: Poor suctioning of the mouth and nostrils during delivery
• Precipitous Delivery: Rapid and unplanned deliveries can contribute to this condition
• Hypothermia: Exposure to cold temperatures can exacerbate the transition difficulties

Predisposing Factors:

• Fetal Distress: Conditions that stress the fetus during labor and delivery.
• Maternal Sedation: Use of sedative drugs by the mother during labor.
• Maternal Diabetes Mellitus: Presence of diabetes in the mother.
• Delivery by Cesarean Section without Labor: Babies born via C-section without the initiation of natural labor.

Presentation:

• Common Among Borderline Preterm Infants: Frequently observed in infants born close to full term.
• Presence of One or More Risk Factors: Infants with any of the mentioned risk factors.
• Tachypnea with Respiratory Rate (RR): Rapid breathing, with RR typically ranging between 60-120 breaths per minute.
• Grunting: Some infants may exhibit grunting sounds during breathing.
• Resolution: Symptoms usually resolve within 48-72 hours (typically within 24 hours).
• Hypoxemia at Room Air: Low oxygen levels in the blood while breathing room air, which can be corrected by providing oxygen with an FiO2 (fraction of inspired oxygen) of 0.40.
• Rarely Requires Ventilatory Support: Most cases do not necessitate the use of mechanical ventilation.

Chest X-Ray Findings:

• Hyperinflation of the Lungs: Increased lung volume seen on X-ray.
• Prominent Vascular Markings: Enlarged blood vessels in the lung fields visible on the X-ray image.

Management:

• Self-Limiting Condition: Transient Tachypnea typically resolves on its own.
• Oxygen Therapy: Oxygen therapy is rarely needed and is usually provided at an FiO2 of 0.4 or lower.
• Complete Recovery: Most infants recover fully without any long-term pulmonary issues.

Definition:

Persistent Pulmonary Hypertension is characterized by the persistent elevation of Pulmonary Vascular Resistance (PVR), leading to a right-to-left shunt (through the ductus arteriosus or foramen ovale) and resulting in hypoxemia.

Risk Factors:

• Post-Term Delivery: Babies born after the full-term gestation period.
• Placental Insufficiency: Inadequate functioning of the placenta, affecting oxygen and nutrient supply to the fetus.
• Meconium Staining: Presence of meconium (fetal stool) in the amniotic fluid, which can be inhaled by the baby.
• Perinatal Asphyxia: Oxygen deprivation during birth and immediate postnatal period.
• Bacterial Pneumonia/Sepsis: Infection in the lungs or systemic infection.
• Hypoglycemia: Low blood sugar levels in the newborn.
• Hypothermia: Abnormally low body temperature.
• Polycythemia: Elevated levels of red blood cells in the blood.

Pathophysiology:

PPHN can result from both maladaptation and maldevelopment of the pulmonary vascular system.

• Maladaptation: In this scenario, the pulmonary vascular bed is structurally normal, but Pulmonary Vascular Resistance remains high. PPHN is primarily due to active vasoconstriction of the pulmonary vessels.
• Maldevelopment: Here, the pulmonary vessels are structurally abnormal, which can lead to impingement on the vascular lumen, further increasing Pulmonary Vascular Resistance (PVR).

Presentation of PPHN

• Labile Hypoxemia: Characterized by variable oxygen levels that are disproportionately low compared to lung parenchymal disease.
• Affected Infants: PPHN is most commonly observed in term infants.
• History of Risk Factors: Presence of risk factors, such as those previously mentioned, should be considered during evaluation.
• Loud Single S2: A loud second heart sound (S2) may be heard on auscultation.

Management of PPHN

• Self-Limiting: PPHN is often self-limiting, and treatment primarily involves supportive care.
• Optimal Thermal Environment: Maintain the infant in a neutral thermal environment to reduce oxygen demand.
• Correction of Underlying Problems: Address and correct any underlying conditions or risk factors.
• Enhance Pulmonary Blood Flow (PBF) and Reduce R to L Shunting: This can be achieved by:
• Providing oxygen and correcting acidosis.
• Using medications like sildenafil to relax pulmonary vessels and reduce resistance.
• Hyperoxia Test: A diagnostic test that involves exposing the baby to 100% oxygen and monitoring the response:
• If oxygen saturation improves significantly, it suggests that the baby may benefit from increased oxygen supply.
• Hyperventilation may also be considered during the test.

Infection of the lungs in newborns (NB) can be acquired through various means, including:

• Transplacentally: Infection can occur from the mother to the fetus during pregnancy.
• During the Birth Process: Newborns can acquire infections during delivery.
• Postnatally: Infections can also be acquired after birth.

Aetiology

The causative agents of pneumonia in newborns may include:

• Gram-Negative Enteric Bacilli: Such as E. coli and Klebsiella.
• Group B Streptococcus: A common bacterial cause.
• Listeria Monocytogenes: An uncommon but serious pathogen.
• Staphylococcus: Including Staphylococcus aureus.

Presentation

The presentation of pneumonia depends on the onset and severity of the infection. Common clinical features include:

• Respiratory Distress:
• Tachypnea (rapid breathing) and chest wall in-drawing (retraction of the chest wall) are characteristic signs of respiratory distress.
• Fever:
• Fever may be present, indicating an infectious process.
• Early Onset Types:
• Early onset pneumonia types may be challenging to distinguish from Respiratory Distress Syndrome (RDS), another common respiratory condition in newborns.

Chest X-Ray Findings

Chest X-rays in newborns with pneumonia may reveal:

• Patchy Opacity:
• Patchy opacities are often seen bilaterally in the lungs.

Management

The management of pneumonia in newborns typically involves:

• Supportive Care: Providing supportive care to maintain the newborn's overall well-being.
• Antibiotics: Administering antibiotics to target the specific causative pathogens and resolve the infection.

Amniotic fluid aspiration refers to the inhalation of amniotic fluid by the newborn during the peripartum period. This condition can have several consequences:

• Dilution of Surfactant: Amniotic fluid aspiration may lead to the dilution of pulmonary surfactant, a substance essential for proper lung function.
• Respiratory Distress: Newborns who aspirate amniotic fluid often exhibit signs of respiratory distress shortly after birth.
• Progressive Symptoms: The respiratory distress experienced by affected infants tends to worsen over the next few hours after birth.
• Peak Symptoms: Symptoms typically reach their peak severity within 24 to 48 hours after birth.
• Steady Improvement: Following the peak of symptoms, affected infants usually show a steady improvement in their respiratory condition.

Meconium Aspiration Syndrome (MAS) is a condition in which a newborn aspirates meconium, leading to chemical pneumonitis and mechanical obstruction of the bronchi following delivery.

• Meconium-Stained Amniotic Fluid (MSAF): MSAF occurs in approximately 9-20% of deliveries and is characterized by the presence of meconium in the amniotic fluid.
• Nature of Meconium: Meconium is a viscous, greenish fluid that fills the fetal gastrointestinal tract. It consists of gastrointestinal secretions, cellular debris, bile, pancreatic juice, mucus, lanugo, and vernix.
• In Utero Meconium Passage: Meconium passage in utero may occur in response to hypoxia, leading to a transient period of hyperperistalsis and relaxation of the anal sphincter. It can also happen as a normal physical event during gut maturation.
• Aspiration Occurrence: Aspiration of meconium may occur in utero as the compromised fetus begins to gasp. However, it more frequently occurs with the initial breaths taken after delivery.
• Severity in Post-Term Infants: MAS is often most severe in post-term infants who have reduced amniotic fluid volume. The less dilute and thicker meconium in these cases is more likely to cause airway obstruction.
• Pathogenesis: MAS involves several pathogenic mechanisms, including:
  • Acute Airway Obstruction: Meconium can mechanically obstruct the airways, acting like a ball valve. This obstruction contributes to air trapping, leading to an increased anterior-posterior (AP) diameter of the chest and an increased functional residual capacity. Complete obstruction of small airways may result in regional atelectasis.
  • Decreased Lung Tissue Compliance: MAS can lead to decreased lung tissue compliance, often accompanied by persistent pulmonary hypertension (PPHN).
  • Lung Parenchymal Damage: Meconium aspiration can cause damage to lung parenchyma.

Clinical Presentation

• Diagnostic Sign: The presence of meconium below the vocal cords on direct laryngoscopy defines MAS.
• Respiratory Distress at Birth: Infants with MAS typically exhibit respiratory distress immediately after birth.
• Progressive Worsening: The respiratory distress progressively worsens during the first 48 hours of life.
• Peak Symptoms: After the initial worsening, MAS reaches its peak severity over the next 3-4 days.
• Slow Improvement: Following the peak, there is slow but gradual improvement over the next 5-10 days.
• Mediastinal Shift: In some cases, air leaks associated with MAS may cause mediastinal shift.

RDS is a syndrome caused by deficient surfactant, clinically characterized by respiratory distress in preterm infants.

Previously Known as HMD (Hyline Membrane Disease)

Risk Factors:

• Prematurity: The incidence increases with decreasing gestational age (GA).
• Male Sex
• Maternal Diabetes
• Non-Black Races

Surfactant Composition:

• Surfactant, or surface-acting material, is an apolipoprotein produced by type II alveolar epithelial cells.
• It is composed of phospholipids (81%), with small amounts of neutral fat (5%), cholesterol (4%), and protein (10%).
• The primary active molecule is saturated dipalmitoyl phosphatidylcholine (DPPC).

Mechanism of Action:

• Surfactant works by lowering the surface tension at the alveolar air-fluid interface, reducing the pressures required to expand the alveoli.
• This action follows Laplace's law: P = 2T/R, where T represents tension, and R stands for radius.
• By lowering T, the pressure (P) required for alveolar expansion is reduced, leading to an increase in compliance (Compliance = ΔV/ΔP).
• Surface tension varies with the size of the alveoli, helping to equilibrate pressure in adjacent alveoli. This prevents smaller alveoli from emptying into larger ones.

Consequences of Surfactant Deficiency

• The alveolar collapse occurs due to insufficient surfactant.
• Increasing interstitial edema independently worsens lung compliance and impairs surfactant production and function, perpetuating the process.
• Overdistended alveoli are interspersed with collapsed alveoli, with overdistension potentially predisposing to air leaks.
• Overall respiratory effort becomes inefficient and ineffective.

Clinical Presentation

• The typical history involves a preterm baby with respiratory distress at birth.
• Infants exhibit tachypnea, retractions, and grunting respiration.
• Cyanosis is observed at room air, and breath sounds are diminished.
• Respiratory distress presents shortly after delivery or within the first hour and progressively worsens.
• It reaches a peak at 72 hours, maintaining the plateau for another 48 hours, followed by gradual resolution over 5 days.
• The total course lasts about 10 days if there are no complications.
• Improvement is often heralded by diuresis.

X-ray Findings

• Diminished lung volume is observed.
• There is a diffuse reticular, granular, ground glass appearance with air bronchogram.
• When severe, complete whiteout may be present on the X-ray.

Prevention

• Avoid preterm delivery if possible.
• Administer corticosteroids before delivery if preterm delivery is inevitable.
• Use 12mg betamethasone intramuscularly every 12 hours for at least 24 hours.

Treatment

• Surfactant replacement therapy is administered through endotracheal (ET) intubation.
• There are two types of surfactant therapy:
• Prophylactic therapy: Surfactant is instilled in the trachea soon after birth before the diagnosis of RDS can be established. This is indicated, especially if gestational age (GA) is less than 30 weeks.
• Rescue therapy: Used for the treatment of established RDS.

Careful Assessment and Resuscitation

Obtain a detailed history, including onset, progression, activity impact, and feeding patterns.

Ensure Adequate Ventilation and Oxygenation

Provide respiratory support and oxygenation as needed.

Maintain Acid-Base Homeostasis

Monitor and manage acid-base balance.

Monitor Blood Gases

Regularly assess blood gases, including PO2, PCO2, pH, and SpO2.

Manage Fluid and Electrolyte Balance

Ensure proper hydration and electrolyte levels, and provide necessary calories.

Infection Surveillance and Control

Implement infection control measures and monitor for signs of infection.

Maintain Neutral Thermal Environment

Ensure the baby's body temperature remains within a normal range to prevent temperature-related complications.

Specific Therapy

Administer targeted therapies based on the underlying cause of respiratory distress.