Respiratory Distress in the Newborn Infant: Evaluation and Etiology

Theodore R. Thompson, M.D.

I. Respiratory Distress

A. Frequent Causes of Respiratory Distress in Newborn Infants

Medical	Surgical
Respiratory distress syndrome (RDS)	Pneumothorax
Wet lung (transient tachypnea, RDS II)	Diaphragmatic hernia/eventration
Aspiration syndromes (meconium, blood)	Lobar emphysema
Persistent pulmonary hypertension of the newborn	Esophageal atresia with or without TE fistula
Pneumonia/sepsis	Pleural effusion
Polycythemia - hyperviscosity	Cystic lesions
Pulmonary edema	Mass lesions
Hypoplastic lungs	Airway disorders (upper, laryngeal, lower)
Cardiac lesions	Phrenic nerve paralysis
Hypoglycemia
Hypovolemia
Central nervous system

B. Evaluation

1. History, physical examination
2. Downes' or RDS score - clinical
3. Arterial blood gases
   Pulse oximetry - SaO2
4. Chest x-ray
5. Serum glucose and calcium; central hematocrit; WBC and differential; platelet count
6. Maternal vaginal culture
7. Newborn surface (e.g., ear canal, gastric aspirate) smears, cultures (?); blood culture; urine culture (?); CSF culture (?)

C. Signs and Symptoms

1. Tachypnea - above 60-80/minute
2. Grunting - prevents alveolar collapse
3. Retractions - compliant chest wall
4. Flaring of alae nasi, open mouth - decreases resistance
5. Cyanosis in room air; PaO2 below 60 mmHg (torr) in FIO2 >0.4
6. Reduced air entry
7. Apnea
8. Stridor

D. Downes' or RDS Score

	0	1	2
Cyanosis	None	In room air	In 40% FIO2
Retractions	None	Mild	Severe
Grunting	None	Audible with stethoscope	Audible without stethoscope
Air entry	Clear	Decreased or delayed	Barely audible
Respiratory rate	Under 60	60-80	Over 80 or apnea
Score: > 4 = Clinical respiratory distress; monitor arterial blood gases > 8 = Impending respiratory failure

E. Arterial Blood Gases

	Normal	Respiratory Failure
pH	7.30-7.40	<7.20
PaCO2	30-35 mmHg	>55-60 mmHg
PaO2	Above 60 mmHg	<60 mmHg in FIO2
FIO2	Room air	= 0.4-0.5*
Base deficit	-5 to 0 mEq/L
O2 saturation (SaO2)	>90-92%	<85%

F. Chest X-Ray - Medical Versus Surgical Causes

Medical	Surgical
Respiratory distress syndrome - hyaline membrane disease	Pneumothorax
Wet lung - transient tachypnea	Diaphragmatic hernia
Pneumonia	Pleural effusion
Aspiration - meconium, amniotic fluid	TE fistula
Hemorrhage	Lobar emphysema
Pulmonary insufficiency - immaturity	Cyst, masses, phrenic nerve paralysis
Congestive heart failure - pulmonary edema	Airway disorders

G. Guidelines for Monitoring Oxygen Saturation Levels by Pulse Oximetry

>95%	Pulmonary hypertension (PPHN)
85 (87) - 96%	28-34 weeks
85 (87) - 93 (96%)	Below 28 weeks gestational age*
90 - 100%	First one to two days¦
>92%	Chronic lung disease

H. Suggested Management of Hypoxemia

1. Maintain PaO2 SaO2	50-90 torr 85 (87) - 96%*
2. O2 administration	Warmed, humidified Headbox, mask/funnel 5 liters/minute, 1/2 inch from nostrils Make small changes in FIO2 (flip-flop) Monitor FIO2, SaO2
3. CPAP - PEEP
4. Positive pressure ventilation
5. ECMO	Oxygenation index [MAP x FIO2 x 100/PaO2] >40-45
*SaO2 = oxygen saturation level; maintain SaO2 <96% for preterm infants when possible, higher (>95%) in infants with pulmonary hypertension

I. Suggested Indications for Positive Pressure Ventilation in the Newborn Infant

1. Downes' or RDS score >8
2. Severe apneic episodes, gasping respiratory efforts
3. pH <7.25 AND PaCO2 >55-60 mmHg or rising >5-10 mmHg/hour
4. Birth weight <1500 grams, gestational age <31 weeks (delivery room)
5. Failure of nasal CPAP: PaO2 <60 mmHg, FIO2=0.6, CPAP=6 cm H2O
6. pH <7.20 despite therapy (metabolic/respiratory acidosis)
7. Shock (PEEP of 2-3 cm H2O)
   

J. Orotracheal Intubation of Newborn Infants

Birth Weight (grams) /Gestational Age (weeks)	InternalDiameter (mm)*	End Tip of ET Tube to Lower Lip Distance (cm) (number at lower lip)
Below 1000	2.5	6-7
1000 / 27-28	2.5 - 3.0	7
2000 / 32-34	3.0 - 3.5	8
3000 / 38-40	3.5 - 4.0	9
4000 / above 39	4.0	10
*Most useful straight ET tube: 3.0 mm internal diameter, 13 cm length (3.5 mm internal diameter full-term infant)

K. Differential Diagnosis

II. Medical Conditions Causing Respiratory Distress (excluding respiratory distress syndrome)

A. Meconium Aspiration - Thick, pea soup, particulate meconium is most often associated with meconium aspiration

1. General

• Full-term, post-term infant
• Fetal hypoxia ? Vagal activity in utero ? Physiologic occurrence ?
• Oligohydramnios often present with fetal distress/placental insufficiency
• Thick, pea soup meconium associated with higher morbidity

2. Pathogenesis

• In utero hypoxia, hypercarbia leads to:

• Meconium passage
• Gasping and deep breathing, which reduces pulmonary blood flow

• In utero pulmonary arterial muscular hypertrophy/extension; pulmonary vascular hyperreactivity/spasm (pulmonary hypertension)
• Obstruction leads to atelectasis and emphysema
• Chemical pneumonitis
• Infection (?)
• Surfactant deficiency (?)

3. Signs and symptoms

• Tachypnea, retractions, grunting, flaring
• Rales with decreased air entry
• Muffled heart tones
• Cyanosis
• Increased AP diameter to the chest

4. Complications

• Atelectasis
• Emphysema with alveolar rupture (20-50%)
• Pneumonitis (chemical, infectious [?])

5. Chest x-ray

• Coarse bilateral infiltrates with hyperaeration
• Pneumomediastinum/pneumothorax
• Atelectasis, emphysema

6. Management as indicated clinically

• Monitor arterial blood gases, SaO2, Downes' score, vital signs

• 100% oxygen
• Ventilatory support with PEEP (short inspiratory time) - alkalosis (pulmonary hypertension)

• High-frequency ventilation if indicated
• ECMO-oxygenation index [MAPxFIO2x100/PaO2 ] >40-45

• Surfactant
• Pulmonary vasodilator (e.g., nitric oxide [?])
• Sodium bicarbonate

• Antibiotics
• Monitor central nervous system, cardiac, renal, hepatic, coagulation function; platelet count
• Pulmonary physiotherapy

7. Prevention

• Amnioinfusion (?)
• Suctioning on the perineum (mouth, pharynx, nasopharynx)
• 100% oxygen
• Orogastric tube to stomach
• Intubation and suctioning of the trachea utilizing a meconium aspirator, 100% oxygen

• Perinatal distress (e.g., late decelerations or severe variable decelerations, lack of fetal accelerations, fetal bradycardia or tachycardia, loss of beat-to-beat variability)
• Thick, pea soup meconium
• Large amounts of meconium in the mouth or pharynx

• No positive pressure ventilation until clear returns from the trachea
• Vigorous infant Plus thin meconium Plus oropharyngeal/nasal suctioning on the perineum Plus no meconium visible in the oropharynx: Observe

B. Pneumonia

1. General

• Organisms

• Group B beta-hemolytic streptococci
• E. coli
• Group D enterococcus
• Alpha-hemolytic streptococci
• Haemophilus influenzae (nontypable)
• Pneumococcus
• Listeria

2. Acquisition

• Prenatally: aspiration of infected amniotic fluid-most common

• Prolonged rupture of membranes (>18 hours)
• Prolonged labor
• Excessive obstetrical manipulation
• Maternal infection or fever (e.g., urinary tract infection)
• Purulent or foul-smelling amniotic fluid

• Delivery process
• Postnatally

• Prematurity
• Perinatal distress
• Respiratory assistance
• Open defect (e.g., myelomeningocele)
• Male

3. Signs and symptoms

• Respiratory distress
• Apnea
• Hypotension
• Hypo- or hyperthermia
• Lethargy
• Petechiae
• "Not acting right" or "not looking right"

4. Diagnosis

• Smear and culture

• Gastric aspirate and ear canal ?
• Skin, umbilicus, throat, stool ?

• Blood, urine, tracheal and CSF cultures; latex agglutination (rapid antigen test)
• Other laboratory: CBC/differential/platelets; arterial blood gases; other organ functions as indicated

5. Chest x-ray

• Reticulogranular appearance or coarse, streaky densities
• Unilateral/bilateral infiltrates
• Pleural fluid

6. Management

• Monitor vital signs, arterial blood gases, SaO2
• Antibiotics (ampicillin plus gentamicin or cefotaxime)-IV preferred
• Ventilatory support with PEEP-alkalosis

• High-frequency jet ventilation
• ECMO

• Systemic blood pressure support (colloid-FFP; inotropic agents)
• Platelets if indicated
• Surfactant ?
• Sodium bicarbonate
• Other (immunotherapy)

• Exchange transfusion (?)
• Granulocyte transfusion (?); specific IgM
• Intravenous immunoglobulin (IVIG) ?
• Hyperimmune human IgG (?)
• Colony stimulating factors (?), and/or
• IgM monoclonal antibody preparations (?)

7. Prevention (most)

• Selective intrapartum antimicrobial therapy

• Preterm labor
• Fever
• ROM >12-18 hours
• Multiple births
• Previously affected child, and/or
• Bacteriuria, Plus
• Positive maternal culture at 26-28 weeks

• Ampicillin or penicillin suggested
• Newborn antimicrobial therapy while awaiting culture results with selective intrapartum maternal therapy

• Symptomatic or positive blood or CSF culture
• Sibling with invasive GBS
• Less than four hours from initiation of maternal antimicrobial therapy
• Preterm (below 34 weeks)

C. Pulmonary Hemorrhage

1. General

• Predisposing factors

• Prenatal, perinatal distress
• Breech
• Infection
• Shock
• Patent ductus arteriosus (PDA) or other congenital heart defect
• Vitamin K deficiency
• Maternal aspirin (within five days of delivery)
• Maternal phenytoin and/or phenobarbital and/or
• DIC
• CNS injury
• Aspiration

• Preterm/term/post-term infants; IUGR infants

2. Signs and symptoms

• Blood-tinged or bloody fluid from the nose, mouth and/or endotracheal tube
• Severe respiratory distress
• Cardiac murmur may or may not be present
• Shock (poor perfusion, pallor, weak pulses, low blood pressure)

3. Chest x-ray

• Diffuse opacification ("white out")
• Reticulogranular or coarse densities

4. Laboratory

• CBC/differential/platelets
• Coagulation studies
• Echocardiogram
• Cultures
• Liver function tests

5. Management

• Ventilatory support with high PEEP
• Blood replacement, fresh frozen plasma; platelets
• Vitamin K
• Antibiotics
• PDA ligation (indomethacin) if indicated

D. Wet Lung

1. General

• Predisposing factors

• Cesarean section
• Perinatal distress
• infants of diabetic mothers
• Breech

• Pathogenesis

• Delayed resorption of fetal lung fluid-engorged lymphatics

2. Signs and symptoms

• Tachypnea (80-120 breaths per minute)
• Cyanosis
• Hyperaeration
• Occasional retractions/grunting

3. Chest x-ray

• Increased markings centrally
• Fluid in fissures and costophrenic angles
• Hyperaeration may be present

4. Blood gases, SaO2

• Hypoxemia
• Acidosis or alkalosis may be present

5. Resolution one to five days; most improve during the first 24 hours

6. Management: oxygen, occasionally CPAP/PEEP

E. Persistent Pulmonary Hypertension (persistent fetal circulation)

1. General

• Secondary to another disorder (e.g., respiratory distress syndrome, aspiration, pneumonia, diaphragmatic hernia) most commonly
• Affects primarily near-, full- and post-term infants
• Increased pulmonary vascular resistance --> intracardiac right-to-left shunt (PDA, foramen ovale) --> hypoxemia, acidosis --> increased resistance --> increased shunt

2. Etiology

• Acute pulmonary vasoconstriction (e.g., acidosis, hypoxia, RDS, pneumonia; hyperviscosity)
• Increased pulmonary vascular smooth muscle with its extension (e.g., perinatal distress, aspiration ?) to arterioles surrounding alveoli
• Decreased number of pulmonary blood vessels with excessive muscle (e.g., diaphragmatic hernia, other thoracic space-occupying lesions)
• Other

3. Signs and symptoms

• Marked lability; cyanosis (desaturation) with any type of stress
• Cyanosis
• Respiratory distress
• Soft murmur of mitral/tricuspid insufficiency

4. X-ray

• Underlying disorder (e.g., respiratory distress syndrome)
• May be normal if primary pulmonary hypertension

5. Management

• PaO2 >70-100 mmHg (torr), SaO2 >95%
• Hyperventilation-PEEP-alkalosis

• Sodium bicarbonate
• High-frequency ventilation
• ECMO-oxygenation index [ MAPxFIO2x100 / PaO2(postductal0 ] >40-45

• Inotropic agents to maintain systemic blood pressure
• Surfactant
• Vasodilators (e.g., nitric oxide ?)
• Slow weaning of oxygen, ventilatory support
• Antibiotics
• Analgesia/sedation

F. Other

1. Congestive heart failure/pulmonary edema
2. Obstruction to air entry

• Nasal: choanal atresia, maternal reserpine or alpha methyldopa administration -oral airway may be needed
• Pharynx/larynx: Robin sequence; vocal cord paralysis; laryngomalacia; laryngeal webs; subglottic stenosis
• Extrinsic: Goiter; malformations of aortic arch

3. CNS muscular weakness; depressant drugs
4. Unilateral interstitial emphysema
5. Abnormality of thoracic cage
6. Chronic pulmonary disorders: Chronic pulmonary insufficiency/Wilson-Mikity; bronchopulmonary dysplasia
7. Shock

III. Surgical Conditions Causing Respiratory Distress

A. Diaphragmatic hernia

1. General

• Left to right: 5 to 1 - foramen of Bochdalek
• Hypoplasia of ipsilateral lung; compression and atelectasis of contralateral lung
• Pulmonary hypertension is often present and severe
• Maternal polyhydramnios if often present with larger lesions

2. Signs and symptoms

• Respiratory distress (delivery room to later in life)
• Cyanosis
• Bowel sounds in the chest (?)
• Scaphoid abdomen
• Right-sided heart tones with left-sided hernia
• Other congenital anomalies

3. X-ray

• Gas-filled loops of bowel in the chest
• Mediastinal displacement to the right
• Heart on the right side with left-sided diaphragmatic hernia
• Absent diaphragmatic shadow
• Pneumothorax
• Reduced intestinal loops in the abdomen

4. Differential diagnosis

• Pulmonary hypoplasia
• Cystic adenomatoid malformation
• Atelectasis
• Pneumatocele (staphylococci, gram-negative bacilli)
• Interstitial emphysema

Note: Gas-filled loops are in the abdomen in the above conditions, but are rare in diaphragmatic hernia

5. Management

• Orogastric tube to suction
• Positive pressure ventilation via endotracheal tube, NOT via mask
• Low pressures if possible in order to reduce the risk of pneumothorax
• Alkalosis to decrease pulmonary vascular resistance
• 100% oxygen often necessary
• Placement of better lung uppermost (usually the right lung if left-sided hernia)
• Surgery (immediate, up to 48 hours or later, depending on resolution of pulmonary hypertension)
• ECMO for severe hypoxemia, oxygenation index >40-45
• Antibiotics
• Observe for pneumothoraces

B. Tracheoesophageal (TE) fistula

1. General

• Esophageal atresia with distal (TE) fistula (85%)
• Esophageal atresia (10%)
• H-type fistula (4-6%)

2. Signs and symptoms

• Maternal polyhydramnios in 30-70% of patients
• Excessive secretions and drooling after birth
• Choking, coughing and cyanosis with feedings
• Inability to pass an orogastric tube to the stomach
• Respiratory distress
• Congenital anomalies (50%) -VACTERL or VATER

Note: V=vertebral anomalies; A=anal atresia; C=cardiac; TE=tracheoesophageal fistula; R=renal dysplasia; L=limb (radius) hypoplasia

3. X-ray

• Dilated proximal pouch in the mediastinum
• Right upper lobe pneumonia or atelectasis (overflow of secretions)
• Gastric dilatation and excessive air in the bowel loops if a fistula is present
• No air in abdomen if a fistula is absent

4. Initial management

• Intermittent suction or aspiration of the upper pouch, nasopharynx
• Head and chest elevated 45 degrees from the horizontal
• Prevent excessive crying
• Antibiotics
• Surgery when stable - gastrostomy should be done early

C. Congenital lobar emphysema

1. General

• Location is usually left upper lobe, right middle lobe or right upper lobe, unless due to an aberrant vessel related to congenital heart disease
• Partial obstruction of the airway on expiration leads to overdistention of the lobe; there is often abnormal bronchial cartilage
• Intraluminal obstruction
• Extraluminal compression, often associated with congenital heart disease (lower lobes)

2. Signs and symptoms

• Progressive respiratory distress
• Wheezing
• Cyanosis
• Asymptomatic

3. Chest x-ray

• Overdistention of the lobe
• Compression of surrounding lobes
• Mediastinal shift
• Radiolucent lobe

4. Differential diagnosis

• Lung cyst
• Tension pneumothorax
• Compensatory emphysema due to contralateral atelectasis
• Pneumatocele

5. Initial management

• Ventilatory support with 100% oxygen
• Alkalosis
• Good lung uppermost
• Surgery

D. Congenital cystic adenomatoid malformation

1. General

• Any lobe may be affected, with increased size of the affected lobe
• Pulmonary hypoplasia may be present
• infection may occur

2. Signs and symptoms

• Progressive respiratory distress
• Anasarca with polyhydramnios occasionally in the maternal history
• Signs and symptoms of pneumonia including respiratory distress, hypotension and poor perfusion

3. X-ray

• Intrapulmonary mass with irregular lucencies and with herniation
• May be completely opacified
• Normal abdominal pattern

4. Differential diagnosis

• Cyst
• Pneumatocele
• Tension pneumothorax

5. Initial management

• Ventilatory support with 100% oxygen
• Alkalosis
• Good lung uppermost
• Early surgery
• ECMO ?

E. Lung cyst

1. General

• Acquired versus congenital
• Peripheral versus central
• May compress other lobes
• Infection may occur

2. Signs and symptoms

• Progressive respiratory distress
• Air trapping with mediastinal displacement and compression of contralateral lobes or rupture of the cyst

3. Differential diagnosis

• Cystic adenomatoid malformation
• Pneumatocele
• Pneumothorax
• Compensatory emphysema

4. Initial management

• Ventilatory assistance, if indicated, with oxygen
• Surgery
• Antibiotics

F. Pneumothorax | Pneumomediastinum | Pneumopericardium | Pneumoperitoneum

1. General

• Pulmonary pathology including meconium or blood aspiration, RDS, pneumonia, need for ventilatory assistance or extensive resuscitation leads to an increased risk for pneumothorax
• CPAP or PEEP increases risk for pneumothorax
• Hypoplastic lungs and cysts increase the risk for pneumothorax

2. Pathogenesis

• Alveolar rupture with dissection of air to mediastinum and/or pleura
• Tension pneumothorax (air sufficient to increase the intrapleural pressure above the atmospheric pressure)

3. Signs and symptoms

• Cyanosis
• Progressive respiratory distress
• Shifted and/or decreased heart sounds
• Increased size of the affected side
• Hypotension
• Decreased aeration on the affected side (often difficult to ascertain)

4. Chest x-ray

• Partial or total collapse of the lung
• Mediastinal displacement
• Absent pulmonary markings
• Flattened diaphragm

5. Initial management

• Tension pneumothorax or progressive respiratory distress - needle aspiration with subsequent chest tube insertion and attachment to suction
• Asymptomatic pneumothorax or with tachypnea alone - 100% oxygen for one to two hours if the infant is full term to wash out nitrogen

6. Other helpful management

• Minimize crying
• Good lung uppermost

7. Differential diagnosis

• Lobar emphysema
• Cyst
• Soft tissue fold

8. Pneumomediastinum rarely needs evacuation

• Air is near the heart with elevation of the thymus; there is lucency between the heart and the sternum
• Close observation for associated pneumothorax

9. Pneumopericardium

• Air completely surrounding the heart often associated with shock

G. Pleural effusion (bilateral or unilateral)

1. Etiology

• Chylothorax
• Hydrops fetalis (immunologic or nonimmunologic)
• Pneumonia
• Turner syndrome
• Wet lung
• Congestive heart failure
• Hemothorax
• Parenteral nutrition or fluid extravasation

2. Signs and symptoms

• Decreased aeration on affected side
• Progressive respiratory distress
• Contralateral shift of heart sounds if there is a unilateral effusion

3. Initial management

• Ventilatory support with oxygen
• Thoracentesis with chest tube placement to suction
• Analysis of the fluid

• Appearance
• Cells (white blood cells and differential, RBC)
• Hematocrit
• Smear and culture (viral and bacterial)
• Protein, albumin levels, LDH
• Specific gravity
• Lipid content
• Glucose content

H. Other

1. Meningocele (thoracic)
2. Teratoma (dermoid)
3. Cystic hygroma (extension from the neck)
4. Bronchogenic cysts, duplication cysts, neurenteric cysts
5. Sequestration
6. Hamartoma
7. Iatrogenic

IV. Space-Occupying Lesions in the Chest

A. General

	Location
Intrathoracic Tumors  Neurogenic - neuroblastoma  Teratoma, dermoids  Cystic Hygroma  Lipoma  Other	Posterior mediastinum  Anterior mediastinum  Anterior mediastinum, neck
Intrathoracic Cysts Bronchogenic cyst Neurenteric, Gi duplication cyst	Mid mediastinum, carina Posterior, mid mediastinum, vertebral
Meningocele (thoracic)	Posterior mediastinum
Intrapulmonary Masses Lung cyst Cystic adenomatoid malformation  Hamartoma Sequestration Congenital lobar emphysema
Pleural Fluid Accumlation
Pneumothorax
Abdominal Viscera in the Chest - Diaphragmatic Abnormalities Diaphragmatic hernia Large eventration Phrenic nerve palsy

B. Useful Diagnostic Tests for Defining Space-Occupying Thoracic Lesions

1. Chest (two views), abdominal x-rays

• Orogastric tube in place
• Decubitus films for fluid and/or air

2. Fluoroscopy
3. Barium esophagram
4. Ultrasonography

• Cystic versus solid lesion
• Vascular ring
• Location of aortic arch

5. CT scan

• Less expensive and more accessible compared to MRI
• Good for airway definition and calcifications
• Good for intrapulmonary masses and bone lesions

6. MRI

• Good for mediastinal, thoracic wall lesions

7. Angiogram

V. Cycle of Events Often Present in the Sick Newborn Infant

VI. Suggested Indications for Transfer of a Newborn Infant*

A. Respiratory Distress

1. Downes' score >4-5
2. PaO2 <60 mmHg in 40-50% oxygen
3. FIO2 >0.4 to relieve cyanosis
4. PaCO2 >55 mmHg with pH <7.30
5. pH <7.25-7.30
6. Apneic episodes
7. Limited capacity to:

• Provide assisted ventilation
• Monitor pH, PaCO2, PaO2, FIO2
• Precise IV fluid support

B. Surgical Emergencies

C. Suspected Congenital Heart Disease

D. Birth Weight <1500 Grams and/or Gestational Age <31-32 Weeks

E. Severe Perinatal Distress (combined Apgar score <6)

F. Severe Infection

G. "Not Doing Well"

VII. Prevent or Detect and Correct for Stabilization of the Ill Newborn Infant

A. Five Hs

1. Hypothermia
2. Hypotension
3. Hypoglycemia
4. Hypoxia
5. Hypercarbia

B. Plus Acidosis