Background

Respiratory distress syndrome, also known as hyaline membrane disease, occurs almost exclusively in
premature infants. The incidence and severity of respiratory distress syndrome are related inversely to the
gestational age of the newborn infant. (See Etiology and Epidemiology.)

Enormous strides have been made in understanding the pathophysiology and management of respiratory
distress syndrome, leading to improvements in morbidity and mortality in infants with the condition. Advances
include the following (see Treatment and Medication):

The use of antenatal steroids to enhance pulmonary maturity

Appropriate resuscitation facilitated by placental transfusion and immediate use of continuous positive
airway pressure (CPAP) for alveolar recruitment
Early administration of surfactant
The use of gentler modes of ventilation, including early use of "bubble" nasal CPAP to minimize
damage to the immature lungs
Supportive therapies, such as the diagnosis and management of patent ductus arteriosus (PDA), fluid
and electrolyte management, trophic feeding and nutrition, and the use of prophylactic fluconazole
These therapies have also resulted in the survival of extremely premature infants, some of who continue to be
ill with complications of prematurity. (See the image below.)

Chest radiographs in a premature infant with

respiratory distress syndrome before and after surfactant treatment. Left: Initial radiograph shows poor lung expansion, air
bronchogram, and reticular granular appearance. Right: Repeat chest radiograph obtained when the neonate is aged 3
hours and after surfactant therapy demonstrates marked improvement.
Complications
Although reduced, the incidence and severity of complications of respiratory distress syndrome can result in
clinically significant morbidities. Sequelae of respiratory distress syndrome include the following (see
Prognosis, Clinical, and Workup):

Septicemia
Bronchopulmonary dysplasia (BPD)
Patent ductus arteriosus (PDA)
Pulmonary hemorrhage
Apnea/bradycardia
Necrotizing enterocolitis (NEC)
Retinopathy of prematurity (ROP)
Hypertension
Failure to thrive
Intraventricular hemorrhage (IVH)
Periventricular leukomalacia (PVL) - With associated neurodevelopmental and audiovisual handicaps
Strategic goals include focusing direct attention on anticipating and minimizing these complications and
preventing premature delivery whenever possible. (See the diagram below.)
 Schematic outlines the pathology of respiratory distress syndrome
(RDS). Infants may recover completely or develop chronic lung damage, resulting in bronchopulmonary dysplasia (BPD).
FiO2 = fraction of inspired oxygen; HMD = hyaline membrane disease; V/Q = ventilation perfusion.
Surfactant formation and physiology
Surfactant is a complex lipoprotein (see the image below) composed of 6 phospholipids and 4 apoproteins.
Surfactant recovered by alveolar wash from most mammals contains 70-80% phospholipids, 8-10% protein,
and 10% neutral lipids, primarily cholesterol. Dipalmitoyl phosphatidylcholine (DPPC), or lecithin, is functionally
the principle phospholipid. Phosphatidylglycerol makes up 4-15% of the phospholipids; although it is a marker
for lung maturity, it is not necessary for normal lung function.

Bar chart demonstrates the composition of lung surfactant.

About 1% of the 10% protein component comprises surfactant apoproteins; the remaining proteins are derived from alveolar
exudate.
Among the 4 surfactant apoproteins identified, surfactant protein B (SP-B) and SP-C are 2 small hydrophobic
proteins that make up 2-4% of the surfactant mass and are present in commercially available surfactant
preparations. SP-B and SP-C work in concert to facilitate rapid adsorption and spreading of DPPC as a
monolayer to lower the surface tension at the alveolar air-fluid interface in vivo during expiration, thus
preventing atelectasis.

The SP-B gene is on human chromosome 2, and its primary translation product is 40 kd, which is clipped to
become an 8-kd protein in the type II cells before entering lamellar bodies to be cosecreted with phospholipids.
The SP-C gene is on chromosome 8; its primary translation product, 22 kd, is processed to an extremely
hydrophobic 4-kd protein that is associated with lipids in lamellar bodies.

SP-A is an innate host defense, large molecular, hydrophilic (water soluble) lectin coded on human
chromosome 10 that regulates lung inflammation. SP-A contributes to the biophysical properties of surfactant
primarily by decreasing protein-mediated inhibition of surfactant function. It binds to multiple organisms, such
as group B streptococcus, Staphylococcus aureus, influenza virus, adenovirus, herpes simplex type 1, and
respiratory syncytial virus. SP-A facilitates phagocytosis of pathogens by macrophages and their clearance
from the airways. Mice that lack SP-A have no tubular myelin and have normal lung function and surfactant
metabolism, indicating that SP-A is not a critical regulator of surfactant metabolism. Patients with SP-A
deficiency have not been described.

SP-D is also a hydrophilic protein of 43 kd that is a collectin with structural similarities to SP-A. It has a
collagenlike domain and a glycosylated region that gives it its lectinlike functions. SP-D is a large multimer that
is synthesized by type II alveolar cells and Clara cells in addition to other epithelial cells in the body. It also
binds pathogens and facilitates their clearance. The absence of SP-D results in increased surfactant lipid pools
in the airspaces and emphysema in mice. No humans with SP-D deficiency have been described.

The components of pulmonary surfactant are synthesized in the Golgi apparatus of the endoplasmic reticulum
of the type II alveolar cell. (See the image below.)

Schematic show surfactant metabolism, with a

single alveolus is shown and the location and movement of surfactant components. Surfactant components are synthesized
from precursors in the endoplasmic reticulum and transported through the Golgi apparatus by multivesicular bodies.
Components are ultimately packaged in lamellar bodies, which are intracellular storage granules for surfactant before its
secretion. After secretion (exocytosis) into the liquid lining of the alveolus, surfactant phospholipids are organized into a
complex lattice called tubular myelin. Tubular myelin is believed to generate the phospholipid that provides material for a
monolayer at the air-liquid interface in the alveolus, which lowers surface tension. Surfactant phospholipids and proteins are
subsequently taken back into type II cells, in the form of small vesicles, apparently by a specific pathway that involves
endosomes, and then are transported for storage into lamellar bodies for recycling. Alveolar macrophages also take up
some surfactant in the liquid layer. A single transit of the phospholipid components of surfactant through the alveolar lumen
normally requires a few hours. The phospholipid in the lumen is taken back into type II cell and is reused 10 times before
being degraded. Surfactant proteins are synthesized in polyribosomes and extensively modified in the endoplasmic
reticulum, Golgi apparatus, and multivesicular bodies. Surfactant proteins are detected in lamellar bodies or secretory
vesicles closely associated with lamellar bodies before they are secreted into the alveolus.
The components are packaged in multilamellar vesicles in the cytoplasm of the type II alveolar cell. They are
secreted by a process of exocytosis, the daily rate of which may exceed the weight of the cell. Once secreted,
the vesicles unwind to form bipolar monolayers of phospholipid molecules that depend on the apoproteins SP-
B and SP-C to properly configure in the alveolus.

The lipid molecules are enriched in dipalmitoyl acyl groups attached to a glycerol backbone that pack tightly
and generate low surface tension. Tubular myelin stores surfactant and depends on SP-B. Corners of the
myelin lattice appear to be glued together with the large apoprotein SP-A, which may also have an important
role in phagocytosis. Surfactant proteins are expressed in the fetal lung with increasing gestational age.

Patient education
Because the risk of prematurity and respiratory distress syndrome is increased for subsequent pregnancies,
counsel the parents.

Education and counseling of parents, caregivers, and families of premature infants must be undertaken as part
of discharge planning. These individuals should be advised of the potential problems infants with respiratory
distress syndrome may encounter during and after their nursery stay. Audiovisual aids and handouts
supplement such education.
Etiology
In premature infants, respiratory distress syndrome develops because of impaired surfactant synthesis and
secretion leading to atelectasis, ventilation-perfusion (V/Q) inequality, and hypoventilation with resultant
hypoxemia and hypercarbia. Blood gases show respiratory and metabolic acidosis that cause pulmonary
vasoconstriction, resulting in impaired endothelial and epithelial integrity with leakage of proteinaceous exudate
and formation of hyaline membranes (hence the name).

The relative deficiency of surfactant decreases lung compliance (see the image below) and functional residual
capacity, with increased dead space. The resulting large V/Q mismatch and right-to-left shunt may involve as
much as 80% of the cardiac output.

Bottom curve reflects findings from lungs

obtained at postmortem from an infant with hyaline membrane disease (HMD). Lungs with HMD require far more pressure
than to achieve a given volume of inflation than do lungs obtained from an infant dying of a nonrespiratory cause. Arrows
indicate inspiratory and expiratory limbs of the pressure-volume curves. Note the decreased lung compliance and increased
critical opening and closing pressures, respectively, in the premature infant with HMD.
Hypoxia, acidosis, hypothermia, and hypotension may impair surfactant production and/or secretion. In many
neonates, oxygen toxicity with barotrauma and volutrauma in their structurally immature lungs causes an influx
of inflammatory cell, which exacerbates the vascular injury, leading to bronchopulmonary dysplasia (BPD).
Antioxidant deficiency and free-radical injury worsen the injury.

Upon macroscopic evaluation, the lungs of affected newborns appear airless and ruddy (ie, liverlike).
Therefore, the lungs require an increased critical opening pressure to inflate. Diffuse atelectasis of distal
airspaces along with distension of distal airways and perilymphatic areas are observed microscopically.
Progressive atelectasis, barotrauma or volutrauma, and oxygen toxicity damage endothelial and epithelial cells
lining these distal airways, resulting in exudation of fibrinous matrix derived from blood.

Hyaline membranes that line the alveoli (see the image below) may form within a half hour after birth. In larger
premature infants, the epithelium begins to heal at 36-72 hours after birth, and endogenous surfactant
synthesis begins. The recovery phase is characterized by regeneration of alveolar cells, including type II cells,
with a resultant increase in surfactant activity. The healing process is complex.

Microscopic appearance of lungs of an infant

with respiratory distress syndrome. Hematoxylin and eosin stain shows hyaline membranes (pink areas).
A chronic process often ensues in infants who are extremely immature and critically ill and in infants born to
mothers with chorioamnionitis, resulting in BPD. In extremely premature infants, an arrest in lung development
often occurs during the saccular stage, resulting in chronic lung disease termed "new" BPD.
Apoprotein deficiency
The hydrophobic SP-B and SP-C are essential for lung function and pulmonary homeostasis after birth. These
proteins enhance the spreading, adsorption, and stability of surfactant lipids required to reduce surface tension
in the alveolus. SP-B and SP-C participate in regulating intracellular and extracellular processes critical for
maintaining respiratory structure and function. [1]

SP-B deficiency is an inherited deficiency caused by a pretranslational mechanism implied by the absence of
messenger ribonucleic acid (mRNA). SP-B deficiency leads to death in term or near-term neonates and
clinically manifests as respiratory distress syndrome with pulmonary hypertension, or congenital alveolar
proteinosis. The genetic absence of SP-B is most often caused by a 2-base pair insertion (121 ins 2) that
produces a frame shift and premature terminal signal, resulting in a complete absence of SP-B.

Approximately 15% of term infants who die of a syndrome similar to respiratory distress syndrome have SP-B
deficiency. The lack of SP-B causes a lack of normal lamellar bodies in type II cells, a lack of SP-C, and the
appearance of incompletely processed SP-C in the airspaces. These pro SP-C forms are diagnostic of SP-B
deficiency.

Analysis of lung tissue with immunologic and biologic methods reveals an absence of one of the surfactant
specific proteins, SP-B, and its mRNA. In an in-vitro study, critical structure and function in the N-terminal
region of pulmonary SP-B was noted. W9 is critical to optimal surface activity, whereas prolines may promote a
conformation that facilitates rapid insertion of the peptide into phospholipid monolayers compressed to the
highest pressures during compression-expansion cycling.

Mutations of SP-B and SP-C cause acute respiratory distress syndrome and chronic lung disease that may be
related to the intracellular accumulation of injurious proteins, extracellular deficiency of bioactive surfactant
peptides, or both. Mutations in the gene for SP-C are a cause of familial and sporadic interstitial lung disease
and emphysema as patients age. Mutations in other genes that cause protein misfolding and misrouting may
contribute to the pathogenesis of chronic interstitial lung disease.

Hydrophilic SP-A and SP-D are lectins. In vivo and in vitro studies provide compelling support for SP-A and SP-
D as mediators of various immune-cell functions. Studies have shown novel roles for these proteins in the
clearance of apoptotic cells, direct killing of microorganisms, and initiation of parturition. None of the currently
available surfactant preparations to treat respiratory distress syndrome have SP-A and SP-D.

ABCA3 mutations
Mutations in the adenosine triphosphate (ATP)binding casette gene (ABCA3) in newborns result in fatal
surfactant deficiency. ABCA3 is critical for proper formation of lamellar bodies and surfactant function and may
also be important for lung function in other pulmonary diseases. Because it is closely related to the ABCA1 -
and ABCA4 -encoded proteins that transport phospholipids in macrophages and photoreceptor cells, it may
have a role in surfactant phospholipid metabolism. [2]

The incidence of genetic abnormalities of pulmonary surfactant disorders is unknown. In a review of 300 term
infants presenting as severe respiratory distress syndrome, 14% had SP-B deficiency and 14% had a
deficiency of ABCA3.

Risk factors
The greatest risk factor for respiratory distress syndrome is prematurity, although the syndrome does not occur
in all premature newborns. Other risk factors include maternal diabetes, cesarean delivery, and asphyxia. [3, 4]

Epidemiology
Occurrence in the United States
In the United States, respiratory distress syndrome has been estimated to occur in 20,000-30,000 newborn
infants each year and is a complication in about 1% pregnancies. Approximately 50% of the neonates born at
26-28 weeks' gestation develop respiratory distress syndrome, whereas less than 30% of premature neonates
born at 30-31 weeks' gestation develop the condition.

In one report, the incidence rate of respiratory distress syndrome was 42% in infants weighing 501-1500g, with
71% reported in infants weighing 501-750g, 54% reported in infants weighing 751-1000g, 36% reported in
infants weighing 1001-1250g, and 22% reported in infants weighing 1251-1500g, among the 12 university
hospitals participating in the National Institute of Child Health and Human Development (NICHD) Neonatal
Research Network.[5]

International occurrence
Respiratory distress syndrome is encountered less frequently in developing countries than elsewhere, primarily
because most premature infants who are small for their gestation are stressed in utero because of malnutrition
or pregnancy-induced hypertension. In addition, because most deliveries in developing countries occur at
 home, accurate records in these regions are unavailable to determine the frequency of respiratory distress
syndrome.

Race-related demographics
Respiratory distress syndrome has been reported in all races worldwide, occurring most often in white
premature infants.

Prognosis
Acute complications of respiratory distress syndrome include the following [6] :

Alveolar rupture
Infection
Intracranial hemorrhage and periventricular leukomalacia
Patent ductus arteriosus (PDA) with increasing left-to-right shunt
Pulmonary hemorrhage
Necrotizing enterocolitis (NEC) and/or gastrointestinal (GI) perforation
Apnea of prematurity
Chronic complications of respiratory distress syndrome include the following:

Bronchopulmonary dysplasia (BPD)

Retinopathy of prematurity (ROP)
Neurologic impairment
Alveolar rupture
Suspect an air leak (eg, pneumomediastinum, pneumopericardium, interstitial emphysema, pneumothorax)
when an infant with respiratory distress syndrome suddenly deteriorates with hypotension, apnea, or
bradycardia or when metabolic acidosis is persistent.

Infection
Infections may complicate the management of respiratory distress syndrome and may manifest in various
ways, including failure to improve, sudden deterioration, or a change in white blood cell (WBC) count or
thrombocytopenia. Also, invasive procedures (eg, venipuncture, catheter insertion, use of respiratory
equipment) and use of postnatal steroids provide access for organisms that may invade the immunologically
compromised host.

With the advent of surfactant therapy, small and ill infants are surviving, with an increased incidence of
septicemia occurring in them secondary to staphylococcal epidermidis and/or candidal infection. When
septicemia is suspected, obtain blood cultures from 2 sites and start appropriate antibiotics and/or antifungal
therapy until culture results are obtained. Some neonatal ICUs use prophylactic fluconazole in the extremely
premature infants, achieving a decrease in the incidence of candidal septicemia. [7]

Intracranial hemorrhage and periventricular leukomalacia

Intraventricular hemorrhage is observed in 20-40% of premature infants, with greater frequency in infants with
respiratory distress syndrome who require mechanical ventilation. Cranial ultrasonography is performed in the
first week in premature neonates younger than 32 weeks' gestation and at 36 weeks or at the time of
discharge, or as indicated (eg, suspected seizures).

Use of antenatal steroids has decreased the frequency of intracranial hemorrhage in these patients with
respiratory distress syndrome. Although a few studies have shown that prophylactic indomethacin therapy may
decrease intraventricular hemorrhage in premature infants, its routine use is discouraged because of the risk of
intestinal perforation. Hypocarbia and chorioamnionitis are associated with an increase in periventricular
leukomalacia.

Patent ductus arteriosus with increasing left-to-right shunt

This shunt may complicate the course of respiratory distress syndrome, especially in infants weaned rapidly
after surfactant therapy. Suspect patent ductus arteriosus (PDA) in any infant who deteriorates after initial
improvement or who has bloody tracheal secretions.

Although helpful in the diagnosis of PDA, cardiac murmur and wide pulse pressure are not always apparent in
critically ill infants. An echocardiogram enables the clinician to confirm the diagnosis. Infants requiring low
fraction of inspired oxygen (FIO 2) or who are clinically stable do not require treatment, as the PDA may close
spontaneously. Ductal-dependant cardiac anomalies should be excluded prior to initiating therapy. Treat PDA
with ibuprofen or indomethacin, which can be repeated during the first 2 weeks if the PDA reopens. [8] In
refractory incidents of respiratory distress syndrome or in infants in whom medical therapy is contraindicated,
surgically close the PDA.

Pulmonary hemorrhage
The occurrence of pulmonary hemorrhage increases in tiny premature infants, especially after surfactant
therapy. Increase positive end-expiratory pressure (PEEP) on the ventilator and administer intratracheal
epinephrine to manage pulmonary hemorrhage. In some patients, pulmonary hemorrhage may be associated
with PDA; promptly treat pulmonary hemorrhage in such individuals.

In a retrospective study, intratracheal surfactant therapy was used successfully, with the rationale that blood
inhibits pulmonary surfactant.

Necrotizing enterocolitis and/or GI perforation

Suspect NEC and/or GI perforation in any infant with abnormal abdominal findings on physical examination.
Radiography of the abdomen assists in confirming their presence. Spontaneous perforation (not necessarily as
part of NEC) occasionally occurs in critically ill premature infants and has been associated with the use of
steroids and/or indomethacin.

Apnea of prematurity
Apnea of prematurity is common in immature infants, and its incidence has increased with surfactant therapy,
possibly because of early extubation. Manage apnea of prematurity with methylxanthines (caffeine) and/or
bubble or continuous flow nasal continuous positive airway pressure (CPAP), nasal intermittent ventilation, or
with assisted ventilation in refractory incidents. Exclude septicemia, seizures, gastroesophageal reflux, and
metabolic and other causes in infants with apnea of prematurity.

Bronchopulmonary dysplasia
BPD is a chronic lung disease defined as a requirement for oxygen at a corrected gestational age of 36 weeks.
BPD is related directly to the high volume and/or pressures used for mechanical ventilation or to manage
infections, inflammation, and vitamin A deficiency. BPD increases with decreasing gestational age.

Postnatal use of surfactant therapy, gentler ventilation, vitamin A, low-dose steroids, and inhaled nitric oxide
may reduce the severity of BPD.[9]

Clinical studies have demonstrated various incidences of BPD, which has been attributed to increased survival
of small and ill infants with respiratory distress syndrome. BPD may also be associated with gastroesophageal
reflux or sudden infant death syndrome. Hence, consider these entities in infants with unexplained apnea
before discharging them from the hospital.

Retinopathy of prematurity
Infants with respiratory distress syndrome who have a partial pressure of oxygen (PaO 2) value of over 100mm
Hg are at increased risk for ROP. Hence, closely monitor PaO 2 and maintain it at 50-70mm Hg. Although pulse
oximetry is used in all premature infants, it is not helpful in preventing ROP in tiny infants because of the flat
portion of the oxygen-hemoglobin dissociation curve.

An ophthalmologist examines the eyes of all premature infants at 34 weeks' gestation and thereafter as
indicated. If ROP progresses, laser therapy or cryotherapy is used to prevent retinal detachment and blindness.
Closely monitor infants with ROP for refractive errors.

Intraocular bevacizumab, a monoclonal antibody targeting the vascular endothelial growth factor, has been
used successfully to treat ROP. Although it is a promising therapy for ROP, further studies are needed before it
can be recommended for routine use.[10]

Neurologic impairment
Neurologic impairment occurs in approximately 10-70% of infants and is related to the infant's gestational age,
the extent and type of intracranial pathology, and the presence of hypoxia and infections. Hearing and visual
handicaps may further compromise development in affected infants. Patients may develop a specific learning
disability and aberrant behavior. Therefore, periodically follow up on these infants to detect those with
neurologic impairment, and undertake appropriate interventions.

In a study that assessed the outcomes of 288 very preterm Chinese infants with severe respiratory distress
syndrome on mechanical ventilation through 18 months of corrected age, the incidence of cerebral palsy and
mental developmental index (MDI) less than 70 were highest among infants born at younger than 28 weeks'
gestation compared to those born at 28-30 and 30-32 weeks' gestation. [11] Factors associated with cerebral
palsy and an MDI below 70 were the administration of antenatal corticosteroids, decreased weight gain, and
the presence of preeclampsia, fetal distress, and early/late bacteremia; factors that increased the risk of
cerebral palsy and an MDI below 70 were increased length of mechanical ventilator support and blood
transfusions.[11]
 History
Respiratory distress syndrome frequently occurs in the following individuals:

White male infants

Infants born to mothers with diabetes
Infants born by means of cesarean delivery
Second-born twins
Infants with a family history of respiratory distress syndrome
In contrast, the incidence of respiratory distress syndrome decreases with the following:

Use of antenatal steroids

Pregnancy-induced or chronic maternal hypertension
Prolonged rupture of membranes
Maternal narcotic addiction
Secondary surfactant deficiency may occur in infants with the following:

Intrapartum asphyxia
Pulmonary infections (eg, group B beta-hemolytic streptococcal pneumonia)
Pulmonary hemorrhage
Meconium aspiration pneumonia
Oxygen toxicity along with barotrauma or volutrauma to the lungs
Congenital diaphragmatic hernia and pulmonary hypoplasia
Physical Examination
Physical findings are consistent with the infant's maturity assessed by using the Dubowitz examination or its
modification by Ballard.

Progressive signs of respiratory distress are noted soon after birth and include the following:

Tachypnea
Expiratory grunting (from partial closure of glottis)
Subcostal and intercostal retractions
Cyanosis
Nasal flaring
Extremely immature in neonates may develop apnea and/or hypothermia.

Diagnostic Considerations
Conditions to consider in the differential diagnosis of respiratory distress syndrome include the following:

Metabolic problems
Hematologic problems
Pulmonary air leaks
Congenital anomalies of the lungs

Differential Diagnoses
Acute Anemia

Aspiration Syndromes

Pediatric Gastroesophageal Reflux

Pediatric Hypoglycemia

Pediatric Pneumonia

Pediatric Polycythemia

Pneumomediastinum

Pneumothorax Imaging

Sudden Infant Death Syndrome

Transient Tachypnea of the Newborn

 Approach Considerations
Several diagnoses may coexist with and complicate the course of respiratory distress syndrome, including the
following:

Pneumonia - Usually secondary to group B beta-hemolytic streptococci and often coexists with
respiratory distress syndrome
Metabolic problems - Eg, hypothermia, hypoglycemia
Hematologic problems - Eg, anemia, polycythemia, jaundice
Transient tachypnea of the newborn - Usually occurs in term or near-term neonates, often after
cesarean delivery; the chest radiograph of an infant with transient tachypnea shows good lung expansion
and, often, fluid in the horizontal fissure
Aspiration syndromes - May result from aspiration of amniotic fluid, blood, or meconium; aspiration
syndrome is observed in more mature infants and is differentiated by obtaining a history and by viewing the
chest radiographs.
Pulmonary air leaks - Eg, pneumothorax, interstitial emphysema, pneumomediastinum,
pneumopericardium; in premature infants, these complications may be due to excessive positive-pressure
ventilation (in rare cases, spontaneous pneumothorax may occur in large infants)
Congenital anomalies of the lungs - Eg, diaphragmatic hernia, chylothorax, congenital cystic
adenomatoid malformation of the lung, lobar emphysema, bronchogenic cyst, pulmonary sequestration
Congenital anomalies of the heart
Congenital anomalies of the lungs and heart are uncommon in premature infants; these entities can be
diagnosed on the basis of chest radiographic or echocardiographic findings. They coexist only rarely with
respiratory distress syndrome.

Fetal lung maturity tests

Prediction of fetal lung maturity is derived by estimating the lecithin-to-sphingomyelin ratio and/or by testing for
the presence of phosphatidylglycerol in the amniotic fluid obtained with amniocentesis.

Antenatal diagnosis of SP-B deficiency, a rare genetic disease, can also be antenatally diagnosed by analyzing
the amniotic fluid; this diagnostic testing should be undertaken in previously affected siblings.

Procedures
Vascular access procedures
Vascular access procedures used in infants with respiratory distress syndrome include:

Intravenous (IV) line placement

Umbilical arterial catheterization
Umbilical artery cut down
Peripheral artery cannulation
Umbilical venous catheterization
Other procedures
The following procedures may also be employed in infants with respiratory distress syndrome:

Sedation, analgesia, or anesthesia whenever feasible

Arterial puncture, venous puncture, and capillary blood sampling
Tracheal intubation or tracheostomy
Bronchoscopy
Placement of thoracotomy tubes
Placement of pericardial tubes
Placement of gastric tubes
Transfusion of blood, blood products, and exchange transfusion
Lumbar puncture
Suprapubic bladder aspiration and bladder catheterization
Blood Gases
Blood gases are usually obtained in respiratory distress syndrome, as clinically indicated, from an indwelling
peripheral or central (umbilical) arterial catheter or by means of arterial puncture. In a multicenter study by
Billman and colleagues, an in-line, ex-vivo, point-of-care monitor was shown to be reliable in critically ill
neonates and infants.[12] It can be reliably used without adverse consequences associated with serial
phlebotomy.

Blood gases show respiratory and metabolic acidosis along with hypoxia. Respiratory acidosis occurs because
of alveolar atelectasis and/or overdistension of terminal airways. Metabolic acidosis is primarily lactic acidosis,
which results from poor tissue perfusion and anaerobic metabolism.

Hypoxia occurs from right-to-left shunting of blood through the pulmonary vessels, patent ductus arteriosus
(PDA), and/or patent foramen ovale.
Pulse Oximetry
Pulse oximetry is used as a noninvasive tool to monitor oxygen saturation, which should be maintained at 90-
95%. However, it is unreliable for determining hyperoxia because of the flat-top portion of the S -shaped
oxygen-hemoglobin dissociation curve. In the past, continuous, in-line arterial PaO 2 monitoring and
transcutaneous monitoring were used. Transcutaneous CO 2 monitors should be used in infants with ongoing
respiratory distress to monitor ventilation if it correlates with PaCO 2.

Chest Radiography and Echocardiography

Chest radiography
Chest radiographs of a newborn infant with respiratory distress syndrome reveal bilateral, diffuse, reticular
granular or ground-glass appearances; air bronchograms; and poor lung expansion. The prominent air
bronchograms represent aerated bronchioles superimposed on a background of collapsed alveoli.

The cardiac silhouette may be normal or enlarged. Cardiomegaly may be the result of prenatal asphyxia,
maternal diabetes, patent ductus arteriosus (PDA), an associated congenital heart anomaly, or simply poor
lung expansion. These findings may be altered with early surfactant therapy and adequate mechanical
ventilation. (See the image below.)

Chest radiographs in a premature infant with

respiratory distress syndrome before and after surfactant treatment. Left: Initial radiograph shows poor lung expansion, air
bronchogram, and reticular granular appearance. Right: Repeat chest radiograph obtained when the neonate is aged 3
hours and after surfactant therapy demonstrates marked improvement.
The radiologic findings of respiratory distress syndrome cannot be reliably differentiated from those of
pneumonia, which is most commonly caused by group B beta-hemolytic streptococci. If the radiograph shows
streaky opacities, the diagnosis of Ureaplasma or Mycoplasma pneumonia should be considered and
confirmed by means of tracheal aspirate cultures grown in the appropriate medium.

Echocardiography
Echocardiographic evaluation is performed in selected infants to assist in diagnosing PDA and in determining
the direction and degree of shunting on Doppler study. It is also useful in diagnosing pulmonary hypertension,
assessing cardiac function, and excluding structural heart disease.

Pulmonary Mechanics Testing

Although pulmonary mechanics testing (PMT) has primarily been used as a research tool in the past, newer
ventilators are equipped with PMT capabilities to assist the neonatologist in adequately managing the changing
pulmonary course of premature newborn infants with respiratory distress syndrome.

Constant PMT may be helpful in preventing volutrauma due to alveolar and airway overdistension. Monitoring
may also facilitate weaning the infant from the ventilator after surfactant therapy or in determining if the infant
can be extubated. However, clinical studies of PMT to date have not proven its long-term outcome benefits in
neonates with respiratory distress syndrome.

Infants with respiratory distress syndrome have substantially decreased lung compliance, with a range of
0.0005-0.0001 L/cm water. Therefore, for the same pressure gradient, the delivered tidal volume is reduced in
premature infants with respiratory distress syndrome compared with healthy newborn infants.

Pulmonary compliance may considerably improve after surfactant administration. Hence, the patient's lung
compliance and end-expiratory tidal volume should be monitored closely after surfactant therapy, and the peak
inspiratory pressure should be adjusted accordingly.

The resistance (airway and tissues) may be normal or increased. The time constant and the corresponding
pressure and volume equilibration are shortened. The anatomic dead space and the functional residual
capacity are increased.