Infantile respiratory distress syndrome (IRDS), also called respiratory distress syndrome of newborn, or increasingly surfactant deficiency disorder (SDD),
and previously called hyaline membrane disease (HMD), is a
syndrome
A syndrome is a set of medical signs and symptoms which are correlated with each other and often associated with a particular disease or disorder. The word derives from the Greek σύνδρομον, meaning "concurrence". When a syndrome is paired ...
in
premature infant
Preterm birth, also known as premature birth, is the birth of a baby at fewer than 37 weeks gestational age, as opposed to full-term delivery at approximately 40 weeks. Extreme preterm is less than 28 weeks, very early preterm birth is between 2 ...
s caused by developmental insufficiency of
pulmonary surfactant
Pulmonary surfactant is a surface-active complex of phospholipids and proteins formed by type II alveolar cells. The proteins and lipids that make up the surfactant have both hydrophilic and hydrophobic
In chemistry, hydrophobicity is t ...
production and structural immaturity in the
lung
The lungs are the primary organs of the respiratory system in humans and most other animals, including some snails and a small number of fish. In mammals and most other vertebrates, two lungs are located near the backbone on either side of t ...
s. It can also be a consequence of
neonatal infection
Neonatal infections are infections of the neonate (newborn) acquired during prenatal development or in the first four weeks of life (neonatal period). Neonatal infections may be contracted by mother to child transmission, in the birth canal dur ...
and can result from a genetic problem with the production of surfactant-associated proteins.
IRDS affects about 1% of newborns and is the leading cause of death in
preterm
Preterm birth, also known as premature birth, is the birth of a baby at fewer than 37 weeks gestational age, as opposed to full-term delivery at approximately 40 weeks. Extreme preterm is less than 28 weeks, very early preterm birth is between ...
infants.
Data has shown the choice of elective
caesarean sections
Caesarean section, also known as C-section or caesarean delivery, is the surgical procedure by which one or more babies are delivered through an incision in the mother's abdomen, often performed because vaginal delivery would put the baby or m ...
to strikingly increase the incidence of respiratory distress in term infants; dating back to 1995, the UK first documented 2,000 annual caesarean section births requiring neonatal admission for respiratory distress. The incidence decreases with advancing
gestational age
In obstetrics, gestational age is a measure of the age of a pregnancy which is taken from the beginning of the woman's last menstrual period (LMP), or the corresponding age of the gestation as estimated by a more accurate method if available. Su ...
, from about 50% in babies born at 26–28 weeks to about 25% at 30–31 weeks. The syndrome is more frequent in males, Caucasians, infants of diabetic mothers and the second-born of premature twins.
IRDS is distinct from
pulmonary hypoplasia
Pulmonary hypoplasia is incomplete development of the lungs, resulting in an abnormally low number or size of bronchopulmonary segments or alveoli. A congenital malformation, it most often occurs secondary to other fetal abnormalities that inter ...
, another leading cause of neonatal death that involves respiratory distress.
Signs and symptoms
IRDS begins shortly after birth and is manifested by
fast breathing
Hyperventilation is irregular breathing that occurs when the rate or tidal volume of breathing eliminates more carbon dioxide than the body can produce. This leads to hypocapnia, a reduced concentration of carbon dioxide dissolved in the blood. ...
(more than 60 breaths per minute), a
fast heart rate
Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal (su ...
, chest wall retractions (recession), expiratory grunting, nasal flaring, and
blue discoloration of the skin during breathing efforts.
As the disease progresses, the baby may develop ventilatory failure (rising carbon dioxide concentrations in the blood) and prolonged cessations of breathing ("
apnea
Apnea, BrE: apnoea, is the temporal cessation of breathing. During apnea, there is no movement of the muscles of inhalation, and the volume of the lungs initially remains unchanged. Depending on how blocked the airways are ( patency), there ...
"). Whether treated or not, the clinical course for the acute disease lasts about two to three days. During the first day, the child worsens and requires more support. During the second day, the baby may be remarkably stable on adequate support and resolution is noted during the third day, heralded by a prompt
diuresis
Diuresis () is increased urination (polyuria) or, in the related word senses more often intended, the physiological process that produces such an increase or the administration of medications to encourage that process. It involves extra urine pro ...
. Despite huge advances in care, IRDS remains the most common single cause of death in the first month of life in the developed world. Complications include metabolic disorders (acidosis,
low blood sugar
Hypoglycemia, also called low blood sugar, is a fall in blood sugar to levels below normal, typically below 70 mg/dL (3.9 mmol/L). Whipple's triad is used to properly identify hypoglycemic episodes. It is defined as blood glucose belo ...
),
patent ductus arteriosus
''Patent ductus arteriosus'' (PDA) is a medical condition in which the ''ductus arteriosus'' fails to close after birth: this allows a portion of oxygenated blood from the left heart to flow back to the lungs by flowing from the aorta, which has ...
,
low blood pressure
Hypotension is low blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Blood pressure is indicated by two numbers, the systolic blood pressure (the top number) and the dia ...
, chronic lung changes and
bleeding in the brain. The syndrome is frequently complicated by prematurity and its additional effect on other organ functions.
Related disorders
Acute respiratory distress syndrome
Acute respiratory distress syndrome (ARDS) is a type of respiratory failure characterized by rapid onset of widespread inflammation in the lungs. Symptoms include shortness of breath (dyspnea), rapid breathing (tachypnea), and bluish skin colo ...
(ARDS) has some similarities to IRDS.
Transient tachypnea of the newborn
Transient tachypnea of the newborn is a respiratory problem that can be seen in the newborn shortly after delivery. It is caused by retained fetal lung fluid due to impaired clearance mechanisms. It is the most common cause of respiratory distres ...
presents with respiratory distress syndrome in the Term child.
Histopathology
The characteristic
histopathology
Histopathology (compound of three Greek words: ''histos'' "tissue", πάθος ''pathos'' "suffering", and -λογία '' -logia'' "study of") refers to the microscopic examination of tissue in order to study the manifestations of disease. Spe ...
seen in babies who die from RDS was the source of the name "hyaline membrane disease". Waxlike layers of
hyaline
A hyaline substance is one with a glassy appearance. The word is derived from el, ὑάλινος, translit=hyálinos, lit=transparent, and el, ὕαλος, translit=hýalos, lit=crystal, glass, label=none.
Histopathology
Hyaline cartilage is ...
membrane line the collapsed
alveoli Alveolus (; pl. alveoli, adj. alveolar) is a general anatomical term for a concave cavity or pit.
Uses in anatomy and zoology
* Pulmonary alveolus, an air sac in the lungs
** Alveolar cell or pneumocyte
** Alveolar duct
** Alveolar macrophage
* ...
of the lung. In addition, the lungs show bleeding, overdistention of airways, and damage to the lining cells.
Pathophysiology
The lungs of infants with respiratory distress syndrome are developmentally deficient in a material called
surfactant
Surfactants are chemical compounds that decrease the surface tension between two liquids, between a gas and a liquid, or interfacial tension between a liquid and a solid. Surfactants may act as detergents, wetting agents, emulsifiers, foaming ...
, which helps prevent the collapse of the terminal air spaces (the future site of
alveolar Alveolus (; pl. alveoli, adj. alveolar) is a general anatomical term for a concave cavity or pit.
Uses in anatomy and zoology
* Pulmonary alveolus, an air sac in the lungs
** Alveolar cell or pneumocyte
** Alveolar duct
** Alveolar macrophage
* ...
development) throughout the normal cycle of inhalation and exhalation. This deficiency of surfactant is related to inhibition from the insulin that is produced in the newborn, especially those of diabetic mothers.
Pulmonary surfactant is a complex system of
lipid
Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include ...
s,
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
s and
glycoprotein
Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycos ...
s that is produced in specialized lung cells called Type II cells or
Type II pneumocyte
A pulmonary alveolus (plural: alveoli, from Latin ''alveolus'', "little cavity"), also known as an air sac or air space, is one of millions of hollow, distensible cup-shaped cavities in the lungs where oxygen is exchanged for carbon dioxide. A ...
s. The surfactant is packaged by the cell in structures called
lamellar bodies
In cell biology, lamellar bodies (otherwise known as lamellar granules, membrane-coating granules (MCGs), keratinosomes or Odland bodies) are secretory organelles found in type II alveolar cells in the lungs, and in keratinocytes in the skin. The ...
, and extruded into the air spaces. The lamellar bodies then unfold into a complex lining of the air space. This layer reduces the
surface tension
Surface tension is the tendency of liquid surfaces at rest to shrink into the minimum surface area possible. Surface tension is what allows objects with a higher density than water such as razor blades and insects (e.g. water striders) to f ...
of the fluid that lines the alveolar air space. Surface tension is responsible for approximately 2/3 of the
inward elastic recoil forces. In the same way that a bubble will contract to give the smallest surface area for a given volume, so the air/water interface means that the liquid surface will tend toward being as small as possible, thereby causing the air space to contract. By reducing surface tension, surfactant prevents the air spaces from completely collapsing on exhalation. In addition, the decreased surface tension allows reopening of the air space with a lower amount of force. Therefore, without adequate amounts of surfactant, the air spaces collapse and are very difficult to expand.
Microscopically, a pulmonary surfactant-deficient lung is characterized by collapsed air spaces alternating with hyperexpanded areas, vascular congestion, and, in time,
hyaline
A hyaline substance is one with a glassy appearance. The word is derived from el, ὑάλινος, translit=hyálinos, lit=transparent, and el, ὕαλος, translit=hýalos, lit=crystal, glass, label=none.
Histopathology
Hyaline cartilage is ...
membranes. Hyaline membranes are composed of
fibrin
Fibrin (also called Factor Ia) is a fibrous, non-globular protein involved in the clotting of blood. It is formed by the action of the protease thrombin on fibrinogen, which causes it to polymerize. The polymerized fibrin, together with platele ...
, cellular debris,
red blood cell
Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek ''erythros'' for "red" and ''kytos'' for "holl ...
s, rare
neutrophil
Neutrophils (also known as neutrocytes or heterophils) are the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. They form an essential part of the innate immune system, with their functions varying in ...
s and
macrophage
Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer cel ...
s. They appear as an eosinophilic, amorphous material, lining or filling the air spaces and blocking gas exchange. As a result, blood passing through the lungs is unable to pick up oxygen and unload carbon dioxide. Blood oxygen levels fall and carbon dioxide rises, resulting in rising blood acid levels and
hypoxia. Structural immaturity, as manifested by a decreased number of gas exchange units and thicker walls, also contributes to the disease process. Therapeutic oxygen and positive-pressure ventilation, while potentially life-saving, can damage the lung.
Diagnosis
The diagnosis is made by the clinical picture and the chest
X-ray
An X-ray, or, much less commonly, X-radiation, is a penetrating form of high-energy electromagnetic radiation. Most X-rays have a wavelength ranging from 10 picometers to 10 nanometers, corresponding to frequencies in the range 30&nb ...
, which demonstrates decreased
lung volumes
Lung volumes and lung capacities refer to the volume of air in the lungs at different phases of the respiratory cycle.
The average total lung capacity of an adult human male is about 6 litres of air.
Tidal breathing is normal, resting breathin ...
(bell-shaped chest), absence of the thymus (after about six hours), a small (0.5–1 mm), discrete, uniform infiltrate (sometimes described as a "ground glass" appearance or "diffuse airspace and interstitial opacities") that involves all lobes of the lung and air-bronchograms (i.e. the infiltrate will outline the larger airways passages, which remain air-filled). In severe cases, this becomes exaggerated until the cardiac borders become indiscernible (a 'white-out' appearance).
Prevention
Giving the baby's mother
glucocorticoids
Glucocorticoids (or, less commonly, glucocorticosteroids) are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every vertebr ...
speeds the production of surfactant. For very premature deliveries, a glucocorticoid is given without testing the fetal lung maturity. The
American College of Obstetricians and Gynecologists
The American College of Obstetricians and Gynecologists (ACOG) is a professional association of physicians specializing in obstetrics and gynecology in the United States. Several Latin American countries are also represented within Districts of ...
(ACOG), Royal College of Medicine and other major organizations have recommended antenatal glucocorticoid treatment for women at risk for preterm delivery prior to 34
weeks of gestation. Multiple courses of glucocorticoid administration, compared with a single course, do not seem to increase or decrease the risk of death or
neurodevelopmental disorder
Neurodevelopmental disorders are a group of disorders that affect the development of the nervous system, leading to abnormal brain function which may affect emotion, learning ability, self-control, and memory. The effects of neurodevelopmental ...
s of the child.
In pregnancies of longer than 30 weeks, the fetal lung maturity may be tested by sampling the amount of surfactant in the amniotic fluid by
amniocentesis
Amniocentesis is a medical procedure used primarily in the prenatal diagnosis of genetic conditions. It has other uses such as in the assessment of infection and fetal lung maturity. Prenatal diagnostic testing, which includes amniocentesis, is ne ...
, wherein a needle is inserted through the mother's abdomen and uterus. Several tests are available that correlate with the production of surfactant. These include the
lecithin-sphingomyelin ratio ("
L/S ratio"), the presence of
phosphatidylglycerol
Phosphatidylglycerol is a glycerophospholipid found in pulmonary surfactant and in the plasma membrane where it directly activates lipid-gated ion channels.
The general structure of phosphatidylglycerol consists of a L-glycerol 3-phosphate backbo ...
(PG), and, more recently, the
surfactant/albumin (S/A) ratio. For the
L/S ratio, if the result is less than 2:1, the fetal lungs may be deficient in surfactant. The presence of PG usually indicates fetal lung maturity. For the S/A ratio, the result is given as milligrams of surfactant per gram of protein. A S/A ratio less than 35 indicates immature lungs, between 35 and 55 is indeterminate, and greater than 55 indicates mature surfactant production (correlating with an L/S ratio of 2.2 or greater).
Epidemiology
Infant respiratory distress syndrome (IRDS) is the leading cause of death in premature infants. Despite only 1% of all birth complications being attributed to respiratory distress syndrome, there is a significantly higher prevalence in prematurely born babies.
Incidence rates of IRDS in premature infants born at 30 weeks of gestational age (GA) are at 50%, and rise even higher to 93% for infants born prematurely at 28 weeks of gestational age or younger.
IRDS is diagnosed within hours of delivery and usually leads to morbidity and mortality in preterm infants. There are many risk factors that can potentially cause IRDS. The most common risks factors that can potentially cause IRDS include male gender, white race, late preterm delivery, maternal diabetes, perinatal hypoxia (exposure to low oxygen) and ischemia (decreased blood flow), and low birth weight. Seventy percent of babies diagnosed with respiratory distress syndrome are born between 29 and 34 weeks of gestational age and are 55% more likely to be male.
A study conducted at the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network studied premature infants born between 22 and 37 weeks and the outcomes leading to IRDS. This study was conducted from 2002 to 2008. The incidence rate of IRDS for 24 weeks was 98%, for 34 weeks the incidence is 5%, and for 37 weeks the incidence rate was less than 1%. The results demonstrate that the incidence of IRDS increases with decreasing age at birth.
According to a study from the University of Miami's Department of Pediatrics and Division of Neonatology, from the time range of 2003 to 2014, respiratory distress syndrome prevalence jumped from 170 per 1000 preterm live births to 360 per 1000 preterm live births nationwide in the United States.
This study population's duration under hospital care averaged 32 days in 2003, increasing by nearly a week to 38 days in 2014.
Additionally, this study yielded average prevalence rates of 260 cases per 1000 livebirths from the years of 2003 to 2014,
which coincided with the results yielded by a report from the Vermont Oxford Network in 2008 of 300 per 1000 livebirths.
Treatment
Oxygen is given with a small amount of
continuous positive airway pressure
Continuous positive airway pressure (CPAP) is a form of positive airway pressure (PAP) ventilation in which a constant level of pressure greater than atmospheric pressure is continuously applied to the upper respiratory tract of a person. The ap ...
(CPAP), and intravenous fluids are administered to stabilize the blood sugar, blood salts and blood pressure. CPAP application to preterm neonates with respiratory distress is associated with a reduction in respiratory failure, mechanical ventilation and mortality.
However, CPAP is associated with an increased rate of pneumothorax compared to spontaneous breathing with or without supplemental oxygen.
If the baby's condition worsens, an
endotracheal tube
A tracheal tube is a catheter that is inserted into the trachea for the primary purpose of establishing and maintaining a patent airway and to ensure the adequate exchange of oxygen and carbon dioxide.
Many different types of tracheal tubes are a ...
(breathing tube) is inserted into the trachea and intermittent breaths are given by a mechanical device. An exogenous preparation of
pulmonary surfactant
Pulmonary surfactant is a surface-active complex of phospholipids and proteins formed by type II alveolar cells. The proteins and lipids that make up the surfactant have both hydrophilic and hydrophobic
In chemistry, hydrophobicity is t ...
, either synthetic or extracted from animal lungs, is given through the breathing tube into the lungs.
Surfactant medications can decrease the risk of death for very low-
birth-weight infants who are hospitalized by 30%.
Such small premature infants may remain ventilated for months. A study shows that an aerosol of a
perfluorocarbon
Fluorocarbons are chemical compounds with carbon-fluorine bonds. Compounds that contain many C-F bonds often has distinctive properties, e.g., enhanced stability, volatility, and hydrophobicity. Fluorocarbons and their derivatives are commerci ...
such as
perfluoromethyldecalin can reduce inflammation in swine model of IRDS.
Chronic lung disease, including
bronchopulmonary dysplasia
Bronchopulmonary dysplasia (BPD; part of the spectrum of chronic lung disease of infancy) is a chronic lung disease in which premature infants, usually those who were treated with supplemental oxygen, require long-term oxygen. The alveoli that are ...
, is common in severe RDS. The etiology of BPD is problematic and may be the result of oxygen, overventilation or underventilation. The mortality rate for babies greater than 27 weeks of gestation is less than 20%.
Extracorporeal membrane oxygenation
Extracorporeal membrane oxygenation (ECMO), also known as extracorporeal life support (ECLS), is an extracorporeal technique of providing prolonged cardiac and respiratory support to persons whose heart and lungs are unable to provide an adequat ...
(ECMO) is a potential treatment, providing oxygenation through an apparatus that imitates the
gas exchange
Gas exchange is the physical process by which gases move passively by Diffusion#Diffusion vs. bulk flow, diffusion across a surface. For example, this surface might be the air/water interface of a water body, the surface of a gas bubble in a liqui ...
process of the lungs. However, newborns cannot be placed on ECMO if they are under 4.5 pounds (2 kg), because they have extremely small vessels for
cannulation
A cannula (; Latin meaning 'little reed'; plural or ) is a tube that can be inserted into the body, often for the delivery or removal of fluid or for the gathering of samples. In simple terms, a cannula can surround the inner or outer surfaces ...
, thus hindering adequate flow because of limitations from cannula size and subsequent higher resistance to blood flow (compare with
vascular resistance
Vascular resistance is the resistance that must be overcome to push blood through the circulatory system and create flow. The resistance offered by the systemic circulation is known as the systemic vascular resistance (SVR) or may sometimes be ca ...
). Furthermore, in infants aged less than 34
weeks of gestation, several physiologic systems are not well-developed, especially the
cerebral vasculature
Cerebral circulation is the movement of blood through a network of cerebral arteries and veins supplying the brain. The rate of cerebral blood flow in an adult human is typically 750 milliliters per minute, or about 15% of cardiac output. Arterie ...
and
germinal matrix In anatomy, the germinal matrix is a highly cellular and highly vascularized region in the brain out from which cells migrate during brain development. The germinal matrix is the source of both neurons and glial cells and is most active between 8 an ...
, resulting in high sensitivity to slight changes in
pH,
PaO2 and intracranial pressure. Subsequently, preterm infants are at unacceptably high risk for
intraventricular hemorrhage
Intraventricular hemorrhage (IVH), also known as intraventricular bleeding, is a bleeding into the brain's ventricular system, where the cerebrospinal fluid is produced and circulates through towards the subarachnoid space. It can result from phys ...
(IVH) if administered ECMO at a gestational age of less than 32 weeks.
Henrik Verder is the inventor and pioneer of the INSURE method, a very effective approach to managing preterm neonates with respiratory distress. The method itself has been shown, through meta-analysis, to successfully decrease the use of mechanical ventilation and lower the incidence of bronchopulmonary dysplasia (BPD). Since its conception in 1989, the INSURE method has been academically cited in more than 500 papers. The first randomised study involving the INSURE method was published in 1994 and a second randomised study in infants less than 30 weeks gestation was published by the group in 1999. In the last 15 years, Verder has worked with lung-maturity diagnostics on gastric aspirates obtained at birth. By combining this diagnostic method with INSURE, Verder has worked to further improve the clinical outcome of RDS. The lung-maturity tests used have included the microbubble test, lamellar body counts (LBC) and measurements of lecithin-sphingomyelin ratio (L/S) with chemometrics, which involved a collaboration with
Agnar Höskuldsson.
The routine use of sedatives and opioid pain killers is not recommended for newborn infants who require mechanical ventilation to breathe.
Culture and society
* In 1963,
Patrick Bouvier Kennedy
Patrick Bouvier Kennedy (August 7–9, 1963) was the infant child of President John F. Kennedy and First Lady Jacqueline Kennedy and the younger brother of Caroline, John Jr., and Arabella.
Born prematurely, Kennedy lived just over 39 hour ...
, son of President
John F. Kennedy
John Fitzgerald Kennedy (May 29, 1917 – November 22, 1963), often referred to by his initials JFK and the nickname Jack, was an American politician who served as the 35th president of the United States from 1961 until his assassination ...
and First Lady
Jacqueline Kennedy
Jacqueline Lee Kennedy Onassis ( ; July 28, 1929 – May 19, 1994) was an American socialite, writer, photographer, and book editor who served as first lady of the United States from 1961 to 1963, as the wife of President John F. Kennedy. A po ...
, died of RDS two days after his premature birth at 34 weeks gestation.
* Two daughters of
Dominick Dunne
Dominick John Dunne (October 29, 1925 – August 26, 2009) was an American writer, investigative journalist, and producer. He began his career in film and television as a producer of the pioneering gay film ''The Boys in the Band (1970 film), ...
and his wife
Ellen Griffin Dunne died of RDS, one in 1958 and one in 1963.
See also
*
Bubble CPAP
*
Bronchopulmonary dysplasia
Bronchopulmonary dysplasia (BPD; part of the spectrum of chronic lung disease of infancy) is a chronic lung disease in which premature infants, usually those who were treated with supplemental oxygen, require long-term oxygen. The alveoli that are ...
*
Pulmonary hypoplasia
Pulmonary hypoplasia is incomplete development of the lungs, resulting in an abnormally low number or size of bronchopulmonary segments or alveoli. A congenital malformation, it most often occurs secondary to other fetal abnormalities that inter ...
*
Surfactant metabolism dysfunction
*
Surfactant therapy
*
Wilson–Mikity syndrome
Wilson–Mikity syndrome, a form of chronic lung disease (CLD) that exists only in premature infants, leads to progressive or immediate development of respiratory distress. This rare condition affects low birth babies and is characterized by rapid ...
References
External links
{{DEFAULTSORT:Infant Respiratory Distress Syndrome
Respiratory diseases
Intensive care medicine
Respiratory and cardiovascular disorders specific to the perinatal period
Syndromes
Preterm birth