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Neonatal Respiratory Distress Syndrome

Respiratory distress syndrome (RDS), also known as hyaline membrane disease, is caused by the lack of adequate pulmonary surfactant Surfactant Substances and drugs that lower the surface tension of the mucoid layer lining the pulmonary alveoli. Acute Respiratory Distress Syndrome (ARDS) production in an immature lung. The syndrome is most commonly seen in preterm infants. The incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency is inversely related to gestational age Gestational age The age of the conceptus, beginning from the time of fertilization. In clinical obstetrics, the gestational age is often estimated as the time from the last day of the last menstruation which is about 2 weeks before ovulation and fertilization. Pregnancy: Diagnosis, Physiology, and Care, with the highest risk in neonates born at less than 28 weeks. Prenatal assessment of lung maturity and steroid administration can improve outcome if an early delivery cannot be prevented. Diagnosis is clinical. Affected newborns show signs of respiratory distress at birth, or soon thereafter, with nasal flaring, grunting Grunting Physical Examination of the Newborn respirations, and retractions. Treatment includes antenatal steroids Steroids A group of polycyclic compounds closely related biochemically to terpenes. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (sterols), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. Benign Liver Tumors, exogenous surfactant Surfactant Substances and drugs that lower the surface tension of the mucoid layer lining the pulmonary alveoli. Acute Respiratory Distress Syndrome (ARDS), and respiratory support. Neonatal RDS is associated with high morbidity Morbidity The proportion of patients with a particular disease during a given year per given unit of population. Measures of Health Status and mortality Mortality All deaths reported in a given population. Measures of Health Status in preterm infants.

Last updated: 29 Apr, 2021

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Overview

Definition

Neonatal respiratory distress syndrome (RDS) is a condition caused by a lack of pulmonary surfactant Surfactant Substances and drugs that lower the surface tension of the mucoid layer lining the pulmonary alveoli. Acute Respiratory Distress Syndrome (ARDS), most commonly seen in preterm infants born at < 28 weeks of gestation.

Epidemiology

  • Risk of RDS:
    • Inversely related to gestational age Gestational age The age of the conceptus, beginning from the time of fertilization. In clinical obstetrics, the gestational age is often estimated as the time from the last day of the last menstruation which is about 2 weeks before ovulation and fertilization. Pregnancy: Diagnosis, Physiology, and Care at delivery
    • Highest incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency in babies born < 28 weeks of gestation
  • Higher incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency in white male infants
  • Significant cause of mortality Mortality All deaths reported in a given population. Measures of Health Status and morbidity Morbidity The proportion of patients with a particular disease during a given year per given unit of population. Measures of Health Status in premature infants Premature infants A human infant born before 37 weeks of gestation. Sudden Infant Death Syndrome (SIDS)

Etiology

  • Prematurity:
  • Surfactant Surfactant Substances and drugs that lower the surface tension of the mucoid layer lining the pulmonary alveoli. Acute Respiratory Distress Syndrome (ARDS) inactivation due to:
    • Meconium Meconium The thick green-to-black mucilaginous material found in the intestines of a full-term fetus. It consists of secretions of the intestinal glands; bile pigments; fatty acids; amniotic fluid; and intrauterine debris. It constitutes the first stools passed by a newborn. Prenatal and Postnatal Physiology of the Neonate or blood in alveoli Alveoli Small polyhedral outpouchings along the walls of the alveolar sacs, alveolar ducts and terminal bronchioles through the walls of which gas exchange between alveolar air and pulmonary capillary blood takes place. Acute Respiratory Distress Syndrome (ARDS) (more common in term infants)
    • Oxidative and mechanical stress such as from mechanical ventilation Ventilation The total volume of gas inspired or expired per unit of time, usually measured in liters per minute. Ventilation: Mechanics of Breathing
  • Maternal diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus: 
    • Maternal hyperglycemia Hyperglycemia Abnormally high blood glucose level. Diabetes Mellitus → fetal hyperinsulinemia Hyperinsulinemia Diabetes Mellitus
    • Insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin antagonizes the action of cortisol Cortisol Glucocorticoids, delaying lung surfactant Surfactant Substances and drugs that lower the surface tension of the mucoid layer lining the pulmonary alveoli. Acute Respiratory Distress Syndrome (ARDS) production
  • C-section without labor Labor Labor is the normal physiologic process defined as uterine contractions resulting in dilatation and effacement of the cervix, which culminates in expulsion of the fetus and the products of conception. Normal and Abnormal Labor
    • In the absence of labor Labor Labor is the normal physiologic process defined as uterine contractions resulting in dilatation and effacement of the cervix, which culminates in expulsion of the fetus and the products of conception. Normal and Abnormal Labor, cortisol Cortisol Glucocorticoids production (as well as other hormonal factors) is decreased.
    • Altered fluid clearance from the fetal lung compared with vaginal delivery
  • Conditions that cause fetal acidosis Acidosis A pathologic condition of acid accumulation or depletion of base in the body. The two main types are respiratory acidosis and metabolic acidosis, due to metabolic acid build up. Respiratory Acidosis (may ↓ surfactant Surfactant Substances and drugs that lower the surface tension of the mucoid layer lining the pulmonary alveoli. Acute Respiratory Distress Syndrome (ARDS) synthesis Synthesis Polymerase Chain Reaction (PCR) and/or activity):
    • Perinatal asphyxia Asphyxia A pathological condition caused by lack of oxygen, manifested in impending or actual cessation of life. Drowning (hypoxic injury to type II alveolar cells)
    • Sepsis Sepsis Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock. Sepsis and Septic Shock
    • Intrapartum hypovolemia Hypovolemia Sepsis in Children
    • Intrapartum hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension

Pathophysiology

Normal fetal lung development

  • Stages of fetal lung development:
    • Embryonic stage Embryonic Stage Development of the bronchial tree begins in the embryonic stage, with budding of the embryonic gut tube to form the larynx, trachea, and lungs by the end of the stage. Development of the Respiratory System (4th–7th week): The fetal lung develops from the fetal foregut Foregut Development of the Abdominal Organs and early branching begins.
    • Pseudoglandular stage Pseudoglandular Stage This stage generates most of the bronchial tree. It gets its name because histologically, the bronchi (which are lined with cuboidal cells at this stage) resemble glands as they branch into the surrounding mesoderm. Development of the Respiratory System (5th–16th week): branching from main bronchi Bronchi The larger air passages of the lungs arising from the terminal bifurcation of the trachea. They include the largest two primary bronchi which branch out into secondary bronchi, and tertiary bronchi which extend into bronchioles and pulmonary alveoli. Bronchial Tree: Anatomy to terminal bronchioles Bronchioles The small airways branching off the tertiary bronchi. Terminal bronchioles lead into several orders of respiratory bronchioles which in turn lead into alveolar ducts and then into pulmonary alveoli. Bronchial Tree: Anatomy
    • Canalicular stage Canalicular Stage During this stage, the respiratory units (also referred to as canaliculi) develop at the end of the terminal bronchioles. Development of the Respiratory System (16th–25th week):
      • Formation of respiratory bronchioles Bronchioles The small airways branching off the tertiary bronchi. Terminal bronchioles lead into several orders of respiratory bronchioles which in turn lead into alveolar ducts and then into pulmonary alveoli. Bronchial Tree: Anatomy and alveoli Alveoli Small polyhedral outpouchings along the walls of the alveolar sacs, alveolar ducts and terminal bronchioles through the walls of which gas exchange between alveolar air and pulmonary capillary blood takes place. Acute Respiratory Distress Syndrome (ARDS)
      • Differentiation to type II alveolar cells begins.
      • Surfactant Surfactant Substances and drugs that lower the surface tension of the mucoid layer lining the pulmonary alveoli. Acute Respiratory Distress Syndrome (ARDS) production by 20 weeks, as indicated by + lamellar bodies in the type II alveolar cell cytoplasm
    • Saccular stage Saccular Stage During this stage, the alveoli begin to mature, as type II pneumocytes (cuboidal cells) flatten into type I pneumocytes capable of gas exchange, creating the gas-exchange surface area. Development of the Respiratory System (24th week to term): expansion of alveoli Alveoli Small polyhedral outpouchings along the walls of the alveolar sacs, alveolar ducts and terminal bronchioles through the walls of which gas exchange between alveolar air and pulmonary capillary blood takes place. Acute Respiratory Distress Syndrome (ARDS) and maturation of surfactant Surfactant Substances and drugs that lower the surface tension of the mucoid layer lining the pulmonary alveoli. Acute Respiratory Distress Syndrome (ARDS) composition:
      • Surfactant Surfactant Substances and drugs that lower the surface tension of the mucoid layer lining the pulmonary alveoli. Acute Respiratory Distress Syndrome (ARDS) appears in amniotic fluid Amniotic fluid A clear, yellowish liquid that envelopes the fetus inside the sac of amnion. In the first trimester, it is likely a transudate of maternal or fetal plasma. In the second trimester, amniotic fluid derives primarily from fetal lung and kidney. Cells or substances in this fluid can be removed for prenatal diagnostic tests (amniocentesis). Placenta, Umbilical Cord, and Amniotic Cavity between 28 and 32 weeks.
      • Mature surfactant Surfactant Substances and drugs that lower the surface tension of the mucoid layer lining the pulmonary alveoli. Acute Respiratory Distress Syndrome (ARDS) ratios are usually present after 35 weeks.
  • Fetal lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs: Anatomy:
    •  Not functional for gas exchange Gas exchange Human cells are primarily reliant on aerobic metabolism. The respiratory system is involved in pulmonary ventilation and external respiration, while the circulatory system is responsible for transport and internal respiration. Pulmonary ventilation (breathing) represents movement of air into and out of the lungs. External respiration, or gas exchange, is represented by the O2 and CO2 exchange between the lungs and the blood. Gas Exchange, and are filled with fluid
    • The placenta Placenta A highly vascularized mammalian fetal-maternal organ and major site of transport of oxygen, nutrients, and fetal waste products. It includes a fetal portion (chorionic villi) derived from trophoblasts and a maternal portion (decidua) derived from the uterine endometrium. The placenta produces an array of steroid, protein and peptide hormones (placental hormones). Placenta, Umbilical Cord, and Amniotic Cavity serves as the fetus’s respiratory organ.
  • Mechanics of requiring surfactant Surfactant Substances and drugs that lower the surface tension of the mucoid layer lining the pulmonary alveoli. Acute Respiratory Distress Syndrome (ARDS):
  • Surfactant Surfactant Substances and drugs that lower the surface tension of the mucoid layer lining the pulmonary alveoli. Acute Respiratory Distress Syndrome (ARDS):
    • Reduces surface tension Surface tension The force acting on the surface of a liquid, tending to minimize the area of the surface. Acute Respiratory Distress Syndrome (ARDS) within the alveoli Alveoli Small polyhedral outpouchings along the walls of the alveolar sacs, alveolar ducts and terminal bronchioles through the walls of which gas exchange between alveolar air and pulmonary capillary blood takes place. Acute Respiratory Distress Syndrome (ARDS)
    • In effect:
      • Prevents alveolar collapse at the end of the expiration Expiration Ventilation: Mechanics of Breathing
      • ↓ Risk of atelectasis Atelectasis Atelectasis is the partial or complete collapse of a part of the lung. Atelectasis is almost always a secondary phenomenon from conditions causing bronchial obstruction, external compression, surfactant deficiency, or scarring. Atelectasis and ventilatory-perfusion (V/Q) mismatch in the alveoli Alveoli Small polyhedral outpouchings along the walls of the alveolar sacs, alveolar ducts and terminal bronchioles through the walls of which gas exchange between alveolar air and pulmonary capillary blood takes place. Acute Respiratory Distress Syndrome (ARDS)
    • Produced in fetal development to prepare for air-breathing at birth

Surfactant Surfactant Substances and drugs that lower the surface tension of the mucoid layer lining the pulmonary alveoli. Acute Respiratory Distress Syndrome (ARDS)

  • Major constituents of surfactant Surfactant Substances and drugs that lower the surface tension of the mucoid layer lining the pulmonary alveoli. Acute Respiratory Distress Syndrome (ARDS):
    • Phospholipids Phospholipids Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. Lipid Metabolism (85%):
      • Dipalmitoylphosphatidyl choline (DPPC), also referred to as “ lecithin Lecithin A complex mixture of phospholipids; glycolipids; and triglycerides; with substantial amounts of phosphatidylcholines; phosphatidylethanolamines; and phosphatidylinositols, which are sometimes loosely termed as 1, 2-diacyl-3-phosphocholines. Lecithin is a component of the cell membrane and commercially extracted from soybeans and egg yolk. The emulsifying and surfactant properties are useful in food additives and for forming organogels (gels). Fatty Acids and Lipids” (main component)
      • Phosphatidylglycerol (↑ in pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care by 35 weeks and can be used as a marker of lung maturity)
      • Phosphatidylcholine, unsaturated
    • Apoproteins (10%): 
      • SP-A
      • SP-B
      • SP-C
      • SP-D
    • Cholesterol Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Cholesterol Metabolism (neutral lipid)
  • Surfactant Surfactant Substances and drugs that lower the surface tension of the mucoid layer lining the pulmonary alveoli. Acute Respiratory Distress Syndrome (ARDS) synthesis Synthesis Polymerase Chain Reaction (PCR)
    • Phospholipid synthesized in the endoplasmic reticulum Endoplasmic reticulum A system of cisternae in the cytoplasm of many cells. In places the endoplasmic reticulum is continuous with the plasma membrane (cell membrane) or outer membrane of the nuclear envelope. If the outer surfaces of the endoplasmic reticulum membranes are coated with ribosomes, the endoplasmic reticulum is said to be rough-surfaced; otherwise it is said to be smooth-surfaced. The Cell: Organelles → alterations done through the Golgi apparatus → stored in lamellar bodies of type II alveolar cells
    • In the lamellar bodies, phospholipid and surfactant Surfactant Substances and drugs that lower the surface tension of the mucoid layer lining the pulmonary alveoli. Acute Respiratory Distress Syndrome (ARDS) proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis form surfactant Surfactant Substances and drugs that lower the surface tension of the mucoid layer lining the pulmonary alveoli. Acute Respiratory Distress Syndrome (ARDS) lipoprotein complexes.
    • These complexes are secreted into the alveoli Alveoli Small polyhedral outpouchings along the walls of the alveolar sacs, alveolar ducts and terminal bronchioles through the walls of which gas exchange between alveolar air and pulmonary capillary blood takes place. Acute Respiratory Distress Syndrome (ARDS), and the surface film created opposes alveolar collapse.
  • Surfactant Surfactant Substances and drugs that lower the surface tension of the mucoid layer lining the pulmonary alveoli. Acute Respiratory Distress Syndrome (ARDS) recycling: 

Respiration Respiration The act of breathing with the lungs, consisting of inhalation, or the taking into the lungs of the ambient air, and of exhalation, or the expelling of the modified air which contains more carbon dioxide than the air taken in. Nose and Nasal Cavity: Anatomy at birth and RDS

  • Normal transition:
  • In surfactant Surfactant Substances and drugs that lower the surface tension of the mucoid layer lining the pulmonary alveoli. Acute Respiratory Distress Syndrome (ARDS) deficiency ( premature Premature Childbirth before 37 weeks of pregnancy (259 days from the first day of the mother’s last menstrual period, or 245 days after fertilization). Necrotizing Enterocolitis lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs: Anatomy), there is ↑ surface tension Surface tension The force acting on the surface of a liquid, tending to minimize the area of the surface. Acute Respiratory Distress Syndrome (ARDS), requiring ↑ pressure for alveolar expansion, resulting in:
    • Lung instability at end- expiration Expiration Ventilation: Mechanics of Breathing
    • Low lung volume and ↓ compliance Compliance Distensibility measure of a chamber such as the lungs (lung compliance) or bladder. Compliance is expressed as a change in volume per unit change in pressure. Veins: Histology 
    • Collapse of portions of the lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs: Anatomy ( atelectasis Atelectasis Atelectasis is the partial or complete collapse of a part of the lung. Atelectasis is almost always a secondary phenomenon from conditions causing bronchial obstruction, external compression, surfactant deficiency, or scarring. Atelectasis) → V/Q mismatch
  • This mismatch leads to hypoxia Hypoxia Sub-optimal oxygen levels in the ambient air of living organisms. Ischemic Cell Damage, hypercapnia, and acidosis Acidosis A pathologic condition of acid accumulation or depletion of base in the body. The two main types are respiratory acidosis and metabolic acidosis, due to metabolic acid build up. Respiratory Acidosis:
    • May result in pulmonary arterial vasoconstriction Vasoconstriction The physiological narrowing of blood vessels by contraction of the vascular smooth muscle. Vascular Resistance, Flow, and Mean Arterial Pressure with increased right-to-left shunting through the foramen ovale Foramen ovale An opening in the wall between the right and the left upper chambers (heart atria) of a fetal heart. Oval foramen normally closes soon after birth; when it fails to close the condition is called patent oval foramen. Patent Foramen Ovale and ductus arteriosus Ductus arteriosus A fetal blood vessel connecting the pulmonary artery with the descending aorta. Patent Ductus Arteriosus (PDA)
    • ↓ Pulmonary blood flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure ischemia Ischemia A hypoperfusion of the blood through an organ or tissue caused by a pathologic constriction or obstruction of its blood vessels, or an absence of blood circulation. Ischemic Cell Damage and injury of alveoli Alveoli Small polyhedral outpouchings along the walls of the alveolar sacs, alveolar ducts and terminal bronchioles through the walls of which gas exchange between alveolar air and pulmonary capillary blood takes place. Acute Respiratory Distress Syndrome (ARDS) and triggering of inflammatory response 
    • Inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation → effusion/ edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema in alveolar spaces → ↑ pulmonary vascular resistance Vascular Resistance The force that opposes the flow of blood through a vascular bed. It is equal to the difference in blood pressure across the vascular bed divided by the cardiac output. Vascular Resistance, Flow, and Mean Arterial Pressure or PVR (which, in normal cases, should be low)
  • Low urine Urine Liquid by-product of excretion produced in the kidneys, temporarily stored in the bladder until discharge through the urethra. Bowen Disease and Erythroplasia of Queyrat output in premature infants Premature infants A human infant born before 37 weeks of gestation. Sudden Infant Death Syndrome (SIDS) contribute to fluid retention.

Clinical Presentation

Signs and symptoms

  • RDS:
    • Starts within minutes or hours after birth
    • Becomes progressively worse over the first 48–72 hours of life
  • The affected infants are typically premature Premature Childbirth before 37 weeks of pregnancy (259 days from the first day of the mother’s last menstrual period, or 245 days after fertilization). Necrotizing Enterocolitis and show signs of respiratory distress:
  • By auscultation:
    • Breath sounds may be normal or diminished, with a harsh tubular quality Quality Activities and programs intended to assure or improve the quality of care in either a defined medical setting or a program. The concept includes the assessment or evaluation of the quality of care; identification of problems or shortcomings in the delivery of care; designing activities to overcome these deficiencies; and follow-up monitoring to ensure effectiveness of corrective steps. Quality Measurement and Improvement.
    • Bilateral fine basal crackles

Course of RDS

  • Uncomplicated RDS typically progresses for 48–72 hours and can be followed by:
    • ↑ Endogenous production of surfactant Surfactant Substances and drugs that lower the surface tension of the mucoid layer lining the pulmonary alveoli. Acute Respiratory Distress Syndrome (ARDS)
    • Resolution of the respiratory distress by 1 week of age
    • Infant may have diuresis in this process.
  • Severe RDS or those inadequately treated may develop:
    • Hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension
    • Cyanosis Cyanosis A bluish or purplish discoloration of the skin and mucous membranes due to an increase in the amount of deoxygenated hemoglobin in the blood or a structural defect in the hemoglobin molecule. Pulmonary Examination
    • Grunting Grunting Physical Examination of the Newborn decrease or disappear
    • Mixed respiratory- metabolic acidosis Metabolic acidosis The renal system is responsible for eliminating the daily load of non-volatile acids, which is approximately 70 millimoles per day. Metabolic acidosis occurs when there is an increase in the levels of new non-volatile acids (e.g., lactic acid), renal loss of HCO3-, or ingestion of toxic alcohols. Metabolic Acidosis
    • Apnea and irregular respirations, which indicate fatigability
  • Complications of neonatal RDS:
    • Respiratory failure Respiratory failure Respiratory failure is a syndrome that develops when the respiratory system is unable to maintain oxygenation and/or ventilation. Respiratory failure may be acute or chronic and is classified as hypoxemic, hypercapnic, or a combination of the two. Respiratory Failure
    • Alveolar air leaks (interstitial emphysema Emphysema Enlargement of air spaces distal to the terminal bronchioles where gas-exchange normally takes place. This is usually due to destruction of the alveolar wall. Pulmonary emphysema can be classified by the location and distribution of the lesions. Chronic Obstructive Pulmonary Disease (COPD), pneumothorax Pneumothorax A pneumothorax is a life-threatening condition in which air collects in the pleural space, causing partial or full collapse of the lung. A pneumothorax can be traumatic or spontaneous. Patients present with a sudden onset of sharp chest pain, dyspnea, and diminished breath sounds on exam. Pneumothorax)
    • Pulmonary hemorrhage
    • Intraventricular hemorrhage Intraventricular hemorrhage Bleeding within the cerebral ventricles. It is associated with intraventricular trauma, aneurysm, vascular malformations, hypertension and in very low birth weight infants. Intracerebral Hemorrhage
  • Treatment with exogenous surfactant Surfactant Substances and drugs that lower the surface tension of the mucoid layer lining the pulmonary alveoli. Acute Respiratory Distress Syndrome (ARDS) improves the course of the disease and leads to a faster resolution of symptoms.

Diagnosis

  • Diagnosis is mainly clinical:
    • Prematurity
    • Clinical exam
  • Chest X-ray X-ray Penetrating electromagnetic radiation emitted when the inner orbital electrons of an atom are excited and release radiant energy. X-ray wavelengths range from 1 pm to 10 nm. Hard x-rays are the higher energy, shorter wavelength x-rays. Soft x-rays or grenz rays are less energetic and longer in wavelength. The short wavelength end of the x-ray spectrum overlaps the gamma rays wavelength range. The distinction between gamma rays and x-rays is based on their radiation source. Pulmonary Function Tests:
  • Arterial blood gas Arterial blood gas Respiratory Alkalosis (ABG):
    • Hypoxemia that improves with oxygen supplementation
    • Hypercapnia as disease progresses
    • Metabolic acidosis Metabolic acidosis The renal system is responsible for eliminating the daily load of non-volatile acids, which is approximately 70 millimoles per day. Metabolic acidosis occurs when there is an increase in the levels of new non-volatile acids (e.g., lactic acid), renal loss of HCO3-, or ingestion of toxic alcohols. Metabolic Acidosis or mixed respiratory- metabolic acidosis Metabolic acidosis The renal system is responsible for eliminating the daily load of non-volatile acids, which is approximately 70 millimoles per day. Metabolic acidosis occurs when there is an increase in the levels of new non-volatile acids (e.g., lactic acid), renal loss of HCO3-, or ingestion of toxic alcohols. Metabolic Acidosis
Chest x-ray respiratory distress syndrome infant

Chest radiograph 1 day after birth of a boy who, after 29 weeks and 3 days of gestational age Gestational age The age of the conceptus, beginning from the time of fertilization. In clinical obstetrics, the gestational age is often estimated as the time from the last day of the last menstruation which is about 2 weeks before ovulation and fertilization. Pregnancy: Diagnosis, Physiology, and Care, developed respiratory distress:
The radiograph shows signs of respiratory distress syndrome (RDS) in the form of generalized fine granular opacities that create air bronchograms Air Bronchograms Imaging of the Lungs and Pleura. The thorax is bell-shaped due to decreased lung volume.

Image: “ X-ray X-ray Penetrating electromagnetic radiation emitted when the inner orbital electrons of an atom are excited and release radiant energy. X-ray wavelengths range from 1 pm to 10 nm. Hard x-rays are the higher energy, shorter wavelength x-rays. Soft x-rays or grenz rays are less energetic and longer in wavelength. The short wavelength end of the x-ray spectrum overlaps the gamma rays wavelength range. The distinction between gamma rays and x-rays is based on their radiation source. Pulmonary Function Tests of infant respiratory distress syndrome (IRDS)” by Mikael Häggström. License: CC0 1.0

Management

Prevention of neonatal RDS

  • As RDS is a disease of prematurity, the most effective preventive method is to avoid preterm delivery, when possible.
  • Determine fetal lung maturity (via amniotic fluid Amniotic fluid A clear, yellowish liquid that envelopes the fetus inside the sac of amnion. In the first trimester, it is likely a transudate of maternal or fetal plasma. In the second trimester, amniotic fluid derives primarily from fetal lung and kidney. Cells or substances in this fluid can be removed for prenatal diagnostic tests (amniocentesis). Placenta, Umbilical Cord, and Amniotic Cavity) for threatened preterm birth Preterm birth Preterm labor refers to regular uterine contractions leading to cervical change prior to 37 weeks of gestation; preterm birth refers to birth prior to 37 weeks of gestation. Preterm birth may be spontaneous due to preterm labor, preterm prelabor rupture of membranes (PPROM), or cervical insufficiency. Preterm Labor and Birth:
    • Phosphatidylglycerol levels
    • Lecithin Lecithin A complex mixture of phospholipids; glycolipids; and triglycerides; with substantial amounts of phosphatidylcholines; phosphatidylethanolamines; and phosphatidylinositols, which are sometimes loosely termed as 1, 2-diacyl-3-phosphocholines. Lecithin is a component of the cell membrane and commercially extracted from soybeans and egg yolk. The emulsifying and surfactant properties are useful in food additives and for forming organogels (gels). Fatty Acids and Lipids/sphingomyelin levels:
      • Level > 2 (by 35 weeks) indicates low risk for RDS.
      • Time consuming
    • Lamellar body counts:
  • If an early delivery cannot be avoided, treatment includes: 
    • Antenatal corticosteroid therapy:
    • Exogenous surfactant Surfactant Substances and drugs that lower the surface tension of the mucoid layer lining the pulmonary alveoli. Acute Respiratory Distress Syndrome (ARDS) replacement therapy:
      • Beneficial to preterm infants born < 30 weeks gestation
      • Provides support until endogenous production begins
      • Administration within 30–60 minutes of life provides the most benefit.
      • Administered via endotracheal or less-invasive route (i.e., aerosolized)

Respiratory management

  • Resuscitation and evaluation in the delivery room focuses on airway Airway ABCDE Assessment, breathing, and circulation Circulation The movement of the blood as it is pumped through the cardiovascular system. ABCDE Assessment (ABCs).
  • Respiratory support especially for babies under 28 weeks gestational age Gestational age The age of the conceptus, beginning from the time of fertilization. In clinical obstetrics, the gestational age is often estimated as the time from the last day of the last menstruation which is about 2 weeks before ovulation and fertilization. Pregnancy: Diagnosis, Physiology, and Care
  • The goal is for effective ventilation Ventilation The total volume of gas inspired or expired per unit of time, usually measured in liters per minute. Ventilation: Mechanics of Breathing and oxygenation in the least invasive manner possible:
    • Keep PaO2 at 50–80 mm MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma Hg:
    • Should maintain pH pH The quantitative measurement of the acidity or basicity of a solution. Acid-Base Balance at > 7.25
  • Interventions:
    • Nasal continuous positive airway Airway ABCDE Assessment pressure (nCPAP):
      • Considered an alternative to endotracheal intubation Intubation Peritonsillar Abscess or mechanical ventilation Ventilation The total volume of gas inspired or expired per unit of time, usually measured in liters per minute. Ventilation: Mechanics of Breathing, if possible
      • CPAP CPAP A technique of respiratory therapy, in either spontaneously breathing or mechanically ventilated patients, in which airway pressure is maintained above atmospheric pressure throughout the respiratory cycle by pressurization of the ventilatory circuit. Noninvasive Ventilation (pressure of 5 cm H2O, and increase to 6–8 cm H2O as indicated)
    • Endotracheal intubation Intubation Peritonsillar Abscess and assisted mechanical ventilation Ventilation The total volume of gas inspired or expired per unit of time, usually measured in liters per minute. Ventilation: Mechanics of Breathing for respiratory failure Respiratory failure Respiratory failure is a syndrome that develops when the respiratory system is unable to maintain oxygenation and/or ventilation. Respiratory failure may be acute or chronic and is classified as hypoxemic, hypercapnic, or a combination of the two. Respiratory Failure:
      • PaO2 < 50 mm MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma Hg despite 100% oxygen 100% Oxygen Cluster Headaches or FiO₂ requirement on CPAP CPAP A technique of respiratory therapy, in either spontaneously breathing or mechanically ventilated patients, in which airway pressure is maintained above atmospheric pressure throughout the respiratory cycle by pressurization of the ventilatory circuit. Noninvasive Ventilation ≥ 0.40
      • PCO2 > 60 mm MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma Hg
      • pH pH The quantitative measurement of the acidity or basicity of a solution. Acid-Base Balance < 7.20
    • High-frequency oscillatory ventilation Ventilation The total volume of gas inspired or expired per unit of time, usually measured in liters per minute. Ventilation: Mechanics of Breathing (HFOV) may be considered in severe cases or to reduce ventilator-associated lung injury.
Newborn premature infant on cpap

Respiratory distress syndrome: newborn Newborn An infant during the first 28 days after birth. Physical Examination of the Newborn premature Premature Childbirth before 37 weeks of pregnancy (259 days from the first day of the mother’s last menstrual period, or 245 days after fertilization). Necrotizing Enterocolitis infant (on continuous positive airway Airway ABCDE Assessment pressure)

Image: “ Premature Premature Childbirth before 37 weeks of pregnancy (259 days from the first day of the mother’s last menstrual period, or 245 days after fertilization). Necrotizing Enterocolitis infant CPAP CPAP A technique of respiratory therapy, in either spontaneously breathing or mechanically ventilated patients, in which airway pressure is maintained above atmospheric pressure throughout the respiratory cycle by pressurization of the ventilatory circuit. Noninvasive Ventilation” by Brian Hall. License: Public Domain

Additional treatment

  • Thermal regulation:
    • Needed to avoid neonatal hypothermia Hypothermia Hypothermia can be defined as a drop in the core body temperature below 35°C (95°F) and is classified into mild, moderate, severe, and profound forms based on the degree of temperature decrease. Hypothermia
    • Place the infant in an isolette or radiant warmer with the core temperature maintained between 36.5°C (97.7°F) and 37°C (98.6°F).
  • Fluids and nutrition:
    • Balance fluids as the neonatal kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys: Anatomy have limited concentrating abilities:
      • Daily weights
      • Close attention Attention Focusing on certain aspects of current experience to the exclusion of others. It is the act of heeding or taking notice or concentrating. Psychiatric Assessment to input and output
      • Regular Regular Insulin electrolyte monitoring
      • Avoid fluid overload (↑ the risk of patent ductus arteriosus Patent ductus arteriosus The ductus arteriosus (DA) allows blood to bypass pulmonary circulation. After birth, the DA remains open for up to 72 hours and then constricts and involutes, becoming the ligamentum arteriosum. Failure of this process to occur results in patent ductus arteriosus (PDA), a condition that causes up to 10% of congenital heart defects. Patent Ductus Arteriosus (PDA)/ PDA PDA The ductus arteriosus (DA) allows blood to bypass pulmonary circulation. After birth, the DA remains open for up to 72 hours and then constricts and involutes, becoming the ligamentum arteriosum. Failure of this process to occur results in patent ductus arteriosus (PDA), a condition that causes up to 10% of congenital heart defects. Patent Ductus Arteriosus (PDA))
    • Nutritional support: total parenteral nutrition Parenteral nutrition The administering of nutrients for assimilation and utilization by a patient who cannot maintain adequate nutrition by enteral feeding alone. Nutrients are administered by a route other than the alimentary canal (e.g., intravenously, subcutaneously). Central Venous Catheter
  • Cardiovascular support:
    • Closely monitor blood pressure and avoid hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension.
    • Options for low blood pressure:
      • Normal saline Normal saline A crystalloid solution that contains 9. 0g of sodium chloride per liter of water. It has a variety of uses, including: as a contact lens solution, in ophthalmic solutions and nasal lavage, in wound irrigation, and for fluid therapy. Intravenous Fluids (with caution), vasopressors Vasopressors Sepsis in Children when indicated
      • Stress doses of hydrocortisone Hydrocortisone The main glucocorticoid secreted by the adrenal cortex. Its synthetic counterpart is used, either as an injection or topically, in the treatment of inflammation, allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some neoplastic conditions. Immunosuppressants (in persistent hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension)

Differential Diagnosis

  • Meconium aspiration syndrome Meconium Aspiration Syndrome A condition caused by inhalation of meconium into the lung of fetus or newborn, usually due to vigorous respiratory movements during difficult parturition or respiratory system abnormalities. Meconium aspirate may block small airways leading to difficulties in pulmonary gas exchange and aspiration pneumonia. Pediatric Chest Abnormalities (MAS): mild-to-severe respiratory distress more often in term or post-term infants who are delivered with meconium Meconium The thick green-to-black mucilaginous material found in the intestines of a full-term fetus. It consists of secretions of the intestinal glands; bile pigments; fatty acids; amniotic fluid; and intrauterine debris. It constitutes the first stools passed by a newborn. Prenatal and Postnatal Physiology of the Neonate-stained fluid. Aspiration of thick meconium Meconium The thick green-to-black mucilaginous material found in the intestines of a full-term fetus. It consists of secretions of the intestinal glands; bile pigments; fatty acids; amniotic fluid; and intrauterine debris. It constitutes the first stools passed by a newborn. Prenatal and Postnatal Physiology of the Neonate can lead to hypoxia Hypoxia Sub-optimal oxygen levels in the ambient air of living organisms. Ischemic Cell Damage and acidosis Acidosis A pathologic condition of acid accumulation or depletion of base in the body. The two main types are respiratory acidosis and metabolic acidosis, due to metabolic acid build up. Respiratory Acidosis with partial airway Airway ABCDE Assessment obstruction causing pneumothorax Pneumothorax A pneumothorax is a life-threatening condition in which air collects in the pleural space, causing partial or full collapse of the lung. A pneumothorax can be traumatic or spontaneous. Patients present with a sudden onset of sharp chest pain, dyspnea, and diminished breath sounds on exam. Pneumothorax or pneumomediastinum Pneumomediastinum Mediastinitis. Chest X-rays X-rays X-rays are high-energy particles of electromagnetic radiation used in the medical field for the generation of anatomical images. X-rays are projected through the body of a patient and onto a film, and this technique is called conventional or projectional radiography. X-rays may be normal or may show parenchymal opacification, patchy infiltrates, and/or flattening of the diaphragm Diaphragm The diaphragm is a large, dome-shaped muscle that separates the thoracic cavity from the abdominal cavity. The diaphragm consists of muscle fibers and a large central tendon, which is divided into right and left parts. As the primary muscle of inspiration, the diaphragm contributes 75% of the total inspiratory muscle force. Diaphragm: Anatomy. Management is ideally antenatal with prevention of delivery past 41 weeks and intrapartum fetal heart monitoring. After delivery, support is based on neonatal resuscitation guidelines.
  • Choanal atresia Atresia Hypoplastic Left Heart Syndrome (HLHS): most common nasal malformation. This deformity Deformity Examination of the Upper Limbs can be isolated or part of a dysmorphic syndrome with bony abnormalities of the pterygoid plate. Choanal atresia Atresia Hypoplastic Left Heart Syndrome (HLHS) can be suspected in infants with cyclic cyanosis Cyanosis A bluish or purplish discoloration of the skin and mucous membranes due to an increase in the amount of deoxygenated hemoglobin in the blood or a structural defect in the hemoglobin molecule. Pulmonary Examination, which is aggravated by feeding and relieved by crying when the mouth is open. Unilateral choanal atresia Atresia Hypoplastic Left Heart Syndrome (HLHS) (⅔ of cases) may not be diagnosed initially. Inability to pass a catheter through the nose Nose The nose is the human body’s primary organ of smell and functions as part of the upper respiratory system. The nose may be best known for inhaling oxygen and exhaling carbon dioxide, but it also contributes to other important functions, such as tasting. The anatomy of the nose can be divided into the external nose and the nasal cavity. Nose and Nasal Cavity: Anatomy 3–4 cm into the oropharynx Oropharynx The middle portion of the pharynx that lies posterior to the mouth, inferior to the soft palate, and superior to the base of the tongue and epiglottis. It has a digestive function as food passes from the mouth into the oropharynx before entering esophagus. Pharynx: Anatomy is suggestive of the diagnosis. Diagnosis is confirmed by a CT scan with intranasal contrast that shows narrowing at the level of the pterygoid plate. Management consists of placing an oral airway Airway ABCDE Assessment and gavage feeding until repair of the obstruction with surgery or endoscopy Endoscopy Procedures of applying endoscopes for disease diagnosis and treatment. Endoscopy involves passing an optical instrument through a small incision in the skin i.e., percutaneous; or through a natural orifice and along natural body pathways such as the digestive tract; and/or through an incision in the wall of a tubular structure or organ, i.e. Transluminal, to examine or perform surgery on the interior parts of the body. Gastroesophageal Reflux Disease (GERD).
  • Transient tachypnea of the newborn Transient tachypnea of the newborn Abnormal increase in respiratory rate in the newborn. It is self-limiting and attributed to the delayed fetal lung fluid clearance often in caesarean section delivery. Physical Examination of the Newborn (TTN): delayed clearance of lung fluid more common in late preterm infants and term infants born via C-section without labor Labor Labor is the normal physiologic process defined as uterine contractions resulting in dilatation and effacement of the cervix, which culminates in expulsion of the fetus and the products of conception. Normal and Abnormal Labor as well as babies born with respiratory depression. This disorder often follows an uneventful normal term vaginal delivery or Cesarean delivery Cesarean Delivery Cesarean delivery (CD) is the operative delivery of ≥ 1 infants through a surgical incision in the maternal abdomen and uterus. Cesarean deliveries may be indicated for a number of either maternal or fetal reasons, most commonly including fetal intolerance to labor, arrest of labor, a history of prior uterine surgery, fetal malpresentation, and placental abnormalities. Cesarean Delivery with early onset of tachypnea Tachypnea Increased respiratory rate. Pulmonary Examination, sometimes with retractions or expiratory grunting Grunting Physical Examination of the Newborn. A chest X-ray X-ray Penetrating electromagnetic radiation emitted when the inner orbital electrons of an atom are excited and release radiant energy. X-ray wavelengths range from 1 pm to 10 nm. Hard x-rays are the higher energy, shorter wavelength x-rays. Soft x-rays or grenz rays are less energetic and longer in wavelength. The short wavelength end of the x-ray spectrum overlaps the gamma rays wavelength range. The distinction between gamma rays and x-rays is based on their radiation source. Pulmonary Function Tests would show prominent pulmonary vascular markings, fluid lines in the fissures, over-aeration, flattened diaphragms, and pleural fluid. This disorder usually resolves in 2–3 days, and treatment is supportive.
  • Congenital Congenital Chorioretinitis diaphragmatic hernia Hernia Protrusion of tissue, structure, or part of an organ through the bone, muscular tissue, or the membrane by which it is normally contained. Hernia may involve tissues such as the abdominal wall or the respiratory diaphragm. Hernias may be internal, external, congenital, or acquired. Abdominal Hernias (CDH): a congenital Congenital Chorioretinitis defect in the fetal diaphragm Diaphragm The diaphragm is a large, dome-shaped muscle that separates the thoracic cavity from the abdominal cavity. The diaphragm consists of muscle fibers and a large central tendon, which is divided into right and left parts. As the primary muscle of inspiration, the diaphragm contributes 75% of the total inspiratory muscle force. Diaphragm: Anatomy that allows herniation Herniation Omphalocele of abdominal contents into the thorax, leading to pulmonary hypoplasia Hypoplasia Hypoplastic Left Heart Syndrome (HLHS) on the affected side. The types are posterolateral Bochdalek hernia Hernia Protrusion of tissue, structure, or part of an organ through the bone, muscular tissue, or the membrane by which it is normally contained. Hernia may involve tissues such as the abdominal wall or the respiratory diaphragm. Hernias may be internal, external, congenital, or acquired. Abdominal Hernias (left-sided Bochdalek in 85% of cases), anterior Morgagni hernia Hernia Protrusion of tissue, structure, or part of an organ through the bone, muscular tissue, or the membrane by which it is normally contained. Hernia may involve tissues such as the abdominal wall or the respiratory diaphragm. Hernias may be internal, external, congenital, or acquired. Abdominal Hernias, paraesophageal hernia Hernia Protrusion of tissue, structure, or part of an organ through the bone, muscular tissue, or the membrane by which it is normally contained. Hernia may involve tissues such as the abdominal wall or the respiratory diaphragm. Hernias may be internal, external, congenital, or acquired. Abdominal Hernias, and hiatal hernia Hernia Protrusion of tissue, structure, or part of an organ through the bone, muscular tissue, or the membrane by which it is normally contained. Hernia may involve tissues such as the abdominal wall or the respiratory diaphragm. Hernias may be internal, external, congenital, or acquired. Abdominal Hernias. Mild cases can be repaired in the first days of life with good long-term prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas. More-severe cases require high levels of support; involve long-term respiratory, neurodevelopmental, and growth issues; and can be lethal.
  • Persistent pulmonary hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension (PPHN): the pulmonary vascular pressure remains high after birth instead of transitioning to a lower-pressure system. This condition leads to right-to-left shunting across the foramen ovale Foramen ovale An opening in the wall between the right and the left upper chambers (heart atria) of a fetal heart. Oval foramen normally closes soon after birth; when it fails to close the condition is called patent oval foramen. Patent Foramen Ovale and patent ductus arteriosus Patent ductus arteriosus The ductus arteriosus (DA) allows blood to bypass pulmonary circulation. After birth, the DA remains open for up to 72 hours and then constricts and involutes, becoming the ligamentum arteriosum. Failure of this process to occur results in patent ductus arteriosus (PDA), a condition that causes up to 10% of congenital heart defects. Patent Ductus Arteriosus (PDA), causing severe hypoxemia. This condition is more common in term and late-preterm (≥ 34 weeks) infants. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship often exhibit distress at delivery or within 24 hours, with tachypnea Tachypnea Increased respiratory rate. Pulmonary Examination, grunting Grunting Physical Examination of the Newborn, cyanosis Cyanosis A bluish or purplish discoloration of the skin and mucous membranes due to an increase in the amount of deoxygenated hemoglobin in the blood or a structural defect in the hemoglobin molecule. Pulmonary Examination, and nasal flaring. Definitive diagnosis is with echocardiogram Echocardiogram Transposition of the Great Vessels (showing pulmonary hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension). Management is supportive and includes oxygen administration, ventilatory support, and circulatory support.

References

  1. Ballast, A. (2019). Respiratory distress syndrome in neonates (Hyaline membrane disease). Merck Manuals. Retrieved March 22, 2021, from https://www.merckmanuals.com/professional/pediatrics/respiratory-problems-in-neonates/respiratory-distress-syndrome-in-neonates
  2. Garcia-Prats, J. (2021). Meconium aspiration syndrome: Prevention and management. UpToDate. Retrieved April 4, 2021, from https://www.uptodate.com/contents/meconium-aspiration-syndrome-prevention-and-management
  3. Gillen-Goldstein, J, MacKenzie, A, Funai, E. (2019). Assessment of fetal lung maturity. UpToDate. Retrieved April 11, 2021, from https://www.uptodate.com/contents/assessment-of-fetal-lung-maturity
  4. Isaacson, G. (2021). Congenital anomalies of the nose. UpToDate. Retrieved April 4, 2021, from https://www.uptodate.com/contents/congenital-anomalies-of-the-nose
  5. Martin, R. (2020). Pathophysiology, clinical manifestations, and diagnosis of respiratory distress syndrome in the newborn. UpToDate. Retrieved March 22, 2021, from https://www.uptodate.com/contents/pathophysiology-clinical-manifestations-and-diagnosis-of-respiratory-distress-syndrome-in-the-newborn
  6. Martin, R, Deakins, K. (2021). Respiratory support, oxygen delivery, and oxygen monitoring in the newborn. UpToDate. Retrieved April 12, 2021, from https://www.uptodate.com/contents/respiratory-support-oxygen-delivery-and-oxygen-monitoring-in-the-newborn
  7. Ramachandrappa, A. (2021). Elective Cesarean section: Its impact on neonatal respiratory outcome. Retrieved March 26, 2021, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2453515/
  8. Stark, A, Eichenwald, E. (2021). Persistent pulmonary hypertension of the newborn. UpToDate. Retrieved April 4, 2021, from https://www.uptodate.com/contents/persistent-pulmonary-hypertension-of-the-newborn
  9. Yadav, S, Lee, B. (2020). Neonatal respiratory distress syndrome. Retrieved March 26, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK560779

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