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.

Differential Diagnoses

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Ammari A, Suri M, Milisavljevic V, et al. Variables associated with the early failure of nasal CPAP in very low birth weight infants. J Pediatr. 2005 Sep. 147(3):341-7. [QxMD MEDLINE Link].
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Lampland AL, Plumm B, Worwa C, Meyers P, Mammel MC. Bi-level CPAP does not improve gas exchange when compared with conventional CPAP for the treatment of neonates recovering from respiratory distress syndrome. Arch Dis Child Fetal Neonatal Ed. 2015 Jan. 100(1):F31-4. [QxMD MEDLINE Link].
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Holleman-Duray D, Kaupie D, Weiss MG. Heated humidified high-flow nasal cannula: use and a neonatal early extubation protocol. J Perinatol. 2007 Dec. 27(12):776-81. [QxMD MEDLINE Link]. [Full Text].
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Media Gallery

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.
Microscopic appearance of lungs of an infant with respiratory distress syndrome. Hematoxylin and eosin stain shows hyaline membranes (pink areas).
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.
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.
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.
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.
Effects of early treatment with low-dose inhaled nitric oxide (iNO) on brain injury (ie, grade 3-4 intracranial hemorrhage [ICH], periventricular leukomalacia [PVL], ventriculomegaly) in premature infants according to birth weight strata. iNO reduced ultrasonography findings of brain injury for the overall group (n = 793), with the largest effect in the 750-g to 999-g group (n = 280). Control = □; iNO = ■.
Effects of early treatment of preterm infants with low-dose inhaled nitric oxide (iNO) on bronchopulmonary dysplasia (BPD) incidence by birth weight strata. No difference in reduction was reported in infants weighing less than 1000 g (n = 129). Control = □; iNO = ■.
Effects of inhaled nitric oxide (iNO) survival without bronchopulmonary dysplasia (BPD) for infants aged 7-21 days. iNO increased survival without BPD in infants who were treated before age 14 days (n = 727).
Assisted ventilation newborn –Intubation and meconium aspiration. Video courtesy of Therese Canares, MD, and Jonathan Valente, MD, Rhode Island Hospital, Brown University.

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Outcome	Number of Trials	Relative Risk (95% CI)	Relative Difference (95% CI)
Pneumothorax	3	0.70 (0.59, 0.82)	-5.2% (-7.5%, -2.9%)
Bronchopulmonary dysplasia (BPD)	3	0.97 (0.88, 1.06)	-1.2% (-4.6%, 2.2%)
Mortality	4	0.87 (0.77, 0.99)	-2.8% (-5.5%, 0.0%)
BPD or death	3	0.94 (0.88, 1.00)	-3.7% (-7.2%, 0.0%)

Type	Source	Composition	Dosing	Comments
Beractant (Survanta)	Bovine lung mince	Dipalmitoyl phosphatidylcholine (DPPC), tripalmitin, SP-B < 0.5%, SP-C 99% of TP wt/wt	4mL/kg (100mg/kg), 1-4 doses every 6h	Refrigerate
Surfactant-TA (Surfacten)	Bovine lung mince		4mL/kg (100mg/kg), 1-4 doses every 6h	Refrigerate
Bovactant (Alveofact)	Bovine lung lavage	99% PL, 1% SP-B and SP-C	45mg/mL	From the Federal Republic of Germany
Bovine lipid extract surfactant (bLES)	Bovine lung lavage	75% phosphatidylcholine (PC) and 1% SP-B and SP-C	135mg/kg/dose (5mL/kg), 1-4 doses every 12h	Canadian
Infasurf	Calf lung lavage	DPPC, tripalmitin, SP-B 290g/mL, SP-C 360g/mL	3mL/kg (105mg/kg), 1-4 doses every 6-12h	6mL vials, refrigerate
Calf lung surfactant extract (CLSE)	Similar to Infasurf
Poractant alpha (Curosurf)	Minced pig lung	Phospholipids (DPPC, phosphatidylglycerol [PG]), neutral lipids, fatty acids; SP-B and SP-C; 80mg/mL of PL/mL [54mg PC (30.5mg DPPC and 1mg protein includes 0.3mg of SP-B)]	Initially 2.5mL/kg (200mg/kg), followed by 1.25mL (100mg)/kg	1.5 and 3mL
Colfosceril palmitate (Exosurf)	Synthetic	85% DPPC, 9% hexadecanol, 6% tyloxapol	5mL/kg (67.5mg/kg), 1-4 doses every 12h	No longer available; lyophilized, dissolve in 8mL
Lucinactant (Surfaxin)	Synthetic	Protein: KL4 (sinapultide) resembles SP-B; Phospholipids: DPPC, palmitoyloleoyl phosphatidylcholine (POPG)	175 mg/kg/dose phospholipid	FDA-approved March 2012; warmed for 15min at 44°C on a heating block, followed by vigorous shaking until a uniform, free-flowing suspension forms
Artificial lung expanding compound (ALEC)	Synthetic	70% DPPC, 30% unsaturated phosphatidylglycerol	No data	Discontinued

	Natural Surfactant Treatment		Synthetic Surfactant Treatment
Outcome	Number of Trials	Relative Risk (95% Confidence Interval [CI]) Relative Difference (95% CI)	Number of Trials	Relative Risk (95% CI) Relative Difference (95% CI)
Pneumothorax	12	0.43 (0.35, 0.52) -17% (-21%, -13%)	5	0.64 (0.55, 0.76) -9% (-12%, -6%)
Bronchopulmonary dysplasia (BPD)	9	0.94 (0.72, 1.22) -2% (-9%, 4%)	5	0.75 (0.61, 0.92) -4% (-6%, -1%)
Mortality	12	0.68 (0.57, 0.80) -9% (-13%, -5%)	6	0.73 (0.61, 0.88) -5% (-7%, -2%)
BPD or death	10	0.76 (0.65, 0.90) -14% (-21%, -7%)	4	0.73 (0.65, 0.83) -8% (-11%, -5%)

	Natural Prophylaxis		Synthetic Prophylaxis
Outcome	Number of Trials	Relative Risk (95% CI) Relative Difference (95% CI)	Number of Trials	Relative Risk (95% CI) Relative Difference (95% CI)
Pneumothorax	8	0.35 (0.26, 0.49) -13% (-20%, -11%)	6	0.67 (0.50, 0.90) -5% (-9%, -2%)
BPD	7	0.93 (0.80, 1.07) -4% (-9%, -3%)	4	1.06 (0.83, 1.36) 1% (-4%, 6%)
Mortality	7	0.60 (0.44, 0.83) -7% (-12%, -3%)	7	0.70 (0.58, 0.85) -7% (-11%, -3%)
BPD or death	7	0.84 (0.75, 0.93) -10% (-16%, -4%)	4	0.80 (0.77, 1.03) -4% (-10%, 1%)

Outcome	Number of Trials	Relative Risk (95% CI)	Relative Difference (95% CI)
Pneumothorax	5	0.68 (0.56, 0.83)	-4.1% (-6.3%, -2.0%)
BPD	4	0.97 (0.88, 1.07)	-1.2% (-5.4%, -2.9%)
Mortality	7	0.88 (0.76, 1.02)	-2.2% (-4.7%, 0.4%)
BPD or death	2	0.94 (0.87, 1.01)	-3.6% (-8.0%, 0.8%)

Study	Number Enrolled	Mean Gestational Age (wk)	Mean Birth Weight (g)	Mean Oxygen Index	Placebo Death Rate	Therapy Duration (d)	Maximum Dose	% Change in Death/BPD
Kinsella et al^[65]	80	27	1000	30	53%	7	5 ppm	-15%
Schreiber et al^[66]	201	27.2	970	10	22.5%	7	10 ppm	-15%
Van Meurs et al^[67]	420	26	839	22	44%	3	10 ppm	-2%
Ballard et al^[68]	587	26	760	7	6%	24	20 ppm	-11%
Kinsella et al^[69]	793	25	792	5	25%	14	5 ppm	-4%

Outcome	Number of Trials	Relative Risk (95% CI)	Relative Difference (95% CI)
Pneumothorax	6	0.62 (0.42, 0.89)	-2.1% (-3.7%, -0.55)
BPD	7	0.95 (0.81, 1.11)	-0.9% (-3.5%, 1.7%)
Mortality	6	0.59 (0.46, 0.76)	-4.6% (-6.8%, -2.5%)
BPD or death	7	0.85 (0.76, 0.95)	-4.5% (-7.4%, -1.5%)
Infants < 30 wk of gestation
Mortality	6	0.60 (0.47, 0.77)	-6.5% (-9.6%, -3.4%)
BPD or death	7	0.86 (0.77, 0.96)	-5.5% (-9.6%, -1.5%)

Respiratory Distress Syndrome Clinical Presentation

History

Physical Examination

References

Tables

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