Respiratory distress syndrome (RDS), also known as hyaline membrane disease, is a respiratory disorder in premature infants. A soap-like substance called surfactant covers small alveoli (sacs responsible for exchanging air in the lungs) in healthy infants’ lungs reducing the surface tension and making lung inflation easier. In premature infants’ lungs however, breathing can be problematic due to lack of surfactant secretion.
 

Epidemiology, Prevalence, Economic Burden, and Vulnerable Populations

Respiratory distress syndrome affects about 1% of premature infants and is their leading cause of death (1). Reports show that about 12% of all babies born in the United States are born prematurely, and about 10% of these babies have RDS (2).
Younger premature infants are more likely to have RDS. Babies born at 29 weeks have a 60% chance of being born with RDS (3). Various factors cause preterm delivery in pregnant women including low prenatal care, previous preterm birth, low maternal body mass, poverty, periodontal disease, etc.
In 2003, the number of live births in the United States was 4,089,950, of which about 0.6% had RDS (about 24,000 or 6:1000 live births). In 2005, the number of live births in the United States was reported 4,138,000 and the rate of preterm births increased from 6.11% to 12.7% due to increasing birth rates (34 to 36 weeks of gestation) (4-6).
Infant mortality rates declined sharply in the United States from 2,500 infant deaths in 1960s to 860 in 2005 due to application of surfactant replacement therapy; however, there was an increase in the number of infants born with RDS (7).
RDS mortality in early African American infant was 2.6 times higher than Caucasian infants, although Caucasian infants were at higher risk. Thousands of infants have been saved with this treatment, but newborns still suffer from pulmonary bronchial dysplasia. Part of the problem is that surfactant replacement therapy and other medical advances and intensive care have kept very premature babies alive whom may face long-term complications of RDS.
It seems that in the current situation, preventing premature birth is the main way to eliminate RDS.
Proper nutrition and delivering intensive care medication to infants will also improve the outcomes. Surfactant replacement therapy is not effective in treating the type of RDS caused by a genetic mutation in SP-B. In most of the cases however, it has been surprisingly successful. Fetal lung maturation has always been a challenge for obstetricians in cases of preterm delivery and premature rupture of membranes (PROM).
Hyaline membrane disease has always been the main cause of infant death and fetal lung immaturity is one of the main health concerns.
Suggested by Liggins and Howie (5), corticosteroid therapy in patients at risk of preterm delivery was an important milestone in fetal lung maturity and reducing RDS morbidity and mortality in neonates. Nowadays, the main treatment applied in the intensive care unit (ICU) is maintaining oxygen saturation and preventing respiratory acidosis using sodium bicarbonate.
This treatment put a heavy financial burden on the patients since the length of neonatal ICU stay was considerable, while the outcomes were not satisfactory. Meanwhile, Liggins and Howie’s (5) treatment (using glucocorticoids to improve fetal lung maturation), not only reduces neonatal mortality and complications from RDS, but also reduces the need for neonatal intensive care and exogenous surfactant therapy which results in economic savings. Steroids may cause the premature release of alveolar surfactant by stimulating an enzyme involved in surfactant biosynthesis.
The steroids used are usually dexamethasone or betamethasone. They are biologically identical, and easily cross the placenta. They have low mineralocorticoid activity and are relatively weak in suppressing immunity. Doses recommended by Howie and Liggins include two doses of 12 mg betamethasone with an interval of 24 hours or four doses of 6 mg of dexamethasone with an interval of 12 hours. (6). Betamethasone is widely used due to patient adaptation between 24 and 34 weeks of pregnancy. Before 24 weeks, type II pneumocytes are not developed enough to release surfactant, and after 34 weeks, the risk of RDS is lower and less severe. Prenatal corticosteroids reduce intraventricular bleeding and infant mortality as well as reducing RDS (7).
The best respiratory results in infants appear after a full period of treatment, and delivery is ideal 3-7 days after this period. The protocol can be used simultaneously to delay labor to allow steroids fully function. The above recommendations are in line with the Royal College of Obstetricians and Gynecologists (RCOG) guidelines (7) and the American College of Obstetricians and Gynecologists (ACOG) Committee (8).
Some physicians believe that the reduction in RDS rate associated with prenatal steroids is not statistically significant in the subgroup of infants who are delivered more than 7 days after a course of treatment. Therefore, the course of treatment is repeated at weekly intervals for women who do not give birth but are at risk of preterm delivery.
This state of repeated steroids has never been properly randomized and there is no evidence that multiple steroid cycles are more effective than a single cycle. Interestingly, both the RCOG guidelines and the ACOG committee emphasized that there was no evidence that state repeated doses were useful after 7 days. In a randomized controlled trial on 502 pregnant women between 24 and 30 weeks, weekly antenatal steroid courses did not reduce the combined neonatal complications in comparison with one course of treatment (8).

 

A comprehensive literature review was performed on paper that have been published from 2004 to 2016 in databases such as NCBI, Science Direct, Springer, Web of Science as well as local databases such as Iran DAC, Islamic science citation (ISC) and Magiran with a special focus on reported articles using the following keywords: Body count, Fetal Lung, Ultrasonic.