Key messages
• Respiratory distress syndrome is a common condition in preterm infants, while the benefits of surfactant therapy guided by tests for lung maturation remain unclear.
• No studies reported neonatal death (first 28 days of life) or neurodevelopmental outcome. It is uncertain whether surfactant therapy guided by tests for lung maturation has an effect on death prior to hospital discharge. Surfactant treatment guided by rapid tests for surfactant deficiency may result in little to no difference in chronic lung disease of prematurity, known as bronchopulmonary dysplasia, need for surfactant treatment, or any pneumothorax, that is a collapsed lung.
• Studies are needed to compare surfactant treatment guided by rapid tests for surfactant deficiency to prophylactic surfactant administration (administration of surfactant before the onset of symptoms) in all high-risk infants.
What are tests for lung maturity?
Surfactant is a complex mixture composed of proteins and phospholipids. The proteins aid in spreading and absorption at the lung surface, while lipids decrease the surface tension and thus prevent the collapse of the lung at the end of expiration, (that is when air leaves the lungs). Preterm infants are at risk of respiratory distress syndrome that occurs when their lungs have not developed properly. It is due to lack of surfactant, therefore surfactant administration is a procedure commonly performed in preterm infants. Up to now, there has been no consensus on the indicators and time for surfactant replacement therapy. Considering the invasiveness and cost, the aim is to allow timely intervention and avoid over treatment. Rapid tests for lung maturity (such as the click test, lamellar body counts and stable microbubble test) are based on measuring the concentration of pulmonary surfactant in any fluid. These tests can be performed on amniotic fluid, first fluid aspirated from the stomach or trachea (windpipe) soon after birth to assess the degree of surfactant deficiency. The use of rapid tests might guide the identification of infants needing surfactant administration.
What did we want to find out?
We wanted to find out if using tests for lung development in preterm infants was better than surfactant administration before the onset of respiratory distress syndrome (prophylactic surfactant administration) in all high-risk infants or surfactant therapy provided to infants with respiratory distress syndrome diagnosed on clinical and radiologic criteria.
We also wanted to find out if using surfactant therapy guided by tests for lung maturity in preterm infants was associated with a decrease in negative outcomes, such as death, chronic lung disease of prematurity, or any collapsed lung. Chronic lung disease of prematurity is a major problem for preterm babies associated with both a higher death rate and worse outcomes among survivors. Persistent inflammation of the lungs due to long use of respirators for providing ventilation is the most likely cause of it. Surfactant administration can assist in weaning from mechanical ventilation, and therefore prevent neonates from developing chronic lung disease of prematurity.
What did we do?
We searched for studies that looked at surfactant therapy guided by different types of rapid tests for lung maturity compared with prophylactic surfactant administration in all high-risk infants or surfactant therapy provided to infants with respiratory distress syndrome diagnosed on clinical and radiologic criteria.
We compared and summarized the results of the studies and rated our confidence in the evidence, based on factors such as study methods and sizes.
What did we find?
We found three studies that involved 562 preterm infants who either received surfactant treatment guided by rapid tests or by clinical and criteria and X-ray or ultrasound images.
The main results of the review showed that it is very uncertain whether the surfactant therapy guided by rapid tests for surfactant deficiency compared with surfactant therapy provided to infants with respiratory distress syndrome diagnosed on clinical and radiologic criteria has an effect on death prior to hospital discharge.
Surfactant treatment guided by rapid tests for surfactant deficiency may result in little to no difference in chronic lung disease of prematurity, need for surfactant treatment and collapsed lung.
There are two large ongoing studies assessing ung ultrasound guided surfactant therapy (one study) and the evaluation of the lung function, together with clinical assessment for surfactant therapy (one study).
What are the limitations of the evidence?
We are not confident in the evidence because there are not enough studies to be certain about the results of our outcomes. Finally, not all the studies provided data about everything that we were interested in.
How up to date is this evidence?
The evidence is up-to-date to October 2022.
No studies compared surfactant treatment guided by rapid tests for surfactant deficiency to prophylactic surfactant administration to all high-risk infants. Low to very low-certainty evidence from three studies is available on surfactant therapy guided by rapid tests for surfactant deficiency versus surfactant therapy provided to infants with RDS diagnosed on clinical and radiologic criteria. No studies reported neonatal mortality, the composite outcome 'bronchopulmonary dysplasia or mortality', or neurodevelopmental outcomes. Compared with surfactant therapy provided to infants with RDS diagnosed on clinical and radiologic criteria, the evidence is very uncertain about the effect of surfactant treatment guided by rapid tests for surfactant deficiency on mortality prior to hospital discharge. Surfactant treatment guided by rapid tests for surfactant deficiency may result in little to no difference in bronchopulmonary dysplasia, surfactant utilization and any pneumothorax.
The findings of the two large ongoing trials identified in this review are likely to have an important impact on establishing the effects of surfactant treatment guided by rapid tests for surfactant deficiency in preterm infants.
Administration of various exogenous surfactant preparations has been shown to decrease lung injury and pneumothorax and improve survival in very preterm infants with respiratory distress syndrome (RDS). There is no consensus on the threshold for surfactant administration, to allow timely intervention and avoid over-treatment, also considering the invasiveness of the procedure and its cost. Rapid tests for lung maturity, which include the click test, lamellar body counts and stable microbubble test, might guide the identification of those infants needing surfactant administration.
To assess the effects of surfactant treatment guided by rapid tests for surfactant deficiency in preterm infants at risk for or having RDS.
Comparison 1: In preterm infants at risk for RDS, does surfactant treatment guided by rapid tests for surfactant deficiency compared to prophylactic surfactant administration to all high-risk infants minimize the need for surfactant treatment and prevent bronchopulmonary dysplasia and mortality?
Comparison 2: In preterm infants who require early respiratory support, does surfactant treatment guided by rapid tests for surfactant deficiency compared to surfactant therapy provided to infants with RDS diagnosed on clinical and radiologic criteria minimize the need for surfactant treatment and prevent bronchopulmonary dysplasia and mortality?
We searched in October 2022 CENTRAL, PubMed, Embase and three additional trial registries. We also screened the reference lists of included studies and related systematic reviews for studies not identified by the database searches.
We included randomized controlled trials (RCTs) and quasi-RCTs evaluating rapid tests after birth for surfactant deficiency in infants at high risk of RDS or requiring respiratory support.
We specified two comparisons: 1)surfactant treatment guided by rapid tests for surfactant deficiency versus prophylactic surfactant administration to all high-risk infants in extremely preterm (less than 28 weeks' gestation) and very preterm (28 to 32 weeks' gestation); 2)surfactant treatment guided by rapid tests for surfactant deficiency versus surfactant therapy provided to preterm infants (less than 37 weeks' gestation) with RDS diagnosed on clinical and radiologic criteria.
We used standard Cochrane methods. We used the fixed-effect model with risk ratio (RR) and risk difference (RD), with their 95% confidence intervals (CIs) for dichotomous data. Our primary outcomes were: neonatal mortality, mortality prior to hospital discharge, bronchopulmonary dysplasia and the composite outcome bronchopulmonary dysplasia or mortality. We used GRADE to assess the certainty of evidence.
We included three RCTs enrolling 562 newborn infants in this review.
No studies compared surfactant treatment guided by rapid tests for surfactant deficiency versus prophylactic surfactant administration to all high-risk infants.
Comparing surfactant therapy guided by rapid tests for surfactant deficiency versus surfactant therapy provided to infants with RDS diagnosed on clinical and radiologic criteria.
No studies reported neonatal mortality. Compared with surfactant therapy provided to infants with RDS diagnosed on clinical and radiologic criteria, the evidence is very uncertain about the effect of surfactant treatment guided by rapid tests for surfactant deficiency on mortality prior to hospital discharge: RR 1.25, 95% CI 0.65 to 2.41, RD 0.01, 95% CI -0.03 to 0.05, 562 participants, 3 studies; I² for RR and RD = 75% and 43%, respectively; very low-certainty evidence. Surfactant treatment guided by rapid tests for surfactant deficiency may result in little to no difference in bronchopulmonary dysplasia: RR 0.90, 95% CI 0.61 to 1.32, RD -0.02, 95% CI -0.08 to 0.04, 562 participants, 3 studies; I² for RR and RD = 0%; low-certainty evidence. No studies reported the composite outcome bronchopulmonary dysplasia or mortality. Surfactant treatment guided by rapid tests for surfactant deficiency may result in little to no difference in surfactant utilization (RR 0.97, 95% CI 0.85 to 1.11, RD -0.02, 95% CI -0.10 to 0.06, 562 participants, 3 studies, I² for RR and RD = 63% and 65%, respectively, low-certainty evidence), and any pneumothorax (RR 0.53, 95% CI 0.15 to 1.92, RD -0.01, 95% CI -0.04 to 0.01, 506 participants, 2 studies, I² for RR and RD = 0%, low-certainty evidence) compared with surfactant therapy provided to infants with RDS diagnosed on clinical and radiologic criteria. No studies reported moderate to severe neurodevelopmental impairment.
We identified two large ongoing RCTs.