Late Surfactant Administration in Very Preterm Neonates With Prolonged Respiratory Distress and Pulmonary Outcome at 1 Year of Age

Because the lungs are one of the last organs to develop, their function is a major concern in infants born prematurely. Premature neonates may require mechanical ventilation if their lungs have not fully developed and they are not able to breathe sufficiently on their own. Mechanical ventilation (along with other factors) in infants can lead to an increased risk of developing bronchopulmonary dysplasia, which leads to chronic lung disease and abnormal neurodevelopment. Surfactant is a substance produced in the lungs that decreases surface tension in the lungs and stabilizes alveoli, ultimately preventing the lung from collapsing when exhaling. Surfactant can also be produced exogenously and can be used to treat premature infants.

This randomized, controlled, double-blind study examined the effects of late surfactant administration in 118 infants who were born before 33 weeks’ gestation and still required mechanical or high-frequency oscillatory ventilation at 14 days old. The primary end point was the time to first successful extubation; secondary outcomes were respiratory outcomes at 36 weeks postmenstrual age and at one year. Infants either received the treatment of surfactant or air. The results showed that the two groups were not significantly different in time to first successful extubation or respiratory outcomes at 36 weeks’ postmenstrual age. Bronchopulmonary dysplasia severity was also similar in both groups. There was a significant difference between the treatment and control in the number of hospitalizations required for respiratory issues at one year of age. The study concluded that surfactant was a safe therapy and that it did allow for better pulmonary outcomes at one year of age.

This study is just one example of the usefulness of synthesis of exogenous versions of endogenous substances to treat certain diseases. Although the study did not show overly successful outcomes, it was very logical to try to replace the substance that was missing in these infants, and this strategy could likely be used to find treatments for other diseases. Also, I really like seeing studies done in infants because they are an extremely vulnerable population and must be treated in different ways than adults or even children. I think it is very important to continue to do research on therapies specifically for infants.


JAMA Pediatr. doi: 10.1001/jamapediatrics.2015.4617 (published February 29, 2016).

Different Levels of Oxygen Saturation in Premature Infants

It has been a long-standing debate on how to treat premature infants with oxygen. Most neonatal intensive care units either treat these babies with either 85 to 89% oxygen saturation or 91 to 95% oxygen saturation. While both of these ranges show therapeutic effect, a research trial conducted in Australia and the United Kingdom compared the two different saturations to see which one was safer and more effective for infants born before 28 weeks gestation.


In the trial the infants were randomly assigned to either the lower range group (85-89%) oxygen saturation or the higher range group (91 to 95%) oxygen saturation. The researchers were studying death or disability at the age of 2 years old to see which infants had less negative outcomes. The results showed that death or disability occurred in 247 of 549 infants (45%) in the group that received the lower saturated oxygen. In addition, 217 of 545 infants (39.8%) in the higher saturation group either died or were diagnosed with disability at 2 years old. Thus those premature infants that received the more saturated oxygen had more positive outcomes as they aged.


It will be interesting to see if the results of this study are put in to everyday practice in the NICU. The results seem to really favor a higher amount of oxygen saturation. If these results of this new study are implemented into everyday practice, hundreds of infants lives could be saved each year.

The BOOST-II Australia and United Kingdom Collaborative Groups. Outcomes of two trials of oxygen-saturation target in preterm infants. N Engl J Med 2016; 374:749-760.



Use of Erythropoietin and Darbepoetin in Improving Brain Development in Premature Infants

Infants born with an extremely low birth rate have the potential to develop neurodevelopmental disabilities, such as cerebral palsy (CP), mental disabilities, and learning and attention deficits during school age. As of today, successful neuroprotective interventions have yet to be developed, but a group of scientists have found that two drugs, erythropoietin and darbepoetin, have a strong potential to have neuroprotective effects in infants.

Erythropoietin and darbepoetin are in a class of drugs called erythropoiesis stimulating agents (ESAs), which have been used clinically over 20 years to help stimulate red cell production. Erythropoietin stimulates red blood cell production in adults who have anemia attributable to end-stage renal disease or cancer. Darbepoetin is a biologically modified long-acting ESA that allows dosing every 1 to  4 weeks due to the increased half-life of the drug. Darbepoetin is also used for adults with anemia attributable to end-stage renal disease or cancer. In addition, darbepoetin was shown to have a similar half-life in infants. Premature infants also lack the ability to make new red blood cells so they often need frequent blood transfusions to replace blood taken for lab tests. However, use of erythropoiesis stimulating agents are shown to decrease the number of blood transfusions in premature infants.

In this research study, scientists performed a randomized, masked, and multicenter study comparing erythropoietin, darbepoetin, and placebo given through 35 weeks post conceptual age, with transfusions administered according to protocol. The surviving infants were evaluated at 3.5 and 4 years of age, and the primary outcome was the infant’s composite cognitive score. Assessments of full-scale IQ, general language, and overall measure of executive function, on the basis of tests evaluating inhibitory control and spatial working memory, were conducted.

Rather gathering data, scientists would that the infants randomized to receive the ESAs had better cognitive outcomes compared with placebo recipients at 3.5 and 4 years of age. Specifically, they scored about 12 points higher on average on IQ tests than the untreated infants, but about 10 points lower than the normal weight infants. Furthermore, on tests measuring memory and impulsive behavior, the treated infants had similar results as the infants born at normal weight.

This study mostly examined white and hispanic infants, so larger studies that include more diverse patient populations are needed to determine whether ESAs can help a broader range of infants. Thus, it is still too soon to recommend the medicines for treating developmental delays. However, treatment for medical problems and developmental delays due to prematurity has not kept pace, so this particular finding was significant.

I am glad to see that there are steps being taken to study the developmental delays in premature infants. Possibly in the future, parents can be relieved that their premature infants will be able to avoid potential developmental issues. However, in the future, I hope that there will be more research focusing on other developmental issues associated with premature birth. Do you believe that this finding will have a large impact in the future? What other areas of study related to premature birth do you think researchers should focus on in the future?


Ohls, R. K., Cannon, D. C., Phillips, J., et al. Preschool Assessment of Preterm Infants Treated With Darbepoetin and Erythropoietin. Pediatrics. 2016