Late preterm infants, born between 34+0 and 36+6 weeks of gestation, account for 70%–74% of all preterm births. They exhibit characteristics that increase their risk of morbidity and mortality, up to 2–3 times greater than those born at term, and their health care costs are twice as high as those of full-term infants.1–3

The 2018 SEN34-36 group study,2 involving 9121 patients from 34 hospitals found that 58.6% of late preterm infants required admission to the Neonatology unit, with up to 15% requiring admission to the Neonatal Intensive Care Unit (NICU), with a mean length of stay of 11 and 12 days, respectively.

One of the main causes of hospital admission in this population is respiratory complications, with respiratory distress syndrome (RDS) developing in up to 10%. This leads to higher morbidity and mortality rates and longer lengths of stay, along with the additional disadvantage of mother-infant separation.1–3 Respiratory treatment, which is better established in more preterm neonates, generates controversy. For this reason, an expectant approach is sometimes taken regarding surfactant administration, deciding to use it later when the expected progression has not been observed.1–5

Current evidence in late preterm infants suggests a lower risk of mortality, air leaks, persistent pulmonary hypertension, and duration of respiratory support when they receive surfactant.6–8 As indicated in the latest European Consensus Guidelines, due to data heterogeneity, there is currently insufficient evidence to establish recommendations.3

Given the above, this study is presented. The primary endpoint was to describe the clinical progression after surfactant use in a group of late preterm infants. The secondary endpoint was to compare based on the timing of application to determine if early use is protective.

In this retrospective study, we analyze the possible benefits that may arise from the early administration of surfactant. Administration before 12 h of life in our study has been associated with less respiratory support and fewer days at the NICU. Additionally, the number of days requiring oxygen has decreased, as well as the time needed to stop requiring it after the first dose. On the other hand, a lower incidence of pneumothorax was also observed in this group.

When comparing the epidemiological characteristics of both groups, no statistically significant differences were found. A higher number of patients who required administration of IPPV during resuscitation in the delivery room was observed in the early surfactant group. However, when analyzing the APGAR score, a median > 8 was obtained at both 1 and 5 min of life in both groups. Therefore, this difference was not considered clinically relevant, as these values suggest that progression was favorable. Most late preterm infants who required IPPV likely received it only within the first few moments of support in the delivery room, with a good response, not needing further resuscitation. In the late group, a higher transfer rate was observed, which may have contributed to a more unfavorable clinical course, both due to the transfer stress and possibility of delayed treatment.

The mean FiO2 before surfactant administration was >0.3 in both groups. In most patients from the late group, radiographic and clinical criteria were met within the first 12 h of life. However, in 12 (44.4%) cases, it was administered non-invasively at a later time, while in the other 15 (55.6%), it was administered only when intubation was needed, at the physician's discretion. This could be due to the tendency to optimize respiratory support and take a watchful waiting approach in late preterms. These infants typically present adequate respiratory effort, and the administration of surfactant involves an invasive maneuver.12 On the other hand, the later implementation of the LISA technique in hospitals without NICUs may have contributed to the delay in reaching the intubation criteria, which were probably later than the surfactant administration criteria.

In terms of respiratory support, NIV was initiated shortly after the onset of distress in both groups, although it was delayed by up to 2 h in the late vs the early group, which could again be due to the difference in the number of transfers. In NICU-free hospitals and if clinical situation allows it, high- or low-flow oxygen therapy may be initiated with a watchful waiting approach, expecting improvement without escalating to NIV, as its initiation would require intensive care and the transfer of the patient to a different center with such a unit. However, literature indicates that delaying the initiation of NIV could also be a factor leading to worse progression.13 It would be important to unify criteria for the initiation of respiratory support and administration of surfactants.

After the early administration of surfactants, most patients no longer required additional FiO2 within the first 24 h, with a high percentage not requiring oxygen just 1 h after receiving it, maintaining this benefit throughout the length of stay. The patient who required a 2nd dose in the early group was the only one who received the first dose at exactly 12 h of life, taking more than 48 h to reach FiO2 values of 0.21. In contrast, in the late group, it took up to 48 h after administration to reach the same percentage of patients without oxygen, while redosing was required in 13 newborns (48.1%). In fact, 8 of the 9 patients who took more than 48 h to stop requiring oxygen received a 2nd dose. The patient who did not receive a 2nd dose had been intubated for developing a pneumothorax, the main complication of RDS.14 In our study, no air leak was observed when surfactant was administered early, while a significantly higher number was seen in those who received it later. Air leaks typically occur in RDS patients with a slow disease progression, so,15 as observed in our study and reflected in the literature, administering treatment within the first hours of life may help reduce this complication.

Current evidence shows that in more immature preterm infants, the administration of surfactants within the first hours of life has beneficial effects.16 However, in newborns closer to term, there is no consensus on the optimal timing for administration.3,15,17 The optimal timeframe should be the subject of further study. The review of the current literature includes a study published by the Cochrane Neonatal Group in 2012 that analyzed the effects of surfactant administration within the first 2 h in intubated newborns with RDS.18 Currently, the SURFON1 study is underway, comparing the effects of surfactants vs a watchful waiting approach in late preterm and early term infants. This study considers the optimal administration time to be within the first 2−8 h of life but accepts administration up to 24 h.

The limitations of this work should be taken into consideration. It is a retrospective study with a small sample size, which leads to potential data loss and allows for only hypothesis generation. These limitations inherent to the study design have been addressed by emphasizing recruitment and minimizing losses. Additionally, the study was conducted in a single center, analyzing years when the LISA technique was being implemented, with its corresponding learning curve. Of note, the potential bias from the higher number of transfers in the late group, which may have impacted the later administration of surfactants. Although the method of administration was not used as a variable in the analysis, the percentage of each method was similar in both groups with no significant differences. The severity of distress was also not considered, as the Silverman score was not recorded in most health records. Moreover, the initiation of feeding and whether it was fully established before surfactant administration or the prior gasometric status were not taken into account.

In the analyzed series, the patients who received surfactant before 12 h of life showed a better progression. Further prospective, multicenter studies with larger sample sizes are needed to establish the true utility of these results and address all the above-mentioned limitations.

In our sample of late preterm infants with RDS, early administration of surfactant has been associated with benefits such as a quick and sustained withdrawal from supplemental oxygen, less need for respiratory support, and shorter NICU stays. Additionally, it has reduced the development of complications.

Therefore, further structured studies are needed to compare the benefits of early surfactant administration with other treatment options in this gestational age range.

Dr. Bartual is the principal investigator of this project and, therefore, responsible for the study design, data collection, data analysis, and drafting of this manuscript. Dr. Vizcaíno has been actively involved in the study design and data analysis, as well as in the drafting of the manuscript. Dr. Ferrández contributed to the study design and drafting of the manuscript.

None declared.