In this retrospective study, we assessed the efficacy and safety of surfactant administration using the LISA technique in late preterm infants diagnosed with RDS.
Data showed a reduced number of pregnant women (35.0%) receiving corticosteroid therapy for fetal maturation, and an elevated number of cesarean deliveries (75.0%). These two factors have been shown to be associated with RDS development. Antenatal steroid therapy, on the one hand, significantly reduces the risk of RDS and other neonatal morbidities in late preterm infants, although the use of antenatal corticosteroids in late preterm deliveries has been reported to be rare [19–21]. These observations are in agreement with our findings and with those observed in a recent multicentric study conducted in Spain, in which only 33.7% of preterm cases underwent prenatal steroids treatment [22]. On the other hand, cesarean delivery is a risk factor for the development of neonatal respiratory problems —including RDS— in preterm infants [23]. In our study, the C-section rate was much higher than the mean rate observed across the Spanish territory (75.0% versus 47.9%) [22]. The causes for this elevated rate were elucidated: in 46.6% of cases, this procedure was conducted after initiation of active labor for reasons that emerged suddenly during childbirth, such as fetal anomalies, placenta previa, or failure to progress; the rest of cases (53.4%) were scheduled for C-section because of trichorionic triamniotic multiple pregnancies, record of previous caesarean delivery, history of uterine rupture, mother’s psychiatric illness, maternal HELLP syndrome, or premature rupture of membrane with fetal distress. Hence, and according to the clinical guidelines of The Spanish Society of Gynecology and Obstetrics, all C-sections were performed for a medically justified reason.
Among all preterm newborns, a high proportion of infants (50.0%) required resuscitation with nCPAP or nIPPV as initial respiratory support. Although these patients experienced difficulties during transition from intrauterine to extrauterine life, none of them had signs of acute fetal distress. Nonetheless, only three infants (15.0%) were hospitalized on the first day of admission at NICU, indicating a late RDS detection in the preterm newborns first admitted to an intermediate neonatal care unit. This fact would explain the higher FiO2 values and mean chronological age at surfactant administration as compared to the rest of preterm infants admitted in the NICU (mean FiO2: 0.40 versus 0.37; mean age: 22 versus 8.5 h).
Despite the fact that two patients (10.0%) were clinically misdiagnosed with RDS, LISA procedure did not have any negative impact on them. On the contrary, FiO2 levels were reduced after LISA, and IMV was only required in one case —the preterm newborn diagnosed with congenital pneumonia—. The infant diagnosed with pulmonary glycogenosis did not require IMV, except to perform lung biopsy, through which the definitive diagnosis was made. However, the observed clinical improvements were transient and clinicians suspected that patients could have been initially misdiagnosed with RDS. These observations highlight the need for a correct diagnosis of RDS, not only based on radiological findings and clinical course. We believe that the use of thoracic ultrasonography, which is considered an accurate and reliable tool in the diagnosis of RDS in the newborn [24, 25], could help early and rigorous diagnosis of the disease.
While the efficacy of surfactant therapy has been reported to improve respiratory function in late preterm infants with RDS [26–28], surfactant administration by minimally invasive methods is still being investigated in this population. The LISA method via thin catheter is widely adapted in Europe [29] and is a recommended method of care according to the latest consensus guidelines [9, 12, 30]. However, there is still large variability in the application of this technique regarding patient population that may benefit from this approach; the catheter type, the adequate dose and type of surfactant; the use of premedication; and the need of pharmacologic sedation during the procedure [31].
A meta-analysis conducted by Lau et al. [32] provides a comprehensive review of the use of LISA via thin catheter in preterm infants, examining the results of several studies [14, 33–35]. Overall, the authors underline the suitability of this technique in preterm infants. However, additional studies are required to address the infant selection issue in this vulnerable population. While the mentioned studies recommend the use of LISA in preterm infants, their outcomes should not be extrapolated to a different pediatric age range or other specific age subgroups.
Up to date, there is only one study reporting on the use of LISA in moderate and late preterm neonates between 320/7 and 366/7 weeks [36]. The authors compared standard RDS management (surfactant administration given only after intubation) with LISA procedure. Their results showed a reduction in mechanical ventilation exposure, RDS complications, and the length of hospital stay after LISA, as compared to standard therapy.
In our study, the LISA procedure performed on —exclusively— late preterm infants appeared to be of benefit for this particular subgroup of premature babies. This method improved respiratory outcomes with no need for IMV after LISA, reducing its associated complications. In addition, the adverse events documented during LISA (surfactant reflux, apnea and desaturation) were low, with mainly mild to moderate desaturations and a small rate of surfactant reflux, indicating that surfactant delivery was optimal for the vast majority of patients.
Other potential advantages of LISA, such as the reduction of the mean duration of NIV and the length of hospital stay, could not be assessed because of the lack of a control group for comparing surfactant administration methods.
Regarding the use of medications during the procedure, sedation and analgesia were administered at the discretion of each neonatologist, since there are not established protocols in our unit. In fact, administration of sedation and analgesia are controversial issues in RDS management [37]. More specifically, sedation for LISA is complex, because while low-dose sedation prior to laryngoscopy is technically attainable and makes the baby less uncomfortable, it increases the risk of CPAP failure. Thus, there is no clear consensus on whether or not to sedate routinely for LISA, and which sedative to use, leaving these decisions up to clinicians [9]. Our neonatologists have the subjective perception that in the absence of pharmacological sedation, technical complications during LISA arise more frequently in late preterm infants than in other premature newborns.
Our conclusions should be considered in light of some intrinsic limitations of the retrospective nature of this study. The single-group design did not allow us to compare the efficacy of different modes of surfactant administration among the study population. Therefore, randomized controlled trials are needed to further evaluate the benefits of LISA in late preterm infants, as well as to give a response to unresolved questions and clinical issues for its successful implementation.