Abstract
Objective
To evaluate the impact of a respiratory care protocol (RCP) including stepwise escalation of continuous positive airway pressure (CPAP) guided by FiO2 and less invasive surfactant administration (LISA) in infants born at 30–34 weeks’ gestational age (GA).
Methods
We compared maternal and neonatal variables between cohorts of preterm infants born January 2017–Sept 2018, (pre-RCP) and Oct 2018–Dec 2020 (post-RCP). Infants receiving CPAP for ≥24 h were included and infants intubated at birth were excluded.
Results
Compared to pre-RCP (n = 325), the post-RCP (n = 395) cohort had higher exposure to antenatal steroid, lower median GA, and received higher CPAP in the delivery room, at admission, and before surfactant therapy. Similarly, the need for mechanical ventilation was lower within the first 72 h of life and during the hospital stay in the post –RCP cohort.
Conclusion
Implementation of an RCP decreased the need for mechanical ventilation in 30–34 weeks’ GA infants.
Subject terms: Paediatrics, Outcomes research
Introduction
Preterm infants born 30–34 weeks’ gestational age (GA) account for 3.9% of all live births but account for 32% of all preterm infants [1]. Furthermore, this group of infants represent 83–89% of infants < 35 weeks’ GA admitted to the neonatal intensive care unit (NICU) [2, 3]. Although this relatively mature group of infants are at a lower risk of mortality and morbidity compared to extremely preterm infants, over 60% require non-invasive respiratory support during the NICU stay and 8–20% require mechanical ventilation (MV) [2, 4]. Despite the high NICU utilization by this group of infants, there is a paucity of studies evaluating respiratory support strategies to limit exposure to mechanical ventilation in this group.
The two most common causes of respiratory distress in 30–36 weeks’ GA are transient tachypnea of the newborn (57%) and respiratory distress syndrome (40%) [4]. Over the last decade, preterm infants are increasingly stabilized on continuous positive airway pressure (CPAP) at birth [5, 6]. Hatch et al. noted that although the proportion of infants receiving MV has decreased and non-invasive support has increased, the duration of respiratory support also increased in the same period [2]. In a large cohort of infants born within the Australia and New Zealand Neonatal Network, Dargaville et al. reported a higher incidence of pneumothorax, BPD, mortality, and composite death or BPD in infants 29–32 weeks’ GA admitted on CPAP requiring MV within 72 h of life, compared to infants successfully managed on CPAP [7]. This highlights the need to develop strategies to optimize non-invasive support to decrease the need for MV even in mature preterm infants.
Traditionally, surfactant has been administered through an endotracheal tube (ETT), either followed by mechanical ventilation [5, 6] or using the INSURE technique - INtubation, SUrfactant administration and Rapid Extubation- to minimize ventilator exposure [8–10]. Over the last decade, less invasive surfactant administration (LISA) using thin catheters has been shown to reduce the need for mechanical ventilation and improve outcomes in preterm infants compared to surfactant administration via ETT [11–13]. However, data on the benefits of LISA in more mature preterm infants remain limited. A single-center randomized control trial (RCT) comparing between LISA and continued CPAP in 32–36 weeks’ GA infants showed reduced need for MV and lower incidence of pneumothorax with LISA [14]. Similarly, another single-center RCT reported no procedural adverse events with LISA when compared to INSURE [15]. In the United States, use of LISA has increased over the past few years [16, 17]. Therefore, it is important to evaluate the benefits of a non-invasive respiratory strategy including LISA.
Starting in October 2018, a respiratory care protocol (RCP) was implemented in the neonatal intensive care unit (NICU) at Parkland Hospital (PHHS). It is well established that the use of bubble CPAP respiratory support systems improves oxygenation and ventilation [18–20]. A stepwise increase of CPAP is known to improve functional residual capacity and oxygenation [21–23]. The RCP involved stepwise escalation of CPAP from 5 to 7 cm H2O and administration of LISA guided by a fraction of inspired oxygen (FiO2) ≥ 0.3 in order to maintain goal saturations. In a previously published analysis, infants ≤ 29 weeks’ GA treated after RCP (post-RCP) implementation required less MV within the first 72 h of life, received less patent ductus arteriosus (PDA) treatment, and experienced a lower incidence of pneumothorax compared to the pre-RCP cohort [24]. This study aims to evaluate the impact of the RCP in infants born at 30–34-weeks’ GA. We hypothesize that the implementation of the RCP reduces the need for MV within 72 h of life and improves clinical outcomes in this population.
Methods
Setting
PHHS is a large public hospital with over 13,000 deliveries annually. Delivery room (DR) resuscitation is conducted per Neonatal Resuscitation Program guidelines [25]. Infants ≤ 34 weeks’ GA who did not require intubation for resuscitation and who exhibited signs of respiratory distress were initiated on CPAP through bi-nasal prongs (Hudson Prongs, Teleflex, Wayne, PA) or nasal masks (Fisher & Paykel, Auckland, NZ) connected to a positive end-expiratory pressure (PEEP) valve. As previously reported, all infants admitted to the NICU on CPAP are started on bubble CPAP (Fisher & Paykel, Auckland, NZ). An arterial blood gas (ABG), usually from the right radial artery, was obtained upon admission [26, 27]. The goal pulse oximeter oxygen saturation (SpO2) was maintained between 88–94%. The nasal cannula was used to administer oxygen in infants without significant respiratory distress but with SpO2 below the goal saturation levels on room air. Regular training session for nurses and respiratory therapists, along with bedside audits of the CPAP delivery system based on previously published guidelines were conducted throughout the study period [28]. In the NICU, pulse oximeter oxygen saturation target was maintained between 88 and 94%. Non-invasive positive pressure ventilation (NIPPV) was used as a rescue mode for hypercarbia and persistent apnea [29].
Beginning in October 2018, all preterm infants admitted on CPAP were managed according to the RCP [24]. CPAP was initiated at 5–7 cm H2O and titrated in 30-min intervals based on oxygen requirements, with escalation for FiO2 ≥ 0.3. Infants on CPAP 7 cm H2O, with FiO2 ≥ 0.3 received LISA. CPAP was weaned or escalated between 5–8 cm H2O guided by FiO2 ≥ 0.3 [12, 30]. Infants were intubated before LISA if FiO2 ≥ 0.7 or if they experienced frequent apnea at admission. Subsequent LISA doses were administered at 12-hour intervals (up to three doses total) for infants on CPAP ≥ 7 cm H2O requiring FiO2 ≥ 0.4. Infants requiring FiO2 ≥ 0.6 or having frequent apneas were intubated (Supplementary Fig. S1).
Study design and population
This is a single-center retrospective study of infants 30–34 weeks’ GA born between January 2017 and December 2020. We compared maternal and neonatal variables between the cohorts of infants born before (January 2017 to September 2018, pre-RCP) and after (October 2018 and Dec 2020, post-RCP) implementation of the RCP. Infants receiving CPAP for ≥24 h were included in the study. Infants with a major congenital anomaly, those requiring intubation at birth, those who received no respiratory support, or only nasal cannula or CPAP < 24 h during NICU stay were excluded from the study. The primary outcome of interest was the need for MV within 72 h of life.
Data elements and definitions
Data on maternal and neonatal demographics, maternal pregnancy, labor and delivery, and neonatal outcomes were obtained from the validated Parkland NICU database [31]. Members of the study team retrospectively collected details of DR management, CPAP, and FiO2 at admission, at hourly intervals for 8 h after LISA, and at the time of CPAP failure from the electronic medical record.
The respiratory severity score (RSS) (CPAP level * FiO2), A-a DO2 = [(FiO2 * 713) - (PaCO2/0.8) - PaO2] and arterial /alveolar PO2 (a/A PO2) = (PaO2 /[(FiO2 * 713) - (PaCO2/0.8)]) were calculated. Bronchopulmonary dysplasia (BPD) was defined as the need for supplemental oxygen at 36 weeks’ postmenstrual age [32]. Severe intraventricular hemorrhage (IVH) was defined as grade III or greater on any head ultrasound scan unilaterally or bilaterally as per Papile criteria [33]. Severe retinopathy of prematurity (ROP) was defined as Stage 3 or greater based on the international classification of ROP [34].
We also calculated the impact of the RCP on the health care cost using the model described by Yao et al. [35]. This model used relevant inputs driving hospital costs in preterm infants with respiratory distress syndrome. The average total cost of care per day was separately calculated for days with and without MV for the entire duration of stay. The cost of surfactant was calculated based on the average birth weight of infants receiving surfactant in each cohort [35].
Statistical analyses
Analyses were performed using SAS version 9.2 (SAS Institute Inc., Cary, NC.). Categorical variables were analyzed by Pearson’s Chi square or Fisher’s exact test as applicable. Continuous variables were analyzed by Student’s T test or Mann–Whitney U test. A two-sided 0.05 level of significance was used for all analyses.
Ethical consideration
The study was approved by the Institutional Review Board of the University of Texas Southwestern Medical Center, and consent for retrospective data collection was waived. All methods were performed in accordance with the relevant guidelines and regulations.
Results
A total of 1652 infants born during the study period, 731 were born between January 2017 and September 2018 (pre-RCP cohort) and 921 between October 2018 and December 2020 (post-RCP cohort). After excluding infants with significant congenital anomalies (2.2% vs 2.6%), those intubated at birth (2.2% vs. 1.7%), and those who received CPAP for less than one day (4.3% vs 1.7%), a total of 325 (44%) and 395 (43%) were included in the pre-RCP and post-RCP cohorts, respectively (Fig. 1).
Fig. 1. Flow chart of 30–34 weeks’ GA infants born between 2017 and 2020.
CPAP continuous positive airway pressure, DR delivery room, GA gestational age, RCP respiratory care protocol.
Baseline maternal and infant characteristics were similar between cohorts, except for a higher median maternal age, greater exposure to ANS, and lower mean GA in the post-RCP cohort (Table 1). The respiratory support provided in the delivery room and NICU was similar between the two cohorts except for higher CPAP in the DR, on admission, and before surfactant therapy in the post-RCP cohort. There was no difference in the proportion of infants admitted on CPAP, those receiving surfactant therapy, or time to surfactant from birth (Table 2).
Table 1.
Comparison of maternal and infant baseline characteristics between the pre- and post-Respiratory Care Protocol cohorts.
| Pre-RCP (n = 325) | Post- RCP (n = 395) | P-value | |
|---|---|---|---|
| Maternal age, yeara | 29 (23, 34) | 30 (25, 35) | 0.05 |
| Hispanic, n (%) | 231 (71) | 261 (66) | 0.15 |
| PIH, n (%) | 135 (42) | 180 (46) | 0.28 |
| Antenatal steroids, n (%) | 229 (71) | 326 (83) | <0.01 |
| Complete antenatal steroid course | 122 (54) | 175 (54) | 0.94 |
| Multiple birth, n (%) | 74 (23) | 72 (18) | 0.13 |
| Chorioamnionitis, n (%) | 13 (4) | 14 (4) | 0.75 |
| Diabetes, n (%) | 51 (16) | 68 (17) | 0.58 |
| Cesarean section, n (%) | 228 (70) | 274 (69) | 0.82 |
| Prolonged ROM (>18 h), n (%) | 77 (25) | 97 (25) | 1.00 |
| Male, n (%) | 183 (56) | 204 (52) | 0.21 |
| GA, weeks (Mean ± SD) | 32.2 ± 1.4 | 32.0 ± 1.4 | 0.02 |
| 30–32 weeks’ GA | 173 (53) | 249 (63) | <0.01 |
| 33–34 weeks’ GA | 152 (47) | 146 (37) | |
| Birth weight, ga | 1845 (1590, 2200) | 1840 (1540, 2130) | 0.41 |
| Apgar score at 1 mina | 7 (5, 8) | 7 (5, 8) | 0.22 |
| Apgar score at 5 mina | 8 (8, 9) | 8 (8, 9) | 0.27 |
| Cord blood gas pHa | 7.26 (7.22, 7.29) | 7.26 (7.22, 7.30) | 0.58 |
| Cord blood gas deficita | −5.5 (−7.4, −3.8) | −5.5 (−7.2, −3.6) | 0.89 |
GA gestational age, PHI pregnancy-induced hypertension, RCP Respiratory Care Protocol, ROM rupture of membrane, SD standard deviation.
aMedian (25th percentile, 75th percentile).
Table 2.
Comparison of respiratory support at birth and in the NICU between pre- and post-RCP cohorts.
| Characteristics | Pre-RCP (n = 325) | Post- RCP (n = 395) | P-value |
|---|---|---|---|
| PPV in DR, n (%) | 138 (43) | 140 (35) | 0.05 |
| Max PIP in DR, cm H2Oa | 25 (25, 25) | 25 (25, 25) | 0.87 |
| Max CPAP in DR, cm H2Oa | 5 (5, 5) | 5 (5, 5) | <0.01 |
| Max CPAP in DR > 5 mmHg, n (%) | 20 (7) | 57 (16) | <0.01 |
| Max FiO2 in DRa | 0.50 (0.40, 0.60) | 0.60 (0.40, 0.70) | 0.38 |
| Admission support, n (%) | 0.53 | ||
| Room air | 25 (8) | 28 (7) | |
| Nasal cannula | 7 (2) | 14 (4) | |
| CPAP | 293 (90) | 353 (89) | |
| FiO2 on admissiona | 0.25 (0.21, 0.30) | 0.25 (0.21, 0.30) | 0.44 |
| CPAP on admission | 5 (5, 5) | 5 (5, 5) | 0.002 |
| CPAP on admission >5 mmHg, n (%) | 26 (9) | 61 (17) | 0.002 |
| RSS on admissiona | 1.25 (1.05, 1.50) | 1.25 (1.05, 1.50) | 0.62 |
| Arterial-alveolar O2 gradienta, b | 56 (27, 102) | 53 (27, 94) | 0.59 |
| CPAP before surfactant, cm H2Oa | 6 (6, 6) | 7 (7, 7) | <0.001 |
| FiO2 prior to surfactanta | 0.40 (0.30, 0.50) | 0.32 (0.29, 0.40) | 0.09 |
| RSS prior to surfactanta | 2.4 (1.8, 3.0) | 2.2 (2.0, 2.8) | 0.61 |
| Surfactant therapy, n (%) | 49 (15) | 71 (18) | 0.30 |
| Time to surfactant from birth (hours)a | 8.5 (4.0, 18.25) | 5.0 (3.0, 22.0) | 0.43 |
CPAP continuous positive airway pressure, DR delivery room, PPV positive pressure ventilation, PIP peak inspiratory pressure, RCP Respiratory Care Protocol, RSS respiratory severity score, TOB time of birth.
aMedian (25th percentile, 75th percentile).
bBased on patient’s first blood gas.
The need for MV within 72 h of life and during hospital stay was lower in the post-RCP cohort compared to the pre-RCP cohort. In gestational-age–stratified subgroup analyses (30–32 and 33–34 weeks), this difference persisted. Rates of pneumothorax, BPD, NEC, mortality and IVH, were similar between cohorts. During the entire study period, two infants died due to NEC, both in the post-RCP cohort. Length of hospital stay (LOS) and hospital costs were higher post-RCP; however, within gestational-age subgroups, LOS and costs were similar (Table 3).
Table 3.
Respiratory care and neonatal outcomes in pre- and post-respiratory care protocol cohorts: analysis of all infants and gestational age subgroups.
| Characteristics | All infants | 30–32 weeks Gestational Age | 33–34 weeks Gestational age | ||||||
|---|---|---|---|---|---|---|---|---|---|
| Pre-RCP (n = 325) | Post-RCP (n = 395) | P- value | Pre-RCP (n = 173) | Post-RCP (n = 249) | P- value | Pre-RCP (n = 152) | Post-RCP (n = 146) | P- value | |
| MV within 72 HOL n (%) | 57 (18) | 14 (4) | <0.01 | 38 (22) | 10 (4) | <0.01 | 19 (13) | 4 (3) | <0.01 |
| MV during hospital stay n (%) | 61 (19) | 20 (5) | <0.01 | 42 (24) | 15 (6) | <0.01 | 19 (13) | 5 (3) | <0.01 |
| Time to intubation from birth, hoursa | 7 (1, 24) | 23 (2,153) | 0.04 | 7 (0, 23) | 23 (2, 168) | 0.04 | 8 (2, 24) | 23 (2, 120) | 0.78 |
| Ventilator daysa | 1 (0, 2) | 1 (0, 2) | 0.65 | 1 (0, 2) | 0 (0, 2) | 0.50 | 2 (0, 2) | 2 (0, 5) | 0.57 |
| CPAP daysa | 3 (2, 5) | 3 (2, 5) | 0.64 | 4 (2, 7) | 4 (2, 6) | 0.52 | 2 (1, 4) | 2 (1, 4) | 0.15 |
| Pneumothorax, n (%) | 8 (3) | 9 (2) | 0.87 | 4 (2) | 6 (2) | 1.00 | 4 (3) | 3 (2) | 1.00 |
| Moderate/Severe BPD, n (%) | 2 (1) | 0 (0) | 0.20 | 2 (1) | 0 (0) | 0.17 | 0 (0) | 0 (0) | N/A |
| NEC stage ≥2, n (%) | 9 (3) | 15 (4) | 0.44 | 9 (5) | 14 (6) | 0.85 | 0 (0) | 1 (1) | 0.49 |
| Severe ROP (≥grade 3), n (%) | 0 (0) | 0 (0) | N/A | 0 (0) | 0 (0) | N/A | 0 (0) | 0 (0) | N/A |
| Severe IVH (≥grade 3), n (%) | 2 (1) | 0 (0) | 0.20 | 1 (1) | 0 (0) | 0.41 | 1 (1) | 0 (0) | 1.00 |
| Death (%), n (%) | 0 (0) | 2 (1) | 0.50 | 0 (0) | 2 (1) | 0.52 | 0 (0) | 0 (0) | N/A |
| Length of stay, daysa | 29 (20,41) | 32 (22,44) | 0.03 | 38 (29,49) | 39 (30,49) | 0.91 | 21 (16,27) | 21 (16,29) | 0.56 |
| Estimated cost of hospital stay (USD)a | 85,557 (50,379, 106,938) | 79,404 (55,740, 110,169) | 0.80 | 93,210 (77,039, 123,501) | 89,659 (71,200, 115,297)) | 0.31 | 42,957 (37,963, 56,298) | 47,116 (32,711, 82,961) | 0.43 |
BPD bronchopulmonary dysplasia, BPD need for supplemental oxygen at 36 weeks GA, IVH intraventricular hemorrhage, HOL hours of life, MV mechanical ventilation, NEC necrotizing enterocolitis, RCP Respiratory Care Protocol, ROP retinopathy of prematurity, USD U.S. Dollars.
aMedian (25th percentile, 75th percentile).
In a subgroup analysis of infants who received surfactant, the need for intubation and MV within 72 h of life and during the hospital stay were significantly lower in the post-RCP cohort, while other outcomes were similar between cohorts (Table 4).
Table 4.
Comparison of outcomes among infants receiving surfactant in pre- and post-RCP cohorts.
| Characteristics | Pre-RCP (n = 49) | Post-RCP (n = 71) | P-value |
|---|---|---|---|
| MV within 72 HOL n (%) | 48 (98) | 12 (17) | <0.01 |
| MV during hospital stay n (%) | 49 (100) | 12 (17) | <0.01 |
| Time to intubation from birth, hoursa | 7 (0, 17) | 3 (2, 22) | 0.96 |
| Ventilator daysa | 1 (0, 2) | 2 (0, 5) | 0.33 |
| CPAP daysa | 6 (4, 9) | 5 (3, 8) | 0.26 |
| Pneumothorax, n (%) | 3 (6) | 6 (9) | 0.74 |
| Mod/Severe BPD, n (%) | 2 (4) | 0 (0) | 0.17 |
| NEC stage ≥ 2, n (%) | 2 (4) | 4 (6) | 1.00 |
| Severe ROP (≥grade 3), n (%) | 0 (0) | 0 (0) | N/A |
| Severe IVH (≥grade 3), n (%) | 0 (0) | 0 (0) | N/A |
| Death (%), n (%) | 0 (0) | 0 (0) | N/A |
| Length of stay, daysa | 41 (24, 53) | 38 (26, 53) | 0.79 |
| Average cost of hospital stay (USD)a | 85,557 (50,379, 111,591) | 79,404 (55,740, 110,169) | 0.85 |
BPD bronchopulmonary dysplasia, BPD need for supplemental oxygen at 36 weeks GA, HOL hours of life, IVH intraventricular hemorrhage, MV mechanical ventilation, NEC necrotizing enterocolitis, RCP Respiratory Care Protocol, ROP retinopathy of prematurity, USD United States Dollar.
aMedian (25th percentile, 75th percentile).
Discussion
Although infants born 30–34 weeks’ GA account for over 30% of all NICU admissions, there is paucity of studies on the strategies to optimize non-invasive support and decrease the need for invasive MV in this population. This single-center study shows that implementation of a respiratory care protocol including LISA reduces the need for MV in preterm infants 30–34 weeks’ GA, both within the first 72 h of life and during the hospital stay. This is the first study to evaluate a non-invasive respiratory support strategy including LISA in 30–34 weeks’ GA infants.
The benefits of LISA over surfactant administration through ETT in decreasing the need for MV and composite death or BPD in preterm infants is well established [13]. However, the beneficial effects on mature preterm infants 30–34 weeks’ GA are unclear as the large studies comparing ETT surfactant and LISA included infants ≤ 29 weeks’ GA [11, 12, 30, 36]. Similarly, observational studies from German Neonatal Network has also reported information only on infants ≤ 30 weeks’ GA [37, 38]. The reduced need for MV in the post-RCP cohort aligns with findings from the RCT by Olivier et al., which compared between early rescue LISA with expectant management using CPAP [14]. However, unlike the RCT, our study did not demonstrate a reduction pneumothorax with LISA, which may be attributed to the lower baseline incidence of pneumothorax in the pre-RCP cohort. While our study showed no difference in the duration of MV between cohorts, this finding may reflect the already low baseline MV duration in 30–34 weeks’ GA at our center. This also aligns with results from Hatch et al. who reported a decreasing trend in MV duration in 30–34 weeks’ GA over the last decade [2].
The need for respiratory support and the severity of respiratory disease have not been extensively evaluated in the 30–34 weeks’ GA population in the era of universal use of antenatal steroid (ANS) and LISA. A 2018 prospective multicenter study conducted in France enrolled 560 infants between 30- and 36-weeks’ GA who required respiratory support within 24 h of life. In this cohort, 6% of 30–34 weeks’ GA infants required intubation at birth. Of the infants admitted on non-invasive respiratory support, 24% subsequently required invasive MV for worsening respiratory distress. Although 28% of infants required surfactant, only a third of those received surfactant through a thin catheter [4]. Similarly, data from the Pediatrix Clinical Warehouse including over 19,000 infants born at 30–34 weeks’ GA in 2018 showed that 8% required MV during the first week of life [2]. The rate of mechanical ventilation in the pre-RCP cohort in our study was comparable (10%). Notably, the need for MV decreased four-fold in the post-RCP, primarily due to the adoption of LISA for surfactant administration.
Despite the reduced need for MV in the post-RCP cohort, there was no reduction in the LOS after accounting for the differences in the gestational age. The duration of stay depends on various factors such as weaning of respiratory support, feeding, growth, apnea of prematurity and variations in NICU practice [39–41]. Our study interventions did not address any of these factors and therefore had limited effect on the overall LOS. Such interventions should be analyzed in this group of infants either individually or as part of quality improvement bundles.
We estimated hospital costs using the model described by Yao et al. [35]. The cost of hospital stay is dependent on LOS, duration of mechanical ventilation and cost of treating complications related to prematurity. There was no difference in the hospital cost between cohorts when stratified by GA despite the decreased need for MV. This can be explained by lack of difference in the LOS despite decreased need for MV in the post RCP, the former being the primary driver of hospital cost [42].
Our study has some important strengths. It is the first study to evaluate the effects of a respiratory care protocol including LISA in moderate to late preterm infants. The higher CPAP level prior to LISA suggests that protocol was consistently followed in the NICU during the study period. The lack of difference in the surfactant usage between two cohorts suggests that the threshold for LISA was appropriate and helped target the population of infants at risk of requiring MV. Second, infants were identified using the validated NICU data base that includes relevant maternal and neonatal information of all infants born ≤ 34 weeks’ GA during the study period [31]. Third, the care of infants on non-invasive support was provided by the respiratory therapists and nurses regularly trained on non-invasive respiratory support measures prior to introducing the new RCP, which limited variability in bedside care.
There are limitations to this study. First, this study included patients born over a period of four years. The effects of any care practices outside the respiratory care protocol might have affected the study outcome. However, we are not aware of any other such factors. Secondly, we have not analyzed the procedure-related adverse events. Our center reported the procedural safety data of LISA on infants ≤ 29 weeks’ GA, which was equivalent to the adverse events with intubations using ETT [24]. Third, we did not monitor the compliance with the study protocol in the post-RCP cohort. However, higher CPAP prior to surfactant therapy in the post-RCP cohort suggests compliance with the RCP.
In conclusion, our single-center study shows that a respiratory care protocol including stepwise escalation of CPAP and LISA guided by FiO2 ≥ 0.3 is effective in decreasing the need for MV in preterm infants 30–34 weeks’ GA. These findings are consistent with the large body of evidence supporting the use of LISA in preterm infants and can be used to guide therapy in other centers with similar settings.
Supplementary information
Acknowledgements
We thank the dedicated NICU nurses, respiratory therapists, and providers at the Parkland Hospital NICU for their commitment to excellence in neonatal care.
Author contributions
All authors contributed to the study conception and design. SA, LD, KM, and PB assisted in acquiring the data. LSB analyzed and interpreted the data. SA, LB and VK wrote the main manuscript text. MC, SH and HW reviewed the manuscript. All authors read, reviewed and approved the final manuscript.
Funding
The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.
Data availability
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Competing interests
VK has received grant support from Chiesi Pharmaceuticals for investigator-initiated randomized control trials at the University of Texas Southwestern Medical Center. He also has financial relationship with Chiesi Pharmaceuticals as a consultant. The remaining authors have no conflicts of interest relevant to this article to disclose.
Footnotes
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
These authors contributed equally: Swathi Ariyapadi, Lorraine Bautista.
Supplementary information
The online version contains supplementary material available at 10.1038/s41372-026-02682-1.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.