Late surfactant administration after 48 hours of age in preterm neonates with respiratory insufficiency: a systematic review and meta-analysis.

OBJECTIVE: To systematically review and meta-analyse the effect of late surfactant administration versus placebo in reducing the incidence of death or bronchopulmonary dysplasia (BPD) in preterm infants. DESIGN: PubMed, EMBASE, CINAHL and Cochrane CENTRAL were searched until 30 May 2023, for randomised controlled trials (RCTs) comparing administration of surfactant after 48 hours of age versus placebo in preterm ventilator-dependent neonates. The primary outcome was incidence of death or BPD at 36 weeks' postmenstrual age (PMA). Secondary outcomes included incidence of BPD at 36 weeks PMA, pre-discharge mortality, use of postnatal steroids, post-discharge respiratory support, treatment with steroids or hospitalisation prior to 1-year corrected age. RESULTS: Pooled analyses of four RCTs (N=850) showed no statistically significant difference between groups in the incidence of death or BPD at 36 weeks' PMA (relative risk (RR) 0.99; 95% CI 0.90 to 1.10; Grades of Recommendation, Assessment, Development and Evaluation (GRADE): moderate). Late surfactant administration significantly decreased the need for post-discharge respiratory support prior to 1-year corrected age (two RCTs; N=522; RR 0.72; 95% CI 0.59 to 0.89; GRADE: low). Other secondary outcomes did not differ significantly between the groups. CONCLUSIONS: Administration of late surfactant does not improve the rates of death or BPD at 36 weeks when administered to preterm infants with prolonged respiratory insufficiency. Additional adequately powered trials are needed to establish the efficacy of late surfactant therapy in preterm infants. PROSPERO REGISTRATION NUMBER: CRD42023432463.

Mucous fistula refeeding in neonates: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Mucous fistula refeeding (MFR) aims to maximise bowel function when an ostomy is active after abdominal surgery, by introducing the proximal ostomy effluent into the distal mucous fistula to maintain intestinal physiology. The aim of the study was to assess the effectiveness and complications of MFR in neonates following abdominal surgery. DESIGN, SETTING AND INTERVENTIONS: Systematic review and meta-analysis of randomised controlled trials and observational studies. PubMed, Embase, Cochrane and CINAHL were searched until June 2022 for studies including neonates with ostomy receiving MFR compared with neonates with ostomy without MFR. OUTCOMES: The primary outcome was duration of parenteral nutrition. Secondary outcomes were time to full enteral feeds, rates of cholestasis, peak total serum bilirubin, sepsis, time to reanastomosis and length of hospital stay. RESULTS: A total of 16 observational studies were included (n=623). Compared with comparator group, neonates who received MFR had fewer days of parenteral nutrition (mean difference 37.17 days, 95% CI -63.91 to -10.4, n=244, 5 studies, GRADE: low). In addition, neonates who received MFR had lower rates of cholestasis, shorter time to reach full feeds and shorter hospital stay. CONCLUSION: Low certainty of evidence suggests that MFR is associated with shorter duration of parenteral nutrition in neonates following abdominal surgery and stoma creation. Results of ongoing and future randomised trials may help to corroborate these findings.

Evaluación renal y multiorgánica en el paciente con encefalopatía hipóxico-isquémica / Renal and multiorgan evaluation in infants with post-asphyxial hypoxic-ischaemic encephalopathy

Resumen Introducción: La encefalopatía hipóxico-isquémica (EHI) moderada-grave secundaria a asfixia perinatal puede afectar a cualquier órgano, empeorando el pronóstico. Objetivo: Evaluar la afectación renal y multiorgánica de estos pacientes. Material y método: Se incluyó a recién nacidos > 35 semanas con EHI moderada-grave tratados con hipotermia activa entre 2010 y 2020. Se evaluó la creatinina en tres periodos: 48-72 horas de vida, entre el 3.o y 7.o día de vida y del 7.o al 28.o día de vida. Resultados: Se incluyeron 135 pacientes: 112 con EHI moderada y 23 con EHI grave. Al comparar ambos grupos, se obtuvieron diferencias significativas a las 48-72 horas y entre 3.o-7.o día de vida. No hubo diferencias al comparar el método de hipotermia. Los pacientes con EHI grave presentaron mayor afectación hemodinámica, respiratoria y hepática. Conclusiones: Neonatos con EHI grave presentan aumento de los niveles de creatinina sérica y mayor afectación multiorgánica respecto a aquellos con EHI moderada.

Abstract Background: Hypoxic-ischemic encephalopathy (HIE) secondary to perinatal asphyxia can affect any organ, worsening the prognosis. Objective: To describe renal and multiorgan involvement in moderate-severe HIE. Material and method: Newborns > 35 weeks diagnosed with moderate-severe HIE who required active hypothermia between 2010-2020 were included. To assess renal involvement, serum creatinine was measured in three different periods: at 48-72 hours, between the 3rd and the 7th day, and from the 7th to the 28th day. Results: A total of 135 patients were included, 112 (83%) with moderate and 23 (17%) with severe HIE. Significant differences were obtained when comparing median creatinine levels at 48-72 hours and between 3-7 days in both groups. There were no differences in creatinine according to the hypothermia method. Patients with severe HIE presented greater hemodynamic, respiratory, and hepatic involvement. Conclusions: Neonates with severe HIE present increased serum creatinine levels and greater multi-organ involvement than those with moderate HIE.

Chylothorax in newborns after cardiac surgery: a rare complication?

The aim of this study was to analyze patients diagnosed with chylothorax after congenital heart disease surgery among a cohort of neonatal patients, comparing the evolution, complications, and prognosis after surgery of patients who were and were not diagnosed with chylothorax, and to analyze possible risk factors that may predict the appearance of chylothorax in this population. Retrospective and observational study included all neonates (less than 30 days since birth) who underwent congenital heart disease surgery in a level III neonatal intensive care department. We included infants born between January 2014 and December 2019. We excluded those infants who were born before 34 weeks of gestational age or whose birth weight was less than 1800 g. We also excluded catheter lab procedures and patent ductus arteriosus closure surgeries. Included patients were divided into two groups depending on whether they were diagnosed with chylothorax or not after surgery, and both groups were compared in terms of perinatal-obstetrical information, surgical data, and NICU course after surgery. We included 149 neonates with congenital heart disease surgery. Thirty-one patients (20.8%) developed chylothorax, and in ten patients (32.3%), it was considered large volume chylothorax. Regarding the evolution of these patients, 22 infants responded to general dietetic measures, a catheter procedure was performed in 9, and 5 of them finally required pleurodesis. Cardiopulmonary bypass, median sternotomy, and delayed sternal closure were the surgical variables associated with higher risks of chylothorax. Patients with chylothorax had a longer duration of inotropic support and mechanical ventilation and took longer to reach full enteral feeds. As complications, they had higher rates of cholestasis, catheter-related sepsis, and venous thrombosis. Although there were no differences in neonatal mortality, patients with chylothorax had a higher rate of mortality after the neonatal period. In a multiple linear regression model, thrombosis and cardiopulmonary bypass multiplied by 10.0 and 5.1, respectively, the risk of chylothorax and have an umbilical vein catheter decreases risk. CONCLUSION: We have found a high incidence of chylothorax after neonatal cardiac surgery, which prolongs the average stay and causes significant morbidity and mortality. We suggested that chylothorax could be an underestimated complication of congenital heart disease surgery during the neonatal period. WHAT IS KNOWN: • Acquired chylothorax in the neonatal period usually appears as a complication of congenital heart disease surgery, being the incidence quite variable among the different patient series (2.5-16.8%). The appearance of chylothorax as a complication of a cardiac surgery increases both mortality and morbidity in these patients, which makes it a quality improvement target in the postsurgical management of this population. WHAT IS NEW: •Most of the published studies include pediatric patients of all ages, from newborns to teenagers, and there is a lack of studies focusing on neonatal populations. The main strength of our study is that it reports, to the best of our knowledge, one of the largest series of neonatal patients receiving surgery for congenital heart disease in the first 30 days after birth. We have found a high incidence of chylothorax after cardiac surgery during the neonatal period compared to other studies. We suggested that chylothorax could be an underestimated complication of congenital heart disease surgery during this period of life.

Lung protection strategy with high-frequency oscillatory ventilation improves respiratory outcomes at two years in preterm respiratory distress syndrome: a before and after, quality improvement study.

INTRODUCTION: Bronchopulmonary dysplasia (BPD) remains one of the major challenges of extreme prematurity. High-frequency oscillatory ventilation (HFOV) with volume guarantee (HFOV-VG) can be used as an early-rescue ventilation to protect developing lungs. However, the studies exploring the impact of this ventilatory strategy on neonatal respiratory morbidity are very limited. This study aimed at documenting the improvement in respiratory outcomes in mechanically ventilated preterm newborns, after the implementation of a new mechanical ventilation respiratory bundle. METHODS: A prospective, quality improvement study was conducted between January 2012 and December 2018 in a third level NICU in Madrid, Spain. Infants born <32 weeks of gestation with severe respiratory distress syndrome (RDS) and requiring invasive mechanical ventilation were included. The intervention consisted of a new ventilation respiratory care bundle, with HFOV as early rescue therapy using low high-frequency tidal volumes (Vthf) and higher frequencies (15-20 Hz). Criteria for HFOV start were impaired oxygenation or ventilation on conventional ventilation, or peak inspiratory pressures >15 cmH2O. Two cohorts of mechanically ventilated patients were compared, cohort 1 (2012-2013, baseline period) and cohort 2 (2016-2018, after implementation of the new bundle). Clinical outcomes at 36 weeks and 2 years of postmenstrual age were compared between the groups. RESULTS: A total of 216 patients were included, the median gestational age was 26 weeks (IQR 25-28) and median birth weight was 895 g (IQR 720-1160). There were no significant differences in survival between the groups, but patients with the protective ventilation strategy (cohort 2) had higher survival without BPD 2-3 (OR 2.93, 95%CI 1.41-6.05). At 2 years of postmenstrual age, patients in cohort 2 also had a higher survival free of baseline respiratory treatment and hospital respiratory admissions than the control group (adjusted OR 2.33, 95%CI 1.10-4.93, p=.03). The results did not suggest significant differences in neurologic development. CONCLUSIONS: In extreme premature related severe respiratory failure, the use of a lung protective HFOV-VG strategy was proven to be a useful quality improvement intervention in our unit, leading to better pulmonary outcomes at 36 weeks and additional improved respiratory prognosis at two years of age.

Lung recruitment in neonatal high-frequency oscillatory ventilation with volume-guarantee.

BACKGROUND AND OBJECTIVES: The optimal lung volume strategy during high-frequency oscillatory ventilation (HFOV) is reached by performing recruitment maneuvers, usually guided by the response in oxygenation. In animal models, secondary spontaneous change in oscillation pressure amplitude (ΔPhf) associated with a progressive increase in mean airway pressure during HFOV combined with volume guarantee (HFOV-VG) identifies optimal lung recruitment. The aim of this study was to describe recruitment maneuvers in HFOV-VG and analyze whether changes in ΔPhf might be an early predictor for lung recruitment in newborn infants with severe respiratory failure. DESIGN AND METHODS: The prospective observational study was done in a tertiary-level neonatology department. Changes in ΔPhf were analyzed during standardized lung recruitment after initiating early rescue HFOV-VG in preterm infants with severe respiratory failure. RESULTS: Twenty-seven patients were included, with a median gestational age of 24 weeks (interquartile range [IQR]: 23-25). Recruitment maneuvers were performed, median baseline mean airway pressure (mPaw) was 11 cm H2 O (IQR: 10-13), median critical lung opening mPaw during recruitment was 14 cm H2 O (IRQ: 12-16), and median optimal mPaw was 12 cm H2 O (IQR: 10-14, p < 0.01). Recruitment maneuvers were associated with an improvement in oxygenation (FiO2 : 65.0 vs. 45.0, p < 0.01, SpO2/FiO2 ratio: 117 vs. 217, p < 0.01). ΔPhf decreased significantly after lung recruitment (mean amplitude: 23.0 vs. 16.0, p < 0.01). CONCLUSION: In preterm infants with severe respiratory failure, the lung recruitment process can be effectively guided by ΔPhf on HFOV-VG.

Nasal Intermittent Positive Pressure Ventilation and Bronchopulmonary Dysplasia Among Very Preterm Infants Never Intubated During the First Neonatal Admission: A Multicenter Cohort Study.

Introduction: While non-invasive positive-pressure ventilation (NIPPV) is increasingly used as a mode of respiratory support for preterm infants, it remains unclear whether this technique translates into improved respiratory outcomes. We assessed the association between NIPPV use and bronchopulmonary dysplasia (BPD)-free survival in never intubated very preterm infants. Methods: This multicenter cohort study analyzed data from the Spanish Neonatal Network SEN1500 corresponding to preterm infants born at <32 weeks gestational age and <1,500 g and not intubated during first admission. The exposure of interest was use of NIPPV at any time and the main study outcome was survival without moderate-to-severe BPD. Analyses were performed both by patients and by units. Primary and secondary outcomes were compared using multilevel logistic-regression models. The standardized observed-to-expected (O/E) ratio was calculated to classify units by NIPPV utilization and outcome rates were compared among groups. Results: Of the 6,735 infants included, 1,776 (26.4%) received NIPPV during admission and 6,441 (95.6%) survived without moderate-to-severe BPD. After adjusting for confounding variables, NIPPV was not associated with survival without moderate-to-severe BPD (OR 0.84; 95%CI 0.62-1.14). A higher incidence of moderate-to-severe BPD-free survival was observed in high- vs. very low-utilization units, but no consistent association was observed between O/E ratio and either primary or secondary outcomes. Conclusion: NIPPV use did not appear to decisively influence the incidence of survival without moderate-to-severe BPD in patients managed exclusively with non-invasive ventilation.

Target volume-guarantee in high-frequency oscillatory ventilation for preterm respiratory distress syndrome: Low volumes and high frequencies lead to adequate ventilation.

BACKGROUND AND OBJECTIVES: Respiratory distress syndrome (RDS) and ventilation-induced lung injury lead to significant morbidity in preterm infants. High-frequency oscillatory ventilation with volume-guarantee (HFOV-VG) has been used as a rescue therapy and might lead to lower rates of death and bronchopulmonary dysplasia, especially when using low tidal volumes and high frequencies. The aim of the study was to define HFOV-VG parameters leading to adequate ventilation in the first 72 h of preterm RDS using a low volume and high-frequency strategy. DESIGN AND METHODS: Retrospective cohort study in a tertiary-level neonatology unit. Infants <32 weeks with severe respiratory insufficiency needing HFOV-VG were included. Patients were ventilated following a standard mechanical ventilation aiming for low tidal volumes and high frequencies. Clinical data, perinatal characteristics and high-frequency parameters corresponding with adequate ventilation were recorded. RESULTS: 116 patients were included. Median gestational age was 25 weeks (interquartile range [IQR] = 24-27), median birth weight 724 g (IQR = 600-900 g). HFOV-VG was started at 2 h, median high-frequency tidal volume was 1.63 ml/kg (IQR = 1.44-1.84) and median frequency was 16 Hz (IQR = 15-18). Weight-adjusted tidal volumes did not depend on gestational age, antenatal corticosteroids nor chorioamnionitis, and were inversely correlated with frequencies (R 2 = -0.10, p = .001). CONCLUSION: HFOV-VG can reach adequate ventilation at high frequencies when using adequate volumes, providing a feasible ventilation strategy that might be of help in preterm infants with RDS.

Comorbilidades y evolución de la función pulmonar de pacientes con atresia esofágica congénita / Comorbidities and course of lung function in patients with congenital esophageal atresia

Objetivo. Describir las características epidemiológicas, el seguimiento hospitalario y la evolución de los pacientes intervenidos por atresia esofágica y su repercusión en la función pulmonar. Población y métodos. Estudio retrospectivo, longitudinal y analítico. Se revisaron las historias clínicas de pacientes con atresia esofágica nacidos entre 1996 y 2017. Se registraron datos perinatales, tipo de atresia, malformaciones asociadas, complicaciones respiratorias y digestivas, y los datos espirométricos durante tres años. Resultados. Se incluyeron 97 pacientes. El tipo de atresia más frecuente fue el III y el síndrome más frecuente, la trisomía 21. El 13,4 % fallecieron en el período neonatal. El 23,8 % de los pacientes estuvo en seguimiento por Neumología y presentó como complicaciones respiratorias exacerbaciones (el 46,4 %), sibilancias o asma (el 36 %), neumonías (el 26,8 %). El reflujo gastroesofágico fue factor de riesgo de sibilancias (OR 5,31; p = 0,002), exacerbaciones (OR 4,00; p = 0,009) y neumonías (OR 3,24; p = 0,02). En la primera espirometría (n = 20), un 65 % presentaba patrón normal; un 30 %, restrictivo, y un 5 %, mixto. En la segunda espirometría (n = 19), un 42,1 % presentaba patrón normal; un 31,6 %, restrictivo; un 15,8 %, obstructivo, y un 10,5 %, mixto. En la tercera espirometría (n = 14), el 50 % presentaba un patrón espirométrico normal; el 21,4 %, restrictivo; el 14,3 %, obstructivo, y un 14,3 %, mixto. Conclusiones. En nuestra muestra de pacientes, una importante proporción presentó comorbilidades respiratorias y digestivas. La función pulmonar empeoró progresivamente.

Objective. To describe the epidemiological characteristics, hospital follow-up, and course of patients who underwent surgery for esophageal atresia and its consequences on lung function. Population and methods. Retrospective, longitudinal, and analytical study. The medical records of patients with esophageal atresia born between 1996 and 2017 were reviewed. Perinatal data, type of atresia, associated malformations, respiratory and gastrointestinal complications, and spirometry data were recorded over 3 years. Results. A total of 97 patients were included. The most common type of atresia was III, and the most frequent syndrome, trisomy 21; 13.4 % of patients died in the neonatal period; 23.8 % were followed up by the Department of Pulmonology, and their respiratory complications included exacerbations (46.4 %), wheezing or asthma (36 %), and pneumonia (26.8 %). Gastroesophageal reflux was a risk factor for wheezing (OR: 5.31; p = 0.002), exacerbations (OR: 4.00; p = 0.009), and pneumonia (OR: 3.24; p = 0.02). In the first spirometry (n = 20), the pattern was normal in 65 %; restrictive in 30 %; and mixed in 5 %. In the second spirometry (n = 19), the pattern was normal in 42.1 %; restrictive in 31.6 %; obstructive in 15.8 %, and mixed in 10.5 %. In the third spirometry (n = 14), the pattern was normal in 50 %; restrictive in 21.4 %; obstructive in 14.3 %, and mixed in 14.3 %.Conclusions. In our sample of patients, a large proportion had respiratory and gastrointestinal comorbidities. Lung function worsened progressively.

Comorbidities and course of lung function in patients with congenital esophageal atresia. / Comorbilidades y evolución de la función pulmonar de pacientes con atresia esofágica congénita.

OBJECTIVE: To describe the epidemiological characteristics, hospital follow-up, and course of patients who underwent surgery for esophageal atresia and its consequences on lung function. POPULATION AND METHODS: Retrospective, longitudinal, and analytical study. The medical records of patients with esophageal atresia born between 1996 and 2017 were reviewed. Perinatal data, type of atresia, associated malformations, respiratory and gastrointestinal complications, and spirometry data were recorded over 3 years. RESULTS: A total of 97 patients were included. The most common type of atresia was III, and the most frequent syndrome, trisomy 21; 13.4 % of patients died in the neonatal period; 23.8 % were followed up by the Department of Pulmonology, and their respiratory complications included exacerbations (46.4 %), wheezing or asthma (36 %), and pneumonia (26.8 %). Gastroesophageal reflux was a risk factor for wheezing (OR: 5.31; p = 0.002), exacerbations (OR: 4.00; p=0.009), and pneumonia (OR: 3.24; p = 0.02). In the first spirometry (n=20), the pattern was normal in 65 %; restrictive in 30 %; and mixed in 5 %. In the second spirometry (n = 19), the pattern was normal in 42.1 %; restrictive in 31.6 %; obstructive in 15.8 %, and mixed in 10.5 %. In the third spirometry (n = 14), the pattern was normal in 50 %; restrictive in 21.4 %; obstructive in 14.3 %, and mixed in 14.3 %. CONCLUSIONS: In our sample of patients, a large proportion had respiratory and gastrointestinal comorbidities. Lung function worsened progressively.

Objetivo: Describir las características epidemiológicas, el seguimiento hospitalario y la evolución de los pacientes intervenidos por atresia esofágica y su repercusión en la función pulmonar. Población y métodos: Estudio retrospectivo, longitudinal y analítico. Se revisaron las historias clínicas de pacientes con atresia esofágica nacidos entre 1996 y 2017. Se registraron datos perinatales, tipo de atresia, malformaciones asociadas, complicaciones respiratorias y digestivas, y los datos espirométricos durante tres años. Resultados: Se incluyeron 97 pacientes. El tipo de atresia más frecuente fue el III y el síndrome más frecuente, la trisomía 21. El 13,4 % fallecieron en el período neonatal. El 23,8 % de los pacientes estuvo en seguimiento por Neumología y presentó como complicaciones respiratorias exacerbaciones (el 46,4 %), sibilancias o asma (el 36 %), neumonías (el 26,8 %). El reflujo gastroesofágico fue factor de riesgo de sibilancias (OR 5,31; p = 0,002), exacerbaciones (OR 4,00; p = 0,009) y neumonías (OR 3,24; p = 0,02). En la primera espirometría (n = 20), un 65 % presentaba patrón normal; un 30 %, restrictivo, y un 5 %, mixto. En la segunda espirometría (n = 19), un 42,1 % presentaba patrón normal; un 31,6 %, restrictivo; un 15,8 %, obstructivo, y un 10,5 %, mixto. En la tercera espirometría (n = 14), el 50 % presentaba un patrón espirométrico normal; el 21,4 %, restrictivo; el 14,3 %, obstructivo, y un 14,3 %, mixto. Conclusiones: En nuestra muestra de pacientes, una importante proporción presentó comorbilidades respiratorias y digestivas. La función pulmonar empeoró progresivamente.