Manoj Biniwale

Decrease in incidence of bronchopulmonary dysplasia with erythropoietin administration in preterm infants: a retrospective study.

Background: Despite advances in clinical care, the incidence of bronchopulmonary dysplasia (BPD) remains high in premature infants. Erythropoietin (EPO) is used for the treatment of anemia of prematurity (AOP) to decrease blood transfusion needs. EPO has been shown to mobilize circulating endothelial progenitor cells and to enhance lung repair in animal models. Objective: To determine whether EPO treatment for AOP was associated with a reduced incidence of BPD in premature infants. Methods: This retrospective study was performed on all live-born neonates with birth weights from 500 to 1,500 g and gestational age (GA) from 22 to 32 weeks admitted from 1994 to 2002. Infants who received EPO and those who did not receive EPO were compared for incidence of BPD and other morbidities. Results: Of 478 patients, 297 received EPO before 36 weeks’ postmenstrual age (group 1) and 181 did not receive EPO (group 2). Group 1 was of similar birth weight but lower GA than group 2. The incidence of BPD was lower in group 1 than group 2 (26 vs. 36%, p = 0.03); after adjusting for significant risk factors, the adjusted odds ratio for BPD was 0.50 (95% CI 0.32, 0.79), p = 0.0028. The BPD rate was much lower when EPO was initiated before 4 weeks of age (16%) as compared to later initiation (44%). Conclusions: This study shows an association between EPO treatment and reduced incidence of BPD in preterm infants, particularly when EPO treatment was initiated within the first 4 weeks of life.

Evolution of surfactant therapy for respiratory distress syndrome: past, present, and future

Respiratory distress syndrome (RDS) due to surfactant deficiency is the most common cause of respiratory failure in preterm infants. Tremendous progress has been made since the original description that surfactant deficiency is the major cause of RDS. Surfactant therapy has been extensively studied in preterm infants and has been shown to significantly decrease air leaks and neonatal and infant mortality. Synthetic and animal-derived surfactants from bovine as well as porcine origin have been evaluated in randomized controlled trials. Animal-derived surfactants generally result in faster weaning of respiratory support, shorter duration of invasive ventilation, and decreased mortality when compared to first- or second-generation of synthetic surfactants, but some of the second-generation synthetic surfactants are at least not inferior to the animal-derived surfactants. Using a higher initial dose of porcine derived surfactant may provide better outcomes when compared with using lower doses of bovine surfactants, likely, due to compositional difference and/or the dose. Third-generation synthetic surfactant containing peptide analogs of surfactant protein B and C are currently being studied. Less invasive intra-tracheal surfactant administration techniques in spontaneously breathing neonate receiving noninvasive ventilator support are also being evaluated. In the present era, prophylactic surfactant is not recommended as it may increase the risk of lung injury or death. In the future, surfactants may be used as vector to deliver steroids, or used in combination with molecules, such as, recombinant Club Cell Protein-10 (rhCC-10) to improve pulmonary outcomes. Also, noninvasive surfactant administration techniques, such as aerosolization or atomization of surfactant may play a greater role in the future.

Circulating hematopoietic and endothelial progenitor cells in newborn infants: Effects of gestational age, postnatal age and clinical stress in the first 3 weeks of life

INTRODUCTION Circulating endothelial progenitor cells (EPC) are bone marrow derived progenitors that can be mobilized by erythropoietin or in response to tissue injury, and participate in vascular repair. EPC are understudied in human neonates. Whether EPC frequency in newborn infants may be influenced by gestational age or postnatal stress is unknown. METHODS Blood samples were collected on day 1 of life and weekly for 3 weeks from hospitalized neonates for plasma erythropoietin and flow cytometry analysis for CD34+, CD34+CD45-, CD34+VEGFR2+ and CD34+CD45-VEGFR2+ cells (EPC). Associations between CD34+ cell subsets and clinical parameters were studied. RESULTS Forty five patients were enrolled. An inverse correlation with gestational age was observed for CD34+ and CD34+ VEGFR2+ cell frequencies in whole blood (WB) on day 1 (p<0.05). In preterm infants, CD34+ cell frequency decreased with increased postnatal age (p=0.0001) and CD34+VEGFR2+ cell frequency was higher at week 3 than on day 1 in WB (p=0.0002). On day one, CD34+ and CD34+CD45- cell frequencies in the mononuclear cell fraction (MNC) were higher in preterm than term infants (p=0.035 and p=0.049, respectively) but CD34+CD45-VEGFR2+ cell frequency (median 2.2/million MNC versus 3.8/million MNC) and erythropoietin levels were not significantly different. Transient increases in EPC were observed in five infants with infection. Four preterm infants who developed bronchopulmonary dysplasia had undetectable or low EPC through the first 3 weeks of life. CONCLUSIONS Gestational age and postnatal age influenced circulating CD34+ and CD34+VEGFR2+ but not CD34+CD45-VEGFR2+ (EPC) cell frequencies. Circulating EPC in neonates may be influenced by clinical stress.

Non-Invasive Ventilation and Surfactant Therapy

The lungs of premature infants are more vulnerable than term infants to the effects of invasive positive pressure ventilation. Published literature supporting the use of non-invasive respiratory support with CPAP, bi-level CPAP mode, such as, SiPAP and Nasal Intermittent Positive Pressure Ventilation (NIPPV), and surfactant administration strategies are discussed. This review focuses on non-invasive respiratory support strategies and selective early use of surfactant that may reduce the incidence of bronchopulmonary dysplasia.

Decrease in delivery room intubation rates after use of nasal intermittent positive pressure ventilation in the delivery room for resuscitation of very low birth weight infants

BACKGROUND The literature supports minimizing duration of invasive ventilation to decrease lung injury in premature infants. Neonatal Resuscitation Program recommended use of non-invasive ventilation (NIV) in delivery room for infants requiring prolonged respiratory support. OBJECTIVE To evaluate the impact of implementation of non-invasive ventilation (NIV) using nasal intermittent positive pressure ventilation (NIPPV) for resuscitation in very low birth infants. STUDY DESIGN Retrospective study was performed after NIPPV was introduced in the delivery room and compared with infants receiving face mask to provide positive pressure ventilation for resuscitation of very low birth weight infants prior to its use. Data collected from 119 infants resuscitated using NIPPV and 102 infants resuscitated with a face mask in a single institution. The primary outcome was the need for endotracheal intubation in the delivery room. Data was analyzed using IBM SPSS Statistics software version 24. RESULTS A total of 31% of infants were intubated in the delivery room in the NIPPV group compared to 85% in the Face mask group (p=<0.001). Chest compression rates were 11% in the NIPPV group and 31% in the Face mask group (p<0.001). Epinephrine administration was also lower in NIPPV group (2% vs. 8%; P=0.03). Only 38% infants remained intubated at 24hours of age in the NIPPV group compared to 66% in the Face mask group (p<0.001). Median duration of invasive ventilation in the NIPPV group was shorter (2days) compared to the Face mask group (11days) (p=0.01). The incidence of air-leaks was not significant between the two groups. CONCLUSION NIPPV was safely and effectively used in the delivery room settings to provide respiratory support for VLBW infants with less need for intubation, chest compressions, epinephrine administration and subsequent invasive ventilation.

Neonatal Resuscitation Using a Nasal Cannula: A Single-Center Experience

OBJECTIVE The aim of the study was to describe our experience using a modified nasal cannula to deliver nasal continuous positive airway pressure and/or nasal intermittent positive pressure ventilation during primary neonatal resuscitation of preterm and term newborns. STUDY DESIGN Data were collected retrospectively for all neonates resuscitated with nasal cannula in the delivery room. The primary outcome was the number of newborns intubated in the delivery room. Secondary outcomes included need for chest compressions, intubations in the first 24 hours, air-leaks, and surfactant administration. RESULTS A total of 102 infants were resuscitated using nasal cannula. Eight (7.8%) were intubated in the delivery room, five (4.9%) required chest compressions, and five (4.9%) had pneumothorax noted on chest X-ray. No deaths occurred in the delivery room. Twenty-eight patients (27.5%) received early rescue surfactant after admission to the neonatal intensive care unit. CONCLUSION Neonatal resuscitation can be effectively performed in preterm and term newborns using a modified nasal cannula in the delivery room.

Early postnatal weight gain as a predictor for the development of retinopathy of prematurity

Abstract Objective: The objective of this study is to validate the reliability of early postnatal weight gain as an accurate predictor of type 1 retinopathy of prematurity (ROP) requiring treatment in a large predominantly Hispanic US cohort with the use of an online tool called WINROP (weight, neonatal retinopathy of prematurity (IGF-1), neonatal retinopathy of prematurity). Study design: Retrospective cohort study consisted of preterm infants <32 weeks gestation and birth weight <1500 g. Weekly weights to 36 weeks post-menstrual age or discharge if earlier were entered into the WINROP tool. This tool generated alarm and risk indicator for developing ROP. The infants with type 1 ROP requiring treatment as well as all stages of ROP were compared with the alarms and risks generated by WINROP tool. Results: A total of 492 infants were entered into the WINROP tool. The infants who developed type 1 ROP requiring treatment, the WINROP tool detected 80/89 (90%) at less than 32 weeks gestation. Nine infants developed type 1 ROP were classified as low risk and did not alarm. Conclusions: Postnatal weight gain alone, in predominantly Hispanic US population, predicted type 1 ROP requiring treatment before 32 weeks of gestation in infants with a sensitivity of 90%. The tool appeared to identify majority of affected infants much earlier than the scheduled screening.