Claudia Aurilia

Early Mannan Detection in Bronchoalveolar Lavage Fluid With Preemptive Treatment Reduces the Incidence of Invasive Candida Infections in Preterm Infants

Background: Candida colonization is an important predictor for development of invasive fungal infection (IFI). We investigated whether early detection of Candida mannan (Mn) in bronchoalveolar lavage fluid (BALF) reduces IFI among preterm infants. Methods: We conducted an observational study of infants with gestational age of ≤28 weeks, where a group undergoing Candida surveillance cultures (pre-Mn detection group) was compared with a group defined after the initiation of routine use of Candida Mn detection in BALF (Mn detection group). Antifungal treatment was started based on positive microbiologic (surveillance culture or Mn-antigen assay) results. Results: No significant differences were detected when the groups were compared for several predictors of IFI. IFI was observed for 12 (23%) of 51 infants in the pre-Mn detection group, and for 0 (0%) of 29 infants in the Mn detection group (P = 0.003). Surveillance cultures in the pre-Mn detection group became positive at 15.0 ± 7.2 days after birth, whereas the mean age at time of positive Mn antigen results in the Mn detection group was 4.3 ± 3.1 days (P < 0.0001). Among 16 infants positive for surveillance cultures, 12 (75%) developed IFI (P < 0.0001). Conclusions: This study suggests that Candida Mn detection in BALF may be useful for earlier identification and preemptive therapy targeting preterm infants at high risk of IFI.

Association of high levels of α-defensins and S100A proteins with Candida mannan detection in bronchoalveolar lavage fluid of preterm neonates

Background:Candida mannan (Mn) detection in bronchoalveolar lavage fluid (BALF) was shown to be useful for earlier identification and preemptive therapy targeting in preterm infants at high risk of invasive Candida infection. We investigated whether early detection of Candida Mn in BALF is associated with the presence of some neutrophilic products, as markers of prenatal infection/inflammation.Methods:BALF specimens were collected during the first 48 h of life from mechanically ventilated preterm newborns. Samples were analyzed by high-performance liquid chromatography–electrospray ionization–mass spectrometry. The relative amounts of α-defensins 1–4 and S100A proteins were measured by extracted ion current peak area. Absolute and differential white cell counts in BALF were obtained. Mn antigen concentrations were determined by the Platelia Candida antigen kit.Results:Twenty-five studied neonates were divided into two groups: Mn-positive group and Mn-negative group. Levels of α-defensins 1–4 and S100A12 were significantly higher in the Mn-positive group than in the Mn-negative group. Moreover, positive significant correlations between the absolute number of neutrophils and the levels of α-defensins 1–4 and S100A8 were observed.Conclusion:The detection of Mn antigen in BALF of preterm infants is consistent with evidence of an innate immune response in their lungs as demonstrated by higher levels of α-defensins and S100A proteins.

Correlation of levels of α-defensins determined by HPLC-ESI-MS in bronchoalveolar lavage fluid with the diagnosis of pneumonia in premature neonates.

The presence of α-defensins in bronchoalveolar lavage fluid (BALF) was investigated in a cohort of preterm newborns with gestational age (GA) ≤30 wk. Specimens were collected during the first week of life from 24 preterm neonates mechanically ventilated. The studied population was divided into two groups: pneumonia group of nine neonates suffering from pulmonary infection (GA: 26.1 ± 2.1 wk; birth weight: 787.4 ± 309.9 g), with or without associated bloodstream infection, and nonpneumonia group of 15 neonates (GA: 27.7 ± 2.0 wk; birth weight: 1019.0 ± 319.8 g). BALF culture was positive for CONS (n = 5), Staphylococcus aureus (n = 1), and Candida spp (n = 3). BALF samples were analyzed by HPLC-electrospray Ionization-mass spectrometer. The α-defensins 1–4 concentration, absolute and differential white cells count were measured. Relative amounts of α-defensins 1–4 and the absolute number of neutrophils were found significantly higher in the pneumonia group with respect to the nonpneumonia group (p < 0.05). Moreover, positive significant correlations between the number of neutrophils and the α-defensins 1–3 levels were observed. In conclusion, our data show that preterm newborns, also at the lower GA, are able to produce α-defensins, underlining that their innate defense system is already active before the at-term delivery date.

Unexpected effect of recruitment procedure on lung volume measured by respiratory inductive plethysmography (RIP) during high frequency oscillatory ventilation (HFOV) in preterm neonates with respiratory distress syndrome (RDS)

Background: In clinical practice, one of the major problems in optimizing recruitment or lung volume during HFOV in preterm infants is the inability to accurately measure direct changes in lung volume at bedside. Objective: To evaluate changes in lung volume during the recruitment phase of elective HFOV in preterm infants with RDS using respiratory inductive plethysmography. Material and methods: The preliminary results of an observational prospective study were reported. Newborns with GA ≤ 27 weeks requiring elective HFOV for a diagnosis of RDS were studied within the first 6 hours of life using RIP technology, before surfactant instillation. HFOV was performed with Draeger Babylog 8000 plus ventilator with “optimum lung volume strategy “(continuous distending pressure (CDP) increased step-by-step until FiO2 ≤ 0.25 was reached). Data on ventilator settings, gas exchange and RIP volume were collected and analyzed. The analysis package used in this study visualizes measured data from the Bicore-II device (CareFusion), Pulse Oximeter Masimo, AX300 FiO2 monitor device and TCM4 shuttle (TCM4, Radiometer, Copenaghen, Denmark). Results: Four preterm infants (two females) with mean ± SD gestational age of 26.5 ± 1.0 weeks and mean ± SD birth weight of 978 ± 188 grams were studied. Relative FRC slightly increased during the first steps of the recruitment phase, while deeply decreased at higher CDP values (≥ 15 cm H2O). Notwithstanding FiO2 decreased until 0.25 in all the newborns except one. Conclusions: Because RIP cannot differentiate between changes in lung fluid or intrathoracic gas, we hypothesized that as CDP increases and total lung capacity is approached, pulmonary vascular resistance increases as a consequence of the compression of intra-alveolar vessels. This increases right ventricular afterload which, combined with re-establishment of right-to left shunting, results in decreased pulmonary blood flow and then decreased lung volume. Caution should then be used when using high CDP values during the recruitment procedure.

Determination of Lung Volume and Hemodynamic Changes During High-Frequency Ventilation Recruitment in Preterm Neonates With Respiratory Distress Syndrome

Objectives:To evaluate the changes in end-expiratory lung volume during an oxygenation-guided stepwise recruitment procedure in elective high-frequency ventilation. We hypothesized that high continuous distending pressure impedes pulmonary blood flow as evidenced by reduced lung volume measurements using respiratory inductive plethysmography. Changes in oxygenation, ventilation, and peripheral perfusion were evaluated as secondary outcomes. Design:A prospective, single center, observational, nonrandomized study. Setting:The study was conducted in a neonatal ICU in Italy. Patients:High-frequency ventilated preterm infants with respiratory distress syndrome. Interventions:During the recruitment procedure, end-expiratory lung volume measured by respiratory inductive plethysmography, oxygen saturation, perfusion index, regional cerebral and perirenal tissue oxygenation, heart rate, transcutaneous PCO2, and tidal volume were simultaneously recorded at each airway pressure step. Measurements and Main Results:In 12 preterm newborns (gestational age, 27.4 ± 0.2 wk; birth weight, 979 ± 198 g), high-frequency ventilation was initiated at a continuous distending pressure of 10 cm H2O and incrementally increased by 1–2 cm H2O every 2–5 minutes until FIO2 was less than or equal to 0.25. End-expiratory lung volume progressively increased during the initial recruitment, but decreased at the maximum airway pressure in nine patients, indicative of a reduction in pulmonary perfusion. At the end of recruitment, tidal volume was significantly higher (p = 0.002) and oxygenation was significantly improved (p = 0.002); however, mean perfusion index, postductal saturation, and mean renal tissue oxygenation values were significantly reduced (p < 0.05) compared with baseline. Mean cerebral tissue oxygenation and mean transcutaneous PCO2 values were reduced but failed to reach significance. Conclusions:High distending lung pressures increased oxygenation but decreased peripheral perfusion with no adverse cerebral side effects. Coupled with the reduction in respiratory inductive plethysmography–derived lung volume, high continuous distending pressure had adverse cardiopulmonary effects. Incorporation of lung volume and hemodynamic and oxygenation variables may guide optimum lung volume determination during high-frequency ventilation recruitment procedure while preventing adverse effects on the pulmonary circulation.

Fetal Doppler velocimetry and bronchopulmonary dysplasia risk among growth-restricted preterm infants: an observational study

Objective To investigate whether fetal growth restriction (FGR) diagnosis, based on pathological prenatal fetal Doppler velocimetry, is associated with bronchopulmonary dysplasia (BPD) independently of being small for gestational age (SGA) per se at birth among very preterm infants. Design Prospective, observational study. FGR was defined as failing fetal growth in utero and fetal Doppler velocimetry abnormalities. Setting Policlinico Universitario Agostino Gemelli, Roma, Italy. Patients Preterm newborns with gestational age ≤30 weeks and birth weight (BW) ≤1250 g. Main outcome measures Bronchopulmonary dysplasia. Results In the study period, 178 newborns were eligible for the study. Thirty-nine infants (22%) were considered fetal growth-restricted infants. Among the 154 survived babies at 36 weeks postmenstrual age, 12 out of 36 (33%) of the FGR group developed BPD versus 8 out of 118 (7%) of the NO-FGR group (p<0.001). BPD rate was sixfold higher among the SGA-FGR infants compared with the SGA-NO-FGR infants. In a multivariable model, FGR was significantly associated with BPD risk (OR 5.1, CI 1.4 to 18.8, p=0.01), independently from BW z-score that still remains a strong risk factor (OR 0.5, CI 0.3 to 0.9, p=0.01). Conclusion Among SGA preterm infants, BPD risk dramatically increases when placenta dysfunction is the surrounding cause of low BW. Antenatal fetal Doppler surveillance could be a useful tool for studying placenta wellness and predicting BPD risk among preterm babies. Further research is needed to better understand how FGR affects lung development.

Nasal high-frequency oscillatory ventilation and CO2 removal: A randomized controlled crossover trial

To compare short‐term application of nasal high‐frequency oscillatory ventilation (nHFOV) with nasal continuous positive airway pressure (nCPAP).

Ventilation Prior to Umbilical Cord Clamping Improves Cardiovascular Stability and Oxygenation in Preterm Lambs After Exposure to Intrauterine Inflammation

Background: Delaying umbilical cord clamping until after aeration of the lung (physiological-based cord clamping; PBCC) maintains cardiac output and oxygenation in preterm lambs at birth, however, its efficacy after intrauterine inflammation is not known. Given the high incidence of chorioamnionitis in preterm infants, we investigated whether PBCC conferred any benefits compared to immediate cord clamping (ICC) in preterm lambs exposed antenatally to 7 days of intrauterine inflammation. Methods: Ultrasound guided intraamniotic injection of 20 mg Lipopolysaccharide (from E. coli:055:B5) was administered to pregnant ewes at 0.8 gestation. Seven days later, ewes were anesthetized, preterm fetuses exteriorised via cesarean section, and instrumented for continuous measurement of pulmonary, systemic and cerebral pressures and flows, and systemic, and cerebral oxygenation. Lambs were then randomized to either PBCC, whereupon ventilation was initiated and maintained for 3 min prior to umbilical cord clamping, or ICC where the umbilical cord was cut and ventilation initiated 30 s later. Ventilation was maintained for 30 min. Results: ICC caused a rapid fall in systemic (by 25%) and cerebral (by 11%) oxygen saturation in ICC lambs, concurrent with a rapid increase in carotid arterial pressure and heart rate. The overshoot in carotid arterial pressure was sustained in ICC lambs for the first 20 min of the study. PBCC maintained cardiac output and prevented the fall in cerebral oxygen delivery at birth. PBCC lambs had lower respiratory compliance and higher respiratory requirements throughout the study. Conclusion: PBCC mitigated the adverse effects of ICC on oxygenation and cardiac output, and therefore could be more beneficial in preterm babies exposed to antenatal inflammation as it maintains cardiac output and oxygen delivery. The increased respiratory requirements require further investigation in this sub-group of preterm infants.