Gianluca Lista

Does Sustained Lung Inflation at Birth Improve Outcome of Preterm Infants at Risk for Respiratory Distress Syndrome

Background: Sustained lung inflation (SLI) applied at birth has been demonstrated to lead to clearance of lung fluid and achievement of a precocious functional residual capacity in animal studies. Objectives: To verify if the application of SLI in preterm infants at birth may reduce the need for mechanical ventilation and improve their respiratory outcome. Methods: We prospectively studied 89 infants with respiratory distress (gestational age (GA) 28.1 ± 2.2 weeks) treated at birth with a SLI (25 cm H2O, sustained for 15 s) in addition to AAP recommendations versus a historical control group (n = 119; GA 28.1 ± 2.0 weeks) treated without SLI with the same device (controlled positive end-expiratory pressure of 5 cm H2O). Results: The SLI group had less need for (51 vs. 76%, p < 0.0001) and shorter duration of mechanical ventilation (5 ± 11 vs. 11 ± 19 days, p = 0.008), a more frequent occurrence of exclusive nasal continuous airway pressure support (49 vs. 24%, p < 0.0001) and INtubation-SURfactant-Extubation (INSURE) treatment (16 vs. 3%, p = 0.01), less need for surfactant (45 vs. 61%, p = 0.027) and postnatal steroids (10 vs. 25%, p = 0.01), a shorter duration of oxygen therapy (21 ± 27 vs. 31 ± 31 days, p = 0.016), and, finally, a lower occurrence of bronchopulmonary dysplasia in survivors (7 vs. 25%, p = 0.004). Multiple regression analysis showed that 23–27 weeks of GA and birth weight <750 g increased the risk of mechanical ventilation, while a clinical risk index for babies (CRIB) score <3 as well as INSURE strategy and SLI treatment in the delivery room decreased it. Conclusions: The application of a SLI at birth in preterm infants with respiratory distress may decrease the need for mechanical ventilation without inducing evident adverse effects.

Sustained Lung Inflation at Birth for Preterm Infants: A Randomized Clinical Trial

BACKGROUND: Studies suggest that giving newly born preterm infants sustained lung inflation (SLI) may decrease their need for mechanical ventilation (MV) and improve their respiratory outcomes. METHODS: We randomly assigned infants born at 25 weeks 0 days to 28 weeks 6 days of gestation to receive SLI (25 cm H2O for 15 seconds) followed by nasal continuous positive airway pressure (nCPAP) or nCPAP alone in the delivery room. SLI and nCPAP were delivered by using a neonatal mask and a T-piece ventilator. The primary end point was the need for MV in the first 72 hours of life. The secondary end points included the need for respiratory supports and survival without bronchopulmonary dysplasia (BPD). RESULTS: A total of 148 infants were enrolled in the SLI group and 143 in the control group. Significantly fewer infants were ventilated in the first 72 hours of life in the SLI group (79 of 148 [53%]) than in the control group (93 of 143 [65%]); unadjusted odds ratio: 0.62 [95% confidence interval: 0.38–0.99]; P = .04). The need for respiratory support and survival without BPD did not differ between the groups. Pneumothorax occurred in 1% (n = 2) of infants in the control group compared with 6% (n = 9) in the SLI group, with an unadjusted odds ratio of 4.57 (95% confidence interval: 0.97–21.50; P = .06). CONCLUSIONS: SLI followed by nCPAP in the delivery room decreased the need for MV in the first 72 hours of life in preterm infants at high risk of respiratory distress syndrome compared with nCPAP alone but did not decrease the need for respiratory support and the occurrence of BPD.

Hypothermia Reduces Neurological Damage in Asphyxiated Newborn Infants

Background: Perinatal asphyxia remains one of the most devastating neurologic processes. There is experimental and clinical evidence that cerebral cooling may suppress the biochemical cascades leading to delayed cerebral damage. Objective: To determine if hypothermia started soon after delivery reduces cerebral damage in term infants. Design/Methods: Retrospective chart analysis with historical controls. Ten asphyxiated newborns treated with hypothermia between October 1998 and October 1999 were compared to 11 asphyxiated newborns admitted from September 1997 to September 1998. Characteristics at birth of infants of the two groups (control and hypothermia) were comparable. After obtaining parental consent, whole-body hypothermia was induced before the 6th hour of life by placing a cold blanket (Polar Air, Augustine Medical Inc., model 600) around the body of the patients. Rectal temperature was maintained between 32 and 34°C for 72 h. Outcome was assessed by neurological evaluation at birth and every 3 months up to the 12th month. Brain MRI was performed in the 2nd month. We had no evidence of severe adverse events related to hypothermia. In the hypothermic group there was a significant (p < 0.05) reduction of major neurologic abnormalities at follow-up and abnormal MRI findings. Conclusions: Hypothermia appears to be safe. Our results on morphological damage evaluated by brain MRI and neurological outcome are encouraging: randomized controlled trials are needed to confirm this experience.

Sustained inflation versus positive pressure ventilation at birth: a systematic review and meta-analysis

Context Sustained inflation (SI) has been advocated as an alternative to intermittent positive pressure ventilation (IPPV) during the resuscitation of neonates at birth, to facilitate the early development of an effective functional residual capacity, reduce atelectotrauma and improve oxygenation after the birth of preterm infants. Objective The primary aim was to review the available literature on the use of SI compared with IPPV at birth in preterm infants for major neonatal outcomes, including bronchopulmonary dysplasia (BPD) and death. Data source MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials, until 6 October 2014. Study selection Randomised clinical trials comparing the effects of SI with IPPV at birth in preterm infants for neonatal outcomes. Data extraction and synthesis Descriptive and quantitative information was extracted; data were pooled using a random effects model. Heterogeneity was assessed using the Q statistic and I2. Results Pooled analysis showed significant reduction in the need for mechanical ventilation within 72 h after birth (relative risk (RR) 0.87 (0.77 to 0.97), absolute risk reduction (ARR) −0.10 (−0.17 to −0.03), number needed to treat 10) in preterm infants treated with an initial SI compared with IPPV. However, significantly more infants treated with SI received treatment for patent ductus arteriosus (RR 1.27 (1.05 to 1.54), ARR 0.10 (0.03 to 0.16), number needed to harm 10). There were no differences in BPD, death at the latest follow-up and the combined outcome of death or BPD among survivors between the groups. Conclusions Compared with IPPV, preterm infants initially treated with SI at birth required less mechanical ventilation with no improvement in the rate of BPD and/or death. The use of SI should be restricted to randomised trials until future studies demonstrate the efficacy and safety of this lung aeration manoeuvre.

Routine Lactobacillus rhamnosus GG administration in VLBW infants: a retrospective, 6-year cohort study.

BACKGROUND In preterm neonates, use of probiotic mixtures is increasingly popular and is effective in preventing NEC, fungal colonization, and improving feeding tolerance. However, concerns exist about safety and tolerability of long-lasting administration of living microrganisms to not-immunocompetent hosts. We report a 6-year, two-NICUs experience of routinary Lactobacillus rhamnosus GG (LGG) use in VLBW infants. METHODS Clinical charts review, retrospective study of VLBW infants admitted to two Italian NICUs in the years 2003-2008. Standard protocol of LGG administration consisted of 3 x 10⁹ CFU/day, in single oral dose, since 4th day-of-life, for 4-to-6-week courses. Nutritional policy relied on administration of fresh, expressed mothers milk, supplementation with preterm formula if needed. Data about LGG safety and tolerability, infections, feeding tolerance, microbiological clinical and surveillance cultures were retrieved and analysed. RESULTS Complete data were obtained for 743 of 811 VLBW infants. Mean birth-weight was 1056 g; mean gestational age 29.5 weeks. A total of 17,108 LGG doses were administered (mean 23.1/infant). No adverse effects or intolerances putatively attributable to LGG occurred. Overall, 5350 clinical and surveillance cultures from 13 different sites/devices were performed (mean: 7.2 cultures from 6.5 different sites/infant). None ever grew LGG, or other Lactobacilli. No clinical sepsis episode was attributable to LGG. Full enteral feeding was achieved at 19.2 mean days-of-life; 73% of infants were exclusively/partially breastfed. Fourteen NEC cases occurred (=1.9%), with 5 (=0.7%) being>2b stage. CONCLUSIONS Routinary supplementation of probiotic LGG in a large, 6-year VLBW infants Italian cohort proved microbiologically safe and clinically well tolerated.

Prognostic Value of Electroencephalograms in Asphyxiated Newborns Treated With Hypothermia

Previous studies described how early electroencephalogram patterns in neonatal hypoxic-ischemic encephalopathy seem to correlate with the severity of the clinical picture and provide prognostic information. This study evaluated whether electroencephalograms of newborns with severe perinatal hypoxic-ischemic encephalopathy, treated with hypothermia, provide information on clinical outcomes. Twenty-three newborns treated with hypothermia underwent electroencephalogram monitoring within 48 hours of age, and were enrolled in a follow-up with sequential electroencephalogram and neurologic controls (at ages 1 week, 1 month, 3-6 months, and 1 year). An inactive electroencephalogram pattern in the first 48 hours of age was associated with death or major neurologic sequelae. At age 1 week, a low-voltage, continuous pattern indicated a worse prognostic value when compared with other patterns. The persistence of electroencephalogram abnormalities at age 1 month was associated with a higher risk of neurologic sequelae. Background electroencephalogram abnormalities, detected in the first days of life after hypoxic-ischemic encephalopathy, can provide prognostic information, even in patients treated with hypothermia. After 1 month of age, the information on clinical outcomes provided by electroencephalograms usually decreases because of the natural trend toward electroencephalogram normalization.

Safety of Deep Hypothermia in Treating Neonatal Asphyxia

Background: Several studies have demonstrated the efficiency and safety of mild hypothermia (33°C) used for treating moderate encephalopathy. In animal models, deep hypothermia proved to be neuroprotective. Objectives: To determine the safety of whole-body deep hypothermia between 30 and 33°C in moderate-severe hypoxic-ischemic encephalopathy in newborn term infants. Methods: Mortality rates, incidence of brain damage detected by magnetic resonance imaging (MRI) and neurological outcomes of 39 term asphyxiated infants were retrospectively compared. A first group of patients (control group C) was treated with routine standard methods, a second group (MH) was treated with mild whole-body hypothermia (32–34°C) and a third group (DH) was treated with deep whole-body hypothermia (30–33°C), for 72 h. Mean arterial pH, basic excess (BE) and lactic acid in the blood were measured. Laboratory and clinical side effects of hypothermia were investigated. A conventional brain MRI was performed after the second week of life. Results: 39 term asphyxiated newborns were enrolled in the study: 11 in group C, 10 in group MH, and 18 in group DH. During the first 72 h, disseminated intravascular coagulation was recorded in 2 cases (18%) in group C, pulmonary hypertension in 2 patients (20%) in group MH, and pneumonia in 3 cases (16%) in group DH. Severe cerebral lesions and poor neurological outcome were observed in 4 cases (36%) in group C, 1 case (10%) in group MH, and 1 case (5%) in group DH. A statistically significant difference in brain damage and major clinical neurological abnormalities was observed between group C and groups MH and DH, whereas no differences were demonstrated between asphyxiated infants treated with mild or deep hypothermia. Conclusions: The results support the safety of deep hypothermia. Further studies are needed to confirm these results and the neuroprotective effect of this approach.

Automated versus Manual Oxygen Control with Different Saturation Targets and Modes of Respiratory Support in Preterm Infants.

OBJECTIVE To determine the efficacy and safety of automated adjustment of the fraction of inspired oxygen (FiO2) in maintaining arterial oxygen saturation (SpO2) within a higher (91%-95%) and a lower (89%-93%) target range in preterm infants. STUDY DESIGN Eighty preterm infants (gestational age [median]: 26 weeks, age [median] 18 days) on noninvasive (n = 50) and invasive (n = 30) respiratory support with supplemental oxygen, were first randomized to one of the SpO2 target ranges and then treated with automated FiO2 (A-FiO2) and manual FiO2 (M-FiO2) oxygen control for 24 hours each, in random sequence. RESULTS The percent time within the target range was higher during A-FiO2 compared with M-FiO2 control. This effect was more pronounced in the lower SpO2 target range (62 ± 17% vs 54 ± 16%, P < .001) than in the higher SpO2 target range (62 ± 17% vs 58 ± 15%, P < .001). The percent time spent below the target or in hypoxemia (SpO2 <80%) was consistently reduced during A-FiO2, independent of the target range. The time spent above the target range or at extreme hyperoxemia (SpO2 >98%) was only reduced during A-FiO2 when targeting the lower SpO2 range (89%-93%). These outcomes did not differ between infants on noninvasive and invasive respiratory support. Manual adjustments were significantly reduced during A-FiO2 control. CONCLUSIONS A-FiO2 control improved SpO2 targeting across different SpO2 ranges and reduced hypoxemia in preterm infants on noninvasive and invasive respiratory support. TRIAL REGISTRATION ISRCTN 56626482.

Volume guarantee versus high frequency ventilation: lung inflammation in preterm infants

Background: Appropriate ventilation together with improvement of clinical care of premature babies can contribute to reducing lung inflammation, known to represent the “primum movens” of bronchopulmonary dysplasia (BPD). High-frequency oscillatory ventilation (HFOV) and volume-guarantee (VG) ventilation are effective in the treatment of neonatal respiratory distress syndrome (RDS). Objective: To assess the potential of HFOV and VG to prevent BPD in the acute phase of RDS, by a randomised clinical study evaluating lung inflammation in premature infants. Study design: Forty infants (gestational age 25–32 weeks) with RDS were assigned to assist-control ventilation plus VG (Vt = 5 ml/kg) or HFOV (both with a Dräger Babylog 8000 plus ventilator). Levels of interleukin (IL) 6, IL8 and tumour necrosis factor were determined in tracheal aspirate on days 1, 3 and 7 of life. Results: In the HFOV group IL6 levels were significantly higher on day 3 (0.5 (0.2) vs assisted-control ventilation plus VG group 0.1 (0.2) ng/ml) and oxygen dependency was significantly longer (36 (23) vs assisted-control ventilation plus VG group 19 (11) days). Conclusion: VG ventilation is an effective lung-protective strategy to be used in acute RDS, inducing a lower expression of early inflammation markers than HFOV. Whether the use of this initial ventilatory strategy contributes to the prevention of BPD requires further studies.

Mothers and Fathers in NICU: The Impact of Preterm Birth on Parental Distress.

Preterm birth is a stressful event for families. In particular, the unexpectedly early delivery may cause negative feelings in mothers and fathers. The aim of this study was to examine the relationship between preterm birth, parental stress and negative feelings, and the environmental setting of NICU. 21 mothers (age = 36.00 ± 6.85) and 19 fathers (age = 34.92 ± 4.58) of preterm infants (GA = 30.96 ± 2.97) and 20 mothers (age = 40.08 ± 4.76) and 20 fathers (age = 40.32 ± 6.77) of full-term infants (GA = 39.19 ± 1.42) were involved. All parents filled out the Parental Stressor Scale: Neonatal Intensive Care Unit, the Impact of Event Scale Revised, Profile of Mood States, the Multidimensional Scale of Perceived Social Support and the Post-Partum Bonding Questionnaire. Our data showed differences in emotional reactions between preterm and full-term parents. Results also revealed significant differences between mothers and fathers’ responses to preterm birth in terms of stress, negative feelings, and perceptions of social support. A correlation between negative conditions at birth (e.g., birth weight and Neonatal Intensive Care Unit stay) and higher scores in some scales of Impact of Event Scale Revised, Profile of Mood States and Post-Partum Bonding Questionnaire were found. Neonatal Intensive Care Unit may be a stressful place both for mothers and fathers. It might be useful to plan, as soon as possible, interventions to help parents through the experience of the premature birth of their child and to begin an immediately adaptive mode of care.