Valentina Vendettuoli

Clinical prediction models for bronchopulmonary dysplasia: a systematic review and external validation study

BackgroundBronchopulmonary dysplasia (BPD) is a common complication of preterm birth. Very different models using clinical parameters at an early postnatal age to predict BPD have been developed with little extensive quantitative validation. The objective of this study is to review and validate clinical prediction models for BPD.MethodsWe searched the main electronic databases and abstracts from annual meetings. The STROBE instrument was used to assess the methodological quality. External validation of the retrieved models was performed using an individual patient dataset of 3229 patients at risk for BPD. Receiver operating characteristic curves were used to assess discrimination for each model by calculating the area under the curve (AUC). Calibration was assessed for the best discriminating models by visually comparing predicted and observed BPD probabilities.ResultsWe identified 26 clinical prediction models for BPD. Although the STROBE instrument judged the quality from moderate to excellent, only four models utilised external validation and none presented calibration of the predictive value. For 19 prediction models with variables matched to our dataset, the AUCs ranged from 0.50 to 0.76 for the outcome BPD. Only two of the five best discriminating models showed good calibration.ConclusionsExternal validation demonstrates that, except for two promising models, most existing clinical prediction models are poor to moderate predictors for BPD. To improve the predictive accuracy and identify preterm infants for future intervention studies aiming to reduce the risk of BPD, additional variables are required. Subsequently, that model should be externally validated using a proper impact analysis before its clinical implementation.

Changes in ventilator strategies and outcomes in preterm infants

Background Although life-saving, intubation and mechanical ventilation can lead to complications including bronchopulmonary dysplasia (BPD). In order to reduce the incidence of BPD, non-invasive ventilation (NIV) is increasingly used. Objective The aim of our study was to describe changes in ventilator strategies and outcomes between 2006 and 2010 in the Italian Neonatal Network (INN). Design Multicentre cohort study. Settings 31 tertiary level neonatal units participating in INN in 2006 and 2010. Patients 2465 preterm infants 23–30 weeks gestational age (GA) without congenital anomalies. Main outcomes measures Death, BPD and other variables defined according to Vermont Oxford Network. Logistic regressions, adjusting for confounders and clustering for hospitals, were used. Results Similar numbers of infants were studied between 2006 and 2010 (1234 in 2006 and 1231 in 2010). The baseline risk of populations studied (GA, birth weight and Vermont Oxford Network Risk-Adjustment score) did not change. After adjusting for confounding variables, infants receiving invasive mechanical ventilation decreased (OR=0.72, 95% CI 0.58 to 0.89) while NIV increased (OR=1.75, 95% CI 1.39 to 2.21); intubation in delivery room decreased (OR=0.64, 95% CI 0.51 to 0.79). Considering outcomes, there was a significant reduction in mortality (OR=0.73, 95% CI 0.55 to 0.96) and in the combined outcome mortality or BPD (OR=0.76, 95% CI 0.62 to 0.94). Conclusions Despite a stable baseline risk, from 2006 to 2010, we observed a lower level of invasiveness, a reduction of mechanical ventilation and an increase of NIV use, and this was accompanied by a decrease in risk-adjusted mortality and BPD.

The role of Candida surveillance cultures for identification of a preterm subpopulation at highest risk for invasive fungal infection.

Candida surveillance cultures were obtained from 51 neonatal intensive care unit patients. Sixteen infants showing positive cultures developed subsequent Candida infection, whereas it did not occur for the 35 infants with negative cultures. Fifteen of 16 infants (<1000 g) had <27 weeks of gestational age. Antifungal treatment was started at the time colonization was detected; only 1 infant died of Candida infection.

Nasal Continuous Positive Airway Pressure With Heliox in Preterm Infants With Respiratory Distress Syndrome

OBJECTIVE: To assess the therapeutic effects of breathing a low-density helium and oxygen mixture (heliox, 80% helium and 20% oxygen) in premature infants with respiratory distress syndrome (RDS) treated with nasal continuous positive airway pressure (NCPAP). METHODS: Infants born between 28 and 32 weeks of gestational age with radiologic findings and clinical symptoms of RDS and requiring respiratory support with NCPAP within the first hour of life were included. These infants were randomly assigned to receive either standard medical air (control group) or a 4:1 helium and oxygen mixture (heliox group) during the first 12 hours of enrollment, followed by medical air until NCPAP was no longer needed. RESULTS: From February 2008 to September 2010, 51 newborn infants were randomly assigned to two groups, 24 in the control group and 27 in the heliox group. NCPAP with heliox significantly decreased the risk of mechanical ventilation in comparison with NCPAP with medical air (14.8% vs 45.8%). CONCLUSIONS: Heliox increases the effectiveness of NCPAP in the treatment of RDS in premature infants.

Calcium signaling-related proteins are associated with broncho-pulmonary dysplasia progression.

UNLABELLED Broncho-pulmonary dysplasia (BPD) is a chronic pulmonary disorder that follows premature birth. It is preceded by respiratory distress syndrome (RDS), characterized by acute respiratory failure due to deficiency of surfactant at birth. Clinical characteristics of infants affected by BPD have widely changed in the last decades: they are extraordinarly immature, with impaired alveolar and vascular lung development. To build up new therapeutic strategies for BPD babies, it is necessary to understand the pathogenic mechanisms, which are complicated by environmental risk factors and genetic predisposition. Therefore, the aim of this study was to highlight protein changes in the broncho-alveolar lavage fluid (BALF), thus providing an appropriate picture on what is happening in the locus of injury. We analyzed BALF samples from preterm babies, born at different stages of lung development. We confirmed that gestational age is relevant for BPD progression, but we also detected few de-regulated proteins in the younger babies; we discovered less abundant calcium signaling-related proteins, consistent with BPD severity, comparing severe to mild BPD babies with matched gestational age. In conclusion, this study suggests a subset of proteins to be investigated to better treat BPD babies and facilitate the definition of potential drug targets for novel therapies. BIOLOGICAL SIGNIFICANCE Pulmonary biomarkers are needed to predict the clinical course of lung disease, status, progression and response to treatment. A key aspect in biomarker discovery is uncovering molecules that appear early during disease initiation, when the natural history of the disease can be modified. Using a proteomic-based approach we compared broncho-alveolar lavage fluid (BALF) protein profile from preterm neonates at different postmenstrual ages, to have a molecular description of broncho-pulmonary dysplasia (BPD) progression. BALF provided a snapshot of local molecular changes, which are relevant for early diagnosis, assessment and characterization of lung disorders. We showed that even if the studied patients had similar clinical phenotype (they all developed severe BPD and they were all cured in the same way in terms of mechanical ventilation, surfactant administration, antenatal steroid treatment and ibuprofen treatment for patent ductus arteriosus), however their BALF protein profiling displayed significant differences in a subset of proteins, which could be exploited to facilitate the development of novel effective therapies, distinct for age and severity of the disease.

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.

Antifungal Prophylaxis: Identification of Preterm Neonates at Highest Risk for Invasive Fungal Infection

reported an increased risk of attention-deficit disorder (ADD) (adjusted relative risk: 1.9 [95% confidence interval (CI): 1.1–3.3]). To investigate a possible association between TSB levels in infancy and subsequent risk of ADD, we linked laboratory, demographic, and outpatient visit databases of infants from 1995 to 2004 in the Northern California Kaiser Permanente Medical Care Program as previously described.2–4 We included infants born at 34 weeks and 2000 g who had at least 1 outpatient visit at 3 years of age (N 161 141). TSB levels were measured at the discretion of the clinicians. We investigated the association between maximum reported TSB levels in the first 30 days after birth and ever having an outpatient visit that included a diagnosis of ADD (International Classification of Diseases, 9th Revision codes 314–314.9). We found no association between TSB levels and ADD diagnoses (Table 1). Dichotomizing at 19 mg/dL, the relative risk was 1.08 (95% CI: 0.91–1.28). A Cox proportional hazards model of time to first ADD diagnosis, controlling for race, gender, birth weight, gestational age, facility of birth, and maternal age, yielded similar results (adjusted hazard ratio for TSB 19 mg/dL: 1.07 [95% CI: 0.90–1.27]). The association between ADD and hyperbilirubinemia seems not to have been hypothesized a priori. This finding could easily be a result of chance, as commonly occurs when investigators look for associations not initially hypothesized (ie, with low previous probability).5 We conclude that hyperbilirubinemia is unlikely to be clinically significantly associated with ADD.

Positional effects on lung mechanics of ventilated preterm infants with acute and chronic lung disease

The role of prone position in preterm infants has not been completely clarified. We investigated prone versus supine posture‐related changes in respiratory system resistance (Rrs) and reactance (Xrs) measured by the Forced Oscillation Technique (FOT) in mechanically ventilated preterm newborns.

Last Word on Point: Counterpoint: High-frequency ventilation is/is not the optimal physiological approach to ventilate ARDS patients

The following letters are in response to Point:Counterpoint: High-frequency ventilation is/is not the optimal physiological approach to ventilate ARDS patients. To the Editor : Mechanical ventilation (MV) may aggravate lung injury due to two primary types of injury: volu- and atelectrauma. There is

A new FOT set-up for the assessment of respiratory system mechanics in mechanically ventilated infants

The assessment of respiratory system mechanics in mechanically ventilated newborns would help in tailoring the ventilatory settings. The Forced Oscillations Technique (FOT) is a non-invasive method for the measurement of the mechanical properties of the respiratory system. The aim of the present work was to develop a measurement set-up suitable to apply FOT in mechanically ventilated newborns. Forced oscillations were generated by a servo-controlled linear motor connected to the inspiratory line of the ventilator. Pressure and flow were measured at the inlet of the tracheal tube and used to compute impedance. The set-up was tested on a mechanical analog of the infants respiratory system showing good agreement with a traditional FOT set-up. The performance of the system was not influenced by the positive pressures generated by the ventilator. Finally, the system was well tolerated by 5 preterm babies and the measurements allowed to track changes in respiratory mechanics associated to changes in the pressure delivered by the ventilator.