F. Bagnoli

Sensorial saturation: an effective analgesic tool for heel-prick in preterm infants: a prospective randomized trial.

Pain is traumatic for preterm infants and can damage their CNS. We wanted to assess whether multisensorial stimulation can be analgesic and whether this effect is only due to oral glucose or sucking. We performed a randomized prospective study, using a validated acute pain rating scale to assess pain during heel-prick combined with five different procedures: (A) control, (B) 10% oral glucose plus sucking, (C) sensorial saturation (SS), (D) oral water, and (E) 10% oral glucose. SS is a multisensorial stimulation consisting of delicate tactile, vestibular, gustative, olfactory, auditory and visual stimuli. Controls did not receive any analgesia. We studied 85 heel-pricks (5 per baby) performed for routine blood samples in 17 preterm infants (28–35 weeks of gestational age). We applied in random order in each patient the five procedures described above and scored pain. SS and sucking plus oral glucose have the greater analgesic effect with respect to no intervention (p < 0.001). The effect of SS is statistically better than that of glucose plus sucking (p < 0.01). SS promotes interaction between nurse and infant and is a simple effective form of analgesia for the NICU.

Procalcitonin in detecting neonatal nosocomial sepsis

Objective To investigate the accuracy of procalcitonin (PCT) as a diagnostic marker of nosocomial sepsis (NS) and define the most accurate cut-off to distinguish infected from uninfected neonates. Setting Six neonatal intensive care units (NICUs). Patients 762 neonates admitted to six NICUs during a 28-month observational study for whom at least one serum sample was taken on admission. Main outcome measures Positive and negative predictive values at different PCT cut-off levels. Results The overall probability of an NS was doubled or more if PCT was >0.5 ng/ml. In very-low-birth-weight (VLBW) infants, a cut-off of >2.4 ng/ml gave a positive predictive value of NS near to 50% with a probability of a false-positive diagnosis of NS in about 10% of the patients. Conclusions In VLBW neonates, a serum PCT value >2.4 ng/ml prompts early empirical antibiotic therapy, while in normal-birth-weight infants, a PCT value ≤2.4 ng/ml carries a low risk of missing an NS.

Determinants of Nosocomial Infection in 6 Neonatal Intensive Care Units: An Italian Multicenter Prospective Cohort Study

BACKGROUND Nosocomial infections are still a major cause of morbidity and mortality among neonates admitted to neonatal intensive care units (NICUs). OBJECTIVE To describe the epidemiology of nosocomial infections in NICUs and to assess the risk of nosocomial infection related to the therapeutic procedures performed and to the clinical characteristics of the neonates at birth and at admission to the NICU, taking into account the time between the exposure and the onset of infection. DESIGN A multicenter, prospective cohort study. PATIENTS AND SETTING A total of 1,692 neonates admitted to 6 NICUs in Italy were observed and monitored for the development of nosocomial infection during their hospital stay. METHODS Data were collected on the clinical characteristics of the neonates admitted to the NICUs, their therapeutic interventions and treatments, their infections, and their mortality rate. The cumulative probability of having at least 1 infection and the cumulative probability of having at least 1 infection or dying were estimated. The hazard ratio (HR) for the first infection and the HR for the first infection or death were also estimated. RESULTS A total of 255 episodes of nosocomial infection were diagnosed in 217 neonates, yielding an incidence density of 6.9 episodes per 1,000 patient-days. The risk factors related to nosocomial infection in very-low-birth-weight neonates were receipt of continuous positive airway pressure (HR, 3.8 [95% confidence interval {CI}, 1.7-8.1]), a Clinical Risk Index for Babies score of 4 or greater (HR, 2.2 [95% CI, 1.4-3.4]), and a gestational age of less than 28 weeks (HR, 2.1 [95% CI, 1.2-3.8]). Among heavier neonates, the risk factors for nosocomial infection were receipt of parenteral nutrition (HR, 8.1 [95% CI, 3.2-20.5]) and presence of malformations (HR, 2.3 [95% CI, 1.5-3.5]). CONCLUSIONS Patterns of risk factors for nosocomial infection differ between very-low-birth-weight neonates and heavier neonates. Therapeutic procedures appear to be strong determinants of nosocomial infection in both groups of neonates, after controlling for clinical characteristics.

Early activation of the hypothalamic-pituitary-adrenal-axis in very-low-birth-weight infants with small thymus at birth

Background. An acute thymic involution in human fetuses and newborns has been described in very-low-birth-weight (VLBW) infants with histological chorioamnionitis. However, the mechanisms of thymic involution remain to be clarified. Here, we tested the hypothesis that an activation of the hypothalamic-pituitary-adrenal (HPA) axis occurs in VLBW infants with acute thymic involution at birth. Methods. A total of 180 randomly selected VLBW newborns (28.8 ± 3.15 wk gestation; 1093 ± 305 g) entered the study. Thymic size was measured on standard chest radiographs at birth, and expressed as the ratio between the transverse diameter of the cardiothymic image at the level of the carina (CT) and that of the thorax (T). CT/T < 0.28 was considered to indicate a small thymic size. Plasma cortisol and adrenocorticotropic hormone (ACTH) concentrations were determined on days 1 (d-1) and 7 (d-7), and at 1 month (mo-1). Results. A total of 66 (36.7%) newborns had CT/T < 0.28. Infants with small thymus had significantly increased cortisol on d-1 (∼5.2-folds) [median: 18.95 (95% CI: 11.20–39.4) μg/dl vs. 3.66 (1.94–6.82) μg/dl, p < 0.0001)] and d-7(∼1.7-folds) [12.0 (4.39–22.97) μg/dl vs. 7.8 (3.63–12.8) μg/dl, p = 0.0384)], as compared with those with normal thymic size, together with higher adrenocorticotropic hormone (ACTH) concentrations on d-1 (∼1.9-folds) [28 (15.6–61.07) pg/ml vs. 14.9 (9.0–23.42) pg/ml, p = 0.0005)], while no significant differences for cortisol at mo-1 or ACTH concentrations on d-7 and mo-1 were evidenced (p > 0.50). From a multivariate logistic regression analysis, a small thymus at birth was a significant independent predictor of plasma cortisol concentrations in the top-quartile (OR = 14.4; 95% CI: 6.079–34.11), and plasma ACTH concentrations in the top-quartile (OR = 4.40 (95% CI: 1.99–9.74) on d-1 (results adjusted for variables significant at univariate analysis). Conclusions. Our data indicated the presence of a previously unrecognized, early activation of the HPA axis in VLBW newborns with a small thymus at birth.

Reduction of exposure of newborns and caregivers to very high electromagnetic fields produced by incubators

The aims of this paper is to measure whether ferromagnetic panels sufficiently reduce the high electromagnetic fields (EMF) to which newborns are exposed in incubators and to which caregivers are exposed when working near the incubators. We measured EMF at mattress level in three neonatal incubators with and without ferromagnetic panels between the electric motor and the mattress. We then measured the EMF at the level of the maximum emission point for caregivers, i.e., near the display panel. The ferromagnetic panels were (a) 5 mm thick iron, (b), (c), (d) respectively, one, two, and three sheets of 0.3 mm thick mu-metal. The weight of iron sheet was 4 g/cm2, and mu-metal 0.2 g/cm2. The use of the ferromagnetic panels significantly reduced the EMF. No significant difference in attenuation was recorded using one, two, or, three sheets of mu-metal, or a single sheet of iron. One, two, and three sheets of mu-metal reduced EMFs by 77%, 82%, and 84.3%, respectively; the reduction with iron was 80%. EMF values measured in incubators were higher than those to which the general population is exposed. The use of ferromagnetic panels significantly reduces the level of EMFs to which neonates and caregivers are exposed.

Congenital cystic adenomatoid malformation of the lung associated with esophageal atresia and tracheoesophageal fistula

Abstract Bronchopulmonary malformations associated with esophageal atresia (EA) and tracheoesophageal fistula (TEF) are extremely rare. The authors describe a case of type II congenital cystic adenomatoid malformation (CCAM) of the right lower lobe associated with EA and TEF (Vogt-Gross type C) in a full-term female infant. The CCAM presented as an incidental radiologic finding, and a contralateral tension pneumothorax developed shortly after surgical repair of the EA. Early recognition of this rare association is essential for correct operative management.

15 Determinants of Nosocomial Infection (NI) in Six Italian Neonatal Intensive Care Units (NICUs).

As care improves many neonates with life-threatening disorders now survive. Nonetheless Nosocomial Infections (NI) are still a major cause of morbidity and mortality in NICUs. A prospective multicentric surveillance study was conducted in six Italian NICUs to describe the epidemiologic profile and determinants of NI in NICU. 1692 neonates, consecutively admitted to the NICUs from July 2000 to October 2002 and monitored for the development of NI were enrolled into the study. The standard definition criteria for NI formulated by the Centers for Disease Control in Atlanta were used. The cumulative probability and hazard ratios (HR) for the first episode of infection were estimated by the Kaplan-Meier method and the Cox model. A total of 217 neonates had 255 episodes of NI. The incidence rate of NI was 7 per 1000 patient-days. The cumulative probability of first infection was 20% (95% CI, 7.50–23.30) and 27.6% (95 CI, 23.20–32.80) at 30 and 60 days after admission to the NICU. After adjustment for the severity of illness, the main risk factors related to NI in very-low-birth-weight neonates (VLBW) were surgical procedures (HR 2.69;95% CI 0.60–12.08), nasal ventilation (CPAP) (HR, 2.51; 95% CI, 0.93–6.76), continuous enteral feeding (HR 1.89; 95% CI, 0.20–17.50), mechanical ventilation (HR, 1.70; 95%CI, 0.72–4.00) and intravenous infusions (HR 1.46; 95% CI, 0.32–6.52). Among neonates with a birth weight over 1500 g, risk factors for NI were parenteral nutrition with lipid emulsion (HR, 12.41; 95% CI, 4.19–36.78), surgical procedures (HR 2.78; 95% CI, 0.82–9.44), and intravenous infusions (HR, 2.63; 95% CI, 0.27–25.53). Risk factors for NI were related more to the severity of illness than to healthcare procedures in VLBW babies and more to medications among neonates weighing more than 1500 g at birth.Supported by a Grant from the Italian Ministry of Health, N 99010661

EEG in assessing hydroxycobalamin therapy in neonatal methylmalonic aciduria with homocystinuria

We performed serial electroencephalograms (EEG) in a newborn with methylmalonic aciduria and homocystinuria to assess the effects of hydroxycobalamin (OHcbl) therapy on the CNS. Diagnosis was made at 22 days of age: she had torpor, failure to thrive and hypotonia of the limbs, and intermittent opisthotonus. The first EEG, performed on the first day of therapy, showed abnormal and immature transients, low voltage and very long flat periods in the discontinuous part of the tracing. These features quickly improved during therapy. After 13 days of OHcbl therapy, the EEG tracing became normal for conceptional age and showed normal sleep phases with only minor anomalies; only mild hypotonia still remained and biochemical parameters normalized. The decrease in blood homocysteine (index of blood detoxification) was statistically correlated to the reduction of the length of flat periods in EEG (p < 0.01). In conclusion, changes in neonatal EEG, particularly the length of interburst periods in the intermittent part of the tracing, appeared to be a reliable index for evaluating drug effectiveness in methylmalonic aciduria and homocystinuria.

65 Subclinical Chorioamnionitis: An Unrecognized Risk Factor for Severe Pulmonary Haemorrhage in Extremely Low Birth Weight Infants

Background: Clinically apparent pulmonary hemorrhage (PH) occurs in 5%–7% of very low birth weight (VLBW) infants with respiratory distress syndrome (RDS), and is associated with significantly increased mortality rate and severe pulmonary and central nervous system morbidities. To date, little information on the pathogenesis of the condition is available, although recent evidence suggests a key role for inflammation. Here, we tested the hypothesis that subclinical chorioamnionitis (s-CA) is associated with the development of PH in extremely low birth weight (ELBW) newborns.Methods: The clinical and placental histology findings of ELBW infants died with severe PH (PH+: n=9; M:2, F:7; gestational age[mean ± SD]: 25.7 ± 1.2 weeks, birth weight: 768 ± 179 g; age at death [median; interquartile range)]: 4 days; 3–7) were compared to those of a gestational age- and birth weight-matched ELBW population without PH (PH-: n=15; M:7, F:8; gestational age: 26.1 ± 3.1 weeks, birth weight: 787 ± 255 g).Results: PH+ ELBW newborns showed significantly higher proportions of histological s-CA [8/9 (88.9%) vs. 1/15 (6.7%), p=0.0001; relative risk = 13.3; 95 % CI: 1.97 - 89.8], preterm premature rupture of membranes [9/9 (100%) vs. 5/15 (33.3%), p=0.0020], together with higher frequency of intraventricular haemorrhage degree 3–4 [IVH3–4: 8/9 (88.9%) vs. 2/15 (13.3%), p=0.0049] than the PH- population. Conversely, no statistical differences were observed between the groups regarding the other examined variables, including coagulation screening work-up, antenatal steroids, multiple gestation, emergency caesarean section, 1-min and 5-min Apgar scores, fetal growth restriction, patent ductus arteriosus, air leak, necrotizing enterocolitis, sepsis, I.M.-vitamin K1 supplementation, fresh frozen plasma administration, surfactant replacement and number of surfactant doses, type of assisted ventilation, as well as energy, fluid, glucose protein, and lipid intakes during the first postnatal week (p≥0.21).Conclusion: These findings appear to support the hypothesis that s-CA, associated with a fetal systemic inflammatory response syndrome, may play a key role in the pathogenesis of severe PH in ELBW infants.

63 Abnormal Oral Mucosal Light Reflectance in Bronchopulmonary Dysplasia

Background: Bronchopulmonary dysplasia(BPD)remains an important cause of mortality and morbidity in preterm infants. A disordered vascular development and a decreased production of angiogenic factors in BPD have been recently reported. Extracellular matrix (ECM) is known to play an important role on angiogenesis and blood vessel geometry and changes in ECM components have been previously reported in experimental models and patients with BPD. In the present study, we tested the hypothesis of abnormal reflectance of the oral mucosa in BPD.Methods: Fifteen preterm infants with BPD(M:9,F:6; gestational age:27.5±2.0 wk, birth weight:850±125 gr) and 15 gender and gestational age-matched control infants without BPD (M:9, F:6; gestational age: 27.6±2.6 wk, birth weight: 865±135 gr) were examined. Mean blood concentrations of major chromophores, including hemoglobin and bilirubin (P= 0.95) and total bilirubin (P= 0.88) were comparable between the groups. Reflectance was measured on high-resolution photographs of the lower lower gingival and vestibular oral mucosa, using an imaging spectrophotometer. Spatially averaged spectra were used in order to estimate the oral mucosal color in the 400–700 nm wavelength electromagnetic spectral range. Derived spectral data were reproducible [intra- and inter-observer coefficients of variation (mean±SD),1.46±0.89% and 3.72±1.75%, respectively], and qualitatively comparable (±2%shift) to those obtained by direct measurements (absolute spectral error∼0.4). Reflectance values from 50–100 different artifact-free and vessel-free areas were measured, and mean values were used for data analysis. The predictive accuracy of oral spectrophotometry was calculated using receiver operating characteristic curve analysis.Results: BPD patients showed significantly lower light reflectance values in the red (610–700 nm; t values range:4.552–6.775, df=28,P<0.0001), with higher values in the violet (400nm, P=.0056;430nm, P=.014), and blue-green (480–500 nm, P≤.024) sections of the spectrum. A low reflectance value in the 640–700 nm wavelengths interval was found to identify BPD patients with 100% sensitivity and 100% specificity (640nm: cutoff≤44.91%;650nm:≤ 45.64%;660nm:≤46.56%; 670nm:≤47.14%;680nm:≤47.56%;690nm:≤ 48.95%;700nm:≤50.81%).Conclusion: These findings indicate the presence of previously unrecognised, early abnormalities of the average optical properties of the oral mucosa in BPD infants.