Carlo Dani

Probiotics feeding in prevention of urinary tract infection, bacterial sepsis and necrotizing enterocolitis in preterm infants: A prospective double-blind study

Background: It has been suggested that probiotics can reduce the overgrowth of pathogens in the bowels of preterm infants and contribute to the reduction of the incidence of nosocomial infections in neonatal intensive care units (NICUs). The purpose of this study was to evaluate the effectiveness of Lactobacillus GG supplementation in reducing the incidence of urinary tract infections (UTIs), bacterial sepsis and necrotizing enterocolitis (NEC) in preterm infants. Methods: A double-blind study was conducted in 12 Italian NICUs. Newborn infants with a gestational age <33 weeks or birthweight <1,500 g were randomized to receive standard milk feed supplemented with Lactobacillus GG (Dicoflor®, Dicofarm, Rome, Italy) in a dose of 6 × 109 colony-forming units (cfu) once a day until discharge, starting with the first feed or placebo. Results: Five hundred eighty-five patients were studied. The probiotics group (n = 295) and the placebo group (n = 290) exhibited similar clinical characteristics. The duration of Lactobacillus GG and placebo supplementation was 47.3 ± 26.0 and 48.2 ± 24.3 days, respectively. Although UTIs (3.4 vs. 5.8%) and NEC (1.4 vs. 2.7%) were found less frequently in the probiotic group compared to the control group, these differences were not significant. Bacterial sepsis was more frequent in the probiotics group (4.4%, n = 11) than in the placebo group (3.8%, n = 9), but the difference was not significant. Conclusion: Seven days of Lactobacillus GG supplementation starting with the first feed is not effective in reducing the incidence of UTIs, NEC and sepsis in preterm infants. Further studies are required to confirm our results in lower birthweight populations.

The role of blood transfusions and iron intake on retinopathy of prematurity

BACKGROUND The role of blood transfusions and iron intake in the pathogenesis or retinopathy of prematurity (ROP) is controversial. AIM To evaluate the influence of packed red cell (PRC) transfusions and iron intake on ROP incidence. STUDY DESIGN Prospective observational study. SUBJECTS Forty-five preterm infants with birthweight <1250 g were studied. After ophthalmological study, they were divided into group A (n=24) that included newborns without ROP, and group B (n=21) that included newborns with ROP. RESULTS Logistic regression analysis demonstrated that gestational age (OR 0.61; 95% C.I. 0.41-0.90), transfusion volume during the first week (OR 1.16; 95% C.I. 1.03-1.3) and during the first 2 months of life (OR 2.93; 95% C.I. 1.52-5.62), and iron intake during the first week of life (OR 1.15; C.I. 1.01-1.32) and during the first 2 months of life (OR 2.93; 95% C.I. 1.52-5.62) were associated with the development of ROP. CONCLUSION Our study showed that gestational age, blood transfusion volume and iron load by transfusions are associated with the risk of occurrence of ROP in infants with a birthweight of less than 1250 g.

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.

Acute neonatal respiratory distress in Italy: a one-year prospective study

A prospective multicentre 12‐month survey of neonatal respiratory disorders in 63 537 Italian infants was performed to evaluate the incidence of acute neonatal respiratory disorders and of the main related complications. A total of 1427 developed respiratory disorders (2.2%), 208 of whom died (14.6%). The incidence of respiratory distress syndrome was 1.16%, with a case fatality rate (CFR) of 24%; that of transient tachypnoea was 0.93%, with a CFR of 1.3%. The rates of meconium aspiration syndrome, persistent pulmonary hypertension and pneumonia were 0.06%, 0.02% and 0.07%, with CFRs of 10.3%, 38.5% and 21.7%, respectively. The occurrences of the main complications in affected newborns were: bronchopulmonary dysplasia 5.6%, necrotizing enterocolitis 1.7%, patent ductus arteriosus 9.8%, 3o and 4o grade intraventricular haemorrhage 6.8% and air leak 4.9%. It was concluded that the incidence of acute neonatal respiratory disorders and the main related complications was lower than that reported two decades ago and that the CFR of acute neonatal respiratory disorders had increased. These results may be the consequences of (i) progress in the management of high‐risk pregnancies, (ii) an increased number of viable infants with extremely low birth weight and (iii) diffusion of antenatal treatment with corticosteroids which, in this series, seemed to reduce the morbidity but not the mortality in the high‐risk infants.

High flow nasal cannula therapy as respiratory support in the preterm infant

We reviewed the literature on the effects of high flow nasal cannula (HFNC) and heated, humidified, high‐flow, nasal cannula (HHHFNC) treatment in preterm infants. We found nine studies, but only two were randomized controlled trials. These studies show that: HFNC application is associated to the delivery of continuous distending pressure (CDP) in patients with closed mouth, whose value is proportional to the delivered flow only in smaller infants; the CDP delivered by HFNC is unpredictable and present large inter‐patient and intra‐patient variability; the use of recently available HHHFNC devices is effective in minimizing nasal mucosa injuries compared to traditional HFNC; the effectiveness of HHHFNC versus NCPAP for the treatment of apnoea of prematurity, respiratory distress syndrome, and the prevention of extubation failure, has been poor investigated and firm conclusions cannot be drawn on this matter. In conclusion, on the basis of published data, the routinary application of HFNC should be limited to patients requiring oxygen‐therapy, HHHFNC devices should be preferred to HFNC, but their employment as an alternative to NCPAP should wait for the conclusion of randomized controlled trials. Pediatr Pulmonol. 2009; 44:629–634.

Epidemiology of Neonatal Acute Respiratory Disorders

A prospective 3-month survey of neonatal respiratory disorders in 17,192 Italian infants born in 65 hospitals, located in 17 Italian regions representative of northern, central and southern Italy, was performed to evaluate the incidence of neonatal acute respiratory disorders and their risk factors. The prematurity rate was 7.3%, while the extremely low birth weight (<1,000 g) and very low birth weight (<1,500 g) rates were 0.58% and 0.99%, respectively. Four hundred and ninety-one infants (2.8%) developed respiratory signs. Lethality or specific fatality rate (SFR) for acute respiratory disorders with regard to the overall study population was 0.45%. The male/female ratio of affected infants was 1.3:1. Among affected newborns the case fatality rate (CFR) for respiratory disorders was 15.88% (78/491) and was higher in males than in females (2:1), in infants with a gestational age of ≤28 weeks (60%) and birth weights of <1,000 g (50%). Moreover, the SFR was higher (p < 0.05) in the infants of mothers older than 34 years. SFR was 3.0% in intrauterine growth-retarded infants, 3.6% in the first twin and 3.2% in the second twin. An Apgar score of ≤3 at 5 min was strongly related to the incidence of respiratory disorders (47.1%). The antenatal prevention of neonatal respiratory distress syndrome with maternal corticosteroid treatment was performed in 84% of newborns (<32 weeks) with respiratory problems in northern Italy, and about 25% and 38% in central and southern Italy, respectively. The CFR was double in southern Italy as compared with northern and central Italy. Prematurity, low birth weight and a low Apgar score (≤3) at 1 and 5 min as well as a maternal age of >34 years are risk factors for acute respiratory disorders.

Blood transfusions increase cerebral, splanchnic, and renal oxygenation in anemic preterm infants.

BACKGROUND: Multiprobe near infrared spectroscopy (NIRS) has been used to study regional cerebral (rSO2C), splanchnic (rSO2S), and renal (rSO2R) tissue oxygenation in newborns. We used this method to study the effects of red blood cell (RBC) transfusions in anemic preterm infants to assess if thresholds for transfusions were appropriate for recognizing a clinical condition permitting tissue oxygenation improvement.

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.

Prophylaxis of patent ductus arteriosus with ibuprofen in preterm infants

The aim of our study was to evaluate whether the prophylactic use of ibuprofen would reduce the incidence of significant patent ductus arteriosus (PDA) and to confirm the effectiveness of ibuprofen as rescue treatment in closing PDA. Eighty preterm infants with gestational age less than 34 wk with infant respiratory distress syndrome (iRDS) were randomized to receive intravenous ibuprofen lysine (10 mg/kg, followed by 5 mg/kg after 24 and 48 h) either within 24 h of life (group A) or after echocardiographic diagnosis of PDA (group B). To evaluate the severity of RDS in each patient, we calculated the initial and highest values of Oxygenation Index (O.I. =mean airway pressure × FiO2 × 100 / PaO2) and Ventilatory Index (V.I. = O.I. × mechanical respiratory rate). Other studied variables were ventilatory support, renal function, biochemical and haematological profiles, frequency of bronchopulmonary dysplasia (BPD), intraventricular haemorrhage (IVH), necrotizing enterocolitis (NEC) and retinopathy of prematurity (ROP). On the 3rd day of life, 8% (3/40) of patients of group A and 53% of patients (21/40) of group B (p < 0.0001) developed a significant PDA. Between patients of group B who presented PDA at 3 d of life 90% (19/21) had a closure of ductus arteriosus after ibuprofen treatment. Initial and highest values of O.I. and V.I. were similar in both groups A and B. No significant differences between the groups were observed in regard to respiratory support, renal function and frequency of BPD, IVH, NEC and ROP. Ibuprofen was not associated with adverse effects.

Methylxanthines Increase Renal Calcium Excretion in Preterm Infants

To determine the effect of a short course of methylxanthines on renal function and on urinary calcium excretion, 20 premature neonates affected by apnea or moderate respiratory distress syndrome were randomly assigned to either a theophylline treatment or to a caffeine treatment group. The protocol included a 24-hour pretreatment study period (I) and a subsequent 24-hour period (II) following 5 days of theophylline (loading dose 5 mg/kg i.v., maintenance dose 2.5 mg/kg/12 h) or caffeine (loading dose 10 mg/kg i.v., maintenance dose 2.5 mg/kg/12 h) administration. Pre- and postxanthine treatment serum sodium, potassium, calcium and phosphorus remained stable, while serum creatinine decreased significantly (p < 0.05). Furthermore, from period I to period II, sodium urine excretion, fractional Na excretion and creatinine clearance remained statistically comparable in both study groups, along with a significant increase (p < 0.05) in calciuria, urinary Ca/creatinine and urinary Ca/Na. Predose caffeine and theophylline serum levels, assessed on the 5th day of treatment, were 12.8 +/- 1.8 and 7.9 +/- 1.7 micrograms/ml, respectively. Compared to control healthy untreated prematures, the studied premature infants showed a statistically significant increase in urine calcium excretion (10- to 15-fold), which was more evident in the theophylline group. Our data suggest further investigation to determine the long-term renal effects of methylxanthines in premature neonates, to improve assessment of the risk of nephrocalcinosis and osteopenia, in particular in association with various diuretic therapies.