Silvia Galletti

Impact of a standardized hand hygiene program on the incidence of nosocomial infection in very low birth weight infants

BACKGROUND This study examined the effects of a standardized hand hygiene program on the rate of nosocomial infection (NI) in very low birth weight (VLBW) infants (birth weight < 1500 g) admitted to our neonatal intensive care unit (NICU). METHODS We compared the rate of NI in VLBW infants in 2 separate periods. In the first period, staff were encouraged to perform handwashing using a plain fluid detergent (0.5% triclosan). In the second period, a standardized hand hygiene program was implemented using antimicrobial soap (4% chlorhexidine gluconate) and alcohol-based hand rubs. RESULTS NI after 72 hours of life was detected in 16 of the 85 VLBW infants in the first period and in 5 of the 80 VLBW infants in the second period. The rate of central venous catheter colonization was significantly lower in the second period (5.8%) than in the first period (16.6%). CONCLUSION In our NICU, the incidence of NI in VLBW infants was significantly reduced after the introduction of a standardized handwashing protocol. In our experience, a proper hand hygiene program can save approximately 10 NI episodes/year, at a cost of

The frequency of apneas in very preterm infants is increased after non‐acid gastro‐esophageal reflux

10,000 per episode. Therefore, improving hand hygiene practice is a cost-effective program in the NICU.

Extensively hydrolyzed protein formula reduces acid gastro-esophageal reflux in symptomatic preterm infants☆

Background  To evaluate whether physical and/or chemical features of gastro‐esophageal reflux (GER) influence its relationship with apnea of prematurity (AOP).

Protein content and fortification of human milk influence gastroesophageal reflux in preterm infants.

BACKGROUND Gastro-esophageal reflux (GER) is diagnosed frequently in preterm infants. Pharmacological treatment of GER has some potential side effects. Conservative treatment of GER should be the first-line approach and should include body positioning and diet modifications. Formula-fed preterm infants experience frequently symptoms of feeding intolerance. Hydrolyzed protein formula (HPF) is often used in these infants due to their effects on gastrointestinal motility. AIMS To investigate the role of an extensively HPF (eHPF) on GER indexes in formula-fed preterm infants with symptoms of both GER and feeding intolerance. STUDY DESIGN Randomized crossover trial. SUBJECTS Preterm infants (gestational age ≤33 weeks) with symptoms of feeding intolerance (large gastric residuals, abdominal distension and constipation) and GER (frequent regurgitations and/or postprandial desaturations). OUTCOME MEASURES GER indexes detected by 24-h combined multichannel intraluminal impedance and pH monitoring. GER indexes detected after 4 feeds of an eHPF were compared to those detected after 4 feeds of a standard preterm formula (SPF) by Wilcoxon signed ranks test. A p<0.05 was considered statistically significant. RESULTS eHPF significantly reduced the number of GERs detected by pH monitoring (p=0.036) and also the reflux index (p=0.044) compared to SPF. No differences in impedance bolus exposure indexes nor in GER height were detected. CONCLUSIONS The use of an eHPF should be evaluated for reducing esophageal acid exposure in preterm infants with feeding intolerance and symptoms of GER. Future research should focus on the evaluation of an eHPF adequate for preterm infants in improving clinical symptoms of GER.

Urinary neutrophil gelatinase-associated lipocalin at birth predicts early renal function in very low birth weight infants.

Objectives: Preterm human milk (HM) may provide insufficient energy and nutrients and thus may need to be fortified. Our aim was to determine whether fat content, protein content, and osmolality of HM before and after fortification may affect gastroesophageal reflux (GER) in symptomatic preterm infants. Methods: Gastroesophageal reflux was evaluated in 17 symptomatic preterm newborns fed naïve and fortified HM by combined pH/intraluminal-impedance monitoring (pH-MII). Human milk fat and protein content was analysed by a near-infrared reflectance analysis. Human milk osmolality was tested before and after fortification. Gastroesophageal reflux indexes measured before and after fortification were compared and were also related to HM fat and protein content and osmolality before and after fortification. Results: An inverse correlation was found between naïve HM protein content and acid reflux index (RIpH: P = 0.041, ρ =−0.501). After fortification, osmolality often exceeded the values recommended for infant feeds; furthermore, a statistically significant (P < 0.05) increase in nonacid reflux indexes was observed. Conclusions: Protein content of naïve HM may influence acid GER in preterm infants. A standard fortification of HM may worsen nonacid GER indexes and, due to the extreme variability in HM composition, may overcome both recommended protein intake and HM osmolality. Thus, an individualised fortification, based on the analysis of the composition of naïve HM, could optimise both nutrient intake and feeding tolerance.

Drug-Induced Renal Damage in Preterm Neonates: State of the Art and Methods for Early Detection

Preterm infants are exposed to conditions that can impair renal function. We evaluated the ability of serum and urinary neutrophil gelatinase-associated lipocalin (sNGAL and uNGAL) to predict renal function in the first weeks of life. From September 2008 to July 2009, infants weighing ≤1500 g at birth with no major congenital anomalies or sepsis were eligible. We measured sNGAL and uNGAL levels at birth. To evaluate renal function, we determined changes in serum creatinine (sCreat) and estimated GFR (eGFR) from birth to d 21. Forty neonates (mean GA, 27 ± 2 wk) completed the study. Renal function improved in 32 of 40 (80%) infants (normal renal function, NRF group) (sCreat, from 0.97 ± 0.2 to 0.53 ± 0.13 mg/dL; eGFR, from 15.3 ± 4.1 to 28.6 ± 7.9 mL/min), whereas renal function worsened in 8 of 40 (20%) infants (impaired renal function, IRF group) (sCreat, from 0.71 ± 0.27 to 0.98 ± 0.43 mg/dL; eGFR from 23 ± 14.7 to 16.4 ± 9.1 mL/min). The uNGAL/urinary creatinine (uCreat) ratio at birth was higher in the IRF group (31.05 ng/mg) than the NRF group (6.0 ng/mg), and uNGAL was significantly higher in IRF group, detecting IRF with a cutoff of 100 ng/mL. uNGAL levels at birth may have a predictive role in very LBW (VLBW) infants.

The Use of Humanized Monoclonal Antibodies for the Prevention of Respiratory Syncytial Virus Infection

Only a small fraction of drugs widely used in neonatal intensive care units (NICU) are specifically authorized for this population. Even if unlicensed or off-label use is necessary, it is associated with increased adverse drug reactions, which must be carefully weighed against expected benefits. In particular, renal damage is frequent among preterm babies, and is considered a predisposing factor for the development of chronic kidney disease in adulthood. Apart from specific conditions affecting premature neonates (e.g. respiratory distress syndrome, perinatal asphyxia), drugs play an important role in impairing renal function because of well-known nephrotoxicity and/or interaction with renal developmental factors. From a review of the available studies on drug use in NICU patients, we identified and described the most commonly administered drugs that are correlated to renal damage. Early detection of kidney injury is becoming an essential aspects for clinicians because of the limited number of biomarkers applicable in the neonatal population. Postnatal changes of biochemical processes that influence pharmacokinetic and pharmacodynamic aspects need to be further investigated in order to better understand the mechanisms of drug toxicity in this population. The most promising strategies for dose adjustment and therapeutic schemes are discussed. The purpose of this review was to describe current knowledge on drug use among premature babies and their implication in kidney injury development, as well as to highlight available strategies for early detection of renal damage.

Intravenous immunoglobulin to treat neonatal alloimmune haemolytic disease

Monoclonal antibodies are widely used both in infants and in adults for several indications. Humanized monoclonal antibodies (palivizumab) have been used for many years for the prevention of respiratory syncytial virus infection in pediatric populations (preterm infants, infants with chronic lung disease or congenital heart disease) at high risk of severe and potentially lethal course of the infection. This drug was reported to be safe, well tolerated and effective to decrease the hospitalization rate and mortality in these groups of infants by several clinical trials. In the present paper we report the development and the current use of monoclonal antibodies for prophylaxis against respiratory syncytial virus.

Generalized Arterial Calcification of Infancy: Fatal Clinical Course Associated with a Novel Mutation in ENPP1

Objective: To compare the efficacy of intravenous immunoglobulin (IVIg) and exchange transfusion (EXT) on rhesus haemolytic disease of the newborn (Rh-HDN) and evaluate treatment-related side effects. Methods: Retrospective chart review of two cohorts of newborns with Rh-HDN, treated with (Group 2) or without (Group 1) IVIg. Length of phototherapy, number of EXT, IVIg infusions, intrauterine and top-up red blood cells transfusions, need and permanence of umbilical venous catheter, and length of hospital stay, as well as treatment-related adverse events, were evaluated. Results: Charts of 88 newborns were reviewed (34 in Group 1, 54 in Group 2). Infants in Group 2 received a significantly lower number of EXT, had a lower risk of neurological impairment and needed an umbilical venous catheter for shorter, but required longer phototherapy, longer length of hospital stay, and more top-up transfusions. EXT was associated with a high number of adverse events. Two newborns treated with IVIg developed necrotizing enterocolitis (NEC). Conclusions: IVIg appear as an effective alternative to EXT, reducing the risk of neurological impairment and complications related to EXT. However, side effects of IVIg treatment (higher need of top-up transfusions and longer hospital stay) should be taken into account and the risk of NEC should be carefully monitored during treatment.

Drug-induced renal injury in neonates: Challenges in clinical practice and perspectives in drug development.

Generalized arterial calcification of infancy (GACI) is a rare condition characterized by arterial calcification within the internal elastic lamina associated with intimal proliferation, leading to stenosis of great and medium-sized vessels. This disease, caused by mutations in multiple exons of ENPP1, frequently results in death in infancy. Nowadays, the most promising therapeutic compounds for this rare disease are bisphosphonates. We describe a case of GACI associated with the novel mutation c.653A>T (p.D218V) in ENPP1 on both alleles. The male infant was delivered prematurely and developed heart failure, severe hypertension, and diffuse calcifications of all arterial districts. He was treated with etidronate (18 mg/kg/day); however, the clinical condition did not improve, and a resolution of calcifications was not observed. The infant died within the 6th month of life of ischemic heart failure. We conclude that even if the diagnosis of GACI is established early and bisphosphonate treatment is started early, the prognosis can be very poor.