Andrea Ronchi

Influenza A/H1N1 MF59-Adjuvanted Vaccine in Preterm and Term Children Aged 6 to 23 Months

OBJECTIVE: This study was designed to evaluate the immunogenicity, safety, and tolerability of a monovalent 2009 pandemic influenza A/H1N1 MF59-adjuvanted vaccine in children aged 6 to 23 months who had different gestational ages (GAs) at birth. METHODS: The study involved 105 children: 35 preterm subjects with a GA of <32 weeks; 35 preterm subjects with a GA of 32 to 36 weeks; and 35 term subjects with a GA of 37 to 42 weeks. Each child received 2 intramuscular vaccine doses (Focetria [Novartis, Siena, Italy]): dose 1 at enrollment and dose 2 after 4 weeks (28 ± 2 days). Serum samples for antibody measurements were collected immediately before administration of dose 1, before administration of dose 2 (28 ± 2 days after baseline), and 4 weeks later (56 ± 2 days after baseline). Local and systemic reactions were assessed during the 14 days after each vaccination. RESULTS: Of the 101 children who completed the study 32 out of 34 preterm subjects with a GA of <32 weeks, all of the preterm subjects with a GA of 32 to 36 weeks, and all of the term subjects seroconverted and were seroprotected after the first vaccine dose. Local and systemic tolerability was good in all of the groups, but fever was significantly more common after the first dose than after the second dose (P < .05), and there were no between-group differences. CONCLUSIONS: A single dose of 2009 pandemic influenza A/H1N1 MF59-adjuvanted vaccine evoked a significant immune response against pandemic influenza A/H1N1 virus in children aged 6 to 23 months even if their GA was <32 weeks. The vaccine had a good safety and tolerability profile.

Chorioamnionitis and neonatal outcome in preterm infants: a clinical overview.

Abstract The term chorioamnionitis is used to refer to an intrauterine infection/inflammation occurring between the maternal tissues and the fetal membranes (choriodecidual space) or in the fetal annexes (chorioamniotic membranes, amniotic fluid, umbilical cord). Histological examination of the placenta is the gold standard for diagnosis. However, clinical, biochemical and microbiological criteria are also used to define the disease. The literature contains a large body of evidence showing that chorioamnionitis is the leading cause of very preterm birth and, therefore, contributes significantly to neonatal morbidity and mortality. In recent decades, numerous studies have attempted to establish whether, and to what extent, intrauterine infection/inflammation might negatively affect the short- and long-term outcome of preterm infants. The question is still unanswered. The discrepancy observed across studies can be attributed largely to the use of different inclusion and exclusion criteria, diagnostic criteria and methods, and to whether or not potential confounding factors, such as gestational age were considered. Anyhow, the association between chorioamnionitis and severe prematurity requires serious efforts by researchers to clarify the mechanisms linking intrauterine infection/inflammation with preterm birth, and thus to identify strategies that may guide clinicians’ diagnostic and therapeutic choices, with regard to both mothers and infants.

Neonatal adenoviral infection: a seventeen year experience and review of the literature.

OBJECTIVES To describe the clinical manifestations and short-term outcomes of adenoviral infections in neonates and review all published cases to better determine impact and treatment outcomes. STUDY DESIGN Retrospective cohort study of all neonates hospitalized at Childrens Medical Center (CMC) and Parkland Memorial Hospital (PMH), Dallas, TX with laboratory-confirmed adenoviral infection from January 1,1995-December 31, 2012. Neonates were identified by review of the CMC Virology Laboratorys prospective database of all positive adenovirus tests performed in the inpatient and ambulatory settings, and at PMH, of a prospective neonatal database that included all neonatal intensive care unit admissions. Patients also were identified by discharge International Classification of Disease, 9th edition codes for adenoviral infection. The medical records were reviewed, and a review of the English literature was performed. RESULTS During 17 years, 26 neonates had adenoviral infection (25, CMC; 1, PMH). The principle reasons for hospitalization were respiratory signs (88%) and temperature instability (65%). Five (19%) had disseminated disease and 4 (80%) of these infants died. Ribavirin or cidofovir treatment, as well as immune globulin intravenous, did not improve outcomes except in 1 neonate. Literature review (n = 72) combined with our data found that disseminated infection was associated with death (68% vs 21% with localized infection, P < .001). In addition, neonates <14 days of age were more likely to have disseminated disease (44% vs 12%, P = .004) and death (48% vs 8%; P < .001). CONCLUSION Adenoviral infection in hospitalized neonates was associated with severe morbidity and mortality, especially when infection was disseminated and involved the respiratory tract. Development of new therapeutic strategies is needed.

Does pulmonary function change during whole-body deep hypothermia?

Whole-body deep hypothermia (DH) could be a new therapeutic strategy for asphyxiated newborn. Aim of this study was to describe how DH (core temperature 30–33°C) modifies the respiratory function if compared with mild hypothermia (MH; core temperature 33–34°C). This is an observational study. Results were obtained from a pilot study of safety of DH and topiramate in neonatal hypoxic-ischaemic encephalopathy. Fifty-seven newborns were enrolled: 29 patients in DH and 28 in MH. Recruitment criteria were moderate-severe hypoxic-ischaemic encephalopathy and gestational age ≥36 weeks. Mechanical ventilation was set to maintain SaO2 between 92% and 95%. Nineteen patients in DH and 18 in MH required mechanical ventilation. Of these patients, 10 and 12, respectively, did not required oxygen. No significant differences were observed in hours of oxygen and ventilation support, respiratory rate and PaCO2. Maximum FiO2, peak inspiratory pressure, positive end-expiratory pressure, minute ventilation and tidal volume during hypothermia were similar. Pulmonary function with different levels of hypothermia was similar.

Exchange Transfusion in the Treatment of Neonatal Septic Shock: A Ten-Year Experience in a Neonatal Intensive Care Unit

Septic shock, occurring in about 1% of neonates hospitalized in neonatal intensive care unit (NICU), is a major cause of death in the neonatal period. In the 1980s and 90s, exchange transfusion (ET) was reported by some authors to be effective in the treatment of neonatal sepsis and septic shock. The main aim of this retrospective study was to compare the mortality rate of neonates with septic shock treated only with standard care therapy (ScT group) with the mortality rate of those treated with ScT and ET (ET group). All neonates with septic shock admitted to our NICU from 2005 to 2015 were included in the study. Overall, 101/9030 (1.1%) neonates had septic shock. Fifty neonates out of 101 (49.5%) received one or more ETs. The mortality rate was 36% in the ET group and 51% in the ScT group (p = 0.16). At multivariate logistic regression analysis, controlling for potentially confounding factors significantly associated with death (gestational age, serum lactate, inotropic drugs, oligoanuria), ET showed a marked protective effect (Odds Ratio 0.21, 95% Confidence Interval: 0.06–0.71; p = 0.01). The lack of observed adverse events should encourage the use of this procedure in the treatment of neonates with septic shock.

Iatrogenic Anetoderma of Prematurity: A Case Report and Review of the Literature

Anetoderma is a skin disorder characterized by focal loss of elastic tissue in the mid dermis, resulting in localized areas of macular depressions or pouchlike herniations of skin. An iatrogenic form of anetoderma has been rarely described in extremely premature infants and has been related to the placement of monitoring devices on the patient skin. Because of the increasing survival of extremely premature infants, it is easy to foresee that the prevalence of anetoderma of prematurity will increase in the next future. Although it is a benign lesion, it persists over time and can lead to significant aesthetic damage with need for surgical correction. Sometimes the diagnosis can be difficult, especially when the atrophic lesions become evident after discharge. Here, we report on a premature infant born at 24 weeks of gestation, who developed multiple anetodermic patches of skin on the trunk at the sites where electrocardiographic electrodes were previously applied. The knowledge of the disease can encourage a more careful management of the skin of extremely premature babies and aid the physicians to diagnose the disease when anetoderma patches are first encountered later in childhood.

Spreading the Benefits of Infection Prevention in the Neonatal Intensive Care Unit

Although infections due to Staphylococcus aureus are infrequent in the neonatal intensive care unit (NICU), they are associated with substantial morbidity and mortality. In this issue of JAMA Pediatrics, Ericson et al1 describe a 15-year (1997-2012) retrospective study with invasive S aureus infections, defined as a positive culture of blood, cerebrospinal fluid, normally sterile body fluid, or abscess for S aureus, in 348 NICUs managed by the Pediatrix Medical Group. Among 887 910 infants admitted to these NICUs, 3888 (0.4%) had at least 1 invasive S aureus infection, which occurred in 2.2% of very low-birth-weight (VLBW) infants (birth weight <1500 g) and in 0.1% of those with a birth weight of 1500 g or higher, for an estimated annual burden of more than 5000 invasive S aureus infections in NICUs in the United States alone. Most important, invasive staphylococcal infections due to methicillin-susceptible S aureus (MSSA) (occurring in 72.7% of infants [2825 of 3888]) were more frequent than those due to methicillin-resistant S aureus (MRSA) (occurring in 27.3% of infants [1063 of 3888]). Only a limited number of risk factors for infection (eg, low birth weight, gestational age, and ventilator or inotropic support) were evaluated, which were similar between the 2 groups, as was mortality overall (9.6% [237 of 2474] for MSSA vs 11.9% [110 of 926] for MRSA, P = .049) and by birth weight categories. However, a significant omission is the lack of information on the presence and duration of intravascular catheters given their known association with bloodstream infections.2 These findings are similar to those reportedpreviously by the Eunice Kennedy ShriverNational Institute of Child Health andHumanDevelopmentNeonatalResearchNetwork,3where among 8444VLBW infants born from2006 to 2008who survivedmore than 72 hours, 316 (3.7%) had bacteremia ormeningitis due toSaureus. Of these 316 infected infants, 88 (27.8% [1.0% of all infants]) had MRSA infections while 228 (72.2% [2.7%of all infants]) hadMSSA infections.Necrotizing enterocolitis, need for mechanical ventilation, and other morbidities did not differ in infants infectedwithMRSAvsMSSA, and mortality was high for both (26.1% for MRSA and 24.1% for MSSA). It is possible that virulence factors on mobile genetic elements that are shared between MRSA and MSSA have led to similar adverse outcomes. These and other reports suggest that measures to prevent MRSA infections should be broadened to include MSSA4,5 and that hospital infection control policies and practices that traditionally have focused only on MRSA should include MSSA as well.6 Prevention of all staphylococcal infections is an important goal. However, any bloodstream infection with any pathogen in preterm infants is associated with higher mortality and worse neurodevelopmental outcomes.7 Moreover, all health care–associated infections in infants of any birth weight or gestational age should be considered a preventable harm. Therefore, in the absence of an organism-specific outbreak, the paradigm for prevention of health care–associated infections has shifted from a pathogen-specific or vertical approach to a broader horizontal approach that will mitigate transmission and infection with many pathogens.8 Traditional vertical approaches reduce risk of colonization, infection, and transmission of specific pathogens, such as MRSA, by focusing on active surveillance testing to identify carriers, followed by implementation of measures aimed at preventing transmisRelated article page 1105 Editorial Opinion

998Detection of Cytomegalovirus (CMV) in Cerebrospinal Fluid of Infants with Congenital CMV Infection: Is It Worth Doing the Lumbar Puncture?

Infants with Congenital CMV Infection: Is It Worth Doing the Lumbar Puncture? Christopher Ouellette, MD; Andrea Ronchi, MD; Asuncion Mejias, MD, PhD; Susana Chavez-Bueno, MD; Douglas Salamon, MB(ASCP)SV; Lorenza Pugni; Fabio Mosca; Pablo J. Sanchez MD, FIDSA; Pediatrics, Division of Infectious Diseases, Nationwide Children’s Hospital, Columbus, OH; Pediatrics, University of Texas Southwestern, Dallas, TX; Center for Vaccines and Immunity, The Research Institute at Nationwide Children’s Hospital, Columbus, OH; University of Oklahoma Health Sciences Center, Oklahoma City, OK; Department of Laboratory Medicine, Nationwide Children’s Hospital, Columbus, OH; Neonatal Intensive Care Unit, Department of Clinical Sciences and Community Health, Universita degli Studi di Milano, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

Detection of cytomegalovirus in saliva from infants undergoing sepsis evaluation in the neonatal intensive care unit: the VIRIoN-C study

Abstract Objective To determine the frequency of detection of cytomegalovirus (CMV) among infants evaluated for late-onset sepsis in the neonatal intensive care unit (NICU). Methods This study was a prospective cohort study. Results During the 13-month study, 84 infants underwent 116 sepsis evaluations, and CMV DNA was detected in saliva in three (4%) infants (median: gestational age 28 weeks, birth weight 950 g), representing 5% (n=6) of all sepsis evaluations. One infant had CMV DNA detected in saliva in all four sepsis evaluations. Two infants had acquired CMV infection, while the timing of CMV acquisition could not be determined in one infant. Two of the three infants had concomitant Gram-negative bacteremia and urinary tract infections (UTIs), two developed severe bronchopulmonary dysplasia (BPD) and none died. Conclusion Detection of CMV DNA in saliva occurred in 4% of infants and 5% of sepsis evaluations. Persistence of CMV DNA shedding in saliva made attribution of clinical illness difficult to ascertain.