Incidence and risk factors of bacterial sepsis and invasive fungal infection in neonates and infants requiring major surgery: an Italian multicentre prospective study.

BACKGROUND: Limited data are currently available on the incidence rates and risk factors for bacterial sepsis and invasive fungal infections (IFIs) among neonates and infants undergoing major surgery. AIM: To assess the incidence of bacterial sepsis and IFI, fungal colonization, risk factors for sepsis, and mortality in neonates and infants aged <3 months undergoing major surgery. METHODS: A multicentre prospective study was conducted involving 13 level-3 neonatal intensive care units in Italy, enrolling all infants aged ≤3 months undergoing major surgery. FINDINGS: From 2018 to 2021, 541 patients were enrolled. During hospitalization, 248 patients had a bacterial infection, and 23 patients had a fungal infection. Eighty-four patients were colonized by fungal strains. Overall, in-hospital mortality was 2.8%, but this was higher in infected than in uninfected infants (P = 0.034). In multivariate analysis, antibiotic exposure before surgery, ultrasound-guided or surgical placement of vascular catheters, vascular catheterization duration, and gestational age ≤28 weeks were all associated with bacterial sepsis. The risk of IFI was markedly higher in colonized infants (odds ratio (OR): 8.20; P < 0.001) and was linearly associated with the duration of vascular catheterization. Fungal colonization in infants with abdominal surgery increased the probability of IFI 11-fold (OR: 11.1; P < 0.001). CONCLUSION: Preventive strategies such as early removal of vascular catheters and the fluconazole prophylaxis should be considered to prevent bacterial and fungal sepsis in infants undergoing abdominal surgery, and even more so in those with fungal colonization.

Management of the mother-infant dyad with suspected or confirmed SARS-CoV-2 infection in a highly epidemic context.

In the context of SARS-CoV-2 pandemic, the hospital management of mother-infant pairs poses to obstetricians and neonatologists previously unmet challenges. In Lombardy, Northern Italy, 59 maternity wards networked to organise the medical assistance of mothers and neonates with suspected or confirmed SARS-CoV-2 infection. Six "COVID-19 maternity centres" were identified, the architecture and activity of obstetric and neonatal wards of each centre was reorganised, and common assistance protocols for the management of suspected and proven cases were formulated. Here, we present the key features of this reorganization effort, and our current management of the mother-infant dyad before and after birth, including our approach to rooming-in practice, breastfeeding and neonatal follow-up, based on the currently available scientific evidence. Considered the rapid diffusion of COVID-19 all over the world, we believe that preparedness is fundamental to assist mother-infant dyads, minimising the risk of propagation of the infection through maternity and neonatal wards.

Hexavalent vaccines in preterm infants: an update by Italian Society of Pediatric Allergy and Immunology jointly with the Italian Society of Neonatology.

Hexavalent vaccines, protecting against six diseases (diphtheria, tetanus, pertussis [DTaP], poliovirus, hepatitis B virus [HBV], and Haemophilus influenzae type b [Hib], are routinely the standard of care in Europe. The use of combined vaccines allows the reduction of number of injections and side effects, the reduction of costs, and the increase in adherence of the family to the vaccination schedule both in terms of the number of doses and timing. The safety profile, efficacy and effectiveness of hexavalent vaccines have been extensively documented in infants and children born at term, and data are accumulating in preterm infants. Hexavalent vaccines are particularly important for preterm infants, who are at increased risk for severe forms of vaccine preventable diseases. However, immunization delay has been commonly reported in this age group. All the three hexavalent vaccines currently marketed in Italy can be used in preterm infants, and recent data confirm that hexavalent vaccines have a similar or lower incidence of adverse events in preterm compared to full-term infants; this is likely due to a weaker immune system response and reduced ability to induce an inflammatory response in preterm infants. Apnoea episodes are the adverse events that can occur in the most severe preterm infants and / or with history of respiratory distress. The risk of apnoea after vaccination seems to be related to a lower gestational age and a lower birth weight, supporting the hypothesis that it represents an unspecific response of the preterm infant to different procedures. High seroprotection rates have been reported in preterm infants vaccinated with hexavalent vaccine. However, a lower gestational age seems to be associated with lower antibody titres against some vaccine antigens (e.g. HBV, Hib, poliovirus serotype 1, and pertussis), regardless of the type of hexavalent vaccine used. Waiting for large effectiveness studies, hexavalent vaccines should be administered in preterm infants according to the same schedule recommended for infants born at term, considering their chronological age and providing an adequate monitoring for cardio-respiratory events in the 48-72 h after vaccination, especially for infants at risk of recurrence of apnoea.

Herpesviruses and breast milk. / Herpesvirus e latte materno

Breast milk has always been the best source of nourishment for newborns. However, breast milk can carry a risk of infection, as it can be contaminated with bacterial or viral pathogens. This paper reviews the risk of acquisition of varicella-zoster virus (VZV) and cytomegalovirus (CMV), herpesviruses frequently detected in breastfeeding mothers, via breast milk, focusing on the clinical consequences of this transmission and the possible strategies for preventing it. Maternal VZV infections are conditions during which breastfeeding may be temporarily contraindicated, but expressed breast milk should always be given to the infant. CMV infection acquired through breast milk rarely causes disease in healthy term newborns; an increased risk of CMV disease has been documented in preterm infants. However, the American Academy of Pediatrics (AAP) does not regard maternal CMV seropositivity as a contraindication to breastfeeding; according to the AAP, in newborns weighing less than 1500 g, the decision should be taken after weighing the benefits of breast milk against the risk of transmission of infection. The real efficacy of the different methods of inactivating CMV in breast milk should be compared in controlled clinical trials, rigorously examining the negative consequences that each of these methods can have on the immunological and nutritional properties of the milk itself, with a view to establish the best risk-benefit ratio of these strategies before they are recommended for use in clinical practice.

[Management of outbreaks of nosocomial pathogens in neonatal intensive care unit]. / Gestione degli eventi epidemici in Terapia Intensiva Neonatale.

Outbreaks of nosocomial pathogens are one of the most relevant problems in Neonatal Intensive Care Unit (NICU). Many factors contribute to the onset of an epidemic, including virulence of the pathogen and vulnerability of the infants hospitalized in NICU. Outbreaks are often caused by multidrug-resistant organisms (MDROs). MDROs are defined as microorganisms, predominantly bacteria, that are resistant to one or more classes of antimicrobial agents. MDROs, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE) and certain gram-negative bacilli (GNB), have important infection control implications. Once MDROs are introduced into a healthcare setting, transmission and persistence of the resistant strain is determined by the availability of vulnerable patients, selective pressure exerted by antimicrobial use, increased potential for transmission from larger numbers of infected or colonized patients ("colonization pressure"), and the impact of adherence to prevention efforts. Often, routine infection control measures are not enough to contain outbreaks, and additional control measures are needed, including implementation of hand hygiene, cohorting of infected/colonized infants, neonatal surveillance cultures, screening of healthcare workers and decolonization of neonates and/or healthcare workers in selected cases. In this review, we report the practices we developed in our NICU to contain an epidemic. These recommendations reflect the experience of the group, as well as the findings of the current literature.

Clinical characteristics and response to prophylactic fluconazole of preterm VLBW neonates with baseline and acquired fungal colonisation in NICU: data from a multicentre RCT.

BACKGROUND: Fungal colonisation by Candida spp. affects a high proportion of VLBW neonates in NICU. However, few data are available on the clinical characteristics of colonisation in preterm infants who are colonised at baseline via vertical transmission, compared to preterms who become colonised during their stay in NICU via horizontal transmission. MATERIAL AND METHODS: We reviewed the database of a multicentre, randomised trial of prophylactic fluconazole in VLBW neonates conducted in 8 Italian NICUs in the years 2004 and 2005 (Manzoni et al., NEJM 2007;356(24):2483-95). Per the protocol, all enrolled infants underwent weekly surveillance cultures from birth till discharge. We investigated the frequency of the two different modalities of Candida colonisation in this population, as well as the clinical and outcome characteristics possibly related to them. RESULTS: Overall, Candida colonisation affected 54 of 336 infants (16.1%). Baseline (i.e., detected <3(rd) day of life) colonisation affected 16 (4.7%), and acquired 38 (11.4%), of the 54 colonised preterms. Infants with baseline colonisation had significantly higher birth weight (1229 ± 28 g vs. 1047 g ± 29, p = 0.01) and gestational age (30.2 wks ± 2.7 vs. 28.5 wks ± 2.6, p = 0.01), and were significantly more likely to limit progression from colonisation to invasive Candida infection when fluconazole prophylaxis was instituted (21.6% vs. 42.7%, p = 0.009). Isolation of C. parapsilosis was significantly more frequent in infants with acquired colonisation. CONCLUSIONS: Infants with baseline and acquired colonisation differ for demographics characteristics and for their response to fluconazole prophylaxis. This information may be useful for targeting more accurate management strategies for these two different groups of colonised preterms in NICU.

[Does chorioamnionitis worsen the outcome of preterm infants? A controversial issue]. / La corioamnionite peggiora l'outcome del neonato prematuro? Una questione controversa.

The term chorioamnionitis is used to describe an intrauterine status of infection/inflammation of either mixed fetal-maternal (choriodecidual space) or fetal origin (chorioamniotic membranes, amniotic fluid, umbilical cord). Histological, microbiological, biochemical and clinical criteria are used to define chorioamnionitis. Histopathological examination of the placenta is the gold standard for evaluating antenatal inflammatory processes that might influence fetal development. Chorioamnionitis is the leading cause of very preterm delivery and its incidence increases with decreasing gestational age. Therefore, it contributes to the high morbidity and mortality of infants born prematurely. In the last decades, several studies have been performed to assess a gestation-independent effect of chorioamnionitis on neonatal and long-term outcome with variable results. The discrepancy observed across studies may be attributable to differences in inclusion and exclusion criteria, disease definitions, methods, and whether potential confounding factors such as gestational age were considered. As underlined by several Authors, the increasingly widespread use of antenatal steroids may have contributed to improve neonatal outcome and can therefore partially explain the different results between studies. In the current review we aim to give an overview and synthesis of a vast amount of existing literature on the association between antenatal infection/inflammation and neonatal and long-term outcome.

Focus on pandemic 2009 H1N1 influenza (swine flu).

At the moment of the onset of the pandemic there were few data about the transmission of the 2009 H1N1 virus infection from the mother to the newborn. Nevertheless neonates born to an ill mother from 2 days before through 7 days after illness onset in the mother were thought to be exposed and potentially infected. In October 2009 the Infectious Disease Group of the Italian Society of Neonatology provided a guide regarded the management of suspected or confirmed maternal infection with 2009 H1N1 influenza virus within labor and delivery, postpartum, and newborn care settings in hospitals. It was based on the available scientific information, according to the U.S. Centers for Disease Control and Prevention (CDC) and the Italian Ministry of Labour, Health and Social Policy recommendations in order to protect the infant from exposure to respiratory secretion during or immediately after delivery. Moreover, we published 300,000 copies of a more popular pamphlet for parents. Rigorous attention to Standard Precautions and Droplet Precautions is required to reduce the opportunities for the transmission of the infection in the health-care setting.

Lactoferrin and prevention of late-onset sepsis in the pre-term neonates.

Late-onset sepsis (LOS) affects a large proportion of pre-term neonates in neonatal intensive care units (NICUs) worldwide, with high morbidity and related mortality, and frequent occurrence of severe late neurodevelopmental impairment. Due to the frequency, severity and difficulties in early diagnosis and prompt therapy, prevention is crucial for decreasing the burden of infection-related complications in NICUs. It is well known that feeding with fresh maternal milk, hygiene measures and the cautious use of H2-blockers are related with a decreased risk of developing sepsis. However, evidence from randomised clinical trials exists only for fluconazole in the prevention of fungal infections in the NICU. Lactoferrin is the main whey protein in mammalian milk, and is involved in innate immune host defences. Notably, human lactoferrin can be found at increased concentrations in colostrum and in milk from mothers of premature neonates. Human (hLF) and bovine lactoferrin (bLF) share a high (77%) amino-acid homology, and the same N-terminal peptide responsible for antimicrobial activity, called lactoferricin. In vitro, bLF shows potent direct antimicrobial activity against all types of pathogens, which occurs via anti-cell wall actions and leads to disintegration of the micro-organism's membranes. bLF is also synergistic with many antimicrobials and antifungals, and promotes growth and differentiation of the immature gut. Based on this background data, a randomised clinical trial was recently conducted in very low birth weight pre-term neonates given bLF alone or with the probiotic Lactobacillus GG. The aim of the trial was to assess the ability of bLF to prevent late-onset sepsis of any origin in the studied infants during their stay in the NICU. This article discusses the preliminary data from this study, along with the proposed mechanisms of action of bLF in pre-term infants.

Cytomegalovirus infection: the state of the art.

Cytomegalovirus (CMV) is the leading cause of congenital infection in humans and constitutes a major public health problem. Congenitally infected infants, both symptomatic and asymptomatic at birth, may develop sequelae, particularly sensorineural hearing loss (SNHL) and brain damage. Transmission of the virus from mother to fetus can occur during either primary or recurrent maternal infection; however it is much higher in primary infected mothers than in mothers with preconceptional immunity. Routine CMV screening for primary infection during pregnancy constitutes a controversial issue, because of the lack of prenatal recommended therapy for congenital CMV infection. Ganciclovir may be used to treat neonates with symptoms at birth. Despite advances in antiviral therapy, congenitally infected infants, both symptomatic and asymptomatic at birth, need a follow up evaluation to detect sequelae. Congenital CMV infection cna be diagnosed at birth by using a test based on detection of viral DNA by PCR in dried blood spots (Guthrie card) collected on filter paper in the first days of life. Therefore, universal newborn screening for CMV by using DBS test should be recommended to detect sequelae as early as possible, so that infants can receive intervention promptly.

Hydrolysed proteins in preterm formula: influence on plasma aminoacids, blood fatty acids and insulinaemia.

The data from the present investigation differ from those of the previous study. The new version of hydrolysed protein formula did not induce changes in insulinaemia or in the insulinaemia/glycaemia ratio in pre- and postprandial samples when compared with the intact protein formula. The investigation also confirmed that branch chain aminoacids regulate insulin secretion and that the length of chain is insulinotropic for fatty acids, while the degree of unsaturation is not able to reduce insulin secretion in the newborn baby. This could be caused by stimulation of insulin output activated by the C20:5 n 3; the effects of fatty acids are probably related more to the variable composition of cell membrane than to the fatty acids circulating levels.

Oxatomide in the treatment of atopic dermatitis in breast-fed and very young infants.

BACKGROUND: This study was designed to assess the efficacy and safety of oxatomide oral suspension, in breast-fed and young babies with atopic dermatitis. METHODS: Thirty-one children (11 females, 20 males) aged between 4 and 35 months (mean+/- SD 15.4+/-7.6 months) were treated with oxatomide (2.5 mg/mL) at a dose of 1 mg/kg/day) split into two doses, every 12 hrs; treatment lasted 30 days. Efficacy was evaluated on the basis of the following signs and symptoms: itching (severity, extension and duration), blisters (number, extension), erythema (severity, extension), papules (number, extension), lesions from scratching (yes/no), dry skin (yes/no). RESULTS: Skin signs improved significantly with oxatomide. Itching was reduced 58.2% from baseline, and erythema 57.6% (both p<0.001). Vesicles, papules, lesions due to scratching and dry skin also improved significantly. Oxatomide had to be stopped only in one child in whom the dermatitis became worse. CONCLUSIONS: These results show the efficacy and safety of oxatomide in breast-fed or very young babies with atopic dermatitis. The oral suspension was particularly easy to use in children less than two years old, on account of the simple dosage schedule.

[Cerebral oxygenation and near-infrared rays spectrophotometry]. / Ossigenazione cerebrale e spettrofotometria a raggi vicino all'infrarosso.

Near infrared spectroscopy (NIRS) is a new technique which allows non invasive bedside monitoring of cerebral oxygenation and hemodynamics by measuring relative changes in cerebral oxy- and deoxyhaemoglobin and cytochrome aa3. We have applied this technique to evaluate the possible effects on cerebral oxygenation and hemodynamics of clinical procedures usually performed on preterm infants:--endotracheal suctioning, and we have demonstrated that the magnitude and the duration of the negative effects of open system are significantly reduced using closed endotracheal suctioning system;--withdrawal and infusion through umbilical vein and artery cause significant changes in cerebral hemodynamics: these effects are significantly reduced after administration of ibuprofen;--treatment of patent ductus arteriosus with ibuprofen does not significantly reduce cerebral perfusion and oxygen availability compared to indomethacin and ibuprofen administration also does not affect cerebral vasoreactivity to arterial carbon dioxide tension;--administration of different types and doses of natural surfactant causes different changes in cerebral hemodynamics and these effects seem to be dose-related. Therefore NIRS is an useful device to investigate cerebral oxygenation state of preterm infants and new possibilities could derive from the introduction of a new NIRS method which allows to measure the tissue oxygenation index.

Priming and inducing effects of interleukin-3 on histamine release from cord-blood basophils.

The effect of interleukin-3 (IL-3) on histamine release from cord and adult blood basophils were evaluated. Leukocyte suspensions, obtained from adult patients with respiratory allergy (n = 15), normal adult subjects (n = 15), and neonates with (n = 15) and without (n = 19) atopic disposition, were stimulated with anti-IgE, fMLP, and IL-3. IgE-mediated histamine release was significantly higher in adult patients, either allergic or normal, than in neonates with or without atopic disposition. A trend toward higher fMLP-induced histamine release was found in allergic adult subjects. IL-3 had a weak direct histamine-releasing activity in allergic adult subjects and in neonates, but not in normal adult donors. A significant enhancing effect of IL-3 on histamine release induced by anti-IgE was observed in neonates with and without atopic disposition and in normal adult subjects, but not in atopic adult patients. IL-3 exerted a priming effect also when basophils were stimulated with fMLP, without any significant difference between neonates and adult subjects. Passive sensitization with IgE-rich serum resulted in a significant increase in anti-IgE-induced, but not in IL-3-induced, histamine release from cord-blood basophils. In conclusion, IL-3 primes cord-blood as well as adult blood basophils for a consecutive anti-IgE- or fMLP-induced histamine release and its activity is not limited by the low density of membrane IgE in cord-blood basophils.

Varying clinical course of large placental chorioangiomas. Report of 3 cases.

Three cases of placental chorioangiomas, from 6.5 to 10 cm in diameter, were diagnosed prenatally by ultrasound and color Doppler imaging at 21-34 weeks of gestation. In 1 case, due to fetal hydrops and maternal 'mirror syndrome', immediate delivery of a neonate, who was severely anemic, thrombocytopenic and had consumption coagulopathy, was required. In the other 2 pregnancies, conservative management was possible, once fetal cardiac failure and anemia were ruled out by the combination of fetal blood sampling and serial echographic and Doppler investigations.

Airway reactivity in parents of infants and young children with recurrent wheeze: a case-control study.

Increased airway reactivity has been found in family members of school age children and adults with asthma. As the relation between recurrent wheeze in infancy and bronchial reactivity is not yet clear, it was decided to test bronchial reactivity to methacholine in both parents of 50 preschool age children with recurrent wheeze and in 200 population based controls matched for sex, age, smoking habits, and atopy. Wheezy children fulfilled the following criteria: first attack of wheezing before the age of 2 years, at least four wheezing episodes triggered by a respiratory infection, negative skin prick tests, and no symptoms related to allergy. Four parents and five controls did not undergo the methacholine challenge because their forced expiratory volume in one second was < 80% of the predicted value. Methacholine reactivity was not significantly different in parents and controls. In summary, an increased bronchial responsiveness was not found in parents of infants and young children with recurrent wheeze triggered by infection.

[Height-weight standards in Lomellina children 0 to 7 years of age: percentile graphs]. / Gli standard staturo-ponderali dei bambini della Lomellina da 0 a 7 anni: i grafici dei percentili.

Recumbent length (or standing height) and weight standards of 1253 infants and children living in Lomellina were studied by a cross-sectional approach. Metric data from birth to 7 years of age were smoothed by a least squares quadratic or cubic spline technique. Growth percentile curves for males and females are subdivided into two sections, the first for the 0-3 and the second for the 3-7 age groups.