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.

Effect of maternal psychopathology on neurodevelopmental outcome and quality of the dyadic relationship in preterm infants: an explorative study.

Background: The literature shows that parents of preterm infants are at risk of psychological distress and that this may impact on the quality of the parent-child relationship and on the child's development.Aim: This longitudinal study was conducted to examine in preterm infants relationships between maternal psychological variables, parental protective factors, perinatal infant variables, and neurodevelopmental outcome. Furthermore, we explored the impact of these variables on the quality of the mother-infant relationship (dyadic synchrony).Subjects and methods: A total of 29 preterm infants (GA < 34 weeks) and their mothers were evaluated twice: at t0, during the infant's hospitalization in the neonatal intensive care unit (NICU), and at 12 months of infant corrected age (t2).Results: With the exception of decreases in anxiety and perceived social support and an increase in the rate of severe depression at follow-up, there were no significant changes between t0 and t1 assessments. The infant's perinatal risk status was the variable that impacted most on maternal psychopathology. Furthermore, our data revealed that baseline maternal stress related to the appearance of the child and to the mother's perception of her parenting role represent a risk factor in relation to developmental outcome at 12 months of corrected age. Finally, no correlations emerged between dyadic synchrony and infant perinatal data, maternal psychological variables (at t0 and at t1), or child developmental outcome at t1.Conclusions: Our results underline the need to identify negative maternal affective states early in the mother-child relationship and to provide mothers with adequate support in the NICU, to enhance their parental role.

Depressive symptoms and maternal psychological distress during early infancy: A pilot study in preterm as compared with term mother-infant dyads.

BACKGROUND: Preterm birth does not only affect infants but also represents an unexpected and traumatic event for parents. There are few reports on parenting stress during early infancy comparing preterm and term mothers, with the results being somewhat inconsistent. METHODS: As part of a longitudinal study, preterm mother-infant and term mother-infant dyads were enrolled. Dyads were assessed twice: during hospitalisation in the neonatal intensive care unit (NICU) and at 3 months of infant age (corrected age for preterm). Each mother completed a self-report set of psychological questionnaire in both time points. All the children underwent a neurological examination at 40 weeks post conceptional age and at 3 months (corrected age for preterm). RESULTS: 20 preterm and 20 term dyads were included. NICU mothers reported elevated postnatal depressive symptoms and high stress level, even if the preterm infants were with low perinatal risk and normal neurological examination. Comparing preterm infant with low perinatal risk and normal neurological examination with term-born children at 3 months, we found higher parental stress in term mothers than in preterm mothers. LIMITATIONS: This study was limited by a relatively small sample size; findings are preliminary and warrant further investigation in larger-scale study. CONCLUSIONS: Findings confirm that becoming a mother of a preterm infant is an event associated with emotional distress. These symptoms may resolve with time, and sometimes are independent of the infant's clinical severity. Assessing parental sources of stress and subsequent follow-up is essential to promote parental support, both for preterm and term mothers.

Placental lesions associated with oligohydramnios in fetal growth restricted (FGR) pregnancies.

INTRODUCTION: Aim of the study was to investigate the association between placental pathology and oligohydramnios in pregnancies complicated by fetal growth restriction (FGR). METHODS: Placentas from 221 consecutive FGR pregnancies and 63 healthy controls were studied. Pathological lesions were described according to consensus nomenclature and standardized criteria; both elementary lesions and constellations of lesions (patterns) were considered. Statistics included analysis of linear trends and multinomial logistic regression. RESULTS: Amniotic fluid index (AFI) was normal in 56 (25.3%) FGR pregnancies, whereas mild, moderate and severe oligohydramnios were diagnosed in 32 (14.5%), 44 (19.9%) and 89 (40.3%) subjects, respectively. In FGR pregnancies, after adjustment for potential confounders, membrane meconium staining (chi-square = 28.6, p < 0.001), chronic villous hypoxia pattern (chi-square = 18.8, p < 0.001) and fetal thrombotic vasculopathy pattern (chi-square = 9.2, p = 0.002) were positively and linearly correlated to AFI decrease. Odds ratios of meconium and chronic villous hypoxia were 9.2 (95% CI = 2.6-32.9) and 4.2 (95% CI = 1.3-13.6) in FGR pregnancies with normal AFI and 25.2 (95% CI = 6.9-91.8) and 9.7 (95% CI = 3-31.5) in those with severe oligohydramnios (p = 0.005 and p = 0.023 compared to normal AFI, respectively). DISCUSSION: In FGR pregnancies, reduction of amniotic fluid volume is directly correlated to histological features of placental under-perfusion, meconium staining of membranes and fetal vascular damage. These findings support the clinical notion that in FGR pregnancies oligohydramnios is a risk factor of fetal hypoxia and possibly of increased adverse neonatal outcomes.

Different subsets of circulating angiogenic cells do not predict bronchopulmonary dysplasia or other diseases of prematurity in preterm infants.

Bronchopulmonary dysplasia (BPD) is a chronic lung disease occurring in very and extremely preterm infants undergoing mechanical ventilation. Given the altered lung vascular growth characterizing BPD, circulating angiogenic cells could be useful biomarkers to predict the risk. The objective of the study was to determine whether the percentages of circulating angiogenic cells (CD34+VEGFR-2+, CD34+CD133+VEGFR-2+, and CD45-CD34+CD133+VEGFR-2+ cells), assessed in the peripheral blood at birth by flow cytometry, could be used as markers for the risk of BPD. In one-hundred and forty-two preterm neonates (gestational age less than 32 weeks and/or birth weight less than 1500 g) admitted to our tertiary care Neonatal Intensive Care Unit between 2006 and 2009, we evaluated the percentages of circulating angiogenic cells at birth, at 7 days, and, in a subset of infants (n=40), at 28 days of life. The main outcome was the correlation between cell counts at birth and the subsequent risk of developing BPD. In our study, all the three cell populations failed to predict the development of BPD or other diseases of prematurity. We suggest that these cells cannot be used as biomarkers in preterm infants, and that research is needed to find other early predictors of BPD.

Variation of B-type natriuretic peptide concentrations and intrauterine growth restriction: mother, fetus and newborn.

To evaluate maternal, fetal, neonatal B-type natriuretic peptide (BNP) concentrations related to Intra Uterine Growth Restriction (IUGR). BNP concentrations in 43 IUGR and 35 healthy, Appropriate for Gestational Age (AGA) infants/paired mothers have been compared, from delivery/birth to first month of life. Maternal and IUGR cord BNP concentrations were coupled to fetal ultrasonography. Neonatal echocardiography was performed too. On delivery BNP was higher in all IUGR mothers, suffering or not from gestational hypertension, than in AGA (median 37.14 vs 11.1 pg/ml p=0.002). Maternal BNP was not associated to cord/neonatal BNP or fetal ultrasonographic parameters. Cord BNP was higher in IUGR than AGA newborns (median 23.9 vs 11.4 pg/ml p=0.0007) independently of gestational age, while varied with amniotic fluid (p=0.0044) and umbilical artery flowmetry (p=0.0121). Earlier drop of BNP on day 3 was reported in IUGR neonates (p=0.0001).Ventricular mass change/body weight varied positively in AGA newborns (p<0.001), while declined in IUGR ones (p=0.003). Carrying IUGR fetus is a stress factor resulting in high maternal BNP concentration. Altered fetal ultrasonographic parameters in IUGR newborns lead to higher BNP cord levels. A rapid BNP drop and probable ventricular mass adjustment of IUGR newborns may indicate earlier post-natal cardiovascular adaptation than AGA infants.

Use and misuse of antibiotics in the neonatal intensive care unit.

Severe infections represent the main cause of neonatal mortality accounting for more than one million neonatal deaths worldwide every year. Antibiotics are the most commonly prescribed medications in neonatal intensive care units (NICUs) and in industrialized countries about 1% of neonates are exposed to antibiotic therapy. Signs and symptoms of sepsis are nonspecific, and empiric antimicrobial therapy is promptly initiated after obtaining appropriate cultures in order to prevent deleterious consequences. However, many preterm infants who do not have infection receive antimicrobial agents during hospital stay and antibiotic treatment in the setting of negative cultures can have serious adverse effects like: promotion of bacterial antibiotic resistance, alteration of gut colonization, increase risk of Candida colonization and subsequent invasive candidiasis, increase risk of death, necrotizing enterocolitis and late-onset sepsis. Appropriate choice of antimicrobial agents and optimal duration of therapy in neonates with suspected or culture-proven sepsis is essential in order to prevent serious consequences. Moreover the establishment of an antibiotic stewardship programme in the NICUs is the best way of ensuring neonatal infections remain treatable while efforts are made for the developing of optimal antibiotic prescribing.

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.

Neonatal cutaneous disseminated aspergillosis in a preterm extremely-low-birth-weight infant with favourable outcome at 3-year follow-up: a case report.

Invasive disseminated neonatal aspergillosis is an uncommon disease, with only scattered reports in literature in the last few years. Here we report on a 25-week gestational age, 730 g at birth preterm female infant who developed on day-of-life 10 multiple cutaneous exhulcerative lesions in her right arm, trunk and abdomen. Early recognition and diagnosis of these lesions as a due to cutaneous initial symptom of cutaneous disseminated aspergillosis, as well as prompt treatment with Liposomal amphotericin B + Itraconazole, secured successful recovery from the systemic infection. Skin lesions healed without any surgical treatment. The infant was discharged in good health. Long-term follow-up at three years of age revealed normality of all neurodevelopmental and cognitive parameters. To our knowledge, this is one of the very few cases of survival, free from sequelae, for a preterm infant affected by neonatal cutaneous disseminated aspergillosis.

Circulating endothelial progenitor cells and diseases of the preterm infant.

During the last decade, multiple techniques have been developed to isolate and quantify human endothelial progenitor cells (EPCs). In parallel, a number of studies have applied these methodologies to investigate the number and function of circulating EPCs in adult diseases characterized by vascular dysfunction. However, very little is known about different subtypes of EPCs during gestation, during the neonatal age or in neonatal diseases. Initial evidence supports the hypothesis that circulating angiogenic cells may play an important role during development, and attention has particularly focused in clarifying the function of EPCs in lung vascular development, and the role of the impairment of EPC mobilization and homing in hyperoxia-induced lung injury characteristic of bronchopulmonary dysplasia. Among different subtypes of EPCs, both the role of angiogenic mononuclear cells (triple-positive CD34+CD133+VEGFR-2+ cells and colony forming unit-Hill cells) and endothelial colony forming cells (ECFCs) in physiological vascular development and during neonatal diseases need to be elucidated. A better understanding of EPC biology during gestation, during the neonatal age and in preterm infants will unravel the pathologic basis of bronchopulmonary dysplasia and other preterm and term neonatal diseases characterized by a prominent defect in vascular growth, including retinopathy of prematurity and persistent pulmonary hypertension of the newborn.

Preterm newborns are provided with triggering receptor expressed on myeloid cells-1.

Triggering receptor expressed on myeloid cells-1 (TREM-1) and soluble fraction (sTREM-1) are useful markers of infection in adults. Neonates, especially preterm infants, are exposed to high risk of sepsis due to the immature immune system and few data are available regarding TREM-1, mainly focused on the soluble form. We therefore decided to investigate the baseline assessment of TREM-1, membrane and soluble receptors, in preterm newborns without clinical or microbiological evidence of infection, in order to precociously measure the possible changes due to sepsis and compare them to the obtained reference values. Fifty-nine newborns were enrolled in the study. Median and Interquartile range of TREM-1 were: in monocytes 96 percent with 71 Mean Fluorescence Intensity (50-94); in PMNs: 80 percent (68-87); soluble TREM-1: 29.1 pg/ml (14.55-103.93). Monocyte expression and soluble TREM-1 concentrations appeared comparable to healthy adults, while not all PMNs expressed this receptor, possibly due to their immaturity. Birth weight negatively correlated with sTREM-1, while there were no statistical significances with gestational age, maternal age, gender, mode of delivery, patent ductus arteriosus, intrauterine growth restriction, premature rupture of membranes and TREM-1 or sTREM-1. We also reported a statistical relationship between monocyte TREM-1 and surfactant administration and between sTREM-1 and antenatal steroid prophylaxis. Even if untrained, the neonatal immune system of preterm newborns is equipped with TREM-1 system, but further studies are needed to evaluate the functionality in newborns.

Group B streptococcus: early- and late-onset infections.

Group B streptococcus has emerged as a prominent neonatal pathogen in developed countries since the late 1960s. The incidence of disease remained fairly constant until the 1990 s, when prevention efforts increased. American consensus guidelines were endorsed in the mid 1990 s; since then a decrease in disease incidence has been reported in the United States. This review summarizes the main issues regarding the prevention of neonatal infection and presents aspects of group B streptococcal disease with the first population data recently obtained in a northern region of Italy.

Changes in soil characteristics and plant species composition along a moisture gradient in a Mediterranean pasture.

Soil physicochemical characteristics, total aboveground biomass, number of species and relative abundance of groups and individual species were measured along a moisture gradient in a pasture, flooded in part during winter through early summer, adjacent to Pamvotis lake in Ioannina, Greece. Soil and vegetation measurements were conducted in 39 quadrats arranged in four zones perpendicular to the moisture gradient. The zone closest to the lake, recently separated from the lake, became part of the pasture and its soil texture was quite different from that of the other zones with a substrate containing 91% sand. Except for pH, this zone had the lowest values in the other five soil physicochemical characteristics measured (organic matter, total and extracted inorganic nitrogen, Olsen extracted phosphorus and extractable potassium); in the other zones organic matter, total nitrogen, phosphorus and potassium tended to increase from the driest to the wettest zone. Total aboveground biomass, ranging from 280 to 840 gm-2, is high for herbaceous pastures in the conditions of Mediterranean climate and it was not related to distance from the lake's shoreline, although the highest values were measured at intermediate distances, or to any of the various soil characteristics measured. Also, the number of species/0.25 m2 was not related to any of the various soil characteristics, but it was highest at the intermediate distances from the lake's shoreline. Species composition varied along the moisture gradient. Forbs as well as annual grasses and legumes declined in abundance from the driest to the wettest places; the reverse was the case for sedges and perennial grasses and legumes. These results indicate that the soil moisture gradient was the principal factor affecting soil characteristics and plant species composition. Since most species were recorded in all the four zones of the pasture, indicating that these can tolerate all variations in abiotic conditions of pasture, the vegetation zonation seems to be influenced by competition. Each functional group of species tends to dominate in a particular range of the soil moisture gradient where it is better suited and tends to exclude competitively other species. Management practices (mowing and grazing) affect the kinds of processes which maintain the observed community structure either by preventing the establishment of later successional species, like reeds and woody species, or by moderating the shoot competition, especially in the wetter zones, and thus permitting the creeping species to grow successfully.

Variation in stakeholder opinion on countermeasures across Europe.

A compendium of agricultural countermeasures and rural waste disposal options has been compiled as part of the EC STRATEGY (Sustainable Restoration and Long-Term Management of Contaminated Rural, Urban and Industrial Ecosystems) project. The compendium was discussed by the FARMING (Food and Agriculture Restoration Management Involving Networked Groups) network of stakeholders during meetings of national panels in the UK, Finland, Belgium, Greece and France in 2002. Their preliminary feedback has been summarised in terms of whether an option is generally acceptable, unacceptable or only acceptable under specific circumstances. A considerable divergence of opinion between national panels was apparent for many of the options considered. This could be attributed to differences in geomorphology, climate, land management, infrastructure, consumer confidence, sociopolitical context and culture. Where consensus was reached between stakeholders it was generally for those countermeasures that provide public reassurance, sustain farming practices and minimise environmental impact. Furthermore, whilst there was general agreement that contaminated food should not enter the food chain, many of the options proposed for its subsequent management were not generally acceptable to stakeholders.

Achievements, difficulties and future challenges for the FARMING network.

The EC FARMING network (Food and Agriculture Restoration Management Involving Networked Groups) was set up to bring together the many and diverse stakeholders who would be involved in intervention following wide scale radioactive contamination of the food chain, so that acceptable strategies can be developed for maintaining agricultural production and safe food supply. The network comprises stakeholder panels in the UK, Finland, Belgium, France and Greece that have met regularly since 2001 to debate, discuss and exchange opinion on the acceptability, constraints and impact of various countermeasure options and strategies. The objectives of this paper are to consolidate the main achievements of the FARMING project over the period 2000-2004, to highlight the various difficulties that were encountered and to discuss the challenges for engaging stakeholders in off-site emergency management and long-term rehabilitation in the future.

Stakeholder involvement in nuclear crisis management in Greece.

The setting up of the Greek Stakeholders Group in the framework of the EC Food and Agriculture Restoration Management Involving Networked Groups (FARMING) project is described. The Group included members from more than 20 governmental and non-governmental organisations, having interest and/or responsibilities in the management of a crisis following a nuclear accident. The stakeholders, during their meetings in 2002, discussed the agricultural countermeasures and rural waste disposal options which have been compiled by the EC Sustainable Restoration and Long-Term Management of Contaminated Rural, Urban and Industrial Ecosystems (STRATEGY) project. All stakeholders agreed that the most preferable were those options that ensure public acceptance, minimise environmental impact and maintain farming practices and acceptable living and working conditions. Their views are synoptically presented along with the major conclusions from the stakeholders meetings regarding nuclear crisis management.

Effect of soil amendments on radiocesium transfer to alfalfa.

Greenhouse experiments were carried out to evaluate the effect of different soil-based countermeasures on radiocesium transfer to Medicago saliva (alfalfa) grown on artificially contaminated loamy-clayey soil. Various rates of potassium, ammonium, and Prussian Blue supplements were applied, and the uptake of radiocesium by control and treated alfalfa plants was monitored during four growth periods. Transfer factors ranging between 0.06 and 0.02 were determined for control plants. Application of potassium at rates higher than 0.1 meq per 100 g soil was found to suppress radiocesium uptake, the effect being more pronounced at increasing fertilization rates. On the contrary, soil treatment with ammonium enhanced the bio-accumulation of radiocesium, indicating that Cs+ ions, previously unavailable to plant roots, were released from soil particles. Prussian Blue supplements had practically no effect on soil-to-alfalfa transfer of the radionuclide.