Background: some consensus guidelines include C-reactive protein (CRP) in the diagnostic workup of early-onset neonatal sepsis (EOS), but its routine use remains debated due to variable diagnostic performance. The experiences and data from individual centers can help clarify its clinical utility and inform local practice. Methods: Retrospective analysis at a level III center assessing the impact of discontinuing routine C-reactive protein (CRP) testing for suspected early-onset sepsis (EOS). Laboratory use, antibiotic therapy, and outcomes in neonates of all gestational ages were compared before (2021-2022) and after (2024-2025) the policy change. Results: A total of 638 neonates were included (period 1, n = 348; period 2, n = 290). CRP testing decreased markedly (218/348 in period 1 vs. 40/290 in period 2; p < 0.001), alongside a significant reduction in the number of complete blood counts performed (285/348 vs. 214/290; p = 0.02). Concurrently, both the proportion of short antibiotic courses (≤48 h) initiated within the first 3 days of life (98/181 vs. 88/133) and the median duration of antibiotic therapy (48.0 h vs. 40.0 h; p < 0.001) decreased without worsening outcomes. The duration of antibiotic therapy was even shorter in infants born before 34 weeks' gestation (48.0 h vs. 37.5 h; p < 0.001). Conclusions: Restricting the use of CRP in the evaluation of EOS was associated with a reduction in unnecessary antibiotic exposure. This strategy may be considered a core component of neonatal antibiotic stewardship programs.

Background:Therapeutic hypothermia (TH) is the standard treatment for moderate to severe hypoxic-ischemic encephalopathy (HIE), yet pain assessment during TH remains challenging. This study compares two validated pain scales in asphyxiated newborns undergoing TH and receiving fentanyl analgesia. Methods:Twenty term infants with HIE treated with TH were enrolled. Pain was assessed using EDIN and N-PASS, while sedation was monitored using the N-PASS sedation subscale. Results:N-PASS pain and sedation scores significantly decreased by day 3, whereas EDIN scores showed no significant temporal change. Effective analgesia significantly increased over time, either when defined based on EDIN (OR 3.12, p = 0.002) and on N-PASS (OR 3.06, p = 0.007), while N-PASS sedation did not show a time-dependent association. No scale showed a significant association with fentanyl dosage. A moderate positive correlation was found between EDIN and N-PASS pain scores (r = 0.409, p < 0.001). Sedation targets were achieved in only 40%-50% of assessments, with early undersedation and later oversedation observed. Conclusions:EDIN and N-PASS pain scores demonstrate moderate concordance, but capture different dimensions of neonatal pain during TH. N-PASS appears more sensitive to temporal changes, likely due to its combined behavioral and physiological components, whereas EDIN may be affected by hypothermia-related behavioral suppression.

In the original publication [...].

AIM:This study assessed neurodevelopmental outcomes in neonates with hypoxic-ischemic encephalopathy (HIE) treated with therapeutic hypothermia (TH) outside randomised controlled trials (RCTs). It also aimed to identify predictors of outcomes and evaluate TH practices across centres. METHODS:A prospective, area-based observational study was conducted in eight Italian NICUs (2016-2021), including neonates treated with TH for any grade of HIE. A 2-year neurodevelopmental follow-up was performed. Severe functional disability (SFD) was defined as cerebral palsy (Gross Motor Function Classification Level > 2), cognitive score < 2 SD, bilateral blindness/deafness, or epilepsy. Demographic, clinical and MRI data were analysed. RESULTS:Among 283 cooled infants, 11 (3.8%) died and 272 (96.2%) survived. HIE severity was mild (14.0%), moderate (76.1%) and severe (9.9%). Follow-up data were available for 232 (85.3%) survivors, with SFD diagnosed in 27 (11.6%). No infants with mild HIE developed SFD. Severe MRI anomalies were found in 51.9% of SFD cases, while 90.7% of non-SFD children had normal findings. cEEG/aEEG-confirmed seizures (OR = 12.9, CI 3.5-65.0) and severe MRI anomalies (OR = 0.24, CI 0.13-0.44) were strong SFD predictors (AUC = 0.95). CONCLUSION:Mortality and SFD rates were lower than in RCTs. Seizures and severe MRI anomalies predicted poor outcomes. Further RCTs are needed to refine treatment criteria.

INTRODUCTION:Group-B Streptococcus(GBS) infections may rarely recur after antibiotic treatment. We aimed to fill existing gaps on epidemiology, clinical features, and outcomes of GBS recurrences. METHODS:A systematic search of PubMed and Embase was conducted, covering the period until 1 July 2024. The demographics, clinical characteristics, treatment, and outcomes of infants withGBS recurrence were analyzed. Recurrence was defined as > 1 episode of invasiveGBS infection (positive blood and/or cerebrospinal fluid culture), occurring after the completion of treatment for the initial episode. RESULTS:Among the 213 recurrences, 146 reported individual data and were included in the analysis. GBS recurrences developed shortly after the completion of antibiotic treatment for the initial infection (median = 10 days 95%CI 6.0-18.8). Most infants were preterm (63.5%) and had received an adequately long course of antibiotics for the initial infection (median = 13 days, 95%CI 10-14). Serotype III waspredominant. Breast milk yielded GBS in most samples cultured (41/62, 66%); 5/15 (33%) infants who discontinued breastfeeding after recurrence had further GBS recurrence. Case fatalities were 3.7%. CONCLUSIONS:Preterm birth is closely associated with GBS recurrences. Adequately long courses of antibiotics or withdrawal of breast milk may not be useful measures to prevent recurrences.

The quality of cranial ultrasound has improved over time, with advancing technology leading to higher resolution, faster image processing, digital display, and back-up. However, some brain lesions may remain difficult to characterize: since higher frequencies result in greater spatial resolution, the use of additional transducers may overcome some of these limitations. The very high-frequency transducers (18-5 MHz) are currently employed for small parts and lung ultrasound. Here we report the first case series comparing the very high-frequency probes (18-5 MHz) with standard micro-convex probes (8-5 MHz) for cranial ultrasound in preterm infants. In this case series, we compared cranial ultrasound images obtained with a micro-convex transducer (8-5 MHz) and those obtained with a very high-frequency (18-5 MHz) linear array transducer in 13 preterm infants ≤ 32 weeks gestation (9 with cerebral abnormalities and 4 with normal findings). Ultrasound examinations using the very high-frequency linear transducer and the standard medium-frequency micro-convex transducer were performed simultaneously. We also compared ultrasound findings with brain MRI images obtained at term corrected age. Ultrasound images obtained with the very high-frequency (18-5 MHz) transducer showed high quality and accuracy. Notably, despite their higher frequency and expected limited penetration capacity, brain size is small enough in preterm infants, so that brain structures are close to the transducer, allowing for complete evaluation. Conclusion: We propose the routine use of very high-frequency linear probes as a complementary scanning modality for cranial ultrasound in preterm infants ≤ 32 weeks gestation.

Background: Bacterial meningitis (BM) in infants is a serious condition that can lead to significant complications. Lumbar puncture (LP) is essential to provide diagnoses, however false negatives may result if LP is performed after the starting of antibiotic therapy. Methods: We conducted a retrospective analysis of infants of any gestational age with BM within their first 90 days of life and admitted to the Neonatal Intensive Care Unit of Modena Policlinico between 1 January 2011, and 31 December 2023. Results: A total of 44 episodes of meningitis were confirmed in 40 infants, diagnosed by positive cerebrospinal fluid cultures (n = 37), polymerase chain reaction testing (n = 4), or both methods (n = 3). Three out of forty infants (8%) experienced a relapse of meningitis. Most episodes (31/44, 70%) occurred in preterm infants. The incidence of early-onset meningitis was lower than that of late-onset (0.18 vs. 0.94 cases per 1000 births, respectively), with Gram-positive accounting for most cases (27/44, 61%). LP was performed prior to antibiotic administration in most episodes (30/44, 68%). Two preterm infants (5%) died from meningitis-related complications. Forty-two episodes occurred among thirty-eight surviving infants; brain lesions were detected through brain ultrasound or MRI in nine out of forty-two episodes (21%). Conclusions: Preterm infants have higher rates of BM, brain lesions or case fatalities. Early diagnosis and prompt antibiotic treatment are critical to improve outcomes.

Background: Centrally inserted central catheters (CICCs) are increasingly used in neonatal care. CICCs have garnered attention and adoption owing to their advantageous features. Therefore, achieving clinical competence in ultrasound-guided CICC insertion in term and preterm infants is of paramount importance for neonatologists. A safe clinical training program should include theoretical teaching and clinical practice, simulation and supervised CICC insertions. Methods: We planned a training program for neonatologists for ultrasound-guided CICCs placement at our level III neonatal intensive care unit (NICU) in Modena, Italy. In this single-centre prospective observational study, we present the preliminary results of a 12-month training period. Two paediatric anaesthesiologists participated as trainers, and a multidisciplinary team was established for continuing education, consisting of neonatologists, nurses, and anaesthesiologists. We detail the features of our training program and present the modalities of CICC placement in newborns. Results: The success rate of procedures was 100%. In 80.5% of cases, the insertion was obtained at the first ultrasound-guided venipuncture. No procedure-related complications occurred in neonates (median gestational age 36 weeks, IQR 26–40; median birth weight 1200 g, IQR 622–2930). Three of the six neonatologists (50%) who participated in the clinical training program have achieved good clinical competence. One of them has acquired the necessary skills to in turn supervise other colleagues. Conclusions: Our ongoing clinical training program was safe and effective. Conducting the program within the NICU contributes to the implementation of medical and nursing skills of the entire staff.

Surfactant is a well-established therapy for preterm neonates affected by respiratory distress syndrome (RDS). The goals of different methods of surfactant administration are to reduce the duration of mechanical ventilation and the severity of bronchopulmonary dysplasia (BPD); however, the optimal administration method remains unknown. This study compares the effectiveness of the INtubate-RECruit-SURfactant-Extubate (IN-REC-SUR-E) technique with the less-invasive surfactant administration (LISA) technique, in increasing BPD-free survival of preterm infants. This is an international unblinded multicenter randomized controlled study in which preterm infants will be randomized into two groups to receive IN-REC-SUR-E or LISA surfactant administration. In this study, 382 infants born at 24+0–27+6 weeks’ gestation, not intubated in the delivery room and failing nasal continuous positive airway pressure (nCPAP) or nasal intermittent positive pressure ventilation (NIPPV) during the first 24 h of life, will be randomized 1:1 to receive IN-REC-SUR-E or LISA surfactant administration. The primary outcome is a composite outcome of death or BPD at 36 weeks’ postmenstrual age. The secondary outcomes are BPD at 36 weeks’ postmenstrual age; death; pulse oximetry/fraction of inspired oxygen; severe intraventricular hemorrhage; pneumothorax; duration of respiratory support and oxygen therapy; pulmonary hemorrhage; patent ductus arteriosus undergoing treatment; percentage of infants receiving more doses of surfactant; periventricular leukomalacia, severe retinopathy of prematurity, necrotizing enterocolitis, sepsis; total in-hospital stay; systemic postnatal steroids; neurodevelopmental outcomes; and respiratory function testing at 24 months of age. Randomization will be centrally provided using both stratification and permuted blocks with random block sizes and block order. Stratification factors will include center and gestational age (24+0 to 25+6 weeks or 26+0 to 27+6 weeks). Analyses will be conducted in both intention-to-treat and per-protocol populations, utilizing a log-binomial regression model that corrects for stratification factors to estimate the adjusted relative risk (RR). This trial is designed to provide robust data on the best method of surfactant administration in spontaneously breathing preterm infants born at 24+0–27+6 weeks’ gestation affected by RDS and failing nCPAP or NIPPV during the first 24 h of life, comparing IN-REC-SUR-E to LISA technique, in increasing BPD-free survival at 36 weeks’ postmenstrual age of life. ClinicalTrials.gov NCT05711966. Registered on February 3, 2023.

Background: There are wide variations in antibiotic use in neonatal intensive care units (NICUs). Limited data are available on antimicrobial stewardship (AS) programs and long-term maintenance of AS interventions in preterm very-low-birth-weight (VLBW) infants. Methods: We extended a single-centre observational study carried out in an Italian NICU. Three periods were compared: I. “baseline” (2011–2012), II. “intervention” (2016–2017), and III. “maintenance” (2020–2021). Intensive training of medical and nursing staff on AS occurred between periods I and II. AS protocols and algorithms were maintained and implemented between periods II and III. Results: There were 111, 119, and 100 VLBW infants in periods I, II, and III, respectively. In the “intervention period”, there was a reduction in antibiotic use, reported as days of antibiotic therapy per 1000 patient days (215 vs. 302, p < 0.01). In the “maintenance period”, the number of culture-proven sepsis increased. Nevertheless, antibiotic exposure of uninfected VLBW infants was lower, while no sepsis-related deaths occurred. Our restriction was mostly directed at shortening antibiotic regimens with a policy of 48 h rule-out sepsis (median days of early empiric antibiotics: 6 vs. 3 vs. 2 in periods I, II, and III, respectively, p < 0.001). Moreover, antibiotics administered for so-called culture-negative sepsis were reduced (22% vs. 11% vs. 6%, p = 0.002), especially in infants with a birth weight between 1000 and 1499 g. Conclusions: AS is feasible in preterm VLBW infants, and antibiotic use can be safely reduced. AS interventions, namely, the shortening of antibiotic courses in uninfected infants, can be sustained over time with periodic clinical audits and daily discussion of antimicrobial therapies among staff members.

BACKGROUND AND AIM:During the 2020 and 2021 Italian COVID-19 pandemic social restrictions and strict hygiene measures were recommended to limit the spread of SARS-CoV-2. We aimed to assess whether rates of respiratory infections and wheezing in preterm infants have changed during the pandemic.METHODS:Single center, retrospective study. Preterm infants in the first 6 months of life discharged home prior to (Period 1, January 2017 - December 2019) or during the pandemic (Period 2, January 2020 - March 2021) were compared. Rates of respiratory infection and wheezing in preterm infants with or without bronchopulmonary dysplasia (BDP) were assessed.RESULTS:During period 2 premature infants had lower rates of respiratory infections (36 out of 55 in Period 1 vs 11 out of 28 in Period 2, P=0.023) and wheezing (20 out of 55 in Period 1 vs 1 out of 28 in Period 2, P=0.001). This difference remained significant when infants with BPD (all grades) were analyzed separately (respiratory infections 26 out of 40 in Period 1 vs 7 out of 24 in Period 2, P=0.005; wheezing 16 out of 40 in Period 1 vs 1 out of 24 in Period 2, P=0.001). In contrast, respiratory infections and wheezing in preterm infants without BPD did not change after pandemic.CONCLUSIONS:Episodes of respiratory infections and wheezing among preterm infants were reduced during pandemic. We highlight the importance of proper family education for preventing respiratory tract infections in preterm infants with BPD, beyond the extraordinary conditions of the COVID-19 pandemic.

Background: Skin-to-skin contact (SSC) is one of the four components of kangaroo care (KC) and is also a valued alternative to incubators in low-income countries. SSC has also become a standard of care in high-income countries because of its short- and long-term benefits and its positive effect on infant growth and neurodevelopmental outcome. However, barriers in the implementation of SSC, especially with preterm infants, are common in NICUs because parents and health care professionals can perceive it as potentially risky for the clinical stability of preterm infants. Previous studies have assessed safety before and during SSC by monitoring vital parameters during short-time intervals. Aims: To demonstrate the safety of early SSC in preterm infants during at least 90 min intervals. Design: Prospective observational monocentric study. Methods: Preterm infants born between June 2018 and June 2020 with a gestational age of ≤33 weeks and a birth weight of <2000 g were monitored while performing an SSC session during the first three weeks of life. Infants with necrotizing enterocolitis, sepsis, and congenital malformations on mechanical ventilation or with more than five apneas in the hour before SSC were excluded. Continuous oxygen saturation (SaO2), heart rate (HR), and respiratory rate (RR) were registered during an SSC session and in the hour before. The minimum duration of an SSC session was 90 min. Information regarding postmenstrual age (PMA), body weight, respiratory support, presence of a central venous catheter and the onset of sepsis within 72 h after a session was collected. Two physicians, blinded to infant conditions and the period of analysis (before or during SSC), evaluated desaturation episodes (SaO2 < 85%, >15 s), bradycardia (HR < 100, >15 s) and apneas (pause in breathing > 20 s associated with desaturation and/or bradycardia). A Wilcoxon rank sum test was used for the statistical analysis. Results: In total, 83 episodes of SSC were analyzed for a total of 38 infants. The mean gestational age at birth was 29 weeks (range 23–33 weeks). Median PMA, days of life, and body weight at SSC were 31 weeks (range 25–34 weeks), 10 days (range 1–20 days), and 1131 g (range 631–2206 g), respectively. We found that 77% of infants were on respiratory support and 47% of them had a central venous catheter (umbilical or peripherally inserted central catheter) during SSC. The total duration of desaturation, bradycardia, and the number of apneas were not statistically different during the SSC session and the hour before. No catheter dislocation or ruptures were reported. Conclusions: These findings highlighted the safety of early SSC in preterm infants and the possibility of performing it in an intensive care setting in the first weeks of life. In addition, these findings should reassure health care professionals offering this practice as a standard of care. SSC plays a key role in the care of preterm infants due to its short- and long-term positive benefits, and it deserves to be increasingly offered to infants and their parents.

Background: Prolonged mechanical ventilation in preterm infants may cause complications. We aimed to analyze the variables affecting extubation outcomes in preterm infants at high risk of extubation failure. Methods: This was a single-center, observational, retrospective study. Extubation failure was defined as survival with the need for reintubation within 72 h. Successfully extubated neonates (group 1) were compared to those with failed extubation (group 2). Multivariate logistic regression analysis evaluated factors that predicted extubation outcomes. Results: Eighty infants with a birth weight under 1000 g and/or gestational age (GA) under 28 weeks were included. Extubation failure occurred in 29 (36.2%) and success in 51 (63.8%) neonates. Most failures (75.9%) occurred within 24 h. Pre-extubation inspired oxygen fraction (FiO2) of 27% had a sensitivity of 58.6% and specificity of 64.7% for extubation failure. Post-extubation FiO2 of 32% had a sensitivity of 65.5% and specificity of 62.8% for failure. Prolonged membrane rupture (PROM) and high GA were associated with extubation success in multivariate logistic regression analysis. Conclusions: High GA and PROM were associated with extubation success. Pre- and post-extubation FiO2 values were not significantly predictive of extubation failure. Further studies should evaluate if overall assessment, including ventilatory parameters and clinical factors, can predict extubation success in neonates.

There is insufficient data regarding antimicrobial stewardship (AS) and outcomes of very low birth weight (VLBW) neonates after AS programs. This observational, retrospective study addressed AS and outcomes of VLBW neonates admitted to an Italian level-three center. Two periods were compared: (i) baseline, before AS (January 2011–December 2012) and (ii) intervention, after AS (January 2016–December 2017). Between these two periods, procedures were put in place to inform medical and nursing staff regarding AS. There were 111 and 119 VLBW neonates in the baseline (6744 live births) and in the intervention period (5902 live births), respectively. The number of infants exposed to antibiotics (70%) during the hospital stay did not change, but the total days of therapy (DOT, median 12 vs. 5) and DOT/1000 patient days (302 vs. 215) decreased in the intervention period (p < 0.01), as well as the median duration of first antibiotic treatment (144 vs. 48 h, p < 0.01). A re-analysis of single cases of culture-proven or culture-negative sepsis failed to demonstrate any association between deaths and a delay or insufficient antibiotic use in the intervention period. In conclusion, AS is feasible in preterm VLBW neonates and antibiotic use can be safely reduced.

Shock is a generalized tissue hypoperfusion that leads to severe cellular distress and complicates some cases of paediatric and neonatal sepsis. Although a reduction in associated sepsis mortality has been observed in the last decades, it remains one of the most important causes of death or long-term neurodevelopmental disabilities in children. Prompt recognition of this condition is therefore essential to improve survival and long-term outcome. The paediatrician and the neonatologist must therefore be able to promptly recognize the signs and symptoms of sepsis and septic shock to set up an adequate treatment according to the most recent international guidelines. This article provides epidemiological data from Italian and international studies, describes the pathophysiology and clinical manifestations of sepsis and septic shock, as well as the therapeutic indications according to very recent recommendations.

The optimal threshold for neonatal platelet transfusions in sick newborns is still uncertain. We report a congenital cytomegalovirus (CMV) infection in a premature neonate with severe thrombocytopenia who subsequently presented with necrotizing enterocolitis and intestinal bleeding. The baby recovered after platelet transfusions were discontinued and the therapy was switched from intravenous ganciclovir to oral valganciclovir. We discuss both measures, speculating on the key role of platelet transfusions.

Infantile pyknocytosis (IP) is a rare, self-limited neonatal haemolytic anaemia that may require multiple blood transfusions. Only a little more than 50 cases have been reported in the medical literature, and the great majority of them concerns term infants. The etiology of IP is not well understood; most likely it results from a transient extra-corpuscular factor, whose nature is unknown, transmitted from mother to child or, alternatively, from a deficiency of an anti-oxidative agent. We report the case of two preterm twins, one of which suffered from IP and developed severe anaemia at age 2 wk, while the other was unaffected. Although no specific agent was identified as the cause of anaemia and IP, we speculate that the transmission of an agent from mother to child was unlikely, as only twin one suffered from IP. Smelly greenish diarrhoea occurred just before the presentation of IP, suggesting that the same agent led to both the diarrhoea and the oxidative injury. Because IP may remain underdiagnosed, it should be considered in cases of early unexplained severe hemolytic anemia.