Ultrasound-Guided Centrally Inserted Central Catheter (CICC) Placement in Newborns: A Safe Clinical Training Program in a Neonatal Intensive Care Unit.

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.

Sustaining the Continued Effectiveness of an Antimicrobial Stewardship Program in Preterm Infants.

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.

Measurement of lung oxygenation by near-infrared spectroscopy in preterm infants with bronchopulmonary dysplasia.

INTRODUCTION: It has recently been reported that it is possible to monitor lung oxygenation (rSO2 L) by near-infrared spectroscopy (NIRS) in preterm infants with respiratory distress syndrome (RDS). Thus, our aim was to assess the possibility of monitoring rSO2 L in infants with evolving and established bronchopulmonary dysplasia (BPD) and to evaluate if rSO2 L correlates with BPD severity and other oxygenation indices. METHODS: We studied 40 preterm infants with gestational age ≤30 weeks at risk for BPD. Patients were continuously studied for 2 h by NIRS at 28 ± 7 days of life and 36 weeks ± 7 days of postmenstrual age. RESULTS: rSO2 L was similar at the first and second NIRS recordings (71.8 ± 7.2 vs. 71.4 ± 4.2%) in the overall population, but it was higher in infants with mild than in those with moderate-to-severe BPD at both the first (73.3 ± 3.1 vs. 71.2 ± 3.2%, p = .042) and second (72.3 ± 2.8 vs. 70.5 ± 2.8, p = .049) NIRS recording. A rSO2 L cutoff value of 71.6% in the first recording was associated with a risk for moderate-to-severe BPD with a sensitivity of 66% and a specificity of 60%. Linear regression analysis demonstrated a significant positive relationship between rSO2 L and SpO2 /FiO2 ratio (p = .013) and a/APO2 (p = .004). CONCLUSIONS: Monitoring of rSO2 L by NIRS in preterm infants with evolving and established BPD is feasible and safe. rSO2 L was found to be higher in infants with mild BPD, and predicts the risk for developing moderate-to-severe BPD and correlates with other indices of oxygenation.

Neurodevelopmental Outcome after Culture-Proven or So-Called Culture-Negative Sepsis in Preterm Infants.

(1) Background: Prematurity is a serious condition associated with long-term neurological disability. This study aimed to compare the neurodevelopmental outcomes of preterm neonates with or without sepsis. (2) Methods: This single-center retrospective case-control study included infants with birth weight < 1500 g and/or gestational age ≤ 30 weeks. Short-term outcomes, brain MRI findings, and severe functional disability (SFD) at age 24 months were compared between infants with culture-proven or culture-negative sepsis or without sepsis. A chi-squared test or Mann-Whitney U test was used to compare the clinical and instrumental characteristics and the outcomes between cases and controls. (3) Results: Infants with sepsis (all sepsis n = 76; of which culture-proven n = 33 and culture-negative n = 43) were matched with infants without sepsis (n = 76). Compared with infants without sepsis, both all sepsis and culture-proven sepsis were associated with SFD. In multivariate logistic regression analysis, SFD was associated with intraventricular hemorrhage (OR 4.7, CI 1.7-13.1, p = 0.002) and all sepsis (OR 3.68, CI 1.2-11.2, p = 0.021). (4) Conclusions: All sepsis and culture-proven sepsis were associated with SFD. Compared with infants without sepsis, culture-negative sepsis was not associated with an increased risk of SFD. Given the association between poor outcomes and culture-proven sepsis, its prevention in the neonatal intensive care unit is a priority.

Neurodevelopmental outcome of neonatal seizures: A longitudinal study.

INTRODUCTION: Neonatal seizures (NS) are the most common neurological emergency in the neonatal period. The International League Against Epilepsy (ILAE) proposed a new classification of NS based on semiology and highlighted the correlation between semiology and aetiology. However, neurodevelopmental outcomes have not been comprehensively evaluated based on this new classification. AIMS: To evaluate neurodevelopmental outcomes and potential risk factors for severe outcomes in NS. METHODS: Patients with video electroencephalogram confirmed NS were evaluated. Seizure aetiology, cerebral magnetic resonance imaging (MRI) data, background electroencephalograms data, general movements, and neurodevelopmental outcomes were analysed. Severe outcomes were one of the following: death, cerebral palsy, Griffiths developmental quotient <70, epilepsy, deafness, or blindness. RESULTS: A total of 74 neonates were evaluated: 62 (83.8 %) with acute provoked NS (primarily hypoxic-ischaemic encephalopathy), and 12 (16.2 %) with neonatal-onset epilepsies (self-limited neonatal epilepsy, developmental and epileptic encephalopathy, cerebral malformations). Of these, 32 (43.2 %) had electrographic seizures, while 42 (56.7 %) had electroclinical seizures - 38 (90.5 %) were motor (42.1 % clonic) and 4 (9.5 %) were non-motor phenomena. Severe outcomes occurred in 33 of the 74 (44.6 %) participants. In multivariate analysis, neonatal-onset epilepsies (odds ratio [OR]: 1.3; 95 % confidence interval [CI]: 1.1-1.6), status epilepticus (OR: 5.4; 95 % CI: 1.5-19.9), and abnormal general movements (OR: 3.4; 95 % CI: 1.9-7.6) were associated with severe outcomes. CONCLUSIONS: At present, hypoxic-ischaemic encephalopathy remains the most frequent aetiology of NS. The prognosis of neonatal-onset epilepsies was worse than that of acute provoked NS, and status epilepticus was the most predictive factor for adverse outcomes.

Maternal singing sustains preterm hospitalized newborns' autonomic nervous system maturation: an RCT.

BACKGROUND: Premature birth is known to affect the newborn's autonomic nervous system (ANS) maturation, with potential short and long-term impact on their neurobehavioral development. The purpose of the study was to investigate the effects of maternal directed singing and speaking on the preterm infants' autonomic nervous system (ANS) maturation as measured by the heart rate variability (HRV) parameters. METHODS: In this multi-center randomized clinical trial, 30 stable preterm infants (m = 29,6 weeks of gestational age), without any abnormalities were randomized into an intervention (16) or a control group (14). HRV was measured weekly, for a total of 80 recordings during hospitalization, as well as before and after each session of singing or speaking. RESULTS: The intervention group showed a significant increase of the percentage value of HRV power in the high frequency range when compared to the control group (p = 0.044). More specifically, the maternal singing significantly increased the high frequency power and decreased the low/high frequency power ratio (p = 0.037). CONCLUSIONS: The preterm infant's vagal activity significantly increased in the intervention group, potentially enhancing their ANS maturation. The effect is specifically evidenced in the singing condition. IMPACT: Maternal singing affects the autonomic nervous system maturation of preterm hospitalized newborns in the NICU. No previous studies investigated how early vocal parental intervention can affect preterm infants developement, throught their autonomic nervous system maturation. Early Vocal Contact as an early intervention involving parents has a positive impact on preterm infant's development and it can be easily implemented in the care of preterm infants. TRIAL REGISTRATION: NCT04759573, retrospectively registered, 17 February 2021.

Minipuberty in Male Full-term Neonates Appropriate and Small for Gestational Age and in Preterm Babies: Data from a Single Centre

Objective: The postnatal activation of the hypothalamic-pituitary-gonadal (HPG) axis is usually known as "minipuberty". There are still open questions about its biological function and significance depending on sex, gestational age (GA) and birth weight (BW) with few available longitudinal data. Methods: A single-centre, longitudinal study to quantify urinary follicle stimulating hormone (uFSH), luteinizing hormone (uLH) and testosterone (uTs) in male neonates. Neonates were enrolled and stratified into three subgroups: full-term boys appropriate for GA (FT AGA); FT boys with BW ≤3rd centile [FT small for gestational age (SGA)]; and preterm (PT) boys ≤33 weeks of GA. Urinary hormones were correlated to simultaneous auxological parameters, linear growth and external genitalia at scheduled time-points. Results: Forty-six boys were recruited, with subgroup sizes FT AGA n=23, FT SGA n=11 and PT n=12. PT boys display a pulsatile pattern of urinary gonadotropins (uGns) with higher levels of uLH and a gradual increase of uTs. Testicular descent started from 29-32 weeks with the peak of uTs. During the first 12-months post-term age (PTA), FT AGA boys displayed a better linear growth (p<0.05). PT showed higher uGns levels until 3-months PTA. PT babies had higher uLH levels than FT AGA, with a peak at 7 and 30 days, during the first 90 days of life (p<0.001) and higher uTs levels. Correlation analysis between penile growth of all neonates and uTs was significant (p=0.04) but not within subgroups. Conclusion: This study investigated postnatal HPG axis activation in term and PT infants. Minipuberty may involve an early window of opportunity to evaluate the functionality of the HPG axis. Further studies with a long-term follow-up are needed with a special focus on possible consequences of GA and BW.

Fetal hepatic calcification in severe KAT6A (Arboleda-Tham) syndrome.

Arboleda-Tham syndrome (ARTHS, MIM 616268) is a rare genetic disease, due to a pathogenic variant of Lysine (K) Acetyltransferase 6A (KAT6A) with autosomal dominant inheritance. Firstly described in 2015, ARTHS is one of the more common causes of undiagnosed syndromic intellectual disability. Due to extreme phenotypic variability, ARTHS clinical diagnosis is challenging, mostly at early stage of the disease. Moreover, because of the wide and unspecific spectrum of ARTHS, identification of the syndrome during prenatal life rarely occurs. Therefore, reported cases of KAT6A syndrome have been identified primarily through clinical or research exome sequencing in a gene-centric approach. In order to expands the genotypic and phenotypic spectrum of ARTHS, we describe prenatal and postnatal findings in a patient with a novel frameshift KAT6A pathogenic variant, displaying a severe phenotype with previously unreported clinical features.

Pharmacokinetic and Pharmacodynamic Considerations of Antibiotic Use in Neonates.

The selection of an appropriate dose of a given antibiotic for a neonate not only requires knowledge of the drug's basic pharmacokinetic (PK) and pharmacodynamic (PD) properties but also the profound effects that organ development might have on the volume of distribution and clearance, both of which may affect the PK/PD of a drug. Interest has grown in alternative antibiotic dosing strategies that are better aligned with the antibiotic's PK and PD properties. These strategies should be used in conjunction with minimum inhibitory concentration measurements and therapeutic drug monitoring to measure their potential success. They can also guide the clinician in tailoring the delivery of antibiotics to suit an individual patient's needs. Model-informed precision dosing, such as Bayesian forecasting dosing software (which incorporates PK/PD population models), may be utilized to optimize antibiotic exposure in neonatal populations. Consequently, optimizing the antibiotic dose and exposure in each newborn requires expertise in different fields. It drives the collaboration of physicians together with lab technicians and quantitative clinical pharmacologists.

Lung UltrasouNd Guided surfactant therapy in preterm infants: an international multicenter randomized control trial (LUNG study).

BACKGROUND: The management of respiratory distress syndrome (RDS) in premature newborns is based on different types of non-invasive respiratory support and on surfactant replacement therapy (SRT) to avoid mechanical ventilation as it may eventually result in lung damage. European guidelines currently recommend SRT only when the fraction of inspired oxygen (FiO2) exceeds 0.30. The literature describes that early SRT decreases the risk of bronchopulmonary dysplasia (BPD) and mortality. Lung ultrasound score (LUS) in preterm infants affected by RDS has proven to be able to predict the need for SRT and different single-center studies have shown that LUS may increase the proportion of infants that received early SRT. Therefore, the aim of this study is to determine if the use of LUS as a decision tool for SRT in preterm infants affected by RDS allows for the reduction of the incidence of BPD or death in the study group. METHODS/DESIGN: In this study, 668 spontaneously-breathing preterm infants, born at 25+0 to 29+6 weeks' gestation, in nasal continuous positive airway pressure (nCPAP) will be randomized to receive SRT only when the FiO2 cut-off exceeds 0.3 (control group) or if the LUS score is higher than 8 or the FiO2 requirements exceed 0.3 (study group) (334 infants per arm). The primary outcome will be the difference in proportion of infants with BPD or death in the study group managed compared to the control group. DISCUSSION: Based on previous published studies, it seems that LUS may decrease the time to administer surfactant therapy. It is known that early surfactant administration decreases BPD and mortality. Therefore, there is rationale for hypothesizing a reduction in BPD or death in the group of patients in which the decision to administer exogenous surfactant is based on lung ultrasound scores. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT05198375 . Registered on 20 January 2022.

A prospective cohort study evaluating exclusive breastfeeding in late preterm infants.

BACKGROUND: Breastfeeding can be challenging in neonates born between 34 0/7 and 36 6/7 weeks gestation (late preterm). METHODS: This prospective cohort study aims to evaluate exclusive breastfeeding at discharge, at three and six months of life in late preterm infants, and to identify facilitators and challenges to it. We included late preterm neonates eligible for the rooming-in. Data about breastfeeding at discharge, at three and six months of life were collected. RESULTS: Two hundred and fourteen late preterm infants were included in the study. At discharge 70 infants (32.7%) were fed with human milk and 144 (67.2%) were not. Non-exclusive breastfeeding was more common in women who were primiparous, had hypertension, and who underwent cesarean sections. Non-exclusive breastfeeding was associated with a low birthweight (<2500 g), ≥2 blood glucose controls, weight loss >10%, and longer hospital stay. Early first latch-on and skin-to-skin contact were more frequently associated with exclusive human milk feeding (P<0.001). Late preterm neonates born at 35 weeks showed a significant increase in exclusive human milk feeding at 3 months compared to the rate at discharge (P=0.004). CONCLUSIONS: In this cohort, early first latch-on and immediate skin-to-skin contact resulted associated with exclusive human milk feeding. Despite formula-fed during hospitalization, infants born at ≥35 weeks gestation who were exclusively breastfed at follow-up increased.

Noninvasive Monitoring Strategies for Bronchopulmonary Dysplasia or Post-Prematurity Respiratory Disease: Current Challenges and Future Prospects.

Definitions of bronchopulmonary dysplasia (BPD) or post-prematurity respiratory disease (PPRD) aim to stratify the risk of mortality and morbidity, with an emphasis on long-term respiratory outcomes. There is no univocal classification of BPD due to its complex multifactorial nature and the substantial heterogeneity of clinical presentation. Currently, there is no definitive treatment available for extremely premature very-low-birth-weight infants with BPD, and challenges in finding targeted preventive therapies persist. However, innovative stem cell-based postnatal therapies targeting BPD-free survival are emerging, which are likely to be offered in the first few days of life to high-risk premature infants. Hence, we need easy-to-use noninvasive tools for a standardized, precise, and reliable BPD assessment at a very early stage, to support clinical decision-making and to predict the response to treatment. In this non-systematic review, we present an overview of strategies for monitoring preterm infants with early and evolving BPD-PPRD, and we make some remarks on future prospects, with a focus on near-infrared spectroscopy (NIRS).

Antimicrobial Resistance Pattern and Empirical Antibiotic Treatments in Neonatal Sepsis: A Retrospective, Single-Center, 12-Year Study.

Neonatal sepsis is an important cause of morbidity and mortality in neonatal intensive care units (NICUs). Continuous evaluation of antimicrobial resistance (AMR) profiles is advised to implement antimicrobial stewardship (AMS) programs and establish effective empiric antibiotic protocols. AMS may reduce AMR in NICUs and improve sepsis outcomes. In this retrospective observational study, we report data on culture-positive neonatal sepsis, assessing differences after the implementation of an AMS program (2011-2016 vs. 2017-2022). A total of 215 positive bacterial cultures from 169 infants were retrieved, with 79 early-onset (36.7%) and 136 late-onset (63.3%) sepsis episodes. Frequent causative agents for early-onset sepsis were S. agalactiae and E. coli, all susceptible to empiric treatment. Late-onset sepsis was mainly caused by Enterobacterales and S. aureus. Aminoglycosides, cefotaxime, and piperacillin-tazobactam resistance among Enterobacterales was substantially low; S. aureus was mostly susceptible to oxacillin and vancomycin. There were no differences in mortality and multidrug-resistant pathogens rates between the two study periods. There were five episodes of fungal late-onset sepsis, mostly due to C. albicans, of which one was fatal. The microbial distribution pattern and AMR profiles overlapped with other European studies. Because susceptibility patterns are rapidly changing worldwide, with the emerging threat of Methicillin-resistant S. aureus and extended-spectrum beta-lactamases producers, infection prevention and control practices and AMS strategies require continuous optimization to limit selection pressure and AMR escalation.

Continuous Fentanyl Infusion in Newborns with Hypoxic-Ischemic Encephalopathy Treated with Therapeutic Hypothermia: Background, Aims, and Study Protocol for Time-Concentration Profiles.

Therapeutic hypothermia (TH) is the standard of care for newborns with moderate to severe hypoxic-ischemic encephalopathy (HIE). Discomfort and pain during treatment are common and may affect the therapeutic efficacy of TH. Opioid sedation and analgesia (SA) are generally used in clinical practice, and fentanyl is one of the most frequently administered drugs. However, although fentanyl's pharmacokinetics (PKs) may be altered by hypothermic treatment, the PK behavior of this opioid drug in cooled newborns with HIE has been poorly investigated. The aim of this phase 1 study protocol (Trial ID: FentanylTH; EUDRACT number: 2020-000836-23) is to evaluate the fentanyl time-concentration profiles of full-term newborns with HIE who have been treated with TH. Newborns undergoing TH receive a standard fentanyl regimen (2 mcg/Kg of fentanyl as a loading dose, followed by a continuous infusion-1 mcg/kg/h-during the 72 h of TH and subsequent rewarming). Fentanyl plasma concentrations before bolus administration, at the end of the loading dose, and 24-48-72-96 h after infusion are measured. The median, maximum, and minimum plasma concentrations, together with drug clearance, are determined. This study will explore the fentanyl time-concentration profiles of cooled, full-term newborns with HIE, thereby helping to optimize the fentanyl SA dosing regimen during TH.

Modeling the Impact of Excipients Selection on Nitrosamine Formation towards Risk Mitigation.

Risk control for nitrosamine impurities in drug products is currently a major challenge in the industry. Nitrosamines can form during drug product manufacturing and storage through the reaction of nitrites with amine-containing APIs or impurities. The level of nitrites in excipients and the rate of reaction often control the build-up of nitrosamine. Although the variability in nitrite levels across excipient types and suppliers is well recognized, the impact of excipient selection on the level of nitrosamine formed has not been systematically studied. This gap of knowledge is addressed in the current work. We present theoretical case studies of formulations where microcrystalline cellulose (MCC), or lactose supplier, or superdisintegrant type are changed in pursuit of lower levels of nitrite. The impact of the average, maximum, and minimum levels of nitrites in each excipient on nitrosamine formation in the dosage form is calculated. The input data for this calculation are the formulation composition, nitrosamine molecular weight (MW), percentage of conversion, and nitrite levels per excipient. The percentage of conversion (based on the formulation and manufacturing variables) and nitrite levels were taken from the recent literature. We show that changing the supplier of a single excipient, or of the three most critical excipients, can reduce nitrosamine formation by up to -59% and -89%, respectively. We also show that high-risk formulations, e.g., high MW nitrosamines, high dosage weights, and high percentages of conversion (e.g., wet granulation), can often be de-risked below regulatory acceptable daily intake via careful excipient selection. Finally, we provide an open-access tool that enables users to calculate the theoretical formation of nitrosamines in their specific formulations. This calculation template can be used for (i) the preliminary screening of the risk of nitrosamine formation in drug products and (ii) the preliminary assessment of the impact of excipient selection for risk mitigation.

The Audiological Follow-Up of Children with Symptomatic Congenital Cytomegalovirus Infection: An Experience in Two Italian Centers.

BACKGROUND: Congenital cytomegalovirus (cCMV) infection is the leading cause of non-hereditary sensorineural hearing loss in children. While about 10% of children reportedly display symptoms at birth, 85-90% of cCMV infection cases are asymptomatic. However, 10-15% of these asymptomatic infants may later develop hearing, visual, or neurodevelopmental impairments. This study aimed to evaluate the impact of cCMV infection on newborns' hearing function with a particular emphasis on progressive and late-onset cases. METHODS: This study is a retrospective chart analysis with longitudinal character and was conducted in two Italian centers: Center 1 (from 1 November 2007 to 31 December 2021) and Center 2 (from 1 January 2012 to 31 December 2021). Data collected included newborn hearing screening results, characterization of hearing loss (unilateral/bilateral, degree of impairment), and audiological follow-up. RESULTS: The cohort consisted of 103 children (42% males, 58% females). In total, 28 children presented with hearing impairment; 71.4% (20 out of 28) of the cases of hearing loss were severe/profound, with 35.7% of the cases due to unilateral hearing loss. Out of twenty-eight, six experienced progression of hearing loss and four had late-onset hearing loss. CONCLUSIONS: In the absence of universal cCMV screening, hearing screening at birth for cCMV remains a critical factor for early diagnosis. A significant percentage of children affected by cCMV with normal audiological evaluations at birth is easily lost to follow-up. Close collaboration between neonatologists, pediatricians, and audiological services is fundamental to ensure timely diagnosis and treatment of cCMV-related hearing loss.

Lumbar Puncture and Meningitis in Infants with Proven Early- or Late-Onset Sepsis: An Italian Prospective Multicenter Observational Study.

Background: To evaluate the rates of lumbar puncture (LP) in infants with culture-proven sepsis. Study design: We prospectively enrolled 400 infants with early- or late-onset sepsis due to Group B streptococcus (GBS) or Eschericha coli, diagnosed within 90 days of life. Rates of LP and potential variables associated with LP performance were evaluated. Moreover, cerebrospinal fluid (CSF) characteristics and results of the molecular analysis were investigated. Results: LP was performed in 228/400 (57.0%) infants; 123/228 LPs (53.9%) were performed after antibiotic initiation, hampering the ability to identify the pathogen in the CSF culture. However, polymerase chain reaction increased the probability of positive results of CSF analysis compared to microbiological culture (28/79, 35.4% vs. 14/79, 17.7%, p = 0.001). Severe clinical presentation and GBS infection were associated with higher LP rates. The rate of meningitis was 28.5% (65/228). Conclusions: Rates of LP are low in culture-proven neonatal sepsis and antibiotics are frequently given before LP is carried out. Thus meningitis may be underestimated, and the chances of giving an effective therapy to the newborn are reduced. LP should be performed before the start of antibiotics when there is a clinical suspicion of infection.

Antibiotic Prophylaxis for the Prevention of Urinary Tract Infections in Children: Guideline and Recommendations from the Emilia-Romagna Pediatric Urinary Tract Infections (UTI-Ped-ER) Study Group.

Background: Urinary tract infection (UTI) represents one of the most common infectious diseases and a major cause of antibiotic prescription in children. To prevent recurrent infections and long-term complications, low-dose continuous antibiotic prophylaxis (CAP) has been used. However, the efficacy of CAP is controversial. The aim of this document was to develop updated guidelines on the efficacy and safety of CAP to prevent pediatric UTIs. Methods: A panel of experts on pediatric infectious diseases, pediatric nephrology, pediatric urology, and primary care was asked clinical questions concerning the role of CAP in preventing UTIs in children. Overall, 15 clinical questions were addressed, and the search strategy included accessing electronic databases and a manual search of gray literature published in the last 25 years. After data extraction and narrative synthesis of results, recommendations were developed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) methodology. Results: The use of CAP is not recommended in children with a previous UTI, with recurrent UTIs, with vesicoureteral reflux (VUR) of any grade, with isolated hydronephrosis, and with neurogenic bladder. CAP is suggested in children with significant obstructive uropathies until surgical correction. Close surveillance based on early diagnosis of UTI episodes and prompt antibiotic therapy is proposed for conditions in which CAP is not recommended. Conclusions: Our systematic review shows that CAP plays a limited role in preventing recurrences of UTI in children and has no effect on its complications. On the other hand, the emergence of new antimicrobial resistances is a proven risk.

Exposure to Prolonged Rupture of Membranes at Term Increases the Risk for Ventilatory Support in Uninfected Neonates.

OBJECTIVE: The effects of prolonged rupture of membranes (ROMs) on perinatal outcomes are still unclear, and it remains controversial for the management of those labors. This study aims to evaluate how the exposure of pregnant women to a prolonged ROM (≥ 24 hours) affects maternal and neonatal outcomes. STUDY DESIGN: This retrospective cohort study included singleton pregnant women at term delivering between January 2019 and March 2020 in a tertiary hospital. All relevant sociodemographic, pregnancy, and perinatal variables (maternal age, prepregnancy body mass index, labor, and delivery outcomes) were collected anonymously. Data were compared between the "ROM < 24 hours" and "ROM ≥ 24 hours" study groups. RESULTS: A total of 2,689 dyads were included in the study and divided according to their ROM-delivery time: ROM <24 hours (2,369 women, 88.1%), and ROM ≥ 24 hours (320 women, 11.9%). Maternal baseline characteristics were comparable except for the rate of nulliparous women, which was significantly higher among patients with ROM ≥ 24 hours. No significant differences were found regarding infectious neonatal outcomes. However, mechanical ventilation and continuous positive airway pressure were more common among neonates born after ROM ≥ 24 hours. The greater likelihood of neonatal respiratory distress was also confirmed among infants born to Group-B Streptococcus-negative women with ROM ≥ 24 hours (15 out of 267 neonates, 5.6% vs. 52 out of 1,529 with ROM < 24 hours, 3.4%, p = 0.04). CONCLUSION: According to the actual expectant policy, prolonged ROM is associated with an increased risk of respiratory support in noninfected neonates. Further investigations are required to explain such an association. KEY POINTS: · The management of women with prolonged rupture of membranes is controversial.. · The exposure of pregnant women to a prolonged rupture of membranes affects neonatal outcomes.. · Prolonged rupture of membranes is associated with an increased risk of respiratory support, in group-B Streptococcus-negative neonates..