Objectives: To standardize the diagnosis of patent ductus arteriosus (PDA) and report its association with adverse neonatal outcomes in very low birth weight infants (VLBW, birth weight < 1500 g). Study design: A multicenter prospective observational study was conducted in Emilia Romagna from March 2018 to October 2019. The association between ultrasound grading of PDA and adverse neonatal outcomes was evaluated after correction for gestational age. A diagnosis of hemodynamically significant PDA (hsPDA) was established when the PDA diameter was ≥ 1.6 mm at the pulmonary end with growing or pulsatile flow pattern, and at least 2 of 3 indexes of pulmonary overcirculation and/or systemic hypoperfusion were present. Results: 218 VLBW infants were included. Among infants treated for PDA closure in the first postnatal week, up to 40% did not have hsPDA on ultrasound, but experienced clinical worsening. The risk of death was 15 times higher among neonates with non-hemodynamically significant PDA (non-hsPDA) compared to neonates with no PDA. In contrast, the risk of death was similar between neonates with hsPDA and neonates with no PDA. The occurrence of BPD was 6-fold higher among neonates with hsPDA, with no apparent beneficial role of early treatment for PDA closure. The risk of IVH (grade ≥ 3) and ROP (grade ≥ 3) increased by 8.7-fold and 18-fold, respectively, when both systemic hypoperfusion and pulmonary overcirculation were present in hsPDA. Conclusions: The increased risk of mortality in neonates with non-hsPDA underscores the potential inadequacy of criteria for defining hsPDA within the first 3 postnatal days (as they may be adversely affected by other clinically severe factors, i.e. persistent pulmonary hypertension and mechanical ventilation). Parameters such as length, diameter, and morphology may serve as more suitable ultrasound indicators during this period, to be combined with clinical data for individualized management. Additionally, BPD, IVH (grade ≥ 3) and ROP (grade ≥ 3) are associated with hsPDA. The existence of an optimal timeframe for closing PDA to minimize these adverse neonatal outcomes remains uncertain.

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.

Background: Improvements in perinatal care have substantially decreased mortality rates among preterm infants, yet their neurodevelopmental outcomes and quality of life persist as a pertinent public health concern. Family-centered care has emerged as a holistic philosophy that promotes effective alliances among patients, families, and healthcare providers to improve the quality of care. Aims: This longitudinal prospective study aims to evaluate the neurodevelopmental outcomes and brain MRI findings in a cohort of preterm newborns admitted to a neonatal intensive care unit (NICU) adopting a family-centered care model. Methods: Very low birth weight (VLBW) infants admitted to the NICU of Modena between 2015 and 2020 were enrolled. Infants who underwent conventional brain magnetic resonance imaging (MRI) at term-equivalent age were included. Neurodevelopmental follow-up was performed until the age of 24 months by a multidisciplinary team using the Amiel-Tison neurological assessment and the Griffiths Mental Developmental Scales (GMDS-R). Neurodevelopmental outcomes were classified as major sequelae (cerebral palsy, DQ ≤ 70, severe sensory impairment), minor sequelae (minor neurological signs such as clumsiness or DQ between 71 and 85), and normal outcomes (no neurological signs and DQ > 85). Risk factors for severe outcomes were assessed. Results: In total, 49 of the 356 infants (13.8%) died before hospital discharge, and 2 were excluded because of congenital disorders. Of the remaining 305 infants, 222 (72.8%) completed the 24 month follow-up and were included in the study. Neurodevelopmental outcomes were classified as normal (n = 173, 77.9%), minor (n = 34, 15.3%), and major sequelae (n = 15, 6.8%). Among 221 infants undergoing brain MRI, 76 (34.4%) had major lesions (intraventricular hemorrhage, hemorrhagic parenchymal infarction, periventricular leukomalacia, and large cerebellar hemorrhage). In the multivariate regression model, the retinopathy of prematurity (OR 1.8; p value 0.016) and periventricular–intraventricular hemorrhage (OR 5.6; p value < 0.004) were associated with major sequelae. Conclusions: We reported low rates of severe neurodevelopmental outcomes in VLBW infants born in an Italian NICU with FCC. Identifying the risk factors for severe outcomes can assist in tailoring and optimizing early interventions on an individual basis, both within the NICU and after discharge.

The effectiveness of “inadequate” intrapartum antibiotic prophylaxis (IAP administered < 4 h prior to delivery) in preventing early-onset sepsis (EOS) is debated. Italian prospective surveillance cohort data (2003–2022) were used to study the type and duration of IAP according to the timing of symptoms onset of group B streptococcus (GBS) and E. coli culture-confirmed EOS cases. IAP was defined “active” when the pathogen yielded in cultures was susceptible. We identified 263 EOS cases (GBS = 191; E. coli = 72). Among GBS EOS, 25% had received IAP (always active when beta-lactams were administered). Most IAP-exposed neonates with GBS were symptomatic at birth (67%) or remained asymptomatic (25%), regardless of IAP duration. Among E. coli EOS, 60% were IAP-exposed. However, IAP was active in only 8% of cases, and these newborns remained asymptomatic or presented with symptoms prior to 6 h of life. In contrast, most newborns exposed to an “inactive” IAP (52%) developed symptoms from 1 to >48 h of life. The key element to define IAP “adequate” seems the pathogen’s antimicrobial susceptibility rather than its duration. Newborns exposed to an active antimicrobial (as frequently occurs with GBS infections), who remain asymptomatic in the first 6 h of life, are likely uninfected. Because E. coli isolates are often unsusceptible to beta-lactam antibiotics, IAP-exposed neonates frequently develop symptoms of EOS after birth, up to 48 h of life and beyond.

Sudden unexpected postnatal collapse (SUPC) is a rare event, potentially associated with catastrophic consequences. Since the beginning of the 2000s, therapeutic hypothermia (TH) has been proposed as a treatment for asphyxiated neonates after SUPC. However, only a few studies have reported the outcome of SUPC after TH. The current study presents the long-term neurodevelopmental outcome of four cases of SUPC treated with TH in a single Italian center. Furthermore, we reviewed the previous literature concerning 49 cases of SUPC treated with TH. Among 53 total cases (of whom four occurred in our center), 15 (28.3%) died before discharge from the NICU. A neurodevelopmental follow-up was available only for 21 (55.3%) out of the 38 surviving cases, and seven infants developed neurodevelopmental sequelae. TH should be considered in neonates with asphyxia after SUPC. However, SUPC is a rare event, and there is a lack of comparative clinical data to establish the risk/benefit of TH after SUPC with different degrees of asphyxia. Analysis of large cohorts of newborns with SUPC, whether treated with TH or untreated, are needed in order to better identify infants who should undergo TH.

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.