Cerebral and systemic near infrared spectroscopy patterns in preterm infants treated by caffeine.

AIM: To investigate the effects of caffeine loading/maintenance administration on near-infrared spectroscopy cerebral, kidney and splanchnic patterns in preterm infants. METHODS: We conducted a multicentre case-control prospective study in 40 preterm infants (gestational age 29 ± 2 weeks) where each case acted as its own control. A caffeine loading dose of 20 mg/kg and a maintenance dose of 5 mg/kg after 24 h were administered intravenously. Near infrared spectroscopy monitoring parameters were monitored 30 min before, 30 min during and 180 min after caffeine therapy administration. RESULTS: A significant increase (p < 0.05) in splanchnic regional oxygenation and tissue function and a decrease (p < 0.05) in cerebral tissue function after loading dose was shown. A preferential hemodynamic redistribution from cerebral to splanchnic bloodstream was also observed. After caffeine maintenance dose regional oxygenation did not change in the monitored districts, while tissue function increased in kidney and splanchnic bloodstream. CONCLUSION: Different caffeine administration modalities affect cerebral/systemic oxygenation status, tissue function and hemodynamic pattern in preterm infants. Future studies correlating near infrared spectroscopy parameters and caffeine therapy are needed to determine the short/long-term effect of caffeine in preterm infants.

Anti-rubella seroprevalence assessment in an adult sample population in Italy.

Introduction: Despite global immunization efforts, rubella remains a public health concern, particularly in high- and middle-income countries. This study focused on rubella seroprevalence in the province of Florence, Italy, aiming to identify susceptibility clusters, especially among women in their childbearing age. Methods: A cross-sectional study was conducted between April 2018 and December 2019, enrolling 430 adult subjects (age over 18 years). Serum samples were collected, and anti-rubella antibodies were quantified using the ELISA test. Data were analyzed descriptively and compared by sex, nationality, and age groups using statistical tests. Results: The overall rubella seroprevalence was high (92.3%), with no significant differences between genders or nationalities. Among childbearing-age females (18-49 years), the highest seroprevalence was observed in the 30-39 age group (94.1%). However, susceptibility clusters exceeding the 5% threshold set by WHO were identified, especially in females aged 40-49 years (7.0%). Conclusions: Despite high overall seroprevalence, the study identified pockets of susceptibility, even in childbearing age women. Continuous monitoring, targeted immunization strategies, and public health interventions are recommended to maintain rubella elimination, emphasizing the importance of sustained vaccination efforts to protect vulnerable populations.

Impact of SARS-CoV2 infection on mortality and hospitalization in nursing home residents during the "Omicron era".

BACKGROUND: Widespread vaccination and emergence of less aggressive SARS-CoV2 variants may have blunted the unfavourable outcomes of COVID-19 in nursing home (NH) residents. We analysed the course of COVID-19 epidemic in NHs of Florence, Italy, during the "Omicron era" and investigated the independent effect of SARS-CoV2 infection on death and hospitalization risk. METHODS: Weekly SARS-CoV2 infection rates between November 2021 and March 2022 were calculated. Detailed clinical data were collected in a sample of NHs. RESULTS: Among 2044 residents, 667 SARS-CoV2 cases were confirmed. SARS-CoV2 incidence sharply increased during the Omicron era. Mortality rates did not differ between SARS-CoV2-positive (6.9%) and SARS-CoV2-negative residents (7.3%, p = 0.71). Chronic obstructive pulmonary disease and poor functional status, but not SARS-CoV2 infection independently predicted death and hospitalization. CONCLUSIONS: Despite that SARS-CoV2 incidence increased during the Omicron era, SARS-CoV2 infection was not a significant predictor of hospitalization and death in the NH setting.

Perinatal presepsin assessment: a new sepsis diagnostic tool?

Perinatal sepsis constitutes a medical emergency and is still one of the major causes of mortality and morbidity. The possibility of an early diagnosis of sepsis is still debated and controversial. In particular, clinical symptoms can be hidden by the association of sepsis with other perinatal diseases and/or by therapeutic strategies performed. In this context, there is evidence that the accuracy of standard of care diagnostic parameters (i.e. blood culture, C-reactive protein, procalcitonin) can be biased by additional confounding factors (gestational age, birth-weight, acute-chronic hypoxia). Therefore, the inclusion in clinical daily practice of new biomarkers of sepsis is of utmost importance. Of a panel of biomarkers, Presepsin (P-SEP) plays an important role in the development and response of the immune system and as an early marker of sepsis both in adult and pediatric patients. Therefore, in the present review we aim to offer an overview of the role of P-SEP in the early detection of perinatal sepsis as a trustworthy marker according to actual statements of official international institutions. Future perspectives regard the possibility of a longitudinal non-invasive biological fluids P-SEP assessment thus limiting the sample stress in high risk newborns.

A machine learning approach for predicting high risk hospitalized patients with COVID-19 SARS-Cov-2.

BACKGROUND: This study aimed to explore whether explainable Artificial Intelligence methods can be fruitfully used to improve the medical management of patients suffering from complex diseases, and in particular to predict the death risk in hospitalized patients with SARS-Cov-2 based on admission data. METHODS: This work is based on an observational ambispective study that comprised patients older than 18 years with a positive SARS-Cov-2 diagnosis that were admitted to the hospital Azienda Ospedaliera "SS Antonio e Biagio e Cesare Arrigo", Alessandria, Italy from February, 24 2020 to May, 31 2021, and that completed the disease treatment inside this structure. The patients'medical history, demographic, epidemiologic and clinical data were collected from the electronic medical records system and paper based medical records, entered and managed by the Clinical Study Coordinators using the REDCap electronic data capture tool patient chart. The dataset was used to train and to evaluate predictive ML models. RESULTS: We overall trained, analysed and evaluated 19 predictive models (both supervised and unsupervised) on data from 824 patients described by 43 features. We focused our attention on models that provide an explanation that is understandable and directly usable by domain experts, and compared the results against other classical machine learning approaches. Among the former, JRIP showed the best performance in 10-fold cross validation, and the best average performance in a further validation test using a different patient dataset from the beginning of the third COVID-19 wave. Moreover, JRIP showed comparable performances with other approaches that do not provide a clear and/or understandable explanation. CONCLUSIONS: The ML supervised models showed to correctly discern between low-risk and high-risk patients, even when the medical disease context is complex and the list of features is limited to information available at admission time. Furthermore, the models demonstrated to reasonably perform on a dataset from the third COVID-19 wave that was not used in the training phase. Overall, these results are remarkable: (i) from a medical point of view, these models evaluate good predictions despite the possible differences entitled with different care protocols and the possible influence of other viral variants (i.e. delta variant); (ii) from the organizational point of view, they could be used to optimize the management of health-care path at the admission time.

Innovation in organizational model of the Health Professions Research Unit in an hospital.

BACKGROUND: The organizational model of the Health Professions Research Unit is unique in Italy. It is a centralized sector within of the Intercompany Department of Integrated Activities Research Innovation, afferent to the Complex Infrastructure Research Training Innovation of the SS Antonio e Biagio e Cesare Arrigo Hospital of Alessandria. It emerges from a need to promote, structure and broaden research in the clinical-healthcare field with the primary aim of improving patient care. Its internal organization is represented by a Coordinator Director (PhD) with a function assignment and three research nurses. AIM: Increase scientific production, promote partnerships with scientific communities, encourage the development of professional healthcare networks. METHODS: The definition of specific result indicators on which to estimate the trend of annual activities. The institution of a company network of Department and Structure and the establishment of collaborations with Institutions and Universities. RESULTS: From 2019 to 2021, 11 departmental and 67 Structure referents have been identified; 13 collaborations with National and 3 International Institutions have been activated (42% Increase), 23 clinical trials have been activated (92% increase), 7 articles on impacted journals have been published (100% increase) and 7 are under publication, 27 grey literature papers have been produced (47% increase)and have participated to 5 sponsored calls (100% increase) CONCLUSIONS: The new organizational model established has achieved the objectives set, proving reproducibility in other national and international realities. NURSING IMPLICATIONS: The model could increase at national and international level the scientific production related to the Healthcare professions with important benefits on the clinical outcomes of patients.

Sensitivity to asbestos is increased in patients with mesothelioma and pathogenic germline variants in BAP1 or other DNA repair genes.

Pathogenic germline variants in the BAP1 tumor suppressor gene can cause a cancer syndrome called BAP1 tumor predisposition syndrome (BAP1-TPDS), which is characterized by predisposition to mesothelioma, melanoma, renal cell carcinoma, basal cell carcinoma, and other tumors. Other genes that may predispose to mesothelioma are CDKN2A and DNA repair genes. Asbestos exposure has often been reported in patients with malignant pleural mesothelioma (MPM) and germline variants in BAP1, but this exposure has never been quantified. We aimed to search for germline variants in BAP1 among 25 new Italian probands with suspected BAP1-TPDS, summarize the prevalence of these variants in 39 Italian patients with familial MPM and other tumors recruited over a 5-year period, and compare cumulative asbestos exposure in 14 patients with MPM and pathogenic germline variants in BAP1, CDKN2A, or DNA repair genes with that of 67 patients without germline variants in 94 cancer-predisposing genes. We report here a new pathogenic germline variant in BAP1: c.783 + 2 T > C. The prevalence of pathogenic germline variants in BAP1 was 7.7% among patients with familial MPM (3/39). Patients with pathogenic germline variants in BAP1, CDKN2A, or DNA repair genes showed lower cumulative asbestos exposure than patients without germline variants in 94 cancer-predisposing genes (P = .00002). This suggests an interaction between genetic risk factors and asbestos in the development of mesothelioma.

A functional assay for the clinical annotation of genetic variants of uncertain significance in Diamond-Blackfan anemia.

Diamond-Blackfan anemia (DBA) is a rare genetic hypoplasia of erythroid progenitors characterized by mild to severe anemia and associated with congenital malformations. Clinical manifestations in DBA patients are quite variable and genetic testing has become a critical factor in establishing a diagnosis of DBA. The majority of DBA cases are due to heterozygous loss-of-function mutations in ribosomal protein (RP) genes. Causative mutations are fairly straightforward to identify in the case of large deletions and frameshift and nonsense mutations found early in a protein coding sequence, but diagnosis becomes more challenging in the case of missense mutations and small in-frame indels. Our group recently characterized the phenotype of lymphoblastoid cell lines established from DBA patients with pathogenic lesions in RPS19 and observed that defective pre-rRNA processing, a hallmark of the disease, was rescued by lentiviral vectors expressing wild-type RPS19. Here, we use this complementation assay to determine whether RPS19 variants of unknown significance are capable of rescuing pre-rRNA processing defects in these lymphoblastoid cells as a means of assessing the effects of these sequence changes on the function of the RPS19 protein. This approach will be useful in differentiating pathogenic mutations from benign polymorphisms in identifying causative genes in DBA patients.

Inference on germline BAP1 mutations and asbestos exposure from the analysis of familial and sporadic mesothelioma in a high-risk area.

Inherited loss-of-function mutations in the BAP1 oncosuppressor gene are responsible for an inherited syndrome with predisposition to malignant mesothelioma (MM), uveal and keratinocytic melanoma, and other malignancies. Germline mutations that were inherited in an autosomal dominant fashion were identified in nine families with multiplex MM cases and 25 families with multiple melanoma, renal cell carcinoma, and other tumors. Germline mutations were also identified in sporadic MM cases, suggesting that germline mutations in BAP1 occur frequently. In this article, we report the analysis of BAP1 in five multiplex MM families and in 103 sporadic cases of MM. One family carried a new truncating germline mutation. Using immunohistochemistry, we show that BAP1 is not expressed in tumor tissue, which is in accordance with Knudson's two hits hypothesis. Interestingly, whereas the three individuals who were possibly exposed to asbestos developed MM, the individual who was not exposed developed a different tumor type, that is, mucoepidermoid carcinoma. This finding suggests that the type of carcinogen exposure may be important for the cancer type that is developed by mutation carriers. On the contrary, the other families or the 103 sporadic patients did not show germline mutations in BAP1. Our data show that BAP1 mutations are very rare in patients with sporadic MM, and we report a new BAP1 mutation, extend the cancer types associated with these mutations, and suggest the existence of other yet unknown genes in the pathogenesis of familial MM.

Gene-asbestos interaction in malignant pleural mesothelioma susceptibility.

Asbestos exposure is the main risk factor for malignant pleural mesothelioma (MPM), a rare aggressive tumor. Nevertheless, on average less than 10% of subjects highly exposed to asbestos develop MPM, suggesting the possible involvement of other risk factors. To identify the genetic factors that may modulate the risk of MPM, we conducted a gene-environment interaction analysis including asbestos exposure and 15 single nucleotide polymorphisms (SNPs) previously identified through a genome-wide association study on Italian subjects. In the present study, we assessed gene-asbestos interaction on MPM risk using relative excess risk due to interaction and synergy index for additive interaction and V index for multiplicative interaction. Generalized multifactor dimensionality reduction (GMDR) analyses were also performed. Positive deviation from additivity was found for six SNPs (rs1508805, rs2501618, rs4701085, rs4290865, rs10519201, rs763271), and four of them (rs1508805, rs2501618, rs4701085, rs10519201) deviated also from multiplicative models. However, after Bonferroni correction, deviation from multiplicative model was still significant for rs1508805 and rs4701085 only. GMDR analysis showed a strong MPM risk due to asbestos exposure and suggested a possible synergistic effect between asbestos exposure and rs1508805, rs2501618 and rs5756444. Our results suggested that gene-asbestos interaction may play an additional role on MPM susceptibility, given that asbestos exposure appears as the main risk factor.

Cervical thymic cyst in childhood: a case report.

Cervical thymic cysts are rare cervical masses which usually present in the first decade of life accounting for 0.3% - 1% of all congenital neck masses. Due to its rarity thymic cysts are seldom included in the differential diagnosis of cystic cervical mass and are often mistaken for more common conditions such as branchial cleft cyst or cystic hygroma. Herein we present a case of a 6-year-old girl with a right lateral cervical cystic mass with multiple septae extended from mandibular angle along the neurovascular bundle of the neck which revealed to be a thymic cyst at histopathology.

The clinical trial activation process: a case study of an Italian public hospital.

BACKGROUND/AIMS: In order to make the centers more attractive to trial sponsors, in recent years, some research institutions around the world have pursued projects to reorganize the pathway of trial activation, developing new organizational models to improve the activation process and reduce its times. This study aims at analyzing and reorganizing the start-up phase of trials conducted at the Research and Innovation Department (DAIRI) of the Public Hospital of Alessandria (Italy). METHODS: A project was carried out to reorganize the trial authorization process at DAIRI by involving the three facilities responsible for this pathway: clinical trial center (CTC), ethics committee secretariat (ESC), and administrative coordination (AC). Lean Thinking methodology was used with the A3 report tool, and the analysis was carried out by monitoring specific key performance indicators, derived from variables representing highlights of the trials' activation pathway. The project involved phases of analysis, implementation of identified countermeasures, and monitoring of timelines in eight 4-month periods. The overall mean and median values of studies activation times were calculated as well as the average times for each facility involved in the process. RESULTS: In this study, 298 studies both sponsored by research associations and industry with both observational and interventional study design were monitored. The mean trial activation time was reduced from 218 days before the project to 56 days in the last period monitored. From the first to the last monitoring period, each facility involved achieved at least a halving of the average time required to carry out its activities in the clinical trials' activation pathway (CTC: 55 days vs 23, ECS: 25 days vs 8, AC 29 days vs 10). Average activation time for studies with agreement remains longer than those without agreement (100 days vs. 46). CONCLUSIONS: The reorganization project emphasized the importance of having clinical and administrative staff specifically trained on the trial activation process. This reorganization led to the development of a standard operating procedure and a tool to monitor the time (KPIs of the process) that can also be implemented in other clinical centers.

HER2/neu as a potential target for immunotherapy in gynecologic carcinosarcomas.

Carcinosarcomas of the female genital tract are rare tumors with an aggressive clinical behavior. Trastuzumab, a humanized monoclonal antibody, acts by binding to HER2/neu extracellular domain and exhibits therapeutic efficacy in HER2/neu-overexpressing cancers. Two uterine carcinosarcomas (UMMT-ARK-1, UMMT-ARK-2) and 2 ovarian carcinosarcomas (OMMT-ARK-1, OMMT-ARK-2) were established as primary tumor cell lines in vitro and evaluated for HER2/neu expression by immunohistochemistry, fluorescent in situ hybridization analysis, quantitative real-time polymerase chain reaction, and for membrane-bound complement regulatory proteins CD46, CD55, and CD59 by flow cytometry. Sensitivity to trastuzumab-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity was studied in 5-hr chromium release assays. HER2/neu expression was demonstrated in OMMT-ARK-1 and OMMT-ARK-2. OMMT-ARK-2 demonstrated an amplification of the c-erbB2 gene by fluorescent in situ hybridization analysis and a high sensitivity to ADCC (mean killing, 45.6%; range, 32.3%-72.6%). A lower level of killing was detected against the fluorescent in situ hybridization analysis-negative OMMT-ARK-1 cell line (mean, 26.5%; range, 21.0%-31.8%). CD46, CD55, and CD59 membrane-bound complement regulatory proteins were expressed at high levels in all primary mixed müllerian tumor cell lines, and all these tumors were found to be highly resistant to complement-dependent cytotoxicity with or without trastuzumab. Addition of untreated and heat-inactivated plasma did not significantly decrease ADCC against OMMT-ARK-2 cell line, suggesting that while the cell line is highly resistant to complement, irrelevant IgG does not significantly alter the ability of trastuzumab to mediate ADCC. Our results suggest that HER2/neu may represent a novel target for the immunotherapy of a subset of human carcinosarcomas refractory to salvage chemotherapy.

[The organization and staff of a centralized Clinical Trial Center: the Alessandria model.] / L'organizzazione e il personale di un Clinical Trial Center centralizzato: il modello Alessandria.

The case study refers to the Clinical Trial Center (CTC) of the Public Hospital "SS. Antonio e Biagio and Cesare Arrigo" (AO AL) and the Local Health Authority of Alessandria (ASL AL), to which Clinical Research Coordinators (CRCs) and Clinical Research Nurses (CRNs) belong, unique in the regional panorama and a rarity into a public health organization not recognized as Scientific Institute for Research, Hospitalization and Healthcare (IRCCS).

Long-Term Survival among Patients Hospitalized for COVID-19 during the First Three Epidemic Waves: An Observational Study in a Northern Italy Hospital.

The mortality rate of hospitalized COVID-19 patients differed strongly between the first three pandemic waves. Nevertheless, their long-term survival has been poorly assessed. The aim of this study was to compare the clinical characteristics and mortality rates of 825 patients with coronavirus disease 2019 (COVID-19) infection who were hospitalized at the Alessandria hub hospital, in Northern Italy, during the first fifty days of the first three pandemic waves. Each subject was followed in terms of vital status for six months from the date of hospital admission or until deceased. Patients admitted during the three waves differed in age (p = 0.03), disease severity (p < 0.0001), Charlson comorbidity index (p = 0.0002), oxygen therapy (p = 0.002), and invasive mechanical ventilation (p < 0.0001). By the end of follow-up, 309 deaths (38.7%) were observed, of which 186 occurred during hub hospitalization (22.5%). Deaths were distributed differently among the waves (p < 0.0001), resulting in being higher amongst those subjects admitted during the first wave. The COVID-19 infection was reported as the main cause of death and patients with a higher mortality risk were those aged ≥65 years [adjusted HR = 3.40 (95% CI 2.20-5.24)], with a higher disease severity [adjusted HR = 1.87 (95%CI 1.43-2.45)], and those requiring oxygen therapy [adjusted HR = 2.30 (95%CI 1.61-3.30)]. In conclusion, COVID-19 patients admitted to our hub hospital during the second and the third waves had a lower risk of long-term mortality than those admitted during the first. Older age, more severe disease, and the need for oxygen therapy were among the strongest risk factors for poor prognosis.

Intragastric prepyloric enteral nutrition, bolus vs continuous in the adult patient: A systematic review and meta-analysis.

Bolus and continuous nutrition are commonly used enteral nutrition (EN) administration methodologies. Currently, there is insufficient evidence to establish which is the most effective method for reducing gastrointestinal complications in adult patients. The aim of this review is to evaluate the impact of bolus/intermittent EN compared with continuous EN for the following outcomes: diarrhea, constipation, emesis/vomiting, gastric residual volume, aspiration, and glycemic control in adult patients receiving intragastric prepyloric EN in the hospital setting. Bibliographical research was performed on the following databases: PubMed, Embase, CINAHL, and the Cochrane Central Register of Controlled Trials. The review included all randomized and nonrandomized controlled trials of patients aged ≥18 years with preserved gastrointestinal function. Meta-analysis was performed by Review Manager V.5.3. Seven studies including 551 patients were included in the meta-analysis. Five of these studies reported that the diarrhea rate was higher in the bolus feeding group (risk ratio [RR] = 2.50; 95% CI, 1.17-5.34; P = 0.02), and another five of these studies indicated that the aspiration rate was higher in the continuous feeding group (RR = 0.55; 95% CI, 0.35-0.87; P = 0.01). There were no significant differences for the other outcomes. In conclusion, intermittent EN appears to reduce the incidence of aspiration in the hospital setting; however, it may increase the risk of diarrhea. For future research, we hypothesize the joint use of continuous nutrition until the patient reaches tolerance and then passing to bolus nutrition, thus reducing the incidence of aspiration and enabling a physiological nutrition intake.

Oxidative stress and visual system: a review.

Different types of tissues respond differently to the action of oxidative stress. The visual system is very sensitive to oxidative action due to continuous exposure to light. In consideration of the growing interest of scientific studies towards various compounds endowed with antioxidant and anti-inflammatory properties, we performed a review of the literature focusing on the use of some antioxidant molecules for the treatment of conditions affecting the visual system. In this study, we focused on the ability of two antioxidant agents, the small molecule α-lipoic acid (ALA) and the enzyme superoxide dismutase (SOD), to influence the neurodegenerative physiological processes related to aging and oxidative stress affecting the ocular segment. The literature data report that ALA and SOD can protect against neurodegenerative effects both the optic nerve and retina and, if administered together, they are able to lower the levels of oxidative stress, thus preventing neurodegeneration and reducing the apoptotic process.

Baseline clinical characteristics and prognostic factors in hospitalized COVID-19 patients aged ≤ 65 years: A retrospective observational study.

BACKGROUND: Individual differences in susceptibility to SARS-CoV-2 infection, symptomatology and clinical manifestation of COVID-19 have thus far been observed but little is known about the prognostic factors of young patients. METHODS: A retrospective observational study was conducted on 171 patients aged ≤ 65 years hospitalized in Alessandria's Hospital from 1st March to 30th April 2020 with laboratory confirmed COVID-19. Epidemiological data, symptoms at onset, clinical manifestations, Charlson Comorbidity Index, laboratory parameters, radiological findings and complications were considered. Patients were divided into two groups on the basis of COVID-19 severity. Multivariable logistic regression analysis was used to establish factors associated with the development of a moderate or severe disease. FINDINGS: A total of 171 patients (89 with mild/moderate disease, 82 with severe/critical disease), of which 61% males and a mean age (± SD) of 53.6 (± 9.7) were included. The multivariable logistic model identified age (50-65 vs 18-49; OR = 3.23 CI95% 1.42-7.37), platelet count (per 100 units of increase OR = 0.61 CI95% 0.42-0.89), c-reactive protein (CPR) (per unit of increase OR = 1.12 CI95% 1.06-1.20) as risk factors for severe or critical disease. The multivariable logistic model showed a good discriminating capacity with a C-index value of 0.76. INTERPRETATION: Patients aged ≥ 50 years with low platelet count and high CRP are more likely to develop severe or critical illness. These findings might contribute to improved clinical management.

Neonatal outcomes and risk of neonatal sepsis in an expectantly managed cohort of late preterm prelabor rupture of membranes.

OBJECTIVE: Expectant management in patients with prelabor preterm rupture of membranes between between 340/7 and 36 6/7 weeks (late preterm pPROM or LpPROM) has been shown to decrease the burden of prematurity, when compared to immediate delivery. As the severity of prematurity depends on gestational age (GA) at PROM, and PROM to delivery interval, we first investigated how such variables affect neonatal outcomes (NO). Second, we assessed the risk of neonatal sepsis. STUDY DESIGN: retrospective cohort study on neonatal morbidity among singleton infants born to expectantly managed mothers with LpPROM in five hospitals affiliated with three Italian academic institutions. The primary NO was a composite of neonatal death, non-invasive (cPAP) or invasive (mechanical ventilation) respiratory support, hypoglycemia (< 44 mg/dl needing therapy), newborn sepsis, confirmed seizures, stroke, intraventricular hemorrhage (IVH), basal nuclei anomalies, cardiopulmonary resuscitation, umbilical-cord-blood arterial pH < 7.0 or base excess < -12.5, and prolonged hospitalization (≥ 5 days). Univariate analysis described differences in the population according to GA at delivery. Multivariate logistic regression was then used to investigate the effects of GA at PROM, and PROM to delivery interval on the NO. RESULTS: 258/606 (42.6 %) women with LpPROM were expectantly managed, as they did not deliver within the first 24 h. The median latency duration was 2 (95 %CI 1-3) days, having no effect on neonatal morbidity on multivariate analysis. Multivariate analysis also showed increased risks of adverse NO among PROM at 34 (OR 2.3 95 %CI 1.03-5.1) but not at 35 weeks when compared to 36 weeks, and among women receiving antenatal corticosteroids (OR 3.6 95 %CI 1.3-9.7), while antibiotic treatment showed a non-significant protective effect (OR 0.2 95 %CI 0.04-1.02). Prevalence of neonatal sepsis was 0.8 % (2/258) CONCLUSION: Expectant management of LpPROM should be encouraged especially between 34+0 and 34+6 weeks', when the burden of prematurity is the greatest. Antibiotics may have beneficial effects, while careful consideration should be given to antenatal corticosteroids until future studies specifically address LpPROM.