Immunometabolic approaches to prevent, detect, and treat neonatal sepsis.

The first days of postnatal life are energetically demanding as metabolic functions change dramatically to accommodate drastic environmental and physiologic transitions after birth. It is increasingly appreciated that metabolic pathways are not only crucial for nutrition but also play important roles in regulating inflammation and the host response to infection. Neonatal susceptibility to infection is increased due to a functionally distinct immune response characterized by high reliance on innate immune mechanisms. Interactions between metabolism and the immune response are increasingly recognized, as changes in metabolic pathways drive innate immune cell function and activation and consequently host response to pathogens. Moreover, metabolites, such as acetyl-coenzyme A (acetyl-CoA) and succinate have immunoregulatory properties and serve as cofactors for enzymes involved in epigenetic reprogramming or "training" of innate immune cells after an initial infectious exposure. Highly sensitive metabolomic approaches allow us to define alterations in metabolic signatures as they change during ontogeny and as perturbed by immunization or infection, thereby linking metabolic pathways to immune cell effector functions. Characterizing the ontogeny of immunometabolism will offer new opportunities to prevent, diagnose, and treat neonatal sepsis.

Serum Markers of Necrotizing Enterocolitis: A Systematic Review.

OBJECTIVE: The aim of the study was to systematically review the diagnostic utility of serum biomarkers for the diagnosis of necrotizing enterocolitis (NEC). METHODS: We conducted an electronic and manual search of the available evidence. We included studies reporting data on the diagnostic accuracy of "serum" biomarkers for the diagnosis of NEC, available until January 2016. RESULTS: We selected 22 studies from the 1296 articles retrieved. Only S100 A8/A9 protein and apolipoprotein-CII showed high sensitivity (100% and 96.4%, respectively) and specificity (90% and 95%, respectively) in the studies using Bell stage II NEC as target condition. High sensitivity and specificity were reported for interleukin-10 (100% and 90%), interleukin1-receptor antagonist (100% and 91.7%), intestinal fatty acid-binding protein (100% and 91%) and ischemia-modified albumin (94.7% and 92%), when tested to predict the evolution from definite to advanced NEC. Given the amount of uncertainty, the limited availability of data and heterogeneity among the populations in the different studies, we were unable to perform a meta-analysis. Major concerns about the applicability stemmed from the spectrum of patients enrolled and the inclusion of diseases different from Bell stage ≥2 NEC as target conditions. CONCLUSIONS: We identified only few markers with good diagnostic accuracy and found an overall low quality of the studies on serum NEC biomarkers. In conclusion, data supporting their use are insufficient.

New architectural design of delivery room reduces morbidity in preterm neonates: a prospective cohort study.

BACKGROUND: A multidisciplinary committee composed of a panel of experts, including a member of the American Academy of Pediatrics and American Institute of Architects, has suggested that the delivery room (DR) and the neonatal intensive care units (NICU) room should be directly interconnected. We aimed to investigate the impact of the architectural design of the DR and the NICU on neonatal outcome. METHODS: Two cohorts of preterm neonates born at < 32 weeks of gestational age, consecutively observed during 2 years, were compared prospectively before (Cohort 1: "conventional DR") and after architectural renovation of the DR realized in accordance with specific standards (Cohort 2: "new concept of DR"). In Cohort 1, neonates were initially cared for a conventional resuscitation area, situated in the DR, and then transferred to the NICU, located on a separate floor of the same hospital. In Cohort 2 neonates were assisted at birth directly in the NICU room, which was directly connected to the DR via a pass-through door. The primary outcome of the study was morbidity, defined by the proportion of neonates with at least one complication of prematurity (i.e., late-onset sepsis, patent ductus arteriosus, intraventricular hemorrhage, periventricular leukomalacia, bronchopulmonary dysplasia, retinopathy of prematurity and necrotizing enterocolitis). Secondary outcomes were mortality and duration of hospitalization. Statistical analysis was performed using standard methods by SPSS software. RESULTS: We enrolled 106 neonates (56 in Cohort 1 and 50 in Cohort 2). The main clinical and demographic characteristics of the 2 cohorts were similar. Moderate hypothermia (body temperature ≤ 35.9 °C) was more frequent in Cohort 1 (57%) compared with Cohort 2 (24%, p = 0.001). Morbidity was increased in Cohort 1 (73%) compared with Cohort 2 (44%, p = 0.002). No statistically significant differences in mortality and median duration of hospitalization were observed between the 2 cohorts of the study. CONCLUSIONS: If realized according to the proposed architectural standards, renovation of DR and NICU may represent an opportunity to reduce morbidity in preterm neonates.

Infant mortality in Italy: large geographic and ethnic inequalities.

BACKGROUND: Neonatal and infant mortality rates are among the most significant indicators for assessing a country's healthcare and social development. This study examined the trends in neonatal, post-neonatal, and infant mortality in Italy from 2016 to 2020 and analysed differences between children of Italian and foreign parents based on areas of residence, as well as the leading causes of death. Special attention was given to the analysis of mortality in 2020, the first year of the Covid-19 pandemic, and its comparison with previous years. METHODS: Data from 2016 to 2020 were collected by the Italian National Institute of Statistics and extracted from two national databases, the Causes of Death register and Live births registered in the population register. Neonatal, post-neonatal, and infant mortality rates were calculated using conventional definitions. The main analyses were conducted by comparing Italian citizens to foreigners and contrasting residents of the North with those of the South. Group comparisons were made using mortality rate ratios. The main causes of death were examined, and Poisson log-linear regression models were employed to investigate the relationships between mortality rate ratios for each cause of death and citizenship, place of residence and calendar year. RESULTS: In Italy, in 2020, the neonatal mortality rate was 1.76 deaths per thousand live births and it was 55% higher in foreign children than in Italian children. Foreign children had a higher mortality rate than Italians for almost all significant causes of death. Children born in the South of Italy, both Italian and foreign, had an infant mortality rate about 70% higher than residents in the North. Regions with higher infant mortality were Calabria, Sicily, Campania, and Apulia. In the South, mortality from neonatal respiratory distress and prematurity was higher. In the first months of 2020, between March and June, the first Covid-19 wave, Italy experienced an increase in neonatal and infant mortality compared to the same period in 2016-2019, not directly related to SARS-CoV-19 infection. The primary cause was neonatal respiratory distress. CONCLUSIONS: The neonatal and infant mortality rates indicate the persistence of profound inequalities in Italy between the North and the South and between Italian and foreign children.

Perinatal outcomes among immigrant mothers over two periods in a region of central Italy.

BACKGROUND: The number of immigrants has increased in Italy in the last twenty years (7.2% of the Italian population), as have infants of foreign-born parents, but scanty evidence on perinatal outcomes is available. The aim of this study was to investigate whether infants of foreign-born mothers living in Italy have different odds of adverse perinatal outcomes compared to those of native-born mothers, and if such measures changed over two periods. METHODS: The source of this area-based study was the regional hospital discharge database that records perinatal information on all births in the Lazio region. We analysed 296,739 singleton births born between 1996-1998 and 2006-2008. The exposure variable was the mother's region of birth. We considered five outcomes of perinatal health. We estimated crude and adjusted odds ratios and 95% confidence intervals (CIs) to evaluate the association between mother's region of birth and perinatal outcomes. RESULTS: Perinatal outcomes were worse among infants of immigrant compared to Italian mothers, especially for sub-Saharan and west Africans, with the following crude ORs (in 1996-1998 and 2006-2008 respectively): 1.80 (95%CI:1.44-2.28) and 1.95 (95%CI:1.72-2.21) for very preterm births, and 1.32 (95%CI:1.16-1.50) and 1.32 (95%CI:1.25-1.39) for preterm births; 1.18 (95%CI:0.99-1.40) and 1.17 (95%CI:1.03-1.34) for a low Apgar score; 1.22 (95%CI:1.15-1.31) and 1.24 (95%CI:1.17-1.32) for the presence of respiratory diseases; 1.47 (95%CI:1.30-1.66) and 1.45 (95%CI:1.34-1.57) for the need for special or intensive neonatal care/in-hospital deaths; and 1.03 (95%CI:0.93-1.15) and 1.07 (95%CI:1.00-1.15) for congenital malformations. Overall, time did not affect the odds of outcomes differently between immigrant and Italian mothers and most outcomes improved over time among all infants. None of the risk factors considered confounded the associations. CONCLUSION: Our findings suggest that migrant status is a risk factor for adverse perinatal health. Moreover, they suggest that perinatal outcomes improved over time in some immigrant women. This could be due to a general improvement in immigrants' health in the past decade, or it may indicate successful application of policies that increase accessibility to mother-child health services during the periconception and prenatal periods for legal and illegal immigrant women in Italy.

Pediatric interregional healthcare mobility in Italy.

BACKGROUND: The analysis of interregional healthcare mobility represents one of the main criteria for evaluating Regional Healthcare Systems, both in terms of its economic-financial relevance and the quality and satisfaction of the services provided. The aim of the study is to analyze healthcare mobility and its associated cost in Italy in 2019 for all children ≤ 14 years of age. METHODS: We collected data from the "Rapporto annuale sull'attività di ricovero ospedaliero - Dati SDO 2019" published by the Italian Ministry of Health. These data represent the tool for collecting information relating to all hospitalization services provided in accredited public and private hospitals present throughout the national territory. We collected data for all Italian regions and clustered them in two geographical areas: Center-North regions and South regions (including Sicily and Sardinia). We have analyzed the magnitude of the mobility of children among regions and in particular from the South to the Center-North and the relative cost of this interregional mobility. RESULTS:  The hospitalization rate of children residing in the South regions was higher than  that of children residing in the Center-North regions (13.9% vs 12.3%). Children residing in the South were more frequently treated in other regions than those living in the Center-North (11.9% vs 6.9%). Even considering the high complexity hospitalizations, children living in the South more frequently underwent treatment in other regions (21.3% vs 10.5% of the Center-North). The cost of passive mobility amounts to € 103.9 million for the South regions (15.1% of the total hospitalizations' expenditure) and the 87.1% of this cost refers to the mobility to the hospitals of Center-North. The cost of healthcare migration from South regions to other South regions was much lower (12.9%, equal to € 13.4 million). CONCLUSIONS: Healthcare mobility, while affecting all Italian regions, is particularly relevant in the South regions and indicates a lack of pediatric care, which should be strengthened by creating services that are currently not evenly distributed throughout the territory.

Morbidity associated with patent ductus arteriosus in preterm newborns: a retrospective case-control study.

INTRODUCTION: Association between persistency of a patent ductus arteriosus (PDA) and morbidity in preterm newborns is still controversial. We aimed to investigate the relation between PDA and morbidity in a large retrospective study. METHODS: A case-control study including neonates consecutively admitted to the Neonatal Intensive Care Unit (NICU), with gestational age (GA) < 32 weeks or body birth weight (BW) < 1500 g, over a 5-year period. Newborns were divided into Cases and Controls, according with the presence or absence of a hemodynamically significant PDA (hs-PDA). RESULTS: We enrolled 85 Cases and 193 Controls. Subjects with hs-PDA had significantly (p < 0.001) lower GA (26.7 w, 95%CI 27.1-28.0 vs. 30.1 w, 95%CI 29.7-30.4), BW (1024 g, 95% CI 952-1097 vs. 1310 g 95%CI 1263-1358) and an increased morbidity (60.0% vs. 18.7%). In a sub-group of extremely preterm newborns (GA ≤ 28 weeks and BW ≤ 1000 g), the rate of bronchopulmonary dysplasia (BPD) was significantly increased in Cases (31.7%) compared with Controls (5.9%, p = 0.033). Multivariate analysis showed that morbidity significantly depended on hs-PDA, GA and BW, and that, in extremely preterms, the hs-PDA represented an independent risk factor for BPD. CONCLUSIONS: Occurrence of the main morbidities of prematurity depended by hs-PDA, in association with GA, BW, and use of prenatal steroids. In extremely premature babies, hs-PDA is a risk factor for BPD, one of the most important morbidity of prematurity, independently by other confounding variables.

Energy-enhanced parenteral nutrition and neurodevelopment of preterm newborns: A cohort study.

OBJECTIVES: Preterm births are at higher risk for neurodevelopment (NDV) disabilities. To limit long-term consequences, guidelines recommend aggressive parenteral nutrition (PN) soon after birth. The aim of this study was to examine the effects of energy-enhanced PN in the first week of life on long-term NDV in preterm neonates. METHODS: We compared two cohorts of newborns (group A: energy-enhanced PN and group B: energy-standard PN) with different energy intake in the first 7 d of life (DoL) given by PN with the same protein amount, to study the influences of an energy-enhanced PN on NDV at 24 mo of life evaluated with the Bayley Scale of Infant Development-III edition. RESULTS: We analyzed 51 newborns (A: n = 24 versus B: n = 27). The two cohorts were similar in baseline characteristics (gestational age group A 29 wk, 95% confidence interval [CI], 28-30 wk versus group B 29 wk, 95% CI, 28-30 wk; birth weight A: 1214 g, 95% CI, 1062-1365 g versus B 1215 g, 95% CI, 1068-1363 g; boys A 62.5% versus B 55.6%). Infants in cohort B showed significantly (P < 0.05) better gross motor, total scaled, and total composite motor scores (A: 8 (1) versus B 9 (2); A 17 (4) versus B 19 (5); A 91 (12) versus B 97 (15); respectively). Cohort A showed a higher percentage of infants with delayed socioemotional competence (A 30.4% versus B 7.7%, P < 0.05). No differences were found in growth parameters at 24 mo of life. Linear regression analysis showed that socioemotional competence and motor score were negatively associated with energy intake of the first 7 DoL given by PN. CONCLUSIONS: A more aggressive PN strategy results in lower motor score and socioemotional competence performance at 24 mo of life. More caution might be advocated for an energy-enhanced PN protocol, particularly in neonates with lower birth weight, for long-term NDV in preterm neonates.

The Protective Role of Maternal Immunization in Early Life.

With birth, the newborn is transferred from a quasi-sterile environment to the outside world. At this time, the neonatal immune system is inexperienced and continuously subject to a process of development as it encounters different antigenic stimuli after birth. It is initially characterized by a bias toward T helper 2 phenotype, reduced T helper 1, and cytotoxic responses to microbial stimuli, low levels of memory, and effector T and B cells and a high production of suppressive T regulatory cells. The aim of this setting, during fetal life, is to maintain an anti-inflammatory state and immune-tolerance. Maternal antibodies are transferred during pregnancy through the placenta and, in the first weeks of life of the newborn, they represent a powerful tool for protection. Thus, optimization of vaccination in pregnancy represents an important strategy to reduce the burden of neonatal infections and sepsis. Beneficial effects of maternal immunization are universally recognized, although the optimal timing of vaccination in pregnancy remains to be defined. Interestingly, the dynamic exchange that takes place at the fetal-maternal interface allows the transfer not only of antibodies, but also of maternal antigen presenting cells, probably in order to stimulate the developing fetal immune system in a harmless way. There are still controversial effects related to maternal immunization including the so called "immunology blunting," i.e., a dampened antibody production following infant's vaccination in those infants who received placentally transferred maternal immunity. However, clinical relevance of this phenomenon is still not clear. This review will provide an overview of the evolution of the immune system in early life and discuss the benefits of maternal vaccination. Current maternal vaccination policies and their rationale will be summarized on the road to promising approaches to enhance immunity in the neonate.

Neonatal anthropometric charts: the Italian neonatal study compared with other European studies.

BACKGROUND AND OBJECTIVE: This was a nationwide prospective study carried out in Italy between 2005 and 2007, involving 34 centers with a neonatal intensive care unit. The study reports the Italian Neonatal Study charts for weight, length, and head circumference of singletons born between 23 and 42 gestational weeks, comparing them with previous Italian data and with the most recent data from European countries. PATIENTS AND METHODS: Single live born babies with ultrasound assessment of gestational age within the first trimester, and with both parents of Italian origin. Only fetal hydrops and major congenital anomalies diagnosed at birth were excluded. The reference set consists of 22,087 girls and 23,375 boys. RESULTS: At each gestational age, boys are heavier than girls by about 4%. Later-born neonates are heavier than firstborn neonates by about 3%. The effects of sex and birth order on length and head circumference are milder. No differences were observed between babies born in central-north Italy and southern Italy. A large variability emerged among European neonatal charts, resulting in huge differences in the percentage of Italian Neonatal Study neonates below the 10th centile, which is traditionally used to define small-for-gestational-age babies. In the last 2 decades prominent changes in the distribution of birth weight emerged in Italy and in the rest of Europe, in both term and preterm neonates. CONCLUSIONS: The existing European neonatal charts, based on more or less recent data, were found to be inappropriate for Italy. Until an international standard is developed, the use of national updated reference charts is recommended.

High risk of macrosomia in newborns of immigrant mothers.

BACKGROUND: In Italy live about 8.7% immigrants, which contribute to more than 15% of all deliveries taking place in Italy. We aimed to investigate whether newborns from high migratory pressure countries (HMPC) mothers have a different macrosomia and post-term pregnancy incidence compared to Italian newborns. METHODS: In this retrospective observational study, we analyzed data on 404.863 babies born between 2010 and 2017. Italian mothers delivered 309.658 (76.5%), HMPC mothers 88.179 (21.8%) and developed country (DC) mothers 7.026 (1.7%) babies. We analyzed the incidence of macrosomia and post term pregnancy. We estimated incidence rate (IR), unadjusted incidence rate ratio (IRR) and 95% confidence intervals (CIs) to evaluate the association between these perinatal parameters and the mother's region of birth. RESULTS: HMPC compared to Italian newborns showed a significantly higher incidence of birthweight > 4000 g (53.3‰ vs 39.1‰, p-value < 0.001; IRR 1.4, 95%CI = 1.36-1.45), birthweight ≥4500 g. (7.0‰ vs 3.8‰, p-value < 0.001; IRR 1.8, 95%CI = 1.67-2.0) and gestational age at birth > 41 weeks (19.9‰ vs 12.8‰, p-value < 0.001; IRR 1.55, 95%CI = 1.47-1.64). The macrosomia incidence between HPMC and Italian newborns was significantly increased at all gestational ages (Fig. 1), especially for mothers coming from Central Eastern Europe (121.79‰ vs 91.1‰, p-value< 0.001; IRR 1.34, 95%CI = 1.11-1.62). CONCLUSION: In Italy immigrant status represents a risk factor for macrosomia and post-term birth, which could be related to socio-economic status and unfavorable life conditions of immigrant mothers during pregnancy.

Early Protein Intake Influences Neonatal Brain Measurements in Preterms: An Observational Study.

Introduction: To limit extrauterine growth restriction, recent guidelines on nutrition of preterm neonates recommended high protein intake since the first day of life (DOL). The impact of this nutritional strategy on the brain is still controversial. We aimed to evaluate the effects of protein intake on early cerebral growth in very low birth weight newborns. Materials and Methods: We performed serial cranial ultrasound (cUS) scans at 3-7 DOL and at 28 DOL in very low birth weight newborns consecutively observed in the neonatal intensive care unit. We analyzed the relation between protein intake and cerebral measurements at 28 DOL performed by cUS. Results: We enrolled 100 newborns (gestational age 29 ± 2 weeks, birth weight 1,274 ± 363 g). A significant (p < 0.05) positive correlation between enteral protein intake and biparietal diameter (r = 0.490**), occipital-frontal diameter (r = 0.608**), corpus callosum (length r = 0.293*, genu r = 0.301*), caudate head (right r = 0.528**, left r = 0.364**), and cerebellum (transverse diameter r = 0.440**, vermis height r = 0.356**, vermis width r = 0.377**) was observed at 28 DOL. Conversely, we found a significant negative correlation of protein intake given by parenteral nutrition (PN) with biparietal diameter (r = -0.524**), occipital-frontal diameter (r = -0.568**), body of corpus callosum (r = -0.276*), caudate head (right r = -0.613**, left r = -0.444**), and cerebellum (transverse diameter r = -0.403**, vermis height r = -0.274*, vermis width r = -0.462**) at 28 DOL. Multivariate regression analysis showed that measurements of occipital-frontal diameter, caudate head, and cerebellar vermis at 28 DOL depend positively on protein enteral intake (r = 0.402*, r = 0.305*, and r = 0.271*) and negatively by protein parenteral intake (r = -0.278*, r = -0.488*, and r = -0.342*). Conclusion: Brain development in neonatal life depends on early protein intake. High protein intake affects cerebral structures' measurements of preterm newborn when administered by PN. Positive impact on brain development encourages the administration of recommended protein intake mainly by enteral nutrition.

Echocardiography-Guided Management of Preterms With Patent Ductus Arteriosus Influences the Outcome: A Cohort Study.

Introduction: Echocardiography (ECHO) with color flow Doppler is considered as the gold standard to identify a hemodynamic patent ductus arteriosus (hs-PDA). However, the optimal diagnostic and therapeutic management for newborns with hs-PDA is still controversial. We aimed to investigate two clinical strategies: (1) targeted treatment based on ECHO criteria and (2) treatment based on ECHO criteria in addition to clinical signs and symptoms. Materials and Methods: This is a cohort study including all neonates consecutively admitted in the Neonatal Intensive Care Unit of University La Sapienza in Rome, with gestational age <32 weeks or body birth weight <1,500 g and with a diagnosis of hs-PDA as confirmed by ECHO evaluation performed within 72 h of life. We classified the babies in two cohorts: (A) pharmacological treatment immediately after ECHO screening and (B) pharmacological therapy for PDA was administered when the relevance of a hs-PDA was associated with clinical signs of hemodynamic instability. Results: We considered as primary outcome newborns who survived without any morbidities (A: 48.1% vs. B: 22.2%, p = 0.022). In particular, we found that the rate of intraventricular hemorrhage stage ≥2 was increased in cohort B (A: 3.7% vs. B 24.4%, p = 0.020). A multivariate analysis showed that assignment to cohort A independently influences the primary outcome. Conclusions: Adopting an hs-PDA management option based on ECHO-directed therapy regardless of symptoms may reduce the morbidity and improve the survival of very low birth weight infants.

Nutritional Intake Influences Zinc Levels in Preterm Newborns: An Observational Study.

(1) Background: Zinc is a key element for protein synthesis in preterm newborns. Early aggressive nutrition, promoting protein synthesis, may increase zinc consumption; (2) Methods: We performed a prospective observational study, to assess the relationship between early macronutrients intake and serum zinc levels, in preterm newborns with Gestational Age (GA) of 24-35 weeks, consecutively observed in Neonatal Intensive Care Unit (NICU). (3) Results: We enrolled 130 newborns (GA 31.5 ± 2.8). A significant negative correlation between serum zinc level at 28 days of life and energy (r -0.587, p < 0.001) and protein intake (r -0.556, p < 0.001) in the first week of life was observed. Linear regression analysis showed that zinc levels depended on energy (ß -0.650; p < 0.001) and protein (ß -0.669; p < 0.001) intake given through parenteral nutrition (PN) in the first week of life; (4) Conclusions: zinc status of preterm neonates was influenced by early protein and energy intake. An additional zinc supplementation should be considered when high protein and energy intake are received by preterm newborns in the first week of life.

Long-term effects on growth of an energy-enhanced parenteral nutrition in preterm newborn: A quasi-experimental study.

AIM: To assess the best energy intake in Parenteral Nutrition (PN) for preterm newborns, considering both possible benefits for growth and risk of complications. METHODS: Quasi-experimental study comparing two cohorts of newborns, receiving Energy-Enhanced vs. Standard PN (Cohort A, from 1st January 2015 to 31 January 2016 and Cohort B from 1st February 2016 to 31 March 2017; respectively) after implementation of a change in the PN protocol. The primary outcome measure was growth at 24 months of life. The PN associated complications were also measured. RESULTS: We enrolled 132 newborns in two Cohorts, similar for prenatal and postnatal clinical characteristics. Although, body weight and length at 24 months of life were significantly higher (p<0.05) in the Cohort A (11.1, 95% CI 10.6 to 11.6 Kg; 85.0 95% CI 83.8 to 86.2 cm) compared with Cohort B (10.4, 95% CI 9.9 to 10.9 Kg; 81.3 95% CI 79.7 to 82.8 cm), body weight and length Z-Score in the first 24 months of life were similar between the two Cohorts. The rate of PN associated complications was very high in both study Cohorts (up to 98% of enrolments). Multivariate analysis showed that length at 24 months was significantly associated with receiving standard PN (cohort A) in the first week of life and on the energy intake in the first week of life. We also found a marginally insignificant association between Cohort A assignment and body weight at 24 months of life (p = 0.060). CONCLUSIONS: Energy-enhanced PN in early life has not significant effects on long-term growth in preterm newborns. The high prevalence of PN associated complications, poses concerns about the utility of high energy intake recommended by current guidelines for PN.

Isolated auditory neuropathy at birth in congenital cytomegalovirus infection.

BACKGROUND: Congenital cytomegalovirus (cCMV) infection is the most frequent non-genetic cause of sensorineural hearing-loss (SNHL) (i.e., hearing loss due to a cochlear and/or auditory nerve damage). It is widely accepted that SNHL at birth, when associated to cCMV symptomatic infection involving the central nervous system, benefits from antiviral therapy started in the neonatal period. Conversely, there is no consensus for antiviral treatment in congenitally infected infants diagnosed with isolated SNHL (i.e., SNHL in an otherwise asymptomatic infant) at birth. Our aim was to assess the frequency and the auditory outcome of isolated SNHL at birth due to auditory neuropathy (AN) (i.e., SNHL in a patient with normal cochlear function and auditory nerve dysfunction) in infants with cCMV infection. METHODS: We retrospectively reviewed the clinical history of 60 infants, born at term, with cCMV asymptomatic infection, without additional risk factors for SNHL, and exhibiting bilateral "pass" otoacustic emissions (OAE). None of them underwent antiviral therapy. Hearing thresholds were assessed by means of Auditory Brainstem Responses (ABR). AN affected children were followed up until possible normalization of the hearing thresholds or definitive diagnosis of AN. Each infant diagnosed with monolateral or bilateral AN was classified according to the worst ear threshold. RESULTS: In our population, the first ABR was performed at a mean age of 5.00 ± 2.79 (SD) months and AN was diagnosed in 16/60 (26.67%) infants; in 4 infants the AN was defined as mild (4/4 monolateral), moderate in 11 (5/11 bilateral), and severe in 1 (bilateral). The mean age at first ABR was 3.69 ± 2.80 (SD) months in the 16 babies with AN and 5.48 ± 2.66 (SD) months in the 44 infants with normal hearing (p = 0.007). All AN cases spontaneously recovered a normal auditory threshold over time. The mean length of the audiological follow-up was 32.44 ± 17.58 (SD) months (range 5-60 months). CONCLUSION: A delayed maturation of the auditory pathways should be considered when a mild/moderate isolated AN at birth is detected in cCMV infected infants. Prospective studies conducted on larger populations, and with a longer audiological follow-up, are needed to confirm our findings.

Neonatal respiratory morbidity and mode of delivery in a population-based study of low-risk pregnancies.

The aim of this study is to evaluate the association between the mode of delivery and the risk of neonatal respiratory complications in a cohort of term newborns in the Lazio region, Italy. Data on 139,379 term singleton infants born in 2003-2005 were retrieved from birth and hospital discharge database. Odds Ratios (ORs) adjusted by age, parity, birth weight, gestational age, and gender were calculated using logistic regression models. The rate of prelabor cesarean section (CS) was 26.2%. The rates of neonatal respiratory morbidity were 29.6/1,000 in infants delivered by prelabor CS and 17.4/1,000 in infants delivered vaginally or by CS in labor. The adjusted risk of neonatal respiratory morbidity associated with prelabor cesarean birth at 37 weeks is four times higher than in intended vaginal birth after 37 weeks. Prelabor cesarean delivery should be performed after at least 38 weeks' of gestation in order to minimize neonatal respiratory morbidity.