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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.

Background To evaluate the early and late clinical outcomes of neonates born to mothers with SARS-CoV-2 infection in pregnancy, the dynamics of maternal IgG trans placental transfer and its persistence during the first month of life. Methods Prospective study enrolling neonates born to mothers with SARS-CoV-2 infection in pregnancy at IRCCS Azienda Ospedaliero Universitaria di Bologna, Italy, between April 2020 and September 2021. Neonates born to women with infection onset before 2 weeks prior to delivery were enrolled in a 12-month follow-up, including clinical and laboratory evaluations, cranial ultrasound, fundoscopy evaluation. Quantitative IgG to S1/S2 subunits of spike protein were assessed in mother-neonate dyads within 48 hours post-delivery and during follow-up until negative. Transplacental IgG transfer ratio was assessed in relation to the type and trimester of maternal infection. Results One hundred and forty-five neonates were included. the rate of preterm delivery was similar between women with and without SARS-CoV-2 infection (6.2% versus 8.7%, P=0.53). No clinical, laboratory, cerebral and fundoscopy abnormalities were detected at birth or during follow-up, through 11 months (range 8–12). MedianIgG level at birth was not different between neonates born to asymptomatic or symptomatic mothers (18.5 AU/mL, IQR 12–49, versus 31.5 AU/mL, IQR 15–71, P=0.07) nor in relation to the trimester of maternal infection (Table 1), even though mothers with third trimester infections had higher IgG level at birth. Transplacental transfer ratio was higher following second trimester maternal infections and was the lowest following third trimester infections (Table 1). Maternally derived IgG were rapidly weaned, with most infants (115/140, 82%) seronegative by 4 months of age. Conclusion Early and later outcomes of infants born to SARS-CoV-2 infected mothers were favorable. IgG trans placental transfer was higher following second trimester maternal infections, which could be relevant to inform studies on appropriate vaccination strategies aimed at neonatal protection. Maternally derived IgG are rapidly weaned in the first months of life. Disclosures All Authors: No reported disclosures.

Background Cytomegalovirus (CMV)-specific CD8 + T-cell responses can be detected early in fetal life, but their role in the manifestations of congenital CMV (cCMV) infection remains largely unknown. Methods CMV-specific CD8 + T-cell responses were assessed in neonates with cCMV using QuantiFERON®-CMV assay, within day 14 of life (T0) and during the second month of life (T1). Detection and quantification of CMV DNA in whole blood and urine samples were performed at both time points. QuantiFERON®-CMV results were evaluated in relation to timing of maternal infection, clinical manifestations of cCMV and CMV DNA levels. Results Thirty neonates were enrolled (10/30 [33%] symptomatic; 20/30 [67%] asymptomatic). At T0 16/30 (53%) subjects had a reactive QuantiFERON®-CMV result and 16/16 (100%) were asymptomatic, whereas 14/30 (47%) had a nonreactive or indeterminate QuantiFERON®-CMV result and 4/14 (29%) were asymptomatic. At T1, 17/29 (59%) subjects had a reactive QuantiFERON®-CMV result, and 17/17 (100%) were asymptomatic, whereas 12/29 (41%) had a nonreactive or indeterminate result and 3/12 (25%) were asymptomatic. At both T0 and T1 reactive QuantiFERON®-CMV results correlated with lack of symptoms (P = .0001). At T1 median CMV DNAemia was lower in subjects with reactive QuantiFERON®-CMV results as compared with subjects with nonreactive or indeterminate results (1.82 log IU/mL [1.82–2.89] vs 2.55 log IU/mL [1.82–4.42], P = .009). No correlation was found between QuantiFERON®-CMV results and gestational age at maternal infection nor with urine CMV DNA levels. Conclusions A detectable CMV-specific CD8 + T-cell response, evaluated using the QuantiFERON®-CMV assay, correlates with the lack of CMV-related symptoms and the control of CMV DNAemia.

BackgroundThe thermal servo-controlled systems are routinely used in neonatal intensive care units (NICUs) to accurately manage patient temperature, but their role during the immediate postnatal phase has not been previously assessed.ObjectiveTo compare two modalities of thermal management (with and without the use of a servo-controlled system) immediately after birth.Study design and settingMulticentre, unblinded, randomised trial conducted 15 Italian tertiary hospitals.ParticipantsInfants with estimated birth weight +6weeks.InterventionThermal management with or without a thermal servo-controlled system during stabilisation in the delivery room.Primary outcomeProportion of normothermia at NICU admission (axillary temperature 36.5°C–37.5°C).ResultsAt NICU admission, normothermia was achieved in 89/225 neonates (39.6%) with the thermal servo-controlled system and 95/225 neonates (42.2%) without the thermal servo-controlled system (risk ratio 0.94, 95% CI 0.75 to 1.17). Thermal servo-controlled system was associated with increased mild hypothermia (36°C–36.4°C) (risk ratio 1.48, 95% CI 1.09 to 2.01).ConclusionsIn very low birthweight infants, thermal management with the servo-controlled system conferred no advantage in maintaining normothermia at NICU admission, while it was associated with increased mild hypothermia. Thermal management of preterm infants immediately after birth remains a challenge.Trial registration numberNCT03844204

Objective: To investigate whether exposure to inhibitors of gastric acidity, such as H2 blockers or proton pump inhibitors, can independently increase the risk of infections in very low birth weight (VLBW) preterm infants in the neonatal intensive care unit. Study design: This is a secondary analysis of prospectively collected data from a multicenter, randomized controlled trial of bovine lactoferrin (BLF) supplementation (with or without the probiotic Lactobacillus rhamnosus GG) vs placebo in prevention of late-onset sepsis (LOS) and necrotizing enterocolitis (NEC) in preterm infants. Inhibitors of gastric acidity were used at the recommended dosages/schedules based on the clinical judgment of attending physicians. The distribution of days of inhibitors of gastric acidity exposure between infants with and without LOS/NEC was assessed. The mutually adjusted effects of birth weight, gestational age, duration of inhibitors of gastric acidity treatment, and exposure to BLF were controlled through multivariable logistic regression. Interaction between inhibitors of gastric acidity and BLF was tested; the effects of any day of inhibitors of gastric acidity exposure were then computed for BLF-treated vs -untreated infants. Results: Two hundred thirty-five of 743 infants underwent treatment with inhibitors of gastric acidity, and 86 LOS episodes occurred. After multivariate analysis, exposure to inhibitors of gastric acidity remained significantly and independently associated with LOS (OR, 1.03; 95% CI, 1.008-1.067; P = .01); each day of inhibitors of gastric acidity exposure conferred an additional 3.7% odds of developing LOS. Risk was significant for Gram-negative (P < .001) and fungal (P = .001) pathogens, but not for Gram-positive pathogens (P = .97). On the test for interaction, 1 additional day of exposure to inhibitors of gastric acidity conferred an additional 7.7% risk for LOS (P = .003) in BLF-untreated infants, compared with 1.2% (P = .58) in BLF-treated infants. Conclusion: Exposure to inhibitors of gastric acidity is significantly associated with the occurrence of LOS in preterm VLBW infants. Concomitant administration of BLF counteracts this selective disadvantage. Trial registration: isrctn.org: ISRCTN53107700.

Background. The neonatal immune system is not fully developed at birth; newborns have adequate lymphocytes counts but these cells lack function.Objective. To assess the activity of T-cells and the influence of the main perinatal factors in very preterm infants (birth weight < 1500 g).Design. Blood samples from 59 preterm infants (21/59 were dizygotic twins) were collected at birth and at 30 days of life to measure CD4+ T-cell activity using the ImmuKnow™ assay. Fifteen healthy adults were included as a control group.Results. CD4+ T-cell activity was lower in VLBW infants compared with adults (p<0.001). Twins showed lower immune activity compared to singletons (p=0.005). Infants born vaginally showed higher CD4+ T-cell activity compared to those born by C-section (p=0.031); infants born after prolonged Premature Rupture of Membranes (pPROM) showed higher CD4+ T-cell activity at birth (p=0.002) compared to infants born without pPROM. Low CD4+ T-cell activity at birth is associated with necrotizing enterocolitis (NEC) in the first week of life (p=0.049).Conclusions. Preterm infants show a lack in CD4+ T-cell activity at birth. Perinatal factors such as intrauterine inflammation, mode of delivery, and zygosity can influence the adaptive immune activation capacity at birth and can contribute to exposing these infants to serious complications such as NEC.

Serology has a pivotal role in the diagnosis of congenital syphilis (CS), but problems arise because of the passive transfer of IgG antibodies across the placenta. The aim of this study was to assess the diagnostic value of a comparative Western blot (WB) method finalized to match the IgG immunological profiles of mothers and their own babies at birth in order to differentiate between passively transmitted maternal antibodies and antibodies synthesized by the infants against Treponema pallidum . Thirty infants born to mothers with unknown or inadequate treatment for syphilis were entered in a retrospective study, conducted at St. Orsola-Malpighi Hospital, Bologna, Italy. All of the infants underwent clinical, instrumental, and laboratory examinations, including IgM WB testing. For the retrospective study, an IgG WB assay was performed by blotting T. pallidum antigens onto nitrocellulose sheets and incubating the strips with serum specimens from mother-child pairs. CS was diagnosed in 11 out of the 30 enrolled infants; 9/11 cases received the definitive diagnosis within the first week of life, whereas the remaining two were diagnosed later because of increasing serological test titers. The use of the comparative IgG WB testing performed with serum samples from mother-child pairs allowed a correct CS diagnosis in 10/11 cases. The CS diagnosis was improved by a strategy combining comparative IgG WB results with IgM WB results, leading to a sensitivity of 100%. The comparative IgG WB test is thus a welcome addition to the conventional laboratory methods used for CS diagnosis, allowing identification and adequate treatment of infected infants and avoiding unnecessary therapy of uninfected newborns.

Human leukocyte antigen-G (HLA-G) is a nonclassical HLA class I antigen that is expressed during pregnancy contributing to maternal-fetal tolerance. HLA-G can be expressed as membrane-bound and soluble forms. HLA-G expression increases strongly during viral infections such as congenital human cytomegalovirus (HCMV) infections, with functional consequences in immunoregulation. In this work we investigated the expression of soluble (s)HLA-G and beta-2 microglobulin (component of HLA) molecules in correlation with the risk of transmission and severity of congenital HCMV infection. We analyzed 182 blood samples from 130 pregnant women and 52 nonpregnant women and 56 amniotic fluid samples from women experiencing primary HCMV infection. The median levels of sHLA-G in maternal serum of women with primary HCMV infection were higher in comparison with nonprimary and uninfected pregnant women (p<0.001). AF from HCMV symptomatic fetuses presented higher sHLA-G levels in comparison with infected asymptomatic fetuses (p<0.001), presence of HLA-G free-heavy chain, and a concentration gradient from amniotic fluid to maternal blood. No significant statistical difference of beta-2 microglobulin median levels was observed between all different groups. Our results suggest the determination of sHLA-G molecules in both maternal blood and amniotic fluid as a promising biomarker of diagnosis of maternal HCMV primary infection and fetal HCMV disease.

This case concerns a premature infant with typical signs of congenital syphilis born to an untreated foreign mother. Syphilis prevalence in pregnant women has been rising in Italy since the beginning of the 21st century, mainly due to immigration. A correct antenatal syphilis screening and consequent adequate therapy of pregnant woman are fundamental to prevent the neonatal infection.

Summary Background Gastro-oesophageal reflux is common in preterm newborns; at present, no studies have evaluated the efficacy of sodium alginate in this population. Aim To evaluate the effect of sodium alginate on gastro-oesophageal reflux features in preterm newborns by combined pH and impedance monitoring (pH-MII). Methods Thirty-two symptomatic preterm newborns underwent a 24 h pH-MII, during which each baby was fed eight times. Sodium alginate was given four times at alternate meals [drug-given (DG) vs. drug-free (DF) meals]. Gastro-oesophageal reflux features (i.e. number, acidity, duration and height of gastro-oesophageal reflux) after DG and DF meals were compared by Wilcoxon signed ranks test. Results Sodium alginate significantly decreased the number of acid gastro-oesophageal reflux detected either by pH monitoring (DG vs. DF: median 17.00 vs. 29.00, P = 0.002) and MII (DG vs. DF: 4.0 vs. 6.00, P = 0.050), and also acid oesophageal exposure (DG vs. DF: 4.0% vs. 7.6%, P = 0.030), without any influence on non-acid gastro-oesophageal reflux. Furthermore, it decreased the number of gastro-oesophageal reflux reaching proximal oesophagus (DG vs. DF: 5.50 vs. 7.50, P = 0.030). Conclusions The use of sodium alginate in preterm infants seems to be promising, because this drug decreases gastro-oesophageal reflux acidity and height with the advantage of a nonsystemic way of action and a more favourable safety profile over H2 blockers and PPIs.

Positive syphilis serology was noted in 119 (0.49%) of the 24 053 pregnant women delivering at St Orsola Hospital in Bologna, Italy, from November 2000 through July 2007. Six presumptive cases of congenital syphilis with IgM western blot positive results were found. Two infants had a positive cerebrospinal fluid (CSF) Venereal Disease Research Laboratory test result (one also had a positive CSF PCR result), another presented long-bone lesions, and the remaining three were preterm. These observations confirmed that antenatal syphilis screening facilitates treatment during pregnancy and offsets vertical transmission; moreover, the use of IgM western blot and careful CSF examination allowed the identification and treatment of high-risk newborns.

Primary immunodeficiencies are rare inherited disorders that may lead to frequent and often severe acute respiratory infections. Respiratory syncytial virus (RSV) is one of the most frequent pathogens during early infancy and the infection is more severe in immunocompromised infants than in healthy infants, as a result of impaired T- and B-cell immune response unable to efficaciously neutralize viral replication, with subsequent increased viral shedding and potentially lethal lower respiratory tract infection. Several authors have reported a severe clinical course after RSV infections in infants and children with primary and acquired immunodeficiencies. Environmental prophylaxis is essential in order to reduce the infection during the epidemic season in hospitalized immunocompromised infants. Prophylaxis with palivizumab, a humanized monoclonal antibody against the RSV F protein, is currently recommended in high-risk infants born prematurely, with chronic lung disease or congenital heart disease. Currently however the prophylaxis is not routinely recommended in infants with primary immunodeficiency, although some authors propose the extension of prophylaxis to this high risk population.

BACKGROUND: Congenital infection with human cytomegalovirus (CMV) is a major cause of morbidity and mortality. In an uncontrolled study published in 2005, administration of CMV-specific hyperimmune globulin to pregnant women with primary CMV infection significantly reduced the rate of intrauterine transmission, from 40% to 16%. METHODS: We evaluated the efficacy of hyperimmune globulin in a phase 2, randomized, placebo-controlled, double-blind study. A total of 124 pregnant women with primary CMV infection at 5 to 26 weeks of gestation were randomly assigned within 6 weeks after the presumed onset of infection to receive hyperimmune globulin or placebo every 4 weeks until 36 weeks of gestation or until detection of CMV in amniotic fluid. The primary end point was congenital infection diagnosed at birth or by means of amniocentesis. RESULTS: A total of 123 women could be evaluated in the efficacy analysis (1 woman in the placebo group withdrew). The rate of congenital infection was 30% (18 fetuses or infants of 61 women) in the hyperimmune globulin group and 44% (27 fetuses or infants of 62 women) in the placebo group (a difference of 14 percentage points; 95% confidence interval, -3 to 31; P=0.13). There was no significant difference between the two groups or, within each group, between the women who transmitted the virus and those who did not, with respect to levels of virus-specific antibodies, T-cell-mediated immune response, or viral DNA in the blood. The clinical outcome of congenital infection at birth was similar in the two groups. The number of obstetrical adverse events was higher in the hyperimmune globulin group than in the placebo group (13% vs. 2%). CONCLUSIONS: In this study involving 123 women who could be evaluated, treatment with hyperimmune globulin did not significantly modify the course of primary CMV infection during pregnancy. (Funded by Agenzia Italiana del Farmaco; CHIP ClinicalTrials.gov number, NCT00881517; EudraCT no. 2008-006560-11.).

Congenital syphilis (CS) is mainly a consequence of the lack of antenatal care and control of sexually transmitted infections.The bedrock of the prevention of CS is syphilis diagnosis by serological screening during pregnancy.Current Italian guidelines suggest that all the pregnant women should be tested in the first trimester. Due to the frequently absence of specific signs of infection at birth, laboratory tests are often the only method for a correct CS diagnosis. The aim of this study was to evaluate the usefulness of Treponema pallidum IgM Western Blot (WB) and Polymerase Chain Reaction (PCR) on cerebrospinal fluid (CSF) as an aid in the diagnosis of CS during a prospective surveillance study carried out at St. Orsola Hospital in Bologna, Italy, from November 2000 through June 2010. All pregnant women during pregnancy and at delivery were screened for syphilis by ARCHITECT® Syphilis TP, Abbott. Positive samples were further analysed by Treponema Pallidum Hemagglutination Test (TPHA) and Rapid Plasma Reagin (RPR) tests, Radim.An in-house Western Blot (WB) was also performed. Infants born to syphilis seropositive mothers were enrolled in a prospective follow up. At birth, tests were performed (including IgM WB). Infants with positive RPR tests at birth born to mothers not adequately treated received also a long bone radiograph as well as a complete CSF analysis, including Veneral Disease Research Laboratori (VDRL) (Siemens Healthcare Diagnostics) and PCR testing. All seroreactive infants received careful follow up examinations and serological testing at 0, 3, 6, 9, 12 months or until the tests became negative. In this study, positive syphilis serology was noted in 151 pregnant women delivering in our hospital. Fifteen women had never been adequately treated, and 9 out 15 gave birth to infected newborns.All these 9 infants had positive IgM WB results on serum samples. Two babies had characteristic long bone lesions at X-ray examination and 3 were born preterm. These observations confirmed that antenatal syphilis screening facilitates treatment during pregnancy and offsets vertical transmission; moreover, the use of IgM WB and careful CSF examination allowed the identification and treatment of high risk newborns.

A male infant born by caesarean section at 38 weeks of gestational age (B.W. 4055 g; Apgar 9-10), in the first two hours of life his right leg became hypovascularizated. Normal values of leukocities, red cells, haematocrit, hemoglobin, platelets. C-Reactive Protein negative. Electrolytes and coagulation tests were normal. Normal vitamin K coagulation proteins levels. Serological tests for TORCH (IgM) and Parvovirus (IgG and IgM) were negative. Sonography showed a reduced blood flow in the iliac artery and reported a 1 cm long vessel thrombosis. From 8 hours of life we administred an intravenous infusion of unfractionated heparin (UFH) 75 UI/Kg for the first 10 minutes then 28 UI/Kg/h. On the 2nd day tests were performed to assess absence of inhibiting-clot factors. The dosage of homocysteine, protein S and antithrombin was normal. FV Leiden and antiphospholipid antibodies were negative. The mapping of G20210A prothrombin's gene resulted normal, whereas the concentration of Protein C was lower than normal: activity 46% (68-150%), antigen 35% (70-150%). The same deficiency was also found in the father. The mother showed normal concentrations. No episodies of thrombosis events were documentated in the family. The intravenous unfractionated heparin (UFH) therapy was replaced after 64 hours by subcutaneous nadroparin 600 UI twice/day, which was stopped 5 days later when the vessel sonografic images were completely normal. During the hospitalization the infant didn't show bleeding. The child was followed-up yearly until 4 years of age: he was well and had a normal body and mental development. The final diagnosis is likely to be of a permanent protein C deficiency in heterozygous form. Our case is interesting because the first manifestation was an important thrombosis of large vessel that occurred within a few hours of life in absence of perinatal risk factors, as if it was a homozygous disease, but the patient had a heterozygotic form. In literature few cases are reported of heterozygous forms that became symptomatic, but only in old age. After a severe first manifestation, a normal and asymptomatic development is uncommon without new thrombotic episodes. In our patient the neonatal thrombosis was the sole event in his life.

Late-onset sepsis is often suspected in the neonatal population, but blood cultures (BC) are rarely positive. This study was aimed at the assessment of the clinical usefulness of a newly commercially available real-time PCR test (LightCycler® SeptiFast) in newborns older than 3 days with clinical suspicion of sepsis. Peripheral blood samples were obtained from preterm and term newborns with clinical signs of sepsis (n = 34) and from healthy neonates (n = 8). The specimens were evaluated for complete blood count, C-reactive protein level, and bloodstream infections (by BC and SeptiFast assays). Sepsis was detected in 7/34 (20.6%) patients by BC and/or SeptiFast. In 3 patients the results of BC and SeptiFast were concordant. However, in 4 cases, only SeptiFast identified the presence of pathogens in blood samples. In the remaining 26 cases (76.5%), both methods were negative. All of the healthy infants tested negative by both BC and SeptiFast. SeptiFast is a clinically usefull method for the laboratory diagnosis of late-onset sepsis in newborns. The major advantage of SeptiFast is the rapid identification of microbes in the blood. Faster availability of results may reduce the inappropriate use of antimicrobial therapy, the risk of antibiotic-resistance and reduce the hospitalization period.

Objective: to evaluate the prevalence of maternal syphilis at delivery and neonatal syphilis infection in an Italian urban area, in connection with the increased flow of immigration. Study design: A prospective surveillance study was carried out in Bologna, Italy, from November 2000 to March 2006. All pregnant women were screened for syphilis at delivery. Infants born to seropositive mothers were enrolled in a prospective follow-up. Results: During the study period 19 205 women gave birth to 19 548 infants. A total of 85 women were seropositive for syphilis at delivery. The overall syphilis seroprevalence in pregnant women was 0.44%, but it was 4.3% in women from eastern Europe and 5.8% in women from Central–South America. Ten women were first found positive at delivery, as they did not receive any prenatal care. Nine of these were from eastern Europe. All their infants were asymptomatic, but six had both reactive immunoglobulin (Ig)M western blot and rapid plasma reagin tests and were considered prenatally infected. Three of six were preterm (gestational age

Aims Congenital toxoplasmosis can cause neurological impairment and ocular disease. To describe clinical profile of infants with suspected congenital toxoplasmosis. Methods Observational study of infants born to mothers with a suspected infection with Toxoplasma gondii during pregnancy between 2002 and 2011. Serological tests were performed at birth: Toxoplasma specific antibodies IgA, IgM, IgG by Enzyme Immune Assay (EIA), Enzyme Linked Fluorescent Assay (ELFA), Western Blot (WB) tests and WB-IgG compared analysis for mother-infant pairs. Infants underwent cranial Ultrasound Scanning, fundoscopy examination, Auditory Brainstem Response, and periodic clinical evaluations. Results One hundred thirty-one infants Toxoplasma IgG-positive at birth were evaluated; 118/131 (90%) become IgG-negative at 12 months of life. Congenital toxoplasmosis was confirmed in 13/131 infants (9.9%). Transmitters pregnant women seroconverted in the third trimester (mean 28±8weeks). IgM-ELFA test was positive in 9/13 infants; in 4/13 infants IgM positivity was detected by WB test (negative IgM-EIA/ELFA). Three of 6 infants had a different IgG-WB reactivity compared to their mothers. Six of 13 infected infants (46%) were symptomatic at birth: 2/13 infants developed chorioretinitis; 4/13 had a pathological neuroimaging (4/4 cerebral calcifications, 1/4 ventriculomegaly). None had hearing loss. Infected infants received one-year therapy (pyrimethamine/sulfadiazine); 1/13 infant developed neutropenia as adverse therapy effect. At a median age of 2 years all infected infants had a normal psychomotor development (range 1–10 years). Conclusions It is advisable to perform IgM/IgG-WB on infant serum and the compared analysis for mother-infant pairs within the first month of life when high risk factors for Toxoplasmosis transmission are present.

BACKGROUND: Congenital cytomegalovirus (CMV) infection is a leading cause of sensorineural hearing loss (SNHL). The mechanisms of pathogenesis of CMV-related SNHL are still unclear. The aim is to study congenital CMV-related damage in the fetal inner ear, in order to better understand the underlying pathophysiology behind CMV-SNHL. RESULTS: We studied inner ears and brains of 20 human fetuses, all at 21 week gestational age, with a high viral load in the amniotic fluid, with and without ultrasound (US) brain abnormalities. We evaluated histological brain damage, inner ear infection, local inflammatory response and tissue viral load.Immunohistochemistry revealed that CMV was positive in 14/20 brains (70%) and in the inner ears of 9/20 fetuses (45%). In the cases with inner ear infection, the marginal cell layer of the stria vascularis was always infected, followed by infection in the Reissner's membrane. The highest tissue viral load was observed in the inner ear with infected Organ of Corti. Vestibular labyrinth showed CMV infection of sensory cells in the utricle and in the crista ampullaris.US cerebral anomalies were detected in 6 cases, and in all those cases, the inner ear was always involved. In the other 14 cases with normal brain scan, histological brain damage was present in 8 fetuses and 3 of them presented inner ear infection. CONCLUSIONS: CMV-infection of the marginal cell layer of the stria vascularis may alter potassium and ion circulation, dissipating the endocochlear potential with consequent SNHL. Although abnormal cerebral US is highly predictive of brain and inner ear damage, normal US findings cannot exclude them either.

Background and Aims Congenital Cytomegalovirus (CMV) infection can lead to neurological sequelae and sensorineural hearing loss (SNHL). To correlate clinical, auditory and neuroimaging findings in the neonatal period to long-term outcome in congenitally CMV-infected infants. Methods Congenitally CMV-infected infants born between 2001 and 2011 were clinically evaluated and underwent cranial Ultrasound (cUS), cerebral Magnetic Resonance Imaging (cMRI), fundoscopy examination and auditory brainstem response (BAER) in the neonatal period. Both symptomatic and asymptomatic infants were followed prospectively to assess physical growth, neurological, visual and audiological outcome. Results Forty-two infants were evaluated. Six of 42(14.2%) infants had symptoms/signs at birth: microcephaly (3), petechiae (4), thrombocytopenia (3), hepatosplenomegaly (3), jaundice (1), elevated serum transaminases (1). Two cases of chorioretinitis and 4 cases of abnormal BAER were found in the neonatal period. cUS demonstrated pathological findings in 6/42(14.2%) infants: ventriculomegaly (4), pseudocysts (3), calcifications (3), cerebellar hypoplasia (1). cMRI showed abnormalities in 10/42(23.8%) infants: pseudocysts (3), white-matter lesions (7), lissencephaly (1), ventriculomegaly (4), calcifications (2), cerebellar hypoplasia (2). At follow-up (mean duration 43±18 months) 8/42(19%) infants showed SNHL and 8/42(19%) showed impaired psychomotor development. The composite outcome (SNHL and/or neurodevelopmental sequelae) was poor in 9/42(21.4%) infants. Neonatal findings in infants with an adverse outcome were: clinical signs (5/9), abnormal BAER (2/9), abnormal cUS (5/9), abnormal cMRI (9/9). Symptomatic infants received antiviral treatment. Conclusions In our series 21.4% of congenital CMV infected infants had one or more sequelae at follow-up evaluations. A pathological neuroimaging at birth was the most sensitive predictor of long-term sequelae.

Background and Aims Cytomegalovirus (CMV) is the most common viral cause of congenital infection. Preexisting maternal immunity strongly reduce CMV transmission. To characterize newborn findings and long-term outcome in infants born to mothers with non-primary CMV infection. Methods Prospective study of infants with congenital CMV infection born between 2005 and 2010. Clinical and neuroimaging findings at birth were recorded. Infants were enrolled in a long-term follow-up program including clinical, ophthalmological, audiological and neurodevelopmental examinations. Results Of the 37 infants with congenital CMV infection identified during the study period, 31/37(84%) were born to mothers with primary CMV infections and 6/37(16%) were born to mothers with confirmed non-primary CMV infections in pregnancy. Three of 6 infants born to mothers with preexisting immunity had symptoms/signs at birth: microcephaly (3), petechiae (2), thrombocytopenia (2), hepatosplenomegaly (2), jaundice (1), chorioretinitis (1). These infants showed abnormal auditory brainstem evoked response at first evaluation and abnormal neuroimaging findings. At follow-up 2/3 infants developed severe neurological sequelae (cerebral palsy and epilepsy in 1 case), and 1/3 showed delayed psychomotor development requiring rehabilitation; 3/3 infants had bilateral sensorineural hearing loss. Symptomatic infants were treated with antiviral drugs. The remaining 3/6 infants were asymptomatic at birth and showed a good long-term neurologic outcome. Conclusions Clinical findings and long-term outcome in infants born to mothers with preexisting CMV immunity are widely variable and may be severe. The presence of symptoms/signs consistent with CMV congenital infection should be closely evaluated even in infants born to mothers with CMV-IgG positivity prior to conception.

Clinical Manifestations and Neurodevelopmental Outcomes of Post Natal CMV infection transmitted through Breast Milk in the ELBW Infants

Background and aims: In many western European countries, the rate of CS has increased over time due to a high serum-prevalence of syphilis serum-positivity in fertile immigrant women. We aimed to study the prevalence of Congenital Syphilis (CS) and its risk factors in Italy. Methods: We performed a prospective national study from July 1st 2006 to June 30th 2007, involving 94 hospitals. Data of mother-child pairs were obtained from adhoc forms for every syphilis serum-positive pregnant woman. Results: 25/207 infants, born to 203 serum-positive mothers, were diagnosed for CS (20 cases in 100.000 live births). Maternal risk factors for CS were age < 20 years (RR 3.44, 95% CI 1.63-7.27), no prenatal care (RR 3.10, 95% CI 1.47-6.21) and no adequate treatment during pregnancy (RR 15.32, 95% CI 5.22-47.31). No association between CS and single marital status, unemployment and coexistence of other maternal infections was found. Infected babies were more probably preterm (RR 5.72, 95% CI 2.93-11.18), with a birth weight < 2000 g (RR 7.85, 95% CI 4.37-14.11) than non-infected ones. The prevalence of syphilis serum-positivity was higher among immigrant women; nevertheless, there was no difference between infants born to foreign and Italian mothers in the risk of CS. Conclusions: The present study highlights the opportunity of prenatal syphilis screening in all pregnant women, both immigrant and Italian, in order to recognize and treat maternal infection, thus preventing mother-to-child transmission.

Background and aims: Although Rotavirus (RV) infection in newborns is usually asymptomatic, outbreaks have been reported, associated with increased incidence of necrotizing enterocolitis (NEC). We conducted a prospective study during the epidemic peak of RV, in order to assess the rate of infection, its clinical importance and the presence of gut inflammation. Materials and Methods: Between February 1st and March 15th, 2009 all the infants hospitalized for more than 48 hours were enrolled. Faeces were collected daily: the presence of RV was evaluated by immunoassay and the value of Calprotectin by ELISA test. Results: 60 infants (381 faecal samples) were evaluated: 17 infants (28%) were RV positive. RV positivity rate was higher in preterm than in term infants (preterm:13/33 vs term:4/27; p=0.04) and in VLBW (VLBW:9/17 vs non-VLBW:8/43; p=0.01); no difference in clinical symptoms between RV+ and RV- infants was found. Two infants had blood mucus stools concomitant to the first RV positivity; three RV+ (17.6%) and three RV- (6.9%) infants had NEC>stageII. No differences in faecal Calprotectin were found among infants non developing NEC (RV+/NEC-: 155±134 mg/g vs RV-/NEC-: 116±124); higher values were detected in infants with NEC, regardless of RV (RV+/NEC+: 287±174 vs RV-/ NEC+: 283±207). Conclusions: RV infection is frequent in NICU during epidemic peak, and more likely in premature than in term infants, partly because of their prolonged hospitalization. Isolated RV infection does not lead to intestinal inflammation and does not seem to favour NEC.

232 Treatment of Chronic Lung Disease Associated Pulmonary Hypertension with Inhaled Nitric Oxide Administered via Nasal Cpap