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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.

Background: Congenital cytomegalovirus (cCMV) infection is responsible of a high burden of neurosensory impairment in children. Objectives: To report incidence and consequences of ophthalmological abnormalities in infants with cCMV infection and better define their long-term ophthalmological management. Study design: Infants with cCMV infection were enrolled in a 6-year follow-up. Infants were classified as symptomatic or asymptomatic based on complete clinical, laboratory and instrumental evaluations. All infants underwent funduscopic evaluation in neonatal period, and yearly complete ophthalmological evaluation, including funduscopic, motility and visual acuity assessments. Results: Forty-eight infants were enrolled, 18/48 (37.5%) symptomatic and 30/48 (62.5%) asymptomatic. Mean duration of follow-up was 34.9 ± 22.2 vs. 34.8 ± 20.1 months (P = 0.98). Funduscopic abnormalities were identified in neonatal period in 7/18 (39%) symptomatic infants and in none of the infants without other clinical and instrumental abnormalities at birth (P < 0.001); chorioretinal scars were the most common finding (5/18 cases, 28%). Strabismus was detected in 1/18 (5.5%) symptomatic infants during the first years of life. Visual impairment at last follow-up evaluation was suspected or detected in 4/18 (22%) symptomatic infants and in none of the asymptomatic infants at birth (P = 0.01). Ophthalmological abnormalities were associated with other signs of central nervous system (CNS) involvement (P < 0.001). No correlation was found with the type of maternal infection. Conclusions: Ophthalmological abnormalities were common in symptomatic infants though often not associated with long-term visual impairment, and correlated with the presence of CNS involvement. Neonatal and periodical ophthalmological evaluations throughout childhood seem prudential for symptomatic babies. No ophthalmological abnormalities were detected in asymptomatic infants, who might therefore undergo more deferred evaluations.

Objective: To evaluate perinatal outcomes in case of non-primary maternal cytomegalovirus (CMV) infection. Methods: We performed a retrospective cohort study of pregnant women with active CMV infection referred to our unit over a 15-year period (January 2000 to December 2014). Non-primary infection was diagnosed on the basis of the results of confirmatory serological and virological tests (avidity test, immunoblotting, real-time PCR-DNA). The vertical transmission rate and the percentage of symptomatic congenital infection were determined in this group of patients. Results: A total of 205 pregnant women were enrolled. Congenital infection occurred in 7 (3.4%) fetuses/neonates. Symptomatic disease was present at birth in 3 of the 7 congenitally infected neonates (1.5%). Two out of 3 symptomatic newborns presented a pathologic second-trimester ultrasound scan. Conclusion: Maternal immunity offers substantial protection against intrauterine transmission of CMV infection, but not against disease once the fetus is infected.

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.

Clinical evaluation of the Elecsys(®) CMV IgM, IgG, IgG Avidity and COBAS AmpliPrep/COBAS TaqMan CMV (COBAS CMV) assays (Roche Diagnostics AG) in the diagnosis and prognosis of congenital CMV infection was performed. In this study, 150 preselected clinical samples (50 primary infection sera, 50 amniotic fluid [AF] and 50 newborn urine) were processed using Roche serological/molecular CMV-specific tests. Results were compared with those obtained by routine assays (comparator assays). The Elecsys(®) CMV IgM and IgG assays showed a perfect agreement (100%) with the comparator assays. Using the combination of the Elecsys(®) CMV IgM and IgG Avidity assays results, a primary infection was identified in 100% of cases. Inappropriate avidity CMV IgG values in two samples with very low IgG values (

Objective To evaluate the incidence of infants with birth weight less than the 10th centile for small for gestational age (SGA) in primary maternal cytomegalovirus (CMV) infection and to determine whether SGA predicts poor neurodevelopmental outcome. Methods A retrospective cohort study, which included singleton live-born infants from pregnancies complicated by primary maternal CMV infection. Infants were classified as uninfected or infected based on viral virus isolation and real-time PCR in urine at birth. SGA neonates rate and long-term sequelae were evaluated. Results Between 2000 and 2012, 848 women with primary CMV infection were referred to our center with 588 infants assessed at birth. Congenital CMV infection was diagnosed in 119 cases (20%), of which 8 were SGA (6.7%) compared with 27 out of the 469 uninfected infants (5.7%) (p-value = 0.69). Among the 119 infected babies, 14 infants were symptomatic at birth or at postnatal follow-up (12%), of whom two were SGA compared with six out of the 105 asymptomatic neonates (5.7% versus 15%, respectively, p-value = 0.22). Conclusion Congenital CMV infection does not seem to be associated with a higher incidence of SGA, and long-term outcomes do not seem to be affected by isolated impaired fetal growth. © 2014 John Wiley & Sons, Ltd.

BackgroundInternational guidelines lack a substantial consensus regarding management of asymptomatic full-term and late preterm neonates at risk for early-onset disease (EOS). Large cohorts of newborns are suitable to increase the understanding of the safety and efficacy of a given strategy.MethodsThis is a prospective, area-based, cohort study involving regional birth facilities of Emilia-Romagna (Italy). We compared cases of EOS (at or above 35 weeks' gestation) registered in 2003-2009 (baseline period: 266,646 LBs) and in 2010-2016, after introduction of a new strategy (serial physical examinations, SPEs) for managing asymptomatic neonates at risk for EOS (intervention period: 265,508 LBs).ResultsThere were 108 cases of EOS (baseline period, n = 60; intervention period, n = 48). Twenty-two (20.4%) remained asymptomatic through the first 72 hours of life, whereas 86 (79.6%) developed symptoms, in most cases (52/86, 60.5%) at birth or within 6 hours. The median age at presentation was significantly earlier in the intrapartum antibiotic prophylaxis (IAP)-exposed than in the IAP-unexposed neonates (0 hours, IQR 0.0000-0.0000 vs 6 hours, IQR 0.0000-15.0000, pConclusionsInfants with EOS exposed to IAP developed symptoms at birth in almost all cases, and those who appeared well at birth had a very low chance of having EOS. The risk of EOS in neonates (asymptomatic at birth) exposed to intrapartum fever was low. Although definite conclusions on causation are lacking, our data support SPEs of asymptomatic newborns at risk for EOS. SPEs seems a safe and effective alternative to laboratory screening and empirical antibiotic therapy.

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.

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.

Perinatal infections remain a significant cause of neonatal morbidity and mortality. Mother-to-child transmission (MTCT) can occur in utero (rubella, CMV, syphilis, Toxoplasma), intrapartum (HBV, HIV, group B streptococci, enteric gram-negative organisms, gonococci, chlamydiae) or during post-natal period (TBC, HIV, CMV) The microorganism type and the timing of infection influence the outcome that includes spontaneous abortion, intrauterine growth restriction, premature birth, stillbirth, congenital malformation and symptomatic or asymptomatic neonatal infection.

Background Cisapride is a possible cause of potentially life threatening QT prolongation. Aims We investigated these cardiac side effects in premature infants, mainly in relation to fetal growth. Patients Forty six preterms (mean birth weight 1.350 g, mean post conceptional age 31 weeks) were studied. Thirty one of them were appropriate for gestational age (AGA) and 15 were small for gestational age (SGA). Cisapride was randomly administered at a 0.3 mg/kg or 0.6 mg/kg daily dose. Fifty preterms (15 SGA/35 AGA) not treated with Cisapride were used as control group. Methods A pre-treatment ECG was performed and the QT-corrected (Bazzet’s formula) intervals were compared with the in-treatment values (normal values ≤440 mseconds). In the control group two different ECG were performed with a timing similar to the treated group (mean interval 5 days). Results and Conclusions No patients showed clinical evidence of drug toxicity. In the small for gestational age group, both baseline QTc (mean 397; range 370–420 ms) and in-treatment QTc (mean 410 range 360–500 ms) were significantly higher than those found in the appropriate for gestational age group (mean 386, range 360–420 ms; mean 396, range 370–420 ms, respectively). This difference was found also in the first ECG of the control group. Moreover the mean QTc lengthening during treatment was significantly higher in small for gestational age group than in the appropriate for gestational age group. Three infants showed a rise in the QTc interval above the value of 440 ms and all were SGA (p = 0.03). No significant correlation was found between birth weight or gestational age and the change in QTc values during Cisapride treatment in the appropriate for gestational age group. Intrauterine growth retardation is a major risk factor for Cisapride-induced QT prolongation in preterm infants.

Congenital/perinatal nervous system (CNS) infections are an important cause of mortality and morbidity in neonatal period, and long-term sequelae. Many pathogens can lead to infections frequently involving the CNS, with possible disruption of brain development, which often is related to gestational age of maternal infection. The mechanism of infection and damage is different among the infectious agents, leading to more specific pathologic findings. It is necessary in newborns with confirmed or suspected CNS infection to undergo investigation by neuroimaging techniques to help healthcare providers, give adequate treatment and follow-up care and counsel parents. Computed tomography, Magnetic Resonance Imaging and cerebral ultrasonography are fundamental tools in evaluating infants with suspected or proved congenital/perinatal infections. Each imaging technique has its advantages, disadvantages and limits, since they are sometimes complementary.

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.).

Purpose: To assess the diagnostic and prognostic value of cerebral magnetic resonance imaging (cMRI) in comparison with that of cerebral ultrasound (cUS) in predicting neurodevelopmental outcome in newborns with congenital cytomegalovirus (CMV) infection. Methods: Forty CMV-congenitally infected newborns underwent cUS and cMRI within the first month of life. Clinical course, laboratory findings, visual/hearing function and neurodevelopmental outcome were documented. Results: Thirty newborns showed normal cMRI, cUS and hearing/visual function in the first month of life; none showed CMV-related abnormalities at follow-up. Six newborns showed pathological cMRI and cUS findings (pseudocystis, ventriculomegaly, calcifications, cerebellar hypoplasia) but cMRI provided additional information (white matter abnormalities in three cases, lissencephaly/polymicrogyria in one and a cyst of the temporal lobe in another one); cerebral calcifications were detected in 3/6 infants by cUS but only in 2/6 by cMRI. Four of these 6 infants showed severe neurodevelopmental impairment and five showed deafness during follow-up. Three newborns had a normal cUS, but cMRI documented white matter abnormalities and in one case also cerebellar hypoplasia; all showed neurodevelopmental impairment and two were deaf at follow-up. One more newborn showed normal cUS and cMRI, but brainstem auditory evoked responses were abnormal; psychomotor development was normal at follow-up. Conclusions: Compared with cUS, cMRI disclosed additional pathological findings in CMV-congenitally infected newborns. cUS is a readily available screening tool useful in the identification of infected newborns with major cerebral involvement. Further studies with a larger sample size are needed to determine the prognostic role of MRI, particularly regarding isolated white matter lesions.

Neonatal congenital infections are an important cause of mortality, morbidity and long-term neurodevelopmental and sensorineural sequelae. Many pathogens can cause in utero infection, and among them, cytomegalovirus (CMV) plays a prominent role. In developed countries, CMV poses major health problems as it is the most common pathogen leading to congenital infection, and the leading cause of nonhereditary deafness in children. Evaluation of central nervous system (CNS) involvement in congenital CMV infected newborns is mandatory to better assess the severity of the disease, to guide adequate treatment, to define prognosis, and to tailor follow-up observations and parents’ counselling. Cerebral ultrasonography (cUS), Computed Tomography (CT), and Magnetic Resonance Imaging (MRI) are the currently available techniques to evaluate infants with suspected or proven congenital CMV infection. In congenital CMV infection, their role in early detection and confirmation of cerebral involvement within the first month of life is crucial to initiate specific treatment with antivirals. Neonatologists, paediatricians and radiologists should be aware of the role, the limitations and the inherent risks related to the use of these specific neuroimaging diagnostic tools in these infants. In this article we will discuss from a neonatological perspective the advantages, disadvantages, risks and limitations of each imaging technique. ©

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.

OBJECTIVE: To assess the risk of post-natal cytomegalovirus (CMV) transmission to very low birth weight (VLBW) infants fed with their mother's fresh milk. STUDY DESIGN: Prospective, observational study of 80 VLBW infants and their 68 mothers. Infants' urine and their own mother's fresh breast milk were tested for CMV by means of culture tests once a week until discharge. CMV in infected milk and urine were genotyped. The clinical course, laboratory findings, and outcome of infants infected with CMV at 2 years of age are reported. RESULTS: Fifty-three mothers (78%) were CMV-seropositive at delivery. CMV was detected in the milk of 21 of 53 seropositive mothers (40%), and CMV was in the urine in 9 of 26 infants (35%) fed with CMV-positive milk. The same gN-genotype was found in milk and urine. Three infected infants

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.

Most in-fected children show no symptoms at birth but are at greatrisk of developing late sequelae during the first years of lifeor in early adulthood. In fact Congenital Toxoplasmosis isoften undiagnosed, thereby predisposing the infant to unto-wardsequelaefromtheinfection,includingdecreasedvisionor blindness, decreased hearing or deafness, and mental andpsychomotor retardation. Therefore, it is important to rec-ognize as soon as possible the newborns at risk of infection,in order to begin therapy to prevent or reduce the numberand severity of the clinical manifestations of the congenitaldisease. Due to the absence of specific signs of infection atbirth the serological tests are often the only method for di-agnosis. Serological diagnosis of Congenital Toxoplasmosisin the newborn depends on the detection of IgM and/or IgAanti

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.

s for 2nd International Conference on Clinical Neonatology Comparison of conventional blood culture method and BacT/Alert system with respect to yield and time to positivity in neonatal sepsis Arti Maria⁎, Sumitha Phalgun, Charoo Hans, N. Dubey, Deepak Goyal PGIMER & Associated Dr RML Hospital, New Delhi, India ⁎Corresponding author. Efficient and faster ways of diagnosing neonatal sepsis than conventional blood culture are needed in clinical practice. Recently, automated systems have been developed to address this issue. We hypothesized that automated compared to conventional methods of blood culture may give better isolation performances and shorter time to yield in the diagnosis of neonatal sepsis. This was a single-center, prospective, cohort study enrolling neonates with suspected neonatal sepsis in tertiary neonatal referral unit of north India. From May 2008 to April 2009, ninety consecutive neonates with suspected sepsis were enrolled with the objective of comparing the sensitivity and the time needed to yield positivity of conventional vs. BacT/Alert blood culture. Conventional and automated cultureswere collected in standardized manner from each baby, the order being alternate in consecutive babies. Refusal to consent, being ELBW and showing hemodynamical unstability were the only exclusion criteria for the neonates screened for inclusion in the study. Statistical analysis was conducted with the SPSS software version 11.0. The results showed that positivity by BacT/Alert was 38.8% (35/90) compared to 14.4% (13/90)with conventionalmethod (p

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.

Background To evaluate whether physical and/or chemical features of gastro-esophageal reflux (GER) influence its relationship with apnea of prematurity (AOP). Methods Fifty-eight preterm newborns (GA ≤33 weeks) with recurrent apneas were studied by simultaneous polysomnography and combined impedance and pH monitoring, to analyze whether the correlation between GER and AOP varies according to the acidity, duration and height of GERs. Key Results The frequency of apnea (number apnea/min) occurring after-GER [median (range) 0.07 (0–0.25)] was higher than the one detected in GER-free period [0.06 (0.04–0.13), P = 0.015], and also than the one detected before-GER [0 (0–0.8), P = 0.000]. The frequency of apneas detected in the 30’’ after pH-GER [median (range), 0 min−1 (0–1.09)] was higher than the frequency detected in the 30’’ before [0 (0–0.91), P = 0.04]; even more, the frequency of apneas detected after non-acid MII-GER episodes [0 (0–2)] was significantly higher than the one detected before [0 (0–1), P = 0.000], whereas the frequency of apneas detected before acid MII-GER episodes [0 (0–0.67)] did not differ from the one detected after [0 (0–2), P = 0.137]. The frequency of pathological apneas detected in the 30’’ after-GER (0 min−1, range 0–0.55) was higher than the frequency detected before (0, range 0–0.09; P = 0.001). No difference in mean height or in mean duration was found between GERs correlated and those non-correlated to apnea. Conclusions & Inferences Non-acid GER is responsible for a variable amount of AOP detected after-GER: this novel finding must be taken into consideration when a therapeutic strategy for this common problem is planned.

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