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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.

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.

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.

Background Group B streptococcus (GBS) is a leading cause of severe infections in newborns. Intrapartum antibiotic chemoprophylaxis (IAP) reduces the rate of early-onset disease. The aim of this study is to determine the degree of clinicians’ compliance with the suggested protocol for GBS prevention in Emilia-Romagna (Italy). Methods Characteristics of each delivery were prospectively recorded in the period between October 2005 to December 2005. Standardized proforma were used to collect data. Results Among 5118 babies, 7.2% (369) were preterm and 92.3% were born at term (4749). Antenatal screening was performed in 86.6% of women who delivered at term, of which 18.1% were GBS culture-positive. Information regarding culture site was available in 93.2% of women screened and recto-vaginal cultures were documented in 42.7%. IAP was administered to 28.7% of 3937 women at term who had either spontaneous delivery or emergency caesarean section. In this cohort, 15.9% were diagnosed GBS culture-positive, of which 92.6% received IAP. Prophylaxis was also administered to 8.4% (331) of women for no apparent reason. Compared with tertiary level hospitals, women delivering in primary/secondary hospitals were more likely to be both GBS screened ( P < 0.0001; OR 3.04; CI 2.33-3.97) and to receive prophylaxis ≥4 hours before delivery ( P = 0.0025; OR 1.57; CI 1.17-2.12). Conclusions GBS screening was performed in > 85% of women and > 90% of culture-positive women received prophylaxis. However, there is a need to educate clinicians about protocol adherence, as most cultures were suboptimal and cases of unnecessary IAP were administered. The screening was more effective in hospitals with fewer deliveries.

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

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

BACKGROUND: This study examined the effects of a standardized hand hygiene program on the rate of nosocomial infection (NI) in very low birth weight (VLBW) infants (birth weight < 1500 g) admitted to our neonatal intensive care unit (NICU). METHODS: We compared the rate of NI in VLBW infants in 2 separate periods. In the first period, staff were encouraged to perform handwashing using a plain fluid detergent (0.5% triclosan). In the second period, a standardized hand hygiene program was implemented using antimicrobial soap (4% chlorhexidine gluconate) and alcohol-based hand rubs. RESULTS: NI after 72 hours of life was detected in 16 of the 85 VLBW infants in the first period and in 5 of the 80 VLBW infants in the second period. The rate of central venous catheter colonization was significantly lower in the second period (5.8%) than in the first period (16.6%). CONCLUSION: In our NICU, the incidence of NI in VLBW infants was significantly reduced after the introduction of a standardized handwashing protocol. In our experience, a proper hand hygiene program can save approximately 10 NI episodes/year, at a cost of $10,000 per episode. Therefore, improving hand hygiene practice is a cost-effective program in the NICU.

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

OBJECTIVE: To report the accuracy of ultrasound scanning (US) in predicting neurodevelopmental and sensorineural outcome in patients with congenital cytomegalovirus (CMV) infection. STUDY DESIGN: Fifty-seven neonates with congenital CMV infection underwent brain US and were observed prospectively for motor skills, developmental quotient, and hearing function. RESULTS: Abnormal results on US were found in 12 of 57 neonates. US lesions were more frequent in newborns with clinical and laboratory signs of congenital CMV infection at birth (10/18) than in newborns who had no symptoms at birth (2/39; P < .001). At least 1 sequela developed in all neonates with symptoms who had abnormal US results, whereas none of the neonates with symptoms who had normal US results had long-term sequelae (P < .001). In the population without symptoms, sensorineural hearing loss developed in 3 of 37 (8.1%) neonates with normal US results, whereas severe sequelae developed in 1 of 2 neonates with abnormal US results. CONCLUSIONS: A good correlation was found between cerebral US abnormalities and the prediction of outcome in newborns who were congenitally infected with CMV and had symptoms at birth. US could be performed as the first neuroimaging study in these newborns. Data are insufficient to permit any suggestions for the population without symptoms.

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 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: 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.

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 Group B streptococcus (GBS) is a leading cause of neonatal early-onset infections (EOI). In USA infections decreased after adoption of prevention guidelines, while in Europe strategies are low-developed. We retrospectively investigated prevention strategies in an Italian area (35 000 live birth/year). Method Twenty-eight birth-centres of Emilia-Romagna were asked to fulfil a questionnaire about prevention strategies adopted during the 2000 and 2003. We promoted periodical meetings to develop and share prevention guidelines. Management of pregnant women and newborns were analyzed. Results: Fifteen and 27 centres participated to the study during 2000 and 2003 respectively. All centres used a screening-based approach. Eight (57,1 %) in 2000 and 19 (70.4%) centres in 2003 collected maternal swabs at the lower third of vagina; rectal cultures or selective broth media were not used in 2000. Fourteen centres (51.9%) used vagino-rectal swabs and 5 (18.5%) selective broth media in 2003. If intrapartum chemoprophylaxis (IAP) was inadequate, thirteen centres (92.8%) in 2000 screened neonatal colonization, most of them (78.6%) treating colonized infants with antibiotics. In 2003 a few centres assessed colonization (37%) and treated (29.6%) infants. In 2000 only two centres (14.3%) collected blood cultures in 'at risk' newborn, while sixteen centres (59.2 %) did in 2003. Changes were more prominent in centres participating since 2000. Conclusion Knowledge of guidelines among professionals and health-care providers is a good tool to obtain changes in GBS policies. Screening of pregnant women and ascertainment of neonatal infection significantly improved, avoiding newborn over treatment.

Background Group B streptococcus (GBS) is the leading cause of early-onset infections (EOI) in the developed world. Few data are available in Europe about incidence and clinical findings of neonatal disease. We reviewed cases occurred in the last 2 years in Emilia-Romagna (an area with about 4 500 000 million people).

Invasive candida infections are a major cause of morbidity and mortality in preterm infants. We performed a multicenter, randomized, double-blind, placebo-controlled trial of fluconazole for the prevention of fungal colonization and infection in very-low-birth-weight neonates.During a 15-month period, all neonates weighing less than 1500 g at birth from eight tertiary Italian neonatal intensive care units (322 infants) were randomly assigned to receive either fluconazole (at a dose of either 6 mg or 3 mg per kilogram of body weight) or placebo from birth until day 30 of life (day 45 for neonates weighing1000 g at birth). We performed weekly surveillance cultures and systematic fungal susceptibility testing.Among infants receiving fluconazole, fungal colonization occurred in 9.8% in the 6-mg group and 7.7% in the 3-mg group, as compared with 29.2% in the placebo group (P0.001 for both fluconazole groups vs. the placebo group). The incidence of invasive fungal infection was 2.7% in the 6-mg group and 3.8% in the 3-mg group, as compared with 13.2% in the placebo group (P=0.005 for the 6-mg group and P=0.02 for the 3-mg group vs. the placebo group). The use of fluconazole did not modify the relationship between colonization and the subsequent development of invasive fungal infection. Overall mortality was similar among groups, as was the incidence of cholestasis. No evidence for the emergence of resistant candida species was observed, but the study did not have substantial power to detect such an effect.Prophylactic fluconazole reduces the incidence of colonization and invasive candida infection in neonates weighing less than 1500 g at birth. The benefit of treating candida colonization is unclear. (Current Controlled Trials number, ISRCTN85753869 [controlled-trials.com]).