Concetta Marsico

Respiratory syncytial virus infection in infants and correlation with meteorological factors and air pollutants

BackgroundRespiratory Syncytial Virus (RSV) is the most important cause of severe respiratory infections in infants with seasonal epidemics. Environmental factors (temperature, humidity, air pollution) could influence RSV epidemics through their effects on virus activity and diffusion.MethodsWe conducted a retrospective study on a paediatric population who referred to our Paediatric Emergency Unit in order to analyze the correlation between weekly incidence of RSV positive cases during winter season in Bologna and meteorological factors and air pollutants concentration.ResultsWe observed a significant correlation between the incidence of RSV infections and the mean minimum temperature registered during the same week and the previous weeks.The weekly number of RSV positive cases was also correlated to the mean PM10 concentration of the week before.ConclusionsRSV epidemic trend in Bologna (Italy) is related to the mean minimum temperature, and the mean PM10 concentration.

Role of cerebral ultrasound and magnetic resonance imaging in newborns with congenital cytomegalovirus infection

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.

Toxoplasmosis in pregnancy in an area with low seroprevalence: is prenatal screening still worthwhile?

Background: The effectiveness of Toxoplasma gondii (Tg) screening during pregnancy in areas with a low prevalence of the infection is debated. We investigate the Tg serological status, the rate of primary infection in a cohort of pregnant women and the rate of congenital toxoplasmosis among their infants during a 3-year period in an urban area with low Tg prevalence. Methods: Demographic and Tg serological data for all pregnant women delivering from January 2009 to December 2011 were collected. All pregnant women with primary Tg infection during pregnancy and their infants were included in the study. Results: In early pregnancy, 10,347 women underwent prenatal screening and 2308 (22.3%) had anti-Tg. The seroprevalence among non-native women was significantly higher than that among native women [32.8% vs. 19.1%, relative risk: 1.71, P < 0.001]. The incidence rate of primary Tg infection during pregnancy was 0.77%. Immigrant women were more likely to be infected during pregnancy than Italian women (relative risk: 4.88, P < 0.001). Tg infection was more frequent in women coming from Africa, Asia, Eastern Europe and South America. The CT incidence rate was 0.06%. All congenitally infected infants were born to immigrant mothers. Conclusions: Tg infection during pregnancy and congenital disease are more frequent in non-native mothers and their infants. Measures to prevent Tg exposition must be carefully explained to pregnant women, with a focus on specific habits in non-native women. Prenatal screening is still effective to select women for prenatal therapy aiming to decrease vertical transmission and to identify foetuses/newborns with congenital disease that could benefit from pre/postnatal antiparasitic therapy.

Silver-Russell syndrome due to paternal H19/IGF2 hypomethylation in a twin girl born after in vitro fertilization.

Silver–Russell syndrome (SRS) is a clinically and genetically heterogeneous syndrome characterized by severe intrauterine and postnatal growth retardation, facial dysmorphism and body asymmetry. One of the main molecular mechanisms leading to the syndrome involves methylation abnormalities of chromosome 11p15. In the last decades, an increase of imprinting disorders have been reported in children born from assisted reproductive technology (ART); however there is currently little evidence linking SRS and ART. Only few infants with SRS born using ART, supported by molecular analysis, have been described. We report on a twin‐girl conceived using intracytoplasmic sperm injection (ICSI) diagnosed with SRS. Molecular studies revealed a hypomethylation of the paternal H19/IGF2 Imprinting Control Region. Her twin sister had a normal prenatal and postnatal growth and a normal methylation pattern of the chromosome 11p15. This is the second reported case of a twin infant with SRS conceived using ART with hypomethylation of H19/IGF2; it provides additional evidence of a possible relationship between ART procedures and methylation defects observed in SRS. Given the clinical heterogeneity of SRS, and the increased risk of multiple and preterm births in the ART‐conceived children, it is possible that a number of cases of SRS remains undiagnosed in this population. Future studies should investigate the possible link between ART and SRS, in order to better understand the causes of epimutations in ART pregnancies, and to help clinicians to adequately counsel parents who approach to ART and to assess the opportunity of a long‐term follow‐up of children conceived using ART.

Congenital Cytomegalovirus infection: advances and challenges in diagnosis, prevention and treatment

Cytomegalovirus (CMV) is the most frequent cause of congenital infection worldwide, with an estimated incidence in developed countries of 0.6–0.7% of all live births. The burden of disease related to congenital CMV in substantial, as it is the leading non-genetic cause of sensorineural hearing loss and an important cause of neurodevelopmental disabilities in children. Despite its clinical significance, congenital CMV infection often goes undetected because the majority of infected infants are asymptomatic at birth and screening programs have not been substantially implemented. Other than behavioral measures, effective interventions aimed at the prevention of maternal infection and of mother-to-child transmission are lacking. Due to a convergence of recent advances in both diagnostic and therapeutic strategies in infants with congenital CMV, though, the field likely will be changing rapidly over just the next few years. Specifically, a highly-sensitive screening test with high throughput potential has been developed, and treatment of infants symptomatically infected with congenital CMV has proven to be well-tolerated and effective in improving long-term hearing and neurodevelopmental outcomes.This review highlights the clinical importance of congenital CMV infection, the developments in laboratory diagnostics, and the benefits of antiviral therapy. It also identifies the global efforts still required in the prevention of maternal infection and in the optimization of antiviral therapy to further reduce the burden of congenital CMV disease.

Evaluation of a New Protocol for Retrospective Diagnosis of Congenital Toxoplasmosis by Use of Guthrie Cards

ABSTRACT The aim of this study was to assess the diagnostic value of IgM Western blotting (WB), IgA enzyme immunoassay (EIA), and DNA amplification by real-time PCR on Guthrie cards to retrospectively establish the diagnosis of congenital toxoplasmosis (CT). To this purpose, Guthrie cards were collected from 18 infants born to mothers with primary Toxoplasma gondii infection during pregnancy. Moreover, the analytical sensitivity of T. gondii PCR was assessed by testing mock dried blood specimens set up with several known DNA dilutions. IgM WB was demonstrated to be the most sensitive method. When the results of T. gondii DNA detection and specific IgM recovery were combined, retrospective CT diagnosis by using Guthrie cards was established in 3 out of 6 infected infants (sensitivity, 50%; 95% confidence interval, 26.8% to 73.2%). No positive PCR or serologic results were found in the group of 12 uninfected infants, demonstrating the excellent specificity of the three methods (95% confidence interval, 78.1% to 99.5%). The findings of the present study suggest that, in cases of missed diagnosis of CT at birth, analysis of Guthrie cards for children with compatible clinical findings after the perinatal period, in particular the combination of recovery of specific IgM antibodies and T. gondii DNA amplification, could be helpful. Nevertheless, since suboptimal conditions of storage of dried blood specimens can seriously affect sensitivity, negative results cannot rule out CT diagnosis. In contrast, because of the excellent specificity shown by IgM serologic testing and T. gondii DNA amplification on Guthrie cards, positive results obtained by either of the two methods should be considered diagnostic.

Neonatal and long-term ophthalmological findings in infants with symptomatic and asymptomatic congenital cytomegalovirus infection

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±20.1months (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.

933 Clinical Findings and Long-Term Outcome in Infants Born to Mothers with Preexisting Immunity to Cytomegalovirus

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.

261 Ten-Year follow-Up of Infants with Symptomatic And Asymptomatic Congenital Cytomegalovirus Infection

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.

924 Diagnosis and Prognosis of Congenital Toxoplasmosis

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.