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

BACKGROUND: Respiratory 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. METHODS: We 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. RESULTS: We 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 PM(10) concentration of the week before. CONCLUSIONS: RSV epidemic trend in Bologna (Italy) is related to the mean minimum temperature, and the mean PM(10) concentration

2300. Neonates born to mothers with SARS-CoV-2 infection in pregnancy: a follow-up and serological study

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

Universal Newborn Screening for Congenital Cytomegalovirus Infection - From Infant to Maternal Infection: A Prospective Multicenter Study

Introduction: Most infants at risk for cytomegalovirus (CMV)-associated sensorineural hearing loss (SNHL) are unrecognized because of the absence of a universal neonatal CMV screening. The search of CMV-DNA by molecular methods in salivary swabs was demonstrated to be a reliable approach. This study describes the results obtained by carrying out a universal screening for congenital CMV (cCMV) infection including all live-born newborns in three Italian sites, as well as the therapeutic interventions and clinical outcome of the CMV-infected neonates. Moreover, CMV maternal infection's characteristics were evaluated. Methods: To confirm or exclude cCMV infection, a CMV-DNA-positive result on a first salivary swab was followed by repeated saliva and urine samples collected within 21 days of age. Breast milk samples were also collected. The search of CMV-DNA was performed with a single automated quantitative commercial real-time PCR assay, regardless of the type of samples used. Results: A total of 3,151 newborns were enrolled; 21 (0.66%) of them were congenitally infected (median saliva viral load at screening, 6.65 [range, 5.03-7.17] log10 IU/ml). Very low/low viral load in screening saliva samples (median value, 1.87 [range, 1.14-2.59] log10 IU/ml) was associated with false-positive results (n = 54; 1.7%). CMV-DNA was detected in almost half of the breast milk samples of mother-infant pairs with a false-positive result, suggesting that contamination from breast milk may not be the only explanation in the study population. cCMV infection confirmation with the search of CMV-DNA in a urine sample proved to be the gold standard strategy, since false-positive results were observed in 4/54 (7.5%) of the repeated saliva samples. Symptomatic cCMV infection was observed in 3/21 (14.3%) infants; notably, one (4.7%) developed moderate unilateral SNHL at 5 months after birth. Finally, two symptomatic cCMV infections were associated with primary maternal infection acquired in the first trimester of gestation; one newborn with severe cCMV symptoms was born to a mother with no CMV checkups in pregnancy. Conclusion: Without universal neonatal CMV screening, some infected infants who develop late neurological sequelae may not be recognized and, consequently, they are not able to benefit early from instrumental and therapeutic interventions to limit and/or treat CMV disease

Neonatal outcomes following maternal SARS-CoV-2 infection in pregnancy - longitudinal follow-up and assessment of transplacental antibody transfer

BACKGROUND: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in pregnancy has been associated with multiple adverse pregnancy outcomes, including the risk of in utero mother-to-child transmission. Short- and long-term outcomes of SARS-CoV-2 exposed neonates and the extent to which maternal SARS-CoV-2 antibodies are transferred to neonates are still unclear. METHODS: Prospective observational study enrolling neonates born to mothers with SARS-CoV-2 infection in pregnancy, between April 2020-April 2021. Neonates were evaluated at birth and enrolled in a 12-month follow-up. SARS-CoV-2 IgG transplacental transfer ratio was assessed in mother-neonate dyads at birth. Maternal derived IgG were followed in infants until negativizing. RESULTS: Of 2745 neonates, 106 (3.9%) were delivered by mothers with SARS-CoV-2 infection in pregnancy. Seventy-six of 106 (71.7%) mothers were symptomatic. Median gestational age and mean birth weight were 39 weeks (range 25+5-41+4) and 3305 grams (SD 468). Six of 106 (6%) neonates were born preterm, without significant differences between asymptomatic and symptomatic mothers (P=0.67). No confirmed cases of in utero infection were detected. All infants had normal cerebral ultrasound and clinical evaluation at birth and during follow-up, until a median age of 7 months (range 5-12). All mothers and 96/106 (90.5%) neonates had detectable SARS-CoV-2 IgG at birth. Transplacental transfer ratio was higher following second trimester maternal infections (mean 0.940.46 versus 1.070.64 versus 0.750.44, P=0.039), but was not significantly different between asymptomatic and symptomatic women (P=0.20). IgG level in infants progressively decreased after birth: at 3 months 53% (51/96) and at four months 68% (63/96) had lost maternal antibodies respectively. The durability of maternal antibodies was positively correlated to the IgG level at birth (r=0.66; P<0.00001). CONCLUSIONS: Maternal SARS-CoV-2 infection was not associated with increased neonatal or long-term morbidity. No cases of confirmed in utero infection were detected. Efficient transplacental IgG transfer was found following second trimester maternal infections

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

Antenatal and Postnatal Sequelae of Oxidative Stress in Preterm Infants: A Narrative Review Targeting Pathophysiological Mechanisms

The detrimental effects of oxidative stress (OS) can start as early as after conception. A growing body of evidence has shown the pivotal role of OS in the development of several pathological conditions during the neonatal period, which have been therefore defined as OS-related neonatal diseases. Due to the physiological immaturity of their antioxidant defenses and to the enhanced antenatal and postnatal exposure to free radicals, preterm infants are particularly susceptible to oxidative damage, and several pathophysiological cascades involved in the development of prematurity-related complications are tightly related to OS. This narrative review aims to provide a detailed overview of the OS-related pathophysiological mechanisms that contribute to the main OS-related diseases during pregnancy and in the early postnatal period in the preterm population. Particularly, focus has been placed on pregnancy disorders typically associated with iatrogenic or spontaneous preterm birth, such as intrauterine growth restriction, pre-eclampsia, gestational diabetes, chorioamnionitis, and on specific postnatal complications for which the role of OS has been largely ascertained (e.g., respiratory distress, bronchopulmonary dysplasia, retinopathy of prematurity, periventricular leukomalacia, necrotizing enterocolitis, neonatal sepsis). Knowledge of the underlying pathophysiological mechanisms may increase awareness on potential strategies aimed at preventing the development of these conditions or at reducing the ensuing clinical burden

Antenatal and Postnatal Sequelae of Oxidative Stress in Preterm Infants: A Narrative Review Targeting Pathophysiological Mechanisms

The detrimental effects of oxidative stress (OS) can start as early as after conception. A growing body of evidence has shown the pivotal role of OS in the development of several pathological conditions during the neonatal period, which have been therefore defined as OS-related neonatal diseases. Due to the physiological immaturity of their antioxidant defenses and to the enhanced antenatal and postnatal exposure to free radicals, preterm infants are particularly susceptible to oxidative damage, and several pathophysiological cascades involved in the development of prematurity-related complications are tightly related to OS. This narrative review aims to provide a detailed overview of the OS-related pathophysiological mechanisms that contribute to the main OS-related diseases during pregnancy and in the early postnatal period in the preterm population. Particularly, focus has been placed on pregnancy disorders typically associated with iatrogenic or spontaneous preterm birth, such as intrauterine growth restriction, pre-eclampsia, gestational diabetes, chorioamnionitis, and on specific postnatal complications for which the role of OS has been largely ascertained (e.g., respiratory distress, bronchopulmonary dysplasia, retinopathy of prematurity, periventricular leukomalacia, necrotizing enterocolitis, neonatal sepsis). Knowledge of the underlying pathophysiological mechanisms may increase awareness on potential strategies aimed at preventing the development of these conditions or at reducing the ensuing clinical burden

Nevirapine prophylaxis to prevent HIV-1 mother-to-child transmission: pharmacokinetic considerations in preterm infants

Prophylaxis with zidovudine and 3 doses of nevirapine (NVP) is recommended for infants born to HIV-1 infected untreated mothers to prevent HIV-1 mother-to-child transmission. However little is known about NVP pharmacokinetics in neonates, mostly in preterm infants. We performed therapeutic monitoring of NVP plasma concentrations in a 32-week preterm HIV-1 exposed infant born to an infected untreated mother. With the recommended regimen, an intense NVP exposure was observed, with NVP plasma levels exceeding the target concentration by up to 40 times, suggesting that when a laboratory assessment of NVP plasma concentrations is available, it may be useful to monitor and optimize drug exposure.Prophylaxis with zidovudine and 3 doses of nevirapine (NVP) is recommended for infants born to HIV-1 infected untreated mothers to prevent HIV-1 mother-to-child transmission. However little is known about NVP pharmacokinetics in neonates, mostly in preterm infants. We performed therapeutic monitoring of NVP plasma concentrations in a 32-week preterm HIV-1 exposed infant born to an infected untreated mother. With the recommended regimen, an intense NVP exposure was observed, with NVP plasma levels exceeding the target concentration by up to 40 times, suggesting that when a laboratory assessment of NVP plasma concentrations is available, it may be useful to monitor and optimize drug exposure

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 \ub1 22.2 vs. 34.8 \ub1 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

Necrotizing Enterocolitis: Overview on In Vitro Models

none9noNecrotizing enterocolitis (NEC) is a gut inflammatory disorder which constitutes one of the leading causes of morbidity and mortality for preterm infants. The pathophysiology of NEC is yet to be fully understood; several observational studies have led to the identification of multiple factors involved in the pathophysiology of the disease, including gut immaturity and dysbiosis of the intestinal microbiome. Given the complex interactions between microbiota, enterocytes, and immune cells, and the limited access to fetal human tissues for experimental studies, animal models have long been essential to describe NEC mechanisms. However, at present there is no animal model perfectly mimicking human NEC; furthermore, the disease mechanisms appear too complex to be studied in single-cell cultures. Thus, researchers have developed new approaches in which intestinal epithelial cells are exposed to a combination of environmental and microbial factors which can potentially trigger NEC. In addition, organoids have gained increasing attention as promising models for studying NEC development. Currently, several in vitro models have been proposed and have contributed to describe the disease in deeper detail. In this paper, we will provide an updated review of available in vitro models of NEC and an overview of current knowledge regarding its molecular underpinnings.openDe Fazio, Luigia; Beghetti, Isadora; Bertuccio, Salvatore Nicola; Marsico, Concetta; Martini, Silvia; Masetti, Riccardo; Pession, Andrea; Corvaglia, Luigi; Aceti, AriannaDe Fazio, Luigia; Beghetti, Isadora; Bertuccio, Salvatore Nicola; Marsico, Concetta; Martini, Silvia; Masetti, Riccardo; Pession, Andrea; Corvaglia, Luigi; Aceti, Ariann