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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.

OBJECTIVES To evaluate outcomes of neonates born to mothers with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy, the dynamics of placental transfer of maternal antibodies, and its persistence during infancy. METHODS Cohort study enrolling neonates born to mothers with SARS-CoV-2 infection in pregnancy. All infants were evaluated at birth. Those born to women with infection onset within 2 weeks before delivery were excluded from further analyses. Remaining infants underwent cerebral and abdominal ultrasound, fundoscopy evaluation, and were enrolled in a 12 month follow-up. Qualitative immunoglobulin G (IgG)/immunoglobulin M and quantitative IgG to S1/S2 subunits of spike protein were assessed in mother–neonate dyads within 48 hours postdelivery and during follow-up. RESULTS Between April 2020 and April 2021, 130 of 2745 (4.7%) neonates were born to mothers with SARS-CoV-2 infection in pregnancy, with 106 of 130 infections diagnosed before 2 weeks before delivery. Rates of preterm and cesarean delivery were comparable between women with and without infection (6% vs 8%, P = .57; 22% vs 32%, P = .06). No clinical or instrumental abnormalities were detected at birth or during follow-up. There was a positive correlation between maternal and neonatal SARS-CoV-2 IgG levels (r = 0.81, P < .001). Transplacental transfer ratio was higher after second-trimester maternal infections as compared with first and third trimester (P = .03). SARS-CoV-2 IgG level progressively decreased in all infants, with 89 of 92 (97%) infants seronegative at 6 months of age. CONCLUSIONS Clinical outcomes were favorable in all infants. Matching peak IgG level after infection and higher IgG transplacental transfer might result in the most durable neonatal passive immunity.

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.

Necrotizing 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.

BackgroundViral loads (VLs) frequently are followed during treatment of symptomatic congenital cytomegalovirus disease, but their predictive value is unclear.MethodsPost hoc analysis of 2 antiviral studies was performed. Seventy-three subjects were treated for 6 weeks and 47 subjects were treated for 6 months. Whole blood VL was determined by real-time polymerase chain reaction before and during therapy.ResultsHigher baseline VL was associated with central nervous system involvement (3.82 log, range 1–5.65 vs 3.32 log, range 1–5.36; P = .001), thrombocytopenia (3.68 log, range 1–5.65 vs 3.43 log, range 1–5.36; P = .03), and transaminitis at presentation (3.73 log, range 1–5.60 vs 3.39 log, range 1–5.65; P = .009), but with overlap in the amount of virus detected between groups. In subjects treated for 6 months, lower VL at presentation correlated with better hearing outcomes at 12 months, but VL breakpoints predictive of hearing loss were not identified. Sustained viral suppression during 6 months of therapy correlated with better hearing outcomes at 6, 12, and 24 months (P = .01, P = .0007, P = .04), but a majority without viral suppression still had improved hearing.ConclusionsIn infants with symptomatic congenital cytomegalovirus disease, higher whole blood VL before initiation of antiviral therapy has no clinically meaningful predictive value for long-term outcomes.

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.

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.

Background Sensorineural hearing loss (SNHL) and neurodevelopmental (ND) outcomes are favorably impacted by antiviral therapy in infants with symptomatic cCMV disease. We correlated blood VL before and during therapy with clinical findings at presentation and follow-up in this population. Methods Post-hoc analysis of two clinical trials conducted by the CASG from 2002 to 2013 evaluating valganciclovir therapy. 120 subjects (73 treated × 6 weeks, 47 treated × 6 months) were included. Whole blood VL was determined by real-time PCR at a central laboratory before therapy (baseline, BL) and periodically for 6 months. Results In subjects treated for 6 months, increases in BL VL correlated with decreased probability of better hearing outcomes at 12 months (Figure 1), but clinically meaningful VL thresholds that predict SNHL were not identified (Table 1). Subjects treated for 6 weeks had no correlation between BL VL and SNHL. No correlation was found between BL VL and Bayley ND testing at 12 and 24 months for subjects receiving either treatment duration. Subjects treated for 6 months who achieved and sustained VL suppression (3 symptoms of congenital CMV at presentation had higher BL VL than subjects with ≤3 symptoms (3.75 log, range 1.00–5.65, vs. 3.38 log, range 1.00–5.36; P = 0.005). Conclusion Blood VL at BL and during therapy has little clinically meaningful predictive value for long-term outcomes in symptomatic congenital CMV. Disclosures J. Englund, Gilead: Consultant and Investigator, Research support; Chimerix: Investigator, Research support; Alios: Investigator, Research support; Novavax: Investigator, Research support; MedImmune: Investigator, Research support; GlaxoSmithKline: Investigator, Research support

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.

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

Background 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.

none 8 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 PM10 concentration of the week before. CONCLUSIONS: RSV epidemic trend in Bologna (Italy) is related to the mean minimum temperature, and the mean PM10 concentration. Vandini S; Corvaglia L; Alessandroni R; Aquilano G; Marsico C; Spinelli M; Lanari M; Faldella G. Vandini S; Corvaglia L; Alessandroni R; Aquilano G; Marsico C; Spinelli M; Lanari M; Faldella G.