Role of Valganciclovir in Children with Congenital CMV Infection: A Review of the Literature.

BACKGROUND: Cytomegalovirus (CMV) is the most common agent of congenital infection in humans. It is a main cause of neurodevelopmental delay and sensorineural hearing loss in infancy. Since the 2000s, a number of studies have used Valganciclovir as a therapy for children with congenital CMV infection. METHODS: In order to evaluate the efficacy of Valganciclovir in preventing clinical sequelae and its possible side effects, we performed a review of the published literature. This search was completed via PubMed for manuscripts published from January 2007 to December 2021, combining the MeSH words "Valganciclovir", "Congenital", and "Cytomegalovirus". RESULTS: A total of 27 articles were included (12 retrospective studies, 4 prospective studies, 1 randomized controlled trial, and 10 case reports). The clinical features were similar to those already described in the literature. The therapeutic protocols used were very different between the various studies included and neonatal antiviral treatments were only moderately effective. The therapy proved to be well-tolerated. CONCLUSIONS: The quality of the included studies and the sample size were limited due to the rarity of the disease. The use of different therapeutic protocols in terms of starting dates, doses, and durations made it impossible to compare and correctly evaluate the efficacy of the treatments. Randomized controlled trials are needed to establish the correct effective dose with the fewest side effects and the most efficient duration of therapy.

The impact of glucocorticoids on bone health and growth: endocrine and non-endocrine effects in children and young patients.

Glucocorticoids have numerous applications in short and/or long-term therapy both in pediatric and young adults, based on their significant anti-inflammatory and immunosuppressive effects. Different routes of administration can be provided including topical, inhalatory and oral. Topical treatments are the first choice for many dermatologic conditions. The inhalatory form is widely used in asthma management while systemic pathologies often require oral administration. The risks for adverse effects are related to the dose and duration of therapy as well as the specific agent used. Therefore, long-term treatment has a negative impact on different metabolic systems and can lead to hypertension, dyslipidemia and insulin resistance. In particular, many studies emphasize the direct and indirect effects of glucocorticoids on bone health. Glucocorticoids are the most common iatrogenic cause of osteoporosis and can alter bone development in young adults. These side effects are due to an early and transient increase in bone resorption and a decrease in bone formation. Glucocorticoid-induced changes can act on the bone multicellular unit, bone cells and intracellular signaling pathways. Chronic use can also modify bone mass though indirect endocrine and non-endocrine effects by reducing the anabolic function of sex steroids and GH/IGF-1 axis, interfere with calcium metabolism, as well as muscle atrophy and central fat accumulation. The aim of our review was to revise the available evidence on the impact of glucocorticoid treatment on bone health related to endocrine and non-endocrine effects in Young patients.

Psychological Impact of the COVID-19 Pandemic on Pregnant Women.

Objective: The aim of this study is to assess the impact of the COVID-19 pandemic on mental health, type of delivery, and neonatal feeding of pregnant women with or without SARS-CoV-2 infection during gestation. Study Design: The study was conducted online, and anonymous survey was distributed to mothers that delivered during the COVID-19 pandemic. Results: The survey was completed by 286 women, and 64 women (22.4%) had COVID-19 during pregnancy. Women that had SARS-CoV-2 infection during pregnancy or at time of delivery had a significantly higher probability of being separated from the newborn (p < 0.0001) and a significantly lower probability of breastfeeding (p < 0.0001). The Edinburg Postnatal Depression Scale, to assess if mothers had symptoms of postnatal depression, showed that items suggestive of postnatal depression were relatively frequent in the whole cohort. However, women with SARS-CoV-2 infection during pregnancy reported higher probability of responses suggestive of postnatal depression in eight out of 10 items, with statistically significant differences in three items. Conclusion: The COVID-19 pandemic affected the type of delivery and breastfeeding of pregnant women, particularly when they had SARS-CoV-2 infection. This, in turn, had an impact on the psychological status of the interviewed mothers, aspects that could benefit of special support.

Central precocious puberty in children after COVID-19 outbreak: a single-center retrospective study.

BACKGROUND: Central precocious puberty (CPP) was an unexplored issue during COVID-19 pandemic and an important disease in the adolescence life. Our aim was to evaluate the incidence of the new cases of central precocious puberty (CPP) during COVID-19 pandemic, comparing these results with the data for the same period over the previous three years. The secondary objective was to analyze the rate of pubertal progression in children during COVID-19 outbreak. METHODS: We performed a retrospective study of all children presented at our hospital for suspected CPP during COVID-19 outbreak, comparing their clinical and endocrinological data to the same over the previous three years. Secondary, endocrinological data of some patients in follow-up, with at least two visits 6 months apart during the COVID-19 period, are compared to evaluate the rate of pubertal progression. RESULTS: We enrolled 90 suspected enrolled CPP cases, 26 (28.9%) referred to our hospital during the COVID-19 outbreak and 64 (71.1%) in the previous 3 years. During COVID-19 outbreak 12 girls (42.9%) were at stage T3 compared to 14 (23%) of the 3 previous years (p=0.01). New CPP diagnosis were found in 11 (39.3%) children during pandemic, while 15 (24.2%) in the previous 3 years. A accelerated pubertal progression rate was observed in 22/45 (48.9%) patients, with a greater number of children at stages T3 and T4-5. CONCLUSIONS: Our data showed a progressive increase of newly diagnosed CPP and a significantly accelerated rate of pubertal progression in children during COVID-19 outbreak. We hypothesize that the increase in the weight and BMI during the lockdown and the psychological effects of the COVID-19 outbreak were involved in triggering and progression of puberty.

Vitamin D and tuberculosis in children: a role in the prevention or treatment of the disease?

Despite the growing number of published studies, the role of vitamin D in the prevention or treatment of tuberculosis remains unclear. In this review we analyze current scientific literature to provide evidence about the relationship between vitamin D and TB, with a special focus on the pediatric population. While in vitro studies have shown relevant antimycobacterial immune-stimulatory and immunosuppressive effects of vitamin D, this has not panned out in vivo with active TB. On the contrary, there is some evidence that this tool could work as prevention - both against TB infection as well as progression from latent to active infection. However, only a few studies have evaluated this correlation in children. The potential link between tuberculosis and vitamin D levels is promising. If effective, vitamin D supplementation of at-risk populations would be an affordable public health intervention, particularly in light of the worldwide increase in identified TB cases and drug-resistance. Vitamin D might represent a new, affordable, safe and easy to access drug for the prevention and treatment of TB. For stronger evidence, considering the features of infection (relative low incidence of reactivation of latent infection in immunocompetent patients) we need clinical trials with large numbers of participants conducted in endemic regions with a prolonged follow-up time.

Spyramicine and Trimethoprim-Sulfamethoxazole Combination to Prevent Mother-To-Fetus Transmission of Toxoplasma gondii Infection in Pregnant Women: A 28-Years Single-center Experience.

BACKGROUND: There is weak evidence on the best treatment of pregnant women with Toxoplasma gondii infection to prevent the vertical transmission to the fetus. METHODS: We conducted a 28-year retrospective study aiming to compare the efficacy of three therapeutic regimens [Spiramicyn alone (Spy) vs. Pyrimethamine-Sulfadiazine (P/S) vs. Spiramicyn with Trimethoprim-Sulfamethoxazole (Spy+TMP-SMX)] for the prevention of mother-to-fetus transmission of T. gondii infection. RESULTS: 170 women were included: 58 (34.1%) had certain congenital toxoplasmosis (CT), 61 (35.9%) a probable infection and 41 (24.1%) possible infection. In total 97 mothers (57.1%) were treated with the Spy+TMP-SMX combination, 64 mothers (37.6%) were treated with Spy only and 8 mothers (4.7%) with P/S. Infected infants were 20/170 (11.7%). However, 8.2% (8/97) of infants born to mothers treated with Spy+TMP-SMX were infected, 20% (11/55) of infants born to women treated with Spy and 12.5% (1/8) of infants born to mothers treated with P/S were infected. Logistic regression analysis demonstrated that Spy treatment alone was associated with an increased risk of CT compared to the Spy+TMP-SMX combination (OR, 2.78, 95% CI 1.04-7.41, P value 0.041). No difference was observed when the Spy+TMP-SMX was compared with the P/S combination (OR 1.59; 95% CI 0.17 - 14.58; P value 0.682). Results were confirmed when the analyses were corrected by trimester of infection and by type of maternal treatment (OR 7.72; 95% CI 3.40-17.53, P value <0.001). CONCLUSIONS: The combination of Spy+TMP-SMX may be more effective in reducing the risk of maternal-fetal transmission of Toxoplasmosis compared to Spy alone; furthermore, this combination is not inferior to P/S, the current international standard-of-care maternal treatment for the prevention of CT. A prospective trial comparing the combination Spy+TMP-SMX with P/S would be necessary to provide definitive evidence on the best regimen for pregnant women with T. gondii infection.

Diagnosis and Therapy of Infectious Encephalitis in Children: A Ten-Years Retrospective Study.

BACKGROUND: Infectious encephalitis represents a rare but potentially severe clinical condition. However, limited international data are available in pediatric age. METHODS: We conducted a retrospective study to review (a) the clinical presentation; (b) laboratory, radiology, and neurophysiology findings; (c) the correlations between these exams and outcome; and (d) the therapy performed. RESULTS: Fifty-six patients were enrolled [22 female (39.6%), mean age 4.7 years, IQR 0.7-8.7 years], 19.6% presented neurologic sequelae. HSV was the single most frequently isolated pathogen (19.6%), although in most cases, the etiology remained undefined. 41.1% children presented prodromal before the development of neurologic signs. Fever was the most frequent constitutional symptom (83.9% of cases). Cerebrospinal fluid was normal in 48.5% of cases and electroencephalograpy in 24.5% cases. Brain computed tomography scans was normal in 33 (91.7%) cases, while cerebral magnetic resonance imaging (MRI) showed pathologic findings in 62.5% of cases. MRI was the only parameter associated with neurologic sequalae [P = 0.01; OR, 8.1 (95% CI: 1.52-42.84)]. CONCLUSIONS: Pediatric encephalitis is a heterogeneous entity with nonspecific clinical and laboratory findings, with undefined etiologies in most times. MRI can play a primary role, both on a diagnostic and prognostic point-of-view, and its role should be implemented and made more accessible. Further studies are needed to define the exact role and timing of steroids.

Long-Term Clinical, Audiological, Visual, Neurocognitive and Behavioral Outcome in Children With Symptomatic and Asymptomatic Congenital Cytomegalovirus Infection Treated With Valganciclovir.

Cytomegalovirus (CMV) is the most common cause of congenital infection in humans. There are no enough data on long-term outcome of newborns with congenital CMV (cCMV) infection, particularly for those asymptomatic at birth. For this reason, we performed this study to evaluate long-term audiological, visual, neurocognitive, and behavioral outcome in patients with symptomatic and asymptomatic cCMV infection treated with oral Valganciclovir (VGC). Thirty-six newborns with confirmed cCMV infection were evaluated: 12 (33.3%) symptomatic at birth and 24 asymptomatic (66.7%). No one had cognitive impairment. Cognitive assessment scales resulted abnormal in 4/35 patients (11.4%). 11/21 patients (52.4%) achieved abnormal scores in neuropsychological tests. The language evaluation gave pathological results in 6/21 (28.5%) patients. 6/35 patients (17.1%) developed SNHL, all symptomatic at birth except one. None of the 34 patients evaluated developed CMV retinopathy. Our study shows that both symptomatic and asymptomatic newborns with cCMV infection develop long-term sequelae, particularly in the behavioral and communicative areas, independently from the trimester of maternal infection.