Drug utilisation in children and adolescents before and after the start of the COVID-19 pandemic: Interrupted time-series analyses in three European countries.

BACKGROUND: The COVID-19 pandemic has affected children and adolescents in several ways, including worsened mental health, improvement of asthma, and increases in diabetes ketoacidosis. Less is known about how medication use in children and adolescents has been affected by the pandemic. OBJECTIVES: To explore how the COVID-19 pandemic affected drug utilisation in children and adolescents in Norway, Sweden, and Italy, by child age. METHODS: We conducted a longitudinal drug utilisation study among all children and adolescents (<18 years old) in Norway and Sweden and a nationwide paediatric database covering 3% of the paediatric population in Italy. We conducted an interrupted time-series analysis from January 2018 to December 2021, with March 2020 as the interruption point. Dispensing or prescription rates of antidepressants, anxiolytics, sleep medications, attention-deficit/hyperactivity disorder (ADHD) medications, insulin, and asthma medications were examined. RESULTS: The study population in January 2018 consisted of 3,455,521 children and adolescents (136,188 from Italy, 1,160,431 from Norway, and 2,158,902 from Sweden). For sleep medications and insulin, there were only minor changes in level or trend in some age groups after March 2020. For asthma medications, the pandemic was associated with an immediate decrease in dispensing in Norway and Sweden (range of change in level: -19.2 to -3.7 dispensings per 1000 person-months), and an increasing trend in all countries afterward (range of change in trend: 0.3-6.4 dispensings per 1000 person-months), especially for the youngest age groups. Among adolescents, the pandemic was associated with an increased trend for ADHD medications, antidepressants, and anxiolytics in Norway and Sweden, but not in Italy. CONCLUSIONS: The increasing trend of psychotropic medication dispensing, especially among adolescents after the start of the pandemic, is concerning and should be investigated further. Aside from a temporary effect on asthma medication dispensing, the pandemic did not greatly affect the dispensing of the medications investigated.

Caregivers' psychosocial assessment for identifying HIV-infected infants at risk of poor treatment adherence: an exploratory study in southern Mozambique.

Psychosocial support (PSS) to caregivers of HIV-infected infants on antiretroviral treatment (ART) is crucial to ensure ART adherence and sustained long-term viral suppression in children. A specific approach including tools to monitor and understand adherence behavior and risk factors that prevent optimal treatment compliance are urgently needed. This qualitative exploratory study, conducted in southern Mozambique, monitored the infants' viral response trajectories during 18 months follow-up, as a measure of adherence, reviewed the caregiver's PSS session notes and the answers to a study questionnaire, to analyze whether the standard PSS checklist applied to infants' caregivers can identify barriers influencing their adherence. Only 9 of 31 infants had sustained virologic response. Reported factors affecting adherence were: difficulties in drugs administration, shared responsibility to administer treatment; disclosure of child's HIV status to family members but lack of engagement; mother's ART interruption and poor viral response. In conclusion, we found that the standard PSS approach alone, applied to caregivers, was lacking focus on many relevant matters that were identified by the study questionnaire. A comprehensive patient-centered PSS package of care, including an adherence risk factor monitoring tool, tailored to caregivers and their children must be developed.

Prevalence and Factors Associated With Intertwin Birth Weight Discordance Among Same-Sex Twins in Lombardy, Northern Italy.

This population-based cohort study investigated the prevalence, potential risk factors, and consequences of birth weight discordance (BWD) among same-sex twins. We retrieved data from the automated system of healthcare utilization databases of Lombardy Region, Northern Italy (2007-2021). BWD was defined as 30% or more disparity in birth weights between the larger and the smaller twin. Multivariate logistic regression was used to analyze the risk factors of BWD in deliveries with same-sex twins. In addition, the distribution of several neonatal outcomes was assessed overall and according to BWD level (i.e., ≤20%, 21-29, and ≥30%). Finally, a stratified analysis by BWD was performed to assess the relationship between assisted reproductive technologies (ART) and neonatal outcomes. We identified 11,096 same-sex twin deliveries; 556 (5.0%) pairs of twins were affected by BWD. Multivariate logistic regression analysis showed that maternal age ≥35 years (OR 1.26, 95% CI [1.05,5.51]), low level of education (OR 1.34, 95% CI [1.05, 1.70]), and ART (OR 1.16, 95% CI [0.94, 1.44], almost significant due to the low power) were independent risk factors for BWD in same-sex twins. Conversely, parity (OR 0.73, 95% CI [0.60, 0.89]) was inversely related. All the adverse outcomes observed were more common among BWD pairs than non-BWD ones. Instead, a protective effect of ART was observed for most neonatal outcomes considered among BWD twins. Our results suggest that conception after ART increases the risk of developing a high disparity between the weights of the two twins. However, the presence of BWD may complicate twin pregnancies, compromising neonatal outcomes, regardless of the modality of conception.

Comparative study showed that children faced a 78% higher risk of new-onset conditions after they had COVID-19.

AIM: Children have largely been unaffected by severe COVID-19 compared to adults, but data suggest that they may have experienced new conditions after developing the disease. We compared outcomes in children who had experienced COVID-19 and healthy controls. METHODS: A retrospective nested cohort study assessed the incidence rate of new-onset conditions after COVID-19 in children aged 0-14 years. Data were retrieved from an Italian paediatric primary care database linked to Veneto Region registries. Exposed children with a positive nasopharyngeal swab were matched 1:1 with unexposed children who had tested negative. Conditional Cox regression was fitted to estimate the adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for the exposure and outcome associations after adjusting for covariates. RESULTS: We compared 1656 exposed and 1656 unexposed children from 1 February 2020 to 30 November 2021. The overall excess risk for new-onset conditions after COVID-19 was 78% higher in the exposed than unexposed children. We found significantly higher risks for some new conditions in exposed children, including mental health issues (aHR 1.8, 95% CI 1.1-3.0) and neurological problems (aHR 2.4, 95% CI 1.4-4.1). CONCLUSION: Exposed children had a 78% higher risk of developing new conditions of interest after COVID-19 than unexposed children.

Baseline and Postoperative C-reactive Protein Levels Predict Long-Term Survival After Lung Metastasectomy.

BACKGROUND: Blood level of C-reactive protein (CRP) at diagnosis is a well-know prognostic bio-marker in different primary tumors, but its role has not been investigated in resectable lung metastases. The aim of our study is to assess the predictive value of baseline (CRP0) and 3rd postoperative day (CRP3) levels on long-term survival of patients undergoing lung metastasectomy. METHODS: A total of 846 consecutive patients underwent the first pulmonary resection for lung metastases between January 2003 and December 2015, including 611 (72%) single surgical procedures, 235 (28%) multiple metastasectomies, 501 (59%) epithelial primary tumors, 276 (33%) sarcomas, 66 (8%) melanomas, 286 (33.8%) with 0 risk factors (CRP0 ≤ 2 and CRP3 ≤ 84 mg/L) and 560 (66.2%) with ≥ 1 risk factor (CRP0 > 2 and/or CRP3 > 84 mg/L). RESULTS: Cumulative 5-year survival was 57% in patients with low CRP (0 risk factors) versus 43% in high CRP (≥ 1 risk factor, p < 0.0002), 62% versus 50% respectively for epithelial tumors (p < 0.0140), and 51% versus 34% for sarcomas (p < 0.0111). Multivariable Cox analysis confirmed a mortality hazard ratio of 2.5 at 1-year and 1.5 at 5-years in patients with high CRP. CONCLUSIONS: Baseline and postoperative CRP levels predict survival of patients with resectable lung metastases. These data provide a rationale for prospective clinical trials testing the efficacy of anti-inflammatory or immune-modulating agents as "adjuvant" therapy after lung metastasectomy, in patients with elevated pre- and/or postoperative CRP levels.

Building reliable evidence from real-world data: Needs, methods, cautiousness and recommendations.

National healthcare systems of advanced countries, including Italy, widely agree on the approach whereby public healthcare decisions should be driven by available evidence on effectiveness and safety of therapeutics. It is equally accepted that randomized controlled clinical trials (RCTs), although universally recognised as the most robust "evidence generators", are insufficient for guiding the decision-making process since they are intrinsically unsuited to capture the impact of treatments in routine clinical practice. The complexity of treatments, as well as the demographic and clinical heterogeneity of patients receiving the treatments, and the long period of many treatments, explain the gap between the evidence generated in the controlled, but artificial, setting of RCTs and their current impact in the real world. The so-called pragmatic RCTs, despite guaranteeing greater flexibility compared to conventional trials, are not always able to reduce this gap. This explains the growing interest in the development of methods able to produce evidence on the real-world impact of care pathways (i.e., real-world evidence). Among them, those based on the Electronic Healthcare Records (EHRs), as the databases on the healthcare services of the National Health System provided to beneficiaries, known as Healthcare Utilization Databases (HCU), are becoming established and receiving increasing attention from the scientific community and healthcare decision-makers. We described the research areas in which HCU databases may be particularly useful, jointly with strength, weakness and potential of this approach. It is concluded that HCU data cannot substitute RCTs but they can usefully complement RCT data for adequately supporting healthcare decision-makers.

Antibiotic Use in Children - A Cross-National Analysis of 6 Countries.

OBJECTIVES: To describe the rates of pediatric antibiotic use across 6 countries on 3 continents. STUDY DESIGN: Cross-national analysis of 7 pediatric cohorts in 6 countries (Germany, Italy, South Korea, Norway, Spain, and the US) was performed for 2008-2012. Antibiotic dispensings were identified and grouped into subclasses. We calculated the rates of antimicrobial prescriptions per person-year specific to each age group, comparing the rates across different countries. RESULTS: A total of 74 744 302 person-years from all participating centers were included in this analysis. Infants in South Korea had the highest rate of antimicrobial consumption, with 3.41 prescribed courses per child-year during the first 2 years of life. This compares with 1.6 in Lazio, Italy; 1.4 in Pedianet, Italy; 1.5 in Spain; 1.1 in the US; 1.0 in Germany; and 0.5 courses per child-year in Norway. Of antimicrobial prescriptions written in Norway, 64.8% were for first-line penicillins, compared with 38.2% in Germany, 31.8% in the US, 27.7% in Spain, 25.1% in the Italian Pedianet population, 9.8% in South Korea, and 8% in the Italian Lazio population. CONCLUSIONS: We found substantial differences of up to 7.5-fold in pediatric antimicrobial use across several industrialized countries from Europe, Asia, and North America. These data reinforce the need to develop strategies to decrease the unnecessary use of antimicrobial agents.

Use of antidepressant medication in pregnancy and adverse neonatal outcomes: A population-based investigation.

BACKGROUND: Untreated depression and antidepressant use during pregnancy may have negative consequences for births. There are still conflicting data on the potential harmful effects of prenatal antidepressant treatment on child health. OBJECTIVE: To investigate the relationship between the use of antidepressant medication during pregnancy and selected neonatal outcomes. METHODS: A population-based cohort study including 9825 deliveries exposed to an antidepressant between 9 months before last menstrual date through to delivery, from January 2005 to December 2010 in the Lombardy region of Italy, was conducted. We evaluated the prevalence ratio (PR) of low Apgar score, small for gestational age, intrauterine hypoxia and birth asphyxia, neonatal convulsion, and other respiratory conditions, among infants born to mothers exposed to an antidepressant during pregnancy using log-binomial regression analysis. Fine stratification was applied to the propensity score to account for all potential confounders. Sensitivity and subgroup analyses restricted to specific types of antidepressant, time of exposure, and women with vaginal deliveries and full-term births were also performed. RESULTS: A total of 33.4% of women filled at least one prescription during pregnancy. Compared to infants born to mothers with exposure to antidepressants only before pregnancy, those with exposure to antidepressants during pregnancy had an increased prevalence ratio of a low Apgar score (PR, 1.63, 95% CI, 1.01-2.61), intrauterine hypoxia and birth asphyxia (aPR, 1.37, 1.08-1.73), neonatal convulsion (aPR, 2.81, 1.07-7.36), and other respiratory condition (aPR, 1.24, 1.00-1.52). Results were similar in the sensitivity and subgroup analyses. CONCLUSIONS: Use of antidepressants during pregnancy may have an increased risk for several neonatal outcomes.

Mother's education and the risk of several neonatal outcomes: an evidence from an Italian population-based study.

BACKGROUND: Maternal socioeconomic disparities strongly affect child health, particularly in low and middle income countries. We assessed whether neonatal outcomes varied by maternal education in a setting where healthcare system provides universal coverage of health services to all women, irrespective of their socioeconomic status. METHODS: A population-based study was performed on 383,103 singleton live births occurring from 2005 to 2010 in Lombardy, an Italian region with approximately 10 million inhabitants. The association between maternal education, birthplace and selected neonatal outcomes (preterm birth, low birth weight, small-for-gestational age, low 5-min Apgar score, severe congenital anomalies, cerebral distress and respiratory distress) was estimated by fitting logistic regression models. Model adjustments were applied for sociodemographic, reproductive and medical maternal traits. RESULTS: Compared with low-level educated mothers, those with high education had reduced odds of preterm birth (Odds Ratio; OR = 0.81, 95% CI 0.77-0.85), low birth weight (OR = 0.78, 95% CI 0.70-0.81), small for gestational age (OR = 0.82, 95% CI 0.79-0.85), and respiratory distress (OR = 0.84, 95% CI 0.80-0.88). Mothers born in a foreign country had higher odds of preterm birth (OR = 1.16, 95% CI 1.11-1.20), low Apgar score (OR = 1.18, 95% CI 1.07-1.30) and respiratory distress (OR = 1.19, 95% CI 1.15-1.24) than Italian-born mothers. The influence of maternal education on neonatal outcomes was confirmed among both, Italian-born and foreign-born mothers. CONCLUSIONS: Low levels of education and maternal birthplace are important factors associated with adverse neonatal outcomes in Italy. Future studies are encouraged to investigate factors mediating the effects of socioeconomic inequality for identifying the main target groups for interventions.

Body mass index and mortality in men with prostate cancer.

BACKGROUND: Body Mass index (BMI) has been shown to affect risk and mortality of several cancers. Prostate cancer and obesity are major public health concerns for middle-aged and older men. Previous studies of pre-diagnostic BMI have found an increased risk of prostate cancer mortality in obese patients. OBJECTIVE: To study the associations between BMI at time of prostate cancer diagnosis and prostate cancer specific and overall mortality. METHODS: BMI was analyzed both as a continuous variable and categorized into four groups based on the observed distribution in the cohort (BMI < 22.5, 22.5 < 25, 25 < 27.5 and ≥27.5 kg/m2). The association between BMI and mortality was assessed using stratified Cox proportional hazards models and by fitting regression splines for dose response analysis in 3,161 men diagnosed with prostate cancer. After 11 years of follow up via linkage to the population-based cause of death registry, we identified 1,161 (37%) deaths off which 690 (59%) were due to prostate cancer. RESULTS: High BMI (BMI ≥ 27.5 kg/m2) was associated with a statistically significant increased risk of prostate cancer specific mortality (HR:1.44, 95% CI: 1.09-1.90) and overall mortality (HR:1.33, 95% CI: 1.09-1.63) compared to the reference group (BMI 22.5 < 25 kg/m2). Additionally, men with a low BMI (<22.5 kg/m2 ), had a statistically significant increased risk of prostate cancer specific mortality (HR:1.33, 95% CI: 1.02-1.74) and overall mortality (HR:1.36, 95% CI: 1.11-1.67) compared to the reference. However, this effect disappeared when men who died within the first two years of follow-up were excluded from the analyses while the increased risk of prostate cancer specific mortality and overall mortality remained statistically significant for men with a BMI ≥ 27.5 kg/m2 (HR:1.44, 95% CI: 1.09-1.90 and HR: 1.33, 95% CI: 1.09-1.63, respectively). CONCLUSION: This study showed that a high BMI at time of prostate cancer diagnosis was associated with increased overall mortality.

Epidemiology of Frequently Occurring Skin Diseases in Italian Children from 2006 to 2012: A Retrospective, Population-Based Study.

BACKGROUND: Recent estimates indicate an increase in the prevalence of skin diseases in children. Few large epidemiologic studies have examined prevalence trends in Europe. This study evaluated the incidence and prevalence of frequently occurring pediatric skin diseases (PSDs) in Italy as seen by family pediatricians (FPs). METHODS: Data were retrospectively extracted from the Pedianet database (2006-2012) in children ages 0 to 14 years presenting with a skin disease at their FP. The incidence and prevalence estimates were calculated per year and stratified according to sex, age, and geographic area. RESULTS: A mean of 145,233 children (52.1% male) across five Italian regions were registered with their participating FP for a total of 913,253 person-years of follow-up. The majority of patients were from the northeast (44.6%) and 37.7% were ages 5-9 years. Incidence estimates (new cases/1,000 person-years) for most PSDs increased from 2006 to 2012, the highest being for atopic dermatitis (AD) (14.1 vs 16.5), acute urticaria (10.1 vs 11.6), and contact dermatitis (9.3 vs 10.8), whereas psoriasis remained unchanged over the 7 years (0.61 vs 0.57). In contrast, prevalence estimates (cases/100 patients) increased two to three times for several PSDs, including AD (2.7% vs 8.5%), seborrheic dermatitis (0.5% vs 1.6%), chronic urticaria (0.4% vs 0.8%), and psoriasis (0.09% vs 0.22%). Differences in prevalence according to age range and geographic area were observed for psoriasis, AD, and urticaria. CONCLUSION: This study provides comprehensive evidence of the increasing prevalence and incidence of PSDs across Italy. Additional causality studies to address this important clinical and psychosocial problem are recommended.

Does preterm birth increase the initiation of antidepressant use during the postpartum? A population-based investigation.

Background: Preterm birth may affect maternal mental health. We explored the relationship between preterm birth and the risk of initiating antidepressant use during the year after birth. Methods: We conducted a population-based investigation using regional healthcare utilization databases. The exposure considered was preterm birth. The outcome was having at least one prescription for antidepressant medications during the year after birth. We used a log-binomial regression model including terms for maternal age at birth, nationality, educational level, parity, modality of conception, modality of delivery, use of other psychotropic drugs, and diabetes to estimate relative risk (RR) and 95% confidence intervals (CI) for the association between preterm birth and the initiation of antidepressant use. In addition, the absolute risk differences (ARD) were also computed according to the timing of birth. Results: The cohort included 727,701 deliveries between 2010 and 2020 in Lombardy, Northern Italy. Out of these, 6,522 (0.9%) women had at least one prescription for antidepressant drugs during the year after birth. Preterm births were related to a 38% increased risk of initiation of antidepressant use during the year after birth (adjusted RR = 1.38; 95% CI: 1.25-1.52) for moderate to late preterm and to 83% (adjusted RR = 1.83; 95% CI: 1.46-2.28) for extremely and very preterm. Excluding women with only one antidepressant prescription, the association was consistent (adjusted RR = 1.41, 95%CI: 1.23-1.61 for moderate to late preterm and adjusted RR = 1.81, 95% CI: 1.31-2.49 for extremely and very preterm). Also, excluding women who used other psychotropics, the association remained consistent (adjusted RR = 1.39, 95%CI: 1.26-1.54 and adjusted RR = 1.91, 95% CI: 1.53-2.38, respectively for moderate to late and extremely and very preterm). Conclusion: Women who delivered preterm may have an excess risk of initiation of antidepressant consumption during the first year after birth.

The COVID-19 Pandemic Was Associated with a Change in Therapeutic Management and Mortality in Heart Failure Patients.

Background: Heart failure (HF)-related mortality has been exacerbated by the COVID-19 pandemic; however, it is unclear how healthcare reassessment has contributed to the excess mortality versus SARS-CoV-2 infection itself. We aimed to assess how the pandemic affected the therapeutic management and prognosis of HF patients. Methods: We retrospectively reviewed the healthcare utilization databases of the Lombardy region (Italy) to identify all newly-diagnosed HF patients from January 2018 to December 2021. Outcomes were the utilization of HF therapies (Sacubitril/Valsartan; cardiac resynchronization therapy [CRT] and/or implantable cardioverter-defibrillator [ICD]; mechanical circulatory support [MCS]; heart transplantation [HTX]) and mortality. Cox regression models were fitted to estimate the hazard ratios (HR) and 95% confidence intervals (CI) for outcomes associated with the pandemic. Results: 36,130 and 17,263 patients were identified in the pre-pandemic and pandemic eras, respectively. The pandemic reduced Sacubitril/Valsartan utilization (HR = 0.77, 95% CI: 0.65-0.91) and CRT/ICD implantation (HR = 0.85, 95% CI: 0.78-0.92), but not MCS (HR = 1.11, 95% CI: 0.86-1.43) and HTX (HR = 0.88, 95% CI: 0.70-1.09). An increased mortality risk was observed during the pandemic (HR = 1.19, 95% CI: 1.15-1.23), which was attributable to SARS-CoV-2 infection (HR for non-COVID-19-related mortality = 1.01, 95% CI: 0.97-1.04). Conclusions: The COVID-19 pandemic was associated with a reduction in medical and interventional therapies for HF and an increase in mortality for HF patients.

Risk of SARS-CoV-2 Reinfection in Children Within the 12 Months Following Mild COVID-19: Insights From a Survey Study.

Understanding the correlation between immune response and protection from COVID-19 will play a pivotal role in predicting the effectiveness of vaccines in children. We studied SARS-CoV-2 reinfection risk in children 12 months post-mild COVID-19. Children under 5 years old exhibited lower reinfection risk than older infected or vaccinated siblings during 12 months postimmunization.

Multiple births from medically assisted reproduction: contribution of different types of procedures and trends over time.

OBJECTIVE: To evaluate the relative impact of different strategies of medically assisted reproduction (MAR), i.e. first line treatment (ovarian stimulation with or without intrauterine insemination) and in vitro fertilization (IVF) procedures (conventional IVF or intracytoplasmic sperm injection), on the risk of multiple births. STUDY DESIGN: We utilized the health care utilization databases of the Lombardy region to identify births resulting from MAR between 2007 and 2022. We gathered data on the total number of multiple births and calculated the prevalence rate by dividing the number of multiples by the total number of births. To examine the temporal trend in the proportion of multiple births after MAR over time, a linear regression model was employed separately for different types of techniques and in strata of maternal age. RESULTS: A total of 30,900 births after MAR were included; 4485 (14.5 %) first line treatments and 26,415 (85.5 %) IVF techniques. Overall, 4823 (15.6 %) multiple births were identified. The frequency of multiple births over the study period decreased from 22.0 % in 2007 to 8.7 % in 2022 (p < 0.01). Multiple births from first line treatments were stable ranging from 13.5 % in 2007-2008 to 12.0 % in 2021-2022 (p = 0.29). Multiple births from IVF procedures decreased from 23.8 % in 2007-2008 to 8.4 % in 2021-2022 (p < 0.01). Stratifying for maternal age (i.e. < 35 and ≥ 35 years), the trends remained consistent. CONCLUSIONS: The reduction in multiple births has been influenced by changes in IVF strategy and procedures. The decline has been gradual but steady since 2009, when a law restricting embryo freezing was repealed in Italy. In contrast, the proportion of multiple births resulting from first line treatments has remained constant over time. Despite declining, multiple births from MAR remained about one order of magnitude higher than those from spontaneous pregnancies.

Predicting Time to Delivery in Hypertensive Disorders: Assessing PlGF and sFlt-1 with the Novel Parameter 'Mtp-Multiples of a Normal Term Placenta'.

Background: Imbalanced angiogenesis is characteristic of normal placental maturation but it also signals placental dysfunction, underlying hypertensive disorders during pregnancy. This study aimed to investigate the relationship between angiogenic placental aging, measured by markers placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) using the new index "Multiples of a normal term placenta" (Mtp) and the duration of pregnancy. Methods: A retrospective observational study was conducted, including singleton pregnancies diagnosed or suspected of hypertensive disorders after the 20th gestational week. Mtp measures how far a single dosage of angiogenic marker deviates from the expected value in an uncomplicated full-term pregnancy (Mpt = sFlt-1/sFlt-1 reference value or PIGF/PIGF reference value). We considered the 90th, 95th, and 97.5th centiles for sFlt-1 and the 2.5th, 5th, and 10th centiles for PlGF as references. Results: The categories with longer time to delivery, regardless of gestational age, were: Mtp PlGF 10th c ≥ 2, ≥3 and Mtp sFlt-1 90th c ≤ 0.5 (median days of 9, 11, 15 days, respectively). These two categories Mtp sFlt-1 90th c ≥ 3 and Mtp sFlt-1 97.5th c ≥ 2 allow the identification of women at risk for imminent delivery within 1 day. Women who were deemed at low/medium risk based on the sFlt-1/PIGF ratio appeared to be at high risk when considering the individual values of sFlt-1 and/or PIGF. Conclusions: This new Mtp index for sFlt-1 and PlGF could be employed to assess the degree of placental aging in women with hypertensive disorders. It represents a valid tool for evaluating the risk of imminent birth, irrespective of gestational age, surpassing the current stratification based on the sFlt-1/PIGF ratio.

Association Between Early-Life Exposure to Antibiotics and Development of Child Obesity: Population-Based Study in Italy.

BACKGROUND: Childhood obesity is a significant public health problem representing the most severe challenge in the world. Antibiotic exposure in early life has been identified as a potential factor that can disrupt the development of the gut microbiome, which may have implications for obesity. OBJECTIVE: This study aims to evaluate the risk of developing obesity among children exposed to antibiotics early in life. METHODS: An Italian retrospective pediatric population-based cohort study of children born between 2004 and 2018 was adopted using the Pedianet database. Children were required to be born at term, with normal weight, and without genetic diseases or congenital anomalies. We assessed the timing of the first antibiotic prescription from birth to 6, 12, and 24 months of life and the dose-response relationship via the number of antibiotic prescriptions recorded in the first year of life (none, 1, 2, and ≥3 prescriptions). Obesity was defined as a BMI z score >3 for children aged ≤5 years and >2 for children aged >5 years, using the World Health Organization growth references. The obese incidence rate (IR) × 100 person-years and the relative 95% CI were computed using infant sex, area of residence, preschool and school age, and area deprivation index, which are the covariates of interest. A mixed-effect Cox proportional hazards model was used to estimate the hazard ratio and 95% CI for the association between antibiotic exposure in early life and child obesity between 24 months and 14 years of age, considering the family pediatricians as a random factor. Several subgroup and sensitivity analyses were performed to assess the robustness of our results. RESULTS: Among 121,540 children identified, 54,698 were prescribed at least an antibiotic within the first year of life and 26,990 were classified as obese during follow-up with an incidence rate of 4.05 cases (95% CI 4.01-4.10) × 100 person-year. The risk of obesity remained consistent across different timings of antibiotic prescriptions at 6 months, 1 year, and 2 years (fully adjusted hazard ratio [aHR] 1.07, 95% CI 1.04-1.10; aHR 1.06, 95% CI 1.03-1.09; and aHR 1.07, 95% CI 1.04-1.10, respectively). Increasing the number of antibiotic exposures increases the risk of obesity significantly (P trend<.001). The individual-specific age analysis showed that starting antibiotic therapy very early (between 0 and 5 months) had the greatest impact (aHR 1.12, 95% CI 1.08-1.17) on childhood obesity with respect to what was observed among those who were first prescribed antibiotics after the fifth month of life. These results were consistent across subgroup and sensitivity analyses. CONCLUSIONS: The results from this large population-based study support the association between early exposure to antibiotics and an increased risk of childhood obesity. This association becomes progressively stronger with both increasing numbers of antibiotic prescriptions and younger age at the time of the first prescription.

Comparison between the Viral Illness Caused by SARS-CoV-2, Influenza Virus, Respiratory Syncytial Virus and Other Respiratory Viruses in Pediatrics.

Respiratory tract infections (RTIs) are the most common infectious syndromes, primarily caused by viruses. The primary objective was to compare the illness courses between historical RTIs and recent SARS-CoV-2 infections. The study cohort consisted of RTI cases evaluated at the Pediatric Emergency Departments of Padua and Bologna, discharged or admitted with microbiologically confirmed viral RTI between 1 November 2018 and 30 April 2019 (historical period) and 1 March 2020 and 30 April 2021 (recent period). We evaluated the risk of oxygen or respiratory support, hospitalization, antibiotic therapy, and complications among different viral infections. The odds ratio (OR) and the 95% confidence intervals (CIs) were estimated through mixed-effect logistic regression models, including a random intercept on the individual and hospital. We identified 767 RTIs: 359 in the historical period compared with 408 SARS-CoV-2 infections. Infections of SARS-CoV-2 had a lower risk of being admitted (OR 0.04, 95% CI 0.03-0.07), receiving respiratory support (OR 0.19, 95% CI 0.06-0.58), needing antibiotic therapy (OR 0.35, 95% CI 0.22-0.56) and developing complications (OR 0.27, 95% CI 0.14-0.51) compared to all other viral RTIs. COVID-19 in children is clinically similar to other viral RTIs but is associated with a less severe infection course. Thus, most prevention strategies implemented for SARS-CoV-2 should still be considered during RSV and Influenza epidemics.

Stronger and durable SARS-CoV-2 immune response to mRNA vaccines in 5-11 years old children with prior COVID-19.

BACKGROUND AND OBJECTIVES: mRNA vaccines elicit a durable humoral response to SARS-CoV-2 in adults, whereas evidence in children is scarce. This study aimed to assess the early and long-term immune response to the mRNA vaccine in children with or without previous SARS-CoV-2 infection. METHODS: In a multicentre prospective observational study, we profiled the immune response to the Pfizer BioNTech (BNT162b2) vaccine in 5-11-year-old children attending the University Pediatric Hospital of Padua and Bambino-Gesù Hospital in Rome (Italy) from December-2021 to February-2023. Blood samples were collected pre-, 1-, and 6-months after vaccination. Neutralizing antibodies (NAbs) and anti-spike-receptor-binding-domain (anti-S-RBD) IgG titers were analyzed through Plaque Reduction Neutralization Test (PRNT) and chemiluminescent immune-enzymatic assay (CLIA), respectively. Immune cell phenotypes were analyzed by flow cytometry. RESULTS: Sixty children (26 [43 %] female, median age = 8 years [IQR = 7-10.7]) were enrolled in the study, including 46 children with a laboratory-confirmed previous COVID-19 (SARS-CoV-2-recovered) and 14 SARS-CoV-2-naïve participants defined as the absence of antigen-specific antibodies before vaccination. SARS-CoV-2-recovered participants recorded higher anti-S-RBD IgG and Wild-type and Omicron BA.2 NAbs titers than SARS-CoV-2-naïve participants at both 1- and 6-months after vaccination. Antibody titers correlated with T (Tregs) and B (Bregs) regulatory cell frequencies in SARS-CoV-2-recovered children. Both SARS-CoV-2-recovered and SARS-CoV-2-naïve participants decreased antibody titers by approximately 100 to 250 % from 1 to 6 months. While children with immunocompromising underlying conditions developed immune responses comparable to those of healthy children, solid organ transplant recipients exhibited lower levels of NAbs and anti-S-RBD IgG titers, as well as reduced frequencies of Tregs and Bregs. CONCLUSIONS: mRNA vaccination triggered a higher production of specific anti-SARS-CoV-2 antibodies along with increased levels of regulatory cells in children with previous SARS-CoV-2 infection up to the following 6 months. These findings provide insights into boosting pre-existing immunity.