Exclusive breastfeeding and length of hospital stay in premature infants at a Brazilian reference center for kangaroo mother care.

OBJECTIVE: To evaluate exclusive breastfeeding at discharge and hospital length-of-stay in preterm infants undergoing or not the Kangaroo-Mother Care Method (KMC). METHODS: A retrospective cohort study was conducted including preterm infants < 1800 g admitted to the neonatal unit of a KMC reference center. The infants were grouped into the KMC group and the non-KMC group. Multiple logistic and Poisson regressions were performed to evaluate the association between the KMC and two outcomes, exclusive breastfeeding at discharge, and hospital length-of-stay, adjusted for potential confounders. RESULTS: 115 mother-infant dyads were included, 78 in the KMC group and 37 in the non-KMC group. In the bivariate analysis, the KMC group had a lower prevalence of maternal adverse conditions (6% vs. 32%, p < 0.001), a higher number of prenatal visits (median 6 vs. 3.5, p < 0.001), higher gestational ages (median 32 vs. 31 weeks, p < 0.05), higher birth weights (median 1530 vs. 1365 g, p < 0.01), a lower prevalence of necrotizing enterocolitis (3.8% vs. 16.2%, p < 0.05), parenteral nutrition (50% vs. 73%, p < 0.05), and deep vascular access (49.7% vs. 78.4%, p < 0.01), a higher prevalence of exclusive breastfeeding (65% vs. 8%, p < 0.001) and a shorter length of hospital stay (median 28 vs. 42 days, p < 0.001). In the multiple regression analysis, the KMC group was 23 times more likely to be exclusively breastfed at discharge (OR = 23.1; 95% CI = 4,85-109,93) and had a 19% reduction in the hospital length-of-stay (IDR = 0.81; 95% CI = 0.76-0.86) compared to the non-KMC group. CONCLUSIONS: The KMC is associated with better short-term neonatal outcomes and should be encouraged in all Brazilian maternity hospitals.

Shift in hospital opioid use during the COVID-19 pandemic in Brazil: a time-series analysis of one million prescriptions.

The pronounced change in the profile of hospitalized patients during COVID-19 and the severe respiratory component of this disease, with a great need for mechanical ventilation, led to changes in the consumption pattern of some medicines and supplies. This time-series study analyzed the in-hospital consumption of opioids during the COVID-19 pandemic in 24 Brazilian hospitals compared to the pre-pandemic period. Data included 711,883 adult patients who had opioids prescribed. In 2020, the mean consumption was significantly higher compared to 2019 for parenteral fentanyl, enteral methadone, and parenteral methadone. It was significantly lower for parenteral morphine parenteral sufentanil, and parenteral tramadol. For remifentanil, it did not differ. The number of patients in 2020 was lower but the mean consumption was higher for fentanyl, parenteral methadone, and remifentanil. It was lower for enteral methadone and parenteral sufentanil. The consumption of parenteral morphine and parenteral tramadol was stable. There was a relevant increase in hospital consumption of some potent opioids during the COVID-19 pandemic in Brazil. These results reinforce the concern about epidemiological surveillance of opioid use after periods of increased hospital use since in-hospital consumption can be the gateway to the misuse or other than the prescribed use of opioids after discharge.

Rare genetic variants involved in multisystem inflammatory syndrome in children: a multicenter Brazilian cohort study.

Introduction: Despite the existing data on the Multisystem Inflammatory Syndrome in Children (MIS-C), the factors that determine these patients evolution remain elusive. Answers may lie, at least in part, in genetics. It is currently under investigation that MIS-C patients may have an underlying innate error of immunity (IEI), whether of monogenic, digenic, or even oligogenic origin. Methods: To further investigate this hypothesis, 30 patients with MIS-C were submitted to whole exome sequencing. Results: Analyses of genes associated with MIS-C, MIS-A, severe covid-19, and Kawasaki disease identified twenty-nine patients with rare potentially damaging variants (50 variants were identified in 38 different genes), including those previously described in IFNA21 and IFIH1 genes, new variants in genes previously described in MIS-C patients (KMT2D, CFB, and PRF1), and variants in genes newly associated to MIS-C such as APOL1, TNFRSF13B, and G6PD. In addition, gene ontology enrichment pointed to the involvement of thirteen major pathways, including complement system, hematopoiesis, immune system development, and type II interferon signaling, that were not yet reported in MIS-C. Discussion: These data strongly indicate that different gene families may favor MIS- C development. Larger cohort studies with healthy controls and other omics approaches, such as proteomics and RNAseq, will be precious to better understanding the disease dynamics.

Maternal-fetal and neonatal characteristics associated with Kangaroo-Mother Care Method adherence.

OBJECTIVE: To describe the association of maternal and neonatal characteristics with the adherence status to the in-hospital stages of the Kangaroo-Mother Care Method - KMC (full, partial, and no-adherence). METHODS: Retrospective cohort study including infants < 2500 g admitted to a reference maternity hospital for the KMC in Rio de Janeiro from January to December 2018. Maternal and neonatal characteristics were distributed according to the adherence status to the KMC in-hospital stages. In the first stage, KMC is performed in Neonatal Intensive Care Unit and Conventional Neonatal Intermediate Care Unit. The second stage is completed in Kangaroo Neonatal Intermediate Care Unit. Multinomial multiple regression was performed with KMC adherence as a three-category dependent variable and maternal and neonatal characteristics as independent variables. RESULTS: Of 166 dyads, 102 (61.5%) participated in two stages. Those who did not participate in any stage (n = 52; 31.3%) had a lower level of education, a higher frequency of adverse conditions, and were more often single mothers; mothers who participated only in the first stage (n = 12; 7,2%) had more premature and sick infants. Conditions associated with adherence to the two stages compared to no adherence were: high school education (OR = 2.34; 95% CI = 1.08-5.07), presence of a partner (OR = 3.82; 95% CI = 1.7-8.61), no adverse conditions (OR = 3.54; 95% CI = 1.59-7.89) and no neonatal resuscitation (OR = 2.73; 95% CI = 1.22-6.1). CONCLUSIONS: The study identified maternal and neonatal conditions associated with adherence status to the KMC. The results suggest opportunities to improve adherence.

Mental Health and Emotional Disorders During the COVID-19 Pandemics: Prevalence and Extent in PICU Staff.

OBJECTIVES: To assess the prevalence of burnout, anxiety and depression symptoms, and posttraumatic stress disorder (PTSD) in PICU workers in Brazil during the first peak of the COVID-19 pandemic. To compare the results of subgroups stratified by age, gender, professional category, health system, and previous mental health disorders. DESIGN: Multicenter, cross-sectional study using an electronic survey. SETTING: Twenty-nine public and private Brazilian PICUs. SUBJECTS: Multidisciplinary PICU workers. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Self-reported questionnaires were used to measure burnout (Maslach Burnout Inventory), anxiety and depression (Hospital Anxiety and Depression Scale), and PTSD (Posttraumatic Stress Disorder Checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition [PCL-5]) in 1,084 respondents. Subjects were mainly young (37.1 ± 8.4 yr old) and females (85%), with a median workload of 50 hours per week. The prevalence of anxiety and depression was 33% and 19%, respectively, whereas PTSD was 13%. The overall median burnout scores were high in the emotional exhaustion and personal accomplishment dimensions (16 [interquartile range (IQR), 8-24] and 40 [IQR, 33-44], respectively) whereas low in the depersonalization one (2 [IQR, 0-5]), suggesting a profile of overextended professionals, with a burnout prevalence of 24%. Professionals reporting prior mental health disorders had higher prevalence of burnout (30% vs 22%; p = 0.02), anxiety (51% vs 29%; p < 0.001), and depression symptoms (32.5% vs 15%; p < 0.001), with superior PCL-5 scores for PTSD ( p < 0.001). Public hospital workers presented more burnout (29% vs 18.6%, p < 0.001) and more PTSD levels (14.8% vs 10%, p = 0.03). Younger professionals were also more burned out ( p < 0.05 in all three dimensions). CONCLUSIONS: The prevalence of mental health disorders in Brazilian PICU workers during the first 2020 peak of COVID-19 was as high as those described in adult ICU workers. Some subgroups, particularly those reporting previous mental disorders and younger professionals, should receive special attention to prevent future crises.

Maternal-fetal and neonatal characteristics associated with Kangaroo-Mother Care Method adherence

Abstract Objective To describe the association of maternal and neonatal characteristics with the adherence status to the in-hospital stages of the Kangaroo-Mother Care Method - KMC (full, partial, and no-adherence). Methods Retrospective cohort study including infants < 2500 g admitted to a reference maternity hospital for the KMC in Rio de Janeiro from January to December 2018. Maternal and neonatal characteristics were distributed according to the adherence status to the KMC in-hospital stages. In the first stage, KMC is performed in Neonatal Intensive Care Unit and Conventional Neonatal Intermediate Care Unit. The second stage is completed in Kangaroo Neonatal Intermediate Care Unit. Multinomial multiple regression was performed with KMC adherence as a three-category dependent variable and maternal and neonatal characteristics as independent variables. Results Of 166 dyads, 102 (61.5%) participated in two stages. Those who did not participate in any stage (n = 52; 31.3%) had a lower level of education, a higher frequency of adverse conditions, and were more often single mothers; mothers who participated only in the first stage (n = 12; 7,2%) had more premature and sick infants. Conditions associated with adherence to the two stages compared to no adherence were: high school education (OR = 2.34; 95% CI = 1.08-5.07), presence of a partner (OR = 3.82; 95% CI = 1.7-8.61), no adverse conditions (OR = 3.54; 95% CI = 1.59-7.89) and no neonatal resuscitation (OR = 2.73; 95% CI = 1.22-6.1). Conclusions The study identified maternal and neonatal conditions associated with adherence status to the KMC. The results suggest opportunities to improve adherence.

NR3C1 gene methylation and cortisol levels in preterm and healthy full-term infants in the first 3 months of life.

Aim: To describe NR3C1 exon-1F methylation and cortisol levels in newborns. Materials & methods: Preterm ≤1500 g and full-term infants were included. Samples were collected at birth and at days 5, 30 and 90 (or at discharge). Results: 46 preterm and 49 full-term infants were included. Methylation was stable over time in full-term infants (p = 0.3116) but decreased in preterm infants (p = 0.0241). Preterm infants had higher cortisol levels on the fifth day, while full-term infants showed increasing levels (p = 0.0177) over time. Conclusion: Hypermethylated sites in NR3C1 at birth and higher cortisol levels on day 5 suggest that prematurity, reflecting prenatal stress, affects the epigenome. Methylation decrease over time in preterm infants suggests that postnatal factors may modify the epigenome, but their role needs to be clarified.

We investigated the methylation of a gene, NR3C1 exon-1F, and cortisol levels in newborns. DNA methylation is a biochemical process that can modify gene activity. In the case of this gene, higher methylation might be associated with higher cortisol levels. We studied 46 preterm infants (born weighing 1500 g or less) and 49 full-term infants. Our results revealed that the preterm infants had hypermethylation at birth and higher cortisol levels on day 5, but decreasing methylation and stable cortisol levels over time. Meanwhile, methylation remained stable and cortisol levels increased in full-term babies with time. These unexpected results suggest that prematurity can be associated with prenatal epigenetic changes in the NR3C1 gene, but postnatal factors may induce further modifications. More research is needed to understand these findings better.

Improvement of 1st-hour bundle compliance and sepsis mortality in pediatrics after the implementation of the surviving sepsis campaign guidelines

Abstract Objectives To study the impact of the implementation of the Pediatric Surviving Sepsis Campaign protocol on early recognition of sepsis, 1 -h treatment bundle and mortality. Methods Retrospective, single-center study, before and after the implementation of the sepsis protocol. Outcomes: sepsis recognition, compliance with the 1 -h bundle (fluid resuscitation, blood culture, antibiotics), time interval to fluid resuscitation and antibiotics administration, and mortality. Patients with febrile neutropenia were excluded. The comparisons between the periods were performed using non-parametric tests and odds ratios or relative risk were calculated. Results We studied 84 patients before and 103 after the protocol implementation. There was an increase in sepsis recognition (OR 21.5 [95% CI: 10.1-45.7]), in the compliance with the 1 -h bundle as a whole (62% x 0%), and with its three components: fluid resuscitation (OR 31.1 [95% CI: 3.9−247.2]), blood culture (OR 15.9 [95% CI: 3.9−65.2]), and antibiotics (OR 35.6 [95% CI: 8.9−143.2]). Significant reduction between sepsis recognition to fluid resuscitation (152min × 12min, p < 0.001) and to antibiotics administration (137min × 30min) also occurred. The risk of death before protocol implementation was four times greater (RR 4.1 [95% CI: 1.2-14.4]), and the absolute death risk reduction was 9%. Conclusion Even if we considered the low precision of some estimates, the lower limits of the Confidence Intervals show that the implementation of the Pediatric Surviving Sepsis Campaign guidelines alongside a qualitive assurance initiative has led to improvements in sepsis recognition, compliance with the 1 -h treatment bundle, reduction in the time interval to fluid resuscitation and antibiotics, and reduction in sepsis mortality.

Multisystem inflammatory syndrome in children (MIS-C) during SARS-CoV-2 pandemic in Brazil: a multicenter, prospective cohort study

Abstract Objective To describe the clinical, laboratory, and radiological characteristics, as well as the outcomes of children with MIS-C. Method Multicenter, prospective cohort study, conducted in 17 pediatric intensive care units in five states in Brazil, from March to July 2020. Patients from 1 month to 19 years who met the MIS-C diagnostic criteria were included consecutively. Results Fifty-six patients were included, with the following conditions: Kawasaki-like disease (n = 26), incomplete Kawasaki disease (n = 16), acute cardiac dysfunction (n = 10), toxic shock syndrome (n = 3), and macrophage activation syndrome (n = 1). Median age was 6.2 years (IQR 2.4−10.3), 70% were boys, 59% were non-whites, 20% had comorbidities, 48% reported a contact with COVID-19 cases, and 55% had a recent SARS-CoV-2 infection confirmed by RT-PCR and/or serology. Gastrointestinal symptoms were present in 71%, shock symptoms in 59%, and severe respiratory symptoms in less than 20%. -Dimer was increased in 80% and cardiac dysfunction markers in more than 75%. Treatment included immunoglobulin (89%); corticosteroids, antibiotics, and enoxaparin in about 50%; and oseltamivir and antifungal therapy in less than 10%. Only 11% needed invasive mechanical ventilation, with a median duration of five days (IQR 5-6.5). The median length of PICU stay was six days (IQR 5-11), and one death occurred (1.8%). Conclusions Most characteristics of the present MIS-C patients were similar to that of other cohorts. The present results may contribute to a broader understanding of SARS-CoV-2 infection in children and its short-term consequences. Long-term multidisciplinary follow-up is needed, since it is not known whether these patients will have chronic cardiac impairment or other sequelae.

Screening of COVID-19 in outpatient children with cancer or solid organ transplantation: preliminary report.

Clinical presentation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pediatric immunosuppressed patients is unknown. Emerging data describe a milder or asymptomatic course in children compared with adults in this scenario. We present the seroprevalence and clinical features of coronavirus disease 2019 in a prospective cohort of 114 immunosuppressed children and adolescents from three groups: kidney transplantation, liver transplantation, and cancer patients. Among the thirty-five (30.7%) patients who had a positive serological test for SARS-CoV-2, 77% did not report previous symptoms and none of them developed any complications of coronavirus disease 2019 (COVID-19) after 30 or more days of follow-up. Among those who were symptomatic, diarrhea, fever, and cough were the most common findings.Conclusion: Seroprevalence of SARS-CoV-2 infection is high among immunosuppressed children and adolescents. COVID-19 has a mild or asymptomatic course in most of these patients. What is Known: • The number of immunosuppressed patients with coronavirus disease 2019 is increasing. • Viral infections have the potential for greater severity in immunocompromised children. What is New: • Seroprevalence for severe acute respiratory syndrome coronavirus 2 in immunocompromised pediatric patients was 31%. • A quarter of the serology-positive patients reported mild symptoms and none of them developed multisystem inflammatory syndrome in children associated with coronavirus disease 2019.

Improvement of 1st-hour bundle compliance and sepsis mortality in pediatrics after the implementation of the surviving sepsis campaign guidelines.

OBJECTIVES: To study the impact of the implementation of the Pediatric Surviving Sepsis Campaign protocol on early recognition of sepsis, 1-h treatment bundle and mortality. METHODS: Retrospective, single-center study, before and after the implementation of the sepsis protocol. OUTCOMES: sepsis recognition, compliance with the 1-h bundle (fluid resuscitation, blood culture, antibiotics), time interval to fluid resuscitation and antibiotics administration, and mortality. Patients with febrile neutropenia were excluded. The comparisons between the periods were performed using non-parametric tests and odds ratios or relative risk were calculated. RESULTS: We studied 84 patients before and 103 after the protocol implementation. There was an increase in sepsis recognition (OR 21.5 [95% CI: 10.1-45.7]), in the compliance with the 1-h bundle as a whole (62% x 0%), and with its three components: fluid resuscitation (OR 31.1 [95% CI: 3.9-247.2]), blood culture (OR 15.9 [95% CI: 3.9-65.2]), and antibiotics (OR 35.6 [95% CI: 8.9-143.2]). Significant reduction between sepsis recognition to fluid resuscitation (152min×12min, p<0.001) and to antibiotics administration (137min×30min) also occurred. The risk of death before protocol implementation was four times greater (RR 4.1 [95% CI: 1.2-14.4]), and the absolute death risk reduction was 9%. CONCLUSION: Even if we considered the low precision of some estimates, the lower limits of the Confidence Intervals show that the implementation of the Pediatric Surviving Sepsis Campaign guidelines alongside a qualitive assurance initiative has led to improvements in sepsis recognition, compliance with the 1-h treatment bundle, reduction in the time interval to fluid resuscitation and antibiotics, and reduction in sepsis mortality.

Multisystem inflammatory syndrome in children (MIS-C) during SARS-CoV-2 pandemic in Brazil: a multicenter, prospective cohort study.

OBJECTIVE: To describe the clinical, laboratory, and radiological characteristics, as well as the outcomes of children with MIS-C. METHOD: Multicenter, prospective cohort study, conducted in 17 pediatric intensive care units in five states in Brazil, from March to July 2020. Patients from 1 month to 19 years who met the MIS-C diagnostic criteria were included consecutively. RESULTS: Fifty-six patients were included, with the following conditions: Kawasaki-like disease (n = 26), incomplete Kawasaki disease (n = 16), acute cardiac dysfunction (n = 10), toxic shock syndrome (n = 3), and macrophage activation syndrome (n = 1). Median age was 6.2 years (IQR 2.4-10.3), 70% were boys, 59% were non-whites, 20% had comorbidities, 48% reported a contact with COVID-19 cases, and 55% had a recent SARS-CoV-2 infection confirmed by RT-PCR and/or serology. Gastrointestinal symptoms were present in 71%, shock symptoms in 59%, and severe respiratory symptoms in less than 20%. d-Dimer was increased in 80% and cardiac dysfunction markers in more than 75%. Treatment included immunoglobulin (89%); corticosteroids, antibiotics, and enoxaparin in about 50%; and oseltamivir and antifungal therapy in less than 10%. Only 11% needed invasive mechanical ventilation, with a median duration of five days (IQR 5-6.5). The median length of PICU stay was six days (IQR 5-11), and one death occurred (1.8%). CONCLUSIONS: Most characteristics of the present MIS-C patients were similar to that of other cohorts. The present results may contribute to a broader understanding of SARS-CoV-2 infection in children and its short-term consequences. Long-term multidisciplinary follow-up is needed, since it is not known whether these patients will have chronic cardiac impairment or other sequelae.