Objective: To describe post-natal risk factors associated with death in Newborns (NB) with Congenital Diaphragmatic Hernia (CDH) in a Brazilian reference center.Methods: In this retrospective cohort study, post-natal clinical factors of all NB diagnosed with CDH were reviewed in an 11-year period (2007-2018). The primary outcome was death. Secondary outcomes included clinical features, prognostic indexes, type of mechanical ventilation, complications during hospitalization and surgical repair.Results: After applying the exclusion criteria, the authors analyzed 137 charts. Overall mortality was 59% (81/ 137), and the highest rates were observed for low-birth-weight NB (87%), syndromic phenotype (92%), and those with major malformations (100%). Prognostic indexes such as Apgar, SNAPPE-II and 24hOI (best oxygenation index in 24 hours) were all associated with poor evolution. In a multivariate analysis, only birth weight and 24hOI were statistically significant risk factors for mortality, with a reduction in mortality risk of 17.1% (OR = 0.829, 95% IC 0.72-0.955, p = 0.009) for each additional 100g at birth and an increase by 26.5% (OR = 1.265, 95% IC 1.113-1.436, p = 0.0003) for each unitary increase at the 24hOI.Conclusion: Prognostic indexes are an important tool for predicting outcomes and improving resource allocation. Post-natal risk factors may be more suitable for settings where antenatal diagnosis is not universal. Classical risk factors, such as prematurity, low birth weight, higher need for supportive care, and poorer prognostic indexes were associated with mortality in our CDH population.

RESUMO O objetivo do estudo foi verificar a aplicabilidade do Test of Infant Motor Performance (TIMP) em recém-nascidos (RN) cirúrgicos como ferramenta para avaliação do desempenho motor; e avaliar o benefício da fisioterapia. RN cirúrgicos, divididos em grupo sem fisioterapia motora (n=38) e com fisioterapia motora (n=38), foram avaliados pelo TIMP e reavaliados duas semanas depois. O grupo com fisioterapia realizou exercícios para estimulação sensório-motora uma vez ao dia, enquanto o grupo sem fisioterapia recebeu os cuidados habituais da Unidade de Terapia Intensiva Neonatal (UTIN). O diagnóstico cirúrgico predominante nos dois grupos foi de gastrosquise, seguido de hérnia diafragmática congênita. Na avaliação, não houve diferença no desempenho motor entre os grupos, classificados como “abaixo da média” para a idade, com escore-z=−1,28 (p=0,992). Na reavaliação, o grupo com fisioterapia apresentou melhor pontuação (p<0,001) e maior diferença de escore (p<0,001), com uma porcentagem maior de RN classificados como “dentro da média” em comparação ao grupo sem fisioterapia (44% e 2,6%, respectivamente); além de maior porcentagem de ganho de peso (p=0,038). Na reavaliação, verificou-se piora do desempenho motor em 10,5% do grupo sem fisioterapia (p<0,001), enquanto a melhora do desempenho motor foi observada em 81,6% do grupo com fisioterapia e em apenas 13,2% do grupo sem fisioterapia (p<0,001). Concluiu-se que o TIMP foi aplicado de forma segura e eficaz e necessita ser realizado por profissionais experientes na abordagem dessa população. A fisioterapia motora melhorou significativamente o desempenho motor, e, se iniciada precocemente, pode ser capaz de adequar o desenvolvimento motor desses RN, antes mesmo da alta hospitalar.

ABSTRACT This study aimed to verify the applicability of the Test of Infant Motor Performance (TIMP) in surgical neonates as a tool for evaluating motor performance and to evaluate the benefit of physical therapy. Surgical neonates, divided into group without physical therapy (n=38) and group with motor physical therapy (n=38), were evaluated by TIMP and reasssment two weeks later. The physical therapy group performed standardized exercises for motor sensory stimulation once a day, whereas the other group received the usual care from the Neonatal Intensive Care Unit. The predominant surgical diagnosis in both groups was gastroschisis, followed by congenital diaphragmatic hernia. In the initial evaluation, motor performance was equal between the groups, classified as “below average” for age, with z-score=−1.28 (p=0.992). In the reassessment, the physical therapy group presented better scores (p<0.001) and a higher difference in z-score (p<0.001), higher percentage of neonates classified as “within average” (44% in the physical therapy group and 2.6% in the no physical therapy group), as well as a higher weight gain percentage (p=0.038). We found a worsening of motor performance in 10.5% of the no physical therapy group (p<0.001) in the reassment. Motor performance improved in 81.6% of the physical therapy group and in only 13.2% of the no physical therapy group individuals (p<0.001). Conclusion: TIMP was safely and effectively applied to newborns; notably, the test must be performed by professionals experienced in care of neonates. Motor intervention was beneficial, significantly improving motor performance, and if applied early, it may adequate the motor development of these neonates, even before hospital discharge.

BACKGROUND:The association between lipoprotein levels and late-onset neonatal sepsis has shown controversial results. The aims are to assess lipid profile, cytokines, and Monocyte-to-HDL (M/H) ratio as diagnostic and prognostic markers for late-onset neonatal sepsis.METHODS:This prospective study included 49 septic neonates and 17 controls. Cholesterol (CT), Triglyceride (TG), Very-Low-Density (VLDLc), Low-Density (LDLc), and High-Density Lipoproteins (HDLc) were measured at admission (D0) and on days 3, 7 and 10 to evaluate septic shock outcomes. Cytokines and monocytes were evaluated by flow cytometry.RESULTS:Septic newborns showed higher IL-6 and IL-8 at D0 and CT levels on D7 and on D10, which also presented higher TG, VLDLc and non-HDL cholesterol concentrations than controls. The septic shock group (n = 22) revealed a higher number of male subjects, CRP, IL-6, IL-8 and IL-10 levels, while lower TG, HDLc, monocyte numbers and M/H ratio at admission compared to the non-shock group (n = 27). M/H ratio and non-HDL cholesterol on D0 were risk factors for septic shock (OR = 0.70, 0.49‒0.99; OR = 0.96, 0.92‒0.99, respectively). Decreasing levels from D0 to D3 of CT (OR = 0.96, 0.93‒0.99), VLDLc (OR = 0.91, 0.85‒0.98), and non-HDL cholesterol (OR = 0.92, 0.87‒0.98) were also predictors of septic shock.CONCLUSIONS:Lower M/H ratios and non-HDL cholesterol at admission and decreasing levels of cholesterol, VLDLc and non-HDL cholesterol during a hospital stay are associated with the development of septic shock in newborns with late-onset neonatal sepsis.

Introduction: Vancomycin is a glycopeptide antibiotic considered the gold standard in the treatment of staphylococcal infections that are oxacillin-resistant.

Introduction: Mechanical ventilation (MV) is indicated in diverse clinical situations in which the individual develops acute or chronic respiratory failure. Objective: To eva- luate the palate shape of preterm infants aged 12 to 24 months who were submitted to orotracheal intubation (OTI) and mechanical ventilation. Methods: This cross-sectional observational study included preterm infants submitted to MV by OTI for at least seven days, who weighed less than 2000 g at birth, and were attended at the Preterm Infant Care Outpatient Clinic of the University Hospital of the University of São Paulo and the Premature Infant Outpatient Clinic of the Children’s Institute of the Clinics Hospital of the School of Medicine of the University of São Paulo. Sociodemographic data were collected from neonatal medical records of the participating children. The oral cavity was examined to classify palate shape into square, narrow or ovoid. Statistical analyses were performed using the ANOVA F, Kruskal-Wallis and Chi-square tests, with a 5% significance level. Results: The mean period of OTI was 25.3 ± 25.8 days, and the children presented a significantly higher percentage of narrow shaped palate (p<0.001). Conclusion: The palate in preterm infants submitted to invasive MV by OTI is predominantly narrow and deep.

Objective: To describe thyroid alterations in term newborns (TNB) with fungal sepsis during NICU hospitalization. Method: The study included six TNB that during the clinical and laboratory manifestations of sepsis with positive cultures for fungus showed changes in thyroid hormones, called low T3 syndrome and low T3-T4 syndrome. TNB that could present hormonal changes caused by disease as those born to mothers with thyroid disease, or who had perinatal asphyxia and major surgeries were excluded. Results: Of six TNB with fungal sepsis, five had positive culture for Candida albicans and one had positive culture for Candida tropicalis. Low T3 syndrome was observed in two TNB (50%), while T3-T4 syndrome was observed in other two (100%). The four children progressed to septic shock. Conclusion: Fungal sepsis is becoming more common among newborns admitted to NICU. Thyroid insufficiency could be a marker of disease severity with possible need for hormone supplementation.

The objective was to investigate whether phagocytes from healthy and septic newborns have a developmental deficiency in their capacity to recognize, phagocytize and generate hydrogen peroxide (H2O2) in response to Escherichia coli and Staphylococcus aureus. TLR expression and phagocytic ability of neutrophils and monocytes from 44 healthy preterm and term neonates, from 13 newborns with late-onset sepsis and from 24 healthy adults were determined using flow cytometry, and H2O2 production was measured by dihydrorhodamine test. TLR-2 and TLR-4 expressions were similar among the groups. The phagocytic ability of monocytes and neutrophils exposed to E. coli and S. aureus in healthy and septic neonates was significantly reduced compared to that of adults. Monocytes from septic newborns exposed to E. coli had higher H2O2 production than those of the other groups. The oxidative burst of monocytes exposed to S. aureus was reduced in preterm newborns compared with term ones and those with sepsis, and no differences were found in the oxidative burst of neutrophils. Even with the ability to recognize bacteria, a decreased clearance of pathogens can cause an imbalance in the immune response, which could lead to a predisposition to sepsis. Once established, the increased production of cytokines and ROS in an attempt to control the infection as well as the lack of full phagocytic activity leads to persistence of the pathogen and a state of constant inflammation.

Introduction: Congenital malformations are major diseases observed at birth. They are the second most common cause of death in the neonatal population, the fi rst one being prematurity. Objective: To characterise the clinical outcome of newborns with gastroschisis (GS) in a neonatal intensive care unit. Methods: A retrospective observational clinical study in 50 infants with GS using the association of intestinal abnormalities, impossibility of primary closure of the abdominal defect and reoperation necessity as classifi cation criteria for the disease. The signifi cance level was p < 0.05. Results: The hospitalisation to primary surgery occurred with a median age of 2 hours. Fourteen percent of children were subjected to a primary silo interposition and 24% had associated intestinal malformation. Nineteen newborns (NB) required more than one surgery. The median length of stay was 33 days, higher in patients with complex GS (56 days). All NB recovered from urine output 48 hours after surgery and 40% had hyponatraemia and oligoanuria in this period. There was no difference between the natraemia and fasting time (p = 0.79). Weight gain was similar in both groups with total parenteral nutrition and became signifi cantly higher in patients with simple GS after enteral feeding (p = 0.0046). These NB evolved 2.4 times less cholestasis. Late-onset sepsis occurred in 58% of patients and was related to the infection of the central venous catheter in 37.9% of cases. Mortality was higher in infants infected with complex GS and the overall mortality rate was 14%. Conclusion: Clinical characterisation of newborns with gastroschisis depends on the complexity and the knowledge and conduct of morbidities to reduce mortality.

Vieira, Renata A. MD, PhD; Ceccon, Maria Esther J. R. MD, PhD; Brunow de Carvalho, Werther MD, PhD Author Information

OBJECTIVETo assess hormonal changes in nonthyroidal illness syndrome (NTIS) in full-term newborns (NT) with sepsis.MATERIALS AND METHODSWe included 28 NT with sepsis divided into 2 groups according to the time of normalization of serum and clinical indicators of infection: group A(A), 16 NT with improvement in up to 8 days; and group B(B), 12 NT improvement after 8 days. Among the 28 NT, 15 NT progressed to septic shock, with 5 NT group A and 10 NT in group B. NT were excluded when they showed severe sepsis and asphyxia, and congenital malformations, as well as those whose mothers had thyroid disease and IUGR.RESULTS17 NT (60.7%) presented NTIS. Low T3 was observed in NTIS in 10 NT (58.8%), and low T4 and T3 in 5 NT (29.5%), all of them with septic shock. Two NT showed mixed changes (11.7%). After sepsis was cured, there was no hormonal change, except in 3 NT. Administration of dopamine, furosemide, and corticosteroids did not affect the results.CONCLUSIONSThis study indicates that nonthyroidal illness syndrome may be transiently present during sepsis in full-term newborns, especially in cases of prolonged sepsis. Low T3 can occur without changes in reverse T3 (different from adults), and low T4 and T3 occur mainly in patients with septic shock.

Resumo A sepse neonatal e uma doenca grave que altera a funcao de varios orgaos inclusive a funcao tireoidiana. Objetivos :Verificar as alteracoes hormonaisnaSindrome da doenca nao Tireoidiana (SDNT) em recem-nascidos a termo(RNT) com sepse. Metodos :Foram incluidos 28 RNT com sepse divididos em 2 grupos de acordo com o tempo de normalizacao dos indicadores sericos e clinicos de infeccao: grupo A: 16 RNT com melhora ate 8 dias e grupo B: 12 RNT alem de 8 dias. Entre os 28 RNT, 15 RNT evoluiram com choque septico sendo 5 RNT do grupo A e 10 do grupo B. Foram excluidos os RNT com sepse e asfixia grave, malformacoes congenitas, filho de mae com doenca tireoidianae com CIUR. Resultados: SDNT presente em 17 RNT(60,7%).OT3 baixo em 10 RNT (58,8%),T4 e T3 baixo em 5 RNT (29,5%) todos com choque septico. Dois RNT apresentaram alteracoes mistas (11,7%). Na cura da sepse, com excecao de 3 RNT, nao havia mais alteracao hormonal.Administracao de dopamina, furosemida e corticoide nao interferiram nos resultados. Conclusoes :Este estudo permite concluir que a Sindrome da Doenca Nao Tireoidiana pode estar presente transitoriamente durante a sepse de recem-nascidos a termo, principalmente na sepse prolongada. T3 baixo pode acontecer sem alteracao do T3 reverso (diferente de pacientes adultos) e T4 e T3 baixo ocorre principalmente na presenca de choque septico. (c) Abstratc e Keywords Summary : Neonatal sepsis is a serious disease that alters the function of several organs including thyroid function. Objectives: To assess the hormonal changes in nonthyroidal illness syndrome in newborn (NTIS) in newborns at term (NT) with sepsis. Methods: We included 28 NT with sepsis divided into 2 groups according to the time of normalization of serum and clinical indicators of infection: group A: 16 NT with improvement up to 8 days and group B: 12 NT beyond 8 days. Among the 28 NT, 15 NT progressed to septic shock and 5 NT group A and 10NT in group B. NT were excluded with severe sepsis and asphyxia, congenital malformations whose mothers with thyroid disease and IUGR. Results: NT present in 17 (60.7%) NTIS. The low T3 in NTIS 10 NT (58.8%), low T4 and T3 in 5 NT (29.5%) all with septic shock. Two NT showed mixed changes (11.7%). In curing sepsis, except 3 NT, there was no hormonal change. Administration of dopamine, furosemide and corticosteroids did not affect the results. Conclusions: This study indicates that the nonthyroidal illness syndrome may be present transiently during sepsis in newborns at term, especially in prolonged sepsis. Low T3 can happen without changing the reverse T3 (unlike adults) and low T4 and T3 occurs mainly in patients with septic shock.

Blood levels of regulators of the complement system in preterm babies were reported in few studies only. The aim of this study was to set up a complement profile in premature and term babies focusing on the development of blood levels of MBL, key regulatory proteins and on classical pathway activity, which may allow an estimation of potential susceptibility to infection. Complement activity (CH50), levels of mannan‐binding lectin (MBL), complement regulators (factors H and I, C1 inhibitor, properdin) and C3a as marker of complement activation were assessed in three groups of healthy newborns: (1) prematures (≤34 weeks); (2) late prematures (>34–<37 weeks) and (3) term neonates (≥37 weeks). CH50 increased with gestational age with lower titres in cord blood than in day 5 post‐delivery venous blood. MBL concentrations were not significantly different among groups. Quantitative and functional C1 inhibitor were below adult normal range in prematures <34 weeks and lower in cord blood as compared to day 5. Factor I, factor H and properdin remained below adult values in all groups. Low C3a levels excluded that low complement titres were due to activation‐induced consumption. These results demonstrate the relative immaturity of the complement system and its regulation, especially in premature infants.

The immune system of neonates has been considered functionally immature, and due to their high susceptibility to infections, the aim of this study was to analyse the phenotypic differences in leucocyte populations in healthy preterm and full‐term newborns. We evaluated the absolute numbers and frequencies of dendritic cells (DCs) and DC subsets, monocytes and T and B lymphocytes and subsets in the cord blood of healthy moderate and very preterm (Group 1), late preterm (Group 2) and full‐term (Group 3) newborns and in healthy adults, as controls, by flow cytometry. The analyses revealed statistically higher absolute cell numbers in neonates compared with adults due to the characteristic leucocytosis of neonates. We observed a lower frequency of CD80+ myeloid and plasmacytoid DCs in Group 1 and reduced expression of TLR‐4 on myeloid DCs in all neonates compared with adults. TLR‐2+ monocytes were reduced in Group 1 compared with Groups 2 and 3, and TLR‐4+ monocytes were reduced in Groups 1 and 2 compared with Group 3. The frequencies and numbers of naïve CD4+ T and CD19+ B cells were higher in the three groups of neonates compared with adults, while CD4+ effector and effector memory T cells and CD19+ memory B cells were elevated in adults compared with neonates, as expected. Our study provides reference values for leucocytes in cord blood from term and preterm newborns, which may facilitate the identification of immunological deficiencies in protection against extracellular pathogens.