Body composition and metabolic consequences of antibiotics most frequently administered to newborns in intensive care units: an experimental study in healthy newborn rats.

Introduction: The increasing overuse of antibiotics in recent years has led to antibiotics being the most prescribed drugs for pediatric patients, and 72% of patients in the neonatal intensive care unit are treated with antibiotics. One effect of antibiotic use is the alteration of the microbiota, which is associated with metabolic disorders, including obesity. Methods: This experimental study in newborn rats compared the administration of ampicillin/meropenem (Access/Watch groups) at 100/10 µg/g every 12 h, cefotaxime 200 µg/g every 24 h (Watch group), and amikacin 15 µg/g every 24 h (Access group) versus saline solution as the control. Each antibiotic was adjusted to the required dosages based on weight, and the doses were administered intraperitoneally daily for 5 days to 10-14 newborn male rats per group. A comparison of the morphometric and biochemical parameters registered on day 28 was performed using ANOVA. Results: Amikacin had the largest effect on morphometric measurements, and low-density lipoprotein cholesterol, while cefotaxime had the largest effect on glucose and triglycerides, whereas ampicillin/meropenem produced the weakest effect on the measured parameters. Discussion: The administration of antibiotics in the neonatal stage can affect the body composition of rats as well as the lipid and carbohydrate serum levels. Future studies should evaluate the toxicity of antibiotics in immature neonatal organs and could help to improve therapeutic decisions and prevent the unjustified use of antibiotics in newborns, thereby reducing metabolic consequences.

A Review Study of the Participation of Late Domains in Sorting and Transport of Viral Factors to Exosomes.

Cellular communication depends heavily on the participation of vesicular systems generated by most cells of an organism. Exosomes play central roles in this process. Today, these vesicles have been characterized, and it has been determined that the cargo they transport is not within a random system. In fact, it depends on various molecular signals and the recruitment of proteins that participate in the biogenesis of exosomes. It has also been shown that multiple viruses can recruit these vesicles to transport viral factors such as genomes or proteins. It has been shown that the late domains present in viral proteins are critical for the exosomal selection and biogenesis systems to recognize these viral proteins and introduce them into the exosomes. In this review, the researchers discuss the evidence related to the characterization of these late domains and their role in exosome recruitment during viral infection.

Regional moderate hyperthermia for mild-to-moderate COVID-19 (TherMoCoV study): a randomized controlled trial.

Background: To prevent COVID-19 progression, low-cost alternatives that are available to all patients are needed. Diverse forms of thermotherapy have been proposed to prevent progression to severe/critical COVID-19. Objective: The aim of this study is to evaluate the efficacy and safety of local thermotherapy to prevent disease progression in hospitalized adult patients with mild-to-moderate COVID-19. Methods: A multicenter, open-label, parallel-group, randomized, adaptive trial is used to evaluate the efficacy and safety of local thermotherapy to prevent disease progression in hospitalized adult patients with mild-to-moderate COVID-19. Eligible hospitalized adult patients with symptoms of COVID-19 with ≤5 days from symptom onset, meeting criteria for mild or moderate COVID-19, were randomly assigned to the intervention consisting of local thermotherapy via an electric heat pad in the thorax (target temperature range 39.5­42°C) continuously for 90 min, twice daily, for 5 days, or standard care. The main outcome was the proportion of patients who progressed to severe-to-critical COVID-19 or death. Patients were randomized in a 1:1 ratio through a centralized computer-generated sequence of minimization with a random component of 20%. Participants and medical staff were not blinded to the intervention. Results: One-hundred and five participants (thermotherapy n = 54, control n = 51) with a median age of 53 (IQR: 41­64) years were included for analysis after the early cessation of recruitment due to the closure of all temporal COVID-19 units (target sample size = 274). The primary outcome of disease progression occurred in 31.4% (16/51) of patients in the control group vs. 25.9% (14/54) of those receiving thermotherapy (risk difference = 5.5%; 95%CI: −11.8­22.7, p = 0.54). Thermotherapy was well tolerated with a median total duration of thermotherapy of 900 (IQR: 877.5­900) min. Seven (13.7%) patients in the control group and seven (12.9%) in the thermotherapy group had at least one AE (p = 0.9), none of which were causally attributed to the intervention. No statistically significant differences in serum cytokines (IL-1ß, IL-6, IL-8, IL-10, IL-17, and IFN-γ) were observed between day 5 and baseline among groups. Conclusion: Local thermotherapy was safe and well-tolerated. A non-statistically significant lower proportion of patients who experienced disease progression was found in the thermotherapy group compared to standard care. Local thermotherapy could be further studied as a strategy to prevent disease progression in ambulatory settings.Clinical Trial registration: www.clinicaltrials.gov, identifier: NCT04363541.

Trends in Gliosis in Obesity, and the Role of Antioxidants as a Therapeutic Alternative.

Obesity remains a global health problem. Chronic low-grade inflammation in this pathology has been related to comorbidities such as cognitive alterations that, in the long term, can lead to neurodegenerative diseases. Neuroinflammation or gliosis in patients with obesity and type 2 diabetes mellitus has been related to the effect of adipokines, high lipid levels and glucose, which increase the production of free radicals. Cerebral gliosis can be a risk factor for developing neurodegenerative diseases, and antioxidants could be an alternative for the prevention and treatment of neural comorbidities in obese patients. AIM: Identify the immunological and oxidative stress mechanisms that produce gliosis in patients with obesity and propose antioxidants as an alternative to reducing neuroinflammation. METHOD: Advanced searches were performed in scientific databases: PubMed, ProQuest, EBSCO, and the Science Citation index for research on the physiopathology of gliosis in obese patients and for the possible role of antioxidants in its management. CONCLUSION: Patients with obesity can develop neuroinflammation, conditioned by various adipokines, excess lipids and glucose, which results in an increase in free radicals that must be neutralized with antioxidants to reduce gliosis and the risk of long-term neurodegeneration.

Perinatal mental health and recommendations for integral care in gyneco-obstetric hospitals.

Mental health is defined as the ability by which individuals recognize their own abilities and cope with the normal stress of life, work productively and fruitfully, contribute to their communities and enjoy the greatest possible well-being. Therefore, it is essential as a part of the health of the individual and its constant evaluation. Recently, special attention has been drawn to the study of the mental health of women, given the greater probability to suffer depression and anxiety disorders during and after pregnancy. The most vulnerable state occurs in adolescence, pregnancy, puerperium and perimenopause; Adequate mental health during pregnancy has shown beneficial effects in the resolution of pregnancy and in the health of the newborn. Regarding this paper, the fundamental aspects in the definition of perinatal mental health were reviewed, its determinants, the main mental disorders in this vital period, its role in perinatal outcomes and the importance of its evaluation. Some basic recommendations for adequate mental health care in gyneco-obstetric hospitals are also proposed.

La salud mental es la aptitud por la cual los individuos reconocen sus habilidades y son capaces de hacer frente al estrés normal de la vida, trabajar de forma productiva y fructífera, contribuir a sus comunidades y gozar del mayor bienestar posible. Por ello, es fundamental para la salud integral del individuo y su evaluación constante. Recientemente se ha prestado especial atención a la salud mental de las mujeres, puesto que se ha observado una mayor propensión a sufrir depresión y trastornos de ansiedad durante y posterior al embarazo. El estado de mayor vulnerabilidad sucede en la adolescencia, el embarazo, el puerperio y la perimenopausia. Una adecuada salud mental durante la gestación ha mostrado efectos benéficos en la resolución del embarazo y en la salud del recién nacido. En este trabajo se revisan aspectos fundamentales en la definición de salud mental perinatal, sus determinantes, los principales trastornos mentales en este periodo vital, su papel en los resultados perinatales y la importancia de su evaluación. Se exponen también algunas recomendaciones básicas para la atención adecuada de la salud mental en los hospitales ginecoobstétricos.

Epidemiological analysis of perinatal depression.

Perinatal depression is a commonly underdiagnosed problem which not only severely affects maternal mental and physical health, but also affects the newborn on a physical, mental and cognitive level with serious repercussions on adult life. Despite efforts to obtain useful information to dimension the problem, most experts in the field agree that this disorder is more frequent than estimated. Thus, the improvement in obtaining information on perinatal mental health will not only allow for a better dimensioning of the problem, but will also allow for better decision making in public mental health to reduce morbidity and mortality and the burden of disease associated with perinatal depression.

La depresión perinatal es un problema habitualmente subdiagnosticado que no sólo afecta de manera importante la salud mental y física materna, sino también al recién nacido en los aspectos físico, mental y cognitivo, con serias repercusiones en la vida adulta. A pesar de los esfuerzos para obtener información útil para dimensionar el problema, la mayoría de los expertos en el tema coinciden en señalar que este trastorno es más frecuente de lo que se estima. La mejora en la obtención de información en salud mental perinatal permitirá dimensionar mejor el problema y una adecuada toma de decisiones en salud mental pública para disminuir la morbimortalidad y la carga de la enfermedad asociada a la depresión perinatal.

Breastfeeding and COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic has affected all dimensions of health care, including exclusive breastfeeding assurance and its promotion. The risk of contagion and the consequences of the pandemic have raised concerns among future mothers or in those who are already breastfeeding due to the risk of possible transmission of the virus through breast milk, although active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has not yet been detected in breast milk. The fear of contagion has favored mother-child isolation policies. So far, there is no evidence of vertical transmission, and the risk of horizontal transmission in the infant is similar to that of the general population. In infants with COVID-19, breastfeeding can even favorably change the clinical course of the disease.

La pandemia de enfermedad por coronavirus 2019 (COVID-19) ha afectado a todas las dimensiones de la atención en salud, entre ellas el aseguramiento de la lactancia materna exclusiva y su promoción. El riesgo de contagio y las consecuencias de la pandemia han provocado preocupación entre las futuras madres o las que se ya encuentran lactando debido al riesgo de una posible transmisión del virus a través de la leche materna. Aunque aún no se ha detectado el coronavirus 2 del síndrome respiratorio agudo grave (SARS-CoV-2) activo en la leche materna. El miedo al contagio ha favorecido las políticas de aislamiento madre-hijo. Hasta el momento no existe evidencia de transmisión vertical y el riesgo de transmisión horizontal en el lactante es similar al de la población general. En lactantes con COVID-19 la lactancia materna incluso puede cambiar favorablemente el curso clínico de la enfermedad.

Lactancia materna y COVID-19 / Breastfeeding and COVID-19

Resumen La pandemia de enfermedad por coronavirus 2019 (COVID-19) ha afectado a todas las dimensiones de la atención en salud, entre ellas el aseguramiento de la lactancia materna exclusiva y su promoción. El riesgo de contagio y las consecuencias de la pandemia han provocado preocupación entre las futuras madres o las que se ya encuentran lactando debido al riesgo de una posible transmisión del virus a través de la leche materna. Aunque aún no se ha detectado el coronavirus 2 del síndrome respiratorio agudo grave (SARS-CoV-2) activo en la leche materna. El miedo al contagio ha favorecido las políticas de aislamiento madre-hijo. Hasta el momento no existe evidencia de transmisión vertical y el riesgo de transmisión horizontal en el lactante es similar al de la población general. En lactantes con COVID-19 la lactancia materna incluso puede cambiar favorablemente el curso clínico de la enfermedad.

Abstract The COVID-19 pandemic has affected the health attention in all dimensions, one of them, the exclusive breastfeeding assurance and her promotion. The high risk of contagion and the pandemic consequences have raised a number of concerns in future mothers or those who are breastfeeding because of the risk of a possible transmission of the virus through breast milk. Although SARS-CoV2 has no evidence of being active on breast milk, the fear of contagion has favored mother-child isolation policies. At this point, there are no evidence of vertical transmission and the risk of horizontal transmission in the infant is similar to the general population. Breastfeeding in newborn with COVID-19, can even favorably change the clinical course of the disease.

Multiparameter flow cytometry analysis of leukocyte markers for diagnosis in preterm neonatal sepsis.

PURPOSE: Neonatal sepsis is an important public health concern worldwide due to its immediate lethality and long-term morbidity rates, Clinical evaluation and laboratory analyses are indispensable for diagnosis of neonatal sepsis. However, assessing multiple biomarkers in neonates is difficult due to limited blood availability. The aim is to investigate if the neonatal sepsis in preterm could be identified by multiparameter analysis with flow cytometry. MATERIALS AND METHODS: The expression of activation-related molecules was evaluated by flow cytometry in newborn with or without risk factors for sepsis. RESULTS: Our analysis revealed that several markers could be useful for sepsis diagnosis, such as CD45RA, CD45RO, or CD71 on T cells; HLA-DR on NKT or classic monocytes, and TREM-1 on non-classic monocytes or neutrophils. However, ROC analysis shows that the expression of CD45RO on T lymphocytes is the only useful biomarker for diagnosis of neonatal late-onset sepsis. Also, decision tree analyses showed that CD45RO plus CD27 could help differentiate the preterm septic neonates from those with risk factors. CONCLUSIONS: Our study shows a complementary and practical strategy for biomarker assessment in neonatal sepsis.

Neurophysiological Mechanisms Related to Pain Management in Bone Tumors.

BACKGROUND: Primary and metastatic bone tumor incidence has increased in the previous years. Pain is a common symptom and is one of the most important related factors to the decrease of quality of life in patients with bone tumor. Different pain management strategies are not completely effective and many patients afflicted by cancer pain cannot be controlled properly. In this sense, we need to elucidate the neurophysiology of cancer-induced pain, contemplating other components such as inflammation, neuropathies and cognitive components regarding bone tumors, and thus pave the way for novel therapeutic approaches in this field. AIM: This study aims to identify the neurophysiology of the mechanisms related to pain management in bone tumors. METHODS: Advanced searches were performed in scientific databases: PubMed, ProQuest, EBSCO, and the Science Citation index to get information about the neurophysiology mechanisms related to pain management in bone tumors. RESULTS: The central and peripheral mechanisms that promote bone cancer pain are poorly understood. Studies have shown that bone cancer could be related to neurochemicals produced by tumor and inflammatory cells, coupled with peripheral sensitization due to nerve compression and injury caused by tumor growth. The activity of mesolimbic dopaminergic neurons, substance P, cysteine/ glutamate antiporter, and other neurochemical dynamics brings us putative strategies to suggest better and efficient treatments against pain in cancer patients. CONCLUSION: Cancer-induced bone pain could include neuropathic and inflammatory pain, but with different modifications to the periphery tissue, nerves and neurochemical changes in different neurological levels. In this sense, we explore opportunity areas in pharmacological and nonpharmacological pain management, according to pain-involved mechanisms in this study.

CD71+ Erythroid Cells in Human Neonates Exhibit Immunosuppressive Properties and Compromise Immune Response Against Systemic Infection in Neonatal Mice.

Newborns are highly susceptible to infectious diseases. The underlying mechanism of neonatal infection susceptibility has generally been related to their under-developed immune system. Nevertheless, this notion has recently been challenged by the discovery of the physiological abundance of immunosuppressive erythroid precursors CD71+erythroid cells (CECs) in newborn mice and human cord blood. Here, as proof of concept, we show that these cells are also abundant in the peripheral blood of human newborns. Although their frequency appears to be more variable compared to their counterparts in mice, they rapidly decline by 4 weeks of age. However, their proportion remains significantly higher in infants up to six months of age compared to older infants. We found CD45 expressing CECs, as erythroid progenitors, were the prominent source of reactive oxygen species (ROS) production in both humans and mice. Interestingly, a higher proportion of CD45+CECs was observed in the spleen versus bone marrow of neonatal mice, which was associated with a higher ROS production by splenic CECs compared to their siblings in the bone marrow. CECs from human newborns suppressed cytokine production by CD14 monocytes and T cells, which was partially abrogated by apocynin in vitro. Moreover, the depletion of CECs in neonatal mice increased the number of activated effector immune cells in their spleen and liver, which rendered them more resistant to Listeria monocytogenes infection. This was evident by a significant reduction in the bacteria load in the spleen, liver and brain of treated-mice compared to the control group, which enhanced their survival rate. Our finding highlights the immunoregulatory processes mediated by CECs in newborns. Thus, such tightly regulated immune system in newborns/infants may explain one potential mechanism for the asymptomatic or mild COVID-19 infection in this population.

Factores asociados a muerte en niños con COVID-19 en México / Mortality risk factors in Mexican children with COVID-19

Resumen Introducción: Se informa que la mayoría de los niños afectados por SARS-CoV-2 cursan asintomáticos y que en ellos la mortalidad por COVID-19 es baja; en México se desconoce la información al respecto en este grupo de la población. Objetivo: Evaluar los factores de riesgo asociados a mortalidad en niños mexicanos con COVID-19. Método: Análisis secundario de la base de datos de la Dirección General de Epidemiología. Se incluyeron niños menores de 19 años, en quienes se confirmó SARS-CoV-2 mediante RT-PCR. Resultados: Se incluyeron 1443 niños. La mediana de edad fue de ocho años; 3.3 % ingresó a la unidad de cuidados intensivos, 1.8 % requirió ventilación mecánica asistida y la mortalidad fue de 1.9 %. En los modelos multivariados, el desarrollo de neumonía constituyó el principal factor de riesgo de mortalidad, con razón de momios (RM) de 6.45 (IC 95 % 1.99, 20.89); los pacientes que requirieron intubación tuvieron RM de 8.75 (IC 95 % 3.23, 23.7). Conclusiones: Los niños con COVID 19 tienen alta mortalidad en México, por lo que en ellos se debe procurar evitar la neumonía, especialmente en los menores de cuatro años, con riesgo cardiovascular o inmunosupresión.

Abstract Introduction: Most children affected by SARS-CoV-2 are reported to be asymptomatic, and COVID-19-related mortality in them is low; in Mexico, there is a lack of information on the subject in this population group. Objective: To assess the risk factors associated with mortality in Mexican children with COVID-19. Method: Secondary analysis of the General Directorate of Epidemiology database. Children younger than 19 years, in whom SARS-CoV-2 infection was confirmed by RT-PCR, were included. Results: 1443 children were included. Median age was eight years; 3.3 % were admitted to the intensive care unit, 1.8 % required assisted mechanical ventilation, and mortality was 1.9 %. In multivariate models, the development of pneumonia was the main risk factor for mortality, with an odds ratio (OR) of 6.45 (95 % CI 1.99, 20.89); patients who required intubation had an OR of 8.75 (95 % CI 3.23, 23.7). Conclusions: Children with COVID-19 exhibit high mortality in Mexico, and avoiding pneumonia should therefore be tried in them, especially in children younger than four years with cardiovascular risk or immunosuppression.

Factors associated with death in children with COVID-19 in Mexico.

INTRODUCTION: Most children affected by SARS-CoV-2 are reported to be asymptomatic, and COVID-19-related mortality in them is low; in Mexico, there is a lack of information on the subject in this population group. OBJECTIVE: To assess the risk factors associated with mortality in Mexican children with COVID-19. METHOD: Secondary analysis of the General Directorate of Epidemiology database. Children younger than 19 years, in whom SARS-CoV-2 infection was confirmed by RT-PCR, were included. RESULTS: 1443 children were included. Median age was eight years; 3.3 % were admitted to the intensive care unit, 1.8 % required assisted mechanical ventilation, and mortality was 1.9 %. In multivariate models, the development of pneumonia was the main risk factor for mortality, with an odds ratio (OR) of 6.45 (95 % CI: 1.99, 20.89); patients who required intubation had an OR of 8.75 (95 % CI: 3.23, 23.7). CONCLUSIONS: Children with COVID-19 exhibit high mortality in Mexico, and avoiding pneumonia should therefore be tried in them, especially in children younger than four years, with cardiovascular risk or immunosuppression. INTRODUCCIÓN: Se informa que la mayoría de los niños afectados por SARS-CoV-2 cursan asintomáticos y que en ellos la mortalidad por COVID-19 es baja; en México se desconoce la información al respecto en este grupo de la población. ­. OBJETIVO: Evaluar los factores de riesgo asociados a mortalidad en niños mexicanos con COVID-19. MÉTODO: Análisis secundario de la base de datos de la Dirección General de Epidemiología. Se incluyeron niños menores de 19 años, en quienes se confirmó SARS-CoV-2 mediante RT-PCR. RESULTADOS: Se incluyeron 1443 niños. La mediana de edad fue de ocho años; 3.3 % ingresó a la unidad de cuidados intensivos, 1.8 % requirió ventilación mecánica asistida y la mortalidad fue de 1.9 %. En los modelos multivariados, el desarrollo de neumonía constituyó el principal factor de riesgo de mortalidad, con razón de momios (RM) de 6.45 (IC 95 % 1.99, 20.89); los pacientes que requirieron intubación tuvieron RM de 8.75 (IC 95 % 3.23, 23.7). CONCLUSIONES: Los niños con COVID 19 tienen alta mortalidad en México, por lo que en ellos se debe procurar evitar la neumonía, especialmente en los menores de cuatro años, con riesgo cardiovascular o inmunosupresión.

Medical Outcomes in Women Who Became Pregnant after Vaccination with a Virus-Like Particle Experimental Vaccine against Influenza A (H1N1) 2009 Virus Tested during 2009 Pandemic Outbreak.

The clinical effects and immunological response to the influenza vaccine in women who later become pregnant remain to be thoroughly studied. Here, we report the medical outcomes of 40 women volunteers who became pregnant after vaccination with an experimental virus-like particle (VLP) vaccine against pandemic influenza A(H1N1)2009 (influenza A(H1N1)pdm09) and their infants. When included in the VLP vaccine trial, none of the women were pregnant and were randomly assigned to one of the following groups: (1) placebo, (2) 15 µg dose of VLP vaccine, or (3) 45 µg dose of VLP vaccine. These 40 women reported becoming pregnant during the follow-up phase after receiving the placebo or VLP vaccine. Women were monitored throughout pregnancy and their infants were monitored until one year after birth. Antibody titers against VLP were measured in the mothers and infants at delivery and at six months and one year after birth. The incidence of preeclampsia, fetal death, preterm delivery, and premature rupture of membranes was similar among groups. All vaccinated women and their infants elicited antibody titers (≥1:40). Women vaccinated prior to pregnancy had no adverse events that were different from the nonvaccinated population. Even though this study is limited by the sample size, the results suggest that the anti-influenza A(H1N1)pdm09 VLP experimental vaccine applied before pregnancy is safe for both mothers and their infants.

The role of complement in preterm birth and prematurity.

Complications of preterm birth (PTB) are the global leading cause of death in children younger than 5 years of age. Almost 15 million children are born prematurely in the world each year. Increasing evidence suggests that labor and delivery have many hallmarks of an inflammatory reaction, where complement activation has an active participation. As one of the most important components of inflammation, the role of complement during labor and PTB is becoming an attractive research target. The complement components C1q and C5b-9 are deposited on fetal membranes and release inflammatory mediators that contribute to uterine contractions, cervical ripening, cell chemotaxis, metalloproteinases production, membrane awaking and rupture, and it participates as a co-adjuvant in the onset and progress of labor. This article reviews a basic description of the complement system, its role in preterm birth and current concepts regarding its contribution in novel therapy strategies and new biomarkers.

Morbidity Trends and Risk of Tuberculosis: Mexico 2007-2017.

Background: To know the current status of the epidemiological and geographic distribution of tuberculosis and its complication meningeal tuberculosis in Mexico, this work analyzes national surveillance data (ten years) issued by the General Directorate of Epidemiology (GDE). Methods: An observational and retrospective analysis of monthly and annual reports of pulmonary and meningeal tuberculosis cases from January 2007 to December 2017 was performed on the annual reports issued by the GDE in Mexico. The number of cases and incidence were classified by year, state, age group, gender, and seasons. Results: A national case distribution map of pulmonary and meningeal tuberculosis incidence was generated. During this period, a total of 184,003 and 3,388 cases were reported with a median of 16,727.5 and 308 cases per year for pulmonary and meningeal tuberculosis diseases, respectively. The number of cases and incidence of pulmonary and meningeal tuberculosis per year showed that male gender presented a continuous increase in both parameters. The geographic analysis of the distribution of cases of tuberculosis showed that states like Guerrero, Tabasco, and Veracruz presented higher means of tuberculosis cases during this period. Northern states had the highest number of cases in the country compared to other states. In Mexico, pulmonary tuberculosis and meningeal tuberculosis are seasonal. Interestingly, cases of meningeal tuberculosis show an increase during October and November (autumn). Conclusions: In Mexico, during the years 2007-2017, there has been an increase in the proportion of male TB patients. It remains necessary to implement strategies to detect TB in the adult population, especially among men, because tuberculosis could be difficult to recognize in an early stage in the population, and the appearance of resistant strains can cause an increase in the incidence of the disease.

Enteral Docosahexaenoic Acid Reduces Analgesic Administration in Neonates Undergoing Cardiovascular Surgery.

BACKGROUND: Neonates undergoing surgery require analgesic medication to ameliorate acute pain. These medications produce negative side effects. Docosahexaenoic acid (DHA) has an antinociceptive effect in animals, but this has not been evaluated in human neonates. We evaluated the DHA effect on cumulative dose and duration of analgesics administered to neonates undergoing cardiovascular surgery. METHODS: A secondary analysis was performed with data from a clinical trial, in which enteral DHA was administered perioperatively compared with sunflower oil (SO). Present study assessed the antinociceptive effect of DHA by measuring the cumulative dose and duration of analgesics administered during postoperative stay in a neonatal intensive care unit. Multivariate linear regression models were performed. RESULTS: Seventeen neonates received DHA and 18 received SO in the control group. Compared with the control group, the DHA group received lower cumulative dose (14.6 ± 2.2 vs. 25.2 ± 4.8 µg/kg, p = 0.029) and shorter duration of buprenorphine (2 days (1-8) vs. 4.5 days (1-12); p = 0.053). After adjusting for confounders, the DHA group received significantly lesser buprenorphine (ß = -27 µg/kg, p = 0.028; R2 model = 0.90) for shorter duration (ß = -9 days, p = 0.003; R2 model = 0.94). No differences in fentanyl or ketorolac were detected. CONCLUSIONS: Buprenorphine administration was reduced in neonates who received DHA, suggesting that DHA likely has analgesic effects.

Beneficial Effects of Enteral Docosahexaenoic Acid on the Markers of Inflammation and Clinical Outcomes of Neonates Undergoing Cardiovascular Surgery: An Intervention Study.

BACKGROUND: Neonates undergoing surgery are at risk for uncontrolled inflammatory response and adverse clinical outcomes. Docosahexaenoic acid (DHA) ameliorates inflammation, improving clinical outcomes. However, its effect has not been evaluated in neonates undergoing surgery. We evaluated the effect of DHA on markers of inflammation and clinical outcomes in neonates undergoing surgery. METHODS: A double-blind clinical trial evaluated the effect of enteral DHA (DHA group) versus sunflower oil (SO group) perioperatively administered in neonates scheduled for cardiovascular surgery. Inflammation was evaluated by percentage of cells+ for cytokines and CD69 in mononuclear cells at baseline, 24 h and 7 days post surgery. Clinical outcomes measured were sepsis, organ dysfunctions (ODs), length of stay in intensive care and bleeding. Repeated measures analysis of variance and logistic regression were applied. RESULTS: Sixteen neonates received DHA and 18 received SO. Cells+ from neonates in the DHA group showed an early increase in receptor antagonist of interleukin (IL)-1+ (IL-1ra+) and IL-10+ and a late decrease in IL-6+. IL-1ß+ and IL-10+ changes were different between groups. After adjusting for confounders, less cells from DHA group were IL-1ß+, IL-6+, IL-1ra+ and IL-10+. DHA group presented less sepsis, ODs and shorter stay, but no difference in CD69+CD4+ cells or bleeding between groups. CONCLUSIONS: Administration of enteral DHA ameliorates markers of inflammation and improves clinical outcomes in surgical neonates.

Inflammatory Response in Preterm and Very Preterm Newborns with Sepsis.

The response of the adaptive immune system is usually less intense in premature neonates than term neonates. The primary objective of this study was to determine whether immunological parameters vary between preterm (PT) neonates (≥32 weeks of gestational age) and very preterm (VPT) neonates (<32 weeks of gestational age). A cross-sectional study was designed to prospectively follow PT and VPT neonates at risk of developing sepsis. Plasma concentrations of IFN-γ, TNF-α, IL-6, IL-4, and IL-10 were detected using flow cytometry. C-reactive protein (C-RP) and the complex SC5b-9 were detected in the plasma using commercial kits. A total of 83 patients were included. The laboratory results and clinical histories showed that 26 patients had sepsis; 14 were VPT, and 12 were PT. The levels of C-RP, SC5b-9 (innate immune response mediators), and IL-10 or IL-4 (anti-inflammatory cytokines) were elevated during sepsis in both groups. IFN-γ, TNF-α, and IL-6 (proinflammatory cytokines) were differentially elevated only in PT neonates. The VPT neonates with sepsis presented increases in C-RP, SC5b-9, and anti-inflammatory cytokines but not in proinflammatory cytokines, whereas PT neonates showed increases in all studied mediators of inflammation.