Disfunción multiorgánica en el recién nacido con Encefalopatía hipóxico-isquémica en la era de la Hipotermia terapéutica

[spa] La aproximación al paciente asfíctico desde el punto de vista neurológico es fundamental por las implicaciones a corto y largo plazo, sin embargo el insulto hipóxico-isquémico altera la homeostasis global del recién nacido afectando a los diferentes órganos y sistemas. La evidencia científica acerca del daño extraneural en el recién nacido asfíctico hasta el momento actual es escasa y los estudios pertenecen a la era previa a la implantación de la hipotermia terapéutica que ha supuesto un cambio de paradigma clínico en este tipo de pacientes. Por otra parte, dado que la mayor parte de recién nacidos con encefalopatía hipóxico-isquémica nacen en centros que no disponen de hipotermia terapéutica, estos pacientes necesitarán ser trasladados en hipotermia pasiva a centros de referencia. El transporte de estos pacientes supone un reto, principalmente por la necesidad de mantener la temperatura en el rango de seguridad. Esta tesis, en base al estudio de una serie amplia de pacientes con el espectro completo de encefalopatía hipóxico-isquémica, ha abordado aspectos determinantes y hasta el momento desconocidos en el manejo del recién nacido asfíctico como son, en primer lugar, la correlación del daño multiorgánico y la encefalopatía hipóxico-isquémica en la era de la hipotermia terapéutica, aportando datos de gran utilidad clínica. Podemos concluir que la disfunción de otros órganos es prácticamente universal en el paciente con cualquier grado de encefalopatía hipóxico-isquémica en la era de la hipotermia terapéutica. El daño extraneural se correlaciona con la gravedad de la encefalopatía hipóxico-isquémica, sin embargo esta correlación se funda básicamente en la diferencia en el grado de afectación multiorgánica entre los pacientes con encefalopatía grave y los pacientes con encefalopatía moderada y leve. De esta manera, podemos establecer los siguientes patrones de afectación sistémica según el grado de EHI: 1) En el paciente con encefalopatía grave se debe anticipar una disfunción moderada o grave de otros órganos desde las primeras 24 horas de vida. En caso de no producirse, es preciso descartar exhaustivamente otras causas de encefalopatía neonatal. 2) Los pacientes con encefalopatía moderada con frecuencia presentan afectación orgánica de escasa relevancia clínica, pero una minoría de casos puede presentar afectación sistémica moderada o grave. 3) Los pacientes con encefalopatía leve presentan habitualmente afectación sistémica leve y resuelven con rapidez las alteraciones en la homeostasis. Respecto al perfil de afectación orgánica, el hígado y el medio interno son los órganos o sistemas que se afectan con mayor frecuencia en el recién nacido con encefalopatía hipóxico-isquémica, sin embargo los órganos afectados con mayor gravedad son el sistema respiratorio y cardiovascular. La disfunción renal y hematológica se producen con menor frecuencia que el resto de órganos o sistemas, sin embargo en el caso del daño renal, su afectación es con frecuencia clínicamente relevante. Así mismo, el daño extraneural en el paciente con encefalopatía hipóxico-isquémica es más intenso en las primeras 24 horas de vida. Los pacientes que sobreviven presentan una tendencia a mejorar a lo largo de las primeras 72 horas de vida. En segundo lugar, el estudio del curso del transporte del recién nacido con encefalopatía hipóxico isquémica nos ha permitido dilucidar como la gravedad de la encefalopatía hipóxico-isquémica se correlaciona inversamente con la temperatura durante el transporte en hipotermia pasiva. Los pacientes con encefalopatía grave presentan un mayor riesgo de sobreenfriamiento durante el transporte en hipotermia pasiva. Por otra parte, los eventos adversos más frecuentemente descritos durante el transporte interhospitalario en hipotermia pasiva son el deterioro cardiovascular, la presencia de hipoglucemia y sangrado endotraqueal, estos podrían disminuir con una mejor estabilización previa al transporte y con un mejor control de la temperatura.[eng] Perinatal asphyxia is a major cause of multiorgan dysfunction in the newborn. Only scarce data about the correlation of extracerebral damage and the severity of hypoxic-ischemic encephalopathy are available. This information might help to anticipate the evolution of multiorgan dysfunction according to the severity of hypoxic-ischemic encephalopathy and vice versa. On the other hand, hypoxic-ischemic encephalopathy has become a time- dependent emergency after clinical trials demonstrated the efficacy of cooling started within 6 hours of birth in reducing the risk of death or disability. Most asphyxiated infants are born in non-tertiary neonatal units and they must be transferred urgently to a center equipped with a hypothermia program. To start hypothermia as soon as possible, transferred infants are passively cooled. Nevertheless, studies do not outline medical complications during transport nor indicate whether the efficacy in maintaining target temperatures and complications are related to the severity of the hypoxic-ischemic encephalopathy in the first 6 h of life. This is the first study to evaluate the correlation of multiple organ dysfunction with the severity of hypoxic-ischemic encephalopathy. In the hypothermia era, multiple organ damage continues to be almost universal in newborns with hypoxic-ischemic encephalopathy. There is a high correlation between the severity of hypoxic-ischemic encephalopathy and multiple organ injury during the first 3 days of life. Therefore, a high index of suspicion of relevant multiorgan dysfunction is required in infants admitted with a diagnosis of severe hypoxic-ischemic encephalopathy. Patients with moderate hypoxic-ischemic encephalopathy present wide variability in the severity of multiorgan dysfunction. Finally, in the absence of multiorgan dysfunction a perinatal hypoxic-ischemic origin of acute severe neonatal encephalopathy should be carefully reconsidered. Secondly, this study shows that the risk of overcooling during transport is greater in newborns with severe hypoxic- ischemic encephalopathy and those with more severe acidosis at birth. The most common adverse events during transport are related to physiological deterioration and bleeding from the endotracheal tube. This observation provides useful information to identify those asphyxiated infants who require closer clinical surveillance during transport

The Effects of Alcohol and Drugs of Abuse on Maternal Nutritional Profile during Pregnancy

Abstract The consumption of alcohol and drugs of abuse among pregnant women has experienced a significant increase in the last decades. Suitable maternal nutritional status is crucial to maintain the optimal environment for fetal development but if consumption of alcohol or drugs of abuse disrupt the intake of nutrients, the potential teratogenic effects of these substances increase. Despite evidence of the importance of nutrition in addicted pregnant women, there is a lack of information on the effects of alcohol and drugs of abuse on maternal nutritional status; so, the focus of this review was to provide an overview on the nutritional status of addicted mothers and fetuses. Alcohol and drugs consumption can interfere with the absorption of nutrients, impairing the quality and quantity of proper nutrient and energy intake, resulting in malnutrition especially of micronutrients (vitamins, omega⁻3, folic acid, zinc, choline, iron, copper, selenium). When maternal nutritional status is compromised by alcohol and drugs of abuse the supply of essential nutrients are not available for the fetus; this can result in fetal abnormalities like Intrauterine Growth Restriction (IUGR) or Fetal Alcohol Spectrum Disorder (FASD). It is critical to find a strategy to reduce fetal physical and neurological impairment as a result of prenatal alcohol and drugs of abuse exposure combined with poor maternal nutrition. Prenatal nutrition interventions and target therapy are required that may reverse the development of such abnormalities. KEYWORDS: Fetal Alcohol Spectrum Disorder (FASD); Intrauterine Growth Restriction (IUGR); alcohol; drugs of abuse; fetal nutrition; maternal nutrition; pregnanc

The Effects of Vegetarian and Vegan Diet during Pregnancy on the Health of Mothers and Offspring

Vegetarian and vegan diets have increased worldwide in the last decades, according to the knowledge that they might prevent coronary heart disease, cancer, and type 2 diabetes. Althought plant-based diets are at risk of nutritional deficiencies such as proteins, iron, vitamin D, calcium, iodine, omega-3, and vitamin B12, the available evidence shows that well planned vegetarian and vegan diets may be considered safe during pregnancy and lactation, but they require a strong awareness for a balanced intake of key nutrients. A review of the scientific literature in this field was performed, focusing specifically on observational studies in humans, in order to investigate protective effects elicited by maternal diets enriched in plant-derived foods and possible unfavorable outcomes related to micronutrients deficiencies and their impact on fetal development. A design of pregestational nutrition intervention is required in order to avoid maternal undernutrition and consequent impaired fetal growth

Alternative consent methods used in the multinational, pragmatic, randomised clinical trial SafeBoosC-III

Background The process of obtaining prior informed consent for experimental treatment does not fit well into the clinical reality of acute and intensive care. The therapeutic window of interventions is often short, which may reduce the validity of the consent and the rate of enrolled participants, to delay trial completion and reduce the external validity of the results. Deferred consent and ‘opt-out’ are alternative consent methods. The SafeBoosC-III trial was a randomised clinical trial investigating the benefits and harms of cerebral oximetry monitoring in extremely preterm infants during the first 3 days after birth, starting within the first 6 h after birth. Prior, deferred and opt-out consent were all allowed by protocol. This study aimed to evaluate the use of different consent methods in the SafeBoosC-III trial, Furthermore, we aimed to describe and analyse concerns or complaints that arose during the first 6 months of trial conduct. Methods All 70 principal investigators were invited to join this descriptive ancillary study. Each principal investigator received a questionnaire on the use of consent methods in their centre during the SafeBoosC-III trial, including the possibility to describe any concerns related to the consent methods used during the first 6 months of the trial, as raised by the parents or the clinical staff. Results Data from 61 centres were available. In 43 centres, only prior informed consent was used: in seven, only deferred consent. No centres used the opt-out method only, but five centres used prior and deferred, five used prior, deferred and opt-out (all possibilities) and one used both deferred and opt-out. Six centres applied to use the opt-out method by their local research ethics committee but were denied using it. One centre applied to use deferred consent but was denied. There were only 23 registered concerns during the execution of the trial. Conclusions Consent by opt-out was allowed by the protocol in this multinational trial but only a few investigators opted for it and some research ethics boards did not accept its use. It is likely to need promotion by the clinical research community to unfold its potential

Incidence, Clinical Characteristics and Management of Inflammatory Bowel Disease in Spain : Large-Scale Epidemiological Study

(1) Aims: To assess the incidence of inflammatory bowel disease (IBD) in Spain, to describe the main epidemiological and clinical characteristics at diagnosis and the evolution of the disease, and to explore the use of drug treatments. (2) Methods: Prospective, population-based nationwide registry. Adult patients diagnosed with IBD-Crohn's disease (CD), ulcerative colitis (UC) or IBD unclassified (IBD-U)-during 2017 in Spain were included and were followed-up for 1 year. (3) Results: We identified 3611 incident cases of IBD diagnosed during 2017 in 108 hospitals covering over 22 million inhabitants. The overall incidence (cases/100,000 person-years) was 16 for IBD, 7.5 for CD, 8 for UC, and 0.5 for IBD-U; 53% of patients were male and median age was 43 years (interquartile range = 31-56 years). During a median 12-month follow-up, 34% of patients were treated with systemic steroids, 25% with immunomodulators, 15% with biologics and 5.6% underwent surgery. The percentage of patients under these treatments was significantly higher in CD than UC and IBD-U. Use of systemic steroids and biologics was significantly higher in hospitals with high resources. In total, 28% of patients were hospitalized (35% CD and 22% UC patients, p < 0.01). (4) Conclusion: The incidence of IBD in Spain is rather high and similar to that reported in Northern Europe. IBD patients require substantial therapeutic resources, which are greater in CD and in hospitals with high resources, and much higher than previously reported. One third of patients are hospitalized in the first year after diagnosis and a relevant proportion undergo surgery

Correction : Chaparro et al. Incidence, Clinical Characteristics and Management of Inflammatory Bowel Disease in Spain: Large-Scale Epidemiological Study. J. Clin. Med. 2021, 10, 2885

The authors wish to make the following corrections to this paper [...]

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

The Effects of Alcohol and Drugs of Abuse on Maternal Nutritional Profile during Pregnancy

The consumption of alcohol and drugs of abuse among pregnant women has experienced a significant increase in the last decades. Suitable maternal nutritional status is crucial to maintain the optimal environment for fetal development but if consumption of alcohol or drugs of abuse disrupt the intake of nutrients, the potential teratogenic effects of these substances increase. Despite evidence of the importance of nutrition in addicted pregnant women, there is a lack of information on the effects of alcohol and drugs of abuse on maternal nutritional status; so, the focus of this review was to provide an overview on the nutritional status of addicted mothers and fetuses. Alcohol and drugs consumption can interfere with the absorption of nutrients, impairing the quality and quantity of proper nutrient and energy intake, resulting in malnutrition especially of micronutrients (vitamins, omega&ndash;3, folic acid, zinc, choline, iron, copper, selenium). When maternal nutritional status is compromised by alcohol and drugs of abuse the supply of essential nutrients are not available for the fetus; this can result in fetal abnormalities like Intrauterine Growth Restriction (IUGR) or Fetal Alcohol Spectrum Disorder (FASD). It is critical to find a strategy to reduce fetal physical and neurological impairment as a result of prenatal alcohol and drugs of abuse exposure combined with poor maternal nutrition. Prenatal nutrition interventions and target therapy are required that may reverse the development of such abnormalities

The Effects of Vegetarian and Vegan Diet during Pregnancy on the Health of Mothers and Offspring

Vegetarian and vegan diets have increased worldwide in the last decades, according to the knowledge that they might prevent coronary heart disease, cancer, and type 2 diabetes. Althought plant-based diets are at risk of nutritional deficiencies such as proteins, iron, vitamin D, calcium, iodine, omega-3, and vitamin B12, the available evidence shows that well planned vegetarian and vegan diets may be considered safe during pregnancy and lactation, but they require a strong awareness for a balanced intake of key nutrients. A review of the scientific literature in this field was performed, focusing specifically on observational studies in humans, in order to investigate protective effects elicited by maternal diets enriched in plant-derived foods and possible unfavorable outcomes related to micronutrients deficiencies and their impact on fetal development. A design of pregestational nutrition intervention is required in order to avoid maternal undernutrition and consequent impaired fetal growth

Foetal Haemoglobin as a Marker of Bone Marrow Suppression Secondary to Anti-Kell Alloimmunisation

Anti-Kell alloimmunisation is a potentially severe minor blood group type incompatibility, not only as a cause of haemolytic disease of the foetus and newborn, but also due to the destruction of red blood cells (RBC) and mature form in the bone marrow with the subsequent hyporegenerative anaemia. In severe cases and when the foetus shows signs of anaemia, an intrauterine transfusion (IUT) may be necessary. When repeated, this treatment can suppress erythropoiesis and worsen the anaemia. We report the case of a newborn who required four IUTs plus an additional RBC transfusion at one month of life due to late onset anaemia. The identification of an adult haemoglobin profile with a complete absence of foetal haemoglobin in the patient’s newborn screening samples at 2 and 10 days of life warned us of a possible late anaemia. The newborn was successfully treated with transfusion, oral supplements and subcutaneous erythropoietin. A blood sample taken at 4 months of life showed the expected haemoglobin profile for that age with a foetal haemoglobin of 17.7%. This case illustrates the importance of a close follow-up of these patients, as well as the usefulness of the haemoglobin profile screening as a tool for anaemia assessment