Juan Arnaez

Neonatal hypoxic‐ischaemic encephalopathy: most deaths followed end‐of‐life decisions within three days of birth

To investigate the circumstances surrounding end‐of life decisions (EoL) of infants with hypoxic‐ischaemic encephalopathy (HIE) and examine changes over a 10‐year period.

Amplitude Integrated Electroencephalogram as a Prognostic Tool in Neonates with Hypoxic-Ischemic Encephalopathy: A Systematic Review.

Introduction Perinatal management and prognostic value of clinical evaluation and diagnostic tools have changed with the generalization of therapeutic hypothermia (TH) in infants with hypoxic-ischemic encephalopathy (HIE) Aim to ascertain the prognostic value of amplitude integrated electroencephalogram (aEEG) in neonates with HIE considering hours of life and treatment with TH. Methods A systematic review was performed. Inclusion criteria were studies including data of neonates with HIE, treated or not with TH, monitored with aEEG and with neurodevelopmental follow-up of at least 12 months. The period of bibliographic search was until February 2016. No language restrictions were initially applied. Consulted databases were MEDLINE, Scopus, CINHAL and the Spanish language databases GuiaSalud and Bravo. Article selection was performed by two independent reviewers. Quality for each individual paper selected was evaluated using QUADAS-2. Review Manager (RevMan) version 5.3 software was used. Forest plots were constructed to graphically show sensitivity and specificity for all included studies, separating patients treated or not with hypothermia. Summary statistics were estimated using bivariate models and random effects approaches with the R package MADA from summary ROC curves. Meta-regression was used to estimate heterogeneity and trends. Results from the 403 articles initially identified, 17 were finally included and critically reviewed. In infants not treated with hypothermia the maximum reliability of an abnormal aEEG background to predict death or moderate/severe disability was at 36 hours of life, when a positive post-test probability of 97.90% was achieved (95%CI 88.40 to 99.40%). Positive likelihood ratio (+LR) at these hours of life was 26.60 (95%CI 4.40 to 94.90) and negative likelihood ratio (-LR) was 0.23 (95%CI 0.10 to 0.44). A high predictive value was already present at 6 hours of life in this group of patients, with a positive post-test probability of 88.20% (95%CI 79.80 to 93%) and a +LR of 4.34 (95%CI 2.31 to 7.73). In patients treated with TH the maximum predictive reliability was achieved at 72 hours of life (post-test probability of 95.70%, 95%CI 84.40 to 98.50%). +LR at this age was 24.30 (95%CI 5.89 to 71.30) and–LR was 0.40 (95%CI 0.25 to 0.57). Predictive value of aEEG at 6 hours of life was low in these patients (59.10%, 95%CI 55.70 to 63%). Conclusion This study confirms that aEEG´s background activity, as recorded during the first 72 hours after birth, has a strong predictive value in infants with HIE treated or not with TH. Predictive values of traces throughout the following 72 hours are a helpful guide when considering and counselling parents about the foreseeable long-term neurological outcome

Neonatal Arterial Ischemic Stroke: Risk Related to Family History, Maternal Diseases, and Genetic Thrombophilia:

The objective of this study was to evaluate the heritability of neonatal arterial ischemic stroke (NAIS) in relation to family history of thromboembolic event, maternal diseases, and thrombophilia in both parents (F5G1691A, F2G20210A, and MTHFRC677 T mutations). Forty-two consecutive infants ≥36 weeks of gestation <28 days of life with acute symptomatic NAIS and their parents, as well as 129 controls, were prospectively recruited. Information on maternal data (age, body mass index, oral contraception, migraine, epilepsy, hypertension, and immune disease) and a 3-generation pedigree regarding myocardial infarction, pulmonary embolism, cerebrovascular event, and deep vein thrombosis were obtained. Thrombophilia and maternal diseases did not differ between cases and controls, except for the use of oral contraceptives (more frequent in mothers of controls). No differences were found regarding each studied antecedent of thromboembolic event in the families. The NAIS group showed a higher presence of positive family history among second-degree maternal relatives than did the control infants (odds ratio 4.10; 95% confidence interval 1.29-12.99). Our study does not support the hypothesis that common genetic thrombophilia or familial predisposition to thromboembolic events is associated with the occurrence of idiopathic NAIS.

Coagulation factor V G1691A, factor II G20210A and methylenetetrahydrofolate reductase C677T gene mutations do not play a major role in symptomatic neonatal arterial ischaemic stroke.

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Extracerebral thrombosis in symptomatic neonatal arterial ischemic stroke

We read with great interest the recent publication by Fluss et al. presenting 16 cases (5 personal and 11 from the literature) of perinatal arterial ischemic stroke with documented carotid occlusion. The main etiological hypothesis addresses the role of thematerno-fetal vascular interface as the origin of thrombi that reach the infant cerebral arterial circulation throughout the physiologically patent foramen ovale and ductus arteriosus. Moreover, regarding cases reported by Fluss et al., further proposedmechanisms for stroke occurring acutely after birth are direct vessel injury during the birth process itself and intrinsic arteriopathy. As part of an ongoing project designed to investigate risk factors of perinatal stroke, we searched for thrombi in a cohort of 42 consecutive infants born at >35 weeks of gestation with the diagnosis of symptomatic arterial ischemic stroke within the first 28 days of life, in three tertiary hospitals fromOctober 2006 to December 2012. Symptomatic neonatal arterial ischemic stroke was defined according to clinical and radiographic criteria: (1) seizures, recurrent apnoea or acute neurological deficit, and (2) MRI confirmation of acute focal brain infarction(s) within arterial territories. Infants with arterial stroke and major congenital anomalies, meningitis, sepsis, congenital infections, ECMO, or metabolic diseases were not included. Thrombophilia workup was performed in all mothereinfant pairs, including protein C, protein S, antithrombin III, coagulation factor V G1691A, factor II G20210A, methylenetetrahydrofolate reductase C677T, lipoprotein(a), homocysteine, and antiphospholipid antibodies. Investigation of extracerebral thrombosis included echocardiography and Doppler ultrasound for abdominal vasculature (renal, cava, suprahepatic, and aorta) and cervical vessels (jugular and carotid). Seventeen out of 42 infants (40%) were screened at the three sites. Thirty-nine of 42 infants (93%) had at least one ultrasound test carried out to look for extracerebral thrombi. These were 37/42 (88%) heart cavities, 31/42 (74%) abdominal vessels, and 18/42 (43%) cervical vessels. Extracerebral thrombi were found in one of 17 infants who underwent full screening: this patient had thrombi at different sites (heart, carotid artery and vena cava). We also

La bioética en el final de la vida en neonatología: cuestiones no resueltas

This document is the result of previous work carried out by different expert groups and submitted to multidisciplinary debate at a Conference about controversial, deficient, or new aspects in the field of neonatal palliative care, such as: 1) the deliberative decision-making process, 2) hospital and domiciliary palliative care, 3) donation after controlled cardiac death, and 4) moral stress in professionals. The most relevant conclusions were: the need to instruct professionals in bioethics and in the deliberative method to facilitate thorough and reasonable decision-making; the lack of development in the field of perinatal palliative care and domiciliary palliative care in hospitals that attend newborns; the need to provide neonatal units with resources that help train professionals in communication skills and in the management of moral distress, as well as delineate operational procedure and guidelines for neonatal organ donation.

Incidencia de la encefalopatía hipóxico-isquémica e implementación de la hipotermia terapéutica por regiones en España

INTRODUCTION There are no data on the incidence of hypoxic-ischaemic encephalopathy (HIE) and the implementation of therapeutic hypothermia (TH) in Spain. METHODS This is a cross-sectional, national study, performed using an on-line questionnaire targeting level III neonatal care units in Spain. Participants were requested to provide data of all newborns ≥ 35 weeks of gestational age diagnosed with moderate-severe HIE over a two year-period (2012-2013), and of the implementation of TH up to June 2015. RESULTS All (90) contacted hospitals participated. HIE incidence rate was 0.77/1000 live newborns (95% CI 0.72 - 0.83). During 2012-2013, 86% of the newborns diagnosed with moderate-severe HIE received TH (active or passive). Active TH was increasingly used, from 78% in 2012 to 85% in 2013 (P=.01). Of the 14% that did not receive TH, it was mainly due to a delay in the diagnosis or inter-hospital transfer, and to the fact that the treatment was not offered. More than half (57%) were born in hospitals where TH was not provided, and passive hypothermia was used for inter-hospital patient transfer, and in 39% of the cases by inappropriately trained personnel. By June 2015, 57 out of 90 centres had implemented TH, of which 54 performed whole-body TH (using servo-controlled devices). The geographical distribution of centres with active TH, and the number of newborn that received TH, was heterogeneous. CONCLUSIONS The incidence of moderate-severe HIE is homogeneous across Spanish territory. Significant progress is being made in the implementation of TH, however it is necessary to increase the availability of active TH between Autonomous Communities, to improve early diagnosis, and to guarantee high quality patient transfer to referral centres.

Asistencia en España del recién nacido con asfixia perinatal candidato a hipotermia terapéutica durante las primeras seis horas de vida

INTRODUCTION The process of care and assistance from birth to the starting of therapeutic hypothermia (TH) is crucial in order to improve its effectiveness and prevent the worsening of hypoxic-ischaemic injury. METHODS A national cross-sectional study carried out in 2015 by use of a questionnaire sent to all level iii units on the care of the newborn≥35 weeks gestation within the first hours of life after a perinatal asphyxia event. According to clinical practice guidelines, the quality of care was compared between the hospitals that carried out or did not carry out TH, and according to the level of care. RESULTS A total of 89/90 hospitals participated, of which 57/90 performed TH. They all used resuscitation protocols and turned off the radiant warmer after stabilisation. All of them performed glucose and blood gas analysis, monitored the central temperature, put the newborn on a diet, and performed at least two examinations for the diagnosis of hypoxic-ischaemic encephalopathy. Greater than one-third (35%) of hospitals did not have amplitude-integrated electroencephalogram, and 6/57 were TH-hospitals. The quality of care among hospitals with and without TH was similar, childbirth being better in those that performed TH, and those with a higher level of care. Level IIIc hospitals had higher scores than the others. The TH-hospitals mentioned not always having neonatologists with experience in neurological assessment and interpretation of amplitude-integrated electroencephalogram (25%), or in brain ultrasound (62%). CONCLUSIONS In response to the recommendations of the asphyxiated newborn, there is a proper national health care standard with differences according to the level of care and whether TH is offered. More amplitude-integrated electroencephalogram devices are necessary, as well as more neonatologists trained in the evaluations that will be require by the newborn with hypoxic-ischaemic encephalopathy.

Perinatal infection and hypoxic-ischemic encephalopathy: a pilot study

Abstract Recent studies suggest a synergic effect of infection and hypoxia-ischemia in the causation of perinatal brain damage. We conducted a prospective pilot study on the presence of infection in hypoxic-ischemic encephalopathy (HIE), focusing on neurotropic viruses. Sixteen newborns with HIE were included in the study. There were no confirmed cases of viral infection. There was a case of bacterial early onset sepsis and four cases of suspected sepsis due to clinical and/or analytical signs, but with negative cultures. Our results do not support universal screening for viral infection in cases of HIE.

PS-154 Has Therapeutic Hypothermia (th) Changed The Prognostic Value Of Clinical Evaluation Of Neonatal Hypoxic-ischaemic Encephalopathy (hie)? A Systematic Review And Meta-analysis

Background Clinical grading of HIE correlates with outcome. TH improves survival and neurodevelopment in HIE. Aim: To review the effect of TH on the prognostic value of clinical grading of HIE and its course. Methods Systematic review and meta-analysis of studies on the ability of Sarnat stage at defined times to predict death/disability at ≥18 m in normothermia and TH-treated term neonates with HIE. Pooled risks were estimated, with random effect models, according to HIE stage and treatment. Results Data on encephalopathy stage at <6 h were available from seven TH trials including 1214 newborns with moderate/severe HIE. Post-hoc studies of two trials (381 infants) provided 72 h data. The proportion of infants with moderate encephalopathy at <6 h who had poor outcome was 52% (95% CI:44–60; I2 = 48%) in normothermia-treated and 35% (95% CI:28–41; I2 = 51%) in TH-treated neonates. The proportion for severe encephalopathy was 83% (95% CI:72–93; I2 = 81%) in normothermia and 67% (95% CI:58–76; I2 = 74%) in TH. At <6 h, the OR for severe vs moderate HIE to predict unfavourable outcome was 4.14 (95% CI:2.40–7.13; I2 = 35%) in normothermia and 3.77 (95% CI:2.62–5.41; I2 = 0%) in TH. TH did not affect HIE grade at 72 h. No improvement of encephalopathy at 72 h increased the risk of poor outcome (OR 8.21, 95% CI:2.01–33.6; I2 = 74%). The ORs for persistent moderate and severe encephalopathy at 72 h to predict unfavourable outcome were 5.09 (95% CI:1.53–16.92; I2 = 66%) and 42.83 (95% CI:13.55–135.37; I2 = 44%). Conclusions While TH has changed the predictive values of initial HIE grades, clinical staging at <6 h correlates with outcome. The course of encephalopathy throughout TH is valuable in outcome prediction.