Gestión del capital venoso de los recién nacidos hospitalizados: catéter de línea media (CM) con técnica adaptada. Servicio de Neonatología, Hospital Público de Chile / Venous capital management of hospitalized newborns: midline catheter (MC) with adapted technique. Neonatology Service, Chilean public hospital

INTRODUCCIÓN: El catéter midline o de línea media (CM) es un dispositivo de acceso vascular que mide de 6 a 20cm, con la punta del dispositivo ubicado en venas basílica, braquial o cefálica debajo del pliegue axilar. El catéter de línea media se caracteriza por ser un acceso confiable y proporcionar menores complicaciones que un catéter intravenoso periférico corto. Este tipo de dispositivo vascular se ha utilizado ampliamente en adultos, pero faltan estudios desarrollados en el área neonatal. OBJETIVO: fue describir las características de la utilización de catéter midline con técnica adaptada en recién nacidos hospitalizados con necesidad de terapia intravascular en un hospital público de Chile, durante 2 años de seguimiento. METODOLOGÍA: Investigación descriptiva y retrospectiva, estuvo orientada a la identificación de las variables relacionadas a: tiempo de permanencia, características de la terapia intravascular, sitio de inserción, complicaciones y causa de retiro. RESULTADOS: La muestra estuvo conformada por 163 usuarios entre 24 y 41 semanas de edad gestacional, peso de nacimiento en un rango de 500 y 4880 gramos. El 87,7% se retiró por término de tratamiento intravascular, mientras que el 12,3% del total de los CM presentó complicaciones. El promedio de rendimiento del CM fue de 7,99 días, el sitio de inserción más frecuente correspondió a extremidad superior derecha, mientras que su utilización estuvo dada principalmente para fleboterapia, antibióticos y nutrición parenteral periférica. CONCLUSIÓN: Se concluye que el CM con técnica adaptada en usuarios neonatales presenta una alta tasa de éxito para completar la terapia intravascular periférica y bajo porcentaje de complicaciones.

INTRODUCTION: The midline catheter (MC) is a vascular access device measuring 6 to 20cm, with the tip of the device located in the basilic, brachial or cephalic veins below the axillary crease. The midline catheter is characterized as a reliable access and provides fewer complications than a short peripheral intravenous catheter. This type of vascular device has been widely used in adults, but studies developed in the neonatal area are lacking. OBJECTIVE: to describe the characteristics of the use of midline catheter with adapted technique in hospitalized newborns in need of intravascular therapy in a public hospital in Chile, during 2 years of follow-up. METHODOLOGY: Descriptive and retrospective research was oriented to the identification of variables related to: length of stay, characteristics of intravascular therapy, site of insertion, complications and cause of withdrawal. RESULTS: The sample consisted of 163 users between 24 and 41 weeks of gestational age, birth weight in the range of 500 and 4880 grams. Eighty-seven point seven percent were withdrawn due to the end of intravascular treatment, while 12.3% of the total MC presented complications. The average MC performance was 7.99 days, the most frequent insertion site corresponded to the right upper extremity, while its use was mainly for phlebotherapy, antibiotics and peripheral parenteral parenteral nutrition. CONCLUSION: The MC with adapted technique in neonatal users presents a high success rate to complete peripheral intravascular therapy and a low percentage of complications.

Implementation of Nationwide Evidence- and Consensus-Based Guidelines to Harmonize Neonatal Care in The Netherlands.

BACKGROUND: A Dutch committee for National Guidelines in Neonatology developed nineteen evidence- and consensus-based guidelines to be used in all Dutch neonatal intensive care units (NICUs). The primary goal was to make clinical practices more uniform and consistent. OBJECTIVE: This study investigated to what extent the guidelines were implemented and which factors played a role in implementation. STUDY DESIGN: A mixed method study design was used to investigate both the level and the process of implementation. A nationwide, multicenter, cross-sectional survey was performed using a validated instrument for measuring the level of implementation (Normalization MeAsure Development questionnaire, NoMAD). The number of implemented guidelines per NICU and the frequency and content of the amendments that NICUs made to the original consensus guidelines were analyzed. Through semi-structured interviews, perceived barriers and facilitators for implementation were explored. PARTICIPANTS: Fellows and neonatologists working at all ten Dutch level 3-4 NICUs were eligible. RESULTS: On an average, NICUs implemented 12.6 (of 19) guidelines (range 6-17). The Normalization Process Scale was 54 (of 65). Main influencing factors impeding implementation were guideline-related (e.g., unpractical, lengthy guidelines) and personal (e.g., an active representative responsible for local implementation). CONCLUSION: The implementation of our guidelines appears to be successful. Ways for improvement can be distinguished in personal, guideline-related and external factors. Empowerment of local representatives was considered most essential.

[Recommendations on organization, design, characteristics and operation of neonatology services]. / Recomendaciones de organización, diseño, características y funcionamiento de servicios o unidades de neonatología.

Neonatal care has undergone important advances involving the technology for treatment and mo nitoring, the design of care spaces, the incorporation of support professionals, and, especially, the strengthening of an organizational model in networks with centers of different levels of care. Neona tal units should be located in centers with maternity services and, ideally, with pediatric ones of an equivalent level of care. This document defines the admission and transfer criteria according to the level of care and among the different levels, respectively. The evidence recommends an individual room design due to the associated benefits such as decreased occurrence and better control of health care-associated infections, improved breastfeeding, and better interaction with parents. The sugges ted room sizes favor the implementation of the family-centered care model. These recommendations establish the possibility of performing emergency surgical procedures in the neonatal unit and define the safety criteria of the physical plant. In addition, they define the human resources according to the level of care, recognizing the time dedicated to non-direct patient care activities, , and the re quirements of non-medical professionals such as psychologists, physical and respiratory therapists, occupational therapists, speech therapists, pharmacists, dietitians, and social workers. Neonatal care should be led by the neonatologist allowing the participation of general pediatricians with training and demonstrated experience in neonatal care. Midwives and neonatal nurses should have accredited formation in such area. The purpose of this document is to update the "Recommendations on the Organization, Characteristics and Operation of Neonatology Services or Units" to serve as an orien tation and guide for the design and management of neonatal care in public and private health care centers in the country.

Prospective comparison of thermometers used in very preterm infants.

We measured temperature on admission to the neonatal unit in a cohort of 54 very preterm infants. We measured rectal temperature with a digital thermometer (Microlife MT-1931) as the gold standard (MT-R). We also measured axillary temperature with the MT (MT-A), with the Welch Allyn SureTemp Plus 692 in 'continuous' (WAC) mode and in the default 'predictive' (WAP) mode. While MT-A and WAC frequently differed from MT-R by ≥0.3°C, they were both reasonably sensitive and specific for hypothermia (MT-R <36.5°C). WAP overestimated MT-R by ≥0.5°C on 37/53 (70%) occasions and had poor sensitivity for hypothermia, identifying only 2 of 29 infants with MT-R <36.5°C as hypothermic.

Status of Multidisciplinary Collaboration in Neonatal Cardiac Care in the United States.

While outcomes for neonates with congenital heart disease have improved, it is apparent that substantial variability exists among centers with regard to the multidisciplinary approach to care for this medically fragile patient population. We endeavored to understand the landscape of neonatal cardiac care in the United States. A survey was distributed to physicians who provide neonatal cardiac care in the United States regarding (1) collaborative efforts in care of neonates with congenital heart disease (CHD); (2) access to neonatal cardiac training; and (3) barriers to the implementation of protocols for neonatal cardiac care. Responses were collected from 10/2018 to 6/2019. We received responses from 172 of 608 physicians (28% response rate) from 89 centers. When compared to responses received from physicians at low-volume centers (< 300 annual bypass cases), those at high-volume centers reported more involvement from the neurodevelopmental teams (58% vs. 29%; P = 0.012) and a standardized transition to outpatient care (68% vs. 52%; P = 0.038). While a majority of cardiothoracic surgery and anesthesiology respondents reported multidisciplinary involvement, less than half of cardiology and neonatology supported this statement. The most commonly reported obstacles to multidisciplinary engagement were culture (61.6%) and logistics (47.1%). Having a standardized neonatal cardiac curriculum for neonatal fellows was positively associated with the perception that multidisciplinary collaboration was "always" in place (53% vs. 40%; P = 0.09). There is considerable variation among centers in regard to personnel involved in neonatal cardiac care, related education, and perceived multidisciplinary collaboration among team members. The survey findings suggest the need to establish concrete standards for neonatal cardiac surgical programs, with ongoing quality improvement processes.

Corrected fortification approach improves the protein and energy content of preterm human milk compared with standard fixed-dose fortification.

OBJECTIVE: To evaluate whether a pragmatic corrected fortification (CF) model achieves recommended target protein and calorie content of human milk (HM) for preterm infants when compared with standard fixed-dose fortification (SF). DESIGN: In this prospective non-interventional study, we enrolled mothers of infants with birth weight ≤1500 g fed exclusive HM. Infants with chromosomal or intestinal disorders were excluded. A total of 405 HM samples from 29 mothers and 45 donor milk samples were analysed for macronutrient content using a real-time HM analyser. A stepwise CF model was derived based on published data on HM calorie and protein content corrected for lactation stage and milk type. We applied both models to the measured protein and calorie content for all HM samples and compared the proportion of samples achieving target nutrient requirement in each group. RESULTS: Target protein and calorie content of feed was achieved in 68% of HM samples with CF, compared with 5% samples with SF model (p<0.0001). For mother's own milk, none of the samples met the target macronutrient range with SF fortification during later lactation periods (≥week 5). With SF, over 40% of infants had poor growth (decline in weight z-score ≥0.8 SD) by 8 weeks. The final feed osmolality was acceptable for all fortification steps of the CF model. CONCLUSION: The proposed CF model significantly improved the final protein and calorie content of HM with acceptable osmolality. It provides a proactive option to improve nutrient intake in premature infants.

Necrotising enterocolitis in newborns receiving diazoxide.

BACKGROUND: Frequent and severe gastrointestinal disturbances have been reported with the use of diazoxide in adults and older children. However, no studies have investigated the incidence of necrotising enterocolitis (NEC) in diazoxide-exposed newborns. OBJECTIVE: To evaluate a possible association between diazoxide treatment for neonatal hypoglycaemia and the occurrence of NEC. DESIGN: Multicentre retrospective cohort study. SETTING: Three tertiary neonatal intensive care units in Toronto, Canada. PATIENTS: All patients treated with diazoxide for persistent hypoglycaemia between July 2012 and June 2017 were included. Overall incidence of NEC during those years on the participating units was obtained for comparison from the Canadian Neonatal Network database. MAIN OUTCOME: Incidence of NEC after diazoxide exposure. RESULTS: Fifty-five neonates were exposed to diazoxide during the study period. Eighteen patients (33%) showed signs of feeding intolerance, and 7 developed NEC (13%). A diagnosis of NEC was more prevalent in the diazoxide-exposed, as compared with non-exposed infants of similar gestational age (OR 5.07, 95% CI 2.27 to 11.27; p<0.001), and greatest among infants born at 33-36 weeks' gestation (OR 13.76, 95% CI 3.77 to 50.23; p<0.001). All but one of the neonates diagnosed with NEC developed the disease within 7 days from initiation of diazoxide treatment. CONCLUSION: The present data suggest a possible association between diazoxide exposure and the development of NEC in neonates. Further evaluation of the diazoxide-associated risk of NEC in neonates treated for persistent hypoglycaemia is warranted.

Observational study of parental opinion of deferred consent for neonatal research.

OBJECTIVE: To evaluate the opinions of parents of newborns following their infant's enrolment into a neonatal research study through the process of deferred consent. DESIGN: Mixed-methods, observational study, interviewing 100 parents recently approached for deferred consent. SETTING: Tertiary-level neonatal intensive care unit, Melbourne, Australia. RESULTS: All 100 parents interviewed had consented to the study/studies using deferred consent; 62% had also experienced a prospective neonatal consent process. Eighty-nine per cent were 'satisfied' with the deferred consent process. The most common reason given for consenting was 'to help future babies'. Negative comments regarding deferred consent mostly related to the timing of the consent approach, and some related to a perceived loss of parental rights. A deferred approach was preferred by 51%, 24% preferred a prospective approach and 25% were unsure. Those who thought prospective consent would not have been preferable cited impaired decision-making, inappropriate timing of an approach before birth and their preference for removal of the decision-making burden via deferred consent. Seventy-seven per cent thought they would have given the same response if approached prospectively; those who would have declined reported that a prospective approach under stressful conditions was unwelcome and too overwhelming. CONCLUSION: In our sample, 89% of parents of infants enrolled in neonatal research using deferred consent considered it acceptable and half would not have preferred prospective consent. The ability to make a more considered decision under less stressful circumstances was key to the acceptability of deferred consent.

Challenges of a simplified opt-out consent process in a neonatal randomised controlled trial: qualitative study of parents' and health professionals' views and experiences.

BACKGROUND: More effective recruitment strategies like alternative approaches to consent are needed to facilitate adequately powered trials. Witholding Enteral feeds Around Transfusion was a multicentre, randomised, pilot trial that compared withholding and continuing feeds around transfusion. The primary clinical outcome was necrotising enterocolitis. The trial used simplified opt-out consent with concise parent information and no consent form. OBJECTIVE: To explore the views and experiences of parents and health professionals on the acceptability and feasibility of opt-out consent in randomised comparative effectiveness trials. METHODS: A qualitative, descriptive interview-based study nested within a randomised trial. Semistructured interview transcripts were analysed using inductive thematic analysis. SETTING: Eleven neonatal units in England. PARTICIPANTS: Eleven parents and ten health professionals with experience of simplified consent. RESULTS: Five themes emerged: 'opt-out consent operationalised as verbal opt-in consent', 'opt-out consent normalises participation while preserving parental choice', 'opt-out consent as an ongoing process of informed choice', 'consent without a consent form' and 'choosing to opt out of a comparative effectiveness trial', with two subthemes: 'wanting "normal care"' and 'a belief that feeding is better'. CONCLUSION: Introducing a novel form of consent proved challenging in practice. The principle of a simplified, opt-out approach to consent was generally considered feasible and acceptable by health professionals for a neonatal comparative effectiveness trial. The priority for parents was having the right to decide about trial participation, and they did not see opt-out consent as undermining this. Describing a study as 'opt-out' can help to normalise participation and emphasise that parents can withdraw consent.

The future of Cochrane Neonatal.

Cochrane Neonatal was first established in 1993, as one of the original review groups of the Cochrane Collaboration. In fact, the origins of Cochrane Neonatal precede the establishment of the collaboration. In the 1980's, the National Perinatal Epidemiology Unit at Oxford, led by Dr. Iain Chalmers, established the "Oxford Database of Perinatal Trials" (ODPT), a register of virtually all randomized controlled trials in perinatal medicine to provide a resource for reviews of the safety and efficacy of interventions used in perinatal care and to foster cooperative and coordinated research efforts in the perinatal field [1]. An effort that was clearly ahead of its time, ODPT comprised four main elements: a register of published reports of trials; a register of unpublished trials; a register of ongoing and planned trials; and data derived from pooled overviews (meta-analyses) of trials. This core effort grew into the creation of the seminal books, "Effective Care in Pregnancy and Childbirth" as well as "Effective Care of the Newborn Infant" [2,3]. As these efforts in perinatal medicine grew, Iain Chalmers thought well beyond perinatal medicine into the creation of a worldwide collaboration that became Cochrane [4]. The mission of the Cochrane Collaboration is to promote evidence-informed health decision-making by producing high-quality, relevant, accessible systematic reviews and other synthesized research evidence (www.cochrane.org). Cochrane Neonatal has continued to be one of the most productive review groups, publishing between 25 tpo to 40 new or updated systematic reviews each year. The impact factor has been steadily increasing over four years and now rivals most of the elite journals in pediatric medicine. Cochrane Neonatal has been a worldwide effort. Currently, there are 404 reviews involving 1206 authors from 52 countries. What has Cochrane done for babies? Reviews from Cochrane Neonatal have informed guidelines and recommendations worldwide. From January 2018 through June 2020, 77 international guidelines cited 221 Cochrane Neonatal reviews. These recommendations have included recommendations of the use of postnatal steroids, inhaled nitric oxide, feeding guidelines for preterm infants and other core aspects of neonatal practice. In addition, Cochrane Reviews has been the impetus for important research, including the large-scale trial of prophylactic indomethacin therapy, a variety of trials of postnatal steroids, trials of emollient ointment and probiotic trials [6]. While justifiably proud of these accomplishments, one needs to examine the future contribution of Cochrane Neonatal to the neonatal community. The future of Cochrane Neonatal is inexorably linked to the future of neonatal research. Obviously, there is no synthesis of trials data if, as a community, we fail to provide the core substrate for that research. As we look at the current trials' environment, fewer randomized controlled trial related to neonates are being published in recent years. A simple search of PubMed, limiting the search to "neonates" and "randomized controlled trials" shows that in the year 2000, 321 randomized controlled trials were published. These peaked five years ago, in 2015, with close to 900 trials being published. However, in 2018, only 791 studies are identified. Does this decrease represent a meaningful change in the neonatal research environment? Quite possibly. There are shifting missions of clinical neonatology at academic medical institutions, at least in the United States, with a focus on business aspects as well as other important competing clinical activities. Quality improvement has taken over as one of the major activities at both private and academic neonatal practices. Clearly, this is a needed improvement. All units at levels need to be dedicated to improving the outcomes of the sick and fragile population we care for. However, this need not be at the expense of formal clinical trials. It is understandable that this approach would be taken. Newer interventions frequently relate to complex systems of care and not the simple single interventions. Even trials that might traditionally have been done as randomized controlled trials, such as the introduction of a new mode of ventilation, are in reality complex challenges to the ability of institutions to create systems to adapt to these new technologies. Cost of doing trials has always been a barrier. The challenging regulatory and ethical environment contributes to these problems as well [7]. Despite these barriers, how does the research agenda of the neonatal community move forward in the 21st Century? We need to reassess how we create and disseminate our research findings. Innovative trial designs will allow us to address complex issues that we may not have tackled with conventional trials. Adaptive designs may allow us to look at potentially life-saving therapies in a way that feel more efficient and more ethical [8]. Clarifying issues such as the use of inhaled nitric oxide in preterm infants would be greatly served if we even knew whether or not there are hypoxemic preterm infant who would benefit from this therapy [9]. Current trials do not suggest so, yet current practice tells us that a significant number of these babies will receive inhaled nitric oxide [10-13]. Adaptive design, such as those done with trials of extracorporeal membrane oxygenation (ECMO), would allow us to quickly assess whether, in fact, these therapies are life-saving and allow us to consider whether or not further trials are needed [14,15]. Our understanding that many interventions involve entire systems approaches does not relegate us only to doing quality improvement work. Cluster designs may allow us to test more complex interventions that have usually been under the purview of quality improvement [16-18]. Cluster trials are well suited for such investigations and can be done with the least interruption to ongoing care. Ultimately, quality improvement is the application of the best evidence available (evidence-based medicine is "what to do" and evidence-based practice is "how to do"). [19,20]. Nascent efforts, such as the statement on "embedding necessary research into culture and health" (the ENRICH statement) call for the conduct of large, efficient pragmatic trials to evaluate neonatal outcomes, as in part called for in the ALPHA Collaboration [21,22]. This statement envisions an international system to identify important research questions by consulting regularly with all stakeholders, including patients, public health professionals, researchers, providers, policy makers, regulators, funders of industry. The ENRICH statement envisions a pathway to enable individuals, educational institutions, hospitals and health-care facilities to confirm their status as research-friendly by integrating an understanding of trials, other research and critical thinking and to teaching learning and culture, as well as an engagement with funders, professional organizations and regulatory bodies and other stake holders to raise awareness of the value of efficient international research to reduce barriers to large international pragmatic trials and other collaborative studies. In the future, if trials are to be done on this scale or trials are prospectively designed to be analyzed together, core outcome measures must be identified and standardized. That clinical trials supply estimates of outcomes that are relevant to patients and their families is critical. In addition, current neonatal research evaluates many different outcomes using multiple measures. A given measure can have multiple widely used definitions. Bronchopulmonary dysplasia (or chronic lung disease just to add to the confusion) quickly comes to mind [23,24]. The use of multiple definitions when attempting to measure the same outcome prevents synthesis of trial results and meta-analysis and hinders efforts to refine our estimates of effects. Towards that end, Webbe and colleagues have set out to develop a core outcome set for neonatal research [25]. Key stakeholders in the neonatal community reviewed multiple outcomes reported in neonatal trials and qualitative studies. Based on consensus, key outcome measures were identified, including survival, sepsis, necrotizing enterocolitis, brain injury on imaging, retinopathy or prematurity, gross motor ability, general cognitive ability, quality of life, adverse events, visual impairment or blindness, hearing impairment or deafness, chronic lung disease/bronchopulmonary dysplasia. Trials registration has to be a continued focus of the neonatal community. Trials registration allows for systematic reviewers to understand whether or not reporting bias has occurred [26]. It also allows for transparent incorporation of these core outcome measures. Ultimately, trials registration should include public reporting of all of these core outcomes and, in the future, access to data on an individual level such that more sophisticated individual patient data meta-analysis could occur. Lastly, there is no reason to see clinical trials and quality improvement as separate or exclusive activities. In fact, in the first NICQ Collaborative, conducted by Vermont Oxford Network, participation in a trial of postnatal steroids was considered part of the quality improvement best practices as opposed to simply choosing an as-of-yet unproven approach to use of this potent drug [27]. What role will Cochrane Neonatal play as we move forward in the 21st Century? As the neonatal community moves forward with its' research agenda, Cochrane Neonatal must not only follow but also lead with innovative approaches to synthesizing research findings. Cochrane Neonatal must continue to work closely with guideline developers. The relationship between systematic review production and guideline development is clearly outlined inreports from the Institute of Medicine [28,29]. Both are essential to guideline development; the systematic review group culling the evidence for the benefits and harms of a given intervention and the guideline group addressing the contextual issues of cost, feasibility, implementation and the values and preferences of individuals and societies. Most national and international guidelines groups now routinely use systematic reviews as the evidence basis for their guidelines and recommendations. Examples of the partnership between Cochrane Neonatal and international guideline development can be seen in our support of the World Health Organization (WHO) guidelines on the use of vitamin A or the soon to be published recommendations from the International Liaison Committee on Resuscitation (ILCOR) on cord management in preterm and term infants [30]. In the future, we need to collaborate early in the guideline development process so that the reviews are fit for purpose and meet the needs of the guideline developers and the end users. Towards this end, all Cochrane Neonatal reviews now contain GRADE assessments of the key clinical findings reported in the systematic review [31]. Addition of these assessments addresses the critical issue of our confidence in the findings. We are most confident in evidence provided by randomized controlled trials but this assessment can be can be downgraded if the studies that reported on the outcome in question had a high risk of bias, indirectness, inconsistency of results, or imprecision, or where there is evidence of reporting bias. Information provided by GRADE assessments is seen as critical in the process of moving from the evidence to formal recommendations [32]. We need to explore complex reviews, such as network (NMA) or multiple treatment comparison (MCT) meta-analyses, to address issues not formally addressed in clinical trials [33]. In conditions where there are multiple effective interventions, it is rare for all possible interventions to have been tested against each other [34]. A solution could be provided by network meta-analysis, which allows for comparing all treatments with each other, even if randomized controlled trials are not available for some treatment comparisons [34]. Network meta-analysis uses both direct (head-to-head) randomized clinical trial (RCT) evidence as well as indirect evidence from RCTs to compare the relative effectiveness of all included interventions [35]. However, Mills and colleagues note that the methodological quality of MTCs may be difficult for clinicians to interpret because the number of interventions evaluated may be large and the methodological approaches may be complex [35]. Cochrane Neonatal must take a role in both the creation of such analyses and the education of the neonatal community regarding the pitfalls of such an approach. The availability of individual patient data will make more sophisticated analyses more available to the community. Although the current crop of individual patient data meta-analyses (including the reviews of elective high frequency ventilation, inhaled nitric oxide and oxygen targets) have not differed substantially from the findings of the trials level reviews (suggesting that, in fact, sick neonates are more alike that unalike), there still will be a large role for individual patient data meta-analysis, at least to end the unfound conclusions that these therapies are effective in various subgroups (be it issues of sex, disease severity, or clinical setting) [36-39]. Future trials should take a lesson from the NeOProM Collaborative [37,39]. Given the difficulty in generating significant sample size and creating funding in any single environment, trials with similar protocols should be conducted in a variety of healthcare settings with an eye towards both study level and individual patient level meta-analysis at the conclusion of those trials, allowing for broader contribution to the trials data, more rapid accrual of sample size, and more precise results. We need to educate the neonatal community regarding the use and abuse of diagnostic tests. Diagnostic tests are a critical component of healthcare but also contribute greatly to the cost of medical care worldwide. These costs include the cost of the tests themselves and the costs of misdiagnosis and treatment of individuals who will not benefit from those treatments. Clinicians may have a limited understanding of diagnostic test accuracy, the ability of a diagnostic test to distinguish between patients with and without the disease or target condition [41,42]. Efforts such as Choosing Wisely have tried to identify these deficiencies [40]. As Cochrane has increased the general literacy of both the medical and general population regarding the interpretation of the results of interventions on various diseases, so should Cochrane move forward and improve the understanding of diagnostic testing. We need to become more efficient at creating and maintaining our reviews. The time spent to produce systematic reviews is far too great. In average, it takes between 2½ to 6½ years to produce a systematic review, requiring intense time input for highly trained and expensive experts. Innovations in the ways in which we produce systematic reviews can make the review process more efficient by outsourcing some of the tasks or crowdsourcing to machine learning. We need to let the crowd and machine learning innovations help us sort the massive amounts of information needed to conduct systematic reviews. It can also allow for "live" updating of critical reviews where the research landscape is quickly changing [43]. Lastly, Cochrane Neonatal must focus more on users of the reviews and not necessarily authors of the reviews. Current Cochrane programming speaks of Cochrane training with an eye towards developing the skills of individuals who will conduct systematic reviews. While this is clearly needed and laudable, the fact of the matter is that most of the community will be "users" of the reviews. Individuals who need to understand how to use and interpret the findings of systematic reviews. These review users include clinicians, guideline developers, policy makers and families. Incorporation of GRADE guidelines has been a huge step in adding transparency to the level of uncertainty we have in our findings. From a family's perspective, we need to overcome the environment of mistrust or misunderstanding of scientific evidence and how we convey what we know, and our uncertainty about what we know, to parents and families.

COVID-19 in Neonates: A Call for Standardized Testing.

The limited evidence on neonatal coronavirus disease (COVID-19) suggests that vertical transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is rare, and most neonates seem to acquire the infection postnatally through respiratory droplets and contact. Testing of neonates with perinatal or postnatal exposure to COVID-19 infection plays a vital role in the early diagnosis, management and institution of infection prevention measures thereby cutting off the chain of epidemic transmission. A recently concluded online neonatal COVID-19 conference conducted by the National Neonatology Forum (NNF) of India and a nationwide online survey pointed to substantial variation in neonatal testing strategies. We, herein, summarize the relevant literature about the incidence and outcomes of neonatal COVID-19 and call for a universal and uniform testing strategy for exposed neonates. We anticipate that the testing strategy put forth in this article will facilitate better management and safe infection prevention measures among all units offering neonatal care in the country.

Strategies to increase the use of mother's own milk for infants at risk of necrotizing enterocolitis.

High-dose mother's own milk (MOM) feedings during the first 14 days post birth reduce the risk of necrotizing enterocolitis in very low birthweight (VLBW; <1500 g birthweight). However, high-dose MOM feedings are only possible if mothers provide sufficient quantities of MOM in a timely manner, and data indicate that the lack of MOM during the early post-birth period is a global problem. This paper reviews the modifiable and unmodifiable barriers to accessing adequate quantities of MOM during the early post-birth period and proposes evidence-based strategies to increase and improve the use of MOM during the neonatal intensive care unit (NICU) hospitalization with an emphasis on the critical first 2 weeks post birth.

Suspected Neonatal Sepsis: Tenth Clinical Consensus of the Ibero-American Society of Neonatology (SIBEN).

Suspected neonatal sepsis is one of the most common diagnoses made in newborns (NBs), but very few NBs actually have sepsis. There is no international consensus to clearly define suspected neonatal sepsis, but each time that this suspected diagnosis is assumed, blood samples are taken, venous accesses are used to administer antibiotics, and the mother-child pair is separated, with prolonged hospital stays. X-rays, urine samples, and a lumbar puncture are sometimes taken. This is of concern, as generally <10% and no more than 25%-30% of the NBs in whom sepsis is suspected have proven neonatal sepsis. It seems easy to start antibiotics with suspicion of sepsis, but stopping them is difficult, although there is little or no support to maintain them. Unfortunately, the abuse of antibiotics in inpatient and outpatient NBs is foolish. Its negative impact on neonatal health and the economy is a public health problem of epidemiological and even epidemic proportions. This manuscript is a shortened version of the 10th Clinical Consensus of the Ibero-American Society of Neonatology (SIBEN) on suspected neonatal sepsis at the end of 2018, updated with publications from its completion to February 2020. This manuscript describes useful strategies for everyday neonatal practice when neonatal sepsis is suspected, along with important aspects about the indisputable value of clinical evaluation of the NB and about obtaining and interpreting blood cultures, urine cultures, and other cultures. Likewise, the low value of laboratory tests in suspected neonatal sepsis is demonstrated with evidence and clinical recommendations are made on the appropriate use of antibiotics.

Reliability and accuracy of EEG interpretation for estimating age in preterm infants.

OBJECTIVES: To determine the accuracy of, and agreement among, EEG and aEEG readers' estimation of maturity and a novel computational measure of functional brain age (FBA) in preterm infants. METHODS: Seven experts estimated the postmenstrual ages (PMA) in a cohort of recordings from preterm infants using cloud-based review software. The FBA was calculated using a machine learning-based algorithm. Error analysis was used to determine the accuracy of PMA assessments and intraclass correlation (ICC) was used to assess agreement between experts. RESULTS: EEG recordings from a PMA range 25 to 38 weeks were successfully interpreted. In 179 recordings from 62 infants interpreted by all human readers, there was moderate agreement between experts (aEEG ICC = 0.724; 95%CI:0.658-0.781 and EEG ICC = 0.517; 95%CI:0.311-0.664). In 149 recordings from 61 infants interpreted by all human readers and the FBA algorithm, random and systematic errors in visual interpretation of PMA were significantly higher than the computational FBA estimate. Tracking of maturation in individual infants showed stable FBA trajectories, but the trajectories of the experts' PMA estimate were more likely to be obscured by random errors. The accuracy of visual interpretation of PMA estimation was compromised by neurodevelopmental outcome for both aEEG and EEG review. INTERPRETATION: Visual assessment of infant maturity is possible from the EEG or aEEG, with an average of human experts providing the highest accuracy. Tracking PMA of individual infants was hampered by errors in experts' estimates. FBA provided the most accurate maturity assessment and has potential as a biomarker of early outcome.