[Perinatal COVID-19 in Latin America]. / COVID-19 perinatal en América Latina.

OBJECTIVE: To evaluate and report the clinical characteristics and outcomes of SARS-CoV-2 infection in pregnant women and newborns in Latin America. METHODS: Descriptive study based on the prospective report of the units of the Ibero-American Society of Neonatology Network. RESULTS: Of 86 pregnant women with COVID-19 confirmed by RT-PCR in seven countries (6 from Latin America, and Equatorial Guinea) 68% (59) were asymptomatic. Of 32% of symptomatic women, 89% (24) had mild symptoms and 3.5% (3) had severe respiratory symptoms. No women died. The cesarean section rate was 38%; gestational age was < 37 weeks in 6% of cases. RT-PCR was performed on all newborns between 16 and 36 hours of age; 6 (7%) were positive. All of them presented mild and transient respiratory distress; none died. Two newborns with negative RT-PCR died from other causes. Breastfeeding was authorized in only 24% of mothers; in 13% milk was expressed and 63% of newborns were fed with formula. In 76% of cases the motherchild pair was separated, and in 95% of cases the mother could not be accompanied at delivery or during the postpartum period. CONCLUSIONS: The lack of maternal accompaniment, the low rate of breastfeeding and the frequent separation of the mother-child dyad are of concern. The health care team must reflect on the need to defend humanized and family-centered care during this pandemic.

Using a novel laminar flow unit provided effective total body hypothermia for neonatal hypoxic encephalopathy.

AIM: This was a clinical observational trial on a laminar flow device that provides total body hypothermia for infants with hypoxic ischaemic encephalopathy (HIE). METHODS: We enrolled infants born at up to 35 weeks of gestation, who presented with HIE within six hours of birth. Total body cooling was achieved using the neonatal laminar flow unit for 72 hours, with continuous rectal temperature servo control, isolation and humidification. Outcome measures were cerebral palsy, a Bayley II Mental Development Index score <70, hearing loss or blindness. We compared findings with previously published studies. RESULTS: We included 26 newborn infants (69% male) with a birthweight of 3.341 ± 1658 g and gestational age of 38.2 ± 3.2 weeks. The majority (62.6%) had a Sarnat HIE score of three and 38.4% had a score of two. Total body cooling (33-34°C) was achieved in 70 minutes and maintained with servo control, showing very little variability until rewarming. At 18-24 months of age, two of the 18 survivors were diagnosed with cerebral palsy and one was diagnosed with impaired hearing. CONCLUSION: The laminar flow unit proved effective in maintaining moderate total body hypothermia under well-controlled conditions, and our results were very similar to other studies.

Perfusion index in newborn infants: a noninvasive tool for neonatal monitoring.

AIM: To review the utility of perfusion index (PI) in the evaluation of neonatal clinical conditions. Twenty-five manuscripts were reviewed. PI provides information about haemodynamic stability, illness severity, early neonatal respiratory outcome, low superior vena cava flow and subclinical chorioamnionitis. CONCLUSION: PI is a valuable tool to assess the newborn's health condition and could become a standardised measure in clinical evaluation. Different study designs are necessary to provide further validation to this method.

A randomised controlled trial of an automated oxygen delivery algorithm for preterm neonates receiving supplemental oxygen without mechanical ventilation.

AIM: Providing consistent levels of oxygen saturation (SpO2 ) for infants in neonatal intensive care units is not easy. This study explored how effectively the Auto-Mixer(®) algorithm automatically adjusted fraction of inspired oxygen (FiO2 ) levels to maintain SpO2 within an intended range in extremely low birth weight infants receiving supplemental oxygen without mechanical ventilation. METHODS: Twenty extremely low birth weight infants were randomly assigned to the Auto-Mixer(®) group or the manual intervention group and studied for 12 h. The SpO2 target was 85-93%, and the outcomes were the percentage of time SpO2 was within target, SpO2 variability, SpO2 >95%, oxygen received and manual interventions. RESULTS: The percentage of time within intended SpO2 was 58 ± 4% in the Auto-Mixer(®) group and 33.7 ± 4.7% in the manual group, SpO2 >95% was 26.5% vs 54.8%, average SpO2 and FiO2 were 89.8% vs 92.2% and 37% vs 44.1%, and manual interventions were 0 vs 80 (p < 0.05). Brief periods of SpO2  < 85% occurred more frequently in the Auto-Mixer(®) group. CONCLUSION: The Auto-Mixer(®) effectively increased the percentage of time that SpO2 was within the intended target range and decreased the time with high SpO2 in spontaneously breathing extremely low birth weight infants receiving supplemental oxygen.

Safe oxygen saturation targeting and monitoring in preterm infants: can we avoid hypoxia and hyperoxia?

UNLABELLED: Oxygen is a neonatal health hazard that should be avoided in clinical practice. In this review, an international team of neonatologists and nurses assessed oxygen saturation (SpO2 ) targeting in preterm infants and evaluated the potential weaknesses of randomised clinical trials. CONCLUSION: SpO2 of 85-89% can increase mortality and 91-95% can cause hyperoxia and ill effects. Neither of these ranges can be recommended, and wider intermediate targets, such as 87-94% or 88-94%, may be safer.

[Consensus on the diagnostic and therapeutic approach to pain and stress in the newborn]. / Consenso sobre el abordaje diagnóstico y terapéutico del dolor y el estrés en el recién nacido.

Pain and stress experienced by the newborn have not been addressed adequately. Infants in neonatal intensive care units often undergo painful and stressful invasive procedures, and inappropriate treatment increases morbidity and mortality. At the 5th Clinical Consensus of the Ibero-American Society of Neonatology, 32 neonatologists from the region were invited to establish recommendations for the diagnosis and treatment of neonatal pain and stress. Key themes were explored based on the best scientific evidence available in indexed databases. All attendees participated actively in a meeting in Santiago, Chile, with the objective of reaching a consensus on recommendations and conclusions. Pain and neonatal stress affect neurological development and long-term behavior and require timely diagnosis and appropriate management and treatment, including the use of drugs with an appropriate balance between effectiveness and toxicity. The Consensus emphasized the importance of assessing pain in the newborn from a multidimensional viewpoint, and provided recommendations on the indications and limitations for an individualized pharmacological therapy. The use of analgesics has precise indications but also important limitations; there is a lack of randomized studies in newborns, and adverse effects need to be considered. Nonpharmacological measures to mitigate pain were proposed. Stress management should begin in the delivery room, including maternal contact, stimulus reduction and the implementation of intervention reduction protocols. Recommendations for improving clinical practices related to neonatal pain and stress are presented.

Monitoring SpO2: The Basics of Retinopathy of Prematurity (Back to Basics) and Targeting Oxygen Saturation.

Oxygen (O2) is a drug frequently used in newborn care. Adverse effects of hypoxia are well known but the damaging effects of excess oxygen administration and oxidative stress have only been studied in the last 2 decades. Many negative effects have been described, including retinopathy of prematurity . Noninvasive pulse oximetry (SpO2) is useful to detect hypoxemia but requires careful evaluation and understanding of the frequently changing relationship between O2 and hemoglobin to prevent hyperoxemia. Intention to treat SpO2 ranges should be individualized for every newborn receiving supplemental O2, according to gestational age, post-natal age, and clinical condition.

End-of-life care in neonatal intensive care units in Iberoamerica: A look from the nursing perspective.

INTRODUCTION: End-of-life care (ELC) represents a quality milestone in neonatal intensive care units (NICU). The objective of this study was to explore how ELC are carried out in NICUs in Iberoamerica. METHODS: Cross-sectional study, through the administration of an anonymous survey sent to neonatal nursing professionals. The survey included general data and work activity data; existence and contents of ELC protocols in the NICU and training received. The survey was distributed by email and published on official SIBEN social networks. REDCap and STATA 14.0 software were used for data collection and analysis. RESULTS: We obtained 400 responses from nurses from 11 countries in the Ibero-American region. 86% of the respondents are directly responsible for providing ELC, although 48% of them said they had not received training on this subject. Only 67 (17%) state that the NICU in which they work has a protocol that establishes a strategy for performing the ELC. Finally, the actions that are implemented during the ELC are globally infrequent (≤50%) in all the items explored and very infrequent (<20%) in relation to allowing free access to family members, having privacy, providing psychological assistance, register the process in the medical record, assist with bureaucratic processes or grant a follow-up plan for grief. CONCLUSION: Most of the nursing professionals surveyed are directly responsible for this care, do not have protocols, have not received training, and consider that the ELC could be significantly improved. Strategies for ELCs in the Ibero-American region need to be optimized.

Capnography in newborns under mechanical ventilation and its relationship with the measurement of CO2 in blood samples.

INTRODUCTION: Monitoring the partial pressure of CO2 (PCO2) in newborns who require ventilation would allow avoiding hypocapnia and hypercapnia. The measurement of end-tidal carbon dioxide (ETCO2) is an alternative rarely implemented in this population. OBJECTIVE: To evaluate the relationship between ETCO2 and PCO2 in newborns. METHODS: Cross-sectional study comparing two PCO2 measurement methods, the conventional one by analysis of blood samples and the one estimated by ETCO2. The study included hospitalized newborns that required conventional mechanical ventilation. The ETCO2 was measured with a Tecme GraphNet® neo, a neonatal ventilator with an integrated capnograph, and we obtained the ETCO2-PCO2 gradient. We conducted correlation and Bland-Altman plot analyses to estimate the agreement. RESULTS: A total of 277 samples (ETCO2 / PCO2) from 83 newborns were analyzed. The mean values ​​of ETCO2 and PCO2 were 41.36mmHg and 42.04mmHg. There was a positive and significant correlation between ETCO2 and PCO2 in the overall analysis (r=0.5402; P<.001) and in the analysis of each unit (P<.001). The mean difference was 0.68 mmHg (95% CI, -0.68 to 1.95) and was not significant. We observed a positive systematic error (PCO2 > ETCO2) in 2 of the units, and a negative difference in the third (PCO2 < ETCO2). DISCUSSION: The correlation between ETCO and PCO2 was significant, although the obtained values ​​were not equivalent, with differences ranging from 0.1mmHg and 20mmHg. Likewise, we found systematic errors that differed in sign (positive or negative) between institutions.

Prevention of retinopathy of prematurity in preterm infants through changes in clinical practice and SpO2technology.

AIM: To identify whether pulse oximetry technology is associated with decreased retinopathy of prematurity (ROP) and laser treatment. METHODS: Inborn infants <1250 g who had eye exams were compared at two centres in three periods. In Period 1, SpO2 target was ≥93% and pulse oximetry technology was the same in both Centres. In Period 2, guidelines for SpO2 88-93% were implemented at both centres and Centre B changed to oximeters with signal extraction technology (SET(®)) while Centre A did not, but did so in Period 3. One ophthalmology department performed eye exams using international criteria. RESULTS: In 571 newborns <1250 g, birth weight and gestational age were similar in the different periods and centres. At Centre A, severe ROP and need for laser remained the same in Periods 1 and 2, decreasing in Period 3-6% and 3%, respectively. At Centre B, severe ROP decreased from 12% (Period 1) to 5% (Period 2) and need for laser decreased from 5% to 3%, remaining low in Period 3. CONCLUSION: In a large group of inborn infants <1250 g, a change in clinical practice in combination with pulse oximetry with Masimo SET, but not without it, led to significant reduction in severe ROP and need for laser therapy. Pulse oximetry selection is important in managing critically ill infants.

Avoiding hyperoxemia during neonatal resuscitation: time to response of different SpO2 monitors.

AIM: To assess the time to obtain reliable oxygen saturation readings by different pulse oximeters during neonatal resuscitation in the delivery room or NICU. METHODS: Prospective study comparing three different pulse oximeters: Masimo Radical-7 compared simultaneously with Ohmeda Biox 3700 or with Nellcor N395, in newborn infants who required resuscitation. Members of the research team placed the sensors for each of the pulse oximeters being compared simultaneously, one sensor on each foot of the same baby. Care provided routinely, without interference by the research team. The time elapsed until a reliable SpO2 was obtained was recorded using a digital chronometer. Statistical comparisons included chi-square and student's T-test. RESULTS: Thirty-two infants were enrolled; median gestational age 32 weeks. Seventeen paired measurements were made with the Radical-7 and Biox 3700; mean time to a stable reading was 20.2±7 sec for the Radical-7 and 74.2±12 sec for the Biox 3700 (p=0.02). The Radical-7 and the N- 395 were paired on 15 infants; the times to obtain a stable reading were 20.9±4 sec and 67.3±12 sec, respectively (p=0.03). CONCLUSION: The time to a reliable reading obtained simultaneously in neonatal critical situations differs by the type of the pulse oximeter used, being significantly faster with Masimo Signal Extraction Technology. This may permit for better adjustments of inspired oxygen, aiding in the prevention of damage caused by unnecessary exposure to high or low oxygen.

[Second Clinical Consensus of the Ibero-American Society of Neonatology: hemodynamic management of newborns]. / Segundo Consenso Clínico de la Sociedad Iberoamericana de Neonatología: manejo hemodinámico del recién nacido.

This study reports on the process and results of the Second Clinical Consensus of the Ibero-American Society of Neonatology. Eighty neonatologists from 23 countries were invited to collaborate and participate in the event. Several questions of clinical-physiological importance in the hemodynamic management of newborns were addressed. Participants were divided into groups to facilitate interaction and teamwork, with instructions to respond to three to five questions by analyzing the literature and local factors. Meeting in Mar del Plata, Argentina, the Consensus Group served as a form for various presentations and discussions. In all, 54 neonatologists from 21 countries attended, with the objective of reaching a consensus on such matters as concepts and definitions of hemodynamic instability, the physiopathology of hemodynamic compromise, recommended therapy strategies, and hemodynamic monitoring. It is hoped that this international experience will serve as a useful initiative for future consensus building and reduction of the existing disparities among the countries of the Region in terms of treatment and outcomes.

Hypoxic Ischemic Encephalopathy in Units Reporting to the Ibero-American Society of Neonatology Network: Prevalence and Mortality.

INTRODUCTION: Hypoxic ischemic encephalopathy is a neurological condition occurring immediately after birth following a perinatal asphytic episode. Therapeutic hypothermia is a safe and effective intervention to reduce mortality and major disability in survivors. In Latin America, perinatal asphyxia is a major problem, but no data are available characterizing its current situation in the region or the impact of hypoxic ischemic encephalopathy on its management. OBJECTIVE: Understand the prevalence, mortality and use of therapeutic hypothermia in newborns at ≥36 weeks gestational age with hypoxic ischemic encephalopathy admitted to neonatal units reporting to the Ibero-American Society of Neonatology Network. METHODS: The Ibero-American Society of Neonatology Network groups various neonatology centers in Latin America that share information and collaborate on research and medical care. We evaluated data on newborns with ≥36 weeks gestational age reported during 2019. Each unit received a guide with definitions and questions based on the Society's 7th Clinical Consensus. Evaluated were encephalopathy frequency and severity, Apgar score, need for resuscitation at birth, use of therapeutic hypothermia and clinical evolution at discharge. Our analysis includes descriptive statistics and comparisons made using the chi-square test. RESULTS: We examined reports of 2876 newborns from 33 units and 6 countries. In 2849 newborns with available data, hypoxic encephalopathy prevalence was 5.1% (146 newborns): 27 (19%) mild, 36 (25%) moderate, 43 (29%) severe, and 40 (27%) of unknown intensity. In those with moderate and severe encephalopathy, frequencies of Apgar scores ≤3 at the first minute (p = 0.001), Apgar scores ≤3 at the fifth minute (p ⟨0.001) and advanced resuscitation (p = 0.007) were higher. Therapeutic hypothermia was performed in only 13% of newborns (19). Neonatal mortality from encephalopathy was 42% (61). CONCLUSIONS: Hypoxic ischemic encephalopathy is a neonatal condition that results in high mortality and severe neurological sequelae. In this study, the overall prevalence was 5.1% with a mortality rate of 42%. Although encephalopathy was moderate or severe in 54% of reported cases, treatment with hypothermia was not performed in 87% of newborns. These data reflect a regional situation that requires urgent action.

Caspase inhibition by cardiotrophin-1 prevents neuronal death in vivo and in vitro.

Our previous studies showed that cardiotrophin-1 (CT-1), a cytokine in the interleukin-6 family, protected the developing rat brain against focal cerebral ischemia (FCI) in vivo and prevented cortical neuron death in vitro. However, the mechanisms by which CT-1 prevents neuronal death are not clearly understood. This in vivo study focused on whether CT-1 treatment prevented FCI-induced brain injuries in the postnatal day 7 (P7) rat through modulating activation of the initiator caspase-8 (C-8) and the downstream effector caspase-3 (C-3). FCI caused a significant increase in expressions of cleaved C-8 and C-3 and, meanwhile, a significant decrease in expression of microtubule-associated protein-2 (MAP2) in the left ischemic cortex of the P7 rat brain after FCI. Exogenous treatment of CT-1 significantly reduced the expression of cleaved C-8 or C-3 and attenuated the decline in MAP2 expression in the ischemic cortex from 12 to 24 hr after FCI. Subsequent in vitro experiments demonstrated that CT-1 treatment inhibited sodium nitroprusside (SNP)-induced activation of C-8 and C-3 and loss of MAP2-positive neurons in cortical neuron cultures. More importantly, CT-1 activated several pathways, including Janus kinase 2, signal transducers and activators of transcription 3, nuclear factor kappa B, mitogen-activated protein kinase (MAPK), and MAPK kinase in the cultures exposed to SNP. This is the first suggestion that CT-1 prevents neuronal injury in the developing central nervous system possibly through mediating multiple signal pathways, inhibiting activation of C-8 and C-3.

Abuse of Antibiotics in Perinatology: Negative Impact for Health and the Economy.

To use medications appropriately, patients need to be treated based on their clinical conditions, in doses that are based on their individual requirements, for an adequate amount of time, and at the lowest expense. The perinatal period is characterized by an excessive use of antibiotics. This antibiotic abuse can lead to antibiotic resistance, microbiome alterations, and dysbiosis, which have been associated with serious complications such as infections, abnormal brain development, allergies, autoimmune disorders, obesity, and an increase in mortality as well as an increase in health care expenditures. The need to optimize antibiotic utilization in perinatal medicine has never been more urgent; there is not much more time to wait.

[Use (and abuse) of antibiotics in perinatal medicine]. / Uso (y abuso) de antibióticos en la medicina perinatal.

INTRODUCTION: The rational use of antibiotics (ATB) implies that patients receive those adequate for their clinical needs, in correct doses according to their individual conditions, during an adequate period of time, and at the lowest cost for them and their community. The highest rate of ATB abuse occurs during the perinatal period, despite the fact that there is evidence of multiple short- and long-term negative effects. Furthermore, this abuse is associated with increased costs of medical care. OBJECTIVE: To update and report the evidence on the use, abuse, and adverse effects of ATB in perinatal medicine, and possible measures to prevent them, and thus improve health care outcomes and costs. METHODS: A review and analysis was performed from the literature related to the use of ATB in perinatal medicine up to February 2020. RESULTS: ATB abuse in perinatal medicine ranges from 50% to 70%, with even higher rates in some neonatal centres. Adverse effects include death, increased microbial resistance, along with microbiome abnormalities and dysbiosis that lead to serious life-long complications such as infections, allergies, autoimmune disorders, gastrointestinal disorders, arthritis, asthma, obesity, and perhaps cancer. Preventing and reducing the abuse of ATB would lead to better health and to significant savings in the health sector. In only 4neonatal intensive care units, with 1000 admissions per year, savings are estimated at US$230,000 per year. CONCLUSION: The need to optimise the use of ATB in perinatal medicine has never been more urgent.

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.

CCHD Screening Implementation Efforts in Latin American Countries by the Ibero American Society of Neonatology (SIBEN).

Congenital heart disease (CHD) is among the four most common causes of infant mortality in Latin America. Pulse oximetry screening (POS) is useful for early diagnosis and improved outcomes of critical CHD. Here, we describe POS implementation efforts in Latin American countries guided and/or coordinated by the Ibero American Society of Neonatology (SIBEN), as well as the unique challenges that are faced for universal implementation. SIBEN collaborates to improve the neonatal quality of care and outcomes. A few years ago, a Clinical Consensus on POS was finalized. Since then, we have participated in 12 Latin American countries to educate neonatal nurses and neonatologists on POS and to help with its implementation. The findings reveal that despite wide disparities in care that exist between and within countries, and the difficulties and challenges in implementing POS, significant progress has been made. We conclude that universal POS is not easy to implement in Latin America but, when executed, has not only been of significant value for babies with CHD, but also for many with other hypoxemic conditions. The successful and universal implementation of POS in the future is essential for reducing the mortality associated with CHD and other hypoxemic conditions and will ultimately lead to the survival of many more Latin American babies. POS saves newborns' lives in Latin America.

Animal models of neonatal stroke and response to erythropoietin and cardiotrophin-1.

Neonatal stroke is increasingly recognized in preterm and term infants, and the rate of arterial ischemic infarction occurring around the time of birth is as high as the annual incidence of large-vessel ischemic stroke in adults. Thus, neonatal stroke is a major contributor to perinatal morbidity and mortality, and a considerable number of these children will develop long-term neurodevelopmental disabilities. Our ability to investigate this situation has been limited by the technical challenges in developing suitable animal models. Our objective is to describe recent evidence in relation to animal models of neonatal stroke. In addition, we review and report potential neuroprotective strategies specific to neonatal stroke, with a focus on erythropoietin and cardiotrophin-1 because of their potential role in protection as well as repair.