Synthesis, biological evaluation and molecular modeling studies of novel 1,2,3-triazole-linked menadione-furan derivatives as P2X7 inhibitors.

The P2X7 receptor (P2X7R) is an ion channel that promotes the passage of ions through the membrane through brief stimulation once activated by ATP, its endogenous opener. However, prolonged stimulation with ATP, which occurs in pathological processes, opens a nonselective pore in the plasma membrane, allowing the passage of large molecules and leading to cytokine release or even cell death. In this sense, the search for new inhibitors for this receptor has attracted a great deal of attention in recent years. Considering the booming of biomass upgrading reactions in recent years and the continued efforts to synthesize biologically active molecules containing the 1,2,3-triazole ring, in the present work, we aimed to investigate whether triazole-linked menadione-furan derivatives could present P2X7R inhibitory activity. The novel compounds were tested for their inhibitory activity on ATP-induced dye uptake in peritoneal macrophages. Some have shown promising results, having displayed IC50 values lower than that of the P2X7R inhibitor BBG. Molecular docking studies also indicated that the active compounds bind to an allosteric site on P2X7R, presenting potential P2X7R inhibition.

Treatment compliance and risk and protective factors for suicide ideation to completed suicide in adolescents: a systematic review

Objective: To review the literature regarding adolescent suicide risk and explore the associations between treatment compliance (expressed as a concept including measured adherence to treatment and/or mental health service utilization) and risk and protective factors for suicidal behavior (SB), as well as the association between treatment compliance and reattempts. Methods: PubMed, LILACS, and Google Scholar were searched using the following terms: (adolescent*) AND (suicide*) AND (risk factor OR protective factors) AND (treatment compliance OR treatment attrition OR treatment adherence OR treatment drop out OR treatment retention OR mental health utilization). We retrieved studies that focused on the relation of treatment compliance to risk and protective factors for SB and that had only adolescent samples. Results: Of 4,841 articles, 30 original articles were selected for review. Most studies indicated high mental health service (MHS) utilization and poor treatment adherence by SB patients. Social minority status and conduct disorder were associated with less treatment adherence, while female sex, parental perceived need for treatment, and major depression were associated with greater treatment adherence. Inpatient and intensive emergency care after SA and family interventions improved MHS utilization and treatment compliance. However, we found no substantial protective effect of treatment compliance against reattempts. Conclusion: Effective treatment planning for compliance requires considering psychopathology, treatment planning, and social, familial, and individual factors.

Treatment compliance and risk and protective factors for suicide ideation to completed suicide in adolescents: a systematic review.

OBJECTIVE: To review the literature regarding adolescent suicide risk and explore the associations between treatment compliance (expressed as a concept including measured adherence to treatment and/or mental health service utilization) and risk and protective factors for suicidal behavior (SB), as well as the association between treatment compliance and reattempts. METHODS: PubMed, LILACS, and Google Scholar were searched using the following terms: (adolescent*) AND (suicide*) AND (risk factor OR protective factors) AND (treatment compliance OR treatment attrition OR treatment adherence OR treatment drop out OR treatment retention OR mental health utilization). We retrieved studies that focused on the relation of treatment compliance to risk and protective factors for SB and that had only adolescent samples. RESULTS: Of 4,841 articles, 30 original articles were selected for review. Most studies indicated high mental health service (MHS) utilization and poor treatment adherence by SB patients. Social minority status and conduct disorder were associated with less treatment adherence, while female sex, parental perceived need for treatment, and major depression were associated with greater treatment adherence. Inpatient and intensive emergency care after SA and family interventions improved MHS utilization and treatment compliance. However, we found no substantial protective effect of treatment compliance against reattempts. CONCLUSION: Effective treatment planning for compliance requires considering psychopathology, treatment planning, and social, familial, and individual factors.

Long-Term Consequences of Severe Maternal Morbidity on Infant Growth and Development.

OBJECTIVE: Severe maternal morbidity (SMM) is already known to be associated with adverse neonatal outcomes, however, its association with long-term deficits of weight and height, and impairment in neurodevelopment among children was not yet fully assessed. We aim to evaluate whether SMM has repercussions on the weight and height-for-age and neurodevelopmental status of the child. METHODS: A retrospective cohort analysis with women who had SMM events in a tertiary referral center in Brazil. They were compared to a control group of women who had not experienced any SMM. Childbirth and perinatal characteristics, weight and height-for-age deficits and neurodevelopmental impairment suspicion by Denver II Test were comparatively assessed in both groups using RR and 95% CI. Multiple regression analysis was used addressing deficit of weight-for-age, height-for-age and an altered Denver Test, estimating their independent adjusted RR and 95% CI. RESULTS: 634 women with perinatal outcomes available (311 with SMM and 323 without) and 571 children were assessed. Among women with SMM, increased rates in perinatal deaths, Apgar lower than 7 at five minutes, shorter breastfeeding period, preterm birth (49.0% × 11.1%), low birthweight (45.8% × 11.5%), deficits of weight-for-age [RR 3.11 (1.60-6.04)] and height-for-age [RR 1.52 (1.06-2.19)] and altered Denver Test [RR 1.5 (1.02-2.36)] were more frequently found than in the control group. SMM was not identified as independently associated with any of the main outcomes. CONCLUSION: SMM showed to be associated with a negative impact on growth and neurodevelopment aspects of perinatal and infant health. These findings suggest that effective health policies directed towards appropriate care of pregnancy may have an impact on the reduction of maternal, neonatal and infant morbidity and mortality.

Prevalence and Outcomes of Congenital Heart Disease in Very Low Birth Weight Preterm Infants: An Observational Study From the Brazilian Neonatal Network Database.

OBJECTIVES: To evaluate the prevalence of congenital heart disease and their outcomes in a Brazilian cohort of very low birth weight preterm infants. DESIGN: Post hoc analysis of data from the Brazilian Neonatal Network database, complemented by retrospective data from medical charts and a cross-sectional survey. SETTING: Twenty public tertiary-care university hospitals. PATIENTS: A total of 13,955 newborns weighing from 401 to 1,499 g and between 22 and 36 weeks of gestational age, born from 2010 to 2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The prevalence of congenital heart disease was 2.45% (95% CI, 2.20-2.72%). In a multivariate regression analysis, risk factors associated with congenital heart disease were maternal diabetes (relative risk, 1.55; 95% CI, 1.11-2.20) and maternal age above 35 years (relative risk, 2.09; 95% CI, 1.73-2.51), whereas the protection factors were maternal hypertension (relative risk, 0.54; 95% CI, 0.43-0.69), congenital infection (relative risk, 0.45; 95% CI, 0.21-0.94), and multiple gestation (relative risk, 0.73; 95% CI, 0.55-0.97). The pooled standardized mortality ratio in patients with congenital heart disease was 2.48 (95% CI, 2.22-2.80), which was significantly higher than in patients without congenital heart disease (2.08; 95% CI, 2.03-2.13). However, in multiple log-binomial regression analyses, only the presence of major congenital anomaly, gestational age (< 29 wk; relative risk, 2.32; 95% CI, 2.13-2.52), and Score for Neonatal Acute Physiology and Perinatal Extension II (> 20; relative risk, 3.76; 95% CI, 3.41-4.14) were independently associated with death, whereas the effect of congenital heart disease was spotted only when a conditional inference tree approach was used. CONCLUSIONS: The overall prevalence of congenital heart disease in this cohort of very low birth weight infants was higher and with higher mortality than in the general population of live births. The occurrence of a major congenital anomaly, gestational age (< 29 wk), and Score for Neonatal Acute Physiology and Perinatal Extension II (> 20) were significantly and independently associated with death, whereas the association of congenital heart disease and death was only evident when a major congenital anomaly was present.

Multidimensional assessment of women after severe maternal morbidity: the COMMAG cohort study.

OBJECTIVES: To perform a multidimensional assessment of women who experienced severe maternal morbidity (SMM) and its short-term and medium-term impact on the lives and health of women and their children. DESIGN: A retrospective cohort study. SETTING: A tertiary maternity hospital from the southeast region of Brazil. PARTICIPANTS: The exposed population was selected from intensive care unit admissions if presenting any diagnostic criteria for SMM. Controls were randomly selected among women without SMM admitted to the same maternity and same time of childbirth. PRIMARY AND SECONDARY OUTCOME VARIABLES: Validated tools were applied, addressing post-traumatic stress disorder (PTSD) and quality of life (SF-36) by phone, and then general and reproductive health, functioning (WHO Disability Assessment Schedule), sexual function (Female Sexual Function Index (FSFI)), substance abuse (Alcohol, Smoking and Substance Involvement Screening Test 2.0) and growth/development (Denver Developmental Screening Test) of children born in the index pregnancy in a face-to-face interview. RESULTS: All instruments were applied to 638 women (315 had SMM; 323 were controls, with the assessment of 264 and 307 children, respectively). SF-36 score was significantly lower in the SMM group, while PTSD score was similar between groups. Women who had SMM became more frequently sterile, had more abnormal clinical conditions after the index pregnancy and a higher score for altered functioning, while proportions of FSFI score or any drug use were similar between groups. Furthermore, children from the SMM group were more likely to have weight (threefold) and height (1.5 fold) for age deficits and also impaired development (1.5-fold). CONCLUSION: SMM impairs some aspects of the lives of women and their children. The focus should be directed towards monitoring these women and their children after birth, ensuring accessibility to health services and reducing short-term and medium-term repercussions on physical, reproductive and psychosocial health.

Suicide Attempts Among French and Brazilian Adolescents Admitted to an Emergency Room. A Comparative Study of Risk and Protective Factors.

BACKGROUND: Suicide is the second most common cause of preventable mortality among Brazilian and French adolescents. The aim of the current study was to compare the main risk and protective factors associated with a suicide attempt (SA) and to highlight differences based on geographical characteristics. METHOD: We compared a Brazilian sample (N = 45) of adolescents admitted to the emergency room of a public hospital in São Paulo for SA to a French sample (N = 320) of adolescents hospitalized for SA across 5 paediatric departments. Then, we ran several multivariate models to examine how each selected variable was related to geographic origin and to the other selected variables linked to geographic origin. RESULTS: The two samples presented no significant differences regarding gender, age or schooling. Both samples had high rates of depressive disorders, anxiety disorders, substance use, disruptive disorders, borderline psychopathology, and lifetime SAs. However, the Brazilian sample presented significantly higher levels of psychopathology and had more insecure attachment relationships (fearful and detached), whereas the French sample had a more secure attachment style. Brazilian adolescents had more recourse to spiritual beliefs and spiritual support, whereas the French adolescents had higher scores on the Reasons for Living Inventory and used more help-seeking strategies from their social network, mainly close friends. Multivariate models showed that two productive coping strategies (seeking spiritual support and social action) and the dependence score were significantly associated with membership in the Brazilian cohort, whereas a secure attachment style and depression severity (evaluated by the Beck Depression Inventory) were significantly associated with membership in the French cohort. CONCLUSION: Despite presenting similar psychopathologies, Brazilian adolescents presented a more insecure attachment style and used the religious kind of coping more commonly than their French counterparts. We hypothesize that religion may compensate for the social vulnerabilities present in a middle-income country such as Brazil. More transcultural studies may help to elucidate this phenomenon.

General and reproductive health among women after an episode of severe maternal morbidity: Results from the COMMAG study.

OBJECTIVE: To assess general and reproductive health in women after severe maternal morbidity (SMM). METHODS: A retrospective cohort study was performed at a tertiary maternity hospital. Women with SMM criteria who delivered during 2008-2012 were included in the SMM group. The control group included a random sample of women without SMM delivering in the same year of cases. Both groups were compared regarding sociodemographic/obstetric characteristics, general and reproductive health, using χ2 , Yates χ2 , Fisher exact, and Mann-Whitney tests. RESULTS: There were 315 women in the SMM group and 323 women in the control group. The SMM group was older and had a history of more medical conditions (hypertension, diabetes, obesity), cesarean deliveries, preterm births, and perinatal deaths. Breastfeeding was negatively affected in these women, as was fertility. The SMM group had a non-significant trend of fewer children after index pregnancy, had new complications in subsequent pregnancies, and required specialized medical care, besides higher risk of death. CONCLUSION: Women experiencing SMM are at higher risk of general and reproductive health problems after pregnancy, including risk of death. Therefore, their surveillance and follow-up should continue beyond 42 days postpartum, highlighting the importance of more specialized health care.

Admission hypothermia, neonatal morbidity, and mortality: evaluation of a multicenter cohort of very low birth weight preterm infants according to relative performance of the center.

This prospective cohort study aimed to assess the association of admission hypothermia (AH) with death and/or major neonatal morbidities among very low birth weight (VLBW) preterm infants based on the relative performance of 20 centers of the Brazilian Network of Neonatal Research. This is a retrospective analysis of prospectively collected data using the database registry of the Brazilian Network on Neonatal Research. Center performance was defined by the relative mortality rate using conditional inference trees. A total of 4356 inborn singleton VLBW preterm infants born between January 2013 and December 2016 without malformations were included in this study. The centers were divided into two groups: G1 (with lower mortality rate) and G2 (with higher mortality rate). Crude and adjusted relative risks (RR) and 95% confidence intervals (95%CI) were estimated by simple and multiple log-binomial regression models. An AH rate of 53.7% (19.8-93.3%) was significantly associated with early neonatal death in G1 (adjusted RR 1.41, 95% CI 1.09-1.84) and G2 (adjusted RR 1.29, 95%CI 1.01-1.65) and with in-hospital death in G1 (adjusted RR 1.29, 95%CI 1.07-1.58). AH was significantly associated with a lower frequency of necrotizing enterocolitis (adjusted RR 0.58, 95%CI 38-0.88) in G2.Conclusion: AH significantly associated with early neonatal death regardless of the hospital performance. In G2, an unexpected protective association between AH and necrotizing enterocolitis was found, whereas the other morbidities assessed were not significantly associated with AH. What is Known: • Admission hypothermia is associated with early neonatal death. • The association of admission hypothermia with major neonatal morbidities has not been fully established. What is New: • Admission hypothermia was significantly associated with early neonatal and in-hospital death in centers with the lowest relative mortality rates. • Admission hypothermia was not associated with major neonatal morbidities and with in-hospital death but was found to be a protective factor against necrotizing colitis in centers with the highest relative mortality rates.

Quality of Life after an Episode of Severe Maternal Morbidity: Evidence from a Cohort Study in Brazil.

OBJECTIVE: To assess quality of life (QOL) in women who experienced a severe maternal morbidity (SMM) event and associated factors, in comparison to those who did not. STUDY DESIGN: Retrospective cohort study performed at the maternity of the University of Campinas in Brazil, including 801 women with or without SMM, within 6 months to 5 years after delivery. Women were interviewed by phone and data were electronically stored, using the Brazilian version of the SF36 to assess women's self-perception of quality of life. To analyze a possible relationship between SMM and perceived impairment in quality of life, χ2 and Fisher's Exact tests were used. Multiple analysis using Generalized Linear Models was applied to identify factors independently associated with the general health score. The main outcome measures were general and domain-specific SF36 scores on quality of life. RESULTS: Maternal morbidity conditions were associated with lower scores of patient perceptions of quality of life in the following domains: physical functioning, role-limiting physical, pain, and general health status. A lower level of school education, not having a partner, caesarean section, and history of previous clinical conditions were associated with a worse perception of general health and quality of life. CONCLUSION: Health professionals should know the association between life conditions, previous chronic health conditions, and SMM for women during prenatal care to beyond 42 weeks postpartum. Longitudinal and interdisciplinary actions should be put into practice to provide healthcare for these women, with special emphasis on the effective reduction in health inequities.

Post-Traumatic Stress Disorder and severe maternal morbidity: is there an association?

OBJECTIVE: To evaluate the occurrence of Post-Traumatic Stress Disorder among women experiencing a severe maternal morbidity event and associated factors in comparison with those without maternal morbidity. METHODS: In a retrospective cohort study, 803 women with or without severe maternal morbidity were evaluated at 6 months to 5 years postpartum for the presence of Post-Traumatic Stress Disorder. Interviews were conducted by telephone and electronic data was stored. Data analysis was carried out by using χ2, Fisher's Exact test, and logistic regression analysis. RESULTS: There was no significant change in the prevalence of Post-Traumatic Stress Disorder related to a previous severe maternal morbidity experience. There were also no differences in diagnostic criteria for severe maternal morbidity (hypertensive syndromes, hemorrhage, surgical intervention or intensive care unit admission required, among other management criteria). Low parity (2.5-fold risk) and increasing age were factors associated with Post-Traumatic Stress Disorder. CONCLUSIONS: A severe maternal morbidity episode is not associated with Post-Traumatic Stress Disorder symptoms within five years of the severe maternal morbidity event and birth. However, a more advanced maternal age and primiparity increased the risk of Post-Traumatic Stress Disorder. This does not imply that women who had experienced a severe maternal morbidity event did not suffer or need differentiated care.

Post-Traumatic Stress Disorder and severe maternal morbidity: is there an association?

OBJECTIVE: To evaluate the occurrence of Post-Traumatic Stress Disorder among women experiencing a severe maternal morbidity event and associated factors in comparison with those without maternal morbidity. METHODS: In a retrospective cohort study, 803 women with or without severe maternal morbidity were evaluated at 6 months to 5 years postpartum for the presence of Post-Traumatic Stress Disorder. Interviews were conducted by telephone and electronic data was stored. Data analysis was carried out by using χ2, Fisher's Exact test, and logistic regression analysis. RESULTS: There was no significant change in the prevalence of Post-Traumatic Stress Disorder related to a previous severe maternal morbidity experience. There were also no differences in diagnostic criteria for severe maternal morbidity (hypertensive syndromes, hemorrhage, surgical intervention or intensive care unit admission required, among other management criteria). Low parity (2.5-fold risk) and increasing age were factors associated with Post-Traumatic Stress Disorder. CONCLUSIONS: A severe maternal morbidity episode is not associated with Post-Traumatic Stress Disorder symptoms within five years of the severe maternal morbidity event and birth. However, a more advanced maternal age and primiparity increased the risk of Post-Traumatic Stress Disorder. This does not imply that women who had experienced a severe maternal morbidity event did not suffer or need differentiated care.

A cohort study of functioning and disability among women after severe maternal morbidity.

OBJECTIVE: To assess functioning and disability related to severe maternal morbidity (SMM) via the WHO Disability Assessment Schedule 2.0 (WHODAS 2.0). METHODS: In a retrospective cohort study, women with or without a history of SMM who delivered at a tertiary public hospital in Brazil between July 2008 and June 2012, completed the WHODAS 2.0 questionnaire by individual interview between August 2012 and November 2013. General WHODAS scores were evaluated by maternal and neonatal characteristics, and specific domain scores according to SMM event. RESULTS: Overall, 638 women were enrolled (315 with SMM and 323 without SMM). The mean general WHODAS score was higher among women with SMM (19.04±16.18) than among women without SMM (15.77±14.46; P=0.015). Domain scores were also higher in the SMM group for mobility (16.00±20.22 vs 11.63±17.51; P=0.003), household activities (26.79±30.16 vs 20.09±26.08; P=0.005), participation (23.55±21.72 vs 17.27±19.17; P<0.001), and work/school activities for women currently studying or working (20.52±26.64 vs 11.66±19.67; P=0.001). Excluding SMM, a parity of two or more was the only factor significantly associated with higher scores overall (P=0.013) and for domain 4 (getting along with people; P=0.017). CONCLUSION: By comparison with women without childbirth complications, SMM impaired self-reported functioning among women 1-5years after delivery.

Neonatal near miss: a systematic review.

BACKGROUND: The concept of neonatal near miss has been proposed as a tool for assessment of quality of care in neonates who suffered any life-threatening condition. However, there are no internationally agreed concepts or criteria for defining or identifying neonatal near miss. The purpose of this study was to perform a systematic review of studies and markers that are able to identify neonatal near miss cases and predict neonatal mortality. METHODS: Electronic searches were performed in the Medline, Embase and Scielo databases, with no time or language restriction, until December 2014. The term "neonatal near miss" was used alone or in combination with terms related to neonatal morbidity/mortality and neonatal severity scores. Study selection criteria involved three steps: title, abstract and full text of the articles. Two researchers performed study selection and data extraction independently. Heterogeneity of study results did not permit the performance of meta-analysis. RESULTS: Following the inclusion and exclusion criteria adopted, only four articles were selected. Preterm and perinatal asphyxia were used as near miss markers in all studies. Health indicators on neonatal morbidity and mortality were extracted or estimated. The neonatal near miss rate was 2.6 to 8 times higher than the neonatal mortality rate. CONCLUSIONS: Pragmatic and management criteria are used to help develop the neonatal near miss concept. The most severe cases are identified and mortality is predicted with these criteria. Furthermore, the near miss concept can be used as a tool for evaluating neonatal care. It is the first step in building management strategies to reduce mortality and long-term sequelae.

Does Severe Maternal Morbidity Affect Female Sexual Activity and Function? Evidence from a Brazilian Cohort Study.

OBJECTIVE: to assess Female Sexual Function Index (FSFI) scores and delay to resume sexual activity associated with a previous severe maternal morbidity. METHOD: This was a multidimensional retrospective cohort study. Women who gave birth at a Brazilian tertiary maternity between 2008 and 2012 were included, with data extraction from the hospital information system. Those with potentially life-threatening conditions and maternal near miss episodes (severe maternal morbidity) were considered the exposed group. The control group was a random sample of women who had had uncomplicated pregnancy. Female sexual function was evaluated through FSFI questionnaire, and general and reproductive aspects were addressed through specific questions. Statistical analyses were performed using Mann-Whitney and Pearson´s Chi-square for bivariate analyses. Logistic regression was used to identify variables independently associated with lower FSFI scores. RESULTS: 638 women were included (315 at exposed and 323 at not exposed groups). The majority of women were under 30 years-old in the control group and between 30 and 46 years-old in the exposed group (p = 0.003). Women who experienced severe maternal morbidity (SMM) had statistically significant differences regarding cesarean section (82.4% versus 47.1% among deliveries without complications, p<0.001), and some previous pathological conditions. FSFI mean scores were similar among groups ranging from 24.39 to 24.42. It took longer for exposed women to resume sexual activity after index pregnancy (mean 84 days after SMM and 65 days for control group, p = 0.01). Multiple analyses showed no significant association of FSFI below cut-off value with any predictor. CONCLUSION: FSFI scores were not different in both groups. However, they were lower than expected. SMM delayed resumption of sexual activity after delivery, beyond postpartum period. However, the proportion of women in both groups having sex at 3 months after delivery was similar. Altered sexual response may be evaluated as one of possible long-term consequences after SMM episodes. Further studies on the growing population of women surviving severe maternal conditions might be worth for improvement of care for women.

Neonatal Near Miss: the need for a standard definition and appropriate criteria and the rationale for a prospective surveillance system

In Latin American, there is currently a regional action with the main purposes of putting the concept of severe neonatal morbidity in practice and formulating proposals for interventions. A general overview of neonatal health conditions, including morbidity and mortality, is provided to update regional knowledge on the topic. An example of the development and implementation of the concept of maternal near miss is also provided, followed by results from a systematic review covering all previously published studies on Neonatal Near Miss. Finally, some proposals for building a common concept on the topic and for launching a prospective surveillance study are presented. A Neonatal Near Miss is a neonate who had a severe morbidity (organ dysfunction or failure) but who survived this condition within the first 27 days of life. The pragmatic criteria recommended to be used are as follows: birth weight below 1700 g, Apgar score below 7 at 5 minutes of life and gestational age below 33 weeks. As a proxy for organ dysfunction, the following management criteria are also confirmed: parenteral therapeutic antibiotics; nasal continuous positive airway pressure; any intubation during the first 27 days of life; phototherapy within the first 24 h of life; cardiopulmonary resuscitation; the use of vasoactive drugs, anticonvulsants, surfactants, blood products and steroids for refractory hypoglycemia and any surgical procedure. Although this study starts from a regional perspective, this topic is clearly globally relevant. All nations, especially low and middle-income countries, could benefit from the proposed standardization.

Neonatal Near Miss: the need for a standard definition and appropriate criteria and the rationale for a prospective surveillance system.

In Latin American, there is currently a regional action with the main purposes of putting the concept of severe neonatal morbidity in practice and formulating proposals for interventions. A general overview of neonatal health conditions, including morbidity and mortality, is provided to update regional knowledge on the topic. An example of the development and implementation of the concept of maternal near miss is also provided, followed by results from a systematic review covering all previously published studies on Neonatal Near Miss. Finally, some proposals for building a common concept on the topic and for launching a prospective surveillance study are presented. A Neonatal Near Miss is a neonate who had a severe morbidity (organ dysfunction or failure) but who survived this condition within the first 27 days of life. The pragmatic criteria recommended to be used are as follows: birth weight below 1700 g, Apgar score below 7 at 5 minutes of life and gestational age below 33 weeks. As a proxy for organ dysfunction, the following management criteria are also confirmed: parenteral therapeutic antibiotics; nasal continuous positive airway pressure; any intubation during the first 27 days of life; phototherapy within the first 24 h of life; cardiopulmonary resuscitation; the use of vasoactive drugs, anticonvulsants, surfactants, blood products and steroids for refractory hypoglycemia and any surgical procedure. Although this study starts from a regional perspective, this topic is clearly globally relevant. All nations, especially low and middle-income countries, could benefit from the proposed standardization.