Bronchopulmonary dysplasia: temporal trend from 2010 to 2019 in the Brazilian Network on Neonatal Research.

OBJECTIVE: To evaluate the temporal trend of bronchopulmonary dysplasia (BPD) in preterm infants who survived to at least 36 weeks' post-menstrual age (PMA) and BPD or death at 36 weeks' PMA, and to analyse variables associated with both outcomes. DESIGN: Retrospective cohort with data retrieved from an ongoing national registry. SETTING: 19 Brazilian university public hospitals. PATIENTS: Infants born between 2010 and 2019 with 23-31 weeks and birth weight 400-1499 g. MAIN OUTCOME MEASURES: Temporal trend was evaluated by Prais-Winsten model and variables associated with BPD in survivors or BPD or death were analysed by logistic regression. RESULTS: Of the 11 128 included infants, BPD in survivors occurred in 22%, being constant over time (annual per cent change (APC): -0.80%; 95% CI: -2.59%; 1.03%) and BPD or death in 45%, decreasing over time (APC: -1.05%; 95% CI: -1.67%; -0.43%). Being male, small for gestational age, presenting with respiratory distress syndrome, air leaks, needing longer duration of mechanical ventilation, presenting with treated patent ductus arteriosus and late-onset sepsis were associated with an increase in the chance of BPD. For the outcome BPD or death, maternal bleeding, multiple gestation, 5-minute Apgar <7, late-onset sepsis, necrotising enterocolitis and intraventricular haemorrhage were added to the variables reported above as increasing the chance of the outcome. CONCLUSION: The frequency of BPD in survivors was constant and BPD or death decreased by 1.05% at each study year. These results show some improvement in perinatal care in Brazilian units which resulted in a reduction of BPD or death, but further improvements are still needed to reduce BPD in survivors.

Exhaled CO2 monitoring to guide non-invasive ventilation at birth: a systematic review.

OBJECTIVE: Measuring exhaled carbon dioxide (ECO2) during non-invasive ventilation at birth may provide information about lung aeration. However, the International Liaison Committee on Resuscitation (ILCOR) only recommends ECO2 detection for confirming endotracheal tube placement. ILCOR has therefore prioritised a research question that needs to be urgently evaluated: 'In newborn infants receiving intermittent positive pressure ventilation by any non-invasive interface at birth, does the use of an ECO2 monitor in addition to clinical assessment, pulse oximetry and/or ECG, compared with clinical assessment, pulse oximetry and/or ECG only, decrease endotracheal intubation in the delivery room, improve response to resuscitation, improve survival or reduce morbidity?'. DESIGN: Systematic review of randomised and non-randomised studies identified by Ovid MEDLINE, Embase and Cochrane CENTRAL search until 1 August 2022. SETTING: Delivery room. PATIENTS: Newborn infants receiving non-invasive ventilation at birth. INTERVENTION: ECO2 measurement plus routine assessment compared with routine assessment alone. MAIN OUTCOME MEASURES: Endotracheal intubation in the delivery room, response to resuscitation, survival and morbidity. RESULTS: Among 2370 articles, 23 were included; however, none had a relevant control group. Although studies indicated that the absence of ECO2 may signify airway obstruction and ECO2 detection may precede a heart rate increase in adequately ventilated infants, they did not directly address the research question. CONCLUSIONS: Evidence to support the use of an ECO2 monitor to guide non-invasive positive pressure ventilation at birth is lacking. More research on the effectiveness of ECO2 measurement in addition to routine assessment during non-invasive ventilation of newborn infants at birth is needed. PROSPERO REGISTRATION NUMBER: CRD42022344849.

Temporal Trend, Causes, and Timing of Neonatal Mortality of Moderate and Late Preterm Infants in São Paulo State, Brazil: A Population-Based Study.

Moderate and late preterm newborns comprise around 85% of live births < 37 weeks gestation. Data on their neonatal mortality in middle-income countries is limited. This study aims to analyze the temporal trend, causes and timing of neonatal mortality of infants with 320/7-366/7 weeks gestation without congenital anomalies from 2004-2015 in the population of São Paulo State, Brazil. A database was built by deterministic linkage of birth and death certificates. Causes of death were classified by ICD-10 codes. Among 7,317,611 live births in the period, there were 545,606 infants with 320/7-366/7 weeks gestation without congenital anomalies, and 5782 of them died between 0 and 27 days. The neonatal mortality rate decreased from 16.4 in 2004 to 7.6 per thousand live births in 2015 (7.47% annual decrease by Prais-Winsten model). Perinatal asphyxia, respiratory disorders and infections were responsible, respectively, for 14%, 27% and 44% of the 5782 deaths. Median time to death was 24, 53 and 168 h, respectively, for perinatal asphyxia, respiratory disorders, and infections. Bottlenecks in perinatal health care are probably associated with the results that indicate the need for policies to reduce preventable neonatal deaths of moderate and late preterm infants in the most developed state of Brazil.

Translating Neonatal Resuscitation Guidelines Into Practice in Brazil.

BACKGROUND AND OBJECTIVES: The Brazilian Neonatal Resuscitation Program releases guidelines based on local interpretation of international consensus on science and treatment recommendations. We aimed to analyze whether guidelines for preterm newborns were applied to practice in the 20 Brazilian Network on Neonatal Research centers of this middle-income country. METHODS: Prospectively collected data from 2014 to 2020 were analyzed for 8514 infants born at 230/7 to 316/7 weeks' gestation. The frequency of procedures was evaluated by gestational age (GA) category, including use of a thermal care bundle, positive pressure ventilation (PPV), PPV with a T-piece resuscitator, maximum fraction of inspired oxygen (Fio2) concentration during PPV, tracheal intubation, chest compressions and medications, and use of continuous positive airway pressure in the delivery room. Logistic regression, adjusted by center and year, was used to estimate the probability of receiving recommended treatment. RESULTS: For 3644 infants 23 to 27 weeks' GA and 4870 infants 28 to 31 weeks' GA, respectively, the probability of receiving care consistent with guidelines per year increased, including thermal care (odds ratio [OR], 1.52 [95% confidence interval (CI) 1.44-1.61] and 1.45 [1.38-1.52]) and PPV with a T-piece (OR, 1.45 [95% CI 1.37-1.55] and 1.41 [1.32-1.51]). The probability of receiving PPV with Fio2 1.00 decreased equally in both GA groups (OR, 0.89; 95% CI, 0.86-0.93). CONCLUSIONS: Between 2014 and 2020, the resuscitation guidelines for newborns <32 weeks' GA on thermal care, PPV with a T-piece resuscitator, and decreased use of Fio2 1.00 were translated into clinical practice.

Tactile Stimulation in Newborn Infants With Inadequate Respiration at Birth: A Systematic Review.

CONTEXT: For many years the International Liaison Committee on Resuscitation has recommended the use of tactile stimulation for initial management of infants born with inadequate respiratory effort at birth without systematically examining its effectiveness. OBJECTIVE: Systematic review to compare the effectiveness of tactile stimulation with routine handling in newly born term and preterm infants. DATA SOURCES: Medline, Embase, Cochrane CENTRAL, along with clinical trial registries. STUDY SELECTION: Randomized and non-randomized studies were included based on predetermined criteria. DATA EXTRACTION: Data were extracted independently by authors. Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I) was used to assess risk of bias in non-randomized studies. Grading of Recommendations, Assessment, Development and Evaluations (GRADE) was used to assess the certainty of evidence. RESULTS: Among 2455 unique articles identified, 2 observational studies were eligible and qualitatively summarized. Because one of the studies was at critical risk of bias, only the other study including 243 preterm infants on continuous positive airway pressure with clinical indications for tactile stimulation was analyzed. It showed a reduction in tracheal intubation in infants receiving tactile stimulation compared with no tactile stimulation (12 of 164 vs 14 of 79, risk ratio of 0.41 [95% confidence interval 0.20 to 0.85]); however, the certainty of evidence was very low. LIMITATIONS: The available data were limited and only from observational studies. CONCLUSIONS: A potential benefit of tactile stimulation was identified but was limited by the very low certainty of evidence. More research is suggested to evaluate the effectiveness as well as the optimal type and duration of tactile stimulation.

Duration of Resuscitation at Birth, Mortality, and Neurodevelopment: A Systematic Review.

CONTEXT: The International Liaison Committee on Resuscitation Neonatal Life Support Task Force reviewed evidence for the duration of cardiopulmonary resuscitation (CPR) for newborns immediately after birth. OBJECTIVE: To summarize evidence for ongoing CPR on the outcomes of survival, neurodevelopment, and the composite of survival without moderate or severe neurodevelopmental impairment (NDI). DATA SOURCES: Medline, Embase, Evidence-Based Medicine Reviews, Cumulative Index to Nursing and Allied Health Literature, and Scientific Electronic Library Online were searched between inception and February 29, 2020. STUDY SELECTION: Two independent reviewers selected studies of newborns with at least 10 minutes of asystole, bradycardia, or pulseless electrical activity for which CPR is indicated. DATA EXTRACTION: Two independent reviewers extracted data and appraised the risk of bias. RESULTS: In 16 eligible studies, researchers reported outcomes of 579 newborns born between 1982 and 2017. Within individual studies, 2% to 100% of infants survived to last follow-up (hospital discharge through 12 years). Summarized across studies, 237 of 579 (40.9%) newborns survived to last follow-up. In 13 studies, researchers reported neurodevelopmental outcomes of 277 newborns. Of these, 30 of 277 (10.8%) survived without moderate or severe impairment, and 240 of 277 (87%) met the composite outcome of death or NDI (191 died and 49 survived with moderate or severe impairment). LIMITATIONS: There was very low certainty of evidence because of risk of bias and inconsistency. CONCLUSIONS: Infants with ongoing CPR at 10 minutes after birth are at high risk for mortality and neurodisability, but survival without moderate or severe NDI is possible. One specified duration of CPR is unlikely to uniformly predict survival or survival without neuroimpairment.

Maintaining normothermia: Why and how?

A high incidence of postnatal hypothermia has been reported in high-as well low-resource countries and it remains an independent predictor of neonatal morbidity and mortality, especially in very preterm infants in all settings. The temperature of newly born infants should be maintained between 36.5 and 37.5 °C after birth through admission and stabilization. Interventions to achieve this may include environmental temperature 23-25 °C, use of radiant warmers, exothermic mattresses, woollen or plastic caps, plastic wraps, humidified and heated gases. Skin-to-skin contact has been used, especially in low-resource settings. The combinations of these interventions applied to quality improvement initiatives, including staff training, use of checklists, and continuous feedback with the staff involved in the management of the neonate, are key factors to prevent heat loss from delivery room to admission to the neonatal intensive care unit. The admission temperature should be recorded as a predictor of outcomes as well as a quality indicator.

Management of late-preterm and term infants with hyperbilirubinaemia in resource-constrained settings.

Hyperbilirubinaemia is a ubiquitous transitional morbidity in the vast majority of newborns and a leading cause of hospitalisation in the first week of life worldwide. While timely and effective phototherapy and exchange transfusion are well proven treatments for severe neonatal hyperbilirubinaemia, inappropriate or ineffective treatment of hyperbilirubinaemia, at secondary and tertiary hospitals, still prevails in many poorly-resourced countries accounting for a disproportionately high burden of bilirubin-induced mortality and long-term morbidity. As part of the efforts to curtail the widely reported risks of frequent but avoidable bilirubin-induced neurologic dysfunction (acute bilirubin encephalopathy (ABE) and kernicterus) in low and middle-income countries (LMICs) with significant resource constraints, this article presents a practical framework for the management of late-preterm and term infants (≥ 35 weeks of gestation) with clinically significant hyperbilirubinaemia in these countries particularly where local practice guidelines are lacking. Standard and validated protocols were followed in adapting available evidence-based national guidelines on the management of hyperbilirubinaemia through a collaboration among clinicians and experts on newborn jaundice from different world regions. Tasks and resources required for the comprehensive management of infants with or at risk of severe hyperbilirubinaemia at all levels of healthcare delivery are proposed, covering primary prevention, early detection, diagnosis, monitoring, treatment, and follow-up. Additionally, actionable treatment or referral levels for phototherapy and exchange transfusion are proposed within the context of several confounding factors such as widespread exclusive breastfeeding, infections, blood group incompatibilities and G6PD deficiency, which place infants at high risk of severe hyperbilirubinaemia and bilirubin-induced neurologic dysfunction in LMICs, as well as the limited facilities for clinical investigations and inconsistent functionality of available phototherapy devices. The need to adjust these levels as appropriate depending on the available facilities in each clinical setting and the risk profile of the infant is emphasised with a view to avoiding over-treatment or under-treatment. These recommendations should serve as a valuable reference material for health workers, guide the development of contextually-relevant national guidelines in each LMIC, as well as facilitate effective advocacy and mobilisation of requisite resources for the optimal care of infants with hyperbilirubinaemia at all levels.

Perinatal asphyxia associated with early neonatal mortality: populational study of avoidable deaths.

OBJECTIVE: To compare the epidemiological profile of avoidable early neonatal deaths associated with perinatal asphyxia according to region of death in the State of São Paulo, Brazil. METHODS: Population-based cohort study including 2,873 avoidable deaths up to six days of life associated with perinatal asphyxia from January 2001 to December 2003. Perinatal asphyxia was considered if intrauterine hypoxia, birth asphyxia, or meconium aspiration syndrome were written in any line of the original Death Certificate. Epidemiological data were also extracted from the Birth Certificate. RESULTS: During the three years, 1.71 deaths per 1,000 live births were associated with perinatal asphyxia, which corresponded to 22% of the early neonatal deaths. From the 2,873 avoidable deaths, 761 (27%) occurred in São Paulo city; 640 (22%), in the metropolitan region of São Paulo city; and 1,472 (51%), in the countryside of the state. In the first two regions, deaths were more frequent in public hospitals, among newborns with gestational age of 36 weeks or less, and among babies weighing less than 2500g. In the countryside, mortality was more frequent in philanthropic hospitals, in term newborns and in neonates weighing over 2500g. Most of these neonates were born during daytime in their hometown and died at the same institution in which they were born within the first 24 hours after delivery. Meconium aspiration syndrome was related to 18% of the deaths. CONCLUSIONS: Perinatal asphyxia is a frequent contributor to the avoidable early neonatal death in the state with the highest gross domestic product per capita in Brazil, and it shows the need for specific interventions with regionalized focus during labor and birth care.

Sepsis and neutropenia in very low birth weight infants delivered of mothers with preeclampsia.

OBJECTIVE: To study the association between maternal preeclampsia and neonatal sepsis in very low birth weight newborns. STUDY DESIGN: We studied all infants with birth weights between 500 g and 1500 g who were admitted to 6 neonatal intensive care units of the Brazilian Network on Neonatal Research for 2 years. Exclusion criteria were major malformations, death in the delivery room, and maternal chronic hypertension. Absolute neutrophil count was performed in the first 72 hours of life. RESULTS: A total of 911 very low birth weight infants (preeclampsia, 308; non-preeclampsia, 603) were included. The preeclampsia group had significantly higher gestational age, more cesarean deliveries, antenatal steroid, central catheters, total parenteral nutrition, and neutropenia, and less rupture of membranes>18 hours and mechanical ventilation. Both groups had similar incidences of early sepsis (4.6% and 4.2% in preeclampsia and non-preeclampsia groups, respectively) and late sepsis (24% and 22.1% in preeclampsia and non- preeclampsia groups, respectively). Vaginal delivery and neutropenia were associated with multiple logistic regressions with early sepsis, and mechanical ventilation, central catheter, and total parenteral nutrition were associated with late sepsis. Death was associated with neutropenia in very preterm infants. CONCLUSIONS: Preeclampsia did not increase neonatal sepsis in very low birth weight infants, and death was associated with neutropenia in very preterm infants.

Variability on red blood cell transfusion practices among Brazilian neonatal intensive care units.

BACKGROUND: Guidelines for red blood cell (RBC) transfusions exist; however, transfusion practices vary among centers. This study aimed to analyze transfusion practices and the impact of patients and institutional characteristics on the indications of RBC transfusions in preterm infants. STUDY DESIGN AND METHODS: RBC transfusion practices were investigated in a multicenter prospective cohort of preterm infants with a birth weight of less than 1500 g born at eight public university neonatal intensive care units of the Brazilian Network on Neonatal Research. Variables associated with any RBC transfusions were analyzed by logistic regression analysis. RESULTS: Of 952 very-low-birth-weight infants, 532 (55.9%) received at least one RBC transfusion. The percentages of transfused neonates were 48.9, 54.5, 56.0, 61.2, 56.3, 47.8, 75.4, and 44.7%, respectively, for Centers 1 through 8. The number of transfusions during the first 28 days of life was higher in Center 4 and 7 than in other centers. After 28 days, the number of transfusions decreased, except for Center 7. Multivariate logistic regression analysis showed higher likelihood of transfusion in infants with late onset sepsis (odds ratio [OR], 2.8; 95% confidence interval [CI], 1.8-4.4), intraventricular hemorrhage (OR, 9.4; 95% CI, 3.3-26.8), intubation at birth (OR, 1.7; 95% CI, 1.0-2.8), need for umbilical catheter (OR, 2.4; 95% CI, 1.3-4.4), days on mechanical ventilation (OR, 1.1; 95% CI, 1.0-1.2), oxygen therapy (OR, 1.1; 95% CI, 1.0-1.1), parenteral nutrition (OR, 1.1; 95% CI, 1.0-1.1), and birth center (p < 0.001). CONCLUSIONS: The need of RBC transfusions in very-low-birth-weight preterm infants was associated with clinical conditions and birth center. The distribution of the number of transfusions during hospital stay may be used as a measure of neonatal care quality.