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Objective: This study aimed to evaluate the Neuropsychomotor Development (NPMD) of newborns exposed to SARS-CoV-2 in the perinatal period using the Bayley III scale at 6 months of age., Methods: Childcare appointments were scheduled for the included newborns in the study. During the 6-month consultation, the Screening Test for Bayley III Scale and, based on it, children were classified as "low risk", "moderate risk" or "high risk" in the domains: of cognitive, receptive language, expressive language, fine motor, and gross motor. Those classified as "moderate risk"; or "high risk" received guidance about NPMD stimuli and were instructed to maintain follow-up., Results: Only 13 (37.1 %) of the newborns were classified as low risk in receptive language and 18 (51.4 %) in gross motor skills, with the domains most affected. Prematurity was a risk for cognitive incompetence (moderate risk/high-risk classification) (coefficient: 1.89, Odds Ratio = 6.7, 95 % CI 1.3‒35, p = 0.02). Lower birth weight that 2.500g had a similar effect on cognitive incompetence (coefficient: 1.9, Odds Ratio = 6.2, 95 % CI 1.2‒32.2, p = 0.02). Exclusive breastfeeding at hospital discharge (n = 8) was protective for incompetence (high risk/moderate risk) in the language domain (coefficient -2.14, OR = 0.12, 95 % CI 0.02‒0.71, p = 0.02)., Conclusions: The children included in the study must be monitored and their development monitored in order to clarify whether there is a relationship between the delay in NPMD and perinatal exposure to COVID-19, as delays were observed in these preliminary results., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 HCFMUSP. Published by Elsevier España, S.L.U. All rights reserved.)

To evaluate milrinone's impact on pediatric cardiac function, focusing on its specific role as an inotrope and lusitrope, while considering its systemic and pulmonary vasodilatory effects. Search of PubMed, EMBASE, and the Cochrane Library up to August 2023. We included all studies that evaluated milrinone in children under 18 years old in neonatal, pediatric, or cardiac intensive care units. We excluded case reports, studies that did not provide tabular information on milrinone's outcomes, and studies focused on non-intensive care populations. We extracted data on the research design, objectives, study sample, and results of each study, including the impact of milrinone and any associated factors. We screened a total of 9423 abstracts and 41 studies were ultimately included. Milrinone significantly improved left ventricular ejection fraction (WMD 3.41 [95% CI 0.61 - 6.21]), left ventricle shortening fraction (WMD 4.25 [95% CI 3.43 - 5.08]), cardiac index (WMD 0.50 [95% CI 0.32 to 0.68]), left ventricle output (WMD 55.81 [95% CI 4.91 to 106.72]), serum lactate (WMD -0.59 [95% CI -1.15 to -0.02]), and stroke volume index (WMD 2.95 [95% CI 0.09 - 5.82]). However, milrinone was not associated with improvements in ventricular myocardial performance index (WMD -0.01 [95% CI -0.06 to 0.04]) and ventricular longitudinal strain (WMD -2.14 [95% CI -4.56 to 0.28]). Furthermore, milrinone was not associated with isovolumetric relaxation time reduction (WMD -8.87 [95% CI -21.40 to 3.66])., Conclusion: Our meta-analysis suggests potential clinical benefits of milrinone by improving cardiac function, likely driven by its systemic vasodilatory effects. However, questions arise about its inotropic influence and the presence of a lusitropic effect. Moreover, milrinone's pulmonary vasodilatory effect appears relatively weaker compared to its systemic actions. Further research is needed to elucidate milrinone's precise mechanisms and refine its clinical applications in pediatric practice., What Is Known: • Milrinone is a phosphodiesterase III inhibitor that has been used to treat a variety of pediatric and neonatal conditions. • Milrinone is believed to exert its therapeutic effects by enhancing cardiac contractility and promoting vascular relaxation., What Is New: • Milrinone may not have a significant inotropic effect. • Milrinone's pulmonary vasodilatory effect is less robust than its systemic vasodilatory effect., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Very low birth weight (VLBW) infants, mostly preterm, have many barriers to feeding directly from the mother's breast, and need to be fed alternatively. Feeding is a major influencer in oral microbial colonization, and this colonization in early life is crucial for the promotion of human health. Therefore, this research aimed to observe the establishment of oral microbiome in VLBW infants during their first month of life through hospitalization, and to verify the impact caused by the implementation of oral diet on the colonization of these newborns. We included 23 newborns followed during hospitalization and analyzed saliva samples collected weekly, using 16S rRNA gene sequencing. We observed a significant decrease in richness and diversity and an increase in dominance over time (q-value < 0.05). The oral microbiome is highly dynamic during the first weeks of life, and beta diversity suggests a microbial succession in early life. The introduction of oral diet does not change the community structure, but affects the abundance, especially of Streptococcus. Our results indicate that although time is related to significant changes in the oral microbial profile, oral feeding benefits genera that will remain colonizers throughout the host's life., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Vanzele et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: Lactate is a marker of hypoperfusion in critically ill patients. Whether lactate is useful for identifying and stratifying neonates with a higher risk of adverse outcomes remains unknown. This study aimed to investigate the association between lactate and morbidity and mortality in neonates., Methods: A meta-analysis was performed to determine the association between blood lactate levels and outcomes in neonates. Ovid MEDLINE, EMBASE, Cochrane Library, and ClinicalTrials.gov were searched from inception to 1 May 2021. A total of 49 observational studies and 14 data accuracy test studies were included. The risk of bias was assessed using the Newcastle-Ottawa Scale for observational studies and the QUADAS-2 tool for data accuracy test studies. The primary outcome was mortality, while the secondary outcomes included acute kidney injury, necessity for renal replacement therapy, neurological outcomes, respiratory morbidities, hemodynamic instability, and retinopathy of prematurity., Results: Of the 3184 articles screened, 63 studies fulfilled all eligibility criteria, comprising 46,069 neonates. Higher lactate levels are associated with mortality (standard mean difference, -1.09 [95% CI, -1.46 to -0.73]). Using the estimated sensitivity (0.769) and specificity (0.791) and assuming a prevalence of 15% for adverse outcomes (median of prevalence among studies) in a hypothetical cohort of 10,000 neonates, assessing the lactate level alone would miss 346 (3.46%) cases (false negative) and wrongly diagnose 1776 (17.76%) cases (false positive)., Conclusions: Higher lactate levels are associated with a greater risk of mortality and morbidities in neonates. However, our results do not support the use of lactate as a screening test to identify adverse outcomes in newborns. Research efforts should focus on analyzing serial lactate measurements, rather than a single measurement.

To use unsupervised machine learning to identify potential subphenotypes of preterm infants with patent ductus arteriosus (PDA). The study was conducted retrospectively at a neonatal intensive care unit in Brazil. Patients with a gestational age < 28 weeks who had undergone at least one echocardiogram within the first two weeks of life and had PDA size > 1.5 or LA/AO ratio > 1.5 were included. Agglomerative hierarchical clustering on principal components was used to divide the data into different clusters based on common characteristics. Two distinct subphenotypes of preterm infants with hemodynamically significant PDA were identified: "inflamed," characterized by high leukocyte, neutrophil, and neutrophil-to-lymphocyte ratio, and "respiratory acidosis," characterized by low pH and high pCO2 levels.    Conclusions: This study suggests that there may be two distinct subphenotypes of preterm infants with hemodynamically significant PDA: "inflamed" and "respiratory acidosis." By dividing the population into different subgroups based on common characteristics, it is possible to get a more nuanced understanding of the effectiveness of PDA interventions. What is Known: • Treatment of PDA in preterm infants has been controversial. • Stratification of preterm infants with PDA into subgroups is important in order to determine the best treatment. What is New: • Unsupervised machine learning was used to identify two subphenotypes of preterm infants with hemodynamically significant PDA. • The 'inflamed' cluster was characterized by higher values of leukocyte, neutrophil, and neutrophil-to-lymphocyte ratio. The 'respiratory acidosis' cluster was characterized by lower pH values and higher pCO2 values., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Acute kidney injury (AKI) in the neonatal period is associated with worst outcomes as increased mortality and increased length of hospital stay. Very low birth weight (VLBW) newborns are at higher risk for developing several other conditions that are associated with worst outcomes. Understanding the risk factors for AKI may help to prevent this condition and improve neonatal care for this population., Methods: This retrospective cohort study included 155 very low birth weight newborns admitted between 2015 and 2017. The authors compared the newborns who developed neonatal AKI with the non-AKI group and analyzed the main risk factors for developing AKI in the population. The authors also performed an analysis of the main outcomes defined as the duration of mechanical ventilation, length of stay, and death., Results: From the cohort, a total of 61 (39.4%) patients had AKI. The main risk factors associated with Neonatal AKI were necrotizing enterocolitis (aOR 7.61 [1.69 - 34.37]; p = 0.008), neonatal sepsis (aOR 2.91 [1.17 - 7.24], p = 0.021), and hemodynamic instability (aOR 2.99 [1.35 - 6.64]; p = 0.007). Neonatal AKI was also associated with an increase in the duration of mechanical ventilation in 9.4 days (p = 0.026) and in an increase in mortality 4 times (p = 0.009), after adjusting for the other variables., Conclusion: The present results highlight the importance of minimizing sepsis and necrotizing enterocolitis, as well as the importance of identifying hemodynamic instability, to prevent AKI and diminish the burden of morbimortality in VLBW newborns., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2022 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.)

Purpose: The authors aimed to develop a Machine-Learning (ML) algorithm that can predict positive blood culture in the neonatal intensive care unit, using complete blood count and C-reactive protein values., Methods: The study was based on patients' electronic health records at a tertiary neonatal intensive care unit in São Paulo, Brazil. All blood cultures that had paired complete blood count and C-reactive protein measurements taken at the same time were included. To evaluate the machine learning model's performance, the authors used accuracy, Area Under the Receiver Operating Characteristics (AUROC), recall, precision, and F1-score., Results: The dataset included 1181 blood cultures with paired complete blood count plus c-reactive protein and 1911 blood cultures with paired complete blood count only. The f1-score ranged from 0.14 to 0.43, recall ranged from 0.08 to 0.59, precision ranged from 0.29 to 1.00, and accuracy ranged from 0.688 to 0.864., Conclusion: Complete blood count parameters and C-reactive protein levels cannot be used in ML models to predict bacteremia in newborns., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2022 HCFMUSP. Published by Elsevier España, S.L.U. All rights reserved.)

Background: The neonatal period is marked by major changes in the cardiovascular system, especially in the first week of life. Unlike the adult population, studies on electrocardiogram (ECG) data in the neonatal period are scarce. This is the first study to describe electrocardiographic changes in a cohort of newborns with normal echocardiograms., Objectives: To analyze the electrocardiographic patterns of a population of full-term NB, without any cardiac morphological or functional anomalies, and compare the results with the literature., Methods: In this observational study, echocardiograms and ECG results from 94 newborns divided in three age groups (up to 24 hours, between 25 and 72 hours, and between 73 and 168 hours of life) were evaluated and compared with those reported by Davignon et al. A p-value &lt;0.05 was considered statistically significant., Results: There were significant differences in T-wave direction in leads V1 (p= 0.04), V2 (p= 0.02), V3 (p= 0.008) and V4 (p= 0.005) between the three age groups. There were differences between our findings and the current literature in most of the parameters., Conclusion: Term newborns within 24 hours of life showed significantly more positive T waves than older ones. Many differences from the Davignon's ECG parameters were found, particularly in the P, Q, R, S amplitudes, QRS duration, R/S and R+S. These findings indicate that more studies are needed for a definitive interpretation of the ECG in newborns.

Background: The effects of antenatal corticosteroids (ANSs) on twins are not well established., Objective: To determine the impact of ANS use according to the number of fetuses., Methods: Retrospective cohort study of newborns between 23 and 33 weeks of gestational age, birth weight from 400 to 1499 g, without malformations, delivered at 20 public university hospitals from 2010 to 2014.Exposed group: Received ANS (any time, any dose) and no exposed group: no received ANS. Analysis of birth conditions and clinical outcomes. Association of variables, relative risks, and 95% confidence intervals estimated from the adjustment of log-binomial regression models., Results: About 7165 premature infants were analyzed: 5167 singleton, 937 twins, and 104 triplets. Characteristics of gestations with one, two, or three fetuses not receiving ANS were similar. Reduced hemodynamic instability in single and twins gestations in the first 72 h were observed (Adj R 2 Twins = 0.78; 95% CI = 0.69-0.86) (Adj R 2 Singles = 0.79; 95% CI = 0.62-0.99). Reduced peri-intraventricular hemorrhage (Adj R 2 Twins = 0.54; 95% CI = 0.36-0.78) (Adj R 2 singles = 0.54; 95% CI = 0.36-0.78); and early sepsis reduction on single and triplex gestations (Adj R 2 triplex = 0.51; 95% CI = 0.27-0.94) (Adj single R 2 = 0.51; 95% CI = 0.27-0.94) were observed., Conclusions: This study demonstrates ANS produces an important protective factor for severe intraventricular hemorrhage and hemodynamic instability in single and multiple pregnancies. ANS had a protective effect on death and birth conditions improvement just in single gestations. Regarding respiratory aspects was not observed the protective effect in the single or multiple gestations.

Fluid overload (FO) is associated with higher rates of mortality and morbidity in pediatric and adult populations. The aim of this systematic review and meta-analysis was to investigate the association between FO and mortality in critically ill neonates. Systematic search of Ovid MEDLINE, EMBASE, Cochrane Library, trial registries, and gray literature from inception to January 2021. We included all studies that examined neonates admitted to neonatal intensive care units and described FO and outcomes of interest. We identified 17 observational studies with a total of 4772 critically ill neonates who met the inclusion criteria. FO was associated with higher mortality (OR, 4.95 [95% CI, 2.26-10.87]), and survivors had a lower percentage of FO compared with nonsurvivors (WMD, - 4.33 [95% CI, - 8.34 to - 0.32]). Neonates who did not develop acute kidney injury (AKI) had lower FO compared with AKI patients (WMD, - 2.29 [95% CI, - 4.47 to - 0.10]). Neonates who did not require mechanical ventilation on postnatal day 7 had lower fluid balance (WMD, - 1.54 [95% CI, - 2.21 to - 0.88]). FO is associated with higher mortality, AKI, and need for mechanical ventilation in critically ill neonates in the intensive care unit. Strict control of fluid balance to prevent FO is essential. A higher resolution version of the Graphical abstract is available as Supplementary information., (© 2021. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

There is increasing evidence that patient heterogeneity significantly hinders advancement in clinical trials and individualized care. This study aimed to identify distinct phenotypes in extremely low birth weight infants. We performed an agglomerative hierarchical clustering on principal components. Cluster validation was performed by cluster stability assessment with bootstrapping method. A total of 215 newborns (median gestational age 27 (26-29) weeks) were included in the final analysis. Six clusters with different clinical and laboratory characteristics were identified: the "Mature" (Cluster 1; n = 60, 27.9%), the mechanically ventilated with "adequate ventilation" (Cluster 2; n = 40, 18.6%), the mechanically ventilated with "poor ventilation" (Cluster 3; n = 39, 18.1%), the "extremely immature" (Cluster 4; n = 39, 18.1%%), the neonates requiring "Intensive Resuscitation" in the delivery room (Cluster 5; n = 20, 9.3%), and the "Early septic" group (Cluster 6; n = 17, 7.9%). In-hospital mortality rates were 11.7%, 25%, 56.4%, 61.5%, 45%, and 52.9%, while severe intraventricular hemorrhage rates were 1.7%, 5.3%, 29.7%, 47.2%, 44.4%, and 28.6% in clusters 1, 2, 3, 4, 5, and 6, respectively (p < 0.001).Conclusion: Our cluster analysis in extremely preterm infants was able to characterize six distinct phenotypes. Future research should explore how better phenotypic characterization of neonates might improve care and prognosis. What is Known: • Patient heterogeneity is becoming more acknowledged as a cause of clinical trial failure. • Machine learning algorithms can find patterns within a heterogeneous group. What is New: • We identified six different phenotypes of extremely preterm infants who exhibited distinct clinical and laboratorial characteristics., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Limited data are available on pregnant women with COVID-19 and their neonates., Objective: This study aimed to describe clinical characteristics and evolution from birth to discharge of a retrospective cohort of 71 neonates, with one set of twins, born to women with COVID-19 diagnosed at the end of pregnancy. The authors included all newborns admitted into a neonatal unit of a tertiary hospital in Brazil, between March 2020 and March 2021, whose unvaccinated mothers had COVID-19 symptoms and RT-PCR (Real-Time Polymerase Chain Reaction) for SARS-CoV-2 positive within fourteen days prior to delivery. Newborns to mothers with COVID-19 symptoms and negative tests for SARS-CoV-2 were excluded., Results: The main route of birth delivery was cesarean, corresponding to 60 pregnant women (84.5%). The foremost indications for cesarean were pregnant with critical disease (24.6%) and acute fetal distress (20.3%). The mean birth weight was 2452 g (865‒3870 g) and the mean gestational age was 34 5/7  weeks (25‒40 weeks). There were 45 premature newborns (63.3%), of which 21 newborns (29.5%) were less than 32 weeks of gestational age. RT-PCR for SARS-CoV-2 on oropharyngeal swabs was positive in 2 newborns (2.8%) and negative in the other 69 newborns (97.2%). Most newborns (51.4%) needed respiratory support. Therapeutic interventions during hospitalization were inotropic drugs (9.9%), antibiotics (22.8%), parenteral nutrition (26.8%), and phototherapy (46.5%)., Conclusion: Maternal COVID-19 diagnosticated close to delivery has an impact on the first days of neonatal life., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2022 HCFMUSP. Published by Elsevier España, S.L.U. All rights reserved.)

Aim: Major congenital anomalies are an important cause of death in the neonatal intensive care unit (NICU). Therapeutic interventions and the suspension of those already in place often raise ethical dilemmas in neonatal care., Methods: We analysed treatments-such as ventilatory support, vasoactive drugs, antibiotics, sedation/or analgesia, central venous access and other invasive procedures-offered up to 48 h before death to all newborns with major congenital anomalies over a 3-year period in a NICU in Brazil. We also gathered information contained in medical records concerning conversations with the families and decisions to limit therapeutic interventions., Results: We enrolled 74 newborns who were hospitalised from 1 January 2015 to 31 December 2017. A total of 81.1% had central venous access, 74.3% were on ventilatory support, 56.8% received antibiotics and 43.2% used some sedative/analgesic drugs in their final moments. Conversations were registered in medical records in 76% of cases, and 46% of the families chose therapeutic intervention limits. Those who chose to limit therapeutic interventions asked for less exposure to vasoactive drugs (P = 0.003) and antibiotics (P = 0.003), as well as fewer invasive procedures (P = 0.046). There was no change in ventilatory support (P = 0.66), and palliative extubation was not performed for any patient., Conclusions: The therapeutic intervention was mainly characterised by maintenance of the current treatment when a terminal situation was identified with no introduction of new treatments that could increase suffering. The families' approach proved to be essential for making difficult decisions in the NICU., (© 2021 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Objectives: Pneumothorax is a catastrophic event associated with high morbidity and mortality, and it is relatively common in neonates. This study aimed to investigate the association between ventilatory parameters and the risk of developing pneumothorax in extremely low birth weight neonates., Methods: This single-center retrospective cohort study analyzed 257 extremely low birth weight neonates admitted to a neonatal intensive care unit between January 2012 and December 2017. A comparison was carried out to evaluate the highest value of positive end-expiratory pressure (PEEP), peak inspiratory pressure (PIP), and driving pressure (DP) in the first 7 days of life between neonates who developed pneumothorax and those who did not. The primary outcome was pneumothorax with chest drainage necessity in the first 7 days of life. A matched control group was created in order to adjust for cofounders associated with pneumothorax (CRIB II score, birth weight, and gestational age)., Results: There was no statistically significant difference in PEEP, PIP, and DP values in the first 7 days of life between extremely low birth weight neonates who had pneumothorax with chest drainage necessity and those who did not have pneumothorax, even after adjusting for potential cofounders., Conclusions: Pressure-related ventilatory settings in mechanically ventilated extremely low birth weight neonates are not associated with a higher risk of pneumothorax in the first 7 days of life.

Objective: To evaluate the orofacial characteristics of very low-birth-weight preterm infants through anthropometric facial measures, orofacial anteroposterior analysis and the relationship between the gum pads., Method: Orofacial examinations was performed in 154 infants, classified into two groups: Group A comprised 54 very low-birth-weight infants who were examined after clinical stabilization and before hospital discharge, and Group B comprised 100 full-term infants., Results: The average anthropometricmeasurements in millimetres for Group A and Group B were as follows: upper third:30.2 and 31.1; middle third: 24.2 and 25.9; lower third: 27.6 and 29.9; facial width: 64.8and 81.4. Regarding the orofacial anteroposterior analysis, the results showed that in99% of these infants, the mandible was in a retrognathic position relative to the maxilla.Group A and Group B had the following distributions of the relationship between thegum pads: overbite-overjet: 43% and 77%; overjet: 39% and 17%; open bite: 15% and3%; end-to-end: 2% and 1%; overbite: both 2%., Conclusion: The very low-birth-weight preterm infants showed the upper third with the highest values in the facialharmony analysis, followed by the lower third and the middle third; and exhibited themandible in a retrognathic position relative to the maxilla, and with overbite-overjet themost prevalent type of gum pad relationship. The study emphasizes the importance of orofacial examination during neonatal hospitalization and the investigation of birth weight and gestational age in a multidisciplinary therapeutic approach that includes orofacial neonatal evaluation and actions that promote oral health, besides foster follow-up studies., (Copyright © 2020. Published by Elsevier Editora Ltda.)

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., Competing Interests: The Brazilian Neonatal Network received funding from Brazilian Ministry of Health (Ministério da Saúde do Brasil). Dr. Silva received support for article research from the National Institutes of Health. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2020 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Recent studies revealed that fluid overload is associated with higher mortality in critically ill children and adults. This study aimed to evaluate the association between fluid overload in the first 3 days of life and mortality in extremely low birth weight infants. This single-center retrospective cohort study included two hundred nineteen newborns with birth weight less than 1000 g who were admitted to the neonatal intensive care between January 2012 and December 2017. Overall mortality was 32.4%, the median gestational age was 27.3 (26.1-29.4) weeks, and birth weight was 770 (610-900) grams. In the group with severe fluid overload, we found a higher rate of deaths (72.2%); mean airway pressure was significantly higher and with longer invasive mechanical ventilation necessity.Conclusion: Early fluid overload in extremely low birth weight infants is associated with higher mortality rate, higher mean airway pressure in invasive mechanically ventilated patients, and longer mechanical ventilation duration in the first 7 days of life. What is Known: • Fluid overload is associated with a higher mortality rate and prolonged mechanical ventilation in children and adults. What is New: • Fluid overload in the first 72 h of life in an extremely premature infant is associated with higher mortality rate, higher mean airway pressure in invasive mechanically ventilated patients, and longer mechanical ventilation duration the first 7 days of life.

Objective: To report a single-center experience with thrombolytic therapy using recombinant tissue plasminogen activator (rt-PA) in preterm neonates with severe thrombotic events, in terms of thrombus resolution and bleeding complications., Study Design: This retrospective study included 21 preterm neonates with severe venous thrombotic events admitted to the neonatal intensive care unit, identified in our pharmacy database from January 2001 to December 2016, and treated with rt-PA until complete or partial clot lysis, no-response or bleeding complications. Our primary outcome was thrombus resolution., Results: Twenty-one preterm neonates were treated with rt-PA for an average of 2.9 cycles. Seventeen patients (80.9%) had superior vena cava thrombosis and superior vena cava syndrome. All patients had a central venous catheter, parenteral nutrition, mechanical ventilation, and sepsis. Fifteen patients (71.4%) were extremely preterm, 11 (52.4%) were extremely low birth weight, and seven (33.3%) were very low birth weight. The patency rate was 85.7%, complete lysis occurred in 11 (52.4%) patients, and partial lysis in seven (33.3%). Minor bleeding occurred in five (23.8%) patients, three patients (14.2%) had clinically relevant nonmajor bleeding events, and major bleeding occurred in six (28%) patients., Conclusion: In this study, the rate of thrombus resolution in preterm neonates treated with rt-PA were similar to the percentages reported in children and adolescents, with a high rate of bleeding. Therefore, rt-PA thrombolytic therapy should only be considered as a treatment option for severe life-threatening thrombosis in premature neonates for whom the benefits of the thrombolytic treatment outweigh the risks of bleeding., (© 2020 Wiley Periodicals LLC.)

Objectives: Renal development is impaired in fetal growth restriction (FGR). Renal size can be considered a surrogate of renal function in childhood, and could be impaired in that condition. Our aim was to evaluate the ratio of total renal volume, measured by three-dimensional ultrasound, to estimated fetal weight (TRV/EFW) among fetuses with and without growth restriction. Furthermore, we correlated TRV/EFW with fetal Doppler velocimetry and renal vascularization indexes and evaluated the association of renal volume and vascular parameters with adverse neonatal events in growth-restricted fetuses., Methods: In a retrospective cohort, TRV and renal vascularization of growth-restricted and normal fetuses were evaluated by three-dimensional ultrasonography and VOCAL technique. Independent samples t-tests and Mann-Whitney test were used for comparisons between groups. Logistic regression model was applied to evaluate the association between renal characteristics and adverse neonatal events., Results: Seventy-one growth-restricted fetuses were compared to 194 controls. The TRV/EFW was lower in the growth-restricted group (P < .001). In our sample, this ratio did not correlate with Doppler velocimetry parameters, renal vascular indexes or any adverse neonatal events., Conclusion: The TRV/EFW ratio is decreased in FGR. Further studies are needed to investigate the association of this ratio with long-term renal outcomes., (© 2020 John Wiley & Sons, Ltd.)

On 11th March 2020, the World Health Organization (WHO) declared the COVID-19 a pandemic. The Obstetrics and Neonatology disciplines needed to be revised to suit the institutional need to expand intensive care beds to care for confirmed or suspected patients with COVID-19 in the state of São Paulo, following the recommendations of the Institutional Crisis Committee. Three different actions were needed: the structuring of teams and advanced medical post to attend COVID-19-free patients and those with suspect or confirmed COVID-19; elaborating the protocols from the delivery room throughout hospitalization. Some special considerations about breastfeeding and rooming-in were needed. The third action was the drafting of a protocol to admit infants from other hospitals with confirmed COVID-19 as the unit never admitted outpatients before.

OBJECTIVE To describe the concentration of total and specific IgG antibodies anti-Streptococcus B, anti-lipopolysaccharide of Klebsiella spp, and anti-lipopolysaccharide of Pseudomonas spp in the umbilical cord of newborn(NB) twins and to analyze the association between neonatal infection and antibody concentration in the umbilical cord blood. METHODS A prospective cross-sectional study of a cohort of NB twins admitted during the period of 20 months. Patients with malformations and mothers with infection were excluded. Variables analyzed: gestational age(GA); birth weight(BW); antibody concentrations in umbilical cord blood; infection episodes. We used the paired Student t-test, Spearman correlation, and generalized estimation equation. RESULTS 57 pairs of twins were included, 4 excluded, making the sample of 110 newborns. GA=36±1.65weeks and BW=2304.8±460g(mean±SD). Antibody concentrations in twins(mean±SD): total IgG=835.71±190.73mg/dL, anti-StreptococcusB IgG=250.66±295.1 AU/mL, anti-lipopolysaccharide of Pseudomonas spp IgG=280.04±498.66 AU/mL and anti-lipopolysaccharide of Klebsiella spp IgG=504.75±933.93 AU/mL. There was a positive correlation between maternal antibody levels and those observed in newborns(p <0.005). The transplacental transfer of maternal total IgG and anti-LPS Pseudomonas IgG antibodies was significantly lower at NB GA <34 weeks(p <0.05). Five newborns were diagnosed with an infection. Infants with infection had significantly lower total IgG concentration(p <0.05). CONCLUSION This study showed a positive correlation between maternal and newborn antibodies levels. In infants younger than 34 weeks there is less transfer of total IgG and anti-LPS Pseudomonas IgG. The highest incidence of infection in the newborn group who had significantly lower total IgG serum antibodies reinforces the importance of anti-infectious protection afforded by passive immunity transferred from the mother.

Objective: These recommendations aim to provide guidance on breastfeeding for mothers with suspected or confirmed Covid-19., Methods: We performed a review of the recent medical literature on breastfeeding mothers with suspected or confirmed Covid-19, focusing on the neonatal period., Results: We analyzed 20 recent publications on breastfeeding, Covid-19, and its transmission through breastmilk. We presented possible options for breastfeeding and their consequences for the mother and the child., Conclusion: All maternal decisions in relation to breastfeeding are justifiable since the infection by Covid-19 is still poorly known. However, puerperal women and their families must be very well informed to make a conscious choice based on the information available in the literature so far.

Purpose: To investigate lexical performance and verbal short-term memory ability in premature infants at preschool age and compare the results with their full-term peers., Methods: Forty preschool children aged between 4 and 5 years and 11 months participated on the study and were equally divided into two groups considering their gestational age: preterm and full-term. Groups did not differ on age, family income and maternal education. Participants were paired according to their chronological age and their socioeconomic status. Their performance was assessed using expressive vocabulary and verbal short-term memory tests. Inferential statistical analysis was performed using the Mann-Whitney and the Fisher exact test., Results: Group performance did not differ on vocabulary, but premature children showed an inferior performance on nonword repetition tasks., Conclusion: These data indicates that preschoolers born premature performed statistically lower than their peers born full-term on nonword repetition task. Thus, premature birth was associated to vocabulary development on typically developing range, but also to verbal short-term memory impairments.

This article presents expert recommendations for assisting newborn children of mothers with suspected or diagnosed coronavirus disease 2019 (COVID-19). The consensus was developed by five experts with an average of 20 years of experience in neonatal intensive care working at a reference university hospital in Brazil for the care of pregnant women and newborns with suspected or confirmed COVID-19. Despite the lack of scientific evidence regarding the potential for viral transmission to their fetus in pregnant mothers diagnosed with or suspected of COVID-19, it is important to elaborate the lines of care by specialists from hospitals caring for suspected and confirmed COVID-19 cases to guide multidisciplinary teams and families diagnosed with the disease or involved in the care of pregnant women and newborns in this context. Multidisciplinary teams must be attentive to the signs and symptoms of COVID-19 so that decision-making is oriented and assertive for the management of the mother and newborn in both the hospital setting and at hospital discharge.

Objective: To investigate the influence of respiratory distress syndrome management on clinical and echocardiographic parameters used for hemodynamic evaluation in ≤ 32- week newborns., Methods: Thirty-three ≤ 32-week newborns were prospectively evaluated and subjected to invasive mechanical ventilation. The need for exogenous surfactant and clinical and echocardiographic parameters in the first 24 hours of life was detailed in this group of patients., Results: The mean airway pressure was significantly higher in newborn infants who required inotropes [10.8 (8.8 - 23) cmH2O versus 9 (6.2 - 12) cmH2O; p = 0.04]. A negative correlation was found between the mean airway pressure and velocity-time integral of the pulmonary artery (r = -0.39; p = 0.026), right ventricular output (r = -0.43; p = 0.017) and measurements of the tricuspid annular plane excursion (r = -0.37; p = 0.036). A negative correlation was found between the number of doses of exogenous surfactant and the right ventricular output (r = -0.39; p = 0.028) and pulmonary artery velocity-time integral (r = -0.35; p = 0.043)., Conclusion: In ≤ 32-week newborns under invasive mechanical ventilation, increases in the mean airway pressure and number of surfactant doses are correlated with the worsening of early cardiac function. Therefore, more aggressive management of respiratory distress syndrome may contribute to the hemodynamic instability of these patients.

Background: Diagnosis of renal function impairment and deterioration in congenital urinary tract obstruction (UTO) continues to be extremely challenging. Use of renal biomarkers in this setting may favor early renal injury detection, allowing for a reliable choice of optimal therapeutic options and prevention or minimization of definitive renal damage., Methods: This longitudinal, prospective study analyzed the first-year profile of two serum renal biomarkers: creatinine (sCr) and cystatin C (sCyC); and six urinary renal biomarkers: neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), transforming growth factor beta-1 (TGF-β1), retinol-binding protein (RBP), cystatin C (uCyC), and microalbuminuria (μALB) in a cohort of 37 infants with UTO divided into three subgroups: 14/37 with unilateral hydro(uretero)nephrosis, 13/37 with bilateral hydro(uretero)nephrosis, and 10/37 patients with lower urinary tract obstruction (LUTO), compared with 24 healthy infants matched by gestational age and birth weight., Results: All urine biomarkers showed significantly higher values at the first month of life (p ≤ 0.009), while NGAL (p = 0.005), TGF-ß1 (p < 0.001), and μALB (p < 0.001) were high since birth compared to controls. Best single biomarker performances were RBP in bilateral hydronephrosis and LUTO subgroups and KIM-1 in unilateral hydronephrosis subgroup. Best biomarker combination results for all subgroups were obtained by matching RBP with TGF-ß1 or KIM-1 and NGAL with CyC ([AUC] ≤ 0.934; sensitivity ≤ 92.4%; specificity ≤ 92.8%)., Conclusions: RBP, NGAL, KIM-1, TGF-ß1, and CyC, alone and especially in combination, are relatively efficient in identifying surgically amenable congenital UTO and could be of practical use in indicating on-time surgery.

Introduction: The diagnosis of renal function impairment and deterioration in congenital urinary tract obstruction (UTO) continues to be extremely challenging. The use of new renal biomarkers in this setting may favor early renal injury detection, allowing for a reliable choice of optimal therapeutic options and the prevention or minimization of definitive renal damage., Objective: The aim of the study was to investigate a selection of promising biomarkers of renal injury with the intention of evaluating and comparing their profile with clinically based decisions for surgical intervention of infants with congenital obstructive uropathies., Study Design: The first-year profile of renal biomarkers, serum creatinine (sCr), serum and urine cystatin C (CyC), neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), transforming growth factor beta-1 (TGF-β1), retinol-binding protein (RBP), and microalbuminuria (μALB), was analyzed in a cohort of 37 infants with congenital UTO, divided into three subgroups, 14 cases with grade III unilateral hydro(uretero)nephrosis, 13 cases with grade III bilateral hydro(uretero)nephrosis, and 10 cases with low urinary tract obstruction (LUTO), compared with 24 healthy infants matched by gestational age and birth weight. Serum and urine samples were stored at -70 °C and thereafter analyzed by quantitative enzymatic immunoassay., Results: Compared with the control group (Figure), all renal biomarker values were significantly increased in patients (P ≤ 0.02). In the unilateral hydronephrosis and LUTO group, RBP (P ≤ 0.043), NGAL (P ≤ 0.043), KIM-1 (P ≤ 0.03), and TGF-β1 (P ≤ 0.034) values dropped significantly after surgery. Neutrophil gelatinase-associated lipocalin alone and in combination with urine and serum CyC demonstrated the best performance in determining the need for surgery (area under the curve, 0.801 and 0.881, respectively). Biomarker profile analysis was suggestive of surgical intervention in 55.4% (7/13) of non-operated cases, and most of the biomarker values were above the cutoff levels within at least 3 months before the clinically based surgical decision in 58% (14/24) of all operated patients., Discussion: To the best of the authors' knowledge, this is the first study to present the clinical use of selected group of serum and urinary biomarkers in the setting of UTO to distinguish between patients who would benefit from surgery intervention. The most promising results were obtained using NGAL, RBP, TGF-β1, and KIM-1, especially in the unilateral hydro(uretero)nephrosis and LUTO subgroups when compared with the control group., Conclusions: Urine biomarkers, alone and in combination, demonstrated high potential as a non-invasive diagnostic tool for identifying infants who may benefit from earlier surgical intervention., (Copyright © 2019 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Since studies show that an unfavorable environment during intrauterine development predisposes individuals to several diseases in adulthood, our objective is to assess the relation between fetal growth restriction and chronic renal disease in adults. We searched four different electronic databases through November 2017: CENTRAL, EMBASE, LILACS and MEDLINE. We selected studies with longitudinal or transversal designs associating kidney function in adulthood with low birth weight. Two reviewers evaluated the inclusion criteria and the risk of bias and extracted data from the included papers. Thirteen studies were selected for the systematic review and meta-analysis. We observed increased risks of presenting end-stage renal disease (risk ratio 1.31, 95% confidence interval: 1.17, 1.47), a lower glomerular filtration rate (ml/min) (mean difference 7.14; 95% confidence interval: -12.12, -2.16), microalbuminuria (risk ratio 1.40; 95% confidence interval: 1.28, 1.52) and a small increase in the albumin/creatinine ratio (mean difference 0.46; 95% confidence interval: 0.03, 0.90) in the low birth weight patients, compared with control group. These findings suggest that low birth weight is associated with renal dysfunction in adults.

Objective: To evaluate whether thrombophilia worsens maternal and foetal outcomes among patients with severe preeclampsia (PE)., Method: From October 2009 to October 2014, an observational retrospective cohort study was performed on pregnant women with severe PE diagnosed before 34 weeks of gestation and their newborns hospitalized at the Clinics Hospital, FMUSP. Patients who had no heart disease, nephropathies, pre-gestational diabetes, gestational trophoblastic disease, foetal malformation, or twin pregnancy and who underwent thrombophilia screening during the postnatal period were included. New pregnancies of the same patient; cases of foetal morphological, genetic, or chromosomal abnormalities after birth; and women who used heparin or acetylsalicylic acid during pregnancy were excluded. Factor V Leiden, G20210A prothrombin mutation, antithrombin, protein C, protein S, homocysteine, lupus anticoagulant, and anticardiolipin IgG and IgM antibodies were analysed. The groups with and without thrombophilia were compared regarding their maternal clinical and laboratory parameters and perinatal outcomes., Results: Of the 127 patients selected, 30 (23.6%) had thrombophilia (hereditary or acquired). We found more white patients in thrombophilia group (p = .036). Analysis of maternal parameters showed a tendency of thrombophilic women to have more thrombocytopenia (p = .056) and showed worsening of composite laboratory abnormalities (aspartate aminotransferase ≥ 70 mg/dL, alanine aminotransferase ≥ 70 mg/dL, platelets < 100,000/mm 3 , serum creatinine ≥ 1.1 mg/dL; p = .017). There were no differences in foetal perinatal outcomes., Conclusion: The presence of thrombophilia leads to worsening of maternal laboratory parameters among patients with severe forms of PE but without worsening perinatal outcomes., (Copyright © 2018 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Objectives: To describe the perinatal outcomes of type II and III selective fetal growth restriction (sFGR) in monochorionic-diamniotic (MCDA) twin pregnancies treated with expectant management or laser ablation of placental vessels (LAPV)., Methods: Retrospective analysis of cases of sFGR that received expectant management (type II, n=6; type III, n=22) or LAPV (type II, n=30; type III, n=9). The main outcomes were gestational age at delivery and survival rate., Results: The smaller fetus presented an absent/reversed "a" wave in the ductus venosus (arAWDV) in all LAPV cases, while none of the expectant management cases presented arAWDV. The median gestational age at delivery was within the 32nd week for expectant management (type II and III) and for type II LAPV, and the 30th week for type III LAPV. The rate of at least one twin alive at hospital discharge was 83.3% and 90.9% for expectant management type II and III, respectively, and 90% and 77.8% for LAPV type II and III, respectively., Conclusion: LAPV in type II and III sFGR twins with arAWDV in the smaller fetus seems to yield outcomes similar to those of less severe cases that received expectant management.

Objective: To verify whether the use of the T-piece resuscitator compared with the self-inflating bag in preterm infants ventilated at birth modifies survival to hospital discharge without major morbidities., Design: Pragmatic prospective cohort study., Setting: 20 Brazilian university hospitals of Brazilian Network on Neonatal Research. Patients were 1962 inborn infants in 2014-2015 ventilated at birth with 23-33' weeks gestation and birth weight 400-1499 g without malformations. Patients transferred until the 27th day after birth were excluded., Interventions: Positive pressure ventilation at birth with T-piece resuscitator or self-inflating bag without positive end expiratory pressure valve. Intervention with ventilation followed the Brazilian Society of Pediatrics guidelines. The choice of the equipment was at the neonatologist's discretion in each delivery. The main outcome measures were survival to hospital discharge without bronchopulmonary dysplasia, severe peri-intraventricular haemorrhage and periventricular leucomalacia. Logistic regression adjusted for confounding variables was applied for main outcome., Results: 1456 (74%) were only ventilated with T-piece resuscitator and 506 (26%) with the self-inflating bag. The characteristics of those ventilated with T-Piece resuscitator versus self-inflating bag were birth weight 969 ± 277 vs 941 ± 279 g, gestational age 28.2±2.5 vs 27.8±2.7 weeks and survival to hospital discharge without major morbidities 47% vs 35%. Logistic regression adjusted for maternal characteristics, obstetric and neonatal morbidities showed that the T-piece resuscitator increased the chance of survival to hospital discharge without major morbidities (OR=1.38; 95% CI 1.06 to 1.80; Hosmer-Lemeshow goodness of fit: 0.695)., Conclusion: This study is the first that highlights the effectiveness of T-piece resuscitator ventilation in improving relevant outcomes in preterm neonates., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objective: The purpose of this study was to investigate the use of vaginal progesterone for the prevention of preterm delivery in twin pregnancies., Study Design: We conducted a prospective, randomized, double-blind, placebo-controlled trial that involved 390 naturally conceived twin pregnancies among mothers with no history of preterm delivery who were receiving antenatal care at a single center. Women with twin pregnancies between 18 and 21 weeks and 6 days' gestation were assigned randomly to daily vaginal progesterone (200 mg) or placebo ovules until 34 weeks and 6 days' gestation. The primary outcome was the difference in mean gestational age at delivery; the secondary outcomes were the rate of spontaneous delivery at <34 weeks' gestation and the rate of neonatal composite morbidity and mortality in the treatment and nontreatment groups., Results: The baseline characteristics were similar in both groups. The final analysis included 189 women in the progesterone group and 191 in the placebo group. No difference (P = .095) in the mean gestational age at delivery was observed between progesterone (35.08 ± 3.19 [SD]) and placebo groups (35.55 ± 2.85). The incidence of spontaneous delivery at <34 weeks' gestation was 18.5% in the progesterone group and 14.6% in the placebo group (odds ratio, 1.32; 95% confidence interval, 0.24-2.37). No difference in the composite neonatal morbidity and mortality was observed between the progesterone (15.5%) and placebo (15.9%) groups (odds ratio, 1.01; 95% confidence interval, 0.58-1.75)., Conclusion: In nonselected twin pregnancies, vaginal progesterone administration does not prevent preterm delivery and does not reduce neonatal morbidity and death., (Copyright © 2015 Elsevier Inc. All rights reserved.)