Risk factors for acute kidney injury in very-low birth weight newborns: a systematic review with meta-analysis.

This study aims to analyze the main risk factors for acute kidney injury in the subgroup of very-low birth weight newborns, using the diagnosing criteria of the Kidney Disease Improving Global Outcomes (KDIGO) or the Acute Kidney Injury Network (AKIN). A systematic review of the literature was performed on the EMBASE® and PubMed® platforms. Studies that evaluated the risk factors for developing AKI in VLBW newborns were included. For the meta-analysis, we only included the risk factors that were associated with AKI in the univariate analysis of at least two studies. After an initial screening, abstract readings, and full-text readings, 10 articles were included in the systematic review and 9 in the meta-analysis. The incidence of AKI varied from 11.6 to 55.8%. All the studies have performed multivariate analysis, and the risk factors that appeared most were PDA and hemodynamic instability (use of inotropes or hypotension), sepsis, and invasive mechanical ventilation. After the meta-analysis, only cesarian delivery did not show an increased risk of AKI, all the other variables remained as important risk factors. Moreover, in our meta-analysis, we found a pooled increased risk of death in newborns with AKI almost 7 times.  Conclusion: AKI in VLBW has several risk factors and must be seen as a multifactorial disease. The most common risk factors were PDA, hemodynamic instability, sepsis, and invasive mechanical ventilation. What is known: • Acute kidney injury is associated with worst outcomes in all ages. It´s prevention can help diminish mortality. What is new: • A synthesis of the main risk factors associated with AKI in very low birth weight newborns.

Reassessing the role of milrinone in the treatment of heart failure and pulmonary hypertension in neonates and children: a systematic review and meta-analysis.

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.

Identifying two distinct subphenotypes of patent ductus arteriosus in preterm infants using machine learning.

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.

Association between fluid overload and mortality in newborns: a systematic review and meta-analysis.

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.

Identifying clinical phenotypes in extremely low birth weight infants-an unsupervised machine learning approach.

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.

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.

Limits of therapeutic intervention in a tertiary neonatal intensive care unit in patients with major congenital anomalies in Brazil.

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.

Thrombolytic therapy in preterm infants: Fifteen-year experience.

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.

Early fluid overload is associated with mortality and prolonged mechanical ventilation in extremely low birth weight infants.

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.

Kidney impairment in fetal growth restriction: three-dimensional evaluation of volume and vascularization.

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.

First-year profile of biomarkers for early detection of renal injury in infants with congenital urinary tract obstruction.

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-ß1), 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.

Sonographic Markers in the Prediction of Fetal Complex Gastroschisis.

OBJECTIVE: To investigate the ultrasound (US) markers predictive of complex gastroschisis (CG), mortality, and morbidity in fetuses with gastroschisis. MATERIALS AND METHODS: This was a retrospective cohort study of 186 pregnancies with isolated fetal gastroschisis. Eight US markers were analyzed. The predictions and associations of US markers with CG, mortality, and morbidity were assessed. Combinations of US markers predictive of CG were investigated. RESULTS: Extra-abdominal bowel dilatation (EABD), intra-abdominal bowel dilatation (IABD), and polyhydramnios were predictive of CG. EABD between 25 and 28 weeks had a sensitivity of 64%, a specificity of 89%, a positive predictive value (PPV) of 56.2%, and negative predictive value (NPV) of 91.8%. The predictions of IABD were sensitivity = 26.7%, specificity = 96.7%, PPV = 61.5%, and NPV = 86.8%. The odds ratios for CG in the presence of 1 and 2 US markers, compared with the absence of a US marker, were 18.3 (95% CI, 3.83-87.64) and 73.3 (95% CI, 6.14-876), respectively. CONCLUSION: US markers predictive of CG were established. The combination of these markers increases the probability of CG.

Short-term prognostic factors in myelomeningocele patients.

PURPOSE: Patients with myelomeningocele have a high mortality and neurological disabilities that are correlated with the anatomical characteristics of the defect and with the development of acquired complications. The challenge in the postnatal management of myelomeningocele (MMC) is the early recognition of cases at risk for complications in order to establish individualized treatment strategies. This study aims to identify short-term prognostic markers for newborns with MMC. Anatomical characteristics of the spinal defect and technical aspects of the neurosurgical correction were analyzed for this purpose. METHODS: A retrospective cohort study was conducted in 70 patients with MMC born between January 2007 and December 2013. Features of MMC anatomy and neurosurgical treatment were analyzed for the following outcomes: neonatal resuscitation, length of hospital stay, need for ventricular shunt, wound dehiscence, wound infection, central nervous system infection, and sepsis. RESULTS: Large MMC was associated with central nervous system (CNS) infection, wound complications, and longer hospital stay. Patients with thoracic MMC required longer hospital stay. Surgical repair performed after 48 h of life increased in 5.72 times the risk of CNS infection. Absence of antenatal hydrocephalus was a favorable prognostic marker. CONCLUSION: Extent of the spinal cord defect and the time of surgical correction influenced the short-term outcomes of patients with myelomeningocele. Extensive lesions were associated with higher rates of CNS infections, surgical wound complications, and prolonged hospital stay. Interventions performed within 48 h after birth significantly reduced occurrence of CNS infections. Absence of antenatal hydrocephalus was associated with fewer complications in the first days of life.

Nonimmune fetal ascites: identification of ultrasound findings predictive of perinatal death.

AIM: To determine the ultrasonographic findings that predict death in fetal ascites. METHODS: This was a retrospective cohort study involving pregnancies with ultrasonographic findings related to fetal ascites. The inclusion criteria were as follows: single pregnancy with a live fetus; ultrasound findings of ascites; ascites unrelated to maternal fetal alloimmunization; and pregnancy follow-up at our institution. The χ2-test was used to evaluate the association of ultrasound findings and death. Multiple logistic regression analysis was performed to determine the ultrasound findings that are predictive of death prior to hospital discharge. RESULTS: A total of 154 pregnancies were included in the study. In 8 (5.19%) cases, ascites was an isolated finding, and in 146 cases, other alterations were observed during the ultrasound evaluation. Death before hospital discharge occurred in 117 cases (76.00%). The following ultrasonographic findings were significantly associated with death: gestational age at diagnosis <24 weeks (P<0.0001); stable/progressive ascites evolution (P=0.004); the presence of hydrops (P<0.0001); and the presence of cystic hygroma (P<0.0001). The presence of hydrops, the presence of respiratory tract malformations, and stable/progressive ascites evolution were significantly associated with the prediction of death. CONCLUSIONS: Based on ultrasound examination, the presence of hydrops, malformation of the respiratory tract, and stable/progressive evolution of ascites increase the chances of death in cases of fetal ascites.

Vaginal progesterone for the prevention of preterm birth in twin gestations: a randomized placebo-controlled double-blind study.

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.

Factors associated with red blood cell transfusions in very-low-birth-weight preterm infants in Brazilian neonatal units.

BACKGROUND: Preterm infants in neonatal intensive care units frequently receive red blood cells (RBC) transfusions due to the anemia of prematurity. A number of variables related to gestational age, severity of illness and transfusion practices adopted in the neonatal unit where the neonate was born may contribute to the prescription of RBC transfusions. This study aimed to analyse the frequency and factors associated with RBC transfusions in very-low-birth-weight preterm infants. METHODS: A prospective cohort of 4283 preterm infants (gestational age: 29.9 ± 2.9 weeks; birth weight: 1084 ± 275 g) carried out at 16 university hospitals in Brazil between January 2009 and December 2011 was analysed. Factors associated with RBC transfusions were evaluated using univariate and multiple logistic regression analysis. RESULTS: A total of 2208 (51.6%) infants received RBC transfusions (variation per neonatal unit: 34.1% to 66.4%). RBC transfusions were significantly associated with gestational age (OR: -1.098; 95%CI: -1.12 to -1.04), SNAPPE II score (1.01; 1.00-1.02), apnea (1.69; 1.34-2.14), pulmonary hemorrhage (2.65; 1.74-4.031), need for oxygen at 28 days of life (1.56; 1.17-2.08), clinical sepsis (3.22; 2.55-4.05), necrotising enterocolitis (3.80; 2.26-6.41), grades III/IV intraventricular hemorrhage (1.64; 1.05-2.58), mechanical ventilation (2.27; 1.74-2.97), use of umbilical catheter (1.86; 1.35-2.57), parenteral nutrition (2.06; 1.27-3.33), >60 days of hospitalization (5.29; 4.02-6.95) and the neonatal unit where the neonate was born. CONCLUSIONS: The frequency of RBC transfusions varied among neonatal intensive care units. Even after adjusting for adverse health conditions and therapeutic interventions, the neonatal unit continued to influence transfusion practices in very-low birth-weight infants.

Should we measure fetal omphalocele diameter for prediction of perinatal outcome?

OBJECTIVE: To evaluate the fetal omphalocele diameter/abdominal circumference ratio (OD/AC) as a predictor of adverse perinatal outcome. METHODS: Analysis involving 47 singleton pregnancies with fetal omphalocele, normal karyotype and absence of other major abnormalities. The OD/AC ratio was determined antenatally by ultrasound and the best cutoff for the prediction of neonatal death was determined by receiver operating characteristic curve analysis. Additional secondary outcomes included need for oral intubation in the first 24 h of life, two-step surgery or use of synthetic mesh, reoperation, parenteral feeding and need for respiratory assistance >21 days, time to first oral feed, and time to hospital discharge. RESULTS: Fetal OD/AC did not change significantly with gestational age. Postnatal death occurred in 10 (21.3%) cases and the best cutoff for prediction was an OD/AC ratio ≥0.26. In pregnancies with the first ultrasound evaluation performed before 31 weeks' gestation and an OD/AC ≥0.26, the likelihood ratio for needing intubation in the first 24 h of life was 2.6 (95% CI: 1.2-5.7), needing two-step surgery or use of mesh was 4.9 (95% CI: 1.9-14.4), and postnatal death was 4 (95% CI: 1.9-7.5). CONCLUSION: A fetal ultrasound OD/AC ratio ≥0.26 is associated with increased postnatal morbidity and mortality.

Assessment of newborn neuropsychomotor development born with exposure to SARS-CoV-2 in the perinatal period using the Bayley III scale at 6 months of age.

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.

Association between Serum Lactate and Morbidity and Mortality in Neonates: A Systematic Review and Meta-Analysis.

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.

Complete blood count and C-reactive protein to predict positive blood culture among neonates using machine learning algorithms.

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.