Neurodevelopment outcomes in the first 5 years of the life of children with transposition of the great arteries surgically corrected in the neonatal period: systematic review and meta-analysis.

OBJECTIVES: In patients with transposition of the great arteries, surgical correction may achieve definitive treatment, so a thorough knowledge of the long-term outcomes, particularly neurodevelopment outcomes, is essential. Therefore, we conducted a systematic review and meta-analysis to study the neurodevelopment outcomes in the first 5 years of the life of children submitted to corrective surgery for transposition of the great arteries in the neonatal period. METHODS: A total of 17 studies from 18 reports were included, assessing 809 individuals with surgically corrected transposition of the great arteries. The neurodevelopmental outcomes were assessed with the Bayley Scales of Infant and Toddler Development (BSID) and the Wechsler Intelligence Scale for Children (WISC). RESULTS: Mean Mental Development Index (MDI) and Psychomotor Development Index (PDI) were within the average values from 1 to 3 years of age, although the proportion of children scoring more than 1 standard deviation below the mean in PDI, MDI, motor, and language composite scores was significantly higher than in the general population. From 4 to 5 years, mean full-scale global intelligence quotient (IQ), verbal IQ, and performance IQ scores did not differ significantly from the general population. CONCLUSION: This study revealed neurodevelopment scores within the normal range at 5 years of age in children submitted to corrective surgery for transposition of the great arteries in the neonatal period. However, these early outcomes may not adequately predict long-term outcomes. Further studies are needed to identify specific risk factors and early markers of later impairment to guide the establishment of early interventions.

Genetic Modulation of the Erythrocyte Phenotype Associated with Retinopathy of Prematurity-A Multicenter Portuguese Cohort Study.

The development of retinopathy of prematurity (ROP) may be influenced by anemia or a low fetal/adult hemoglobin ratio. We aimed to analyze the association between DNA methyltransferase 3 ß (DNMT3B) (rs2424913), methylenetetrahydrofolate reductase (MTHFR) (rs1801133), and lysine-specific histone demethylase 1A (KDM1A) (rs7548692) polymorphisms, erythrocyte parameters during the first week of life, and ROP. In total, 396 infants (gestational age < 32 weeks or birth weight < 1500 g) were evaluated clinically and hematologically. Genotyping was performed using a MicroChip DNA on a platform employing iPlex MassARRAY®. Multivariate regression was performed after determining risk factors for ROP using univariate regression. In the group of infants who developed ROP red blood cell distribution width (RDW), erythroblasts, and mean corpuscular volume (MCV) were higher, while mean hemoglobin and mean corpuscular hemoglobin concentration (MCHC) were lower; higher RDW was associated with KDM1A (AA), MTHFR (CC and CC + TT), KDM1A (AA) + MTHFR (CC), and KDM1A (AA) + DNMT3B (allele C); KDM1A (AA) + MTHFR (CC) were associated with higher RDW, erythroblasts, MCV, and mean corpuscular hemoglobin (MCH); higher MCV and MCH were also associated with KDM1A (AA) + MTHFR (CC) + DNMT3B (allele C). We concluded that the polymorphisms studied may influence susceptibility to ROP by modulating erythropoiesis and gene expression of the fetal/adult hemoglobin ratio.

Complete blood count parameters as biomarkers of retinopathy of prematurity: a Portuguese multicenter study.

PURPOSE: To evaluate complete blood count (CBC) parameters in the first week of life as predictive biomarkers for the development of retinopathy of prematurity (ROP). METHODS: Multicenter, prospective, observational study of a cohort of preterm infants born with gestational age (GA) < 32 weeks or birth weight < 1500 g in eight Portuguese neonatal intensive care units. All demographic, clinical, and laboratory data from the first week of life were collected. Univariate logistic regression was used to assess risk factors for ROP and then multivariate regression was performed. RESULTS: A total of 455 infants were included in the study. The median GA was 29.6 weeks, and the median birth weight was 1295 g. One hundred and seventy-two infants (37.8%) developed ROP. Median values of erythrocytes (p < 0.001), hemoglobin (p < 0.001), hematocrit (p < 0.001), mean corpuscular hemoglobin concentration (p < 0.001), lymphocytes (p = 0.035), and platelets (p = 0.003) of the group of infants diagnosed with ROP any stage were lower than those without ROP. Mean corpuscular volume (MCV) (p = 0.044), red blood cell distribution width (RDW) (p < 0.001), erythroblasts (p < 0.001), neutrophils (p = 0.030), neutrophils-lymphocytes ratio (p = 0.028), and basophils (p = 0.003) were higher in the ROP group. Higher values of MCV, erythroblasts, and basophils remained significantly associated with ROP after multivariate regression. CONCLUSION: In our cohort, the increase in erythroblasts, MCV, and basophils in the first week of life was significantly and independently associated with the development of ROP. These CBC parameters may be early predictive biomarkers for ROP.

Platelet transfusions in preterm infants: current concepts and controversies-a systematic review and meta-analysis.

Platelet transfusions (PTx) are the principal approach for treating neonatal thrombocytopenia, a common hematological abnormality affecting neonates, particularly preterm infants. However, evidence about the outcomes associated with PTx and whether they provide clinical benefit or harm is lacking. The aim of this systematic review and meta-analysis is to assess the association between PTx in preterm infants and mortality, major bleeding, sepsis, and necrotizing enterocolitis (NEC) in comparison to not transfusing or using different platelet count thresholds for transfusion. A broad electronic search in three databases was performed in December 2022. We included randomized controlled trials, and cohort and case control studies of preterm infants with thrombocytopenia that (i) compared treatment with platelet transfusion vs. no platelet transfusion, (ii) assessed the platelet count threshold for PTx, or (iii) compared single to multiple PTx. We conducted a meta-analysis to assess the association between PTx and mortality, intraventricular hemorrhage (IVH), sepsis, and NEC and, in the presence of substantial heterogeneity, leave-one-out sensitivity analysis was performed. We screened 625 abstracts and 50 full texts and identified 18 reports of 13 eligible studies. The qualitative analysis of the included studies revealed controversial results as several studies showed an association between PTx in preterm infants and a higher risk of mortality, major bleeding, sepsis, and NEC, while others did not present a significant relationship. The meta-analysis results suggest a significant association between PTx and mortality (RR 2.4, 95% CI 1.8-3.4; p < 0.0001), as well as sepsis (RR 4.5, 95% CI 3.7-5.6; p < 0.0001), after a leave-one-out sensitivity analysis. There was also found a significant correlation between PTx and NEC (RR 5.2, 95% CI 3.3-8.3; p < 0.0001). As we were not able to reduce heterogeneity in the assessment of the relationship between PTx and IVH, no conclusion could be taken.    Conclusion: Platelet transfusions in preterm infants are associated to a higher risk of death, sepsis, and NEC and, possibly, to a higher incidence of IVH. Further studies are needed to confirm these associations, namely between PTx and IVH, and to define the threshold from which PTx should be given with less harm effect. What is Known: • Platelet transfusions are given to preterm infants with thrombocytopenia either to treat bleeding or to prevent hemorrhage. • Lack of consensual criteria for transfusion. What is New: • A significant association between platelet transfusions and mortality, sepsis, and NEC.

Prevalence, risk factors and predictors of severity of neonatal thrombocytopenia in neonatal Intensive Care Units: a single center study.

BACKGROUND: Thrombocytopenia is a common hematological disorder seen in the neonatal period, especially in newborns admitted to the Neonatal Intensive Care Unit (NICU). The clinical and laboratorial presentation is heterogeneous, with different underlying causes and risk factors. There are still few studies about some possible risk factors and their influence on the newborn's clinical outcome. The aim of this study was to assess the prevalence, risk factors and predictors of severity of thrombocytopenia in a level III NICU. METHODS: The present analysis was the retrospective study of newborns with thrombocytopenia (platelet count less than 150×109/L) admitted from January 1, 2008, to December 31, 2017. Patients included newborns admitted after the first 72 hours of life and those with thrombocytopenia related to surgical intervention were excluded. RESULTS: Out of 187 neonates with thrombocytopenia, a total of 134 neonates were included in the study, corresponding to a prevalence of 3.3%. One hundred fourteen (85%) neonates had an early onset presentation (EOT), and 20 (15%) neonates had a late onset presentation (LOT); 68 (50.7%) neonates had severe and 66 (49.3%) had non-severe thrombocytopenia. Sepsis was identified as an independent predictor of LOT. Sepsis by gram-negative bacteria was identified as an independent predictor for severe thrombocytopenia. CONCLUSIONS: Identification of risk factors, early diagnosis and treatment of the underlying causes are crucial for a better approach of neonatal thrombocytopenia. A strong association between sepsis and sepsis by gram-negative bacteria with LOT and severe thrombocytopenia, respectively, enhances the importance of nosocomial sepsis control in NICU.

A maternal age of 35 years and over may increase the risk for cystic periventricular leukomalacia in very preterm infants.

BACKGROUND: Some studies have shown increased risk for neonatal morbidity and mortality with increasing maternal age. The aim of this study was to assess the influence of a maternal age of 35 years, and older, on the neonatal morbidities and mortality of very preterm infants. METHODS: Obstetrical and neonatal data on mothers and preterm infants with gestational age 24 to 30 weeks, born during 2015 and 2016 after a surveilled pregnancy at 11 Portuguese level III centers were analyzed according to a mother's age <35 years versus ≥35. Statistical analysis was performed using IBM SPSS statistics 23 (IBM, Armonk, NY, USA) and a P value <0.05 was considered significant. RESULTS: A total of 415 mothers and 499 infants were included; 340 (68.1%) infants were delivered to mothers <35 years old and 159 (31.9%) to mothers ≥35. There were no differences in birthweight, gestational age and gender in both groups of preterm infants. Rupture of membranes over 18 hours and chronic hypertension with superimposed preeclampsia were significantly more frequent in mothers ≥35 years. Cystic periventricular leukomalacia (cPVL) assessed by cranial ultrasound was significantly more prevalent in infants delivered to mothers ≥35 years. The multivariate analysis by logistic regression revealed an association between cPVL and a maternal age ≥35 years (OR=2.34, 95% CI: 1.20-4.54; P=0.012). CONCLUSIONS: Our study revealed a significant association between a maternal age ≥35 years and echographic cPVL in preterm infants below 30 weeks of gestational age.

Neonatal outcomes of multiple versus single very preterm infants.

BACKGROUND: Neonatal morbidity and mortality differ between very preterm infants that result from single and those that result from a multiple order pregnancy. The aim of our study was to assess and compare the neonatal morbidity and mortality of multiple versus single very preterm infants. METHODS: Obstetrical and neonatal data on mothers and preterm infants with gestational ages between 24 and 30 weeks, born during 2015 and 2016 at 11 level III perinatal centers after a surveilled pregnancy, were analyzed and compared. Statistical analysis was performed using IBM SPSS® statistics 25 and a p-value < 0.05 was considered statistically significant. RESULTS: A total of 494 infants delivered from 410 women were enrolled in the study; 320 (64.8%) infants resulted from single gestation and 174 (35.2%) resulted from multiple order gestation (153 double, 21 triple). Multiples were associated with a higher maternal age, a greater use of medically assisted reproduction techniques, higher C-section rates, more frequent full cycle use of antenatal corticosteroids, higher gestational age with adequate birth weight, spent less days on oxygen therapy, presented less prevalence of BPD and cPVL, needed less surgical closure of PDA and had a lower length of stay in NICU. Abruptio placenta, hypertensive disorders of pregnancy and preeclampsia were more frequent in single pregnancies. The multivariate analysis by logistic regression adjusted to gestational age and confounding variables did not show any significant difference on the outcomes of multiples compared to singles. CONCLUSIONS: The results of our study support the scientific evidence that, with the current practices, the neonatal morbidity and mortality of very premature infants are not different between those resulting from single and multiple gestations.

Non-pharmacological management of neonatal pain: a systematic review.

INTRODUCTION: Shortly after birth, neonates are exposed to several painful medical procedures, such as newborn metabolic screening, vaccination and venipuncture, without proper management of pain. Unpleasant experiences during the neonatal period are proven to be associated with negative long-term consequences. Non-pharmacological interventions have been studied, although rarely administered and seldom documented. The aim of this systematic review was to assess non-pharmacological approaches to neonatal pain during diagnostic and treatment procedures. EVIDENCE ACQUISITION: Extensive literature research to access randomized controlled trials on non-pharmacological pain management in neonates was performed in MEDLINE (through PubMed), Scopus and Web of Science from October 2011 to September 2021. First analysis included all article titles and abstracts screening to identify relevant studies, and second analysis included a full-text screening of previously selected studies. Eligibility was assessed independently by two authors, and disagreements were resolved by discussion and consensus. In the end, 19 published studies were included, representing a total of 1930 newborns. Main outcome, neonatal pain, was assessed by different neonatal pain evaluation scales. EVIDENCE SYNTHESIS: Non-pharmacological interventions including sucrose/glucose solutions, non-nutritive sucking, breastfeeding, olfactive stimulus, auditory stimulus and sensory stimulus (skin-to-skin care, kangaroo/maternal holding, heat, therapeutic massage, swaddling/facilitated tucking and acupressure) showed decreased behavioral and physiologic pain responses. CONCLUSIONS: Evidence suggests non-pharmacological approaches are safe, effective and can be easily applied in daily practice. There is the need for continued research on non-pharmacological interventions on neonatal pain to help healthcare providers build a tailored pain treatment plan for neonates submitted to procedural pain.

Retinopathy of prematurity: A review of pathophysiology and signaling pathways.

Retinopathy of prematurity (ROP) is a vasoproliferative disorder of the retina and a leading cause of visual impairment and childhood blindness worldwide. The disease is characterized by an early stage of retinal microvascular degeneration, followed by neovascularization that can lead to subsequent retinal detachment and permanent visual loss. Several factors play a key role during the different pathological stages of the disease. Oxidative and nitrosative stress and inflammatory processes are important contributors to the early stage of ROP. Nitric oxide synthase and arginase play important roles in ischemia/reperfusion-induced neurovascular degeneration. Destructive neovascularization is driven by mediators of the hypoxia-inducible factor pathway, such as vascular endothelial growth factor and metabolic factors (succinate). The extracellular matrix is involved in hypoxia-induced retinal neovascularization. Vasorepulsive molecules (semaphorin 3A) intervene preventing the revascularization of the avascular zone. This review focuses on current concepts about signaling pathways and their mediators, involved in the pathogenesis of ROP, highlighting new potentially preventive and therapeutic modalities. A better understanding of the intricate molecular mechanisms underlying the pathogenesis of ROP should allow the development of more effective and targeted therapeutic agents to reduce aberrant vasoproliferation and facilitate physiological retinal vascular development.

Comparison Between Continuous Positive Airway Pressure and High-Flow Nasal Cannula as Postextubation Respiratory Support in Neonates: A Systematic Review and Meta-Analysis.

OBJECTIVE: The interest in noninvasive respiratory support has been increasing, including continuous positive airway pressure and recent respiratory methods, namely high-flow nasal cannula. It is discussed if high-flow nasal cannula can reduce continuous positive airway pressure or invasive ventilation use. This systematic review and meta-analysis aimed to compare continuous positive airway pressure and high-flow nasal cannula as postextubation respiratory support in neonates. MATERIALS AND METHODS: A literature search, based on Preferred Reporting of Items of Systematic Reviews and Meta-Analyses guidelines, was conducted across MEDLINE (through PubMed), Scopus, and Web of Science in 15 years (2006-2021) assessing randomized controlled trials that compared continuous positive airway pressure with high-flow nasal cannula as postextubation interventions in neonates. The primary outcome was extubation failure at 72 hours and/or at 7 days and the secondary outcomes included air leak syndrome, pneumothorax, bronchopulmonary dysplasia, nasal trauma, abdominal distension, and mortality. RESULTS: Seven studies were included, comprising 1044 neonates. No statistically significant differences were found between high-flow nasal cannula and continuous positive airway pressure in extubation failure (at 72 hours and 7 days), air leak syndrome, pneumothorax, bronchopulmonary dysplasia, abdominal distension, and mortality. High-flow nasal cannula was associated with a lower incidence of nasal trauma (odds ratio = 0.21; 95% CI 0.08-0.52; P = .0008). Studies assessing extreme premature infants (<28 weeks) raised some efficacy and safety concerns. CONCLUSION: High-flow nasal cannula may be as effective and safe as continuous positive airway pressure, with similar extubation failure and risk of air leak syndrome, pneumothorax, bronchopulmonary dysplasia, abdominal distension, and mortality with the advantage of less nasal trauma. High-flow nasal cannula should be considered as an alternative to continuous positive airway pressure in postextubation settings in neonates. Further studies are needed to establish efficacy and safety in lower gestational ages.

Retinopathy of prematurity: contribution of inflammatory and genetic factors.

Retinopathy of prematurity (ROP) is a retinal vasoproliferative disorder that represents an important cause of childhood visual impairment and blindness. Although oxidative stress has long been implicated in ROP etiology, other prenatal and perinatal factors are also involved. This review focuses on current research involving inflammation and genetic factors in the pathogenesis of ROP. Increasing evidence suggests that perinatal inflammation or infection contributes to ROP pathogenesis. Cytokines and chemokines with a fundamental role in inflammatory responses and that significantly contributing to angiogenesis are analyzed. Microglia cells, the retinal-resident macrophages, are crucial for retinal homeostasis, however, under sustained pathological stimuli release exaggerated amounts of inflammatory mediators and can promote pathological neovascularization. Current modulation of angiogenic cytokines, such as treatment with antibodies to vascular endothelial growth factor (anti-VEGF), has shown efficacy in the treatment of ocular neovascularization; however, some patients are refractory to anti-VEGF agents, suggesting that other angiogenic or anti-angiogenic cytokines need to be identified. Much evidence suggests that genetic factors contribute to the phenotypic variability of ROP. Several studies have implicated the involvement of candidate genes from different signaling pathways in the development of ROP. However, a genetic component with a major impact on ROP has not yet been discovered. Most studies have limitations and did not replicate results. Future research involving bioinformatics, genomics, and proteomics may contribute to finding more genes associated with ROP and may allow discovering better solutions in the management and treatment of ROP.

Extrauterine growth restriction at discharge in very-low-birth weight infants: a retrospective study in a level III neonatal intensive care unit.

BACKGROUND: Extrauterine growth restriction (EUGR) remains a serious problem among very low birth weight (VLBW) infants and is a marker of severe nutritional deficit during the first weeks of life. It can lead to a higher risk of growth impairment during childhood and long-term medical problems. The aim of this study is to determine the prevalence and risk factors of EUGR in preterm infants below 1500 grams. METHODS: Descriptive retrospective study of all preterm infants with birth weight below 1500 grams who were born at and discharged from our center, from January 1st, 2012 to December 31st, 2016. Those with major congenital malformations, congenital TORCH infections, death before 36 weeks of postmenstrual age and those transferred during hospitalization were excluded. RESULTS: A total of 101 VLBW newborns were studied, 35 (34.7%) had EUGR. Fifty-four (52.9%) newborns were male. The median gestational age was 29 weeks (25-35) and the median birth weight was 1205 grams (580-1500). Fetal growth restriction, moderate-severe bronchopulmonary dysplasia, invasive mechanical ventilation, patent ductus arteriosus and its surgical treatment, retinopathy of prematurity, cystic periventricular leukomalacia, anemia requiring red blood cells transfusions, as well as duration of parenteral nutrition, day of start of enteral nutrition (EN), day of achievement of full EN and a longer duration of hospitalization were identified as independent risk factors for EUGR. CONCLUSIONS: EUGR is a serious concern in neonatal intensive care. Some of its potential long-term consequences include a higher risk of growth impairment during childhood, poorer neurodevelopment and motor outcomes, as well as cardiovascular disease and type II diabetes later in life. Therefore, it is necessary to carefully assess the nutritional status of VLBW infants, as well as to increase the knowledge of the risk factors for EUGR, which will be crucial for its prevention.

Patent ductus arteriosus in preterm newborns: A tertiary hospital experience.

INTRODUCTION: Patent ductus arteriosus (PDA) in preterm infants has been associated with increased mortality and comorbidities. This study aimed to characterize the population of preterm infants diagnosed with PDA and to identify predictive factors of response to medical treatment of PDA. METHODS: An eight-year retrospective observational study was carried out, which included all preterm infants with a gestational age (GA) between 23 and 32 weeks diagnosed with PDA, admitted to the Neonatal Unit of the CHUSJ. Univariate comparative analysis was performed, and models for predicting the effectiveness of PDA treatment with ibuprofen were explored by multivariate logistic regression analysis. RESULTS: 115 cases were included and 34 were excluded, with a final sample of 81 preterm infants with PDA. The univariate analysis revealed significant differences in the closure efficacy via medical treatment with ibuprofen in several variables, and a multivariate logistic regression model was obtained (discriminative capacity 72.2%, sensitivity 98.1%, specificity 57.1%), taking into account the effect of GA, type of delivery, need for diuretics treatment and platelet transfusion. CONCLUSION: This study enabled the population of preterm infants diagnosed with PDA to be characterized and the identification of a predictive model that can help predict the efficacy of medical treatment and thus contribute to optimizing the medical approach to the non-responders.

Assessment of a score's performance in predicting positive culture studies in preterm neonates with clinical suspicion of sepsis.

The goal of this study is to assess the use of a score composed of markers of inflammation and organ failure to predict positive cultures for preterm newborns with clinical suspicion of late-onset sepsis. The score was calculated at the first suspicion and 24-48 hours later. We retrospectively compared score results between neonates with positive and negative cultures. Neonates with positive cultures had a significantly higher score at the second instance; the receiver operator characteristics curve presented an area under the curve of 0.798 (p=0.007). A score for early prediction of sepsis could be an important tool for prognostic improvement in the future.

Nephrotoxicity in Neonates.

Acute kidney injury (AKI) is classified based on prerenal, intrinsic, and postrenal causes. In the newborn, AKI can occur after an insult during the prenatal, perinatal, or postnatal period. AKI is usually an underrecognized condition and its true incidence is unknown. AKI may result from the administration of a number of different nephrotoxic medications, which are often used concurrently in critically ill neonates, exponentially increasing the risk of renal injury. Drug toxicity may also compromise the formation and development of nephrons, and this is particularly important in preterm infants, who have incomplete nephrogenesis. Little is known about the pharmacokinetics and pharmacodynamics of different medications used in neonates, especially for the most immature infant, and the use of most medications in this population is off label. Strategies to prevent AKI include the avoidance of hypotension, hypovolemia, fluid imbalances, hypoxia, and sepsis as well as judicious use of nephrotoxic medications. Treatment strategies aim to maintain fluids and electrolytic and acid-base homeostasis, along with an adequate nutritional status. Neonates are especially prone to long-term sequelae of AKI and benefit from long-term follow-up. This review summarizes the most relevant aspects of nephrotoxicity in neonates and describes the prevention, treatment, and follow-up of AKI in neonates.

The Role of Nutrition in the Prevention and Management of Bronchopulmonary Dysplasia: A Literature Review and Clinical Approach.

Bronchopulmonary dysplasia (BPD) remains the most common severe complication of preterm birth, and nutrition plays a crucial role in lung growth and repair. A practical nutritional approach for infants at risk of BPD or with established BPD is provided based on a comprehensive literature review. Ideally, infants with BPD should receive a fluid intake of not more than 135-150 mL/kg/day and an energy intake of 120-150 kcal/kg/day. Providing high energy in low volume remains a challenge and is the main cause of growth restriction in these infants. They need a nutritional strategy that encompasses early aggressive parenteral nutrition and the initiation of concentrated feedings of energy and nutrients. The order of priority is fortified mother's own milk, followed by fortified donor milk and preterm enriched formulas. Functional nutrient supplements with a potential protective role against BPD are revisited, despite the limited evidence of their efficacy. Specialized nutritional strategies may be necessary to overcome difficulties common in BPD infants, such as gastroesophageal reflux and poorly coordinated feeding. Planning nutrition support after discharge requires a multidisciplinary approach to deal with multiple potential problems. Regular monitoring based on anthropometry and biochemical markers is needed to guide the nutritional intervention.

Neonatal Atypical Hemolytic Uremic Syndrome in the Eculizumab Era.

The atypical hemolytic uremic syndrome (aHUS) in the newborn is a rare disease, with high morbidity. Eculizumab, considered a first-line drug in older children, is not approved in neonates and in children weighing less than 5 kg. We present a 5-day-old female newborn, born at 36 weeks' twin gestation, by emergency cesarean section due to cord prolapse, with birth weight of 2,035 g and Apgar score of 7/7/7, who develops microangiopathic hemolytic anemia, thrombocytopenia, and progressive acute renal failure. In day 5, after diagnosis of aHUS, a daily infusion of fresh frozen plasma begins, with improvement of thrombocytopenia and very slight improvement in renal function. The etiologic study (congenital infection, Shiga toxin, ADAMTS13 activity, directed metabolic study) was normal. C3c was slightly decreased. On day 16 for maintenance of anemia and severe renal failure, she started 300 mg/dose eculizumab. Anemia resolves in 10 weeks and creatinine has normal values after 13 weeks of treatment. The genetic study was normal. In this case, eculizumab is effective in controlling microangiopathy and in the recovery of renal function. Diagnosis of neonatal aHUS can be challenging because of phenotypic heterogeneity and potential overlap with other manifestations that may confound it, such as perinatal asphyxia or sepsis/disseminated intravascular coagulation.

Multisystem inflammatory syndrome in children (MISC): A systematic review.

OBJECTIVE: The aim of this systematic review was to analyse current literature and reported cases of multisystem inflammatory syndrome in children (MISC), concerning its clinical spectrum, complications associated, therapeutic strategies and distinguishing features of other clinical syndromes. METHODS: Extensive literature research was performed in MEDLINE (through PubMed), Scopus and Web of Science from December 2019 to December 2020. First analysis included all article titles and abstracts screening to identify relevant studies, and second analysis included a full-text screening of previously selected studies. Eligibility was assessed independently by two authors, and disagreements were resolved by discussion and consensus. Data were extracted on MISC definition, demographic data, clinical features, diagnostic tests, laboratory analysis and imaging, therapeutical approach and outcomes. RESULTS: Common symptoms included gastrointestinal (70%), rash (57%) and cardiovascular (52% with shock). Notable differences with Kawasaki disease were identified including age, clinical presentation and cardiac involvement. Thirty per cent presented positive severe acute respiratory syndrome coronavirus-2 reverse transcription polymerase chain reaction and 51% positive serologies. Sixty-two per cent received intravenous immunoglobulin and 42% glucocorticoids. Sixty-two per cent required intensive care and 21 children died (<2%). Severe presentations were associated with neurological symptoms, hepatitis and acute kidney injury. CONCLUSIONS: MISC raises concern on its severe cardiac involvement at presentation, with frequent intensive care and immunomodulatory therapy need. Short-term outcomes seem to be favourable, with cardiac dysfunction recovery and low mortality rates.

Massive sacrococcygeal teratoma in a preterm infant.

In extreme preterm infants, massive congenital sacrococcygeal teratomas with great hemodynamic commitment may be a situation for limitation of care.

Renal Dysplasia and Progressive Renal Failure in a Newborn with Interstitial Chromosome 4 Deletion 4q25-28.3: A New Phenotype?

The deletion of the long arm of chromosome 4 is rare, presenting with a variable phenotype depending on the chromosomic area affected. A term newborn with prenatal diagnosis of anhydramnios, dysplastic cystic kidneys, and cardiomegaly was born with generalized subcutaneous edema, several dysmorphic features, and progressive renal failure requiring dialysis. The infant continued to deteriorate and died at 52 days of age. Autopsy confirmed bilateral renal dysplasia with cysts. Array-comparative genomic hybridization (CGH) identified a large deletion on 4q25-q28.3, which is not yet described in association with renal disease. The clinical progression could be expected due to the severity of the perinatal clinical presentation.