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.

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.

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.

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.

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.

Risk Factors and Outcomes of Tetralogy of Fallot: From Fetal to Neonatal Life.

Tetralogy of Fallot (ToF) is the most prevalent cyanotic congenital heart disease. Genetic syndromes are present in up to one quarter of patients with this condition, leading to increased morbidity and mortality. Our aim in this work is to characterize our population, evaluate ToF based on the presence of genotype anomalies, and investigate early intervention predictors and outcomes. A retrospective study was performed on neonates with ToF born between August 1, 2008, and August 31, 2018, and admitted to a level III neonatal intensive care unit (NICU). Patients were categorized based on the presence of genotype anomalies and timing of intervention. Thirty-nine neonates were included. The overall mortality during the follow-up period was 5.1% (n = 2). Threatened preterm labor/preterm labor was more prevalent in patients with associated genotype anomalies (p = 0.015). Multivariate analysis showed an association between an abnormal amount of amniotic fluid and ToF with altered genotype, adjusted for smoking, maternal age, gestational age and birth weight [OR = 29.92, 95% CI (1.35-662.44), p = 0.032]. We also found an association between cesarean delivery and neonatal procedures (p = 0.006). Mortality was significantly higher in neonates who underwent early intervention (p = 0.038). Our results indicate that an abnormal amount of amniotic fluid is an independent predictive factor for ToF with genotype alterations. This finding could ultimately have an impact on both prenatal and neonatal counseling and management.

Preventing bronchopulmonary dysplasia: new tools for an old challenge.

Bronchopulmonary dysplasia (BPD) is the most prevalent chronic lung disease in infants and presents as a consequence of preterm birth. Due to the lack of effective preventive and treatment strategies, BPD currently represents a major therapeutic challenge that requires continued research efforts at the basic, translational, and clinical levels. However, not all very low birth weight premature babies develop BPD, which suggests that in addition to known gestational age and intrauterine and extrauterine risk factors, other unknown factors must be involved in this disease's development. One of the main goals in BPD research is the early prediction of very low birth weight infants who are at risk of developing BPD in order to initiate the adequate preventive strategies. Other benefits of determining the risk of BPD include providing prognostic information and stratifying infants for clinical trial enrollment. In this article, we describe new opportunities to address BPD's complex pathophysiology by identifying prognostic biomarkers and develop novel, complex in vitro human lung models in order to develop effective therapies. These therapies for protecting the immature lung from injury can be developed by taking advantage of recent scientific progress in -omics, 3D organoids, and regenerative medicine.

Effect of allopurinol in addition to hypothermia treatment in neonates for hypoxic-ischemic brain injury on neurocognitive outcome (ALBINO): study protocol of a blinded randomized placebo-controlled parallel group multicenter trial for superiority (phase III).

BACKGROUND: Perinatal asphyxia and resulting hypoxic-ischemic encephalopathy is a major cause of death and long-term disability in term born neonates. Up to 20,000 infants each year are affected by HIE in Europe and even more in regions with lower level of perinatal care. The only established therapy to improve outcome in these infants is therapeutic hypothermia. Allopurinol is a xanthine oxidase inhibitor that reduces the production of oxygen radicals as superoxide, which contributes to secondary energy failure and apoptosis in neurons and glial cells after reperfusion of hypoxic brain tissue and may further improve outcome if administered in addition to therapeutic hypothermia. METHODS: This study on the effects of ALlopurinol in addition to hypothermia treatment for hypoxic-ischemic Brain Injury on Neurocognitive Outcome (ALBINO), is a European double-blinded randomized placebo-controlled parallel group multicenter trial (Phase III) to evaluate the effect of postnatal allopurinol administered in addition to standard of care (including therapeutic hypothermia if indicated) on the incidence of death and severe neurodevelopmental impairment at 24 months of age in newborns with perinatal hypoxic-ischemic insult and signs of potentially evolving encephalopathy. Allopurinol or placebo will be given in addition to therapeutic hypothermia (where indicated) to infants with a gestational age ≥ 36 weeks and a birth weight ≥ 2500 g, with severe perinatal asphyxia and potentially evolving encephalopathy. The primary endpoint of this study will be death or severe neurodevelopmental impairment versus survival without severe neurodevelopmental impairment at the age of two years. Effects on brain injury by magnetic resonance imaging and cerebral ultrasound, electric brain activity, concentrations of peroxidation products and S100B, will also be studied along with effects on heart function and pharmacokinetics of allopurinol after iv-infusion. DISCUSSION: This trial will provide data to assess the efficacy and safety of early postnatal allopurinol in term infants with evolving hypoxic-ischemic encephalopathy. If proven efficacious and safe, allopurinol could become part of a neuroprotective pharmacological treatment strategy in addition to therapeutic hypothermia in children with perinatal asphyxia. TRIAL REGISTRATION: NCT03162653, www.ClinicalTrials.gov , May 22, 2017.

Hypertensive Disorders during Pregnancy and Risk of Bronchopulmonary Dysplasia in Very Preterm Infants.

INTRODUCTION: It is not yet fully known whether hypertensive disorders (HTD) during pregnancy impose an increased risk of development of bronchopulmonary dysplasia (BPD) in preterm newborn infants. OBJECTIVE: To test the hypothesis that preeclampsia and other HTD are associated with the development of BPD in preterm infants. MATERIALS AND METHODS: Data on mothers and preterm infants with gestational age 24 to 30 weeks were prospectively analyzed in 11 Portuguese level III centers. Statistical analysis was performed using IBM SPSS statistics 23. RESULTS: A total of 494 preterm infants from 410 mothers were enrolled, and 119 (28%) of the 425 babies, still alive at 36 weeks, developed BPD. The association between chronic arterial hypertension, chronic arterial hypertension with superimposed preeclampsia, and gestational hypertension in mothers and BPD in preterm infants was not significant (p = 0.115; p = 0.248; p = 0.060, respectively). The association between preeclampsia-eclampsia and BPD was significant (p = 0.007). The multivariate analysis revealed an association between preeclampsia-eclampsia and BPD (odds ratio [OR] = 4.6; 95% confidence interval [CI] 1.529-13.819; p = 0.007) and a protective effect for BPD when preeclampsia occurred superimposed on chronic arterial hypertension in mothers (OR = 0.077; 95%CI 0.009-0.632; p = 0.017). CONCLUSION: The results of this study support the association of preeclampsia in mothers with BPD in preterm babies and suggest that chronic hypertension may be protective for preterm babies.

Acute kidney injury in preterm neonates with ≤30 weeks of gestational age and its risk factors.

BACKGROUND: Acute kidney injury (AKI), an abrupt decline in kidney function, is a challenging diagnosis among preterm infants due to some specific features of this population. The aim of this study was to determine the risk factors of developing AKI and the predictive factors for its severity in preterm neonates with less than 31 weeks of gestational age. METHODS: All neonates with less than 31 weeks of gestational age, admitted in our NICU between January 2012 and December 2015, were included. Maternal and neonatal records about demographics, placental abnormalities, perinatal and neonatal period and evolution in NICU, as well as electrolytic analysis and serum creatinine and urea values during their hospitalization were retrospectively collected and analyzed. RESULTS: A total of 106 neonates were included. Of those, 24 were diagnosed with AKI, resulting in a prevalence of 22.6%, and 82 were used as controls. Gestational age (OR=0.39; 95% CI=0.2-0.76; P=0.006), congenital malformations (OR=36.93; 95%CI=2.48-550.59; P=0.009), vasoactive drugs (OR=27.06; 95%CI=3.58-204.45; P=0.001), nonsteroidal anti-inflammatory drugs (OR=9.61; 95%CI=1.78-51.73; P=0.008) and sepsis (OR=7.78; 95%CI=1.32-46.04; P=0.024) were found to be independent risk factors. Cardiac surgery was a predictive factor for AKI severity (OR=25; 95%CI=2.09-298.29; P=0.011). The mortality rate in the AKI group was 41.7%. CONCLUSIONS: AKI in preterm neonates is an important feature that contributes to increase the mortality in NICUs. Thus, it is crucial to know its risk factors to establish prompt diagnosis and prevention and, in this way, be able to improve the prognosis.

Morbidity and mortality of preterm infants less than 26 weeks of gestational age.

BACKGROUND: Extreme preterm infants have a high risk of morbidity and mortality. Newborns delivered between 23+0 and 25+6 weeks, are considered to be in the "gray zone" and have uncertain prognosis. For these children medical decision-making becomes complex and controversial. The present study intends to evaluate the neonatal morbidity and mortality of preterm infants born between 23 weeks and 25+6 weeks of gestational age. METHODS: A retrospective study was conducted including all inborn preterm infants, with a gestational age between 23+0 and 25+6 weeks, admitted to a level IIIC NICU, between January 1st, 1996 and December 31st, 2014. RESULTS: A total of 72 preterm neonates were included, 18.1% had a full cycle of antenatal steroids. The most frequent major morbidities were RDS (95.4%), patent ductus arteriosus (81.3%), sepsis (55.7%, being 19.7% early sepsis, and 36.1% late sepsis), intraventricular hemorrhage (34.4%), retinopathy of prematurity (21.9%) and necrotizing enterocolitis (10.9%). Fifty-four (75%) children died. The only factor adjusted to age associated with high mortality founded was hypotension (OR=4.99, P<0.019). Morbidity at discharge was: severe bronchopulmonary dysplasia (77.8%), retinopathy of prematurity (72.2%), intraventricular hemorrhage (16.7%), cystic periventricular leukomalacia (11.1%), and sequalae of necrotizing enterocolitis (5.6%). CONCLUSIONS: The survival rate was 25% and a high morbidity at discharge was observed, which leave us with the huge responsibility to improve this result in a near future. Extreme prematurity is still a very controversial and complex issue and particular challenge for neonatologists. The use of antenatal steroid in the more immature preterm infants should be encouraged.

Radiation exposure in very low birth weight infants.

BACKGROUND: The survival of very low birth weight (VLBW) infants increased in the past few decades. These neonates often require multiple diagnostic and management image procedures that involve ionizing radiation, which can have long term implications. The aim of our study was to evaluate the level of radiation exposure in VLBW infants during their stay in the Neonatal Intensive Care Unit (NICU). METHODS: We collected demographic and medical data of 149 VLBW who were admitted to our NICU between January 2011 and December 2014. All radiographic procedures were reviewed retrospectively. Absorbed ionizing radiation was calculated according to literature reference values. RESULTS: A total of 1496 images were obtained. Infants underwent 10.0±11.3 examinations, and the maximum of images registered per patient was 65. Four babies (2.7%) received more than 1000 µSv, the recommended maximum of ionizing radiation exposure. Infants of lower birth weight, who needed invasive ventilation, with bronchopulmonary dysplasia, sepsis, and surgical pathology required significantly more radiographs (P<0.001). CONCLUSIONS: In this study, lower birth weight, need of invasive ventilation, bronchopulmonary dysplasia and sepsis were associated with the need of more X-ray studies. In order to protect the vulnerable population of severely-ill newborns, guidelines for radiation exposure in newborns should be issued and implemented.

Respiratory morbidity in late preterm infants.

BACKGROUND: Late preterm delivery (74% of all preterm births) increases the incidence of respiratory pathology, namely respiratory distress syndrome (RDS), transient tachypnea of the newborn (TTN) and the need of ventilator support when compared to term delivery. The aim is to evaluate the respiratory morbimortality in late preterm infants and the risk factors associated with RDS and TTN. METHODS: Descriptive retrospective study of all newborns of 34+0 to 36+6 weeks of gestational age, born at our center between September 1, 2012 and August 31, 2015. Those with major malformations, chromosomopathies, hydrops fetalis and congenital TORCH infection were excluded. RESULTS: A total of 498 newborns were studied, 44 (8.83%) of them with either RDS or TTN. Respiratory morbidity was significantly associated with lower gestational age, male gender, caesarean section, exposure to peripartum antibiotics, overweighed and nulliparous mothers. RDS newborns had a significantly higher need for resuscitation, endotracheal intubation, oxygen therapy, early invasive ventilation, parenteral nutrition and a longer NICU stay when compared to newborns with TTN. 55% of the patients with RDS had 35+0 to 36+6 weeks of gestational age, moderate or severe RDS and required mechanical ventilation; six needed surfactant. Caesarean section and resuscitation with ETT were independent risk factors for respiratory morbidity. CONCLUSIONS: Late preterm remain at risk for adverse respiratory outcomes, particularly newborns delivered after 35 weeks, whose mothers are not given ACS and still have considerable morbidity. Growing evidence supports the possibility of extending the management window further into the LPT period. Caesarean section was an independent risk factor for respiratory morbidity and efforts should be undertaken to reduce the procedure rate.

Persistent grunting respirations after birth.

BACKGROUND: Grunting respirations occurring in the first hours of life is a frequent nonspecific clinical sign. Our objective was to assess the clinical significance of grunting lasting over two hours of birth in term and near term newborns. METHODS: A five years retrospective study of all newborns ≥35+0 weeks of gestational age admitted for grunting to a level III Neonatal Intensive Care Unit (NICU). RESULTS: Prolonged grunting occurred in 1.2% of the delivered newborns. Data on 151 grunter newborns and 302 controls were reviewed. Higher mother's age, pregnancy complications, lower gestational age, male gender, resuscitation need at birth, respiratory signs and therapy were associated to prolonged grunting. Poor adaptation to extrauterine life was the most frequent cause of grunting occurring in 73 (48.3%) of the cases, followed by transient tachypnea of the newborn (40 cases, 26.5%); RDS (7 cases, 4.6%) and infection (sepsis and pneumonia, 7 cases, 4.6%). Less common causes were: birth trauma (4 cases, 2.6%); pneumomediastinum (4 cases, 2.6%); hypoxic-ischemic encephalopathy (2 cases, 1.3%); polycythemia (1 case, 0.6%); anemia (1 case; 0.6%); meconium aspiration (1 case, 0.6%); congenital heart defect (1 case, 0.6%); congenital diaphragmatic hernia (1 case; 0.6%); malformation of the nose (1 case;0.6%); and immature teratoma of the thymus (1 case, 0.6%). Complications occurred in two patients (pneumothorax=1; pneumomediastinum=1). No mortality was observed. NICU stay was 5 days (1-23) CONCLUSIONS: Although persistent grunting respirations after birth follow a benign course in the majority, all affected term and near term newborns should be carefully observed and treated.

Autonomic nervous system in newborns: a review based on heart rate variability.

PURPOSE: Heart rate variability (HRV) has been a relevant tool in the assessment of the autonomic nervous system (ANS). How autonomic control normally develops in newborns and how it is affected by gestational age (GA) is not fully understood. We aimed to review the current evidence on HRV in preterm (PT) and term neonates (TN) and investigate the relation between GA and the maturation of ANS. METHODS: Electronic databases (Pubmed, World of Science, and Scopus) were searched for studies from 1997 to 2017 examining HRV (time and frequency domain) in PT and TN who followed to the Task Force (1996) guidelines. Ten studies met our inclusion criteria and were analyzed. RESULTS: An increasing postnatal age was related to a significant rise of HRV parameters. Several significant differences were established between PT and TN (lower values on PTN), also found when PTN are evaluated at their theoretical term age. In general, there were no relevant results on LF/HF (low frequency/high frequency) ratio, as being an adequate marker of sympathovagal balance, but this was not a universal finding of this review. Frequency parameters that were more often used to evaluate newborns and HF showed the most relevant increase with GA. CONCLUSIONS: HRV is an important tool to assess the maturation of ANS in newborns and there is a progressive increasing on cardiac parasympathetic activity, according to GA. HF appears as a relevant parameter in measurements of vagal maturation. HRV is higher in TN when compared with PTN and is more studied in newborns in terms of frequency domain. Standard recommendations in newborns remain to be fully defined.

Vascular access in neonates.

The aim of this review was to provide updated and recent literature on vascular access in neonates in order to help neonatologists in their clinical practice, using as data sources textbooks, recent published articles from Pubmed, Cochrane reviews and web guidelines.

Pertussis in the newborn: certainties and uncertainties in 2014.

Bordetella pertussis infection remains a serious potential health risk to infants, specially in those too young to be vaccinated. Over the recent years, numerous sources highlighted a widespread resurgence, making it, again, a challenging disease. Globally, pertussis is ranked among the 10 leading causes of childhood mortality. This review summarizes the most recent literature and will address the most important aspects that pediatricians and neonatologists must be familiar with, when treating a newborns pertussis infection.

The role of the human leukocyte antigen system in retinopathy of prematurity: a pilot study.

AIM: To assess the association between the human leukocyte antigen system and retinopathy of prematurity. METHODS: Neonates of <32 weeks of gestational age, born at two level III neonatal intensive care units from January 2000 to December 2001 and from January 2006 to June 2009, were included in the study. Demographic and clinical data were recorded, and retinopathy was classified according to the International Classification. Epithelial cells were collected from the oral cavity and the HLA were studied using the PCR/SSO method. Univariate and multivariate analyses were performed using SPSS® v.18. RESULTS: We evaluated 156 neonates, including 82 (52.6%) males. Median gestational age was 29 (23-31) weeks, and median birth weight was 1030 (525-1935) grams. Seventy (44.9%) of the neonates developed retinopathy. Alleles HLA-B*38, HLA-Cw*12, HLA-DRB1*09, HLA-DRB1*14 (univariate analysis) and HLA-A*68 and HLA-Cw*12 were associated to retinopathy (multivariate analysis). CONCLUSION: The results suggest that the HLA system may be associated with the development of retinopathy of prematurity. A large-scale population-based study should be performed to clarify this association.