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There is an increasing evidence that strict evaluation of clinical signs is effective in detecting newborns at risk of early-onset sepsis (EOS) that require antibiotic therapy. In a retrospective case control design, we compared EOS antibiotic indication by clinical signs surveillance with multivariate risk analysis (EOSCalc), and estimate their costs. Newborns ≥ 34 weeks who received EOS antibiotics from June 2014 to December 2016 were studied. Were considered symptomatic those with three clinical signs within first 24 h or two signs and one risk factor present. Cost estimative was done using bottom-up hospital's perspective. Eight thousand three hundred twenty-one were born, 384 were included. Two hundred nineteen (57%) would receive antibiotics by EOSCalc and 64 (16.7%) by clinical signs (p 0.001). All patients with blood cultures were detected and false-negatives were absent. Total cost was US$ 574,121, estimate US$ 415,576 by EOSCalc, and US$ 314,353 by clinical signs (p 0.001).Conclusions: The use of EOSCalc and clinical signs surveillance seem to be safe and accurate methods in EOS management. Additionally, the two approaches have shown an economic advantage when compared with the hospital's current practice. What is Known: • EOSCalc is a useful method for screening of EOS in late preterm and term infants. • Presence of clinical signs and/or maternal risk factors are present newborns with EOS. What is New: • Rigorous observation of clinical signs is a more accurate method than EOSCalc to screen for EOS in late preterm and term newborns. • Rigorous observation of clinical signs is more economic than EOSCalc in managing EOS in late preterm and term neonates.

Very preterm/very low birth weight (VP/VLBW) newborns can have lifelong morbidities, as attention-deficit/hyperactivity disorder (ADHD). Clinicians have no markers to discriminate which among those individuals will develop later ADHD, based only on the clinical presentation at birth. Our aim was to develop an individualized risk calculator for ADHD in VP/VLBW newborns.This retrospective prognostic study included a consecutive sample of all VP/VLBW children (gestational age32 weeks and/or birth weight1.5 kg) born between 2010 and 2012 from a clinical cohort in a Brazilian tertiary care hospital. Children were clinically assessed at 6 years of age for ADHD using the Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS). The least absolute shrinkage and selection operator (LASSO) method was used for model-building.Ninety-six VP/VLBW children were assessed at 6 years of age (92% follow-up), of whom 32 (33%) were diagnosed with ADHD. The area under the ROC curve (AUC) for ADHD prediction based on seven parameters (late-onset sepsis confirmed by blood culture, necrotizing enterocolitis, neonatal seizures, periventricular leukomalacia, respiratory distress syndrome, length of hospital stay, and number of maternal ADHD symptoms) was .875 (CI, 0.800-0.942, p .001; AUC corrected for optimism with bootstrapping: .806), a performance that is comparable to other medical risk calculators. Compared to approaches that would offer early intervention to all, or intervention to none, the risk calculator will be more useful in selecting VP/VLBW newborns, with statistically significant net benefits at cost:benefits of around 1:2 to around 10:6 (range of ADHD risk thresholds of 32%-62%, respectively). It also showed specificity for ADHD compared to other prevalent child psychopathologies.The risk calculator showed good performance for early identification of VP/VLBW newborns at high risk of future ADHD diagnosis. External validity in population-based samples is needed to extend clinical usefulness.

Introduction: Macrolides have anti-inflammatory and immunomodulatory properties that give this class of antibiotics a role that differs from its classical use as an antibiotic, which opens new therapeutic possibilities. Objective: The aim of this study was to evaluate the anti-inflammatory effect of azithromycin in preventing mechanical ventilation (MV)-induced lung injury in very-low-birth-weight preterm neonates. Methods: This is a randomized, double-blind, placebo-controlled trial of preterm neonates who received invasive MV within 72 h of birth. Patients were randomized to receive intravenous azithromycin (at a dose of 10/mg/kg/day for 5 days) or placebo (0.9% saline) within 12 h of the start of MV. Two blood samples were collected (before and after intervention) for measurement of interleukins (ILs) and PCR for Ureaplasma. Patients were followed up throughout the hospital stay for the outcomes of death and broncho­pulmonary dysplasia defined as need for oxygen for a period of ≥28 days of life (registered at ClinicalTrials.gov, No. NCT03485703). Results: Forty patients were analyzed in the azithromycin group and 40 in the placebo group. Five days after the last dose, serum IL-2 and IL-8 levels dropped significantly in the azithromycin group. There was a significant reduction in the incidence of death and O2 dependency at 28 days/death in azithromycin-treated patients regardless of the detection of Ureaplasma in blood. Conclusions: Azithromycin has anti-inflammatory effects, with a decrease in cytokines after 5 days of use and a reduction in death and O2 dependency at 28 days/death in mechanically ventilated preterm neonates.

Preterm birth remains the main contributor to early childhood mortality. The vaginal environment, including microbiota composition, might contribute to the risk of preterm delivery. Alterations in the vaginal microbial community structure might represent a risk factor for preterm birth. Here, we aimed to (a) investigate the association between preterm birth and the vaginal microbial community and (b) identify microbial biomarkers for risk of preterm birth. Microbial DNA was isolated from vaginal swabs in a cohort of 69 women enrolled at hospital admission for their delivery. Microbiota was analyzed by high-throughput 16S rRNA sequencing. While no differences in microbial diversity measures appeared associated with the spontaneous preterm and full-term outcomes, the microbial composition was distinct for these groups. Differential abundance analysis showed Lactobacillus species to be associated with full-term birth whereas an unknown Prevotella species was more abundant in the spontaneous preterm group. Although we studied a very miscegenated population from Brazil, our findings were similar to evidence pointed by other studies in different countries. The role of Lactobacillus species as a protector in the vaginal microbiome is demonstrated to be also a protector of spontaneous preterm outcome whereas the presence of pathogenic species, such as Prevotella spp., is endorsed as a factor of risk for spontaneous preterm delivery.

Objective This study aimed to describe the experience with a protocol of therapeutic hypothermia (TH) in southern Brazil. Study Design Newborns with gestational age > 35 weeks with evidence of perinatal asphyxia plus moderate or severe encephalopathy were recruited between March 2011 and November 2017. Whole-body hypothermia for 72 hours, starting within the first 6 hours of life was used. Survivors underwent magnetic resonance imaging (MRI) and electroencephalogram (EEG). The primary outcome was death during hospitalization and neurodevelopment assessed using the Bayley Scales of Infant Development III (BSID III) at 12 months of age. Results A total of 72 newborns were treated (41 with moderate encephalopathy and 31 with severe encephalopathy), of whom 16 died. MRI was performed in 56 patients, and 24 presented some alterations. Fifty-three patients had an EEG: 11 normal, 20 mildly altered, 12 moderately altered, and 10 severely altered. Forty patients were evaluated through BSID III: 45% presented with some delay in neurodevelopment, 8 (20%) had motor retardation, 15 (37.5%) had language delay, and 13 (32.5%) had a delay in cognitive development. Conclusion Mortality and adverse events were similar to those described in large randomized controlled trials. TH is a safe and an effective method of neurologic protection in asphyxiated newborns in a developing country when performed adequately.

Objective: To assess the prevalence of metabolic syndrome-like symptoms in a population of preterm infants with very low birth weight (

Objective Prematurity and low birth weight predispose preterm infants to cardiovascular disease in later life. Is the metabolic profile of these children impacted by the relation between birth weight and gestational age (GA)? This study aimed to evaluate whether the relationship between birth weight and GA of preterm infants has a positive correlation with the metabolic profile from birth to the sixth month of corrected age. Subjects and methods This is a longitudinal, prospective study with a cohort of 70 preterm and 54 term infants, who were enrolled in the study and shared into two groups: Appropriate for GA (AGA) and Small for GA (SGA), both classified at birth by Fenton and Kim curves. Longitudinal evaluation of anthropometry measures and blood samples of total cholesterol, glucose, triglycerides, and insulin were collected at birth, NICU discharge, and the sixth month of corrected age. Data were analyzed using descriptive and inferential statistical analysis (ANOVA, Fisher test, Shapiro-Wilk, and Cochran test). The effect size was 0.15, power was 0.92, and confidence interval 95%. Results No significant statistical differences were observed in relation to biochemical tests between AGA and SGA groups. However, a significant increase in triglyceride results above the reference values for age in the SGA group was observed throughout the follow-up. Conclusions Changes observed in the preterm infant metabolic profile show no correlation with adequacy of birth weight. Preterm lipid profile requires continuous evaluation at follow-up, due to the increased cardiovascular risk in later life.

Background: This study extended previous research by investigating the combined effects of neonatal birth risks, neonatal adverse outcomes, and socioeconomic status on preterm neurodevelopment. Method: A total of 184 preterm infants were assessed using the Bayley Scales of Infant Development III in a follow-up clinic in southern Brazil. Structural equation modeling was conducted with 3 latent variables (neonatal birth risks, neonatal adverse outcomes, and socioeconomic status) and 3 outcomes (cognitive, language, and motor development). Results: The analyses showed that neonatal adverse outcomes were associated with infants’ cognitive (b = –0.45, P < .001), language (b = –0.23, P = .001), and motor (b = –0.51, P < .001) development. Socioeconomic status also explained the variances (cognitive: b = 0.20, P = .006; language: b = 0.28, P = .001; and motor: b = 0.21, P = .004), whereas neonatal birth risks remained significant only in the motor development (b = 0.15, P = .040). Conclusion: This study suggests that the most evident contributors to poor neurodevelopment were adverse outcomes and socioeconomic risk factors.

Early-onset neonatal sepsis (EONS) remains one of the leading causes of morbidity and mortality related to premature birth, and its diagnosis remains difficult. Our goal was to evaluate the intestinal microbiota of the first meconium of preterm newborns and ascertain whether it is associated with clinical EONS.In a controlled, prospective cohort study, samples of the first meconium of premature infants with a gestational age (GA) ≤32 weeks was obtained at Hospital de Clínicas de Porto Alegre and DNA was isolated from the samples. 16S rDNA based microbiota composition of preterm infants with a clinical diagnosis of EONS was compared to that of a control group.40 (48%) premature infants with clinical diagnosis of EONS and 44 (52%) without EONS were included in the analysis. The most abundant phylum detected in both groups,These findings suggest that the first-meconium microbiota is different in preterm neonates with and without clinical EONS.

Background Jaundice due to indirect hyperbilirubinemia affects more than 60% of neonates and phototherapy is the treatment for severe types. There are no previous studies evaluating the effect of phototherapy on the function of neonates neutrophils. The aim of this study was to assess and compare the function of neutrophils by measuring the expression of neutrophils main surface markers in icteric neonates before and after phototherapy. Methods Neonates at a gestational age ≥35 weeks and birth weight ≥2,000 g who met the American Academy of Pediatrics criteria for phototherapy were included. Flow cytometry evaluation of the mean fluorescence intensities of CD10, CD11b, CD11c, CD15, CD16, CD18, CD62L, CD64, and CD66acde was performed before and 24 h after the initiation of phototherapy. Results Twenty-five neonates at a mean age of 53 h of life were included in the study with a mean bilirubin level of 13.60 ± 2.85 mg/dL. There was no statistical difference in the expression of CD11b, CD15, CD18, CD62L, and CD64 or in the percentage of neutrophils before and after 24 h of phototherapy. There was an increase in the expression of CD10 and CD16 and a decrease in the expression of CD11c and CD66acde after 24 h of phototherapy. Conclusions Newborns submitted to phototherapy had an increase in the expression of CD10 and CD16 and a decreased in the expression of CD11c and CD66acde after 24 h of treatment, which may be related to an anti-inflammatory effect of phototherapy. © 2018 International Clinical Cytometry Society.

Neurological sequelae are common in very low-birth-weight preterm infants. The prevention of brain injury and development of neuroprotective strategies have been the main objectives of modern neonatal neurology. Amplitude integrated electroencephalogram (aEEG) is a continuous brain monitoring method that can aid in early diagnosis and detect patients who are at risk. While its role in the assessment of full-term newborn infants is already well established, there are still doubts about its use in preterm infants. The objective of this review was to describe the main recommendations for the use of aEEG in very low-birth-weight preterm infants and its accuracy in assessing the prognosis and detecting epileptic seizures in this population.

ObjectiveTo evaluate the effect of an oral stimulation program in preterm on the performance in the first oral feeding, oral feeding skills and transition time from tube to total oral intake.Study designerDouble-blind randomized clinical trial including very preterm newborns. Congenital malformations, intracranial hemorrhage grade III or IV, bronchopulmonary dysplasia, and necrotizing enterocolitis were excluded. Intervention group (GI) received an oral stimulation program of tactile extra-, peri-, and intraoral tactile manipulation once a day for 15 minutes, during a 10-day period. Control group (GII) received sham procedure with same duration of time. Feeding ability was assessed by a speech-language pathologist blinded to group assignment. The classification of infants' oral performance was determined by Oral Feeding Skills (OFS). Neonates were monitored until hospital discharge.ResultsSeventy-four (37 in each group) were randomized. Mean gestational ages and birth weights were 30±1.4 and 30±1.5 weeks, and 1,452±330g and 1,457±353g for intervention and control groups, respectively. Infants in the intervention group had significantly better rates than infants in the control group on: mean proficiency (PRO) (41.5%±18.3 vs. 19.9%±11.6 (pConclusionInfants who were breast-fed and an oral stimulation program proved beneficial in reducing transition time from tube feeding to oral feeding.Trial registrationClinicalTrials.gov number NCT03025815.

Objective: To determine risk factors during neonatal hospital stay and follow-up associated with failure to thrive in the first year of life of very low birth weight newborns. Methods: Study of preterm very low birth weight newborns followed from 2006 to 2013 in a public institutional hospital program. The study included newborns that attended at least one appointment in each of the three periods: Period I, up to 3 months of corrected age (CA); Period II, 4–6 months of CA; and Period III, 7–12 months of CA. The variables were analyzed by logistic regression with XLSTAT 2014 software (Microsoft®, WA, USA). Failure to thrive (Z-score below −2 SD) was classified as a dichotomous dependent variable (0 – failure/1 – success), while the other variables were classified as explanatory variables for the hospitalization periods and for each of the follow-up periods (I, II, and III). Results: Children born adequate for gestational age increased the chance of Z-score for weight at discharge > −2 SD (OR = 10.217; 95% CI: 1.117–93.436). Metabolic bone disease and retinopathy of prematurity in Period I, as well as hospital readmissions in Periods II and III during follow-up increased the chance of Z-score

Objective To verify the prevalence of systemic arterial hypertension (SAH) and to identify possible early predictors of SAH at ages 2 and 4 years in very low birth weight (VLBW) infants. Study Design This is a prospective cohort study including inborn children with birth weight (BW) Results A total of 198 patients were included during the 5-year study period, of whom 56% had SAH at age 4. In model 1, white matter injury (WMI) and catch-up growth at age 2 were predictors of SAH at age 4. In model 2, bronchopulmonary dysplasia, WMI, catch-up growth at age 2, and BW were predictors of SAH at 2 and 4 years. SAH at age 2 was an independent risk factor for SAH at age 4. After a multivariate analysis of model 2, BW and catch-up growth were associated with SAH. Conclusion Prevalence of SAH was high in VLBW infants; it was associated with low BW and catch-up growth at age 2.

Phototherapy in neonates for treatment of pathological jaundice is an effective therapeutic tool that is widely used in neonatal units. Over the past years, a greater concern has emerged about the effects on the immune and inflammatory system and its potential genotoxic and side effects, especially the late ones, possibly associated with childhood diseases, showing that this treatment is not as harmless as previously believed. Numerous studies assessing these possible adverse effects of phototherapy on neonates have been published over the past years. Through this review, we seek to analyze what we know about the side effects of phototherapy in the neonatal period. The main causes of jaundice, phototherapy techniques, acute and late side effects, and effects on the immune and inflammatory system were reviewed. It was concluded that phototherapy is not a treatment free of side effects and further studies need to be conducted to elucidate its harmful effects on neonates.

Purpose: To evaluate the relationship between abnormal early amplitude integrated electroencephalography (EEG) and severe lesions in imaging tests performed during the neonatal period in very low birth weight infants. Methods: An amplitude-integrated EEG was performed in 70 patients with a mean birth weight of 1226 g during the first 48 hours of life. Severe lesions on magnetic resonance imaging (MRI) or ultrasonography (US) during the neonatal period were considered as adverse conditions. Variables were compared using the χ2 test or analysis of variance. Sensitivity, specificity, and positive likelihood ratio were calculated. Results: Adverse outcomes were observed in 6 patients. There was a significant relationship ( P < .001) between abnormal amplitude-integrated EEG background and severe lesions on MRI and US. Sensitivity and specificity were 100% and 89%, respectively. Conclusion: Early amplitude-integrated EEG with moderate/severe abnormalities in the background is associated with severe structural lesions detected in imaging studies and should be considered as an auxiliary screening tool for the detection of neonatal brain lesions in very low birth weight infants.

To determine the neurodevelopment outcomes after therapeutic hypothermia for neonatal hypoxic-ischemic encephalopathy (HIE) and identify the neonatal magnetic resonance imaging (MRI) findings associated with neurological outcome in a middle-income country.All infants born after 35 completed weeks' gestation with signs of moderate to severe encephalopathy and evidence of perinatal asphyxia before 6 hours of life were submitted to whole-body hypothermia and were imaged at 18 ± 8.4 days of life (range 7-33 days) after birth. Surviving infants had the neurodevelopment outcome assessed at 12 to 18 months of age by trained professional masked to MRI findings.Forty-eight infants included, MRI scans were obtained from 34 infants; 14 (29.1%) patients died during hospitalization before MRI was performed. Nine (64.3%) of 14 patients were classified as severe encephalopathy presented Posterior Limb Internal Capsule (PLIC) sign at the MRI, 10 (71.4%) thalamus and basal ganglia (TBG) lesion, 9 (64.3%) white matter (WM) lesion, and 7 (50.0%) cortical lesion. Severe encephalopathy was associated with the motor delay at 12-18 months by Bayley III, Alberta Infant Motor Scale (AIMS), and Gross Motor Function Classification System (GMFCS) scores (p = .020, p = .048, p = .033, respectively), but not for the cognitive (p = .167) or language skills (p = .309). Lower BSID-III motor, cognitive, and language composite scores were associated with PLIC sign (p = .047; p = .006 and p = .003, respectively). TBG lesion (p = .051) and cortical lesion (p = .030) were associated with lower language composite score. Motor delay by AIMS and the presence of PLIC sign, TBG lesion, WM lesion, and Cortical lesion on MRI were observed (p .001; p = .002; p = .001 and p = .027, respectively); as well as higher GMFCS score were associated with the presence of PLIC sign, TBG lesion, WM lesion, and Cortical lesion on MRI (p .001; p = .001; p = .001, and p = .011, respectively).Brain MRI in neonates with HIE after therapeutic hypothermia is a valuable tool for diagnosis of encephalopathy cerebral abnormalities and is an early predictor of outcome in infants treated with whole body hypothermia for HIE in the Brazilian experience.

Background Angiogenic and antiangiogenic factors are altered in pregnant women with preeclampsia (PE), but the pattern of expression of these factors in their newborns remains unknown. Objective This study aims to measure vascular endothelial growth factor (VEGF) and soluble fms-like tyrosine kinase 1 (sFlt-1) levels in preterm neonates born to mothers with PE. Methods Neonates with birth weight < 2,000 g and gestational age � 34 weeks were included and divided into the following two groups: born to mothers with PE and without PE. Blood was collected from neonates within the first 72 hours of life. VEGFand sFlt-1 levels were measured using the enzyme-linked immunosorbent assay method. Results A total of 88 neonates were included (37 born to mothers with PE and 51 born to mothers without PE), with a mean gestational age of 29.12 � 2.96 weeks and birth weight of 1,223.80 � 417.48 g. In the multivariate analysis, VEGF was 80% lower and sFlt-1 was 13.48 times higher in the group with PE. sFlt-1 concentration was higher in neonates small for gestational age (SGA) than in those appropriate for gestational age. Conclusion Higher sFlt-1 and lower VEGF levels in the group with PE, as well as higher sFlt-1 levels in SGA neonates, reflect a predominance of antiangiogenic mechanisms in PE and growth restriction.

Made available in DSpace on 2018-11-26T17:55:40Z (GMT). No. of bitstreams: 0 Previous issue date: 2016-03-18 Health Ministry of Brazil (Ministerio da Saude do Brasil) Objective: To analyze unfavorable outcomes at hospital discharge of preterm infants born at Brazilian public university centers.Methods: Prospective cohort of 2646 inborn infants with gestational age 23-33 weeks and birth weight 400-1499g, without malformations, born at 20 centers in 2012-2013. Unfavorable outcome was defined as in-hospital death or survival at hospital discharge with 1 major morbidities: bronchopulmonary dysplasia (BPD) at 36 corrected weeks, intraventricular hemorrhage (IVH) grades 3-4, periventricular leukomalacia (PVL) or surgically treated retinopathy of prematurity (ROP).Results: Among 2646 infants, 1390 (53%) either died or survived with major morbidities: 793 (30%) died; 497 (19%) had BPD; 358 (13%) had IVH 3-4 or PVL; and 84 (3%) had ROP. Logistic regression adjusted by center showed association of unfavorable outcome with: antenatal steroids (OR 0.70; 95%CI 0.55-0.88), C-section (0.72; 0.58-0.90), gestational age

CONTEXT: Although very preterm (VP), extremely preterm (EP), very low birth weight (VLBW), and extremely low birth weight (ELBW) newborns seem to have a higher risk of later attention-deficit/hyperactivity disorder (ADHD), the magnitude of the risk is not well-defined. OBJECTIVE: To systematically review and meta-analyze the risk of VP/VLBW and EP/ELBW individuals to develop a ADHD categorical diagnosis or dimensional symptomatology compared with controls with normal weight and/or birth age. DATA SOURCES: We used PsycINFO, Medline, Embase, and Cochrane databases. STUDY SELECTION: We selected cross-sectional, prospective, or retrospective studies with no time or language restriction. DATA EXTRACTION: Independent reviewers screened and extracted data using predefined standard procedures. RESULTS: In 12 studies (N = 1787), researchers relying on a categorical diagnosis showed that both VP/VLBW and EP/ELBW subjects have a higher ADHD risk (odds ratio [OR] = 3.04 higher than controls; 95% confidence interval [CI] 2.19 to 4.21). In subgroup analyses, we demonstrated that the more extreme the cases, the higher the ORs (VP/VLBW: OR = 2.25 [95% CI 1.56 to 3.26]; EP/ELBW: OR = 4.05 [95% CI 2.38 to 6.87]). We drew data from 29 studies (N = 3504) on ADHD symptomatology and found significant associations with inattention (standardized mean difference [SMD] = 1.31, 95% CI 0.66 to 1.96), hyperactivity and impulsivity (SMD = 0.74, 95% CI 0.35 to 1.13), and combined symptoms (SMD = 0.55, 95% CI 0.42 to 0.68) when compared with controls. LIMITATIONS: Heterogeneity was significantly high for all analyses involving the 3 ADHD dimensions. CONCLUSIONS: With our results, we provide evidence that VP/VLBW subjects have an increased risk of ADHD diagnosis and symptomatology compared with controls, and these findings are even stronger in the EP/ELBW group. Future researchers should address which risk factors related to prematurity or low birth weight lead to ADHD.

Objective The objective of this study was to investigate the neurodevelopment and growth of very low birth weight (BW) preterm infants, at 8 and 18 months corrected age (CA), compared with full term in Brazil. Methods Prospective cohort study including 83 preterm infants with BW ≤ 1,500 g and gestational age ≤ 32 weeks, and 52 full-term control infants. Preterm infants free from significant sensory and motor disability, and from congenital anomalies were included. Alberta infant motor scale (AIMS) and Brunet–Lèzini scale (BLS) were used to evaluate the neurodevelopment at 8 and 18 months. Anthropometric measurements were collected to evaluate the growth in both age groups. Results At 8 months CA, preterm infants scored significantly lower in total AIMS score (p = 0.001). At 18 months, they scored significantly lower on the stand subscale from AIMS (p = 0.040) and exhibited poor psychomotor development in the BLS (p = 0.006). The nutritional status showed significant differences between the groups, in both age groups (p Conclusion Very low BW preterm infants at 8 and 18 months CA showed significant differences in the neurodevelopment and growth pattern when compared with their full-term peers.

Summary Objective: To determine the prevalence of iron-deficiency anemia and iron deficiency at 1 year of corrected age (CA) in preterm very-low-birth-weight infants, and to identify risk factors for iron-deficiency anemia. Methods: A cohort of infants with birth weight

There are few studies concerning adiponectin and insulin concentration in cord blood of very low birth weight (VLBW) preterm and full-term newborns, small and appropriate for gestational age (GA).To compare adiponectin and insulin concentrations between preterm and full-term infants, and to determine their relation with birth weight (BW) and size for GA.A cross-sectional study of VLBW preterm newborns with GA 32 weeks and BW 1500 g, and full-term newborns with GA 37 weeks born at our hospital between January 2010 and May 2011, was conducted.major congenital malformation, inborn errors of metabolism, chromosomal anomalies. Adiponectin was determined by enzimoimunoassay with ELISA kits (RD Systems, Minneapolis, MN) and insulin was assayed by chemiluminescence method.A total of 127 newborns were studied, 55 VLBW preterm (28 SGA), and 72 full-term (7 SGA). Insulin cord blood concentrations in preterm and full-term newborns were similar. Adiponectin concentrations were significantly lower in preterm than in full-term infants: 1.57 ± 0.74 pg/ml versus 2.4 ± 0.22 pg/ml (p 0.001), respectively. Regression analyses showed that, after controlling for several neonatal and maternal factors, preterm birth was the only significant predictor of adiponectin concentrations.Being born prematurely is the main determinant factor for lower adiponectin concentration in umbilical cord blood of newborns.

Introduction Bronchopulmonary dysplasia (BPD) is a frequent, long-term complication in very low-birth-weight (VLBW) newborns. Its etiology is multifactorial and the oxidative stress is one of its main causes. Breast milk (BM) reduces oxidative stress and provides antioxidant protection, therefore, BM may have a protective effect against BPD. Objectives This study aims to assess the possible protective effects of BM on BPD. Methods This is a cohort study including infants with a birth weight below 1,500 g and/or gestational age of less than 32 weeks, born between January 2011 and October 2014. BPD was defined as the need for supplementary oxygen for 28 days or more. Results The incidence of BPD was 29.1%. The median amount of BM received by the patients in the first 6 weeks of life was significantly higher in patients without BPD (10.8 mL/kg/day) than in those with BPD (2.3 mL/kg/day). The amount of BM received was inversely associated with the incidence of BPD, even after multivariate analysis. The cutoff point at which the protective effect emerged was an average amount of 7 mL/kg/day of BM during the first 42 days of life. Conclusion Feeding VLBW infants with BM is associated with a lower risk of developing BPD.

Aim To evaluate bone metabolism in newborn preterm infants before and after a physical therapy protocol. Method This randomized controlled clinical trial included 30 newborn preterm infants with gestational age ≤35 weeks and appropriate weight for gestational age, who were randomized into control group (CG) and physiotherapy group (PG). The PG protocol consisted of 15 minutes of daily passive movements with gentle joint compression 5 days a week. Daily data were obtained on feeding and body weight. Measurements of bone-specific alkaline phosphatase (BAP) and urinary deoxypyridinoline (DPD) were collected before and after intervention in both groups. The analysis of covariance test was performed to compare the means of both groups. Results At baseline, gestational age and corrected gestational age, birth weight, and gender were similar between both groups. Nutrient supply, length of total parenteral nutrition, and mechanical ventilation were also similar. BAP level increase in PG was 22.44 ± 3.49 U/L, whereas in CG was 2.87 ± 3.99 U/L (p = 0.003). There was a reduction of DPD levels in PG of 28.21 ± 11.05 nmol/mmol, and an increase of 49.95 ± 11.05 nmol/mmol (p Conclusion The benefits of prevention and treatment of metabolic bone disease of prematurity, in addition to an adequate diet, should include these passive exercises with gentle joint compressions to improve the quality of premature infant's bones.

To examine the association among interleukin-6, interleukin-8, tumor necrosis factor-α, interleukin-10, and interleukin-1β and white matter injury in very-low-birth-weight infants with clinical sepsis and to help predict infants at risk for development of white matter injury.A prospective cohort study was carried out.Neonatal intensive care unit.Very low birth weight infants with clinical early-onset sepsis. Exclusion criteria were death before 14 days, major malformations, and congenital infections.Ultrasound brain scans were carried out on the third day and weekly until the sixth week of life or discharge and confirmed by a magnetic resonance image performed in the first year. Plasma was assayed for interleukin-6, interleukin-8, tumor necrosis factor-α, interleukin-10, and interleukin-1β in the same sample collected for sepsis work-up. Mann-Whitney, chi-square, t tests, multiple regression, and receiver operating characteristic analysis were applied.From July 2005 to October 2007 we studied 84 very-low-birth-weight infants, 27 (32%) with white matter injury, and 57 (68%) control subjects (with no white matter injury). Proven early-onset sepsis and necrotizing enterocolitis were high risk for white matter injury after adjustment for gestational age and birth weight (relative risk, 3.04; 1.93-4.80 and relative risk, 2.2; 1.31-3.74, respectively). Interleukin-6, interleukin-8, and tumor necrosis factor-α levels were higher in infants with white matter injury than in control subjects (p.0001). Interleukin-1β and interleukin-10 were similar. The areas under the curve for interleukin-6, interleukin-8, and tumor necrosis factor-α were 0.96 (0.92-0.99), 0.97 (0.94-1.0), and 0.93 (0.86-0.99), respectively. Interleukin-8 ≥100 pg/mL was the best predictor of white matter injury; the sensitivity and specificity were 96% and 83%, respectively, and negative predictive value was 98%.Very-low-birth-weight infants with proven early-onset sepsis, necrotizing enterocolitis, and high plasma levels of interleukin-6, interleukin-8, and tumor necrosis factor-α are at high risk for white matter injury.

To determine the prevalence of Ureaplasma urealyticum and Ureaplasma parvum bacteremia in very low birth weight (VLBW) infants and to evaluate the associated factors.Ninety-five VLBW newborns with gestational age ≤32 weeks were included in the study conducted between March 2009 and July 2010. DNA was extracted from the blood samples collected during the first 72 hours of life, and U. urealyticum and/or U. parvum were identified by polymerase chain reaction. The newborns were followed up until hospital discharge.The prevalence of U. urealyticum and/or U. parvum bacteremia was 12.6% (12 cases): 5 (5.2%) for U. urealyticum, 5 (5.2%) for U. parvum, and 2 (2.1%) for both. Based on the univariate analysis, the presence of Ureaplasma was associated with clinical chorioamnionitis and spontaneous preterm labor. Preeclampsia and small for gestational age were associated with lower incidence of Ureaplasma. When spontaneous preterm labor was present, the prevalence of Ureaplasma bacteremia was 25%. Only spontaneous preterm labor was a statistically significant factor after step-by-step logistic regression analysis (P = 0.006), with 9-fold increase in chance of neonatal Ureaplasma bacteremia.Ureaplasma bacteremia is common in VLBW infants, especially among those born after preterm labor.

Information on leukocyte activation in newborn infants of preeclamptic mothers is scarce. IL-8 and GRO-α are the main pro-inflammatory cytokines involved in leukocyte activation. The objective was to evaluate IL-8 and GRO-α plasma levels in preterm newborns infants of preeclamptic mothers. Newborns with gestational age36 weeks and birth weight2000 g were included and divided: non-preeclamptic (n=64) and preeclamptic groups (n=55). Exclusion criteria were major congenital malformations, inborn errors of metabolism or chromosomal anomalies, congenital infections, death in delivery room, and maternal chronic hypertension without preeclampsia. IL-8 and GRO-α were measured by enzyme immunoassay in the first 48 h. Groups were similar in birth weight, gestational age, Apgar scores at 5 min, sepsis, RDS, mechanical ventilation, TPN, NEC, intraventricular hemorrhage and death. The preeclamptic group had more neutropenia, SGA, cesarean section, and less rupture of membranes18 h. IL-8 was higher in the non-preeclamptic [157.1 pg/mL (86.4-261.3) and 26.54 pg/mL (3.6-87.2) p0.001]. GRO-α levels were similar in both groups [229.5 pg/mL (116.6-321.3) and 185.5 pg/mL (63.9-306.7) p=0.236]. After multiple regression analysis only absence of preeclampsia was associated with high IL-8 levels. Our data suggest that leukocyte activation may be impaired in infants of preeclamptic mothers.

Controversy exists regarding association of high levels of proinflammatory cytokines, neonatal morbidities and poor neurodevelopment outcome in very low birth weight infants.To determine association between severity of early inflammatory response and neurodevelopment outcome in high risk very low birth weight infants.Sixty-two very preterm infants with high risk for early-onset sepsis were followed up to 24 months corrected age. Blood sample was collected for IL-6, IL-8, IL-10, IL-1β, and TNF-α analysis. Neurodevelopment outcome by Bayley Scales of Infant Development II was assessed at 22 to 24 months. Magnetic Resonance Image was performed at least once during the first 12 months.In 24 (38.7%) MDI was85, and 16 (25.8%) had PDI85. Low birth weight was significantly associated with low MDI, and birth weight and periventricular leukomalacia were significantly associated with low PDI by multiple regression analysis. After controlling for birth weight and gestational age, none of the studied variables was associated with low MDI, and only periventricular leukomalacia with low PDI. Each additional 100g in the birth weight reduced the probability of low MDI and PDI scores in 14%.There was no association of high cytokines plasma levels with poor neurodevelopment outcome at 22 to 24 months' corrected age, suggesting that elevations of plasma proinflammatory cytokines early in life do not play an important role in pathophysiology of brain injury in high risk preterm infants.

Objective: To determine the influence of presence of caffeine in umbilical cord blood on apnea occurrence. Methods: A prospective cohort study with preterm newborns with birth weight lower than 2,000 g was undertaken. Exclusion criteria were: mothers who received opioids; mechanical ventilation during the first 4 days of life; cerebral and major cardiac malformations; perinatal asphyxia; severe periintraventricular hemorrhage; exchange transfusion before the fourth day of life; and those who received methylxantine prior to extubation. Neonates were divided into detectable and undetectable caffeine in umbilical cord blood. Newborns were followed for the first 4 days for occurrence of apnea spells. Results: Eighty-seven newborns with and 40 without detectable caffeine in umbilical cord blood were studied. Median caffeine concentration of the 87 patients with detectable caffeine in umbilical blood was 2.3 µg/mL (0.2-9.4 µg/mL). There was no association between occurrence of apnea spells and presence of caffeine in umbilical cord blood. Neonates with detectable caffeine in umbilical blood had borderline later apnea (66.3±4.14 hours) than those with undetectable levels (54.2±6.26 hours). Conclusion: Detected levels of caffeine in umbilical cord blood did not decrease occurrence of apnea of prematurity, but it had a borderline effect delaying its occurrence, suggesting that even a low level of caffeine in umbilical cord blood might delay occurrence of apnea spells.

Prematurity and intrauterine growth restriction are associated with neurodevelopment delay. A prospective cohort study included all 96 very low birth weight infants discharged from our neonatal unit from November 2003 to June 2005. The authors compared 41 appropriate and 55 small for gestational age very low birth weight infants' neurodevelopment at 24 months corrected age. Bayley Scales were similar between both groups at 8, 12, 18, and 24 months corrected age even after adjustment for gestational age and improved from 8 to 24 months corrected age. Small for gestational age infants with and without severe intrauterine growth restriction had similar neurodevelopment outcome. Neurodevelopment delay is frequent in very low birth weight infants with no differences between appropriate and small for gestational age. The authors suggest that Bayley Scales evaluation should be performed in every very low birth weight infant at least at 24 months corrected age to detect those requiring therapeutic stimuli.

Aim: To evaluate the use of the Score for Neonatal Acute Physiology and Perinatal Extension (SNAPPE-II) at admission to predict the development of retinopathy of prematurity (ROP) among very-low-birth-weight preterm babies. Methods: A prospective cohort study included 304 infants screened for ROP from July 2004 to October 2007. The main outcomes were the development of any stage ROP and severe ROP. The main variable was the SNAPPE-II obtained at admission. Seventeen risk factors for ROP were studied by univariate analysis (χ2 and Student’s t test). A simple descriptive analysis was used for the SNAPPE-II (mean, median, standard deviation and interquartile range: p25–p75). Logistic regression and receiver-operating characteristic (ROC) curve were calculated for SNAPPE-II. Ophthalmological examinations started at the 6th week of life and were repeated until the 45th week of corrected gestational age (GA). Results: The mean GA and mean birth weight of the whole cohort were 30.3 weeks (±2.2) and 1,209.2 g (±277.7), respectively. The median SNAPPE-II among non-ROP and ROP patients were 6.0 and 15.0, respectively (p = 0.001). When compared with severe ROP patients (25.0) there was also a significant difference (p = 0.003). After logistic regression, the SNAPPE-II adjusted odds ratio for ROP was 1.024. The area under the ROC curve was 0.62 (95% confidence interval: 0.55–0.70, p < 0.001). The best discriminative cutoff value was 8.5 (sensitivity: 68%; specificity: 54%; positive predictive value: 37.3%; negative predictive value: 80.6%). Conclusions: The SNAPPE-II values at admission were significantly higher among babies with ROP, suggesting a positive association between higher scores with the development of ROP, but after adjusted logistic regression and ROC curve results, the SNAPPE-II scores at admission did not enhance the assessment of risk for ROP.

OBJETIVO: Verificar a associação de leucomalácia periventricular (LPV) e sepse neonatal em recém-nascidos de muito baixo peso (RNMBP). MÉTODOS: Foram incluídos RNMBP com suspeita clínica de infecção nascidos na instituição de 01/08/2005 a 31/07/2007. Foram excluídos óbitos antes dos 14 dias, malformações do sistema nervoso central e infecções congênitas. Foi realizado ultra-som cerebral no terceiro dia e semanalmente até a sexta semana de vida ou alta. LPV foi diagnosticada por hiperecogenicidade difusa periventricular persistente por mais de 7 dias, ou por cistos periventriculares. RNMBP foram divididos em grupos com e sem LPV. Sepse foi definida por manifestação clínica com cultura positiva. Os testes t, Mann-Whitney, qui-quadrado e regressão logística foram usados. RESULTADOS: Foram incluídos 88 RNMBP, sendo que 62 (70,5%) sobreviveram e 51 (57,8%) tiveram LPV. Os grupos foram semelhantes no peso de nascimento, idade gestacional, escore de Apgar, tipo de parto, SNAPPE-II, presenças de enterocolite necrosante, persistência de canal arterial e óbitos. Sepse e ventilação mecânica foram mais freqüentes no grupo com LPV (23,5 e 2,7%, p = 0,005; 86 e 59%, p = 0,004, respectivamente). Na regressão logística, ambos foram fatores de risco independentes para LPV (p = 0,027 e 0,015, respectivamente). CONCLUSÃO: Corioamnionite é fator de risco definido para LPV. Demonstramos que sepse neonatal também é fator de risco importante. Acreditamos que a resposta inflamatória sistêmica seja o principal fator envolvido na etiopatogenia da LPV em RNMBP.

Bronchopulmonary dysplasia (BPD) is associated with changes in pulmonary angiogenesis. However, the role of the vascular endothelial growth factor/placental growth factor (VEGF/PlGF) heterodimer, an antiangiogenic factor, remains unknown in this disease.To compare VEGF/PlGF levels in preterm infants with and without BPD.This study was approved by the Institutional Review Board. Preterm neonates with birth weight2,000 g and gestational age ≤ 34 weeks were included. Exclusion criteria were: neonates transferred from other institutions after 72 hours of life; death before blood collection; presence of major congenital malformations, inborn errors of metabolism, and early sepsis; and mothers with multiple pregnancies, TORCH infections, HIV infection, or autoimmune diseases. BPD was defined as the need for oxygen therapy for a period equal to or greater than 28 days, accompanied by radiographic changes compatible with the disease. Blood was collected from neonates in the first 72 hours of life. VEGF/PlGF levels were measured using the enzyme-linked immunosorbent assay method. The chi-square test, t-test, Mann-Whitney test, analysis of variance, and Kruskal-Wallis test were used for statistical analysis. Variables found to be significant in the univariate analysis were included in the multivariate analysis.Seventy-three patients were included (19 with BPD, 43 without BPD, and 11 neonates who died in the first 28 days of life), with a mean (SD) gestational age of 30.32 (2.88) weeks and birth weight of 1,288 (462) g. Median VEGF/PlGF levels were higher in the groups with BPD and death in the first 28 days of life than in the group without BPD (16.46 [IQR, 12.19-44.57] and 20.64 [IQR, 13.39-50.22], respectively, vs. 9.14 [IQR, 0.02-20.64] pg/mL], p0.001). Higher VEGF/P1GF levels remained associated with BPD and death in the first 28 days of life in the multivariate analysis.Higher plasma VEGF/PlGF levels were found in preterm neonates with BPD and in those who died in the first 28 days of life, suggesting an important role of this substance in pulmonary vascular development.

OBJETIVO: Avaliar os diferentes achados perinatais e o tempo da coleta da amostra em recém-nascidos com sepse neonatal precoce, comparando os recém-nascidos com nível baixo e alto de IL-6. MÉTODOS: Oitenta e cinco recém-nascidos com sinais clínicos de sepse e/ou hemoculturas positivas tiveram plasma coletado na avaliação inicial da sepse neonatal precoce nas primeiras 96 horas de vida. Foram divididos em: a) acima (grupo de nível elevado) e b) igual ou abaixo (grupo de nível baixo) da mediana da IL-6 do grupo total. RESULTADOS: A mediana da IL-6 para o grupo total foi de 89 pg/ml. Os grupos de nível elevado e de nível baixo foram constituídos por 42 e 43 recém-nascidos, respectivamente. Não houve diferença significativa entre ambos os grupos quanto a idade gestacional, peso de nascimento, proporção de parto cesariano, escores de Apgar, número de recém-nascidos cujas mães tiveram fator de risco para infecção, número de mães que receberam antibiótico intraparto e número de hemoculturas positivas. A mediana da IL-6 plasmática do grupo de nível elevado foi 287 pg/ml, e do grupo de nível baixo foi 46 pg/ml (p < 0,001). A mediana do tempo de coleta foi 17,5 horas de vida no grupo de nível elevado e 36 horas de vida no grupo de nível baixo (p < 0,001). Houve uma significante correlação negativa entre níveis de IL-6 e tempo de coleta da amostra. CONCLUSÃO: O tempo de coleta da amostra é um fator importante para a detecção de níveis elevados de IL-6 em recém-nascidos com sepse neonatal precoce. OBJECTIVE: To assess different perinatal findings and sample collection timing in newborns with early-onset sepsis comparing those with low IL-6 levels to the ones with high levels. METHODS: Eighty-five newborn infants, with clinical signs of sepsis and/or positive blood cultures, had plasma IL-6 collected in the initial evaluation for early-onset sepsis in the first 96 hours of life. They were classified in two groups according to their plasma IL-6 levels: higher, and equal to or lower than IL-6 median value for the whole septic group RESULTS: Median IL-6 for the whole group was 89 pg/ml. High and low level groups were formed by 42 and 43 newborns respectively. There were no differences between the two groups regarding gestational ages, birth weights, cesarean-section proportion, Apgar scores, number of neonates with maternal risk factors for infection, number of maternal intrapartum antibiotic therapy, and number of positive blood cultures. Median plasma IL-6 in the high level group was 287 pg/ml, and in the low level group 46 pg/ml (p < 0.001). Median sample timing was 17.5 hours of life for the high level group and 36 hours of life for the low level group (p < 0.001). There was a significant negative correlation coefficient between IL-6 levels and sample collection timing. CONCLUSION: Sample collection timing is an important factor for detection of high plasma IL-6 level in newborn infants with early-onset sepsis.

To measure VEGF/PlGF heterodimer levels in preterm infants born to mothers with preeclampsia.Neonates with birth weight2000 g and gestational age ≤34 weeks were divided into two groups: born to mothers with Preeclampsia (PE) and controls. Neonates transferred from outside after the 72nd hour of life, death before blood collection, major congenital malformations or inborn errors of metabolism, and mothers with multiple pregnancies, STORCH complex infections, HIV or autoimmune conditions were excluded. Blood was collected within 72 h of birth and again at 28 days. VEGF/PlGF heterodimer levels were measured by ELISA.We included 73 neonates (24 born to mothers with PE and 49 without PE). Mean gestational age was 30.32 ± 2.88 weeks and mean birth weight was 1288.62 ± 462.22 g. Median VEGF/PlGF levels were significantly higher in infants born to mothers with PE. VEGF/PlGF levels were inversely proportional to birth weight. There were no between-group differences in blood samples collected at age 28 days.Higher VEGF/PlGF levels were higher in neonates exposed to PE, and there was a significant negative correlation between birth weight and VEGF/PlGF levels. Further studies to elucidate the role of this substance in the fetal and neonatal period are needed.

OBJECTIVE: To evaluate the Score for Neonatal Acute Physiology and the Score for Neonatal Acute Physiology Perinatal Extension as neonatal mortality predictors in our neonatal intensive care unit, and to compare their results. METHODS: All newborn infants admitted to our neonatal intensive care unit from March 1997 through December 1998 were prospectively evaluated just at completion of 24 hours of life for SNAP and SNAP-PE. Exclusion criteria were: death or discharge from the neonatal intensive care unit in the first 24 hours of life, congenital malformations incompatible with life, and outborn infants. RESULTS: 553 newborn infants were included in the study and 54 died. The median SNAP and SNAP-PE values were higher in those who died. Infants were allocated to five different raising ranges of SNAP and SNAP-PE severity. SNAP: up to 6, 7-11, 12-15, 16-24, higher than 24 (mortality: 3%, 11%, 29%, 48%,75%, respectively). SNAP-PE: up to 11, 12-23, 24-32, 33-50, higher than 50 (mortality: 3%, 10%, 53%, 78%, 83%, respectively). The optimal cut off points based on ROC curve were 12 for SNAP, and 24 for SNAP-PE. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for death were figured out. SNAP 12: sensitivity 79.6%, specificity 71.7%, PPV 23.4%, NPV 97%. SNAP-PE 24: sensitivity 79.6%, specificity 80%, PPV 30%, NPV 97.3%. The area under the curve (Az) were 81.4% for SNAP, and 85.1% for SNAP-PE, both statistically significant. There were no statistical differences between the two areas under the curve. CONCLUSIONS: SNAP and SNAP-PE are excellent predictors of neonatal survival. Therefore, we recommend their use in Neonatal Intensive Care Units.

OBJECTIVE: Review the literature on diagnosis and treatment of neonatal sepsis. METHODS: The most important articles on neonatal sepsis were selected through MEDLINE. RESULTS: The present review analyzes the different methods of diagnosis, laboratory and clinical, as well as the different therapeutic managements of neonatal sepsis. CONCLUSION: Neonatal sepsis is a severe disease that must be diagnosed early and properly treated in order to avoid lethal outcome.

OBJECTIVE: To study plasma levels of IL-1beta and IL-6 in order to distinguish the presence of bacterial infection in newborn infants with fever. METHODS: A cohort of 117 newborn infants with postnatal age equal to or less than 5 days, with no previous use of antibiotic therapy, and with clinical suspicion of bacterial infection was studied from July 1995 through August 1996. Those with definite criteria for sepsis were considered infected. Fever was defined as axillar temperature > 37.5 degrees C in three independent measurements. The patients were classified in four different groups: Group 1: infected with fever; Group 2: infected without fever; Group 3: not infected with fever; Group 4: not infected without fever. Complete blood count, platelet count, blood or other fluid cultures, and plasmatic levels of IL-1beta and IL-6 were collected before the beginning of antibiotic therapy. RESULTS: Of the 117 newborn infants studied were 66 infected and 51 not infected. Fever was present in 45 (38.46%). The median values of IL-1beta and IL-6 were significantly higher in newborn infants with fever than in those with no fever. There were significant differences between groups 1 and 2, 1 and 4, and 2 and 3 for IL-1beta. There were no significant differences between groups 2 and 4, and 1 and 3 for IL-1beta. Eight (72%) newborn infants with no infection and no fever had environment heating, and 3 had dehydration. There were no differences in median IL-6 levels between groups 1 and 2, and 3 and 4. There were significant differences in the median IL-6 levels between groups 1 and 3, and 1 and 4. CONCLUSIONS: IL- 6 is a marker of early neonatal sepsis. IL-1beta is related to neonatal fever response independently of the presence of bacterial infection.

In preterm infants, the need for intubation and mechanical ventilation is associated with ventilator-induced lung injuries and subsequent bronchopulmonary dysplasia. The aim of the present review was to improve the understanding of the mechanisms of injury that involve cytokine-mediated inflammation to contribute to the development of new preventive strategies. Relevant articles were retrieved from the PubMed database using the search terms "ventilator-induced lung injury preterm", "continuous positive airway pressure", "preterm", and "bronchopulmonary dysplasia". The resulting data and other relevant information were divided into several topics to ensure a thorough, critical view of ventilation-induced lung injury and its consequences in preterm infants. The role of pro-inflammatory cytokines (particularly interleukins 6 and 8 and tumor necrosis factor alpha) as mediators of lung injury was assessed. Evidence from studies conducted with animals and human newborns is described. This evidence shows that brief periods of mechanical ventilation is sufficient to induce the release of pro-inflammatory cytokines. Other forms of mechanical and non-invasive ventilation were also analyzed as protective alternatives to conventional mechanical ventilation. It was concluded that non-invasive ventilation, intubation followed by early surfactant administration and quick extubation for nasal continuous positive airway pressure, and strategies that regulate tidal volume and avoid volutrauma (such as volume guarantee ventilation) protect against ventilator-induced lung injury in preterm infants.

OBJECTIVE To analyze the frequency of unlicensed (UL) and off-label (OL) prescriptions in neonates admitted to the neonatal intensive care unit of a tertiary care hospital and to determine their association with patients' severity. METHODS Observational cohort study including drugs prescribed during hospitalization of neonates over a 6-week period between July and August 2011. The drugs were classified as UL and OL for dose, frequency, presentation, age group, or indication, according to an electronic list of drugs approved by the Food and Drug Administration. Patients were followed until hospital discharge or 31 days of hospitalization, with daily records of the Neonatal Therapeutic Intervention Scoring System (NTISS). RESULTS We identified 318 prescription items for 61 patients (average of five items/patient); there were only 13 patients with appropriate use of medications (21%). A prevalence of 7.5% was identified for UL prescriptions and 27.7% for OL, and the most prevalent OL use was that related to age group - 19.5%. Fifty-seven medications were computed - one patient received 10 UL/OL drugs during hospitalization. The prevalence of OL uses was higher in preterm infants < 35 weeks and in those with higher severity scores (p = 0.00). CONCLUSIONS The prevalence of neonates exposed to UL/OL drugs during hospitalization was high, especially for those with higher NTISS scores. Although there is general appreciation that neonates, especially preterm infants, have a high rate of drug use, an assessment including different cultures and countries is still needed to prioritize areas for future research in the pharmacotherapy of this vulnerable population.

We sought to determine cytokine response in term and late preterm newborn infants on phototherapy. Twenty newborn infants with gestational age > or = 35 weeks and birth weight > or = 2000 g in the first week of life had serum interleukin (IL)-6, IL-8, IL-10, IL-1beta, and tumor necrosis factor (TNF)-alpha measured immediately prior to and after 24 hours on phototherapy. Exclusion criteria were newborns with severe congenital malformations, congenital infections, birth asphyxia, sepsis, hemolytic anemia that required blood transfusion, maternal-infant Rh incompatibility and those who required exchange transfusion or intravenous immunoglobulin treatment for hyperbilirubinemia. Median IL-6 concentrations significantly decreased after 24 hours on phototherapy (18.3 pg/mL and 7.85 pg/mL, respectively, p = 0.005). IL-6 concentrations decreased in 17 out of the 20 newborns. There were no statistical differences in IL-8, IL-10, IL-1beta, and TNF-alpha concentrations before and after 24 hours on phototherapy. There was a statistically significant correlation between IL-6 decline and irradiance (r = 0.57, p = 0.009). The finding that serum IL-6 decreases in newborn under phototherapy suggests that phototherapy possibly has an anti-inflammatory effect, although the clinical implications of this study deserve further studies.

Objective To evaluate plasma levels of interleukin (IL)-1β, IL-6, IL-8, IL-10, and tumor necrosis factor (TNF)-α in newborn infants immediately before and after 2 hours of mechanical ventilation. Study design Term and late preterm neonates with no history of mechanical ventilation and/or ventilatory support were studied prospectively. Exclusion criteria were congenital malformations, congenital infections, use of nitric oxide, resuscitation with positive-pressure ventilation, and any procedure in the delivery room or neonatal intensive care unit that resulted in tracheal intubation. Blood samples for IL-1β, IL-6, IL-8, IL-10, and TNF-α levels were collected before intubation and mechanical ventilation and 2 hours later. Results Nineteen newborn infants with gestational age 35.8 ± 1.9 weeks and birth weight 2280 ± 370 g were included. Pro-inflammatory cytokines increased: IL-8 (2.5-fold), IL-1β (7.5-fold), and TNF-α (10-fold), and the anti-inflammatory cytokine IL-10 decreased by 90%. Although median IL-6 levels were similar between before and after ventilation, IL-6 increased in 89.4% of infants. Conclusions A short period of mechanical ventilation promotes an imbalance of plasma levels of pro-inflammatory and anti-inflammatory cytokines. The systemic alteration of cytokines in response to mechanical ventilation may lead to ventilator-induced lung injury.

OBJETIVO: Verificar a associação de leucomalácia periventricular (LPV) e sepse neonatal em recém-nascidos de muito baixo peso (RNMBP). MÉTODOS: Foram incluídos RNMBP com suspeita clínica de infecção nascidos na instituição de 01/08/2005 a 31/07/2007. Foram excluídos óbitos antes dos 14 dias, malformações do sistema nervoso central e infecções congênitas. Foi realizado ultra-som cerebral no terceiro dia e semanalmente até a sexta semana de vida ou alta. LPV foi diagnosticada por hiperecogenicidade difusa periventricular persistente por mais de 7 dias, ou por cistos periventriculares. RNMBP foram divididos em grupos com e sem LPV. Sepse foi definida por manifestação clínica com cultura positiva. Os testes t, Mann-Whitney, qui-quadrado e regressão logística foram usados. RESULTADOS: Foram incluídos 88 RNMBP, sendo que 62 (70,5%) sobreviveram e 51 (57,8%) tiveram LPV. Os grupos foram semelhantes no peso de nascimento, idade gestacional, escore de Apgar, tipo de parto, SNAPPE-II, presenças de enterocolite necrosante, persistência de canal arterial e óbitos. Sepse e ventilação mecânica foram mais freqüentes no grupo com LPV (23,5 e 2,7%, p = 0,005; 86 e 59%, p = 0,004, respectivamente). Na regressão logística, ambos foram fatores de risco independentes para LPV (p = 0,027 e 0,015, respectivamente). CONCLUSÃO: Corioamnionite é fator de risco definido para LPV. Demonstramos que sepse neonatal também é fator de risco importante. Acreditamos que a resposta inflamatória sistêmica seja o principal fator envolvido na etiopatogenia da LPV em RNMBP. OBJECTIVE: To investigate the association between periventricular leukomalacia (PVL) and neonatal sepsis in very low birth weight infants (VLBWI). METHODS: We studied VLBWI with a clinical suspicion of infection who had been born at our institution between the 1st of August, 2005 and the 31st of July, 2007. Children were excluded if they died before reaching 14 days, had malformations of the central nervous system or congenital infections. Ultrasound brain scans were carried out on the third day and weekly up until the sixth week of life or discharge. Periventricular leukomalacia was diagnosed by persistent diffuse periventricular hyperechogenecity for more than 7 days, or by periventricular cysts. The VLBWI were separated into two groups on the basis of the presence or absence of PVL. Sepsis was defined as clinical manifestation plus a positive culture. The Mann-Whitney, chi-square and t tests were applied followed by logistic regression. RESULTS: A total of 88 VLBWI were studied. Of these, 62 (70.5%) survived and 51 (57.8%) had PVL. Both groups were similar in terms of birth weight, gestational age, Apgar score, type of delivery, SNAPPE-II score, presence of necrotizing enterocolitis, persistent ductus arteriosus and deaths. Sepsis and mechanical ventilation were more common in the group with PVL (23.5 and 2.7%, p = 0.005; 86 and 59%, p = 0.004, respectively). Both of these were identified as, independent risk factors for PVL by logistic regression (p = 0.027 and 0.015, respectively). CONCLUSIONS: Chorioamnionitis has been defined as a risk factor for PVL. We have demonstrated that neonatal sepsis is also an important risk factor. We believe that the systemic inflammatory response is the principal factor involved in the etiopathogenesis of PVL among VLBWI.

The objective of this article is to describe growth of very low birth weight infants born in southern Brazil. All infants weighingor =1500 g were followed up until 12 months corrected age (CA). Growth was recorded at 40 weeks, 6 and 12 months CA. Catch up was considered if the measures wereor =-2 SD of World Health Organization growth charts for weight and length; and of National Center for Health Statistics for head circumference. One hundred and ninety three infants born were followed up for the study. At 40 weeks CA, 57.8% patients achieved catch-up in weight and 50.9% in length. At 6 months CA, 82.2% achieved catch-up for weight and length and at 1 year CA, 92% achieved catch-up in weight and 86.9% in length. Catch-up in head circumference was achieved for 93.4%, 85.9% and 85% patients at 40 weeks, 6 months and 12 months CA, respectively. At 12 months CA, no catch-up in weight, length and head circumference was related to higher SNAPPE-II (P = 0.046) and periventricular leukomalacia (PVL) (P = 0.003); longer time to achieve full enteral nutrition at the neonatal intensive care unit (NICU) (P = 0.037), lower maternal education (P = 0.018) and PVL (P = 0,003); higher SNAPPE-II (P = 0,004), PVL (P = 0.005) and longer time to achieve full enteral nutrition at the NICU (P = 0.044), respectively. In conclusion, PVL and higher SNAPPE-II were important factors to catch-up delay. Catch-up growth was high at 12 months CA.

Aim: To investigate growth and neurodevelopment outcome of very low birth weight (VLBW) infants delivered by preeclamptic mothers. Methods: A cohort including all VLBW infants delivered between December 2003 and May 2005 was followed up to 12 and 18 months corrected age (CA). Exclusion criteria: death before 1 year corrected age, major malformations, deafness and blindness. Weight, length and head circumference were plotted on NCHS curves. Bayley Scales were performed at 12 and 18 months CA. Results: 40 infants in preeclamptic and 46 in control groups were studied. Birth weight and gestational age were 1148 g ± 236 and 1195 g ± 240, and 31.3 weeks ± 1 and 30.6 weeks ± 2 for preeclamptic and control groups, respectively. At 12 and 18 months, CA, weight for age (Z score) was significantly higher in control than in preeclamptic. PDI scores were higher in preeclamptic than in controls at 18 months CA. Conclusions: Catch-up of body weight did not occur in the first 18 months CA in preeclamptic infants. Neurodevelopment outcome was better in infants delivered by preeclamptic mothers than in controls at 18 months CA.

Introduction Early nCPAP seems to prevent ventilator-induced lung injury in humans, although the pathophysiological mechanisms underlying this beneficial effect have not been clarified yet. Objective To evaluate plasma levels IL-1β, IL-6, IL-8, IL-10, and TNF-α immediately before the start of nCPAP and 2 hours later in preterm infants. Methods Prospective cohort including preterm infants with 28 to 35 weeks gestational age with moderate respiratory distress requiring nCPAP. Extreme preemies, newborns with malformations, congenital infections, sepsis, surfactant treatment, and receiving ventilatory support in the delivery room were excluded. Blood samples were collected right before and 2 hours after the start of nCPAP. Results 23 preterm infants (birth weight 1851±403 grams; GA 32.3±1.7 weeks) were treated with nCPAP. IL-1β, IL-10, TNF-α levels were similar, IL-8 levels were reduced in 18/23 preterm infants and a significant decrease in IL-6 levels was observed after 2 hours of nCPAP. All newborns whose mothers received antenatal steroids had lower cytokine levels at the onset of nCPAP than those whose mothers didn’t receive it; this effect was not sustained after 2 hours of nCPAP. Conclusion Early use nCPAP is not associated with rising of plasma pro-inflammatory cytokines and it seems to be a less harmful respiratory strategy for preterm with moderate respiratory distress.